Promotions of goat farming by both public and private sectors encouraged considerable goat raising in central Thailand. Gastrointestinal nematodes (GIN) infection is a major health and economic problem; however, evidence of resistance to broad-spectrum anthelmintics is frequently reported. Investigation of anthelmintic resistance (AR) status and identification of factors related to the development of AR is important components for sustainable GIN control. However, no information is available on this topic in the study area. The present study aimed to gather information on GIN control practices and to evaluate the effectiveness of albendazole, ivermectin, and levamisole for treating GIN infestation in goat herds in Sing Buri Province.Twenty-nine herds were randomly selected. Information on management practices was collected by face-to-face interview using a structured questionnaire. Three field experiments for routinely used anthelmintics, including albendazole, ivermectin, and levamisole were conducted from June 2019 to November 2019. Fecal samples were collected pre- and post-treatment and examined for fecal egg count reduction to determine the status of anthelmintic resistance of goat GIN.Several improper practices were identified that lead to AR, especially chronic use of albendazole and ivermectin. All herds were considered resistant to albendazole and ivermectin, and levamisole resistant nematodes were detected in two herds. AR was strongly linked with the continuous use of anthelmintics.Levamisole, which was still effective in the province, should be used with caution to minimize the selection of resistant strains. Farmers should be provided with updated information for sustainable parasite control. Further, the efficacy of anthelmintics should be routinely monitored. Gastrointestinal nematodes (GIN) are a major health issue for goats. GIN infestation causes significant economic loss and welfare concerns worldwide. Control of GINs requires at least three elements: 1) Eliminating GINs from hosts, 2) avoiding exposure of hosts to an infective stage of GINs, and 3) enhancing host resistance )Fecal egg count reduction % = (1/n) Σ is <90%. If one condition is met, AR is suspected . Data frFrom all 29 participating farmers, 27, 24, and 23 agreed to participate in the evaluation of the effectiveness of albendazole, ivermectin, and levamisole, respectively. Twenty of 29 farmers participated in all three experiments. Reasons for non-participation included no longer having goats, receiving the last anthelminthic treatment <8 weeks after previous treatment, and unavailable of farmers. Twenty-eight farmers consented to be interviewed.Deworming practices are shown in Conversely, underdosing and overdosing with benzimidazole were uncommon. Combined administration of ivermectin and benzimidazole was used in a few herds. Four farmers reported no improvement in goat health after routine deworming. Most participating farmers considered diarrhea, stunted growth, and weight loss as health issues in their animals.Strongyloides spp. Eggs of Moniezia spp. and oocysts of Eimeria spp. were also detected in some samples. Mean pre-treatment fecal GIN egg count was >150 eggs/g of feces in every herd in all three experiments. All herds participating in albendazole and ivermectin treatment showed AR. Medians FECR were −97% and −71%, which reflect increased numbers of eggs post-treatment compared to pre-treatment findings. Only two herds were considered to have levamisole-resistant GINs. The median FECR for levamisole experiment was 97%, with seven herds having 100% mean FECR. Of 20 herds where all three experiments were completed, resistance to albendazole, ivermectin and levamisole was found in two (10%). In addition, resistance to both albendazole and ivermectin was found in the 18 remaining herds (90%)  .The present study could not statistically identify the contributing factors of AR against albendazole and ivermectin because all participating herds showed resistant GINs to these two anthelmintics. For levamisole, only two herds displayed resistant GINs and they reported applying an anthelmintic once a month. Similar to the other factors, the use of levamisole in the herd was not related to its resistance status (p=0.311). One of these two herds had some experience using levamisole, while another herd had never used it. However, the latter reported introducing new goats into the herd.Our results demonstrated trends of association between introducing of new goat into the herd, herd size ≥54 animals, number of adult goats ≥38, frequently used of anthelmintic and history of pale mucous membrane and infertile goats within herd and multi-AR status; however, no statistically significant association was presented .Most farmers accepted that GIN infection was common in their herds. Several approaches were used to address this problem, such as using anthelmintics, alternating classes of anthelmintics, rotational grazing of common pastures, and avoiding grazing in mornings and evenings to minimize parasite exposure. However, the prevalence of GIN infection was still high. Some farmers thought that AR parasites existed in their herds, based on an absence of clinical improvement of goats after treatment, even after increased doses of anthelmintics above doses recommended in prescriptions, especially for ivermectin.In the present study, we focused on the efficacy of anthelmintics against GINs because all three anthelmintics used are typically effective against this group of parasites. In albendazole and ivermectin experiments, FECRs in almost all herds were negative, indicating that no reduction in their egg excretion after treatment and these anthelmintics might be less efficacious. A similar finding was reported from a study of herds where anthelmintics had been used for long periods. The underlying mechanism of this phenomenon is not understood, and reconsideration of anthelmintic use as a cause is needed .Our findings of AR in GINs concurs with the previous studies on Malaysian and southern Thai goats that reported the lowest degree of resistance for levamisole compared to albendazole and ivermectin ,21. An eet al. [Frequent anthelmintic use was reported as the most important cause of AR development ,22,23. Aet al. . Anthelmet al. . In the et al. . In the Underdosing is a major factor in AR development ,22; howeTypically, farmers select and administer anthelmintics to their goats without supervision by veterinarians. Misuse of drugs, such as inaccurate calculation of doses or improper administration methods, can result in underdosing. Further, farmers mostly purchased anthelmintics from local animal feed and drug stores. Products available in these stores are rarely inspected. Farmers are more likely to buy veterinary products at lower prices to reduce production costs. Low priced anthelmintics might be expired or low quality and promote AR . DiffereAn influence of pasture rotation on delaying AR is well recognized ,22,29. UThe mass anthelmintic treatment reported as a risk factor of AR  was implBased on statistical analysis and data mining, frequent use of anthelmintic and new goat introduction might be responsible for levamisole resistance in study herds. More study populations with a variation of AR status are required to determine factors critical for the development of AR. A case-control study and a survey questionnaire based on AR status of herds would be suggested for further study to determine factors critical for the development of AR.et al. [All farmers in the present study were informed of AR status in their herds by the research team, as recommended by Crook et al. . LevamisOur study shows a high prevalence of AR, especially to albendazole and ivermectin, in goats in In Buri district. Levamisole was still effective; however, it should be used in a program to minimize selective pressure on GINs and the occurrence of resistance. Local veterinarians should provide information and promote an education campaign to establish sustainable GIN control. In addition, the efficacy of anthelmintics should be routinely monitored to ensure their effectiveness.NR and SP: Conceived and designed the study. NR and NT: Conducted experiment. NR and SP: Analyzed the data, drafted and revised the manuscript. All authors read and approved the final manuscript.


Background: Atherosclerosis is a major cause of coronary artery disease (CAD), and CAD is one of the main causes leading to death in most countries. It has been reported that lncRNAs play important roles in the development of atherosclerosis; thus, we aimed to explore lncRNAs that are closely related to the occurrence and development of atherosclerosis.Methods: The data GSE113079 from the GEO database was used to explore the dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) between 93 patients with CAD and 48 healthy controls. Next, RT-qPCR was performed to detect the level of lncRNAs in HUVEC cells and CCK-8 was performed to detect cell viability. Then, flow cytometry assays were used to determine the apoptosis of HUVEC. In addition, ELISA assay was used to measure the concentrations of triglyceride (TG), low density lipoprotein cholesterin (LDL-C), and high density lipoprotein cholesterol (HDL-C). Moreover, western blot assay was used to detect the expression of proteins.Results: lnc-KCNC3-3:1 was significantly upregulated in PBMCs of patients with CAD. In addition, oxidized low density lipoprotein (oxLDL) notably inhibited the proliferation and induced the apoptosis of HUVEC, while this phenomenon was notably reversed by lnc-KCNC3-3:1 knockdown. Moreover, oxLDL significantly promoted the migration of HUVECs, which was significantly restored by knockdown of lnc-KCNC3-3:1. Moreover, lnc-KCNC3-3:1 siRNA1 could reverse oxLDL-induced HUVEC growth inhibition, and lnc-KCNC3-3:1 silencing could inhibit the expressions of p-JAK1 and p-STAT3 in oxLDL-treated HUVECs. Animal study revealed that knockdown of lnc-KCNC3-3:1 alleviated the symptom of atherosclerosis, and it could inhibit the expressions of p-JAK1, p-STAT3 and p-Akt in tissues of atherosclerosis mice.Conclusion: Knockdown of lnc-KCNC3-3:1 alleviates the development of atherosclerosis via downregulation of JAK1/STAT3 signaling pathway. These data indicated that lnc-KCNC3-3:1 might serve as a potential target for the treatment of atherosclerosis. Atherosclerosis (AS) is the main cause of the development of cardiovascular and cerebrovascular diseases –3. It isvia regulating miRNA-21/PTEN pathway  is a class of RNA molecules with a transcript length of >200 nt , 8. It i pathway . Howeverhttps://www.ncbi.nlm.nih.gov/geo/) database. R language was used to analyze the differentially expressed genes (DEGs) in PBMCs of 93 patients with CAD and 48 healthy controls. P < 0.05 and |log2 (FC)| > 2 were set as the threshold. LncRNA-related genes were analyzed by Gene Set Enrichment Analysis (GSVA) method to obtain their related pathways.Atherosclerosis-related datasets (GSE113079) were downloaded from the Gene Expression Omnibus  was obtained from American Type Culture Collection . HUVEC cells were maintained in DMEM medium containing 10% FBS, penicillin 100 U/ml, and streptomycin 100 mg/ml in a humidified incubator containing 5% CO−ΔΔCT method was used for data analysis.Trizol reagent  was used to extract the RNA from cells. RNA was reversed transcribed into cDNA using an EntiLink™ 1st Strand cDNA Synthesis Kit (ELK Biotechnology). Next, RT-qPCR was performed using the EnTurbo™ SYBR Green PCR SuperMix  on the StepOne™ Real-Time PCR . The primers were as follows: H-ACTIN, forward, 5′-GTCCACCGCAAATGCTTCTA-3′, reverse, 5′-TGCTGTCACCTTCACCGTTC-3′; H-LOC100129516, forward, 5′-GCTGTGGTTATCCAATCCCTC-3′, reverse, 5′-GGCAAATGACTTCACCTCCC-3′; H-lnc-KCNC3-3:1, forward, 5′-GAAGATTGGGAACCGACAACA-3′, reverse, 5′-TTGCATCGAGAATCGTGCTC-3′; ENSG00000236780.1, forward, 5′-GATGCTCTCCACACCAGTCCA-3′, reverse, 5′-TGTGAACAGGGCTGGAATGAG-3′; ENSG00000205959.3, forward, 5′-GCTGTCCGAGCAAATGTCTCT-3′, reverse, 5′-GTGGCACTGCTGAGAAGAGGA-3′; ENSG00000261482.1, forward, 5′-GGGCTGCTGACTTCCACAG-3′, reverse, 5′-AATATCCACTCTGGGTGCAGC-3′. β-actin acted as the inner control. The 24/ml). After treatments, the cells were stained with 5 μl Annexin-V-FITC and 5 μl PI staining solution for 15 min in darkness. Finally, a flow cytometer was used to analyze the cell apoptosis.Annexin-V-FITC apoptosis detection kit  was used to detect cell apoptosis. Briefly, HUVECs were maintained in DMEM medium and cultured in six-well plate  were purchased from RiboBio .LOC100129516 siRNA1, LOC100129516 siRNA2, LOC100129516 siRNA3; lnc-KCNC3-3:1 siRNA1, lnc-KCNC3-3:1 siRNA2, lnc-KCNC3-3:1 siRNA3; ENSG00000261482.1 siRNA1, ENSG00000261482.1 siRNA2, ENSG00000261482.1 siRNA3 or siRNA-ctrl was transfected into HUVEC cells using Lipofectamine® 2000 .The sequences of siRNAs were presented as following: LOC100129516 siRNA1, 5′-CCCAGGCTACCATCCCTCCAAATAA-3′; LOC100129516 siRNA2, 5′-CACCATTCACTTTCCGGCAGCTTAG-3′; LOC100129516 siRNA3, 5′-CCGCTCCTTCTTGTCAGAGTAAGTA-3′; siRNA-ctrl, 5′-CCCATCGTACCTCCCAACCAGATAA-3′; lnc-KCNC3-3:1 siRNA1, 5′-ACAACATGCGTGGGAGGCGACAGGT-3′; lnc-KCNC3-3:1 siRNA2, 5′-ACAGGTCGCGACGGCAGCCACAGGT-3′; lnc-KCNC3-3:1 siRNA3, 5′-GAGGCTCCCTGAACCACCCTCCCTC-3′; siRNA-ctrl, 5′-ACACGTAGGTGGGAGCAGCACAGGT-3′; ENSG00000261482.1 siRNA1, 5′-TGGCTGCTGGAGAGGATTCTCACAA-3′; ENSG00000261482.1 siRNA2, 5′-GGCTGCTGGAGAGGATTCTCACAAA-3′; ENSG00000261482.1 siRNA3, 5′-GCTGCTGGAGAGGATTCTCACAAAG-3′; siRNA-ctrl, 5′-GCTGCTGTCAAGGATTCTGGAGCAA-3′.3/ well. After treatments, the cells were incubated with 10 μL CCK-8 solution at 37C for 4 h. Then, the absorbance at 450 nm was detected using a spectrophotometer.HUVEC cell viability was determined by Cell Counting Kit-8 . The cells were placed into 96-well plate at density of 51 × 0The plasma samples were collected from five patients with CAD and five healthy donators in the First Affiliated Hospital of Jinzhou Medical University. Plasma was stored in liquid nitrogen immediately after collection. This study was confirmed by the Ethics Committee of the First Affiliated Hospital of Jinzhou Medical University, and each patient's written informed consent was obtained. Meanwhile, the information of healthy donators and patients with CAD were presented in Protein Lysis Buffer  was used to extract the protein from cells or arterial tissues of mice. BCA kit  was used to detect the protein concentration. Then, 30 μg proteins were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to polyethylenedi fluoride (PVDF). The membrane was blocked with 3% skim milk for 1 h at room temperature followed by the incubation of the primary antibodies at 4°C overnight. The primary antibodies used as follows: anti-Bax , anti-p-Akt 1:1000, Abcam), anti-Bcl-2 , anti-Cleaved caspase 3 , anti-p-JAK1 , anti-JAK1 , anti-p-STAT3 , anti-STAT3 , anti-β-actin . The β-actin worked as an internal control. Next, the membranes were incubated with goat anti-rabbit or mouse IgG secondary antibodies  for 1 h at room temperature. Finally, the protein bands were detected using an efficient chemiluminescence (ECL) kit (Thermo Fisher Scientific).5) were added into the upper chamber suspended in 200 μL serum-starved medium. Next, the lower chamber was added with 600 μL of DMEM medium containing 10% FBS. After 24 h of incubation, the cells on the lower membrane surface were stained with 1% crystal violet for 30 min and pictured with a fluorescence microscope.Transwell chambers  with a pore size of 8 μm were used to detect the migration ability of HUVEC. The Cells (11 × 0−/− mice (aged 7 weeks) were purchased from Vital River  and housed in a specific-pathogen-free animal facility. To establish atherosclerosis model in vivo, these mice were fed a high-fat diet containing 60% of total calories from fat  or a standard 4% fat diet  for 12 weeks. An lnc-KCNC3-3:1 knockdown mouse model was constructed by injecting a lentivirus (Lenti) expressing RNA inference (RNAi) targeting lnc-KCNC3-3:1 (lnc-KCNC3-3:1 Lenti-siRNA1), which was purchased from Genepharma . Next, lnc-KCNC3-3:1 Lenti-siRNA1 was injected into the tail vein of mice in atherosclerosis + lnc-KCNC3-3:1 siRNA1 group. Finally, mice were sacrificed for collection of arterial tissues and serum. All animal procedures were approved by the Committee of the First Affiliated Hospital of Jinzhou Medical University. The National Institute of Health Guide for the Care and Use of Laboratory Animals was strictly followed , low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the plasma of mice were measured with ELISA assays, respectively. These ELISA assays were obtained from Nanjing Jiancheng Bioengineering Institute .P < 0.05 was regarded as statistically significant differences.All experiments were repeated three times. Statistical analyses were performed using GraphPad Prism software . The measurement data were shown as the mean ± SD. The one-way analysis of variance was used for comparison between multiple groups and Tukey's test was used for comparison between the two groups. P < 5E−63. Next, the differentially expressed lncRNA-related pathways were explored by gene set variation analysis (GSVA)  . As indiin vitro, HUVECs were treated with oxLDL  for 24 h and CCK-8 assay was used to detect the cell viability. As shown in in vitro model of atherosclerosis. Among these five lncRNAs, the increases of LOC100129516, lnc-KCNC3-3:1, and ENSG00000261482.1 were much higher in the in vitro model of atherosclerosis compared with the other two lncRNAs; thus, we focused on these 3 lncRNAs in the following experiments . Thus, we next focused on exploring the role of lnc-KCNC3-3:1 in the progression of atherosclerosis. The result of apoptosis assay indicated that oxLDL dramatically increased the apoptosis of HUVEC cells, while this phenomenon was notably reversed by lnc-KCNC3-3:1 siRNA1 . As we kWe next investigated the effect of lnc-KCNC3-3:1 knockdown on the migration of HUVEC. As indicated in in vivo atherosclerosis mouse model was established. H&E and Oil-red O staining were used to observe the cross section of the mouse arteries. In atherosclerosis model group, there was a significant increase in lipid accumulation and vascular wall thickening; however, these symptoms were notably alleviated by lnc-KCNC3-3:1 knockdown  can be found in the article/supplementary material.This animal study was reviewed and approved by the Committee of the First Affiliated Hospital of Jinzhou Medical University. The studies involving human participants were reviewed and approved by Ethics Committee of the First Affiliated Hospital of Jinzhou Medical University. The patients/participants provided their written informed consent to participate in this study.LS made major contributions to the conception, design, and manuscript drafting of this study. XH and TZ were responsible for data acquisition, data analysis, data interpretation, and manuscript revision. LS and GT made substantial contributions to conception and design of the study and revised the manuscript critically for important intellectual content. All authors agreed to be accountable for all aspects of the work, read, and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Long non-coding RNAs (lncRNAs) have been found to play critical roles in regulating gene expression, but their function in translational control is poorly understood. We found lnc-OPHN1-5, which lies close to the androgen receptor (AR) gene on chromosome X, increased prostate cancer (PCa) Enzalutamide (Enz) sensitivity via decreasing AR protein expression and associated activity. Mechanism dissection revealed that lnc-OPHN1-5 interacted with AR-mRNA to minimize its interaction with the RNA binding protein (RBP) hnRNPA1. Suppressing lnc-OPHN1-5 expression promoted the interaction between AR-mRNA and hnRNPA1, followed by an increase of ribosome association with AR-mRNA and translation. This effect was reversed by increasing lnc-OPHN1-5 expression. Consistently, the in vivo mice model confirmed that knocking down lnc-OPHN1-5 expression in tumors significantly increased the tumor formation rate and AR protein expression compared with the control group. Furthermore, knocking down hnRNPA1 blocked/reversed shlnc-OPHN1-5-increased AR protein expression and re-sensitized cells to Enz treatment efficacy. Evidence from Enz-resistant cell lines, patient-derived xenograft (PDX) models, clinical samples, and a human PCa study accordantly suggested that patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. In summary, targeting this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex may help develop novel therapies to increase Enz treatment sensitivity for suppressing the PCa at an advanced stage. Prostate cancer (PCa) is the most frequently diagnosed malignancy among men in the western world –4. The aPrevious studies have shown mutations, genomic amplifications, and deletions, which were commonly found in the AR gene during the development of CRPC, ultimately contributed to the continued and enhanced AR activity , 6. Morevia post-translational mechanisms  to wash each well 3 times, followed by 1 × Apollo solution incubating for 30 min at RT away from light. Finally, the cell nuclei were stained with 1 × Hoechst for 30 min, and the stained cells were visualized by fluorescence microscopy .Cells were mixed with RPMI media, and we added 500 µl media mix containing 5000 cells/well into the 24-well plates. Before collecting, we added 50 µL MTT reagent  to each well and incubated at 37 °C for 2 h. After removing supernatants, we added 1 mL dimethyl sulfoxide  to dissolve the crystals. The optical density (OD) was determined at a wavelength of 570 nm on a microplate reader. The effects of lnc-OPHN1-5 on PCa cell Enz sensitivity were also tested by EdU incorporation assay using Cell-Light™ EdU Apollog, and washed twice with pre-chilled 0.15 M NaCl. The detailed steps followed T Masse et al.’s We obtained the tumor tissues from each mouse and embedded them in paraffin. These samples were cut into 5 µm thick slices and dehydrated with xylene. We stained the AR  and hnRNPA1  antibodies at 4 °C incubator overnight and then incubated with the secondary antibody at RT for 1 h. The detailed steps of the IHC process and the score quantification were described in our previous work , 26. Thet-test or non-parametric test (Mann–Whitney test) depending on the homogeneity test of variance. Data were presented as the mean and standard error of the mean (mean ± SEM) or the mean+/-standard deviation (mean+/-SD) unless mentioned otherwise. A P-value < 0.05 was considered statistically significant.The results for each treatment group were presented as a representative of multiple repeated experiments with each data point performed in triplicate. Statistical studies between the two groups were conducted using the two-tailed unpaired Student’s Previous studies reported that aberrations of AR  are frequently found in PCa patients Fig. S 27–29].–29.27–29https://lncipedia.org/). To implicate their potential role in PCa progression, we generated four short hairpin RNAs (shRNAs) to knock down their expression to test whether there is a lncRNA that could influence Enz treatment sensitivity. The results revealed one lncRNA, lnc-OPHN1-5, whose silencing (sh), with two different shRNAs to eliminate off-target effects, significantly decreased Enz treatment sensitivity in C4-2 cells  dataset (GSE48403) analysis. Results revealed that in some PCa patients with a higher grade or higher Gleason score of PCa, their lnc-OPHN1-5 expressions were decreased after ADT , and examined the associated ribosome through the measurement of 18S ribosomal RNA, and results revealed that knocking down lnc-OPHN1-5 expression led to significantly increase the abundance of ribosomes that were associated with AR mRNA, and increasing lnc-OPHN1-5 expression led to suppress their interaction Fig. .Fig. 4ThFurthermore, in the ribosome fraction upon cellular organelle fractionation, we found that knocking down lnc-OPHN1-5 expression led to increasing the abundance of AR mRNA, while overexpressing lnc-OPHN1-5 expression decreased AR mRNA in the ribosome fraction . To test whether this binding was critical for the lnc-OPHN1-5 function, we then constructed a mutant (mut) lnc-OPHN1-5 by deleting the presumptive AR-mRNA interaction regions  to target this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex to increase the Enz treatment sensitivity, thus better suppress the PCa progression. We first applied the shhnRNPA1 to reverse/block the lnc-OPHN1-5 increased AR protein expression Fig. . The resχ2 = 9.798, P = 0.0017)  were mixed with Matrigel  and subcutaneously injected into the left hind limb of the NCG male mice at six weeks of age. Two months later, we found that only two if 12 mice formed tumors in the pLKO.1 group , while 11 of 12 mice developed tumors in the shlnc-OPHN1-5 group  Fig.  and tumo17) Fig.  between oup Fig.  comparedoup Fig. , using MTaken together, the data from Figs. Enz has been in clinical use to extend mCRPC patients’ survival an extra 4.8 months –4. Howev.’s work [Han et al.  found th.’s work , they chAR gene on chromosome X, and these lncRNAs potentially have a role on AR function. Notably, we found that only lnc-OPHN1-5 suppresses AR expression and associates with enhanced Enz treatment sensitivity. In addition, evidence from resistant cell lines, the PDX mouse models, PCa tissues, and a human PCa study all indicated that PCa patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. Consistently, our in vivo data shows a vast difference in tumor formation rate between the vector group and shlnc-OPHN1-5 group , further supporting the notion that the expression of lnc-OPHN1-5 is negatively associated with PCa patients’ poor prognosis. The mechanism study found that the lnc-OPHN1-5 directly interacts with the AR mRNA, reducing the interaction between AR mRNA and hnRNPA1, therefore, suppresses the AR mRNA translation and protein synthesis, enhancing the Enz treatment sensitivity. Consistent with that, knocking down hnRNPA1 reverses shlnc-OPHN1-5 induced AR protein expression and re-sensitizes cells to Enz treatment.Thus, we hypothesized that there might exist some lncRNAs that are located surrounding the etc. Nadiminty et al. [The involvement of hnRNPA1 in mRNA splicing has been recognized for a long time , 50, buty et al.  found thOne weakness of our work is that we did not provide evidence to demonstrate the Enz sensitivity in the mice xenograft model due to the inefficiency, therefore no statistical power of tumor formation with the parental cells. Similarly, clinical samples from the existing GEO dataset are limited to provide statistical power to support our hypothesis that low expression of lnc-OPHN1-5 links to unfavorable Enz treatment response. More clinical samples before and after Enz treatment are needed to test this hypothesis in PCa patients rigorously. In addition, since Enz treatment sensitivity might be influenced by cell growth rates at a certain timepoint, in our case, the cell growth could be slightly decreased by the lnc-OPHN1-5 expression. The caveat notwithstanding we have the evidence to support the role of lnc-OPHN1-5 from clinical samples, in vivo mice models, and PDX xenograft models, we still need more evidence to rigorously demonstrate that its impact on Enz treatment sensitivity of PCa is not derived from its minor impact on cell proliferation.In summary, we characterized a novel lncRNA, lnc-OPHN1-5, which influences anti-androgen Enz treatment sensitivity by decreasing AR mRNA translation and protein synthesis. Targeting the lnc-OPHN1-5/hnRNPA1/AR axis represents a potential strategy for the treatment of CRPC.Legends of Supplementary Figures and TablesFig. S1Fig. S2Fig. S3Fig. S4Table S1Table S2Table S3Table S4


In order to design the perception system of the lower limb wearable rehabilitation robot, this study established the kinematics theoretical model of human lower limb and conducted the kinematics analysis of human body. By using the dynamic attitude analysis system, combined with the human body mark points, the position data of human body mark points in the process of standing up, sitting up, walking, stepping up, and squatting were collected. Combined with the movement mechanism of human lower limbs, the characteristics of human motion state transition are analyzed, and the perceptual algorithm for judging human motion intention is studied, so as to determine the wearer's current posture, standing intention while sitting, walking intention while standing, moving intention, and stopping intention during walking. The results show that the angle of the hip joint changes regularly between 0° and 37° and the angle of the knee joint changes regularly between 0° and 70°during the standing process, which is consistent with the angle change trajectory collected by the dynamic attitude analysis system. The angle trajectories of the hip and knee joints measured by the absolute angle sensor are the same as those obtained by the dynamic attitude analysis system. 1.5 rad and 0.3 rad were selected as reasonable and effective thresholds for determining sitting and standing states. In recent years, in the field of nervous system diseases, some progress has been made in the research on the rehabilitation of the central nervous system (CNS). Experts have found that the central nerves such as the brain and spinal cord can stimulate the nervous system of the lost limbs through repeated learning and training in a passive form, so that its function is restored and strengthened . TherefoThe research of rehabilitation robot field originates from the development and maturity of military exoskeleton industry. Industrial control technology and mechanical manufacturing technology have developed rapidly in the middle of last century. The research of the enhanced exoskeleton robot system started in the 1960s. In 1960, the United States General Electric Company developed the Hardiman series of exoskeleton robots, hoping to help the wearer lift a weight of up to 700 kg . HoweverWith the rapid development of industrial technology, advanced science and technology are introduced into rehabilitation training, and a wearable rehabilitation robot system is formed by combining robotics, mechatronics, biological rehabilitation, intelligent control, information fusion, and rehabilitation medicine theories . The rehBased on the research status of the rehabilitation robot perception system at home and abroad, combined with the characteristics of rehabilitation robot audience, the kinematics analysis system of human lower limbs was developed and designed, and on this basis, the sensing system of the wearable lower limb rehabilitation robot was studied.The wearable health monitoring system is a typical application of wearable computing in the field of medicine. Wearable sensor-based monitoring of external vital signs in clinical settings ensures better support for assessing a patient's health status and can send automatic alerts to care providers in the event of health deterioration , 7. ArgeAt present, the research on the monitoring system of wearable sensors is developing continuously. Jie et al. proposed a wearable human body monitoring system based on wireless acceleration sensor technology, which is used to real-time monitor the daily exercise amount of human body . Ivacu eThe main research is to design the perception system of the lower limb wearable rehabilitation robot, establish the kinematics theoretical model of the human lower limb, conduct the kinematics analysis of the human body, design the hardware circuit of the perception system, study the algorithm of the perception of the human body, and finally carry out the experimental verification on the industrial computer platform. The results show that the angle of the hip joint changes regularly between 0° and 37° and the angle of the knee joint changes regularly between 0° and 70° during the standing process, which is consistent with the angle change trajectory collected by the dynamic attitude analysis system. The angle trajectories of the hip and knee joints measured by the absolute angle sensor are the same as those obtained by the dynamic attitude analysis system. 1.5 rad and 0.3 rad were selected as reasonable and effective thresholds for determining sitting and standing states.The motion feedback information selected by the perceptual system of a rehabilitation robot is as follows. Lower extremity EMG signal: collect and amplify muscle bioelectric information. EMG signal can be measured according to muscle activity before exercise, which can effectively make the rehabilitation robot and user move synchronously. However, EMG signals cannot be collected for patients with lower limb disability and loss of motor ability. Contact force information: collect and process the contact force between the rehabilitation robot parts and the ground force, as well as the contact force between the human and the rehabilitation equipment, and determine the current motion state and the movement intention of the user according to the size and distribution change of the force. Because the pressure sensor has some shortcomings such as nonlinearity, it needs to work with other sensor signals. Because there are too many contact points between human lower limbs and the rehabilitation robot system, it is impossible to determine and accurately place the contact force sensor to accurately locate the contact force . RelativIn summary, the motion feedback signals that need to be collected in this project are determined as follows: plantar pressure information, joint angle information, angular acceleration information of back and lower limbs, and linear acceleration information. As shown in θlg, θrg) of the crutch and the direction of the pressure switch  of the crutch bottom.When the wearer is in a standing posture, the movement intention is judged by the ground force distribution and the deviation of the center of gravity. The wearer extends the left crutch/right crutch forward, while the upper torso tilts to the left/right front, indicating that the wearer wishes to step forward with the right/left leg , 20. Detflh or frh of the swinging leg is greater than the threshold value fs, the leg support phase is entered. If the swing of the walking stick stops and the swing of the trunk stops at the same time, the wearer is considered to have the intention to stop walking, and the rehabilitation robot will assist in walking and change to a standing state.Walking intention is divided into swinging the right leg and swinging the left leg. When  and 3)  3) are sla is the length of the rehabilitation robot's single foot.In the process of rise, sit, and walk through the foot pressure acquisition of real-time detection of horizontal axis ZMP information, if the ZMP stable signal exceeds the threshold (one foot in the threshold size of rehabilitation robots length), namely, the rehabilitation robot system is in unstable condition, need to issue instructions to the control system, make its provide auxiliary torque, and restores the balance of the healing machine. Equation  should bIPC has the characteristics of easy transplantation and powerful computing power. The development and verification platform of experimental methods and algorithms can be built on IPC, which can greatly shorten the development cycle. At the same time, the data acquisition card can be used to analyze the collected signals conveniently, which provides a basis for algorithm research.IPC experimental verification platform refers to the hardware system of IPC and the supporting software based on this hardware. In the rehabilitation robot system, the IPC experimental verification platform includes PC, signal acquisition board card, sensor signal acquisition module, Matlab software and Visual Studio software.A software debugging platform based on Matlab + Simulink and ADAMS software is developed based on IPC hardware platform. ADAMS is a software for the analysis of kinematics, dynamics, and statics of mechanical structures developed by MDI Corporation (now incorporated into MSC Software Corporation) in America. The body limb model was established by ADAMS, and the mechanical structure of the rehabilitation robot system was simulated and optimized. The moment of inertia of each limb is calculated to provide reference data for the selection of the actuator.During the experiment, after wearing the rehabilitation robot, the posture was first adjusted to the sitting or standing state, and after the judgment was completed, the corresponding state transition actions were made to express the motion intention, namely, the intention of standing while sitting and the intention of standing or walking while standing. After the rehabilitation robot assists to complete the corresponding action, it makes the next state transition action again. The rehabilitation robot can detect the current posture and judge the movement intention to carry out the next auxiliary action.Through D/A transformation, filtering, and other processing, the PIC microcontroller transmits the foot pressure to the top computer through CAN bus and obtains the real-time pressure information through the digital filtering circuit.First, the FlexiForce thin film pressure sensor is calibrated. Place the nominal weight on the FlexiForce sensor, record the voltage values, and draw a table as given in The pressure-voltage curve is drawn as shown in The detection and drawing of the pressure distribution of six foot pressure sensors in different motion states are carried out. After filtering, the foot pressure distribution map can be obtained in the walking process and the standing process.Combined with phase differentiation, the pressure distribution of feet in a gait cycle is analyzed, as shown in As can be seen from GOF information of lower limbs can be detected through the information of foot pressure. The switching rules of GOF information during walking are as follows: the left leg enters the swing phase, the right leg starts in the support phase, and the left leg swings to the highest point. In the horizontal plane, the GOF changes from left back to right front. When the left leg swings to the highest point and the left foot falls to the ground completely, the right leg enters the swing phase. During this process, the change of GOF in the horizontal plane changes from right back to left front. When moving forward, the right leg of the lower limb enters the swing phase and swings to the highest point of the right leg. In the horizontal plane, GOF changes from right back to left front. The right leg starts to swing to the highest point until the right foot completely lands, and the left leg enters the swing phase. During this process, the GOF changes from left back to right front in the horizontal plane. At this point, a periodic gait process is completed, during which the trajectory of GOF also completes a periodic change. In one cycle, the change in the horizontal plane is left back to right front, right back to left front, and left back to right front.The angle of hip joint and knee joint measured by the OMRON absolute angle encoder was transmitted to the top computer, and the absolute angle changes of hip joint and knee joint were obtained during the process of standing up, sitting up, and walking. In the process of standing up, when the angular velocity of the knee joint reaches the maximum value, the time point is about 70% of the whole standing up process, so it is reasonable and effective to select this point as the phase conversion point in the standing up process.The angle trajectories of the hip and knee joints measured by the absolute angle sensor are the same as those obtained by the dynamic attitude analysis system. 1.5 rad and 0.3 rad were selected as reasonable and effective thresholds for determining sitting and standing states.The lower limb motion state transition model based on a finite state machine was established, the human body sensing algorithm was studied, the sensor group information was collected and fused, the current motion mode was judged, and the algorithm to determine the human motion intention was verified. The signal of the sensor group enters the signal acquisition board for centralized preprocessing, and then, it is sent to the industrial computer. The industrial computer calculates the sensor signal, locates the current motion mode of the wearer, and perceives the motion intention of the wearer through the perception algorithm. With the rapid development of industrial technology, advanced science and technology introduced rehabilitation training, using the combination of robotics, electromechanical technology, biological rehabilitation technology, intelligent control technology, information integration technology, rehabilitation medicine, form a wearable rehabilitation robot system, created the first of enhanced exoskeleton research, and research institutions in the field of enhanced exoskeleton. By comparing the experimental results with the theoretical results of the perceptual algorithm, the perceptual algorithm is verified. The experimental results show that the angle of the hip joint changes regularly between 0° and 37° and that of the knee joint changes regularly between 0° and 70°, which is consistent with the trajectory of angle change collected by the dynamic attitude analysis system. The angle trajectories of the hip and knee joints measured by the absolute angle sensor are the same as those obtained by the dynamic attitude analysis system. 1.5 rad and 0.3 rad were selected as reasonable and effective thresholds for determining sitting and standing states.


In this brief review we present an outline of the current state of research on examples of hyperandrogenism that can be strongly associated with diverse modifications in the androgen signaling pathway. We discuss the most prominent clinical features of androgen excess and correlate them with studies on androgen receptor (AR) alterations. For the first time we summarize the confirmed localizations of all known AR receptors in women. The knowledge of ARs may be the basis for AR-targeted therapies of androgenic disorders in women, including malignancy, as it has recently been demonstrated for triple-negative breast cancer. Moreover, we summarize the structure and characterization of key AR splice variants, which could be involved in the androgenization in women. Hyperandrogenism in women is a highly important clinical and social problem affecting 5-10% of the population of reproductive age . Often dIn recent years the pace of research on ARs has been gaining a particular momentum since more and more scientific evidence supports their importance for tissue homeostasis in women. For example, roles of ARs have been studied in such complex processes as reproductive failure , endometrial hyperplasia, and cancer , 5, 6, 7AR includes 8 different exons forming the AR protein consisting of 4 domains, each of specialized function: 1) the N-terminal domain (NTD); 2) the DNA binding domain (DBD); 3) a hinge region (HR); and 4) the C-terminal ligand binding domain (LBD) [The expression of full-length AR (AR-FL) has been proven across most of the female reproductive tissues, which emphasizes its apparent functional importance, especially within the endometrium . Tuckermin (LBD) . When ARin (LBD) .AR structure and the most prevalent AR transcripts compositions [ositions .AR gene [V567es  have been commonly identified in cancer tissue and ascribed an important role in cancer pathogenesis [AR-V7 gene in these cells is relatively less pronounced than that of the AR-FL gene. However, such a high yield protein transcription can be explained by excessive constitutive activity of AR-Vs, especially in the absence of any ligand, compared to AR-FL ligand-activated transcription [It should be noted that AR-FL coexists in tissues with its truncated isoforms lacking LBD that are referred to as AR splice variants (AR-Vs), and with variant 2 of the AR named AR45. The truncated variants are products of alternative splicing of the human AR gene , 14. As AR gene . OverallAR gene . It has AR gene . SecondlAR gene , 19. Finogenesis . For exaogenesis , 21. Morcription , 22. Botcription . Nonethecription .In the light of ARs abundance in women (Tab. I), their pivotal role in the pathogenesis of hyperandrogenism should be thoroughly analyzed. Hence, it is important to distinguish the most common clinical manifestations facilitating the diagnosis of this disorder and select appropriate patients for further in-depth hormonal and receptor validation. One of such manifestations is hirsutism which affects up to 15% of all women and 70-80% of women with hyperandrogenism . Visual To date, AR-Vs have been studied to some extent in human breast cancer cell lines and ovarian granulosa cells (GCs) , 38. RecAll in all, we are currently experiencing an exciting era of new discoveries in the field of ARs and their possible multiple roles in women. Our brief review highlights that the knowledge of AR signaling and receptor structure alterations is crucial for the understanding of the pathogenesis of many androgenic disorders. Therefore, future scientific efforts targeted to further decipher the AR significance in women’s health and disease will be of utmost importance.


Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China.Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed.ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts . According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children .Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.This study provides evidence that early-life pet exposure and low methylation level of  Allergic rhinitis (AR) is a common IgE-mediated disorder involving troublesome symptoms of nasal congestion, nasal itch, sneezing, and associated eye symptoms . AR is aConsidering the dramatic increase in the prevalence of AR , the epiLike many chronic health conditions, AR is complex and stems from complex gene–environment interactions . Recent Considering the established roles of DNA methylation and important effects of the early-life environment on AR development, we conducted a cross-sectional study to explore the association between early-life environment risk factors, methylation of AR susceptibility genes and AR risk in a population of Chinese children.This study was approved by the Ethics Committee of Tongren Hospital Affiliated to Shanghai JiaoTong University, School of Medicine (NO: TR2019.050.01). Written informed consent was obtained from all legal guardians of the participating childrens prior to blood collection. A total of 130 subjects with AR were recruited from the Department of Otorhinolaryngology. The control population included 154 healthy children who underwent a regular physical examination in the same ear, nose and throat (ENT) clinic as the AR patients. Individuals with history of asthma or atopic dermatitis were excluded. All subjects were born in and permanent residents of Shanghai. Genomic DNA extraction was performed on PBMC samples collected and isolated using the QIAamp DNA Blood kit , according to the manufacturer’s instructions. Venous whole-blood eosinophil counts were performed using an XN-9000 .According to the Initiative on Allergic Rhinitis and its Impact on Asthma guidelines, a thorough history including typical AR symptoms, physical examinations and an allergen skin prick test (SPT) was used to establish the diagnosis of AR . SPT wasA questionnaire was answered by mothers of all of the study subjects, and the following variables were recorded: gender, weight, height, history of maternal allergic disease, season of birth , secondhand smoke exposure (yes or no), and pet exposure (yes or no) in the child’s home before their kindergarten life.https://phgkb.cdc.gov/PHGKB/startPagePhenoPedia.action). Genes were ranked according to the number of previously published gene-disease association studies, thus providing a disease-centered view of genes involved in AR [Top twenty-five AR-susceptibility genes were selected using Phenopedia database . The validity and reliability of this method have been previously reported –24. SpecOne gene on X-chromosome and seven genes without CpG islands or failed to be amplified were excluded from the following analysis. In total, 34 amplicons of CpG regions in the promoter of 17 genes were sequenced  curve and area under curve (AUC) were used to evaluate the predictive power or feasibility of the methylation as a biomarker for AR. False discovery rate (FDR) was applied for the multiple test correction. Associations were considered significant when P values were less than 0.05.The data were analyzed using SPSS version 18.0 software . For basic characteristics and potential risk factors, the differences between the groups were measured using the χA total of 130 patients with AR  and 154 controls  were recruited. No statistically significant differences were found between cases and controls in terms of sex, age, weight, and height . Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) significantly increased the risk of developing AR. However, no effects were found on season of birth or exposure to second-hand smoke for AR risk. The demographic details of the sample are given in Table ACE or ADAM33, were differently methylated in AR patients compared to controls    were differently methylated in AR patients compared to controls . Location of each amplicon is shown in Fig. ADAM33 and GSTP1 genes were significantly different between AR patients and controls . The differences were still significant after correcting for multiple testing (P = 0.0483)  analysis was performed on all the CpG sites in ene Fig. . Mean me3) was 372.35 ± 108.02 cells/mL3 in AR patients. Spearman correlation analysis revealed that the hypermethylation of ADAM33 was significantly associated with lower eosinophil count  was not significantly associated with the total eosinophil count    Table .Table 6MADAM33 was significantly lower in the AR group than controls and the difference was still significant after correcting for multiple testing. Furthermore, we showed that pet exposure was related to the higher risk for AR with respect to DNA methylation level in promoter region of ADAM33.The aim of the study was to investigate the relationship among environmental risk factors, the methylation level of AR candidate genes reported from polymorphism association studies and AR risk in a cohort of children aged 3–6 years in China. We found that among the 17 investigated genes, the DNA methylation level of In our study, maternal allergic history was a strong risk factor for AR among a cohort of Chinese children. This result is consistent with that of a previous study involving a cohort of 6 year-old children, reporting that maternal allergic history was associated with higher risk for AR development . The bioGenetic association studies have advanced our understanding of genetic risk factors for allergic diseases. In the latest GWAS of AR, 41 AR-related risk loci have been reported, including 20 loci that had not previously been related to the disease , howeverACE was found as the only CpG site remained significant after correcting for multiple testing in our study. Although methylation level of this CpG site was not significantly associated with the total eosinophil count in the case group, however, methylation of ACE might still play an important role in the development of AR, considering transcription of the mRNA might be regulated by DNA methylation at one specific site in its promoter [One CpG site in the promoter region of promoter .ADAM33 has been extensively reported as a susceptibility gene in bronchial hyperresponsiveness, asthma and AR [ADAM33 is expressed in the smooth muscle, myofibroblasts, and fibroblasts of asthmatic airways, thus the function of this protein might be involved in the airway remodeling [ADAM33 was upregulated during acute or chronic lung inflammation [ADAM33 and allergic airway inflammation, its role in the pathophysiology of AR is still to be clarified.Disintegrin and metalloproteinase 33 (ADAM33), the first asthma-susceptible gene identified by positional cloning, was the only gene identified with significant methylation level differences between the groups at the CpG site level, amplicon level and gene level. Notably, a and AR , 32–34. modeling . Variousammation . Even thAdam33−/− knock out mouse, a recent report has shown substantial interaction between Adam33-mediated airway remodeling and sensitivity to allergen exposure, leading to allergic inflammation and bronchial hyperresponsiveness in early life [ADAM33 and AR risk in terms of the interaction between pet-exposure and ADAM33 gene promoter methylation. The underlying disease mechanism of this effect remains unknown. However, this study suggests that it is important to examine not only the effect of early-life risk factors, but also their interaction with the DNA methylation level of candidate AR genes.The dramatic increase in the prevalence of allergic diseases during the past decades is more likely to be the result of changes in environmental factors, accompanied by epigenetic changes in the human genome. By using rly life . The preADAM33 methylation with AR. Furthermore, the fact that all the children recruited from only one ENT clinic might introduce selection bias into the study. However, we speculate that the relationship between ADAM33 methylation and pet exposure is involved in AR onset. Second, there were several risk factors that could confound the interaction between pet exposure and the DNA methylation levels of ADAM33 in children with AR, including disinfection habits of pet owners, mode of delivery, etc. Furthermore, since RNA quality was not good enough for measuring expression level of ADAM33, further studies are needed to investigate the potential differential expression pattern of ADAM33 in AR. To overcome these limitations, a prospective cohort study with bigger sample size will be conducted in the future.There are several limitations to our study. First, we used a relatively small sample size, hence there could be a possibility of overestimating the significance of the association of ADAM33 methylation level in a cohort of Chinese children. We provide evidence for the important roles of gene-environment interaction in the development of AR.In conclusion, the present findings suggest that early-life pet exposure is related with higher risk of developing AR, interacting with Additional file 1: Table S1. Description of data: twenty-five AR genes retrieved from Phenopedia database and references to the original publication reporting their association to AR.Additional file 2: Table S2. Description of data: Target DNA methylation sequence information.Additional file 3: Figure S1. Description of data: Bisulfite conversion efficiency in PBMC samples from AR patients and controls.Additional file 4: Table S3. Description of data: Different methylation CpG sites between AR patients and healthy controls.Additional file 5: Figure S2. Description of data: Correlation of methylation status of the CpG site at the position of 24 bp of the first amplicon of ACE with eosinophil counts (Spearman’s rank correlation).


Severe burn disrupts cardiovascular function which can lead to critical shock. To counteract cardiovascular collapse, there is a systemic increase of catecholamines released in response to severe burn. Previous studies showed that β1- adrenergic receptor (AR)_ protein expression was significantly increased in the cardiac right ventricles (RV) following burn injury, which is correlated with compromised cardiac dysfunction. Vascular smooth muscle contraction served to modulate blood pressure and improve circulatory perfusion. We hypothesize that ARs expression in major arteries are modified to initiate vascular functional changes following severe burn. In the current study, we report temporal ARs expression in murine carotid artery smooth muscle following severe burn.Thirty-four adult Sprague-Dawley male rats received a 40% total body surface area (TBSA) scald burn followed by fluid resuscitation using the Parkland formula. Control animals received a sham burn procedure. Animals were serially euthanized between 6 hours and 14 days after burn and endothelium-intact common carotid arteries were harvested for histological analysis.Immunohistochemical staining data demonstrated expression of adrenergic receptors (AR)  were differentially changed in response to injury over time. α1a-AR expression significantly increased within the carotid artery tunica media 7-days after burn (p< 0.05). As a negative feedback of inhibitory of norepinephrine signaling, AR-α2a expression did not significantly change. AR-β1 expression also had no change over time after burn. Interestingly, functioning to relax vascular smooth muscle, a significant elevation of β2-AR expression within the carotid artery tunica media was observed only at 1-day after burn (p< 0.05).In summary, immunohistochemistry showed that carotid arterial adrenergic receptor expressions of α1a-AR and β2-AR are significantly altered in response to severe burn, which may contribute to vascular contractility in burn rats.


P < 0.05). When the number of neurons was 23, the prediction accuracy of the test set reached a maximum of 89.83%. Using traingda as the training function, the model had the lowest training time and root mean squared error (RMSE) value of 2.5 s and 0.29, respectively, which were significantly lower than the traingd and traingdm functions (P < 0.01). The error percentage and RMSE of the model reached a minimum of 7.56% and 0.25, respectively, when the transfer functions of both the hidden and input layers were tansig. The prediction accuracy in stages III~VI was 90.63%. It indicated that the mobile medical management system established based on Internet of Things technology and medical data collection has certain application value for the prevention and rehabilitation nursing of stroke patients, which provides a new idea for the diagnosis, treatment, and rehabilitation of stroke patients.This research was aimed at exploring the application value of a mobile medical management system based on Internet of Things technology and medical data collection in stroke disease prevention and rehabilitation nursing. In this study, on the basis of radio frequency identification (RFID) technology, the signals collected by the sensor were filtered by the optimized median filtering algorithm, and a rehabilitation nursing evaluation model was established based on the backpropagation (BP) neural network. The performance of the medical management system was verified in 32 rehabilitation patients with hemiplegia after stroke and 6 healthy medical staff in the rehabilitation medical center of the hospital. The results showed that the mean square error (MSE) and peak signal-to-noise ratio (PSNR) of the median filtering algorithm after optimization were significantly higher than those before optimization ( Cerebral stroke is a common acute cerebrovascular disease, and its clinical manifestations are local neurological deficits . CerebraIn recent years, with the continuous development of computer technology and Internet of Things technology, mobile medical and health service systems are gradually applied to the prevention, diagnosis, treatment, and nursing of diseases and have become a new type of medical and health care model . The IntIn summary, there are few studies on the mobile management system for disease prediction and rehabilitation nursing tracking of cerebral stroke patients. Based on the mobile medical monitoring system and combined with RFID technology, this study studies the tracking and management of the prevention and rehabilitation process of cerebral stroke patients, so as to establish a mobile medical management system for cerebral stroke disease prevention and rehabilitation nursing, and improve the timeliness and efficiency of cerebral stroke disease diagnosis.The remote mobile medical monitoring system for cerebral stroke patients based on Internet of Things is mainly composed of three layers: physiological parameter acquisition node (data access layer), business logic layer, and intelligent mobile Android terminal layer. The data access layer mainly identifies and transmits the basic clinical data of patients through PDA equipment according to the RFID tag carried by patients, including the hospital information system (HIS) such as patients' physiological characteristics and signs. The business logic layer mainly processes and analyzes the data through mobile hospital information system (MobHIS) and network platform. The intelligent mobile Android terminal layer receives, processes, and displays patient disease information. The framework of the mobile medical system based on Internet of Things in this study is illustrated in In this study, the wireless intrusion detection system (WIDS) and wireless network controller (WNC) are mainly used as the medical dedicated wireless network system. WIDS realizes that multiple networks cover a target area at the same time through multifrequency combination and can realize the linear expansion of the wireless network capacity . WNC canIn this study, a mobile monitoring system model of human-computer interaction is established by combining remote communication technology, computer intelligence technology, and rehabilitation nursing methods. Cerebral stroke prevention and rehabilitation mobile monitoring system is mainly composed of two modules: patient clinical data acquisition and remote cerebral stroke rehabilitation nursing. The clinical data acquisition mainly obtains the patient's identification (ID) and clinical information by scanning RFID wristband tags and acceleration sensors; transmits the data to the rehabilitation nursing database through the Internet; preprocesses and identifies the data through the rehabilitation nursing system, such as denoising and normalization; and finally obtains the rehabilitation nursing results. The doctor shall timely feedback the recovery status of patients according to the results of the rehabilitation nursing system. The structure diagram of the cerebral stroke rehabilitation nursing mobile monitoring system is shown in Ax, Ay, Az, and the calculation method of sensor roll angle α and pitch angle β is as follows. The data related to rehabilitation training are collected by binding three-dimensional acceleration sensors to the patient's forearm and upper arm. The collected data are transmitted to the wireless data receiver through the built-in Zigbee wireless transmission module and uploaded to the client software system. It is assumed that the accelerations of the acceleration sensor in three directions are n, it can be expressed as follows. Signals are often disturbed by random noise or Gaussian noise in the process of generation and transmission. The commonly used signal filtering methods include linear filtering and nonlinear filtering . Linear fi−n, fi−n+1, ⋯, fi+n represents the result sequence of one-dimensional odd window. The two-dimensional median filter slides in the image in order, and its calculation method is as follows. med represents the extraction median function and xij is the pixel value of the input area for the window, and yij represents the intermediate value after sorting the pixel values in the window area. The median filter input signals are Gaussian distributed, and the approximate noise variance can be expressed as follows. n′ is the noise mean, χi2 represents the input noise variance, n represents the filter window length, and g2(n′) represents the noise density function.The output noise distribution of the median filter has a certain correlation with the input noise model and the probability density distribution . The freA represents the frequency response of median filter system, and C and F represent the spectrum of input signal and output signal.N, i, j, A) function is introduced to optimize it. It is assumed that the pixel position before filtering is ; the row vector of the filtered pixel position template matrix can be expressed as follows:For the check noise processing in the data, pixelmedianfiler, variance, and energy characteristics. The calculation method is as follows. N is the sequence length, δ is the mean, and Bi is the signal Fourier transform amplitude.RMS is the root mean square, Var is the variance, En is the energy characteristic, Mean square error (MSE), root mean square error (RMSE), and peak signal-to-noise ratio (PSNR) were used to evaluate the filtered data. The MSE, RMSE, and PSNR were calculated as follows. j) is the pixel position, m is the number of measurements, X is the measured value, Y is the true value, L is the peak signal, and MSE is the MSE of the image., the calculation method of the network weight matrix W1 between the input layer and the hidden layer neurons and the network weight matrix W2 between the hidden layer and the output layer neurons are as follows. The back propagation (BP) neural network learns a certain number of sample pairs. After the hidden layer and output layer are calculated, the predicted values of each neuron output in the output layer are calculated. Through the back propagation error, the error between the network, output, and expected output is gradually reduced . For theσ1 of the hidden layer neuron and the threshold σ2 of the output layer neuron can be expressed as follows. The threshold Oj of the hidden layer neuron and the output Zk of the output layer neuron are expressed as follows. The output f represents the transfer function of the hidden layer, and g is the transfer function of the output layer.The error between network output and expected output of the BP neural network can be expressed as follows. The number of hidden layer neurons has a significant impact on the performance of the BP neural network. The number of hidden layer neurons can be calculated by empirical equation. a and b are the number of neurons in the input layer and the output layer, respectively, and c is the constants within 10.The database and its application system are the core and foundation of the database design of the mobile monitoring system. The design of the database needs to meet the principles of integrity, small number, small number of fields, and high efficiency . Storage1The test system running the platform environment is as follows: computer operating system Windows 10 flagship version 64-bit operating system, server-side scripting language PHP 5.3.5, relational database management system MySQL 5.5.8, and web server software Apache 2.2.17. The development environment is as follows: project development compiler EclipsePHP studio3, data management library PhpMyAdmin3.39, and Javascript and Ajax are used as code programming tools.The rehabilitation of cerebral stroke patients was evaluated by the Brunnstrom staging method. According to the results of Wang et al. , the mot32 hemiplegic rehabilitation patients after cerebral stroke and 6 healthy medical staff from the hospital from December 2019 to March 2021 were selected as the research objects. The motion quality was evaluated according to the acceleration physical characteristics collected in the process of the rehabilitation nursing exercise. Most of the cerebral stroke patients were in Brunnstrom stages II-V, and the 6 medical staff were in the stage VI rehabilitation group. Patients with severe cognitive or communication disorders were excluded. 75% of the data were randomly selected from Brunnstrom cerebral stroke patients at different stages as the training set and the remaining 25% as the test set.The rehabilitation nursing method refers to the method of Ikbali et al.  to carryt-test was used. The counting data was expressed by percentage (%). P < 0.05 indicated that the difference was statistically significant.The test data were processed by SPSS19.0 statistical software. The measurement data were expressed by mean ± standard deviation (P < 0.001) (P < 0.05)  function in the optimization algorithm, which can filter all noise points at one time, but also well preserve the image details and enhance the noise reduction effect of the median filtering algorithm.The signal processing results before and after the optimization of the median filtering algorithm are compared and analyzed. With the increase of noise intensity, the mean square error (MSE) of the signal showed a significant upward trend. When the noise intensity was 5%, 10%, 20%, 40%, and 60%, the MSE values of the optimized median filtering algorithm were 54.17 ± 4.52, 103.52 ± 8.63, 215.42 ± 17.95, 1302.17 ± 108.51, and 4865.22 ± 455.26, respectively, and the MSE values of the median filtering algorithm before optimization were 2.17 ± 0.34, 15.41 ± 1.48, 21.52 ± 1.99, 52.42 ± 4.87, and 116.92 ± 8.63, respectively. At different noise intensities, the MSE values of the median filtering algorithm after optimization were significantly inferior than those before optimization, and there was a highly significant difference between the two (< 0.001) . The pea < 0.05) . It suggX, Y, and Z axes were significantly reduced  values of the model under different numbers of neurons in the hidden layer were analyzed . With thP < 0.01). The training steps of the traingda training function were significantly different from those of traingd and traingdm functions (P < 0.001), so traingda was selected as the training function.At present, the training functions for the BP neural network algorithm mainly include the traingd function of the gradient descent algorithm, traingdm function of the momentum backpropagation gradient descent, and traingda function of the dynamic adaptive learning rate . In thisThe transfer function has a significant influence on the prediction accuracy of the neural network. At present, the commonly used node transfer functions are logsig, tansig, and purelin functions . The errThe Brunnstrom staging results of the subjects included in the study were compared with the prediction results of the mobile monitoring system . In 32 sIn this study, a mobile medical management system for stroke prevention and rehabilitation care was established based on Internet of Things technology and medical data collection, and the results revealed that the system was feasible. However, there are still some shortcomings: the number of cases is small and the amount of collected data is insufficient, so the number of cases will be increased in the future work to further evaluate the rehabilitation nursing model and management system. In conclusion, the rehabilitation nursing mobile medical management system established based on Internet of Things technology and medical data collection has certain application value for the prevention and rehabilitation nursing of stroke patients, which provides a new idea for the diagnosis, treatment, and rehabilitation of stroke patients.


Background: While several publications have focused on the intuitive role of augmented reality (AR) and virtual reality (VR) in neurosurgical planning, the aim of this review was to explore other avenues, where these technologies have significant utility and applicability. Methods: This review was conducted by searching PubMed, PubMed Central, Google Scholar, the Scopus database, the Web of Science Core Collection database, and the SciELO citation index, from 1989–2021. An example of a search strategy used in PubMed Central is: “Virtual reality” [All Fields] AND  OR “neurosurgical procedures” [All Fields] OR “neurosurgery” [All Fields] OR “neurosurgery” [MeSH Terms]). Using this search strategy, we identified 487 (PubMed), 1097 , and 275 citations (Web of Science Core Collection database). Results: Articles were found and reviewed showing numerous applications of VR/AR in neurosurgery. These applications included their utility as a supplement and augment for neuronavigation in the fields of diagnosis for complex vascular interventions, spine deformity correction, resident training, procedural practice, pain management, and rehabilitation of neurosurgical patients. These technologies have also shown promise in other area of neurosurgery, such as consent taking, training of ancillary personnel, and improving patient comfort during procedures, as well as a tool for training neurosurgeons in other advancements in the field, such as robotic neurosurgery. Conclusions: We present the first review of the immense possibilities of VR in neurosurgery, beyond merely planning for surgical procedures. The importance of VR and AR, especially in “social distancing” in neurosurgery training, for economically disadvantaged sections, for prevention of medicolegal claims and in pain management and rehabilitation, is promising and warrants further research. Virtual reality (VR) and augmented reality (AR) have intuitively found utility in neurosurgical planning, considered the increasing availability of papers available on this subject. However, the utility of VR and AR beyond neurosurgical planning remains unexplored and, therefore, opens avenues to expand their applicability. We intend to provide an overview of this vast expanse, beyond mere neurosurgical planning.VR involves the user being placed in a system that occludes the natural world and generates a virtual world that the user can experience. Depending on whether the virtual world is designed as a virtual environment or convincing substitute for the real world, VR is further classified as non-immersive and immersive, respectively . AR diffThough the present review is not intended to be a systematic review of the literature, we systematically conducted our search to remove redundancy and be more comprehensive in our narrative review. Systematic review for VR in neurosurgery, beyond planning, is not feasible, owing to limited homogenous studies. The lack of sufficient studies exemplifies the infancy of this aspect of VR and AR to conduct a systematic review. To construct this narrative review, we searched PubMed, PubMed Central, Google Scholar, the Scopus database, the Web of Science Core Collection database, and the SciELO citation index, from 1989–2021. Two authors (RM and HD) independently reviewed the retrieved studies, with title and abstract for further detailed review. An example of search strategy used in PubMed Central is as: “Virtual reality” [All Fields] AND  OR “neurosurgical procedures” [All Fields] OR “neurosurgery” [All Fields] OR “neurosurgery” [MeSH Terms]). The search was started on 1 November 2020 and finished on 25 August 2021. Title and abstract were screened to identify articles providing discussion on the utility of VR, in addition to neurosurgical planning. Only articles in the English language were included. The full text of the articles was retrieved and reviewed from the eligible list to identify their inclusion to synthesize this review. In addition, the bibliography of the included articles was screened to identify other potentially eligible articles. We have excluded studies on neurosurgery planning and focused on studies exploring the use of VR in other scenarios in neurosurgery.Using the search strategy, we identified 487 (PubMed), 1097 , 275 citations (Web of Science Core Collection database). This review is based on 95 references ,93,94,95Though VR was in use for panoramic viewing in the early eighteenth century, the first VR simulator was a flight simulator, invented in 1929, and the term “Virtual reality” was coined in 1987 . The evoThroughout the literature, VR has been used interchangeably to denote VR, AR, and even mixed reality (MR). However, VR, AR, and MR are fundamentally different technologies. VR refers to computed generated three-dimensional (3D) immersive environments, AR refers to the projection of computer-generated images onto real-world images, and MR refers to the projection of virtual objects into the real world, where the objects are spatially aware and responsive . DisadvaAR and VR facilitate navigation during complex and otherwise difficult neurosurgical interventions, in addition to their other potential functions . Two decCerebrovascular surgery and neuro-interventional surgery rely heavily upon advanced neuroimaging techniques for operative decision-making and prognostication . ClinicaAnother example of the clinical application of VR in diagnostics is to compare preoperative imaging with postoperative imaging, in order to identify junctional kyphosis in adult spinal deformity correction and eliminate its confounding effects on the sagittal alignment after the deformity correction procedure . Taken tA detailed roadmap of neuroanatomy confers a higher degree of confidence and success in neurosurgical procedures . This guResearch and technical developments in spinal surgery exceed other surgical specialties with advancements in navigation, endoscopy, and the advent of robotic spinal surgery. However, the development of AR, VR, and MR in spine and orthopedic surgery is similar to brain surgery, in terms of cost-effectiveness, levels of recommendations, evidence, and lack of standardized measures. Common spinal procedures, for which simulation-based training is currently used, in order of frequency, are pedicle screw insertion, vertebroplasty, posterior cervical laminectomy, and foraminotomy ,23,24. LIn pain management, VR has initially been studied to treat trigeminal rhizotomy. Specifically, VR-assisted percutaneous radiofrequency trigeminal rhizotomy has shown safety and efficacy in studies and stresses the utility of virtual 3D CT scans in assessing the position and depth of the needle ,58,61. VVR has been used in several novel ways, from creating a virtual environment to allow the patient to train in to the establishment of telerehabilitation services, in order to allow patients (who are understandably hard-pressed to travel) to pursue rehabilitation services at home, while their therapist can monitor progress from a different location ,67,69,71The advantages conferred by VR stem from the ability to gradually increase the complexity of tasks, facilitate simultaneous audio, visual, motor, and cognitive rehabilitation remain engaging and entertaining and offer positive, reward-based feedback, which are of paramount importance in preventing patient frustration and dropouts. Additionally, future strategies would be to make VR-based rehabilitation more universally accessible to promote patient compliance. When considering patients with long-term rehabilitative needs, VR and AR would be more economically viable, thereby alleviating the financial burden of an already distressed portion of society. In a seminal article, Weiss et al.  poignantThe neuroArm leads this movement as an image-guided teleoperated neurosurgical robot . As withAn exciting vision of the future of robotics integrated with AR was presented by Madhavan et al. , where ap < 0.001) [Informed consent (IC) is defined as “the communication process between a patient and physician that results in the patient’s authorization or agreement to undergo a specific medical intervention”. Neurosurgery is a high-risk specialty, with the highest rates of legal claims among all other specialties . In a re< 0.001) . AlthougVR has been utilized for training non-technical skills, such as communication, teamwork, and situational awareness in health care professionals . ExtrapoSignificant technical hurdles faced during awake surgery, such as mapping of the optic radiation, have also been overcome with the utility of VR .Finally, VR has also been used to improve patient compliance and comfort. Studies have shown the utility of VR in preparing patients for MRI examinations and VR headsets are commonly used to prevent the intense discomfort faced by patients while undergoing the MRI ,68. ThesVR has faced challenges, predominantly due to the technical complexities in designing clinically valuable and relevant models. The main issues that have halted the monumental rise of VR in neurosurgery include, but are not limited to, feasibility in application and transference to real-life scenarios, ethics in supplementing with standard practices, and cost-effectiveness analyses. One of the critical drawbacks of VR application in neurosurgery, beyond presurgical planning, is the learning curve associated with it, when used to augment surgical procedures; this is much more significantly evident with the advancement of robotic neurosurgery ,86. ThisThe evaluation of neurosurgical performance, in which VR is used, is a newborn field of interest. This review has the feature of showing the different fields in which AR and VR are used in neurosurgery, as well as their possible implications in the next future. However, it has the limitations that, in order to limit the broad topic dealt and not disperse the information gathered in this review, tractography and white matter integrity in neuronavigation were not discussed.VR and AR show benefits in preoperative planning and multimodal neuronavigation for spine and brain surgery. In addition, the included studies suggested that VR and AR have beneficial effects for medical education and neurosurgical training. This paper reported the immense possibilities of VR in neurosurgery, beyond merely planning for surgical procedures. To generate relevant evidence in the next future, we need to rigorously evaluate AR and VR implementations, in order to better understand the strengths and limitations of HMD and other tools used during surgery, as well as in all fields of neurosurgery. The importance of VR and AR, especially in “social distancing”, in neurosurgery training for economically disadvantaged sections, prevention of medicolegal claims, and pain management and rehabilitation is promising and warrants further research.


COVID-19 is a recent major event, adding to planet Earth’s contexts of chaos, crime, injustice, illness, and violence. The HeartMath system has produced research evidence for scientific interventions that alter contexts characterized by chaos and stress, promoting health, coherence, and interconnectedness. This study provides an updated overview of HeartMath as an interdisciplinary, scientific, coherent, integral heart-based healthcare system, operated locally through various initiatives and globally through the Global Coherence Initiative. The HeartMath approach integrates ancient and contemporary, indigenous and mainstream, popular and folk, Eastern, Western, and African forms of healing. The HeartMath interdisciplinary, personal, social, and global vision and mission have considerable theoretical and practical potential for promoting planetary health, education, and development. COVID-19 is only one recent example of a factor influencing planet Earth’s contexts of chaos, incoherence, illness, and violence. In addition, endemic struggles for survival and subsistence stresses consume human energy, distort consciousness, and exacerbate inhumanity and disorder. All of this occurs within a planet in desperate need of healing. The compound word healthcare combines the quintessentially human notion of care with that of healing, in all its meanings: making whole, transferring from illness to health, and various forms of illness prevention and health promotion. At quantum information level, healthcare translates into dynamic human, social, and environmental energy patterns . At a glThe HeartMath system has revealed various coherent, interconnected energetic patterns within and between human persons and populations . As a coThe HeartMath system was specifically created and developed by Doc Childre, a stress researcher who gathered an expert, interdisciplinary, multi-professional research team to reduce stress through the study and development of heart intelligence ,3. The sAn overview follows of HeartMath as a scientific, coherent, integral heart-based, healthcare system that postulates and promotes planetary interconnectedness ,11,12,13This article was specifically motivated by the theoretical considerations and considerable evidence-based studies available in the HeartMath research library as to the scientific foundations and effectiveness of the HeartMath Institute in promoting coherent personal, social, and global healthcare. It is intended as an updated overview for instructional purposes.From a transcultural perspective, the heart has received perennial recognition as the font of sentience, awareness, and consciousness; it is considered to be the center of the spiritual, intellectual, and emotional life. Various scientific disciplines provide evidence  that heaThe integral heart appears to have dimensions of increasing depth: physical, emotional, transpersonal, and transcultural . For exaFor millennia, the major great wisdom traditions, including Islam, Christianity, Buddhism, Hinduism, Taoism, and ancestral reverence ,24,25, hImproved healthcare innovations concerning coherent, heartfelt intentions and actions are in short supply. HeartMath is an interdisciplinary approach that bridges the natural, human, social, spiritual, and ecological sciences in its focus on heart-based research . CoherenHealthcare research findings from over 8000 researchers are freely downloadable from the research library 8000 compiled by HeartMath researchers. Over 400 additional studies undertaken by independent researchers have provided extensive external validity for the effectiveness of the HeartMath system, its methods, tools, and techniques. This is to be expected, as findings are generally based on evidence related to: 1. Physics; 2. Electromagnetics; 3. Cardiorespiratory activity, especially related to communication networks involving the vagus nerve; 4. The natural mechanism of respiratory sinus arrhythmia (RSA), whereby heart rate increases during inhalation and decreases during exhalation; 5. Coherent and incoherent heart rhythms, associated with positive and negative emotion, respectively; 6. Correlated heart rhythm mathematics; 7. Biofeedback conditioning principles and practices.Pribram’s  holonomiTheoretically, the HeartMath coherence model includes all the usual meanings of the term coherence, as implied in such terms as relationship, harmony, order, stability, consistency, synchrony, logic, and by the idea of the whole being more than the sum of its parts . In acadFrom a psychophysiological perspective, coherence interconnects positive emotions with the cardiovascular, respiratory, immune, and nervous systems . From a Various HRV-related psychophysiological theories resonate with the HeartMath coherence model. Resonance theory is founded on heart rate variability biofeedback (HRVB) studies, which indicate that optimal heart rate oscillations occur via paced respiration at a frequency of about 0.1 Hz. Polyvagal theory, which hypothesizes social evolutionary mechanisms, advocates RSA and enhanced HRV for improved health and well-being. The neurovisceral integration model postulates a central autonomic network (CAN) related to social, cognitive, affective, and physiological regulation .Psychophysiological studies indicate that bidirectional heart–brain communication has been recognized for over a century . The heaSocial coherence refers to harmonious relationships that facilitate efficient energy communication, cohesion, and action . Effectiwww.Heartmath.org and www.glcoherence.org (accessed on 4 April 2021). These websites also contain information on various online courses, for example, courses for any individual needing HeartMath Coach/Mentor training.Ample evidence indicates that the Earth’s magnetic field generates and facilitates an interconnecting global information network ,33,34. Gfilesusr.com accessed on 4 April 2021) and Steps for Moving Psychoenergetics Science Research Into the Hands of Interested General Public Researchers (filesusr.com accessed on 4 April 2021)], Stanford University Emeritus Professor William Tiller has initiated the Global Intention project through which concerned individuals the world over can create focused intention to improve our world. An example of this is the use of the intention suggested on the Global Intention|The Tiller Foundation website for healing the world from the effects of the COVID-19 virus. While in a meditative (coherent) state, participants create a positive intention that is “broadcast” worldwide.In a similar initiative, based upon his work researching the measurable effects of human intention [Steps for Moving Psychoenergetics Science Research Into the Hands of Interested General Public Researchers  tools are freely available at: https://www.heartmath.org/resources/downloads/12-heartmath-tools/, accessed on 4 April 2021.Biofeedback instruments that have been scientifically developed to provide heart rate variability and heart rhythm coherence include:The emWave2, which gives readings of and feedback on heart rate, heart rate variability, and physiological coherence. The instrument can be handheld for field use.The emWave Pro is a sophisticated coherence biofeedback program for use by professional specialists in education, psychology, medicine, etc.The Inner Balance Application (app) for personal coherence training is available to iPhone or smartphone users who download HeartMath programs from the internet.The Global Coherence (GC) app records mean coherence levels at individual, group and global levels. The app is freely downloadable from the internet. A HeartMath Pulse sensor provides biofeedback.https://www.hearthmath.org/, accessed on 4 April 2021. The website and annual report provide further practical healthcare information. For example, it lists programs, including Add Heart and Children’s Heart Smarts and the 100,000 Coherent Kids Initiative, active in 93 countries. Since its inception, the HeartMath Institute has facilitated links with other health, educational, and research institutions. These established linkages are combined with the interdisciplinary originality and operational autonomy to lead to ground-breaking research in interdisciplinary fields such as biofield physiology and vibroengineering, which have impressed with their robust, scientific grounding [The HeartMath website can be found at rounding .As concerns in-depth personal healthcare, the Heart Lock-In is one of the earliest HeartMath techniques developed. In a recently published study, 104 participants from five countries completed 15 days of ambulatory HRV monitoring. Analysis of participants HRV before, during, and after a Heart Lock-In meditation period indicated significantly increased coherence, as well as correlation with magnetic field activity on the day of the meditation .This study may be regarded as cutting-edge quantitative scientific evidence for the claims of many earlier mass meditation studies to decrease violence and facilitate moral consciousness and behaviour, creativity, and health promotion . From a “Beyond the unique nature of each event, with their individual integrity and superficial differences, the essential structure of the coherence experience initially appears as some variation on the conscious practise of the cardiorespiratory, rhythmic process of breath connecting heart beats, warming and softening the heart, heralding a sense of stillness, alignment, harmony and peace, as scattered energy is felt to collect in the heart area, bringing deepening heart awareness and, typically, at some point a sense of “lift off” to unlimited self or space. This gathering energy seems to be distributed throughout the body and beyond, resonating with increasing subtlety and/or refinement into a higher, vibrational level typically experienced as love, accompanied by finer feelings of centeredness, wholeness, oneness and interconnectedness. Unique, individual experiences vary. They may be concrete, abstract, diffuse, definite, ordinary, mixed, mystical and/or paradoxical, of, for example, homecoming, unboundedness, spaciousness, timelessness, emptiness, freedom, happiness, bliss, joy and infinite creativity. Experiences typically have local, social or global action implications, insights, intuitions and moral directions, as, for example, for “making the world a better place” through writing, healing and teaching”.From this qualitative experiential perspective, it is instructive to note the great wisdom traditions of Judaism, Christianity, and Islam view the heart as the principal organ of spiritual perception. The great healing value of the Prayer of the Heart is commonly extolled by Christian and Sufi mystics ,48. HearThe HeartMath Institute formally reviews its activities in the form of annual reports. A variety of these activities regularly feature in update formal reviews by independent researchers, more of which are needed ,50. The The present study has provided an overview of HeartMath as a coherent, integral heart-based healthcare system. Various forms of evidence have been presented to support this contention. There does not appear to be any contradictory evidence to this effect, although further gold-standard, empirically orientated, randomized controlled trials are needed . Future