Metastatic prostate cancer is incurable and lethal. Tumor growth is initially reduced by radiation, surgery, or hormone therapy and later, by pairing them with chemotherapy for advanced cancer. Recent innovations have helped to develop prescription drugs against certain prostate cancer types, showing gene alterations that prevent the repair of damaged DNA or activate the body’s anti-cancer natural immune defense. A panel of genes has been identified whose cancer genome alterations may predict whether non-metastatic prostate cancer would go on to metastasize. The activity of these genes may help to guide treatment decision for non-metastatic cancer with the choice for non-aggressive versus debilitating aggressive options. The probing of prostate cancer genome has uncovered hormonal abnormalities and genome changes specific to individual patients and studies are revealing how these changes can lead to treatment failure. The discovery of new druggable vulnerabilities of the cancer cells has presented opportunities to develop precision treatments of metastatic prostate cancer tailored to individual patients.AR upregulation and discuss AR-degrading molecules as promising anti-AR therapeutics. New biomarkers and druggable targets are shaping innovative intervention strategies against high-risk localized and metastatic PCa, including AR-independent small cell-neuroendocrine carcinoma, while presenting individualized treatment opportunities through improved design and precision targeting.Organ-confined prostate cancer of low-grade histopathology is managed with radiation, surgery, active surveillance, or watchful waiting and exhibits a 5-year overall survival (OS) of 95%, while metastatic prostate cancer (PCa) is incurable, holding a 5-year OS of 30%. Treatment options for advanced PCa—metastatic and non-metastatic—include hormone therapy that inactivates androgen receptor (AR) signaling, chemotherapy and genome-targeted therapy entailing synthetic lethality of tumor cells exhibiting aberrant DNA damage response, and immune checkpoint inhibition (ICI), which suppresses tumors with genomic microsatellite instability and/or deficient mismatch repair. Cancer genome sequencing uncovered novel somatic and germline mutations, while mechanistic studies are revealing their pathological consequences. A microRNA has shown biomarker potential for stratifying patients who may benefit from angiogenesis inhibition prior to ICI. A 22-gene expression signature may select high-risk localized PCa, which would not additionally benefit from post-radiation hormone therapy. We present an up-to-date review of the molecular and therapeutic aspects of PCa, highlight genomic alterations leading to  As the second most common male cancer worldwide, next only to lung cancer, prostate cancer affects roughly 1.3 million people and kills more than 360,000 people annually. In the U.S.A., the year 2020 saw nearly 192,000 new cases of prostate cancer (PCa) along with around 33,000 deaths [In 1941, Charles Huggins discovered revolutionary aspects of PCa by demonstrating reduced cancer progression for the metastatic disease via androgen deprivation therapy (ADT) in the form of surgical castration. The Huggins discovery pioneered PCa management employing ADT and additional forms of hormone therapy, while also paving the way for a multitude of modern-day therapeutics . AndrogeAndrogen precursors in the form of androstenedione and dehydroepiandrosterone are secreted into circulation following biosynthesis in the adrenal glands. Adrenal androgens are converted to testosterone intratumorally in the prostate via multiple enzymatic steps, and 5α-dihydrotestosterone (DHT) is the reduced metabolite of testosterone, generated by the catalytic action of 5α-reductase. DHT and testosterone are high-affinity AR ligands. Cytosolic AR, when bound to androgens at the ligand-binding domain (LBD) of the receptor, dissociates from multiple AR-interacting proteins, including heat shock proteins hsp90 and hsp70, undergoes a conformational change that exposes a nuclear localization signal and facilitates transport of the androgen/AR complex to the nucleus . ChromatAR gene amplification. Continued AR activity also occurs due to AR mutants with ligand affinity for steroids beyond androgens; AR splice variants (AR-Vs) lacking LBD; and altered AR coregulator(s) abundance/activity. Hormone therapy, chemotherapy, and emerging genome targeted therapy are principal treatments for metastatic castration-resistant prostate cancer (mCRPC). Genome alterations impacting non-AR pathways can also lead to late-stage, treatment-resistant prostate cancer.AR activity is upregulated in advanced PCa, principally from increased AR expression due to Recent insights into genome alterations in prostate cancer that impact signaling pathways beyond the androgen receptor axis, subtypes of early stage and advanced PCa, and the dynamics of tumor-promoting and tumor-suppressive effects of immune cells are revealing new approaches to disease intervention. A generally immunosuppressive tumor microenvironment makes most prostate cancer cases unresponsive to current immunotherapy except for genome instability in two contexts. New laboratory results are suggesting that the reach of immunotherapy for advanced PCa management may be extended by targeting selected pro-tumorigenic pathways in combination therapy. This review is a synthesis of key findings on genetic, epigenetic, and molecular changes impacting PCa aggressiveness and elaborates how the information has contributed to innovations in treatment strategies and has led to genome-targeted precision medicine and cancer immunotherapy. Finally, a future scenario built on current research is presented when routine personalized treatment decision for high-risk non-metastatic and advanced metastatic prostate cancer would be a reality.The risks of localized prostate cancer for recurrence and metastasis are determined from the Gleason score, tumor stage and size, and blood PSA levels. Treatment options for localized PCa deemed low-to-moderate risk entail active surveillance, radical prostatectomy (RP) by surgery, and radiation therapy (RT) with external beam radiation or brachytherapy, while watchful waiting  is the norm for very low-risk cases . IndividFor histologically progressed non-metastatic PCa that is castration sensitive, a multimodal treatment design entailing ADT with or without RP and/or RT or combined with an AR inhibitor offers the greatest potential for improved long-term outcomes for patients who may harbor occult metastatic disease ,10. ADT The development of non-metastatic CRPC is evidenced by rapidly rising blood PSA despite ADT. Disease progression in this case can be delayed by AR axis targeted therapy (ARAT) with a second-generation AR antagonist  ,15. In aAndrogen sensitive metastatic PCa is managed by ADT monotherapy or with RT or RP. The disease invariably progresses on ADT to develop into metastatic castration resistant prostate cancer (mCRPC), when ADT together with ARAT, which employs an AR antagonist or an androgen biosynthesis inhibitor that prevents intratumoral steroidogenesis, is temporarily successful as a first line treatment. ADT plus chemotherapy (with docetaxel) is another widely used first line option. Immunotherapy using immune checkpoint inhibitors and therapy that targets the DNA repair enzyme PARP (poly (ADP-ribose) polymerase) are more recent additions to the medical armamentarium as a second line treatment against mCRPC. Common treatment practices for prostate cancer at different stages are summarized in Treatment choices for high-risk, localized PCa and advanced PCa, which has metastasized, are expected to grow in the future due to the discovery of new druggable targets, many of which are under clinical evaluation. The underlying molecular and biochemical principles for each therapy shown in AR and its enhancer regions [Hormone therapy in prostate cancer implies the inhibition of androgen action in cancer cells by the systemic ablation of androgens through castration , or by ARAT, which entails either inactivation of the AR due to its binding to an antagonist or suppression of intratumoral androgen biosynthesis by inactivating CYP17A1, a cytochrome P450 enzyme that catalyzes a rate limiting step in the steroidogenic pathway to testosterone and DHT production. Hormone therapy reduces cancer spread, prolongs life and controls disease-associated symptoms, such as skeletal related events. CRPC inhibition by ARAT is, however, short-lived, effective for about 4 to 5 months. Enhanced AR signaling in CRPC due to increases in AR expression and de novo androgen production leads to CRPC progression on hormone therapy. Treatment-induced stress may in part account for the upregulation of hormonal signaling in the ARAT setting. Elevated CYP17A1 in CRPC has been reported [ regions ,20,21,22AR antagonists, upon binding to AR’s LBD, promote corepressor recruitment to DNA-bound AR, which in turn triggers regulatory events that lead to androgen action suppression and tumor growth reduction . EnzalutAbiraterone acetate  is a steroidal CYP17A1 inhibitor approved for blocking the adrenal production of androgen precursors, which lowers de novo androgen synthesis in tumor tissue. Prednisone co-administered with abiraterone acetate prevents corticosteroid deficiency. ADT paired with abiraterone-prednisone is approved for metastatic castration-resistant prostate cancer (mCRPC). A phase III trial (STAMPEDE) on non-metastatic castration-sensitive prostate cancer has shown superior patient outcomes with ADT plus abiraterone acetate/prednisone compared to stand-alone ADT . In a phOngoing studies are focusing on mechanisms of ARAT resistance, predictive biomarkers for resistance, and AR pathway independent targets toward the goal of new and improved treatments for high-risk non-metastatic PCa and advanced PCa that has progressed on ARAT. AR ablation as a next-generation therapy  and denosumab , which is a human monoclonal antibody against the RANK ligand (RANKL), are FDA approved for managing adverse skeletal events from bone metastasis . BisphosRecombinant interleukin-24 (IL24) is potentially a novel therapeutic for preventing bone metastasis since IL24 suppressed colonization of CRPC cells to bone in a mouse prostate cancer metastasis model . IL24-di177Lu-PSMA-617 is one such payload where the radioactive lutetium-177 is coupled to a ligand that binds PSMA with high selectivity and delivers radiation to PSMA-expressing cells. The outcome of 177Lu-PSMA-617 radioligand therapy (RLT) combined with the standard of care was compared with the standard of care alone in a phase III trial when inclusion of RLT improved OS and progression-free survival (PFS) [177Lu-PSMA-617 positively correlated to AR amplification detected in circulating DNAs [225Ac, an alpha particle emitter, is 1000-fold more potently radioactive than 177Lu, which emits beta particles.Prostate specific membrane antigen (PSMA) is a cell surface protein expressed in PCa cells, not in normal prostate cells. PSMA is targeted for the delivery of a radioactive payload to metastasized PCa cells. al (PFS) . AR stating DNAs . In addiing DNAs . 225Ac, In contrast to PSMA-targeting radioactive agents, which destroy PCa cells anywhere in the body, radium-223 dichloride , an injectable radionuclide, is approved for targeting bone metastasis of ADT-resistant PCa . Radium-BRCA2, BRCA1, which regulate homologous recombination repair (HRR) of DNA double strand breaks (DSBs). Cases of mCRPC with alterations in other HRR pathway genes, such as ATM, RAD51, MRE11, ATR, CHK2, MMR, MSH and CDK12, are also known. Cancer genome exome sequencing identified somatically altered HRR genes in roughly 23% of mCRPC cases and germline events in 8% of cases [The exploitation of the DNA repair gene mutation by targeting PARP (poly (ADP-ribose) polymerase) is an example of genome-targeted precision medicine. PARP inhibition therapy is approved for mCRPC with inactivating mutations of of cases ,39. Evenof cases .PARP inhibition is synthetically lethal for HRR-mutant cells due to the buildup of DNA DSBs leading to stalled DNA replication forks. DSBs accumulate due to unrepaired single strand breaks (SSBs). It was initially thought that, without ADP-ribosylation, XRCC1 (a DNA repair enzyme) cannot be recruited to SSBs, which then prevents activation of base excision repair (BER), causing the failed repair of DNA SSBs. A more likely model based on additional results is that the inhibitor-bound PARP is trapped onto SSB repair intermediates, especially during BER, leading to DNA DSBs. Unresolved DSBs lead to replication block and cell death. Thus, PARP inhibition induces synthetic lethality in HRR-mutant cells . PARP maBRCA2 or BRCA1 genotype [BRCA1/BRCA2 mutation.Two oral PARP inhibitors—Olaparib and Rucaparib—which inactivate PARP1 and other PARP family members, are approved, as of May 2020, for clinical targeting of mCRPCs harboring a mutant genotype . The inhgenotype . TalazopThe functional interplay of PARP with AR has been demonstrated. For example, PARP-1 is recruited to AR-occupied genomic sites in PCa cells ; PARP-2,Two FDA-approved immunotherapy options for mCRPC are the vaccine Sipuleucel-T  and the immune checkpoint inhibitor Pembrolizumab . Sipuleucel-T, approved in 2010 for mildly symptomatic mCRPC, is an autologous cellular immunotherapy entailing incubation of patient-derived dendritic cells, isolated from peripheral blood mononuclear cells, with the vaccine immunogen PA2024 and re-administering the immunogen/dendritic cell complex to patients . PA2024 Immune checkpoint inhibitors (ICIs) are approved against mCRPC and other solid tumor metastases that harbor genome alterations leading to high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) ,51. ICI Another target for immune checkpoint suppression is CTLA-4 (cytotoxic T-lymphocyte antigen-4), which is a cell surface protein of CD8+T cells. Normally, immune blockade results from the inactivation of cytotoxic CD8+T cells following CTLA-4 binding to B7-1/B7-2 cell surface proteins that are expressed in APCs. Ipilimumab  is a monoclonal antibody to CTLA-4 that disrupts the interaction between B7 and CTLA-4. T-cell receptors’ recognition of exposed antigens and major histocompatibility complex proteins on APCs and the binding of CD28 to B7-1/B7-2 lead to T-cell activation and tumor cell killing. Ipilimumab plus Nivolumab (anti-PD-1 antibody) reduced mCRPC progression in a phase II study .CDK12 inactivation, identified so far in a limited number of mCRPC cases, may also present an opportunity for immune checkpoint blockade [Somatic biallelic blockade . CDK12 iblockade ,58.Prostate tumor is generally adept at immune evasion except when the cancer genome alterations lead to MSI-H or dMMR, as mentioned above. For a subgroup of patients, response to immunotherapy may be augmented by reducing neoangiogenesis, a hallmark of cancer progression. For example, anti-CTLA-4, anti-PD1 and other immune checkpoint inhibition therapies lead to elevated interferon-gamma (IFNγ) in the tumor microenvironment because of increased IFNγ expression in immune cells ,60. IFNγA sequential treatment modality as above may suppress PCa with high VEGFR2 and low miR-221 since sunitinib-treated PC3 prostate cancer cells showed increased miR-221 expression, which is likely an escape response to VEGFR2 inhibition given that sunitinib-mediated cell proliferation blockade was prevented by ectopic overexpression of miR-221 . The uprCurrent practices for managing prostate cancer are guided by the stage of malignancy, the nature of cancer genome alterations and the response of progressively advanced cancer to chemo-hormonal interventions. While low-to-moderate risk cancer is kept under active surveillance or subjected to surgery and/or radiation, a more aggressive intervention is needed for high-risk localized disease. ADT is the foundational hormone therapy and at biochemical recurrence, an AR antagonist or abiraterone acetate (plus prednisone), which inhibits intratumoral androgen biosynthesis, is added to ADT. ADT/anti-AR combination continues to be standard of care for CRPC—both non-metastatic and metastatic. Enzalutamide, apalutamide and darolutamide are second generation AR antagonists used interchangeably and their selection is based on adverse effects profiles. First-line treatment of mCRPC entails ADT plus AR axis targeted therapy—the latter employing abiraterone acetate/prednisone or an AR antagonist. Options also include combining ADT with docetaxel, a microtubule binding chemotherapy drug, or sipuleucel-T, an immunotherapy drug, or radium-223, which selectively targets PCa that has metastasized to bone. Skeletal-related events ensuing from bone metastasis of PCa are alleviated by osteoprotection with bisphosphonate therapy or denosumab-mediated antibody therapy. Both therapies inhibit osteoclast development and activity, albeit through different mechanisms. More recently, a genome-targeted precision treatment employing PARP inhibitors has been approved for second-line treatment along with ADT in the case of mCRPC, which shows deregulated DNA damage response leading to the deficient homologous recombinant repair (HRR) of DNA double strand breaks. Tumors of mCRPC patients carrying BRCA1 or BRCA2 gene mutation are approved for PARP inhibition therapy. PARP inhibition in a setting of aberrant DNA damage response, and thus deficient repair of DNA double-strand breaks, causes synthetic lethality that culminates in tumor cell death. Promising clinical responses to PARP inhibition have been observed for mCRPC patients with mutation in additional genes in the HRR pathway. This raises optimism that PARP inhibition will be an approved therapy for a wide variety of genomic mutations that interfere with HRR. Finally, immunotherapy with immune check point inhibitors (ICIs) is an approved second-line treatment for mCRPC presenting with genome alterations that cause microsatellite instability (MSI) and deficient mismatch repair (dMMR) and lead to excessive neoantigen burden and strongly immunogenic tumor cells as a consequence. These genomic alterations also promote increased PD-L1 expression and increased tumor infiltration of cytotoxic T cells.Genome-wide sequencing revealed distinct PCa subtypes and mechanistic studies uncovered affected signaling pathways. The TCGA cohort of 333 primary PCa cases identified 7 major molecular subtypes for 74% of early stage PCa and 26% of cases showed heterogeneous genome alterations . The subAR activity is variable across all cases and between seven subtypes. Sub-clonal heterogeneity within each subtype, arising from variable genome and epigenome signatures, is believed to set the disease course. Primary and metastatic PCa show a similar subtype distribution except that the IDH1-mutant subtype is absent in mCRPC. Actionable alterations affecting PI3 kinase or MAP kinase pathways were found in 20% of the TCGA cohort. The clinical translation of these findings holds promise for precision medicine.ETS gene fusion with an upstream androgen-inducible promoter. The most prevalent fusion involves the ETS protein ERG and the androgen-inducible promoter of TMPRSS2 encoding a transmembrane serine protease. Less common promoter fusions involve other androgen-inducible genes, such as SLC45A3, encoding a sucrose: proton symporter [ETS members ETV1, ETV4 and FLI1 also exist. ETS overexpression without fusion was detected in limited examples. ETS fusion-positive tumors show chromoplexy leading to extensive genome rearrangement. The deletion of the PTEN tumor suppressor gene, prevalent in TMPRSS2-ERG-positive PCa and a likely outcome of chromoplexy, activates the PI3K oncogenic axis. TP53 alteration, leading to p53 tumor suppressor inactivation, is frequently detected in ERG-rearranged PCa. In PTEN-deleted PCa, activating the mutation of PIK3CB  is a dominant driver of PI3K signaling [PTEN deletion and activating mutation of PIK3CB [This category includes four subtypes of ymporter . Promoteignaling ,69. AR if PIK3CB . In tranf PIK3CB . The assf PIK3CB .SPOP (encoding a Speckle Type BTB/POZ domain protein), FOXA1 (encoding a pioneering factor promoting AR-mediated transactivation), and IDH1 encoding isocitrate dehydrogenase1, which catalyzes isocitrate conversion to 2-oxoglutarate.ETS fusion-negative genetic subtypes involve mutations in SPOP mutations are most common  loss, along with the loss-of-function mutation of CDK12, BRCA2, BRCA1. The PI3K/AKT pathway, which regulates tumor growth, survival, and therapy resistance [PTEN [PIK3CA, PIK3CB, PIK3R1, and AKT1 is less frequent. Beyond gene deletion, PTEN loss-of-function can occur from mutation, methylation, microRNA directed post-transcriptional regulation and post-translational modification [The subtype distribution for mCRPC is similar to that for castration-sensitive primary, locally advanced, and metastatic PCa, except that pathways ,75. Othesistance , is actice [PTEN ,77. The fication ,79.The reciprocal feedback inhibition of AR and PI3K/AKT signaling, demonstrated in PCa experimental models, revealed the activation of AKT upon AR inhibition and activation of AR when AKT is inactivated . In our BRCA2, BRCA1, and ATM, which have central roles in HRR of DNA DSBs [BRCA2/BRCA1 mutated mCRPCs that progress on ARAT are approved for PARP inhibition therapy. Exceptional responses to platinum-based chemotherapy for HRR-deficient mCRPC cases are known [The aberration of DNA repair genes is found in 20–30% of mCRPC cases. Among frequently altered genes are DNA DSBs . HRR genre known ,84.MSH2, MSH6, PMS2 and MLH1—leads to deficient mismatch repair (dMMR), genome hypermutation and microsatellite instability-high (MSI-H). A total of 3–12% of mCRPC cases showed dMMR and/or MSI-H, which associate with elevated tumor-expressed neoantigens and PD-L1, and increased tumor infiltration of cytotoxic T cells [Alteration in mismatch repair genes— T cells . MSI-H i T cells .CDK12 inactivating mutations are more prevalent in mCRPC than primary PCa [CDK12-/-tumors, which are mutually exclusive with tumors bearing ETS fusions, SPOP mutations or DNA repair deficiency, show focal tandem duplications that lead to gene fusions, chimeric coding sequences and expression of neoantigens. CDK12-/-mCRPC responded to anti-PD-1 monotherapy [Biallelic somatic mary PCa . No germotherapy ,58.AR locus and at a far upstream enhancer locus occurs recurrently in mCRPC and correlates to a shorter time on ARAT without any influence on OS [AR locus harboring a proximal enhancer [AR locus and a far-away enhancer at a 66.94 mega base upstream of the AR locus [AR locus amplification was also detected. Increased AR mRNA scores strongly associated with the two amplified loci. The far upstream amplified locus independently associated with upregulation of AR mRNAs.Heightened AR activity and AR pathway outputs—the outcomes of increased AR expression, AR activating mutations, and AR splice variants that are activated in an androgen-independent manner—are prominent features of mCRPC. Copy number gain at the genomic ce on OS . CRPC meenhancer . In anotAR locus . Copy nu® degrades the wild-type AR and a clinically relevant mutant AR that confers enzalutamide resistance to PCa. ASC-J9® inhibited PCa growth/proliferation and prevented AR upregulation in docetaxel-resistant CRPC [An alternative approach to AR pathway inhibition is to reduce the receptor in tumor cells by its degradation via the ubiquitin-proteasomal pathway, which can be initiated by a small-molecule SARD (Specific AR Degrader) or AR-selective PROTAC (proteolysis-targeting chimera) ,85. One ant CRPC ,88. AZD-ant CRPC .ARAT resistance [AR. A031 inhibited VCaP xenograft growth [Several AR PROTACs are in clinical or pre-clinical testing. The ARCC-4 PROTAC ablated cellular AR inhibited PCa cell proliferation, and degraded AR point mutants that convert enzalutamide to an AR agonist . The ARDsistance . The A03t growth . AR-targUnlike full-length AR, the tumor levels of the splice variant AR-V7 did not correlate to time on ARAT, although the association of AR-V7 mRNA expression in circulating tumor cells with time to ARAT resistance and clinical outcome has been reported in other studies ,95. Of nRB1 loss has emerged as a strong predictor of poor survival based on a study with taxane-naïve mCRPC patients receiving ARAT, whereas Rb1, AR and TP53 alterations associated with a shorter time on ARAT [RB1-encoded tumor suppressor regulates the E2F transcription factor activity and G1→S checkpoint. A subset of ARAT-unresponsive mCRPC tumors bypasses AR pathway dependence due to lineage switch. This switch leads to a phenotype shift from luminal epithelial-like prostate adenocarcinoma to AR-independent, basal-like cells expressing neuroendocrine markers, such as synaptophysin and chromogranin A. RB1 inactivation is the major driver of this lineage crossover to neuroendocrine-type prostate cancer (NEPC). SOX-2, a stem cell factor and regulator of neuronal progenitor differentiation, is a downstream effector of RB1-dependent lineage transition [ on ARAT . The RB1ansition .RB1 and TP53, low or absent AR and AR pathway outputs, and induction of SOX2 and the epigenetic enzymes EZH2 and DNMT1. EZH2 is a lysine methyltransferase that confers a repressive epigenetic mark on histone H3 by trimethylating lysine-27 (H3K27-Me3) and DNMT1 mediates cytosine methylation at genomic context-specific CpG motifs. EZH2 is a component of polycomb repressive complex2 (PRC2). EZH2 can also coactivate AR in a PRC2-independent manner [NEPC is a poorly differentiated mCRPC variant associated with low serum PSA and poor prognosis. A subset of NEPC histologically resembles small cell carcinoma. Variants with NEPC/small cell traits are diagnosed in up to 20% of mCRPC patients who progress on ARAT ,99. Promt manner , which it manner . EZH2 int manner ,103.RB1 and TP53 [Aurora kinase A (AURKA), a G2→M regulating cell cycle kinase, and delta-like protein 3 (DLL3), a cell surface notch signal inhibiting ligand, are other examples of proteins enriched in NEPC and its small-cell variant compared to adenocarcinoma . N-MYC oand TP53 . EZH2, Aand TP53 . PlatinuPrecision medicine entails diagnosis and disease management after considering individual differences in genomics and gene interactions with environment and lifestyle. The recent finding that intestinal microbiota produces androgen precursors and promotes CRPC presents the exciting possibility for antibiotics therapy in future prostate cancer management . InnovatImmune checkpoint inhibition in monotherapy normally fails to inhibit PCa, in part due to an immunosuppressive tumor environment—the exception being mCRPC with an MSI-H or dMMR genotype that leads to enhanced cancer cell immunogenicity from high neoantigen burden. For a subgroup of mCRPC patients, tumor-suppressive immune functions may be augmented by the prior inhibition of angiogenesis. A microRNA (miR-221) has been identified as a potential biomarker for selecting patients who would possibly benefit from the neoadjuvant use of an angiogenesis-blocking drug in a cancer immunotherapy setting . The cliThe inevitable progression of prostate cancer on hormone therapy leaves other strategies and actionable targets open to experimental probing and clinical validation. AR degradation by small-molecule PROTACs and SARDs as an approach to overcome AR axis blockade is in early stage clinical investigation. A clinically viable approach may be in the horizon where AR expression would be disrupted epigenetically by a long non-coding RNA known as NXTAR. The reciprocal negative regulation of gene expression for NXTAR and AR has been demonstrated, and a xenograft study showed that a small-molecule AR inhibitor restored NXTAR expression and sensitized enzalutamide-resistant prostate tumor to growth inhibition .Finally, progress in CRISPR/Cas-enzymes assisted gene editing in clinical settings has ushered optimism for a future arena of prostate cancer management utilizing this cutting-edge technology. Vast possibilities for genome-targeted interventions as well as other avenues of intervention that are coming to light from mechanistic studies are advancing clinical-translational research on prostate cancer through both personalized approach and precision targeting.


Atrioventricular block (AVB) during pregnancy is rare. Case study for pregnancy with AVB have been reported but a consensus guideline for peripartum management has not been established. This study aimed to investigate cardiac and obstetric complications and outcomes in our pregnant women with AVB and share our management experience.This was a retrospective study. We reviewed a total of 74 pregnant women with AVB who delivered at our tertiary care center in the past 10 years. The patients were categorized into four groups according to the degree of block. The data were analyzed and compared among the four groups of patients.P>0.05). Caesarean section was performed more in patients with high-degree AVB than in patients with low-degree AVB. No maternal or neonatal death in our cases.Regarding the cardiac complications, the cardiac function level showed significant difference among patient groups. The higher NYHA class were observed in patients with higher degree AVB. Pacemaker was placed before delivery in 32/33 patients with III° AVB, 8/25 patients with II° AVB, and 0/16 patient with I° AVB. Other types of arrhythmias except AVB were present in all groups of patients but more frequently observed in type I patients with II° AVB. No other heart abnormalities were observed among the patient groups. Obstetric complications were found in 21 women (28.4%), including premature labor, premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), preeclampsia, etc. The incidence rate of fetal cardiac abnormalities was 6.58%. But no statistical difference was detected among four groups of patients for fetal and maternal complications and fetal cardiac abnormalities (Most women with AVB could achieve successful pregnancy and delivery. Patients with II° AVB type II and III° AVB should be monitored vigilantly during pregnancy and post-partum. Temporary pacing before delivery appeared to be beneficial for women with III°AVB, and accurate diagnosis and care by a multidisciplinary team was recommended. As a serious cardiac arrhythmia, atrioventricular block (AVB) is rarely observed in women during pregnancy. This type of arrhythmia is featured by the loss of the regular function of the cardiac electroconductive pathways through the atrioventricular node (AV node). Without normal conduction through the AV node to ventricle, the sinoatrial node (SA node) cannot control the heart rate, and cardiac output can diminish secondary to the loss of coordinated contraction of the atria and the ventricles , 2. AccoThis was a retrospective study. Approval was obtained from the Institutional Review Board of West China Second University Hospital. We reviewed the medical records of 656 pregnant women with cardiac arrhythmias, who were admitted at West China Second University Hospital  during the period from January 2010 to March 2020. Prevalence of atrioventricular block was 11.28% (74/656) in pregnancy with all cardiac arrhythmias.All patients underwent clinical examination, ECG and transthoracic echocardiography, and fetal echocardiography. The following co-morbidities were taken into consideration in the clinical characterization of the patients: hypertension, diabetes mellitus, and other pregnancy associated diseases. Each pregnant woman in our center is individually analyzed to determine the delivery mode.24-h ambulatory ECG was performed in patients who had abnormal electrocardiographic pattern (such as a slow heart rate) or normal ECG but had symptoms of dizziness, weakness, and syncope in early pregnancy.All the patients were evaluated by echocardiography in order to screen other heart diseases. Fetal echocardiography also performed determine fetal heart disease.As necessary, vascular ultrasound was employed for diagnosing peripheral embolism. Cardiac ultrasound was also employed for excluded the presence of pulmonary hypertension. If a patient had signs of pulmonary hypertension such as tightness and cyanosis even if the patient was at rest, it needed to be jointly consulted by cardiologists and Intensive care physician, and then central venous catheterization (CVT) or right heart catheterization may be taken into account to monitor central venous pressure (CVP) and pulmonary artery pressure gradients according to the patient serious symptom.p-Value of 0.05 was used as the cutoff for significance. This statistical analysis methods have also been described in our previous study for pregnancy complicated with tetralogy of Fallot , and III° AVB (n = 33).According to the degree of atrioventricular block, the patients were divided into three groups: I° AVB . While 35 patient (47.3%) had AVB alone, more than half of patients (52.7%) were also complicated with other types of arrhythmias. Of note, the other types of arrhythmia were mainly observed among II° AVB patients. More or less other arrhythmias were also found in other groups. However, only sinus arrhythmia and APB showed statistical difference among the four groups of patients, the other arrhythmias had no significant differences. Regarding other heart abnormalities, left atrial enlargement and pericardial effusion were observed in all groups of patients with no significant difference.The Left ventricular systolic function was in normal range in the majority of studied patients, except one patient with III° AVB. There was no significant difference in the condition of heart valve among the four groups of patients, though MR condition showed a The clinical data of obstetric complications including fetal complication and maternal complications are summarized in the upper part of Table The most common fetal complications related to the maternal AVB were prematurity, which was observed in 11 fetuses (14.47%). In addition, we observed two cases (2.63%) of oligohydramnios, two cases of small for gestational age , and one case (1.32%) of fetal distress. The maternal complications, including premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), preeclampsia, placental adhesion, velamentous placenta, thrombocytopenia in pregnancy, proteinuria + pedal edema, were reviewed and analyzed. None of these maternal complications showed significant difference among the four groups of patients. Other obstetric conditions frequently encountered in normal pregnancy, such as nuchal cord  and breech presentation , thromboembolism  were also reviewed, none of them appeared to be more concerning in AVB patients than in general population.Among the studied cases, 60 (81.08%) women underwent caesarean section and 14 (18.92%) women had vaginal delivery. As shown in the middle section of Table P < 0.05). Among the 76 fetuses, fetal cardiac abnormalities were observed in 3 cases (3.95%). Prenatal screening with genome sequencing was performed for two cases of hyperechoic fetal heart, and no abnormality was found.There was no maternal or neonatal death in our patients. And no difference for postpartum hemorrhage, mean neonatal weight, hospital day among the four groups of patients. But the blood loss during delivery was significantly differents  on the second day after operation transfer to ICU and was given medical treatment such as atropine and isoprenaline. One patient with II° AVB type II was not implanted with a temporary pacemaker before deliver, postpartum ECG showed frequent ventricular premature beats and induced supraventricular tachycardia. Another one patient with II° AVB type II was placed the temporary pacemaker before the birth, but the patient had edema of lower limbs and urine protein  during her 3rd trimester, there was no relief after the birth and progress to acute left heart failure with symptoms of rapid breathing difficulties and orthopnea, and the distribution of scattered wheeze of lungs could be heard. Two patients transfer to cardiology department for permanent pacemaker placement after the operation immediately all were the patients with III° AVB .Atrioventricular block (AVB) is caused by the dysfunction of the cardiac electroconductive pathways and characterized by a prolongation of the PR interval on the electrocardiogram (ECG) . AccordiThe high-grade heart block can cause palpitations, fatigue, dyspnea, and/or syncope, and associated with significant mortality . ImportaIn general, with the increase in the degree of AVB, the complications and mortality of patients increased. Most pregnant patients with I° AVB were asymptomatic and did not have significant complications. While the treatment was not necessary for these patients, regular evaluation is essential because the risk of atrial fibrillation and development of higher degree AVB increases with the growth of gestational age . In our Regarding II° AVB, the block may be temporary or permanent depending on the impairment of the conduction system and divided into two types (Mobitz type I and Mobitz type II). Patients with II° AVB may be asymptomatic or have symptoms like syncope and lightheadedness . Of noteThe III° AVB indicates a complete loss of communication between the atria and the ventricles, so it’s also called complete heart block. Without appropriate conduction through the AV node, the SA node cannot control the heart rate, and cardiac output can diminish secondary to the loss of coordination between the atria and the ventricles. The condition can be fatal if not promptly treated. Most patients usually receive a temporary pacemaker and later replaced by a permanent one. Pacemaker can improve the survival rate of patients with III° AVB during pregnancy , 8. In tIn the literature, several studies demonstrated that pregnancy in women with high-grade AVB was associated with high maternal and fetal mortalities, if pacemaker placement could not be achieved before delivery , 13, 14.Atrioventricular block could be congenital or acquired post birth. Congenital AVB may be caused by cardiac malformations or damaged by maternal antibodies (autoimmune AVB). Family history of AVB is one of the risk factor for congenital AVB , 17. DurIn our study, 28.4% patients showed obstetric complications, including premature labor, premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), preeclampsia, placental adhesion, velamentous placenta, thrombocytopenia in pregnancy, proteinuria. The most common fetal complications were prematurity, oligohydramnios, SGA and fetal distress. No neonatal and maternal death was observed in the current study.For pregnant women with AVB, in addition to obstetric conditions, the baseline cardiac function and the risk for exacerbation of cardiac function during delivery were also taken into the consideration. In the current study, while most patients (81.08%) with high NYHA-FC and/or high-grade AVB received caesarean section, 14 women  had successful vaginal delivery. Of note, all patients with II° AVB type II received cesarean section. Two of our patients with III° AVB who have received pacemaker showed good outcome for the vaginal delivery. Accordingly, the presence of a pacemaker in a patient may not necessarily be an indication for cesarean section . The detIn summary, most women with AVB could achieve successful pregnancy and delivery. Patients with II° AVB type II and III° AVB should be monitored vigilantly during pregnancy and post-partum. Temporary pacing before delivery appeared to be beneficial for women with III° AVB. In the patients without pacing, especially those with II° AVB type II should be closely monitored with precautious plan for unexpected complications.


Rehabilitation 2030: A call for action – has introduced the objective of ‘upscaling’ rehabilitation globally to meet demand. This research explored what upscaling stroke rehabilitation might mean for health professionals from countries at different stages of economic development.Demand for stroke rehabilitation is expected to grow dramatically; with the estimated prevalence of stroke survivors rising to 70 million worldwide by 2030. The World Health Organization’s (WHO) report - Qualitative descriptive study design using semi-structured interviews was employed. Purposively sampled, clinical leaders in stroke rehabilitation were recruited for interviews from low through to high-income countries.Twelve rehabilitation professionals  from high , upper-middle (Colombia and Turkey), lower-middle , and low-income countries  were interviewed. Upscaling was seen as a necessity. Successful scaling up will require initiatives addressing: political governance and managerial leadership, increasing knowledge and awareness of the value of rehabilitation, financial support, workforce developments, physical space and infrastructure, and the development of community services and reintegration.. For the WHO to be successful in implementing their objective to upscale rehabilitation, specific attention will need to be paid to political, professional, economic, and sociocultural issues at global and local levels.Although there have been many gains within the development of stroke rehabilitation internationally, further investment is required to ensure that this patient population group continues to receive the best quality servicesThe online version contains supplementary material available at 10.1186/s12913-021-06293-8. Rehabilitation 2030 - “a call for action to scale up rehabilitation so that countries can be prepared to address the evolving needs of populations up to 2030.” . Between 1990 and 2010, the total global years lived with disability (YLD) from all causes increased from 583 million to 777 million, largely due to population growth and aging  is low because there is a lot of emphasis on the spiritual aspect of the disease. So, a lot of them [patients/families] believe it’s either a curse or a spiritual cause, or it can be cured with herbal preparations. So, a lot of them after being discharged from the acute stroke inpatient ward are going to see a traditionalist, herbalist, or spiritualist to help. Then they are coming back weeks or months later with complications. Furthermore, sociocultural factors and health education influenced the knowledge of the causes of stroke among the general population and therefore, directly influenced patients and families choosing to access rehabilitation services in a timely manner. In Ghana and Sierra Leone, some people attributed stroke to a curse or spiritual cause; this resulted in family members not accessing rehabilitation services at all, or only accessing services after impairments had become significant health problems . In the United Arab Emirates some patients and families, who had a strong belief that divine intervention would heal them, did not easily accept the rehabilitation interventions offered. Therefore, education of the public was required in some countries for patients and families to engage with rehabilitation services and access them promptly when needed.It’s not very helpful to be saying … we want you to upscale your rehab – for that to be said without any extra resources of finance attached to it. Otherwise, they can say it until they are blue in the face, but it is never going to happen. All participants reported that financial investment was required to scale up stroke rehabilitation. In some of the lower-income countries, funding was required to establish and expand the coverage of rehabilitation services. However, even in high-income countries the participants reported that the upscaling of stroke rehabilitation would require more than just the reorganization of existing services and resources.That is more of a big problem for the future because the statistics say – the forecast says in 2030, we will have 70 million stroke survivors in the world. So, we will have a lot more people in our rehab center, and we can’t take care of them if we don’t have the basic (staff) for working. That’s the biggest problem … it’s like running with closed eyes in front of a wall. When investing in the development of stroke services, the participants all emphasized the need to invest in the healthcare workforce first – before investing in buildings, equipment, or other physical resources for rehabilitation. The participants argued that their governments and health service leaders needed to have a long-term strategy to recruit and cultivate these professionals within their countries. In the high-income countries, the participants discussed that this might also mean establishing new roles to support the healthcare system as a whole. Suggested roles were those with a focus on stroke service development or evidence-based practice implementation, case management, rehabilitation nurse specialist, and new or expanded ‘lay’ caregiver roles including patient advocate, educator or navigator.What we want first of all is to provide the right human resources. That’s very key those are the services providers. We want to ensure the right human resources are available. In addition, participants in the middle and low-income countries stated that there needed to be more rehabilitation professionals recruited, especially in rural areas, to improve access to services. These countries needed more of the specialist rehabilitation professional groups represented, who were often not available at all  and up-skilling of all rehabilitation professionals in stroke rehabilitation, the application of EBP, and multidisciplinary team approaches.We can’t send more than twenty staff to foreign countries, but we can teach or educate more than 50 people at the same center, which is conducted in Turkey. So, I think first we need a real education [in rehabilitation] in Turkey. Access to specialist training in rehabilitation was another limitation in middle and lower-income countries. Often specialist training was only available if people traveled to higher-income countries, which limited how many people could receive this training. Many participants thought a more efficient way of training was to invite a trainer or a trained professional from a high-income country.My personal challenge is that I don’t have adequate space. I mean if you see my department on any busy day, it would resemble more of a fish market than a rehab department .All participants believed that they needed further access to physical resources for rehabilitation if upscaling were to be successful. However, differences were apparent in what resources were required depending on the local context. Participants in the upper-middle and high-income countries emphasized the need for funding of additional equipment or technology to support assessment, diagnosis, and treatment, to increase the number of rehabilitation beds available. Participants in lower-middle and low-income countries experienced more challenges with inadequate space for rehabilitation.In some countries, patients and families without health insurance or the ability to pay privately had limited access to diagnostic tests as well as primary rehabilitation interventions. This situation directly influenced their opportunity to receive evidence-informed rehabilitation.They (patients) lose their jobs, they cannot go back to their normal activities, and these are people that are very much useful in society The participants from all countries spoke of the importance of rehabilitation services moving into communities  and of developing support for community reintegration after stroke, with a particular emphasis on helping patients return to work.Returning these patients to work as useful, earning members of society could help reduce the stigma of disability in Pakistan .Community-based rehabilitation and returning to work was also viewed as a way of tackling some of the disability-associated stigma, especially in the LMIC’s.However, gaps in services after discharge from the hospital were apparent even in high-income countries, with variable coverage for community-based rehabilitation. The participant from the UK used the phrase ‘postcode lottery’ to refer to the arbitrary influence of where patients happened to live on the quality of community rehabilitation they received.Only if the government understood that we need the services of rehabilitation in the primary care level. For example, in the tiny hospital that I talked about which is in the distant areas, they should have some rehabilitation care because if the patient has to come to the big city to have it, it is not good .Participants from the middle and low-income countries said community services were sparse (to non-existent), which affected the patients’ opportunity for reintegration into their communities. Investing in community services in the rural areas was seen as an essential area for upscaling rehabilitation. Some wanted specialist members of the multidisciplinary team in the rural areas so that patients did not have to travel to the larger cities to receive the same level of care and rehabilitation. Telerehabilitation was suggested by one participant as a way to improve rural service access, and this was being tested by supporting general practitioners in rural towns and hospitals by connecting them with a specialist doctor in a larger centre.Rehabilitation 2030: A call for action [This study provides insights into what health professionals working in stroke rehabilitation in a variety of international settings think might be required to achieve the WHO’s Much of the prior research on rehabilitation in LMIC has focused on highlighting or quantifying the lack of rehabilitation services, especially in rural and economically poorer regions, and this impact on poorer health outcomes –19. EvenLike other areas of healthcare , upscaliWe suggest two topics worthy of further research. First, to ask those in governance roles  to consider what is needed to meet ‘evolving needs’  in strokWe interviewed one health professional in each country: different health professionals from different backgrounds and regions might well have emphasized other issues when discussing upscaling stroke rehabilitation in their countries. We were also limited to interviews in English, which restricted the type of information we were able to gather and from whom. There may be cultural factors related to upscaling stroke rehabilitation that we failed to identify.Rehabilitation is now a core part of the definition of Universal Health Coverage  and therAdditional file 1. Overview of the interview guide.


Environmental factors play an important role in the development and exacerbation of allergic rhinitis (AR) in childhood. Indoor air pollution, such as house dust mites and secondhand smoke, can significantly increase the onset of AR, while pet dander may affect the exacerbation of AR symptoms in children. Furthermore, traffic related air pollution and pollen are outdoor air pollutants that can affect immune competency and airway responsiveness, increasing the risk of AR in children. Climate change has increased AR in children, as growth patterns of allergenic species have changed, resulting in longer pollen seasons. More extreme and frequent weather events also contribute to the deterioration of indoor air quality due to climate change. Additionally, viruses provoke respiratory tract infections, worsening the symptoms of AR, while viral infections alter the immune system. Although viruses and pollution influence development and exacerbation of AR, a variety of treatment and prevention options are available for AR patients. The protective influence of vegetation (greenness) is heavily associated with air pollution mitigation, relieving AR exacerbations, while the use of air filters can reduce allergic triggers. Oral antihistamines and intranasal corticosteroids are common pharmacotherapy for AR symptoms. In this review, we discuss the environmental risk factors for AR and summarize treatment strategies for preventing and managing AR in children. A global health problem with significant economic burden, allergic rhinitis (AR) has established itself as the most common chronic allergic disease and affects approximately 40% of the population worldwide ,2,3. In The most common symptoms of AR include nasal congestion, nasal pruritus, sneezing, and runny nose, leading to impairment in daily activities, sleep habits, cognitive function, work and school productivity, and overall quality of life ,11,12. CPollution, considered the largest single environmental risk for health, is the introduction of harmful substances into the environment, contaminating air, soil, or water with chemical substances or energy . Polluti10), and 66% are exposed to carbon dioxide (CO2) over 1000 ppm [Indoor air pollution including tobacco smoke, indoor allergens , and other pollutants  all contribute to the development of AR and the aggravation of symptoms . Individ1000 ppm . It was 1000 ppm .2), carbon monoxide (CO), and volatile organic compounds (VOC) [2, while VOCs are frequently released by consumer products such as cleaning chemicals, cosmetics, and air fresheners [Common indoor pollutants include nitrogen dioxide (NOds (VOC) . Gas fueesheners . Evidencesheners . Additioesheners .Several studies have evaluated whether tobacco smoke exposure could cause AR, as tobacco smoke has already been demonstrated to play a major negative impact on global public health ,25. The A meta-analysis found that children actively smoking had an increased risk of AR, while those exposed to second-hand smoke (passive smoking) had a much larger increased risk for AR . In a FrHouse dust mites (HDM), molds, and pet dander are common examples of indoor allergens . Indoor A meta-analysis suggests that the risk for AR is significantly increased with exposure to home dampness and mold . DampnesAdditionally, HDM are perpetual triggers for airway allergy . Data haAnimal-derived allergens are one of the most common sources of aeroallergens and triggers for AR with over 15% of the world’s population sensitized to furred animals with a high rate of cross-reactivity within species ,35. Cats3), NO2, sulfur dioxide (SO2), and particulate matter (PM), contributes to AR development and symptoms in children [The major outdoor exposures that play a role in AR include outdoor air pollution and pollen. Outdoor air pollution caused by traffic, which produces ozone  per pollen grain than the ozone free trees [3 exposed trees demonstrated a larger wheal diameter than the less exposed trees [Studies have inconsistently demonstrated that urban dwellings pose a higher risk of AR than suburban dwellings because of the loss of biodiversity with urbanization ,38. Withe pollen . Pollen e pollen . Additioe pollen . In thise pollen . The maje pollen . Furthere pollen . A Germaee trees . PALMs aee trees . Moreoveed trees .2, methane, black carbon, nitrogen oxides, and sulfate aerosols into the environment [Climate change, long-term shifts in weather patterns including changes in temperature, has an impact on respiratory allergies because changes in meteorological variables affect the prevalence of airborne allergens and ambient pollution . Currentironment ,57,58. Gironment . Climateironment .The seasonality and severity of AR are affected by the growth patterns of different allergenic species, and global warming and air pollution are known to affect these patterns . Global 2, NO2, O3, and SO2, from air pollution [2 can be consumed [10, 73 tons of O3, 55 tons of NO2, 7 tons of SO2 and 6 tons of CO) [Greenness, areas with increased presence of trees and green spaces, helps mitigate air pollution . Greenneollution . During consumed . In 2008s of CO) . Speciess of CO) . The Nors of CO) . NDVI ras of CO) . Healthys of CO) . Overalls of CO) .2 based on an Austrian study [2 levels are lower [Betulaceae pollen during tree pollen season assessed exposure to green space and allergenic trees while tracking daily symptom severity scores [Although findings from studies of greenness are inconsistent, greater greenness may prevent AR and its symptoms ,71. A poan study . Furtherre lower . A studyy scores . The stuy scores .Viruses, such as adenoviruses, coronaviruses, influenza viruses, parainfluenza viruses, rhinoviruses, and respiratory syncytial viruses, trigger upper respiratory infections (URI), which are the most common infections in humans . Viral iRhinovirus infection has been shown to increase early and late phase reactions to allergens and, thus, may promote the development of allergic airway disease . In a stFor prevention of AR, general allergen and pollution avoidance are recommended when possible . Nasal f2, PM, and CO correlated with a yearly decrease in rates of AR [Multiple studies have shown that exposure to clean air helps decrease the prevalence of AR in children. For example, a retrospective study conducted between 1997 and 2006 found that a decrease in NOes of AR .2, SO2, PM, and mercury [Air pollution monitoring is essential to help prevent the development and exacerbation of AR in individuals as well. Many countries are now enforcing new policies to help with the prevention of climate change, which in turn will help decrease the onset of AR and aggravation of symptoms. The European Union’s framework for environmental policy has already significantly contributed to diminishing the emissions of air pollutants and improving air quality across Europe . Moreove mercury . In the  mercury . Another mercury .A variety of treatment options for AR symptoms exist. The most commonly used pharmacotherapy for AR is oral antihistamines with a preference for second-generation antihistamines  over first-generation antihistamines  because of fewer side effects related to sedation, disrupted sleep, and anticholinergic symptoms ,82. IntrSome epidemiological data suggest that the intake of dietary antioxidants may decrease the prevalence of AR . Some stFuture studies could help advance prevention and treatment of AR in children. First, definitive studies of whether vitamin D supplementation could treat AR are needed as vitamin D is an inexpensive, simple intervention. The development of new treatments to mitigate or counteract the effects of environmental pollutants on the immunologic regulation of AR can also be considered. More importantly, strategies to reduce environmental factors associated with AR need to be more aggressively studied and implemented. Finally, additional studies demonstrating the positive impact that environmental policies have on health, including prevention of AR, may help policy makers make decisions.Lifestyle and environmental factors play an important role in the development of allergic rhinitis, one of the most common chronic conditions in the world. Specifically, indoor air pollution, such as HDM, tobacco smoke, and pet dander can significantly increase the onset of AR. Moreover, outdoor air pollution, including TRAP and pollen can increase the risk of AR in children. Preventive measures for AR control through environmental protection policies also have great promise to improve public health. Additionally, viruses may increase the risk and exacerbate the symptoms of AR. The avoidance of these environmental triggers may reduce the development of AR and AR symptoms.


Percutaneous endoscopic lumbar discectomy (PELD) is a promising minimally invasive treatment for lumbar disc herniation (LDH). Postoperative rehabilitation can improve patient outcomes. Not only rehabilitation for surgical trauma but also rehabilitation for lumbar spine and lower kinetic chain dysfunction should be performed. The aims of this study were to investigate the efficacy of a lumbar kinetic chain training for staged rehabilitation after PELD for LDH.Fifty one LDH patients treated with PELD were studied. After surgery, patients underwent lumbar kinetic chain training for staged rehabilitation( staged group) or regular low back rehabilitation (regular group). The staged rehabilitation programme included three phases from 2 to 6, 7–12, and 13–24 weeks postoperatively, and different physical therapies were performed during these phases. The low back pain visual analogue scale (VAS), JOA score, ODI, SF-36, and cross-sectional area of the lumbar multifidus on MRI were assessed, and gait analysis was performed.p > 0.05). The VAS score decreased and the JOA and SF-36 scores increased in both groups from baseline to 6 weeks (P < 0.05). In the staged group, compared with the regular group, the VAS and ODI scores were lower and the JOA and SF-36 scores were higher at 6 weeks (P < 0.05); the VAS and ODI scores were lower and the SF-36 score was higher at 12 weeks (P < 0.05); the SF-36 score was higher at 24 weeks (P < 0.05); the cross-sectional area of the lumbar multifidus showed no differences at 12 weeks (P > 0.05); and the left-right support ratio of gait was higher at 24 weeks (P < 0.05).Twenty five patients in staged group and twenty six patients in regular group were included. There were no significant differences in age or sex between the two groups at baseline (The staged rehabilitation programme for LDH after PELD promoted postoperative recovery, and the efficacy of lumbar kinetic chain training was higher than that of regular low back muscle exercise. Minimally invasive surgeries of the lumbar spine have been developing rapidly in recent years. Many patients with lumbar disc herniation (LDH) have been effectively treated with percutaneous endoscopic lumbar discectomy (PELD). The procedure has been indicated to be minimally invasive and lead to a fast recovery , 2. PELDPhysical therapy and rehabilitation after lumbar decompression surgery are helpful for the functional recovery of patients –9. HowevPELD removes the herniated intervertebral disc, the corresponding ligamentum flavum and articular process. Physical therapy and rehabilitation are needed to achieve important postoperative goals such as increasing the strength of the low back muscles to compensate for surgical damage, preventing degeneration and instability of the adjacent segments, adjusting postural and kinetic models, correcting the mechanical imbalance of the pelvis and lower extremities and improving gait performance.Disc degeneration is closely related to the paraspinal muscles –14. LDH The aims of this study were to design a specific kinetic chain staged rehabilitation programme, compare it with regular low back muscle exercise and evaluate its efficacy.The study was approved by the ethics board of the Chinese Rehabilitation Research Center (register No. 2019-121-1), and all participants signed written informed consent forms. This study included 51 LDH patients treated with PELD in the Department of Spine Surgery of the Chinese Rehabilitation Research Center from January 2019 to June 2020. All patients underwent lateral-approach single-segment PELD. The inclusion criteria were an age of 35–60 years, a diagnosis of LDH according to the clinical diagnostic criteria, and clinical manifestations consistent with the imaging findings [Postoperatively, two rehabilitation programme were performed for patients randomly. The staged group (25 cases) underwent a lumbar-pelvic-leg kinetic chain staged rehabilitation programme. The regular group (26 cases) underwent a regular low back muscle exercise programme.The rehabilitation programme was divided into three stages performed from 2 to 6, 7–12, and 13–24 weeks postoperatively, according to the characteristics of PELD recovery. This programme mainly involved lower extremity activity to prevent perioperative complications and active spine extension to reduce intervertebral disc stress in the early stage, muscle stretching to increase muscle flexibility in the middle stage, core muscle strengthening and posture and gait correcting components in the later stage. The specific staged rehabilitation programme is shown in Table After discharge, all patients returned to the clinic once a week to receive instructions from the therapist. Additionally, all patients received a standard informational booklet on the staged rehabilitation programme. Lumbar and hip muscle training was performed with bridging exercises, supine arch movement, and supine curly hug. Each exercise was held for 5 s and then repeated. Abdominal muscle training was performed with plank training and supine leg lift exercises. Pelvis and lower extremity training was performed with alternating pronation movements of the pelvis in the supine position, pelvic lateral strengthening exercises, and crawling training. The spine was protected, and the programme was adjusted according to each patient’s level of dysfunction, back pain and/or radiation pain.Regular lumbar postoperative rehabilitation focused on low back muscle exercises that progressed gradually, without consideration of the specific recovery stages –7. AfterRehabilitation assessment were performed by a trained doctor and a senior physical therapist blinded to the grouping at baseline and 6, 12, and 24 weeks postoperatively. The efficacy of the different programmes was evaluated by the low back pain visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry dysfunction index (ODI), simplified Chinese version of the SF-36 health survey (40–850 points), cross-sectional area (CSA) of the lumbar multifidus on MRI, and the ratio of the left to the right supporting phase of gait.The CSA of the lumbar multifidus muscle was determined with a Philips MRI machine. On the axial view of the T2-weighted images at the level of surgical intervertebral space , 20, theGait analysis was performed with a MyoMotion 3D motion capture and analysis system. A 3D model of the human body with sensors was established. The movement angles, acceleration and movement directions of the joints were quickly obtained. The left-right support ratio was used to evaluate the symmetry of gait in this study. A ratio of 1 indicates ideal symmetry.P < 0.05 was considered statistically significant.Statistical analysis was performed with SPSS for Windows (version 21.0). The descriptive statistics reported are the mean and standard deviation (S.D.). The baseline characteristics were evaluated by the chi-square test for sex and the independent-samples t test for age. Intergroup and intragroup differences in the measurement parameters were evaluated by the paired-samples t test and independent-samples t test, and Levene’s Test for the equality of variances was used with the independent-samples t test. p > 0.05). The baseline characteristics of the study population are shown in Tables In total, 51 LDH patients were included according to the inclusion criteria after PELD, and 25 patients in staged group and 26 patients in regular group completed the rehabilitation programme in the Chinese Rehabilitation Research Center from January 2019 to June 2020. No adverse events occurred in this study, such as tumbling or muscle sprains. There was no statistically significant difference in sex or age between two groups (P < 0.05). The ODI score of the regular group at 6 weeks and the CSA of the lumbar multifidus muscle on MRI in both groups at 12 weeks did not change significantly (P > 0.05) (Tables The follow-up results of the two groups were compared with the baseline results (intragroup comparisons). The VAS score decreased and the JOA and SF-36 scores increased in both groups at 6 weeks  Tables  and 5.Tp > 0.05). The follow-up results were compared between the two groups (intergroup comparisons) at different rehabilitation stages. In the staged group, compared with the regular group, the VAS and ODI scores were lower and the JOA and SF-36 scores were higher at 6 weeks (P < 0.05); the VAS and ODI scores were lower and the SF-36 score was higher at 12 weeks (P < 0.05); the SF-36 score was higher at 24 weeks (P < 0.05); the CSA of the lumbar multifidus showed no differences at 12 weeks (P > 0.05); and the ratio of the left to the right supporting phase of gait was higher at 24 weeks (P < 0.05) , paravertebral muscle system (active system) and neuromuscular control system (regulatory system) work together to execute spine-related movements. Coordinated control of the human spine and extremity kinetic chain is the key to normal motor function , 22. TheMcKenzie therapy is a widely recognized nonsurgical treatment for low back pain , 24, espThe core of the human body is defined as the lumbar-pelvic-hip complex, which is where all movement in the body begins, and 29 muscles are connected to this complex . EffectiPatients with LDH often present with pelvic kinetic dysfunction, which causes gait abnormalities , 16. PelEarly rehabilitation after PELD is mainly conducted to promote healing of the tissues around the surgical site, enable standing as early as possible with waist support, and prevent early complications, such as venous thrombosis of the lower extremities. In this study, both groups underwent the same type of rehabilitation for 2 weeks postoperatively, which was in accordance with the medical ethics guidelines. When the patients were discharged from the hospital, the two groups began to undergo strict staged rehabilitation or regular rehabilitation, respectively. Significant improvements in low back pain, lumbar spine function and ability to perform activities of daily living were found in the staged group at the 6th and 12th weeks postoperatively. Early and targeted postoperative rehabilitation improves surgical efficacy, improves symptoms, and promotes the recovery of physical function. At 24th weeks postoperatively, there was improvement in pain and lumbar function in both groups, but only the SF-36 score in the staged group improved significantly. Both groups of patients underwent rehabilitation exercises, and after 6 months of rehabilitation, the patients recovered from surgical trauma, which allowed the body to reorganize its structure and function in daily life. Staged rehabilitation was targeted more, with more systematic exercises of the lumbar, abdominal, and back muscles, and patients exhibited better recovery of core strength, greater adaptability and better SF-36 scores. Thus, staged rehabilitation is important not only to promote symptomatic improvement and functional recovery after surgery but also to help patients relearn proper movement patterns. There were even some patients who exhibited higher levels of athletic performance after staged rehabilitation than before surgery.Previous studies  have sugThe staged rehabilitation programme proposed in this study showed higher efficacy than did regular low back muscle exercise during rehabilitation after PELD for LDH. A specific staged rehabilitation programme and lumbar kinetic chain training are helpful for improving the clinical effect of PELD.


The results showed that the expression of lnc-ZNF281 in glioma tissues was decreased compared with normal tissues. lnc-ZNF281 overexpression inhibited the proliferative and migrative abilities of glioma cells, while lnc-ZNF281 knockdown obtained the opposite findings. Besides, overexpression of lnc-ZNF281 in glioma cells inactivated the AKT/GSK-3β/β-catenin signaling pathway. Furthermore, β-catenin activation reversed the suppressive effects of lnc-ZNF281 on glioma cells. Taken together, lnc-ZNF281 inhibits glioma cell proliferation and migration via AKT/GSK-3β/β-catenin pathway and may serve as a potential target for glioma treatment.The purpose of this study is to elucidate the roles and potential underlying mechanisms of long noncoding RNA lnc-ZNF281 in glioma. We performed qRT-PCR to detect the expression levels of lnc-ZNF281 in glioma tissues. The effects of lnc-ZNF281 on the proliferative and migrative abilities of T98G and HS683 glioma cells were examined by cell proliferation assay, colony formation assay, wound-healing assay, and transwell assay. Also, the effects of lnc-ZNF281 on AKT/GSK-3 Glioma is one of the most prevalent and fatal brain tumors with low 5-year survival, approximately 5% . Maximalβ-catenin signaling pathway and then promoted the proliferation and chemoresistance in colorectal cancer cells [α expression and VEGF. After that, increased HIF-1α and VEGF promoted glioma cell proliferation, migration, and angiogenesis [β-mediated invasion in glioma cells by modulating the activity of p38/MAPK and NF-κB signaling pathways [Long noncoding RNAs (lncRNAs) are one type of RNA without protein-coding ability and have a length exceeding 200 nucleotides . A growier cells . By inteer cells . Meanwhier cells . lncRNA ogenesis . lncRNA-pathways .κB signaling pathway [Among the known lncRNAs, lncRNA zinc finger protein 281 (lnc-ZNF281) is characterized as a tumor suppressor in osteosarcoma by downregulating the expression of miR-144 . Besides pathway . lnc-ZNF pathway . AccordiThirty glioma tissues and 22 normal brain tissues were collected from the Department of Neurosurgery of the Second People's Hospital of Huai'an City between January 2013 and November 2015. The diagnosis of glioma was confirmed by two or more experienced pathologists. After surgical removal, all samples were placed into liquid nitrogen for further experiments. Both the enrolled patients and healthy participants signed the written informed consent. The Research Ethics Committee of Renmin Hospital of Wuhan University approved this study.2 and a temperature of 37°C was used for cell culture.HS683 and T98G glioma cells were purchased from the American Type Culture Collection. All cells were cultured in DMEM , which contains 10% fetal bovine serum (FBS) and 1% antibiotics . A humid environment with 5% COlnc-ZNF281 lentiviral overexpression vectors LV-lnc-ZNF281 and the negative control (NC) LV-NC were purchased from GenePharma Company . The small interfering RNA (siRNA) used to knock down lnc-ZNF281 (si-lnc-ZNF281) was also purchased from GenePharma. Cells were grown in 6-well plates and then transfected by lentiviral vectors according to the manufacturer's protocols. Transfected cells were treated by puromycin to establish stably transfected cell lines, and qRT-PCR was used to detect transfection efficiency. The transfection of si-lnc-ZNF281 was performed using the reagent kit (GenePharma) based in its instruction. Similarly, the transfection efficiency was detected at 48 hours after transfection.β-catenin forward, 5′-AAAGCGGCTGTTAGTCACTGG-3′ and reverse, 5′-CGAGTCATTGCATACTGTCCAT-3′; GAPDH forward, 5′-GACTCATGACCACAGTCCATGC-3′ and reverse, 5′-AGAGGCAGGGATGATGTTCTG-3′. Every experiment was performed three times, and the 2-∆∆Ct method was used to analyze all data.Total RNAs were extracted from clinical samples and glioma cell lines by TRIzol Reagent . The complementary DNA (cDNA) was synthesized from total RNAs using a Reverse Transcription Kit . Then, quantitative real-time PCR (qRT-PCR) detection was performed using the SYBR Green real-time PCR Kit . The expression of GAPDH was used as the internal reference. The sequences of specific primers were as follows: ZNF281 forward, 5′-GGACACATAGTGGAGAAAAG-3′ and reverse, 5′-GAGACAACACAGCCAGATTA-3′; μL Cell Counting Kit-8  reagent was added to every well and cells were further cultured for another 2 hours at 37°C. In the SKL2001  activated group, this agonist was added into the medium to activate target cells. The optical density of each well at 450 nm was detected using a microplate reader .The transfected cells were seeded in a 96-well microplate at a density of 3000 cells/well and then cultured overnight. After 1, 2, 3, or 4 days of incubation, 10 The transfected cells were seeded in a 6-well plate at a density of 1000 cells/well and cultured for 2 weeks at 37°C. Then, cell colonies were fixed with 4% paraformaldehyde for 20 minutes and stained with 0.1% Crystal Violet  for 30 minutes. Finally, cell colonies with at least 50 cells were counted and photographed under an ordinary optical microscope .4 cells with 200 μl serum-free medium. The lower chambers were fixed with 500 μl medium containing 10% FBS . After being incubated for 48 hours at 37°C, cells on the lower surface of the chamber were fixed with 4% paraformaldehyde and stained with 0.1% Crystal Violet, and cells on the upper surface were brushed. The chambers were placed under a light microscope and photographed to count cell numbers. In the SKL2001  activated group, this agonist was added into the serum-free medium to activate target cells.The transfected HS683 and T98G cells were cultured into the upper chamber in transwell inserts  at a density of 8 × 10μl pipette tip was used to create the straight wounds. Cells were washed using PBS for 3 times to eliminate cell fragments and unattached cells, and then, cells were cultured in a serum-free medium at 37°C. At 0 and 24 hours after the wounding, photographs were taken under a light microscope.The transfected HS683 and T98G cells were passaged in a 6-well plate and grew to 90% of the whole well. Then, a 200 β , p-GSK-3β , β-catenin , and GAPDH  were incubated overnight at 4°C. The membranes were incubated with corresponding horseradish peroxidase-conjugated secondary antibodies  at room temperature on the next day. The protein bands were then detected using an enhanced chemiluminescence detection kit .According to the protocol, total protein was extracted from transfected cells using RIPA buffer  and a bicinchoninic acid assay kit  was used to measure the concentration of protein. Equal amounts of protein samples were separated by 12% SDS-PAGE and then transferred onto a polyvinylidene fluoride membrane . The membranes with primary antibodies specific for AKT , p-AKT , GSK-3t-test or one-way ANOVA. It was considered a significant difference when p < 0.05.All experiments were performed 3 or more times. All data are expressed in the form of mean ± SD and analyzed using SPSS 19.0 . Differences between groups were analyzed using unpaired Student's Firstly, we measured the expression level of lnc-ZNF281 in 30 glioma tissues and 22 normal brain tissues using qRT-PCR. The results showed that lnc-ZNF281 was lowly expressed in glioma tissues compared with normal brain tissues . For subin vitro. We next performed wound-healing assay and transwell assay to explore the effect of lnc-ZNF281 on the migration of glioma cells. The wound-healing assay results showed that overexpression of lnc-ZNF281 inhibited the migrative ability of glioma cells significantly (Figures We performed CCK-8 cell proliferation assay and colony formation assay for assessing the effect of lnc-ZNF281 on the proliferation of glioma cells. The CCK-8 assay results showed that overexpression of lnc-ZNF281 decreased the growth rate of glioma cells Figures . The col Figures . Similar Figures .si-lnc-ZNF281 was transfected into T98G and HS683 glioma cells to construct lnc-ZNF281 silencing glioma cell lines . After tβ, and β-catenin, by Western blotting assay. qRT-PCR was performed to examine the expression level of β-catenin mRNA. The results showed that overexpression of lnc-ZNF281 decreased the protein expression levels of p-AKT and p-GSK-3β, while had almost no effect on total AKT and GSK-3β protein levels (Figures β-catenin mRNA and protein levels (Figures β/β-catenin pathway.To further study the potential molecular mechanisms of lnc-ZNF281 affecting glioma cells, we detected the protein levels of some classical markers, like AKT, GSK-3 Figures . lnc-ZNF Figures . These rβ/β-catenin signaling pathway, we treated lnc-ZNF281 overexpressing glioma cells with β-catenin agonist SKL2001 for 30 min [β-catenin were upregulated (Figures β-catenin agonist SKL2001, compared with lnc-ZNF281 overexpression alone (Figures β/β-catenin pathway.To further investigate whether lnc-ZNF281 suppressed glioma cell proliferation and migration via AKT/GSK-3r 30 min . After t Figures . Further Figures . These fβ-catenin pathway [β-catenin pathway, lnc-ZNF281 promoted cell proliferation and invasion in pancreatic cancer cells [lncRNA, as a research hotspot in recent years, has been confirmed to be closely related to the biological process of many tumors, including gastric cancer, breast cancer, liver cancer, and colorectal cancer –20. As a pathway . Moreoveer cells . On the er cells –25. HoweIn our study, we extracted total RNAs from 30 glioma tissues and 22 normal brain tissues. Then, we detected the expression level of lnc-ZNF281 using qRT-PCR. Results showed that lnc-ZNF281 had a low expression in glioma tissues. For exploring the role of lnc-ZNF281 in glioma, we transfected T98G and HS683 cells with lentiviral vectors and siRNAs to structure stably transfected glioma cell lines, which was confirmed by qRT-PCR. Then, a series of experiments were performed to investigate whether lnc-ZNF281 could regulate the progression of glioma cells. The cell proliferation results revealed that overexpression of lnc-ZNF281 inhibited cell proliferation in both T98G and HS683 cells. The wound-healing assay and transwell assay results showed that overexpression of lnc-ZNF281 repressed the migrative abilities of glioma cells. Moreover, silencing lnc-ZNF281 obtained the opposite findings. Consequently, these results above demonstrated that dysregulation of lnc-ZNF281 does regulate the biological process of glioma cells, which is worthy of further study.β-catenin pathway promotes cell proliferation, migration, and angiogenesis in glioma [β, which is known as the degradation factor of β-catenin [β regulates the stability of β-catenin protein directly to influence Wnt/β-catenin signaling pathway [β-catenin pathway to influence the progression of colorectal cancer [β/β-catenin pathway. We performed Western blot and qRT-PCR assays to measure the levels of p-AKT, AKT, p-GSK-3β, GSK-3β, and β-catenin. The results of Western blot and qRT-PCR showed that overexpression of lnc-ZNF281 inhibited phosphorylation of AKT and GSK-3β and decreased β-catenin mRNA and protein levels. These results suggested that lnc-ZNF281 regulated the progression of glioma via AKT/GSK-3β/β-catenin signaling pathway.Many studies indicate that changes of signaling pathways are closely related to the occurrence of glioma , 26, whin glioma . Interes-catenin . Additio pathway . Besidesl cancer . We wondβ/β-catenin signaling pathway. However, the research is in a very early stage and lacks animal and clinical experiments. It will be of significance to further test the effects of lnc-ZNF281 in the treatment of human glioma. Besides, there are some limitations in our study. First, the numbers of glioma tissues and normal brain tissues are insufficient. More clinical tissues should be used to confirm the expression levels of lnc-ZNF281 in glioma tissues and cell lines. Second, the expression level of lnc-ZNF281 in blood samples should be detected to explore the potential to be a biological marker for diagnosis and treatment.The importance of lncRNAs in diagnosis and treatment has been reported in glioma and numerous other cancers , 12, 31.β/β-catenin signaling pathway. Therefore, lnc-ZNF281 might become a novel direction for the research of biological progression of glioma, and it may be an effective target for glioma patients.Our study confirmed the downregulation of lnc-ZNF281 in glioma tissues. Moreover, we revealed that lnc-ZNF281 might inhibit proliferation and migration in glioma via AKT/GSK-3


Arisaematis, such as ScienceDirect, Wiley Online Library, Springer Link, Web of Science, CNKI, and WanFang Database. In this paper, the traditional uses, botany, phytochemistry, pharmacology, and toxicology of AR were reviewed. Finally, the existing problems and research directions of the research on AR are discussed.  This review is a collection of all possible studies on AR, published in scientific journals, papers, and books. Using the papers related to  Ninety-eight chemical constituents were isolated from AR. AR has a wide range of pharmacological effects, such as the effects on the central nervous system and cardiovascular system. It also has anti-tumor, sedative, analgesic, anticonvulsant, anti-inflammatory, expectorant, antiarrhythmic, anticoagulant, and other effects. It is also considered an effective drug for in vitro and in vivo validation.  AR is an excellent traditional medicinal plant in China. Pharmacological studies support the traditional use of AR and may verify the folk use of AR in the treatment of different diseases. The anti-tumor effect of AR has been widely concerned by scholars at home and abroad. It has become a hot spot in recent years and has made great contributions to the survival and development of human beings. Although it has a high value of comprehensive utilization, its development and utilization are far from enough. Therefore, the comprehensive development of AR is worthy of further analysis. Arisaematis rhizoma (hereafter referred to as AR) is a tuber of the Arisaema plant of the Araceae family . Th. ThA. erA. amurense Maxim. (东北天南星) is about 35–60 cm (see Arisaema amurensis), and they are obovate or broadly obovate, with a length of 11–15 cm and a width of 6–8 cm, all of which have irregular teeth. The inflorescence is 20–40 cm long, and the spathes are green or purple, with a total length of 11–14 cm. The inflorescence has rod-shaped appendages at the top. It is in berry red, flowers from July to August, and grows in a shady and humid forest on a shady slope.The height of 0 cm see , and theA. Heterophyllum Blume (异叶天南星) is a perennial herb  are oblate  are oblate and spherical   Table 5. Among ttosterol , ethyl gtosterol –29, galltosterol  . A variety of lectins have been found in AR, and blood agglutinin, lymph agglutinin, and sperm agglutinin have been found through cell research of humans and animals . Wu Hao toxicity , 35. Fentoxicity .It is rich in amino acids in AR. Wang Xing found 14 kinds of amino acids were obtained from the qualitative and quantitative analysis of AR  Table 8.Yi Jinghai eight nucleoside compounds were found in AR  Table 9. NucleosIn addition, Fu Ming obtained 8 compounds from 80% ethanol extract of rhizome of AR  Table 1. Zheng XAR has been reported to have a wide range of pharmacological activities, including the effects on the central nervous system and cardiovascular system; it is also used in the clinic for anti-tumor, sedation, analgesia, anti-convulsant, anti-inflammatory, expectorant, anti-arrhythmic, and anti-coagulant. In this section, we mainly introduce and analyze the pharmacological effects of AR .AR is a common traditional Chinese medicine for reducing phlegm. It has the effect of dryness and dampness reducing phlegm. The experiment was carried out by phenol red excretion method in mice showed AR aqueous solution (19 g/kg) had an expectorant effect . Nie RonArisaema (30°C10 g/kg) could significantly inhibit the convulsion rate of strychnine and reduce the convulsion mortality , and the inhibition rate of high dose group was 33.3%. It was found that all the treatment groups could inhibit the growth of S180 tumor, and the inhibition rate of the high-dose group was 33.3% [−1 [50 of 133.5 g/mL [50 of 0.24 mg/mL, 0.78 mg/mL, and 82.17 mg/mL [With the research on chemical constituents of AR in recent years, the study of its anti-tumor effect has become a hot spot in recent years. Zhang Zhilin found that 2.5 g/L and 1.25 g/L ethanol extracts of AR had significant effects on the proliferation of mouse spleen cells . Li Ling in mice . Jiang Sas 33.3% . Yang Zoas 33.3% . Zhao Ch3.3% [−1 . Liang F3.5 g/mL , 67. In 3.5 g/mL . Qiu Lim3.5 g/mL . Tang Hu3.5 g/mL . Li Feng3.5 g/mL . Qi Xiao3.5 g/mL . Qian Ji3.5 g/mL . Dong We3.5 g/mL . Tang Ji17 mg/mL –77.Oncomelania hupensis [Oncomelania hupensis and the examination of the scanning electron microscope has a cough-relieving effect [In addition to the pharmacological effects described above, AR also has some other pharmacological effects. Rats were given 60% ethanol extract of AR (1.4 g/kg), which could not only delay the occurrence time of arrhythmia but also shorten the duration of arrhythmia . It was hupensis . Sensitihupensis . In addihupensis . In addig effect .Araceae. Thus, the toxicities of AR have been comprehensively recorded and investigated. The toxic or irritant components of Araceae plants may be produced by special biological metabolites contained in the plants. It may include calcium oxalate needle crystal and its surface glycoprotein, and some trace polysaccharides [In China, AR is traditionally and commonly recognized as a toxic plant as other plants in charides , 81. Thecharides . The calcharides , resulticharides . The toxcharides , 86. Aft50 was 155.78 g/kg [50 of 21.58 g/kg [50 of the AR needle crystal group was 42.53 mg·kg−1, the LD50 of the raw AR powder group was 1062 mg·kg−1, and the LD50 of the processed product powder group was 2788 mg·kg−1 [Yang Zhonglin and Wu Lianying carried out an acute toxicity study and maximum tolerance test of AR , 88 Tab. Dong We.78 g/kg . In addi.58 g/kg . Tang Li mg·kg−1   = 149.106 ± 26.249 h·μg–1·mL–1, t1/2 = 2.300 ± 0.756 h, Cmax = 33.259 ± 3.192 μg/L, AUC (0⟶t) = 167.122 ± 95.766 h·μg–1·mL–1, AUC (0⟶∞) = 181.974 ± 108.915 h·μg–1·mL–1, t1/2 = 2.592 ± 1.175 h, and Cmax = 36.635 ± 19.53 μg/L. It can be seen from the blood concentration-time curve of the two flavonoids that the blood concentration of the two flavonoids rises obviously at 3 h, which may be related to the enterohepatic circulation, absorption, and distribution in vivo [So far, the pharmacokinetic studies on the extracts and compounds of this plant are very few. The pharmacokinetic studies of AR were mainly focused on flavonoid compounds, including schaftoside and isoschaftoside. Luo Fen studied the pharmacokinetic characteristics of schaftoside and isoschaftoside. In rats, the data are as follows: AUC (0⟶t) = 143.378 ± 26.249 h·To sum up, AR is a traditional Chinese medicine with a long history. It has more than 2,000 years of application history and continuous research of modern science. At present, many chemical constituents have been isolated and identified from this plant. There is no doubt that AR is an important traditional Chinese medicine, although it has certain toxicity. For this reason, in the past many years, many experts are constantly studying the south star and have made great contributions in many aspects. At the same time, in the process of continuous research, there are still some new problems and challenges, which need further research and exploration to meet the clinical needs.in vivo and in vitro verification to improve the safety of the clinical medication. So that AR can be better used better for the guidance of clinical medication to lay a certain foundation.First of all, as a traditional Chinese medicine, AR contains glycosides, sugars, flavonoids, alkaloids, saponins, and other chemical components with expectorant, anti-inflammatory, anti-convulsant, anti-tumor, and other pharmacological effects. There are many studies on it, and the anti-tumor effect of AR has also been widely concerned by scholars at home and abroad and has become a research hotspot in recent years. However, the material basis of other pharmacological effects is not clear, and how and what kind of effects some chemical components play are not clear. It is necessary to further study its monomer compounds and clarify the material basis through certain methods and experiments; AR has certain toxicity. Toxicity studies showed that most of them were irritant, and the long-term toxicity was not obvious. There are some problems in toxicity evaluation methods; for example, oral generated AR can stimulate the throat and make the throat smooth and hoarseness, and it is difficult to enlarge the throat so it is necessary to find a toxicity evaluation model to better evaluate the toxicity of AR. There are too few studies on the pharmacokinetics of AR, which should be paid more attention to In general, as a commonly used traditional Chinese medicine, AR still needs further study. This paper systematically and comprehensively introduces the research status of AR at home and abroad in recent years, including traditional application, phytochemistry, pharmacology, and toxicology. Although great progress has been made in its research, there are still some problems in all aspects. Therefore, we still need to make continuous efforts to develop and utilize AR.