Donor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown.This retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced.A total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually.The incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable. Infection transmission from donor to recipient is one of the primary causes that affect early survival rate of recipients after transplantation . The useB19V is a small single-stranded DNA virus which is highly infectious and can cause a wide range of pathological conditions . For immHowever, due to the lack of surveillance studies, the incidence of donor-derived B19V infections in kidney transplantations still remains unknown. In addition, a series of clinical issues regarding donor-derived B19V infections are all uncertain currently, such as whether the kidney donor needs to be routinely screened for B19V, whether the kidneys from the donor with B19V DNAemia are acceptable, what are the clinical features of donor-derived B19V infections, how to treat donor-derived B19V infections, etc. Thus, this study provides further information on addressing these problems mentioned above.We carried out this study with the purposes of determining the incidence, clinical features, and treatment of donor-derived B19V infections in kidney transplant recipients (includes living and deceased donor kidney transplantations).This was a single-center, retrospective, cohort study with the aim of evaluating the donor-derived B19V infections occurring in living and deceased donor kidney transplantations. For living donor kidney transplantation, all donors and the corresponding recipients included in this study were related. Since January 2015, the use of executed prisoners as a source of organs for transplantation had been comprehensively terminated in China . For decFrom January 2016 to December 2020, we performed 927 living donor kidney transplants and 1,267 deceased donor kidney transplants in the Center of Kidney Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University. The following exclusion criteria were applied for patients: 1) those who received an organ other than a kidney, 2) those who received ABO incompatible kidney transplantation, or 3) those whose blood specimens could not be retained. Demographics, clinical characteristics, laboratory findings, and outcomes of donors and recipients were collected from kidney transplantation electronic database and medical records.3 copies/ml and the linear range of detection ranged from 2 × 103 to 1 × 108 copies/ml. A serum sample with viral load corresponding to ≥1 × 103 copies/ml was considered to be positive.Commercial human parvovirus B19 real-time polymerase chain reaction (PCR) kit  was used for the detection and quantification of B19V-DNA in serum. The lowest detection limit for this test was 1 × 10The serum of the living donors and their corresponding recipients were evaluated for B19V-DNA on the day before transplantation and within 7 days after the transplantation, while the serum from recipients of deceased donor were evaluated within 7 days after the transplantation. Furthermore, the serum from recipients with unexplained anemia and reticulocytopenia within 6 months after kidney transplantation were also tested. In post-transplantation setting, if recipients of deceased donor developed B19V infection, blood samples that were collected within 24 h before transplantation from both recipients and corresponding donors would be further evaluated for B19V-DNA.Serum creatinine and the estimated glomerular filtration rate (eGFR) of recipients with donor-derived B19V infections were checked prior to B19V infection, during B19V infection, and 12 months after B19V infection. The eGFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula.Standard triple-drug maintenance immunosuppression includes tacrolimus , mycophenolic, and prednisone. All patients were treated with methylprednisolone 10 mg/kg/day on days 0, 1, and 2. Dosage of prednisone was slowly tapered from 60 to 10 mg/day in 1 month after transplantation. All patients received induction with antithymocyte globulin (ATG) or interleukin-2 receptor antagonist (basiliximab). Basiliximab was given with a dose of 20 mg on the operation day and the 4th day after transplantation. From baseline, ATG was administered at a dose of 1 mg/kg/day and a maximum of five doses was given. All recipients received prophylactic ganciclovir treatment with a dose of 500 mg three times daily for 3 months post-transplant. A daily dose of 40 mg/200 mg to 80 mg/400 mg sulfamethoxazole/trimethoprim was applied for 9–12 months to prevent pneumocystis carinii pneumonia (PCP) except patients with sulfa allergies.t-test, while the non-parametric Mann–Whitney U test was used for data that were not normally distributed. Chi-square or Fisher’s exact test was used for categorical data. All statistical tests were two-tailed, and p <0.05 was considered statistically significant.Hemoglobin, serum creatinine, and eGFR in this article were described in the form of mean values plus standard deviations (SDs). Viral load and time of B19V infections were described as median values with ranges. Categorical variables were presented as percentages. For normally distributed data, continuous comparisons between the two groups were conducted using Student’s From January 2016 to December 2020, we performed 927 living and 1,267 deceased donor kidney transplantations. According to the exclusion criteria, 104 living and 42 deceased donor recipients were excluded in this study. Recipients were followed up for an average of 27.9 months.3 copies/ml, ranging from 1 × 103 to 1.5 × 104 copies/ml. All 15 donors had no clinical manifestations of B19V infection such as fever, flu-like symptoms, weakness, dyspnea, arthralgias, rashes, and orthostatic hypotension during the follow-up period from 1 to 34 months. For these 15 corresponding recipients, B19V DNAemia  could be detected in three patients within 7 days after transplantation , it was possible to detect B19V-DNA in serum samples before donation. The median viral load was 3.1 × 10antation Table 1.3 copies/ml, ranging from 2.2 × 103 to 2.5 × 105 copies/ml. The hemoglobin of 16 recipients raised from 10.3 ± 1.2 g/dl before transplantation to 11.4 ± 1.4 g/dl after 1-month transplantation. Two recipients with low-level DNAemia after transplantation had no clinical manifestation of B19V infection during follow-up. Moreover, B19V DNAemia of 14 recipients turned negative within 7 days after operation. However, one recipient was diagnosed with PRCA at the 41th day after transplantation. At that time, viral load of the serum sample was 6.06 × 109 copies/ml and the reticulocyte was 0.1%. During the course of infection, the lowest hemoglobin concentration was 5.6 g/dl. Eventually, his B19V DNAemia turned into negative at the 510th day after transplantation by treatment.Among 823 recipients, 16 (1.9%) were found to be B19-DNA positive before transplantation although no B19-DNA could be detected in the serum from their corresponding donors. The median viral load was 4.45 × 109 copies/ml, ranging from 3.4 × 107 to 1.1 × 1011 copies/ml. In addition, all of these recipients and their corresponding donors were both negative for B19V DNAemia before transplantations. In the process of infection, the mean lowest hemoglobin concentration was 6.4 ± 1.3 g/dl (ranging from 4.3 to 9.2 g/dl) and the reticulocyte was no more than 0.4%.B19V DNAemia, along with pure red cell aplasia, had occurred in 32 (3.9%) recipients at the median time of 42 days (ranging from 7 to 237 days) after transplantation, and their median viral load was 2.95 × 105 copies/ml, ranging from 1.1 × 103 to 8.5 × 1010 copies/ml. It was noteworthy that 9 corresponding donors in 18 of 48 recipients were B19V DNAemia positive, and the detailed information is shown in p = 0.001).Among 1,225 deceased donor kidney transplantations, 48 (3.9%) recipients who were B19V DNAemia negative before transplantation switched to positive within 7 days after the transplantation. The median viral load was 2.1 × 109 copies/ml (ranging from 1.5 × 108 to 2.3 × 1010 copies/ml) at the diagnosis of PRCA. Seventeen recipients had no clinical manifestation of B19V infection during follow-up. Additionally, B19V DNAemia of these corresponding donors was negative before transplantation. Interestingly, the allograft of eight recipients came from the same four donors.Of the remaining 30 recipients who developed B19V DNAemia within 7 days after transplantation, 13 recipients were diagnosed with PRCA at the median time of 14 days (ranging from 7 to 48 days) after transplantation. The median viral load was 7.5 × 109 copies/ml (ranging from 7.6 × 107 to 6.8 × 1010 copies/ml). In the process of infection, the mean lowest hemoglobin concentration was 5.6 ± 0.6 g/dl (ranging from 4.9 to 6.8 g/dl) and the reticulocytes were no more than 0.3%.Among the other 1,177 deceased donor kidney transplantations, B19V infection occurred in 14 (1.2%) recipients who were B19V DNAemia negative before and within 7 days after transplantation. Moreover, these corresponding donors were both B19V DNAemia negative before donation. For the other 14 recipients who received the same donor kidney, B19V DNAemia was also negative. The median time of infection was 30 days (ranging from 21 to 666 days) after transplantation, and the median viral load was 7.85 × 102 prior to infection, during the infection, and 12 months after infection, respectively. In this study, recipients infected with B19V from the donor did not develop B19V-related graft damage that compromises allograft function. We can observe that transient elevated serum creatinine occurred in 6/21 (28.6%) recipients . At the latest follow-up, these recipients were all alive with functioning allografts.As noted in Unlike bacterial infections, donor-derived virus infections are rarely reported in the past due to difficulty of diagnosis, other than the hepatitis B virus, the hepatitis C virus, and the cytomegalovirus . This stIn our study, kidney recipients with B19V infection predominantly presented with unexplained anemia, reticulocytopenia, and no response to erythropoietin therapy, and bone marrow examination  is also an important diagnostic basis . RecipieWe found that 15 (1.8%) living donors and 16 (1.9%) living recipients with low-level B19V DNAemia had no clinical manifestations of B19V infection before transplantation. The incidence of B19V DNAemia in living donors and recipients was very low before transplantation, and even if it occurred, the level of DNAemia was too low to cause serious consequences. Therefore, it did not appear to be necessary for the living donors and recipients to do the routine B19V screening before transplantation. Of course, if anemia of donors and recipients could not be explained clearly, B19V screening is still needed.For 32 living recipients with pure red cell aplasia, the B19V infection seemed to be irrelevant to their corresponding donors. B19V has been shown to be transmitted mainly through inhalation of infected aerosol droplets in immunocompetent individuals . As ther9 copies/ml, and five of the six corresponding recipients developed pure red cell aplasia. Although not statistically significant, it was noteworthy that the viral load of the donor was seemingly related to the incidence of developing pure red cell aplasia in recipients. What is more, our study demonstrated that a higher B19V viral load in recipients within 7 days after transplantation was positively correlated with the incidence of developing pure red cell aplasia in recipients with donor-derived B19V infection in deceased donor kidney transplantation. Thus, we need to pay more close attention to these patients and perform treatment in time. Moreover, we recommend that timely treatment is necessary if the B19V viral load is greater than 1.0 × 106 copies/ml in recipient within 7 days after transplantation, and conservative observation can be adopted if the B19V viral load is less than 1.0 × 106 copies/ml. For blood transfusion, as the B19V can also be transmitted by blood or pooled blood products, immunocompromised individuals were at high risk of severe complications due to B19V infection from contaminated blood products. Therefore, in 2004, the U.S. Food and Drug Administration suggested that a serum sample containing more than 1 × 104 copies/ml of B19V-DNA should be excluded because of the risk of transmission  recipients receiving the kidneys from the nine corresponding donors were positive for B19V DNAemia within 7 days after transplantation. By analyzing the pre-transplant blood samples of these recipients and their corresponding donors, we can conclude that the recipients were infected with B19V from the donor. Among these 18 recipients, 11 developed pure red cell aplasia. The viral loads of donors E, F, and J were more than 1.0 × 10smission .Eid et al., in 2006, reported that allograft dysfunction after solid organ and hematopoietic stem cell transplant was observed in 10% of cases at the time of B19V disease . In kidnAll recipients with donor-derived B19V infections showed excellent prognosis, and the kidney graft survival rate at 1 year was 100%, which suggested that the kidneys from B19V-infected donors were acceptable for kidney transplantation. In particular, in cases where the donor had low-level B19 DNAemia, the recipients were less likely to have obvious clinical manifestations and the B19V could be quickly cleared even if the recipient was infected. If the donor had high-level B19V DNAemia, as well as the recipient, timely treatments including the adjustment of immunosuppressant and/or the infusion of large doses of immunoglobulin were needed to be given to the recipient . This stSeveral limitations in our study are worth declaring. First, the present study was limited by its retrospective design. Another limitation was that we did not routinely detect for B19V in deceased donors. B19V of the donor would be retrospectively tested only when B19V infection occurred in their corresponding recipients. What is more, serological assays for detection of IgM/IgG antibodies from the living donors were not performed before transplantation. This may explain why B19 DNAemia was found only in three recipients of living donor transplantation. Lastly, there is still a lack of robust evidence to confirm that the infection was 100% derived from the donor.6 copies/ml in recipients within 7 days after transplantation, and conservative observation can be adopted if the viral load is less than 1 × 106 copies/ml. We hope that our work will provide some theoretical basis for future research and clinical practices.In this study, we firstly reported the epidemiological data of donor-derived B19V infections in kidney transplantation through routinely monitoring B19V infection in living and deceased donors and recipients before and after transplantation. Considering the low incidence of donor-derived B19V infection and that the infection can be well controlled by treatment even if it happened, it seems unnecessary to screen for B19V among the donors. We reached the conclusion that kidneys from donors with B19V infection were acceptable for transplantation. Moreover, the DNAemia of the corresponding recipient should be closely monitored and early treatment should be initiated according to the virus level. We recommended that timely treatment is necessary if the viral load is greater than 1 × 10The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.WP conceived the study. YY, CW, JL, XW, RW, HH, and JW performed the data collection and analyses. YY prepared the first manuscript draft. WP and JC provided major revisions and comments to the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Health and Family Planning Commission of the People’s Republic of China (WKJ-ZJ-1924), Basic Public Welfare Research Program of Zhejiang Province (GF20H150031), and National Natural Science Foundation of China .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We report on three patients with mesencephalic aqueduct obstruction, which completely blocked the cerebrospinal fluid communication between the third and fourth cerebral ventricle, demonstrated by standard and high-resolution magnetic resonance sequences. Only one patient developed radiological and clinical presentation of hydrocephalus, without radiological signs of increased intraventricular pressure. The remaining two patients did not show clinical signs of hydrocephalus and had a normal radiological presentation of the ventricular system. These findings contradict the classical concept of cerebrospinal fluid physiology. This concept assumes a unidirectional circulation of cerebrospinal fluid through the mesencephalic aqueduct from the secretion site, predominantly in the choroid plexuses, to the resorption site, predominantly in the dural venous sinuses. Therefore, the obstruction of the mesencephalic aqueduct would inevitably lead to triventricular hypertensive hydrocephalus in all patients. The current observations, however, accord with the new concept of cerebrospinal fluid physiology, which postulates that cerebrospinal fluid does not circulate unidirectionally because it is both formed and resorbed along the entire capillary network within the central nervous system. The generally accepted classical concept of cerebrospinal fluid (CSF) physiology postulates the mesencephalic aqueduct's patency as one of the preconditions for maintaining physiological volumes and pressures in the CSF system. According to the classical concept, CSF is secreted predominantly by the choroid plexuses within the ventricular system. It then flows unidirectionally into the subarachnoid space at the skull base, from where it circulates to the resorption site, located predominantly in the dural sinuses and to a lesser extent in the perineural lymphatic system -7. The CIn this study, we report on three patients of different ages with mesencephalic aqueduct obstruction. We analyzed their clinical and neuroradiological findings from the perspective of the classical concept of CSF physiology -7 and thPatient 1 was a male preterm infant born at a gestational age of 25 weeks and 2 days  . EnteralFIT, Siemens, Germany) using a 64-channel head and neck coil. In addition to the standard T1 and T2 sequences, we also used a 3D T2 SPC sequence, which is sensitive to CSF movement artifacts , high-resolution 3D T2 space ZOOMit sequence , and high-resolution T1 MPRAGE sequence .MRI exams, at term-equivalent age and at age 2, were performed on a 3T MR device . After delivery, the patient developed respiratory distress syndrome requiring non-invasive and invasive mechanical ventilation. She also developed sepsis, but recovered completely after antibiotic therapy. The child was discharged at a corrected age of 38 weeks and 6 days, with a bodyweight of 2490 g (3 centiles), head circumference of 32 cm (5 centiles), and normal clinical status. MR exam was performed at term-equivalent age with the same MR sequences as described for Patient 1. The scan showed an obstruction of the cranial portion of the mesencephalic aqueduct , which cPatient 3 was a 56-year-old man referred for MR exam due to poor concentration, headache, forgetfulness, balance disorder, tinnitus, and double vision lasting seven months. He also complained of occasional urinary incontinence for many years. The scanning was performed with the same 3T MR device as described for the two other patients. In addition to standard T1 and T2 cross-sections, high-resolution T2 CISS cross-sections  were obtained through the area of the mesencephalic aqueduct.MR exam showed a complete obstruction of the central part of the mesencephalic aqueduct by an aqueductal membrane . Axial  and coroIn this study, we demonstrated in three patients how a blocked mesencephalic aqueduct could result in different neuroradiological and clinical outcomes, ranging from an entirely normal neuroradiological and clinical status to clinically and neuroradiologically verified hydrocephalus.MRI scans performed in Patient 1 and Patient 2 at a neonatal age showed that it was possible for patients to have a completely obstructed mesencephalic aqueduct without showing clinical and radiological signs of triventricular hypertensive hydrocephalus. This finding is in contrast to the classical concept of CSF physiology, which postulates that about 500 mL of CSF a day is actively secreted (which is independent of intraventricular pressure) predominantly in the choroid plexuses of the lateral ventricles ,9. This However, both patients' findings accord with the Bulat-Orešković-Klarica hypothesis, which assumes that the intracranial fluids exchange is controlled by osmotic and hydrostatic forces in the capillaries and interstitium and that it takes place on the capillary membrane along the entire nervous system -17. ThisAnimal experiments showed no expected increase in CSF pressure or ventricular dilation proximal to the obstruction site in the case of an aqueduct blockade lasting several hours . In addiAlthough Patients 1 and 2 had aqueduct obstruction without signs of hydrocephalus, a significant number of patients with aqueduct obstruction/stenosis do develop LAMO hydrocephalus, and some undergo endoscopic ventriculostomy (Patient 3) or placing of a drainage shunt due to a worsening clinical status -25. DespThus, the cases described in the current article do not accord with the generally accepted classical hypothesis, warranting a new explanation of the pathophysiological consequences of the mesencephalic aqueduct obstruction. Obstruction/stenosis of the mesencephalic aqueduct has been shown to decrease/interrupt the bidirectional oscillatory movement of CSF through the mesencephalic aqueduct that physiologically occurs during systole and diastole. This interruption changes the biomechanical load of the periventricular tissue . ProlongIn patients with Chiari type 1 malformation, hydrocephalus often occurs due to the reduction/interruption of bidirectional CSF movement at the cranio-cervical junction. However, in Chiari type 1 malformation, assumed intracranial secretion, circulation, and CSF resorption are not disturbed ,34. A siIn Patient 1, a spontaneous rupture of the aqueduct membrane established the CSF communication between the third and fourth brain ventricle. Clinical practice has shown that sometimes patients with an obstructed mesencephalic aqueduct experience spontaneous ventriculostomy, which establishes the CSF communication between the third ventricle and suprasellar cisterns -38. ThisTherefore, CSF obstruction at the aqueduct level causing ventricular dilatation without pressure rise is completely inexplicable by the classical hypothesis of CSF physiology. The described examples, however, accord with the Bulat-Orešković-Klarica hypothesis, which postulates that the obstruction of the mesencephalic aqueduct does not necessarily imply hydrocephalus development. This hypothesis defines hydrocephalus as a pathological state where CSF is excessively accumulated inside the cranial part of the CSF system, predominantly in one or more brain ventricles, as a consequence of impaired hydrodynamics of intracranial fluids between the CSF, brain , and blood compartments .


About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon.A total of 60 autistic individuals  (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents.P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG , HDLC , TG/TC  and TG/LDLC , and were negatively correlated with CARS . Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors.Compared with control subjects, autistic individuals had lower levels of TC (Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon. Autism spectrum disorder (ASD) is mainly manifested in the deficits of social communication and social interaction, as well as repetitive behavior, limited or restricted interest or activity . EpidemiThe exact etiology and mechanism of the autistic regression phenomenon remain unclear. Current research assumes that it may be related to the interaction between biological and environmental factors , 11, 12.Former studies have identified that plasma RBP4 levels both in the first trimester and second trimester are dose-dependently associated with increased risk of gestational diabetes mellitus (GDM) . In addiAdditionally, abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy of autism –21. FurtAutistic participants were 60 children and adolescents aged 3 to 14 years old, 39 males and 21females, the average age was 7.3 ± 3.2 years. Healthy control participants were 36 children and adolescents aged 3 to 14 years old, 12 females and 24males, the average age was 7.3 ± 3.1 years. Autistic participants were recruited from the outpatient department of child and adolescent psychiatry in Shanghai Mental Health Center between September 2018 and August 2019. All autistic participants were by the diagnostic criteria of autism spectrum disorders proposed by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Healthy controls were recruited from the children who came to the same hospital during the same period for regular consultation but had not been diagnosed with any mental disorders. Individuals with Fragile X syndrome or other pervasive developmental disorders, obsessive-compulsive disorder, affective disorder or other neuropsychiatric disorders, neurodegenerative disorders, brain trauma or cerebrovascular disorders, metabolic disorders, or immunological disorders were excluded.This study was performed in strict accordance with the Declaration of Helsinki and other relevant national and international regulations. All procedures for this study were approved by the institutional review boards of Shanghai Mental Health Center. Written informed consent was obtained from the parents before enrollment of the children and adolescents.Child Autism Rating Scale (CARS) was applied to evaluate autistic symptoms . Total sAutistic participants were further assessed based on the following questionnaire  and wereThe venous blood was collected and the serum and cellular components were separated within 2 h after 3000 g centrifugation for 10 m. The obtained supernatant (serum) was stored at -80 °C for further analysis. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured by the enzymatic method on Olympus AU5400 automatic biochemical analyzer .Serum RBP4 levels were assayed in duplicate by using a sandwich enzyme-linked immunosorbent assay (ELISA) kit  according to the manufacturer’s protocol.2 test was used to compare the gender between the two groups. Mann-Whitney U test was used for statistical comparison of continuous data without normal distribution. Spearman’s rho test was used to analyze the correlations with the data of nonnormal distribution. Normally distributed data were tested using Pearson’s correlation. Logistic regression was used to analyze the risk factors for the autistic regression phenomenon, and the odds ratio (OR) and 95 % confidence interval (CI) were calculated. Crude OR and adjusted OR were estimated by bivariate and multivariate logistic regression analysis, and the crude model analyzed the crude data only, the adjusted model was adjusted for age, gender, BMI, TC, TG, LDL-C, HDL-C, CARS. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of RBP4 and TG to predict the autistic regression phenomenon. All statistical tests were two-tailed, and p < 0.05 was considered statistically significant.IBM SPSS Statistics was used for data analysis. The normality of data distribution was determined with the Shapiro–Wilk test. Normally distributed data were expressed as (mean ± standard deviations). The skewness distributed variables were reported as the median (interquartile range). An independent sample t-test was used to compare the normally distributed continuous data between the two groups. Χ P < 0.01), and a lower level of HDLC (P = 0.027).The demographic data and biochemical characteristics are presented in Table P < 0.01).Sixty autistic participants were subdivided into 18 participants with regression phenomenon and 42 individuals without regression phenomenon. Compared with those without regression phenomenon, individuals with regression phenomenon had lower TG and RBP4  and TG/LDHC , were negatively correlated with CARS . In ASD-NR group, the levels of RBP4 were also positively correlated with TG  and TG/LDHC , were negatively correlated with CARS . In the whole ASD group, the levels of RBP4 were positively correlated with TG , HDLC , TG/TC , TG/LDLC , were negatively correlated with CARS .The correlation of RBP4 with clinical parameters in autistic participants are shown in Table P = 0.005). In addition, the optimal cut-off value of RBP4 for the prediction of the autistic regression phenomenon was 20.6 ug/ml, with a sensitivity of 94.4 % and a specificity of 42.9 % .As shown in Fig. After the adjustment of the potential confounding factors including age, gender, BMI, CARS, and the levels of TG, TC, HDL-C, LDL-C, logistic regression demonstrated that decreased RBP4 concentration increased the risk of the autistic regression phenomenon  Table .The present study demonstrated that autistic participants had lower levels of TC, RBP4, and HDLC. Additionally, autistic participants with regression phenomenon had lower levels of TG and RBP4. Furthermore, the levels of RBP4 were positively correlated with TG and were negatively correlated with the severity of autism. Moreover, decreased RBP4 concentration increased the risk of the autistic regression phenomenon.Consistent with the present study, some researchers also found that there were significant differences in TG, TC, HDL-C, non-HDL-C, and TC/HDL ratio in ASD group and healthy volunteers regardless of their diets , 26. DifWhen compared with those without regression phenomenon, the present study demonstrated that autistic participants with regression phenomenon had lower TG. However, the present study didn’t detect the significant difference of TC or HDLC between ASD-R and ASD-NR groups. This indicates that TG may be related to the autistic regression phenomenon, whereas TC and TG may play different roles in the progression of the autistic regression phenomenon. Similarly, some researchers have found that mainly amino acid, lipid, and nicotinamide metabolism were significantly different between ASD with regression phenomenon group and ASD without regression phenomenon group . In geneFormer studies have found that Serum RBP4 levels of major depressive depression individuals were significantly lower than that of the healthy control group . HoweverThe results provide evidence that lipids and RBP4 were related to the presence and regression phenomenon of ASD. They can jointly predict the early diagnosis of ASD, guide early clinical intervention, early identification of regression phenomenon, and evaluate the prognosis of ASD.The present study observed a significant difference in the serum level of RBP4 in ASD and healthy controls for the first time as well as the correlation between RBP4 and lipids. Nevertheless, several limitations of the present study should also be considered. As the study was performed in the Chinese Han population, the results need to be confirmed in other regions and ethnicities. In addition, the relatively small sample size may cause a potential low power of our results. Besides, the age range of the subjects included in this study was 3 to 14, whether those autistic participants who are out of this age range have similar characteristics is not clear. Further study is needed to expand the age range to demonstrate the changes in lipid and RBP4 throughout the life cycle of autistic participants.In summary, autistic participants had lower levels of RBP4, TC, and HDLC. Furthermore, compared with those autistic participants without regression phenomenon, autistic participants with regression phenomenon had lower TG and RBP4. Meanwhile, the levels of RBP4 were positively correlated with TG and were negatively correlated with CARS. Moreover, decreased RBP4 concentration increased the risk of the autistic regression phenomenon. Altogether, these results suggest that the serum RBP4 in combination with lipids may be considered predictors associated with the autistic regression phenomenon. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon. The results indicate that correcting lipids and RBP4 to appropriate levels may help clinicians and practitioners in early intervention of the autistic regression phenomenon. However, it is important to note that the results must be interpreted with caution. Due to the heterogeneity of the condition, as well as the huge difference in developmental trajectories, the intervention should be tailored to that particular child regardless of being in a possible regression-risk group or not.


To evaluate the difference and efficacy of two donor liver procurement methods for treatment of pediatric acute liver failure (PALF) by living donor liver transplantation (LDLT).A total of 17 patients  with PALF who underwent LDLT in our hospital between October 2016 and October 2020, and prognostic efficacy of donors and recipients using two donor liver procurement methods were analyzed.P ≤ 0.01). No death or serious complication occurred in either donor group.The donors and recipients were both divided into laparoscopic (7 cases) and open (10 cases) donor liver procurement groups. In the recipients, two deaths occurred in the laparoscopic group and one in the open group, and there were three postoperative complications in the laparoscopic group and six in the open group. The cumulative 1-year and 3-year survival rates in the laparoscopic group and the open group were 80.0% and 85.7% separately. There was no difference in the postoperative survival and complications rates between the two groups. In the donors, the operation time, postoperative hospital stay, and blood loss of the laparoscopic group was significantly reduced compared with the open group (Laparoscopic donor liver procurement is worth recommending than open donor liver procurement for treatment of PALF combined with LDLT in qualified transplant centers. Pediatric acute liver failure (PALF) is a rapidly progressive, end-stage disease of the liver. Even with symptomatic supportive treatment for PALF, such as drugs or an artificial liver, it is sometimes difficult to save lives. Liver transplantation (LT) sometimes is the only effective treatment. Due to the rapid progression of the disease, the shortage of donor livers makes it difficult for some children to receive rapid and effective LT. It is estimated that the mortality rate of PALF on the waiting list for LT is about 20% . Living We collected data from 140 pediatric LT recipients from October 2016 to October 2020; 19 of whom had PALF. We reviewed and included data from 17 patients with PALF who underwent LDLT, including sex, age, weight, blood type, pediatric end-stage liver disease (PELD) score, initial symptoms, prognosis, and complications. At the same time, the donor data were included: sex, age, weight, surgical method, intra-operative blood loss, length of hospital stay, survival status, and postoperative complications.Donor operations were divided into laparoscopic and open access groups. In the laparoscopic group, puncture instruments with a diameter of 1 cm were placed in the left and right mid-clavicular line and left and right axillary line, respectively. The first hilum of the liver was dissected; the left hepatic artery and the left branch of the portal vein were separated; the peripheral hepatic ductile band was fully dissected, exposing the left lateral lobe; the left lateral lobe was turned to the right; the second hilum of the liver was exposed and dissected; the left branch or the left upper margin branch of the hepatic vein was isolated and marked with blue ribbon. The liver tissue, blood vessels, and bile ducts were clipped and dissected with an ultrasonic knife along the right side of the falciform ligament with the pre-resection line marked by an electro-knife. The left hepatic duct was isolated at the level of the first hilum, then the proximal end was clipped, and the distal end was dissected until the left hepatic vein remained at the second hilum. The donor liver obtained by laparoscopy cannot be cold perfused in advance, which is different from a liver donated after cardiac death. To prevent coagulation in the graft from affecting the graft quality, after heparinization, the left hepatic artery, left portal vein, and left hepatic vein were successively clipped, and the liver was divided into two parts. Then, the liver was removed from the incision above the symphysis pubis of the lower abdomen or the woman donor's original cesarean section incision with a specimen bag. Then protamine was used for deactivating heparin after the liver was detached and removed. In the open group, a subxiphoid L-shaped incision (~15 cm in length) was made, and the remaining donor liver was obtained using the same procedure as in the laparoscopic group.All the recipient operations were performed with the piggyback technique. The left hepatic vein of the donor, portal vein of the donor, and hepatic vein of the recipient were trimmed, and the left and right hepatic veins were trimmed into a common opening. A 5-0 polydioxanone suture was used to continuously suture the opening of the left hepatic vein of the donor liver and the opening of the recipient hepatic vein. A 6-0 polydioxanone suture was used to continuously suture the bridging vessels to the portal vein of the donor and recipient. After the end of the anastomosis, the inferior vena cava and portal vein occlusion forceps were opened, respectively. The patency of each anastomotic site and the presence of leakage were examined. A 9-0MAXON suture was used to perform end-to-end anastomosis between the donor's and recipient's left hepatic artery. After the operation, B ultrasound was used to examine the portal vein, hepatic artery patency of blood flow. Choledochoenterostomy/end-to-end bile duct anastomosis was performed after the donor and recipient bile ducts were trimmed. After checking for active bleeding and placing the drainage tube, the abdomen was closed.P < 0.05 was considered to be a significant difference.We used SPSS version 23.0 to study cumulative survival of recipients and outcomes of donors in the laparoscopic and open groups. The mean value, median value, and maximum and minimum values of continuous variables were calculated. Mann-Whitney U test and chi-square test were used to judge the difference between the two groups. Immunotherapy for LT recipients included a combination of steroids and tacrolimus (FK506).Methylprednisolone was 5 mg/kg on the first day after surgery and reduced daily thereafter. Prednisone was 0.25–1 mg/kg orally on Day 8 after surgery and was stopped about 6 months after surgery. The initial dose of tacrolimus was 0.1–0.15 mg/kg/day, and the maintained plasma concentration was 8–12 ng/mL within 1 month after surgery, 7–10 ng/mL within 2–6 months after surgery, 5–8 ng/mL within 7–12 months after surgery, and 5 ng/mL 1 year after surgery and long-term thereafter.This study was approved by the Institutional Review Board at the Huashan Hospital of Fudan University. Our work complies with the Declaration of Helsinki and the Declaration of Istanbul. No illegal commercial transactions were involved.Among the 17 recipients, 12 were men and 5 were women, with a mean age of 26.7 ± 7.0 months. In donors, 8 were men and 9 were female, the mean age of the donors was 31.8 ± 1.4 years, all were parents of the recipients . The medP > 0.05). The causes of death were tension pneumothorax, cerebral hernia, and primary graft failure separately. There was no difference in postoperative survival and complication rates between the laparoscopic and open groups (Three children (17.6%) died: two in the laparoscopic group and one in the open group, all within 1 month after surgery. The cumulative 1-year and 3-year survival rates in the laparoscopic group and the open group were 80.0% and 85.7%, respectively, there is no difference between the two groups 2 years after surgery. He was treated with ERCP (endoscopic retrograde cholangiopancreatography) at first, but failed, and then underwent a second choledochoenterostomy a month later and recovered at last; one case of chylous leakage was cured by conservative treatment; one recipient died of liver failure.P ≤ 0.01), and the blood loss in the laparoscopic group was less than the open group. But there was no significant difference in the WIT and costs between the two groups (Table 5). One donor with postoperative biliary leakage was discharged after conservative treatment. Another donor with postoperative bile duct stenosis, presenting as obstructive jaundice, was discharged after treatment with percutaneous transhepaticcholangial drainage (PTCD). There was no difference in the incidence of complications between the two groups. The laparoscopic donors were more satisfied with their postoperative wounds than the open donors and there was no significant psychological discomfort in the two groups  of total laparoscopic procurement and 8 cases (53.3%) of open access. Another two donor livers were derived from the left lobe of the liver, procured by open access. The mean preoperative preparation time for all 17 cases was 1.9 ± 1.1 d. In the laparoscopic group, the mean postoperative hospital stay was 5.3 ± 0.5 d, the mean operation time was 3.3 ± 0.75 h, the mean intra-operative blood loss was 147.1 ± 35.0 mL, and no donor transfusion was performed. The mean warm ischemia time (WIT) is 183.1 ± 21.8 s in the laparoscopic group and the mean costs are about $5,364 USD. In the open group, the mean postoperative hospital stay was 8.7 ± 2.8 d, the mean operation time was 5.0 ± 1.6 h, and the mean intra-operative blood loss was 230.0 ± 53.7 mL. The mean WIT is 190 ± 19.3 s in the open group and the mean costs are about $5,768.1 USD. Both the mean operation time and the mean length of hospital stay of the laparoscopic group was significantly shorter than that of the open group  of pediatric LT in our center, which was basically similar to the 12.9% reported by Baliga et al. 0 of pedi, 7. Oh eWith the rapid development of laparoscopic surgery and the exploration of laparoscopic donor liver procurement, which liver procurement method is better remains clear. The 1-year and 5-year survival rates of PALF recipients was reported as from 74 to 87% , 8, 9. TAlthough there are few empirical reports on the use of LDLT combined with total laparoscopic donor liver procurement for treatment of PALF, the minimally invasive and safe use of laparoscopic donor liver procurement is not in doubt. In 2016, our center carried out the first total laparoscopic donor liver procurement operation in East China . Then thLaparoscopic donor liver procurement also has limitations. Total laparoscopic donor liver procurement requires the surgeons to be proficient in laparoscopic surgery and liver resection, and to overcome surgical space narrowing. Removal of the liver grafts from the abdominal cavity is also a very demanding procedure, which may significantly increase the WIT. But in our study, the WIT between the two groups was similar and there is also no statistical difference. Moreover, for donors with complex structures of the left hepatic vein, laparoscopic donor liver resection is not suitable. For example, donors with multiple branches of S2 and S3 hepatic vein openings have a risk of tearing and bleeding of the middle and left hepatic veins . FurtherWhat is more, in our study, the small number of cases is our limitation. We will collect more cases in the future and make efforts to conduct multi-center studies to expand the sample size.In conclusion, despite the disadvantage above, we believe that the combination of minimally invasive laparoscopic donor liver procurement will certainly become the future direction of LDLT. We recommend LDLT combined with total laparoscopic left lobe donor liver procurement as the first option for PALF patients in qualified transplant centers.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board at Huashan Hospital of Fudan University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.JP: study concept and design, acquisition of data, analysis and interpretation of data, and drafting of manuscript. CS, RL, YT, LL, WC, and XX: critical revision of manuscript. ZW: critical revision of manuscript. All authors contributed to the article and approved the submitted version.This work was supported by National Natural Science Foundation of China (81873874 and 82071797), Clinical Research Plan of SHDC (Nos. SHDC2020CR2021B and SHDC2020CR5012).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cryptorchidism in horses is a commonly occurring malformation. The molecular basis of this pathology is not fully known. In addition, the origins of high intratesticular estrogen levels in horses remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor (GPER) and establish histological and biochemical cryptorchid testis status, healthy and cryptorchid horse testes were subjected to scanning electron microscopy analysis, histochemical staining for total protein , acid content , and polysaccharide content . The expression of GPER was analyzed by immunohistochemistry and Western blot. GPER-mediated intracellular cAMP and calcium (Ca2+) signaling were measured immunoenzymatically or colorimetrically. Our data revealed changes in the distribution of polysaccharide content but not the protein and acid content in the cryptorchid testis. Polysaccharides seemed to be partially translocated from the interstitial compartment to the seminiferous tubule compartment. Moreover, the markedly decreased expression of GPER and GPER downstream molecules, cAMP and Ca2+, suggests their potential role in testis pathology. Increased estrogen levels in cryptorchid conditions may be linked to disturbed GPER signaling. We postulate that GPER is a prominent key player in testis development and function and may be used as a new biomarker of horse testis in health and disease. Testicular descent is an integral part of the male differentiation process. Testes migrate from the abdominal cavity to the scrotum. This process is essential for proper testis functioning and it consists of two phases: transabdominal and inguinoscrotal. The migration involves the regression of the cranial suspensory ligament and the development of the gubernaculums. The gubernaculum is subject to the superior hormonal regulation of androgens and insulin-like 3 (INSL3), which are absolutely required for testis descent . In addiEpidemiological studies together with laboratory cryptorchidism models have shown a strong link between testis descent impairment and xenoestrogen exposure. Such exposure is also associated with increased estrogen levels and expression of ER in the undescended testes ,26,27,28In horses, cryptorchidism is a common congenital malformation associated with the failure to descend by one or both testes into the scrotal sac. The major clinical consequences resulting from elevated temperatures in the undescended testes are impaired fertility and a significantly increased risk of testicular malignancy . It is aIn addition, in some cryptorchid horses, the testes are capable of producing testosterone, leading to undesirable sexual behaviors . Of noteThe mode of cryptorchidism inheritance remains unclear and appears to have a multifactorial etiology, and the phenomenon of high intratesticular estrogen levels is still an unresolved issue. The present studies were designed to provide additional insight into estrogen regulation and the role of GPER in healthy and cryptorchid horse testes. These comparative data can help to elucidate the molecular basis of cryptorchidism in horses.The typical topography of a healthy testis with full spermatogenesis and spermatozoa visible in tubule lumen was compared to a cryptorchid testis with severe alterations  using scanning electron microscopy A,A’,B–D.The general biochemistry of the testes revealed typical histological features of healthy testis tissue, i.e., normal size of interstitial tissue. In the cryptorchid testis, it was overgrown; the observed increase was approx. 60% in comparison to the healthy testis. In addition, the cryptorchid seminiferous tubule diameter was decreased compared to healthy testes; the observed decrease was approx. 40% B,D. Histp < 0.001) was revealed in cryptorchid testes when compared to healthy ones  and Ca2+ (p < 0.001) were found when compared to the control (p < 0.001) and interstitial tissue (p < 0.001) and for Ca2+ channel marker (IP3 I) measured in the seminiferous tubules (p < 0.001) and interstitial tissue (p < 0.001), respectively, in cryptorchid testes when compared to healthy ones  is a splicing factor expressed in germ cells and Sertoli cells. In mice, NSSR1 expression increases significantly during testes development, descent, and spermatogenic function . In crypIn conclusion, a coexistence of (i) global biochemical changes in the testis compartments (referred to as polysaccharide distribution and amounts) and (ii) local molecular changes (decreased GPER expression in Leydig cells and decreased GPER downstream pathways via cAMP and Ca2+) in the cryptorchid horse testis is reported here .Our results, considered with those by Zhang et al. , suggestn = 3; left testis in inguinal canal (n = 1) and right testis n = 2) Arab horses during open surgical castration (private studs in Warsaw and Krakow). Before castration, their libido was normal, indicating the presence of sufficient testosterone levels secreted by healthy testes.Testes were obtained from 2–3-year-old unilaterally cryptorchid  were obtained from Arab horses that had been euthanized due to serious injury, e.g., fracture of the limb or spine during their moving around the stud, or fighting between horses.Healthy testes .Pieces of testicular tissue were fixed in a mixture of 2.5% formaldehyde with 2.5% glutaraldehyde in a 0.05 M cacodylate buffer  for several days, washed three times in a 0.1 M sodium cacodylate buffer, and later dehydrated and subjected to critical-point drying. Specimens were then sputter-coated with gold and examined at an accelerating voltage of 20 kV or 10kV using a Hitachi S-4700 scanning electron microscope .Pieces of testicular tissue were embedded in Technovit 7100 . The tissue was fixed in Bouin’s solution  at 4 °C overnight and dehydrated in a graded ethanol series. Then, the tissue was preserved overnight in absolute ethanol and subsequently infiltrated with mixtures of absolute ethanol and Technovit. The samples were stored in pure Technovit, followed by polymerization of the resin with the addition of a hardener. Serial 5-µm-thick sections were prepared with the use of a rotary microtome . For general histology and for total protein, sections were stained with naphthol blue black (NBB) in acetic acid. Then, the slides were immersed briefly in acetic acid, air-dried, and mounted in Entellan synthetic resin . For acid content, sections were stained with 0.1% toluidine blue O (TBO) and mounted in Entellan synthetic resin . In order to detect insoluble polysaccharides, a periodic acid–Schiff (PAS) reaction was performed. Slides were oxidized in periodic acid and stained in Schiff’s reagent, then rinsed in potassium metabisulfite and mounted in Entellan synthetic resin .Testicular tissues were cut into 4-µm-thin sections. For antigen retrieval, endogenous peroxidase neutralization and blocking of non-specific binding sites were performed as described previously . Thereafhttps://imagej.nih.gov/ij/docs/intro.html (accessed on 5 January 2021). Measurements of freehand outlines drawn along the circumference of interstitial cell areas or seminiferous tubule areas were performed. On average, 60 areas of interstitial tissue or tubules were measured per slide. Relative optical density (ROD) of immunostaining insensitivities was determined for each animal testicular tissue and finally expressed as means ± SD.The amount of PKA or IP3 I produced in the individual interstitial cells or seminiferous tubule cells was measured at ×100 magnification using ImageJ software ® 20. Next, the membranes were incubated with anti-GPER antibody the same as for immunohistochemistry at 4 °C overnight, followed by a horseradish peroxidase-conjugated secondary antibody  at room temperature. Proteins were detected by chemiluminescence and documented with a ChemiDocTM XRS+ System . The specificity of antibodies was assessed with the use of blocking peptides and/or positive controls (not shown). All immunoblots were stripped and re-probed with an anti-β-actin antibody  as the loading control. The molecular weights of target proteins were estimated by reference to standard proteins . To obtain quantitative results, immunoblots were analyzed densitometrically  using the ImageLab software  by an independent observer.Separation of protein preparations were performed by SDS-PAGE under reducing conditions and the transfer of proteins to polyvinylidene difluoride membranes. Nonspecific binding sites were blocked with non-fat dry milk containing TweenThe amount of cAMP produced by healthy and cryptorchid horse testes was determined by Direct cAMP Elisa kit assay , according to the manufacturer’s instructions for the acetylated assay. The sensitivity of the assay was 0.037 pmol/mL. The cAMP concentrations were calculated as pmol/mL.Three independent experiments were performed, each in triplicate.The amount of Ca2+ produced by healthy and cryptorchid horse testes was determined by ab102505 Calcium Assay Kit (Colorimetric)  according to the manufacturer’s instructions. The Ca2+ concentrations were calculated as ng/mL (OD = 575 nm). Three independent experiments were performed, each in triplicate.p < 0.05. All experimental measurements were performed in triplicate from material derived from different animals.Each variable was tested using the Shapiro–Wilk W-test for normality. The homogeneity of variance was assessed with Levene’s test. The distribution of the variables was normal and the values were homogeneous in variance. All statistical analyses were performed using a one-way analysis of variance (ANOVA) followed by Tukey’s post hoc comparison test to determine which values differed significantly from controls. The analysis was performed using Statistica software . Data were presented as a mean ± SD. Data were considered statistically significant at


Dear Editor,Central nervous system lymphomas (CNSL) are difficult to diagnose. Although flow cytometry (FCM) and cytology using tumor cells in cerebrospinal fluid (CSF) are conventionally performed, the sensitivity is still problematic. Recently, cell-free circulating tumor DNA (ctDNA) has been detected in the CSF of patients with malignancies –3. Here,9/µL, total protein level was 168 mg/dL, and sIL-2R was 251 U/mL. Cytological diagnosis and FCM did not detect lymphoma cells  from CSF (Table MYD88L265P and CD79BY196N mutations were detected in both DNA from CSF supernatant and the pellet obtained at diagnosis (CSF-3). Then we performed ddPCR using CSF-cfDNA obtained 24 and 17 days before diagnosis (CSF-1 and -2) and after chemotherapy without obvious clonal B-cell population in FCM (CSF-4). The MYD88L265P and CD79BY196N mutations were detected in mostly all the CSF-cfDNA samples analyzed.After obtaining an informed consent, we performed SF Table . Gel eleSF Table  4, 5]. , 5. MYD8SF Table . MYD88L2We also analyzed DNA from the formalin-fixed paraffin-embedded specimen of the testis obtained 1 year before diagnosis. DNA was extracted from both B-cell rich and sparse lesion. Those mutations were detected only in DNA from the B-cell rich lesion with VAF of 10% and 10.7%, respectively. This phenomenon may suggest that the lymphocytes in his testicular lesion were in pre-lymphoma state.MYD88/CD79B mutations may be a more sensitive strategy to detect CNSL than cytology and FCM, even in the period when a pathological diagnosis has not been made. We analyzed the most frequently reported mutations of MYD88L265P and CD79BY196 [Our results indicate that tumor DNA in CSF was detected even at the time of negative results with cytology and FCM, and almost 1 month earlier than diagnosis. Genetic analysis with CSF-cfDNA to detect D79BY196 , 7, 8. HSupplementary file1 (PDF 372 KB)Below is the link to the electronic supplementary material.


Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods: A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results: The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions: Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health. Evaluating the abuse potential of new substances, particularly that of those that are able to affect the central nervous system, is necessary to determine future prescription conditions and the possible risk of misuse and addiction. In fact, the Prescriber Information (PI for US-FDA) and the Summary of Product Characteristics (SPC in Europe-EMA) include a specific section on this topic.Research assessing abuse potential is performed in accordance with the methodology recommended by the Food and Drug Administration (FDA) in its industry guidelines entitled “Assessment of abuse potential of drugs”, published in 2017 . Th. Th63]. Regarding diethylpropion, five publications (six studies) were retrieved  64,65,66,67,68. Two studies assessed participant preferences for diethylpropion compared to placebo or d-amphetamine. This type of research is considered the paradigm of abuse potential assessment.Diethylpropion produced effects that were qualitatively similar, but less intense, to those of d-amphetamine, with euphoria, increased blood pressure and body temperature, and decreased food intake being observed. Some adverse effects such as anxiety, irritability, dry mouth, and insomnia did, however, appear within the first three months of treatment.To the best of our knowledge, this is the first systematic review that is aimed at investigating and comparing the abuse-related effects and pharmacokinetic profiles of cathinone and other synthetic derivatives such as mephedrone, methylone, and diethylpropion. Our search was focused on cathinone, which is the main compound of the khat plant, and three synthetic cathinones, one of which was approved for therapeutic purposes and two others that are considered substances of abuse. Information regarding the abuse potential of synthetic cathinones is scarce despite representing the second largest group monitored by the European Union Early Warning System and their relevant impact on public health and security. Synthetic cathinones have been related to several cases of intoxication and fatalities over the years . The varThe studies included in this systematic review provided data about the subjective effects related to the abuse potential of cathinone and some of its synthetic derivatives. They employed validated methods recognized by the FDA and Health Canada for the assessment of abuse potential . Most ofIn the majority of studies involving cathinone, the selected route of administration was chewing khat leaves for 1 h. As it has been previously mentioned, this is, by far, the most popular way of cathinone administration due to its traditional background in several African and West Asian countries. Cathinone that was ingested by khat-chewing demonstrated slower pharmacokinetics and the delayed onset of pharmacological effects compared to when cathinone was contained in capsules. This was mainly due to the delayed release of the alkaloid from the leaf matrix during mastication . During In some studies, cathine and norephedrine, the main metabolites of cathinone as well as the components of the khat plant , were anAccording to our search, mephedrone is the most investigated synthetic cathinone in humans. Mephedrone users reported consuming this substance as a substitute for MDMA due to its similar pharmacological effects. The pharmacological profile and pharmacokinetics of mephedrone were evaluated following oral and intranasal administration, both of which are considered the most conventional routes.In terms of oral administration, mephedrone was employed in comparison with MDMA, which was used as a prototypical psychostimulant reference . Under cMephedrone administration has been also studied in combination with alcohol, the substance it is most commonly combined with on the nightlife scene. In this study, 200 mg of mephedrone was administered in combination with 0.8 g/kg alcohol or placebo ,59. The The most popular mephedrone administration route is insufflation, and few studies have analyzed the pharmacokinetics of mephedrone and its metabolites in human plasma and oral fluid after intranasal administration ,49,62. AIn a similar manner, methylone, another synthetic cathinone of abuse potential comparable to mephedrone, has been shown to produce the prototypical psychostimulant and empathogenic effects associated with MDMA. These include euphoria, stimulation, perception alteration, energy increase, and sociability, although to a lesser extent. The results suggest that methylone induced a similar profile of effects to its non-β-analogue MDMA and mephedrone ,63, both® and Tepanil®. Tenuate® has, however, currently been discontinued on the North American market according to the FDA. The efficacy of diethylpropion for the treatment of overweight and obese patients has been previously discussed [In contrast to cathinone, mephedrone, and methylone, which are considered substances of abuse, diethylpropion, due to its relatively lower abuse potential compared to amphetamine, has been commercialized as an appetite suppressant and obesity treatment under the trade names of Tenuateiscussed ,73,74.Most studies regarding diethylpropion have focused on its therapeutic effects, for instance, as an anorectic agent. A few other studies have, however, evaluated the abuse potential of this synthetic cathinone i compared to other substances, such as d-amphetamine ,66 and lIn a study evaluating diethylpropion, healthy participants received a single oral dose of 75 mg, and its pharmacokinetics were assessed according to the metabolizer profile, distinguishing among slow, intermediate, normal, and fast metabolizers . The meaOverall, in terms of pharmacological effects, cathinone, diethylpropion, mephedrone, and methylone shared a similar stimulant profile to other recreational substances, such as MDMA and amphetamine ,63,75. TThe correlation between the oral administration dose and Cmax in blood is the only possible method through which mephedrone could be calculated since the pharmacokinetic data of cathinone, methylone, and diethylpropion were insufficient. Doses of mephedrone that were administered orally through capsules and Cmax in the blood presented a significant moderate to strong correlation. This suggests that the absorption of mephedrone is constant at these evaluated doses, which may prove useful for predicting or extrapolating the Cmax value at any mephedrone dose between the evaluated ranges.This systematic review has some limitations that should be considered. Firstly, only one database, PubMed, was consulted for publication retrieval. Moreover, the search was limited to English. Inclusion was restricted to prospective studies, so the results obtained from retrospective studies, such as surveys about previous consumption, were not accepted. Due to the scarcity of studies about the abuse potential of synthetic cathinones in humans, only those concerning mephedrone, methylone, and diethylpropion were included in this review. The variety of study designs hindered the identification of consistent differences among the compared substances. We included both experimental placebo-controlled trials and observational prospective studies. Whilst it may be a limitation, inclusion was based on the fact that evaluation was performed with similar questionnaires and methods to assess abuse potential.In conclusion, despite the large number of existing synthetic cathinones and the constant appearance of other derivatives, research about their abuse potential and pharmacokinetics is still very limited. Mephedrone is the most studied synthetic cathinone used for recreational purposes; little is known, however, about the great majority of other synthetic cathinones. Regardless of their legal status, cathinone and its synthetic derivatives induce a range of desirable and reinforcing effects that may result in some degree of abuse potential. All four substances share a similar psychostimulant profile that is close to the profiles of amphetamines and MDMA. The different intensities of the desirable effects they present may be associated with varying levels of abuse potential. Mephedrone showed a moderate correlation between the administration dose and Cmax in experimental studies administering single oral doses.Further investigation is needed to shed light on the abuse potential of cathinone and its synthetic derivatives to minimize the impact of their consumption on society and to detect and prevent any medical complications associated with their use and abuse.


There is no detailed biomechanical research about the hybrid CBT-TT  and TT-CBT  techniques with finite element (FE) method. Therefore, the purpose of this study was to evaluate and provide specific biomechanical data of the hybrid lumbar posterior fixation system and compare with traditional pedicle screw and cortical screw trajectories without fusion, in FE method. Specimens were from the anatomy laboratory of Xinjiang Medical University. Four FE models of the L4-L5 lumbar spine segment were generated. For each of these, four implanted models with the following instruments were created: bilateral traditional trajectory screw fixation (TT-TT), bilateral cortical bone trajectory screw fixation (CBT-CBT), hybrid CBT-TT fixation, and hybrid TT-CBT fixation. A 400 N compressive load with 7.5 Nm moments was applied so as to simulate flexion, extension, left lateral bending, right lateral bending, left rotation, and right rotation, respectively. The range of motion (ROM) of the L4-L5 segment and the posterior fixation, the von Mises stress of the intervertebral disc, and the posterior fixation in four implanted models were compared. CBT-TT displayed a lower ROM of the fixation segment (3.82 ± 0.633°) compared to TT-TT (4.78 ± 0.306°) and CBT-CBT (4.23 ± 0.396°). In addition, CBT-TT showed a lower ROM of the posterior fixation (0.595 ± 0.108°) compared to TT-TT (0.795 ± 0.103°) and CBT-CBT (0.758 ± 0.052°). The intervertebral disc stress of CBT-TT (4.435 ± 0.604 MPa) was lower than TT-TT (7.592 ± 0.387 MPa) and CBT-CBT (6.605 ± 0.600 MPa). CBT-TT (20.228 ± 3.044 MPa) and TT-CBT (12.548 ± 2.914 MPa) displayed a lower peak von Mises stress of the posterior fixation compared to TT-TT (25.480 ± 3.737 MPa). The hybrid CBT-TT and TT-CBT techniques offered superior fixation strength compared to the CBT-CBT and TT-TT techniques. The pedicle screw fixation technique has become the mainstay for the treatment of various lumbar diseases, providing considerable biomechanical stability , 2. HoweTo increase the purchase and stability of the screw-bone interface and obtain superior posterior fixation strength in patients with osteoporosis or lumbar revision surgery, numerous attempts have been made by researchers over the years, from the shape design of screws to the curing of screw tracks, including screw augmentation with allograft or cement , 6, expaSantoni et al.  proposedHigh-resolution computed tomography (CT) data  of the L4 to L5 vertebrae in four lumbar specimens  from the Anatomy Teaching-Research Office of Xinjiang Medical University were acquired. The mean age of the four specimens was 71, ranging from 64 to 77 years, and they were free from lumbar fracture, tumor, tuberculosis, and malformation. Among them, the L5 vertebra of one specimen had an isthmus breakage and spondylolisthesis. Anatomical three-dimensional (3D) models of the L4–L5 lumbar spine vertebrae were generated using mimics 16.0 . The models were embedded into hypermesh 18.0  for further operation, including repairing the damaged and missing areas, retriangulation and smoothing of the polygon mesh, making triangles more uniform in size, and generating a nonuniform rational B-spline (NURBS) surface on the object. This meshing process was performed for screws implanted into lumbar spine together with the lumbar spine model itself to ensure the continuity of the mesh. Cortical bone was defined as a 0.5 mm thickness outward from the outer layer of the cancellous bone . The areFour different posterior fixations used in this study were as follows: (1) TT-TT, TT screws at the cranial and caudal levels ; (2) CBTThe axial displacement of the model was calculated by applying compressive loads of 500, 1000, 1500, and 2000 N to the reference points on the superior surface of the L4 vertebra, respectively, and compared with the in vitro experimental results of Markolf , Virgin To achieve a clinical simulation, a compressive load of 400 N and a torque of 7.5 Nm were applied to the reference point on the superior surface of the L4 vertebra to simulate flexion, extension, left lateral bending, right lateral bending, left rotation, and right rotation, respectively. The ROM of the L4-L5 segment and posterior fixation, von Mises stress of the intervertebral disc, and posterior fixation were recorded to make a biomechanical comparison of the hybrid CBT-TT and TT-CBT techniques with the TT-TT and CBT-CBT techniques. In the present study, the von Mises stress was selected as the equivalent stress for the disc and posterior fixation.P < 0.05 was considered statistically significant for all analyses.SPSS 22.0 software was used for data analysis and processing. The data distribution was expressed as the mean ± standard deviation. The difference analysis was performed by one-way analysis of variance (ANOVA). When there were statistical differences in different indicators, the Bonferroni pairwise comparison method was used as the post hoc test. The final model contained 195,858 nodes and 58,085 elements, and the axial displacements of the models under the four increasing compressive loads were 0.336, 0.654, 0.813, and 1.132 mm, respectively . The resP ≤ 0.013), except for left rotation (P ≥ 0.113), and with no differences in each of the six conditions (P ≥ 0.106) in comparison to CBT-CBT. Among the four fixation models, the highest ROM at the L4–L5 level was found for TT-TT, followed by CBT-CBT, TT-CBT, and CBT-TT , except for the left and right rotations . In flexion, extension, and right lateral bending, the ROMs of posterior fixation were significantly decreased in comparison to CBT-CBT (P ≤ 0.021). Among the four fixation models, the highest ROM was found for TT-TT, followed by CBT-CBT, CBT-TT, and TT-CBT (The ROMs of posterior fixation of CBT-TT and TT-CBT were significantly reduced in comparison to TT-TT (d TT-CBT . In compP ≤ 0.021), while the disc stress of TT-CBT was significantly decreased in comparison with CBT-TT in flexion and extension (P ≤ 0.008). The highest ROM was found for TT-TT, followed by CBT-CBT, TT-CBT, and CBT-TT , except for left lateral bending, and this in CBT-TT was also significantly decreased (P ≤ 0.048), except for lateral bending and right rotation. A typical minimal von Mises stress of TT-CBT is presented in A similar change in the maximal von Mises stress in the posterior fixations was observed, with the highest stress of the fixations found in TT-TT, followed by CBT-CBT, CBT-TT, and TT-CBT . As can FE analysis has been increasingly applied in spinal-related biomechanical studies , 31, 32 In the present study, a single-stage lumbar FE model was selected to investigate the biomechanical stability of osteoporotic lumbar spine models in different posterior fixation techniques. Several previous biomechanical studies by Matsukawa et al. , 34 demoThe stress distribution characteristics in the present study showed that the posterior fixation  has a clear restraint effect on the movement trend of the vertebral unit with the action of positive pressure and torque. Comparing the effect of different movement trends on the stress of the posterior fixation, it was found that the stress distribution of the screw inside the cancellous bone was superior to counterparts during flexion and extension, which was clear in TT-TT. The reason was that the direction of the movement trend was in the same plane as the axial direction of the screw and rod during flexion and extension. McLachlin et al.  found thAs with any FE analysis, certain limitations were inherent in the present study. First, there was a lack of ligaments and muscles, which play an important role in supporting the stability of the lumbar spine. Second, there was a lack of an adjacent segment which provides an indispensable role in evaluating the relationship between hybrid techniques and ASD. Third, linear elastic and homogeneous material properties for the vertebral body and the disc were lacking. Fourth, the limited number of specimens was insufficient to allow more convincing conclusions. Fifth, the rods in the hybrid techniques were not perpendicular to the horizontal line, but formed a certain included angle. From the stress nephograms of the hybrid techniques, it can be seen that the stress was reduced, but the force magnitude of the rod was not analyzed in considerable detail. Consequently, there is only one size of TT and CBT screws, thus the biomechanical effects of varies screw diameters and lengths in the hybrid techniques have not been considered extensively in the present literature. The present study did not standardize the sizes of the CBT and TT screws in the hybrid techniques.Aim of this study is to provide posterior fixation with higher purchase and superior fixation strength. Among the different fixation techniques, CBT-TT and TT-CBT offered superior fixation strength, followed by CBT-CBT, while TT-TT was the least stable and resulted in the increased stress of the screws. Considering its superior segmental stability, the hybrid techniques might be effective in short segment fusion after limited spinal decompression or discectomy, particularly in elderly patients with osteoporosis. Hybrid techniques might be alternative in patients with pars fracture when CBT-CBT cannot be used. The results of this study reflected important factors to be considered in further biomechanical study, and more clinical studies with long-term follow-up are also necessary to validate the findings of the present study.


The prepared PO-PdNPsn had a small size for PdNPs and good stability in solution. Noteworthily, PO-PdNPs150 had the highest catalytic activity in reducing 4-nitrophenol (4-NP) (Knor = 18.53 s−1mM−1) and oxidizing morin (Knor = 143.57 s−1M−1) in aqueous solution than other previous catalysts. The enhanced property was attributed to the improving the stability of PdNPs by PEI-oleic acid micelles. The method described in this report has great potential to prepare many kinds of stable noble metal nanoparticles for treating aqueous pollution.Water soluble organic molecular pollution endangers human life and health. It becomes necessary to develop highly stable noble metal nanoparticles without aggregation in solution to improve their catalytic performance in treating pollution. Polyethyleneimine (PEI)-based stable micelles have the potential to stabilize noble metal nanoparticles due to the positive charge of PEI. In this study, we synthesized the amphiphilic PEI-oleic acid molecule by acylation reaction. Amphiphilic PEI-oleic acid assembled into stable PEI-oleic acid micelles with a hydrodynamic diameter of about 196 nm and a zeta potential of about 34 mV. The PEI-oleic acid micelles-stabilized palladium nanoparticles (PO-PdNPs In addition, morin is a kind of polyphenol dye that belongs to flavonoid dyes. Morin has been used as a model matrix for the study of catalytic bleaching processes in laundry detergents  in PdNPsn and hydrogen peroxide were 7.8 mM and 10 mM, respectively. The concentration of morin was from 0.5 to 1.25 mM. The next experiment had similar procedure. The concentration of [N] in the catalyst was fixed at 0.78–5.47 mM with 3 mM morin.The effects of different catalyst concentrations and different morin concentrations on the catalytic reaction were determined by UV-TU1810  at 403 nm. One mM morin, carbonate buffer, PO-PdNPskapp data of the PO-PdNPsn of 4-NP and the morin treatment were analyzed by SPSS 25 to assess the statistical differences between the groups. p < 0.05 is considered statistically significant.The Acylation reaction was employed into the synthesis of the amphiphilic molecules of PEI-oleic acid, which is illustrated in The PEI-oleic acid amphiphilic molecules self-assembled in water to form micelles, and the hydrophilic PEI segment acted as a shell layer of the micelles. The critical micelle concentration (CMC) of the PEI-oleic acid micelles was [N] = 0.12 mg/mL based on the fluorescence method using pyrene. The hydrodynamic diameter and zeta potential of PEI-oleic acid micelles were determined to be 196 nm and 34 mV by DLS , respectively. The positive charge of the micelles was attributed to the hydrophilic PEI shell.n, Na2PdCl4 was mixed with PEI-oleic acid micelles and then further reduced with NaBH4. As shown in 2PdCl4. After the reduction of Na2PdCl4 by NaBH4 to produce PdNPs, a new absorption spectrum appeared, which indicated the formation of PdNPs. This was consistent with the results reported in the previous literature [75.To prepare PO-PdNPsterature . As the n was measured by TEM . n. The mean particle sizes of PdNPs within PO-PdNPsn at [N]:[Pd] = 75, 100, and 150 were 2.01 ± 0.30, 1.85 ± 0.25, and 1.67 ± 0.27 nm, respectively. The size of the PdNPs decreased with the increasing the molar ratio of [N]:[Pd]. In short, the prepared PdNPs of PO-PdNPsn had a small particle size and a narrow size distribution.The size of the PdNPs of PO-PdNPsn in aqueous solution, the hydrodynamic diameter and zeta potential were measured by DLS  :[Pd] = 75, 100, and 150, respectively. The positive charge on the surface of PO-PdNPsn was larger than 20 mV. Thus, the strong electrostatic repulsion was good for the high stability of PO-PdNPsn in aqueous solution. In summary, PO-PdNPsn had high stability in solution and big positive charge, so it kept from coagulation within one month.In order to determine the stability of the prepared PO-PdNPsire, UK) ,22. As sire, UK) ,24. Figun. Due to the high toxicity of 4-NP and its pollution of water resources, it has attracted great attention. 4-AP is the reduction product of 4-NP. 4-AP has low toxicity and important applications in industry. It is important to study the method to transform 4-NP into 4-AP. The concentration of PdNPs in the solution of the reacting mixture was as low as 10−7 mM. Therefore, the absorption spectra of PdNPs almost had no effect on the absorbance of the mixed solution. The absorption peak of 4-NP existed at 317 nm. When the NaBH4 solution was added, the color of the solution rapidly turned yellow, and the obvious absorption peak appeared at 400 nm, which corresponded to 4-hydroxyaminophenol [75 reached 1796.4 h−1 in this experiment.The catalytic reduction of 4-NP was employed to evaluate the catalytic activity of PO-PdNPsnophenol . In Figun  had a linear relationship between ln (t/CC0) and reaction time (t). Thus, the catalytic reduction of 4-NP by using PO-PdNPsn followed pseudo-first-order kinetics. This was attributed to excess NaBH4 in the mixed solution. Thus, the apparent rate constant (kapp) was calculated as follows:As shown in kapp values were calculated from the slope of the lines as shown in kapp was shown in kapp value increased with increasing catalyst concentration of PO-PdNPsn, indicating that the reduction rate was linear correlated with the concentration of PO-PdNPsn. norK was used to compare the catalytic activity of different catalysts, norK was defined as the ratio of kapp to molar concentration of catalyst (norK = kapp/Ccat). PO-PdNPs150 had the highest norK (18.53 s−1mM−1) in PO-PdNPsn. Knor and the TOF of the PO-PdNPsn and other catalysts. PO-PdNPs150 had the highest Knor, indicating that they had the highest activity. PdNPs were located in the micelles’ shells, which may contribute to their high catalytic activity caused by the low mass transfer resistance of the substrates. In short, this catalytic reaction followed pseudo-first-order kinetics and PO-PdNPs150 had the highest activity.The n were evaluated with the addition of H2O2 [2O2. 75, the absorbance at 403 nm decreased rapidly with time, while the absorbance at 325 nm gradually increased with time. This phenomenon indicated that the morin underwent catalyzed oxidation to benzofuranone [Morin is a polyphenol dye that has been used as a model to study the catalytic ability of precious metal nanoparticle catalysts. The catalytic activity and catalytic mechanism of PO-PdNPs of H2O2 ,30. In afuranone . After afuranone . Therefokapp and PO-PdNPsn concentration, the effect of changing the concentration of PO-PdNPsn on the catalytic reaction under the conditions of constant concentration of morin and H2O2 was measured. kapp and the catalyst concentration was linear. With the increase of catalyst concentration, kapp became higher. The three proportions of catalysts had the same trend as follows: PO-PdNPs75 > PO-PdNPs100 > PO-PdNPs150. The norK of PO-PdNPs75, PO-PdNPs100, and PO-PdNPs150 were 105.77, 129.49, and 143.57 s−1M−1, respectively, so the catalytic activity was increased according to the order of PO-PdNPs75 <PO-PdNPs100 <PO-PdNPs150. This was because the particle size of PdNPs in PO-PdNPsn decreased in the order of PO-PdNPs75 <PO-PdNPs100 <PO-PdNPs150. At the same concentration, the smaller particle size resulted in the larger specific surface area and the higher catalytic efficiency.To study the relationship between kapp and the morin concentration, this experiment monitored the process of morin reaction by fixing the H2O2 concentration during the reaction process. As shown in kapp decreased with increasing morin concentration. This was consistent with the previously reported results of catalytic oxidation of morin by MnOx [2O2. Generally, during the reaction of morin, the adsorption constant morinK is higher than KH2O2. Therefore, compared with H2O2, morin is more easily adsorbed on the catalyst surface. As the concentration of morin increased, the active sites on the surface of noble metal nanoparticles are covered, resulting in a decrease in the active sites available for H2O2 adsorption, which gradually decreases the reaction rate when the concentration of morin increases.To study the relationship between  by MnOx . Surfacen should also meet the equation. 4-NP was quickly reduced to a stable intermediate 4-hydroxyaminophenol. The electrons from sodium borohydride and 4-hydroxyaminophenol ions combined on the surface of PdNPs to produce 4-AP ions, and then 4-AP ions were desorbed to form 4-AP molecules. In this process, the adsorption/desorption equilibria of all related compounds on the surface of PdNPs were rapidly achieved. In the oxidation process of morin by PO-PdNPsn, the Langmuir –Hinshelwood kinetics method was also followed [During the catalytic reduction of 4-NP, the Langmuir–Hinshelwood kinetics method was followed according to previous reports ,36. Simifollowed ,37.n was between 1.67 and 2.01 nm with a narrow size distribution. The PO-PdNPsn maintained high stability due to its zeta potentials larger than 20 mV. In addition, the prepared PO-PdNPsn effectively catalyzed the reduction of 4-NP to form 4-AP. PO-PdNPsn also had high catalytic efficiency for morin. The catalytic ability of PO-PdNPsn was higher than those of other catalysts, which could result from the small size and high stability of Pd NPs. The location of PdNPs in the PEI-oleic acid micelles was good for low mass transfer resistance. The prepared PO-PdNPsn has great potential applications in treating various organic contaminants in solution in the future.In conclusion, PEI-oleic acid micelles were prepared and used to stabilize PdNPs in aqueous solution. The size of PdNPs in the PO-PdNPs