Objective:To evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis (MG).Methods:Case series study. The clinical manifestations, laboratory tests, treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children′s Medical Center of Peking University First Hospital were retrospectively collected.Results:There were 5 males and 22 females in 27 MG children. The onset age was 2.1 (1.6, 4.8) years, ranging from 8 months to 11 years. The clinical classification included 20 children (74%) of ocular MG and 7 children (26%) of generalized MG. Seventeen children (63%) had positive MG-related pathogenic antibodies, including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody. Rituximab was used as first-line immunosuppressant in 13 children, second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child. Immunosuppressants used before rituximab including 8 children of cyclosporine, 3 children of tacrolimus, 1 child of azathioprine, 1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine. Rituximab was used for at least half a year with a follow-up period of more than 12 months. At the last follow-up after rituximab treatment, all children achieved improved or above, 14 children (52%) achieved complete stable remission, 7 children (26%) achieved pharmacologic remission, 1 child (4%) achieved minimal manifestations, and 5 children (18%) improved. After rituximab treatment, 27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy, and 22 children (81%) had stopped the glucocorticoid therapy. Among the 14 children with poor efficacy of other immunosuppressants, rituximab had complete stable remission of 7 children. The most common adverse reaction was respiratory infection (4 children (15%)). Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment.Conclusions:Rituximab has good efficacy and tolerance in pediatric MG. Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.

Objective To investigate the predictive value of pre-treatment prognostic nutritional index (PNI) and nutrition-related indicators on the prognosis of patients with brain glioma. Methods The clinical data of 210 patients with brain glioma admitted to two hospitals in Yibin City from January 2015 to December 2020 were retrospectively collected, with the follow-up deadline on December 30, 2022. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) and the optimal cut-off value of each indicator for predicting patients′prognosis. The Kaplan-Meier method was used to plot the survival curve, and the influencing factors of prognosis of patients were explored through Log-rank test and multivariate Cox regression analysis. Results The average overall survival time of 210 patients was 21.8 months, and 140 patients (66.7%) died during the follow-up period, with a 1-year survival rate of 54.6%. ROC curve analysis results showed that the AUCs of albumin, prealbumin, lymphocytes, PNI, and body mass index for predicting the prognosis of patients with brain glioma were 0.856, 0.689, 0.833, 0.927, and 0.647, with the optimal cut-off values of 36.0 g/L, 205.0 mg/L, 1.85×10⁹/L, 46.5, and 21.0 kg/m², respectively. The results of multivariate Cox regression analysis showed that PNI, albumin, and World Health Organization (WHO) grading were all influencing factors for the prognosis of patients with brain glioma (P < 0.05). The survival curve analysis results showed that the 1-year survival rates of patients with PNI < 46.5 and PNI≥46.5 were 35.1% and 84.2%, respectively, were 35.8% and 74.3%, respectively in patients with albumin < 36.0 g/L and albumin ≥ 36.0 g/L, and were 90.2%, 55.2%, and 16.3%, respectively in patients with WHO grades of Ⅱ, Ⅲ, and Ⅳ. Conclusion The prognosis of patients with brain glioma is related to PNI, albumin, and WHO grading, and PNI has a high predictive value for the prognosis of patients with brain glioma.

Objective:The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited.This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse. Methods:Patients who completed the treatment in the Third Xiangya Hospital,Central South University were screened,and were divided into 2 groups based on different treatment plans.There were 28 patients who completed magnetic stimulation therapy(the magnetic stimulation therapy group)and 21 patients who completed radiofrequency combined with magnetic stimulation therapy(the combined treatment group).The pelvic organ prolapse quantitation(POP-Q),pelvic floor muscle strength,and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups,and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode. Results:The POP-Q evaluation results of Aa,Ap,and C points after the treatment in both groups were better than those before the treatment,with statistical significance(all P＜0.05).The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group,with statistical significance(P＜0.05).Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group,with statistical significance(P＜0.05).The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group,with significant statistical significance(P＜0.01). Conclusion:The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.

Objectives:To compare the effects of manual and mechanical chest compression on patients receiving extracorporeal cardiopulmonary resuscitation (ECPR).Methods:Patients who underwent extracorporeal cardiopulmonary resuscitation admitted to Jinhua Municipal Central Hospital, Hangzhou First People's Hospital and the First Hospital of Jiaxing from September 2014 to July 2022 were enrolled in the study. The patients were divided into the manual group and mechanical group according to the compression method, and the clinical data of the two groups were compared. To explore the effects of the two compression method on the ECPR implementation, proportion of return of spontaneous circulation (ROSC) and hospital survival.Results:A total of 108 patients who underwent ECPR were included in the study, 50 patients in the manual group and 58 patients in the mechanical group. There were no significant differences in sex, age, laboratory tests before ECPR, ROSC proportion (90.0% vs. 86.2%) and survival (34.0% vs. 39.7%) between the two groups (all P>0.05). The puncture time in the mechanical group was shorter than that in the manual group [12 (9,15) min vs. 13 (11,16) min, P<0.05]. Conclusions:Compared with manual compression, mechanical compression during ECPR neither increase the probability of ROSC nor reduce in-hospital mortality in patients with cardiac arrest. However, mechanical compression may help to shorten the puncture time.

ObjectiveTo understand the concentration of heavy metal cadmium and cadmium in portunus and mantis shrimp， and to timely identify food safety problems and potential hazards. MethodsPortunus and mantis shrimp samples from different provinces were collected and categorized based on different regions and locations， and some samples were made from tissue parts. Graphite furnace atomic absorption spectrometry was used to detect cadmium items， the cadmium exposure of portunus and mantis shrimp was evaluated simultaneously ResultsThe detection rate of cadmium in 124 batches of portunus sold in Shanghai was 100% （124/124）， the detection rate of cadmium in 63 batches of mantis shrimp sold in the market was also 100% （63/63）. The cadmium content varied in different tissue parts， and the cadmium enrichment in hepatopancreas was the highest in the edible parts of portunus and mantis shrimp. The average detection value， 50th percentile value， 95th percentile value of cadmium in the hepatopancreas of portunus accounted for 52.64%， 49.28% and 98.65% of the PTMI， respectively. The average detection value， 50th percentile value and 95th percentile value of cadmium in the hepatopancreas of mantis shrimp accounted for 30.76%， 32.04% and 46.16% of the PTMI， respectively. ConclusionThe average residual levels of heavy metal cadmium in portunus and mantis shrimp are within the safe range.

ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg^-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

OBJECTIVE To compare the dosage forms and specifications of over-the-counter drug （OTC）（chemical drugs ） for children at home and abroad ，and to provide reference for the addition of new dosage forms and specifications of OTC for children in China . METHODS Data analysis was used to comb the active ingredients of OTC single -ingredient preparation for children in China . The similarities and differences of the dosage forms and specifications of OTC for children with the same active ingredients among China and 8th edition of WHO Model List of Essential Medicines for Children （WHO EMLc ）and US/UK/EU （this article refers specifically to EU countries ）/Japan were analyzed by comparative analysis . RESULTS There were 72 active ingredients of OTC single -ingredient preparation for children in China ，corresponding to 34 dosage forms and 216 specifications； 39 same active ingredients of OTC for children were retrieved in WHO EMLc and US/UK/EU/Japan ，corresponding to 38 dosage forms and 258 specifications. Among OTC for children corresponding to 39 active ingredients ，there were 10 unique dosage forms in China ，and 16 unique dosage forms in WHO EMLc and US/UK/EU/Japan ，of which some dosage forms have advantages for children（such as chewing gums ，gels for external use ，spray for oral liquid ，etc.），were included in the latter while not included in China . There were 107 unique specifications in China ，and 214 unique specifications in WHO EMLc and US/UK/EU/Japan ，of which the division of applicable age groups for specifications was more detailed . In addition ，the dosage forms and specifications corresponding to a few active ingredients （such as ibuprofen ，cetirizine hydrochloride ）were not included in OTC for children in China， while included in UK/EU . CONCLUSIONS The dosage forms and specifications of OTC for children in WHO EMLc and US/UK/EU/Japan are generally more abundant and E-mail：zjfyouyou@163.com flexible than in China . Relevant departments in China should learn from the advanced experience of WHO and foreign countries and increase the research and development of dosage forms and specifications of OTC for children .

Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.
Core Binding Factor Alpha 2 Subunit/metabolism* ; DNA Methylation ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Promoter Regions, Genetic

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*