OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

Objective By organizing and implementing a laboratory proficiency validation plan for air change rate testing, this study aims to explore proficiency testing approaches in laboratory animal facilities, assess the current status of relevant laboratories regarding standard application and test capabilities, standardize air change rate testing methods, and ensure the accuracy and reliability of test results. Methods From September to November 2023, the National Institutes for Food and Drug Control (NIFDC) organized a laboratory proficiency validation plan for air change rate testing in laboratory animal facilities (Plan Number: NIFDC-PT-417). The proficiency testing was conducted on-site and consisted of two parts: a written test and practical operation. The written test was open-book. True/false questions focused on participants' understanding of specific clauses in relevant standards, while application-based questions assessed their ability to handle data processing in simulated testing scenarios. The practical operation was conducted according to the relevant criteria of the China National Accreditation Service for Conformity Assessment (CNAS). Two laboratory animal rooms were prepared as proficiency testing samples using a sample splitting approach. These rooms underwent uniformity and stability testing according to CNAS requirements and were approved. Participating laboratories were required to conduct three tests on each of the two laboratory animal rooms, complete the testing and calculation of air change rate within the specified timeframe, and submit their test result reports and original records. Results A total of 27 laboratories registered and participated in the proficiency testing. All participating laboratories submitted their results within the designated timeframe, and the outcomes of all tested laboratories were rated as satisfactory. Conclusion This proficiency validation program objectively and scientifically evaluates the air change rate testing capabilities of selected domestic laboratories, effectively promoting the overall improvement of testing capabilities in the industry. It provides technical support for regulatory authorities to standardize testing institutions and offers reliable references for the purchase of testing services. Through this activity, it was identified that some laboratories need to further enhance their calibration of instruments and the utilization of calibration results. Future efforts should focus on refining related standards to improve the accuracy and reliability of testing.

Objective Through organizing a proficiency evaluation activity for animal illuminance testing laboratories,to assess the accuracy of testing data from participating laboratories,and to propose suggestions for testing methods.Methods In September 2024,China National Institute for Food and Drug Control(NIFDC)organised reference laboratories to conduct on-site testing through open registration.A total of 35 laboratories participated,completed on-site testing,and submitted their reports.The samples to be tested were two adjacent guinea pig breeding rooms in the NIFDC laboratory animal facility.In order to reduce the impact of room voltage fluctuations on animal illumination,chip on board(COB)light sources powered by regulated power supply were used,and brightness was adjusted by regulating voltage output.Split-level test sample pairs were used to set animal illuminance in both rooms,and the reference laboratories conducted testing according to Laboratory animals——Environment and housing facilities(GB 14925-2023).Each reference laboratory was assigned a 3-digit random code,conducted 2 tests for each breeding room,and submitted an on-site test report,original records,and illuminance meter verification or calibration certificate.WPS Spreadsheet 12.1 was used to summarize data,Grubbs' test(α=0.01)was used to check the data and remove outliers,and SPSS 26.0 software was used for data processing and graph drawing.The median value from each reference laboratory was used as the specified value,the robust standard deviation was used as the uncertainty,the robust z-score method(both intra-laboratory and inter-laboratory z-scores)was used to evaluate the test results from each laboratory,and the factors affecting results were analyzed from aspects of personnel,equipment,and operational environment.Results Under the detection level of α=0.01,no outliers were identified.The specified values for Room 1 and Room 2 were 17.80 lx and 19.00 Ix,respectively.The results obtained from 34 laboratories were evaluated as"satisfactory",while the results from one laboratory were"unsatisfactory".Through analysis of illuminance meter calibration certificates from various laboratories,it was found that some reference laboratories had insufficient calibration points and coverage,which caused test results to fail to accurately reflect the actual illuminance of the facility.Conclusion The present study reveals that factors such as personnel,equipment,and operation environment have different impacts on animal illuminance measurements.The present study concentrates exclusively on animal illuminance in guinea pig breeding rooms,where the testing environment is relatively dim.Future research should focus on the development of more efficient methods for selecting measurement sites,with the combination of illuminance meters equipped with wireless probes and storage functions to enhance testing efficiency.

In recent years,artificial intelligence(AI)has been introduced into the field of mental health interventions,which not only brings innovation and progress,but also causes a series of ethical problems.This paper systematically analyzes the triple ethical challenges of AI applying to mental health interventions.Firstly,the current ethical frameworks for AI-based mental health interventions primarily expand upon medical ethics principles,emphasizing benefit maximization,risk minimization,and patient autonomy.However,these frameworks face challenges such as insufficient standardization and difficulties in dynamically capturing and regulating ethical risks arising from rapid technological iteration.Secondly,ethical challenges related to data governance in AI-based mental health applications include data privacy issues and decision fairness concerns stemming from algorithmic bias.Finally,AI as a proxy resource risks eroding user autonomy and fostering interpersonal alienation,primarily through exerting influence beyond comprehension to undermine autonomous decision-making capabilities.Overreliance and blind trust in AI systems during usage may weaken social motivation,thereby threatening autonomy and psychological integrity.

Objective:To assess the efficacy and safety of Gongxuening Capsules in reducing post-abortion bleeding following artificial abortion.Methods:A multicenter, randomized, double-blind study was conducted. From May 31, 2022 to March 31, 2023, 484 women who underwent vacuum aspiration abortion for early intrauterine pregnancy were enrolled in 11 centers and randomly assigned to control group and the study group at a 1∶1 ratio using a center-block randomization method. Control group were administered a placebo of Gongxuening Capsules for 9 d, while the study group received the actual Gongxuening Capsules for the same duration. The outcomes measured included vaginal bleeding volume, duration of vaginal bleeding, endometrial thickness, time to menstrual recovery, and complications.Results:1) A total of 484 subjects were enrolled, and 472 completed the study. Totally 450 subjects were included in the efficacy analysis set, with 224 in control group and 226 in the study group; 468 subjects were included in the safety analysis set, with 236 in control group and 232 in the study group. The baseline characteristics of the two groups were comparable (all P>0.05). 2) The vaginal bleeding volume was lower in the study group [(13.30±12.14) mL] than in control group [(19.00±17.67) mL, P<0.001]. The proportion of subjects in the study group with bleeding days less than 4 d [29.65% (67/226)] was higher than that in control group [19.20% (43/224), P=0.010]. 3) No significant differences were observed between the two groups in terms of time to menstrual recovery and endometrial thickness (all P>0.05). 4) In the study group, 3 subjects experienced non-therapeutic-related complications, while 11 subjects in control group. The incidence of complications was lower in the study group [1.29% (3/232)] than in control group [4.66% (11/236), P=0.033]. Conclusion:The administration of Gongxuening Capsules to women following artificial abortion significantly reduced vaginal bleeding volume and was associated with good safety, with the treatment being well-tolerated by the subjects.

Objective To explore the effect of scalp combined with intradermal-needle acupuncture synchronized rehabilitation ther-apy on upper limb motor function in stroke patients.Methods From December,2022 to December,2023,144 stroke patients with upper limb motor dysfunction in the Affili-ated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into control,intra-dermal-needle,scalp-acupuncture and acupuncture groups(36 cases repectively).All groups received convention-al treatment and upper limb rehabilitation training,the intradermal-needle group added intradermal-needle thera-py,the scalp-acupuncture group added scalp-acupuncture therapy,and the acupuncture group added both scalp-and intradermal-needle therapies,for four weeks.They were assessed with Fugl-Meyer Assessment-Upper Ex-tremities(FMA-UE),Wolf Motor Function Test(WMFT)and modified Barthel Index(MBI)before and after treatment.Twenty cases were selected randomly from each group,fractional anisotropy(FA)values and ratio of fractional anisotropy(rFA)of the lesion area and the posterior limb of the internal capsule were also measured with diffusion tensor imaging.Results Two cases dropped out in both the control group and the intradermal-needle group,while one case dropped out in both the scalp-acupuncture group and the acupuncture group.All groups showed significant improvement in FMA-UE,WMFT and MBI scores,as well as in the FA and rFA values of the lesion area and the posterior limb of the internal capsule(t>5.532,P<0.001)after treatment.The acupuncture group demonstrated the greatest pre-to post-treatment differences in FMA-UE scores,lesion-area FA and rFA values,and posterior-limb rFA val-ues compared with the other three groups(|Z|>3.256,P<0.05),and more WMFT and MBI improvements than those of the intradermal-needle group and the control group(|Z|>5.483,P<0.001).A significant interaction ef-fect was observed between intradermal and scalp acupuncture in improving FMA-UE scores(partial η2=0.035,P=0.029).The change in FMA-UE scores was positively correlated with the change in FA values of the posteri-or limb of the internal capsule(r>0.453,P<0.05)across four groups.Conclusion Scalp combined with intradermal-needle acupuncture synchronized rehabilitation therapy can more effec-tively improve upper-limb motor function in stroke patients,which may associate with the recovery of internal capsule.

Objective:To explore the treatment methods and prognosis of pregnancy-related uterine arteriovenous malformation (UAVM).Methods:A retrospective analysis was conducted on clinical data from 81 patients with UAVM treated at Peking Union Medical College Hospital between March 2019 and March 2024. Clinical manifestations, diagnostic approaches, treatment strategies and prognosis were evaluated.Results:(1) General Information: the age of patients with UAVM was (32.7±4.6) years, with median gravidity and parity of 1 (quartile range: 1, 2) and 0 (0, 1), respectively. Pregnancy termination methods included surgical abortion or curettage in 46 cases (57%, 46/81), medical induction in 17 cases (21%, 17/81), spontaneous abortion in 16 cases (20%, 16/81), vaginal delivery in 1 case (1%, 1/81), and laparoscopic pregnancy tissue removal in 1 case (1%, 1/81). (2) Clinical manifestations: clinical presentations comprised vaginal bleeding in 59 cases [73%, 59/81; median blood loss: 740 ml (440, 1 360 ml)], massive hemorrhage in 9 cases (11%, 9/81, and bleeding combined with lower abdominal pain in 8 cases (10%, 8/81). Ultrasonography revealed intrauterine masses in 65 cases [80%, 65/81; median size: 2.5 cm (1.8, 4.2 cm)]. Elevated serum human chorionic gonadotrophin-β subunit (β-hCG) levels were observed in in 55 cases [85%, 55/65; median: 62.6 U/L (14.9, 300.1 U/L)]. The median time to UAVM diagnosis via ultrasound was 30.0 days (16.0, 52.0 days) after pregnancy termination, with median peak systolic velocity (PSV) and resistance index of 59.8 cm/s (45.0, 79.6 cm/s) and 0.39 (0.36, 0.43), respectively. (3) Treatment and prognosis: treatment modalities included expectant management in 49 cases (36%, 29/81), medication in 13 cases (16%, 13/81), lesion resection in 31 cases (38%, 31/81), and uterine artery angiography in 8 cases (10%, 8/81; 5 confirmed as arteriovenous fistula). The median time of PSV returning to normal after treatment was 53.8 days (36.0, 93.4 days). The average time for β-hCG returning to normal was (60.4±20.4) days. The median return time of menses was 59.0 days (43.0, 75.4 days).Conclusions:Pregnancy-related UAVM carries a high risk of life-threatening hemorrhage, necessitating management in centers equipped for emergency uterine artery embolization. Informed consent must emphasize disease progression risks and prognosis. Treatment stratification should integrate clinical parameters and imaging features.

A 34-year-old female patient with multiple injuries in a car accident was admitted to hospital and received inosine injection.After 11 days,leukemioid reaction mainly characterized by"abnormal increase in white blood cell count"occurred,and the white blood cell count reached up to 38.26×109·L-1.Considering that inosine injection was the cause,the white blood cell count gradually decreased to 15.84×109·L-1 after the drug was stopped.Naranjo's assessment scale was used to evaluate the association of adverse reactions,with a score of 6,and the result was"very likely to be relevant".The cases reported in this paper belong to new adverse reactions caused by inosine injection,suggesting that inosine injection as an adjunct should pay attention to drug safety.If there is an abnormal increase in white blood cell count,it is necessary to be alert to the possibility of"leukemioid reaction"and stop the drug in time if necessary.