Oligodendrocytes(OLs)play a crucial role in myelination during the development and repair of the central nervous system.ATP serves not only as an important signaling molecule involving in the intercellular com-munications,but also as an energetic molecule,with its purinergic receptor subtypes widely present in neurons and glial cells.These subtypes are composed of two purinergic receptors:P1 and P2:The former are primarily activated by adenosine,and the latter mainly by ATP,ADP,and UTP.The two receptors paly their respective role in various regions of the CNS under physiological or pathological conditions through distinct mechanisms.In this paper,we review recent literature on the roles and mechanisms of the purinergic receptors in OL development,myelination,and myelin repair.It may be of great significance for further understanding the role of purinergic signaling in demy-elinating diseases and myelin dysplasia and exploring potential therapeutic targets.

Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.

BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCsExo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood.This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCsExo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess b-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry.Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

[摘 要] 目的：系统评价基于PD-1/PD-L1抑制剂的免疫联合治疗（以下称“免疫联合治疗”）对比舒尼替尼治疗晚期肾细胞癌（RCC）的安全性和有效性。方法：检索PubMed、Embase、Cochrane Library及中国知网（CNKI）数据库，收集国内外公开发表的免疫联合治疗对比舒尼替尼应用于晚期RCC的随机对照试验（RCT），检索时间均为自建库时间至2022年10月。由两名研究者独立评价纳入研究的质量、提取资料并交叉核对，采用StataMP16.0软件进行Meta分析。结果：共纳入6项RCT，Meta分析结果显示，（1）有效性：与舒尼替尼相比，免疫联合治疗显著提高了晚期RCC患者的总生存期[OS，HR=0.74，95% CI （0.67，0.80），P<0.01]和无进展生存期[PFS，HR=0.66，95% CI （0.51，0.81），P<0.01]；（2）安全性：两治疗组均有较高的不良反应（AE）发生率，差异无统计学意义。但免疫联合治疗组发生皮肤及内分泌系统AE显著高于舒尼替尼治疗组，而血液系统相关AE则明显低于舒尼替尼治疗组；（3）以1%为临界点，免疫联合治疗组的RCC患者，无论是PD-L1阳性或阴性的，其OS和PFS均高于舒尼替尼组。结论：免疫联合治疗可显著延长晚期RCC患者的OS和PFS，但不同系统发生AE有差异，且RCC患者PD-L1表达状态（1%为临界点）并不影响免疫联合治疗的获益。

Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin′s team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class Ⅲ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.

Objective To investigate the vaccine efficacy (VE) of two doses of inactivated enterovirus 71 (EV71) vaccine on severe hand, foot, and mouth disease (HFMD) in eligible children. Methods A retrospective case-control study was conducted in this project. A total of 109 patients with EV71 severe HFMD aged between 6 months to 5 years old who were admitted to the Pediatric Intensive Care Unit (PICU) of Guangxi Maternity and Child Health Hospital from September 2016 to September 2020, and reported to the Chinese Disease Prevention and Control Information System were selected as the case group. According to 1:1 matching,109 healthy children aged between 6 months to 5 years old were selected as the control group. The vaccine efficacy of EV71 inactivated vaccine was calculated. Results The vaccination rate of the two doses of inactivated EV71 vaccine in the case group was significantly lower than that in the control group（9.17% to 54.13%，χ²=50.911, P<0.05；OR=0.086(95%CI:0.040-0.182)). The vaccine efficacy of two doses of inactivated EV71 vaccine was 91.44% (95% CI:81.8%-96%). Conclusion The inactivated EV71 vaccine has a good protective effect on hand, foot, and mouth disease caused by EV71. The vaccination of EV71 inactivated vaccine should be continuously promoted.

Objective:To evaluate the clinical efficacy of Guizhi Mahuang Geban Decoction combined with conventional western medicine in the treatment of post infections cough (PIC), and to explore the mechanism.Methods:A total of 100 PIC patients in our hospital from January 2020 to July 2021 who met the inclusion criteria were divided into 2 groups according to the random number table method, with 50 in each group. The control group was treated with conventional western medicine, and the study group was treated with Guizhi Mahuang Geban Decoction and the treatment of the control group. Both groups were treated for 10 days. TCM symptom scores were performed before and after treatment. The levels of neurokinin A (NKA), substance P (SP), neurokinin B (NKB) and calcitonin gene related peptide (CGRP) were detected by ELISA. Adverse events were recorded and clinical effects were evaluated.Results:The total clinical effective rate was 90.0% (45/50) in the study group and 68.0% (34/50) in the control group, and there was significant difference between the two groups ( χ2=7.29, P=0.007). The scores of cough, expectoration, pharyngeal itch and total score in the study group were significantly lower than those in the control group ( t values were 8.04, 6.30, 9.03, 9.71, all Ps<0.01). After treatment, NKA [(86.08±18.21) ng/L vs. (137.68±28.29) ng/L, t=10.85], SP [(54.23±11.28) ng/L vs. (71.75±15.34) ng/L, t=6.51], NKB [(96.15±20.19) ng/L vs. (149.84±30.22) ng/L, t=10.45], CGRP [(62.93±18.35) ng/L vs. (89.59±23.25) ng/L, t=6.37] levels in the study group were significantly lower than those in the control group ( P<0.01). The incidence of adverse events was 8.0% (4/50) in the control group and 10.0% (5/50) in the study group, and there was no significant difference between the two groups ( χ2=0.13, P=0.727). Conclusions:Compared with western medicine alone, Guizhi Mahuang Geban Decoction combined with western medicine can rapidly improve patients' symptoms, improve curative effect and have better safety for PIC. Its mechanism may be related to the regulation of NKA, SP, NKB and CGRP levels.

As guided by the policy of building national regional medical centers, it is imperative to advance the construction of the national regional medical centers for mental health to achieve the sustainable and balanced development of the mental health cause of the country. The authors summarized the current status of national regional medical centers, and analyzed challenges faced in management and operation mode, government investment and compensation mechanism, expansion of high-quality psychiatric medical resources, as well as research and innovation of mental diseases of these centers. On such basis, the authors put forward corresponding countermeasures and suggestions for the next stage of development.