Volume 135 · Issue 19 · 2022

World Health Organization recommends that influenza vaccines should benefit as much of the population as possible, especially where resources are limited. Corona virus disease 2019 (COVID-19) has become one of the greatest threats to health systems worldwide. The present study aimed to extend the evidence of the association between influenza vaccination and COVID-19 to promote the former.

In this systematic review, four electronic databases, including the Cochrane Library, PubMed, Embase, and Web of Science, were searched for related studies published up to May 2022. All odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by meta-analysis.

A total of 36 studies, encompassing 55,996,841 subjects, were included in this study. The meta-analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provided an OR of 0.80 (95% CI: 0.73–0.87). The statistically significant estimates for clinical outcomes were 0.83 (95% CI: 0.72–0.96) for intensive care unit admission, 0.69 (95% CI: 0.57–0.84) for ventilator support, and 0.69 (95% CI: 0.52–0.93) for fatal infection, while no effect seen in hospitalization with an OR of 0.87 (95% CI: 0.68–1.10).

Influenza vaccination helps limit SARS-CoV-2 infection and severe outcomes, but further studies are needed.

PROSPERO, CRD42022333747.

Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes.

We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS).

In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was 1.89 with 95% confidence interval (95% CI) 1.46–2.45 (HbAlc-CV 1.47, 95% CI 1.26-1.72; HVS 1.67, 95% CI 1.34–2.09).

High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes.

高血压脑出血（HICH）是指有高血压病史的患者脑实质或脑室内突然发生出血。在诊断HICH时，应排除具有潜在致病病理学（如创伤、血管结构异常、凝血或血液学疾病、全身性疾病或肿瘤）的继发性脑出血（ICH）。HICH的特点是发病率、致残率、死亡率和复发率高。2015年，中华医学会神经外科分会、中国医师协会急诊医师与卒中筛查分会、中华人民共和国国家卫生健康委员会防治专委会专家齐聚一堂，制定起草了《中国自发性脑出血管理多学科专家共识》。^[1]这一共识对我国自发性ICH的管理起到了重要的指导和规范作用。随着过去5年多学科研究的重大进展和该领域新证据的发表，将以前的共识声明升级为指南将有助于中国各级医疗机构在临床实践中做出更好的决策。本指南主要针对HICH，这是最常见的自发性脑出血类型。^[2,3]

到1980年底，由于用于移植的尸体器官供应非常有限，日本团体已经开始了ABO不相容肾移植项目。从那时起，他们结合血浆置换和脾切除术成功地完成了跨越血型屏障的移植。在日本，随着2000年他克莫司（FK）/霉酚酸酯（MMF）联合用药和2005年利妥昔单抗的开发，ABO血型不合移植的策略发生了变化。^[1]此外，术前1周给予FK/MMF产生了更好的结果。在9年随访时，ABO不相容的两种肾移植的当前移植物存活率（2005-2013年）几乎超过90%，这与ABO相容的肾移植相当。^[1]来自瑞典、美国以及英国等其他国家的许多研究人员也报道了无数与ABO不相容的肾/肝移植相关的文章。不幸的是，从他们的报告中常见的观察结果是导致移植物丢失的超急性抗体介导的排斥反应的高风险，以及术后并发症如传染病的高发生率，这可能是由于胸腺球蛋白方案。^[2]因此，在ABO和/或人类白细胞抗原不相容移植时，一些国家ABO不相容移植的未来方向可能会直接转向供体交换计划，而不是重度免疫抑制计划。^[3]

Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen.

From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death.

After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P = 0.787, P= 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% vs. 10.5%, P= 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR (P = 0.714) compared to that of the Rittreated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12–0.78, P = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen (P = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01–7.31, P = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year.

An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.

Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China.

A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression.

A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P < 0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%.

Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.

Endoscopic retrograde cholangiopancreatography (ERCP) is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases. However, patients with cirrhosis, particularly those with decompensated cirrhosis, are believed to be at increased risk for complications associated with ERCP. There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis. This study aimed to investigate the outcomes of ERCP for cirrhosis patients, especially adverse events, and evaluated its safety and efficacy.

We performed a multicenter, retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University, Xijing Hospital affiliated to Air Force Military Medical University, Beijing Youan Hospital affiliated to Capital Medical University, and the Fifth Medical Center of the People’s Liberation Army General Hospital from June 2003 to August 2019. The adverse events of inpatient ERCP for patients with (n = 182) and without liver cirrhosis (controls; n = 385) were compared.

A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study. Compared to patients without cirrhosis, patients with cirrhosis were at higher risk for postoperative complications (odds ratio [OR], 4.172; 95% confidence interval [CI], 1.232–7.031; P < 0.001) such as postoperative pancreatitis (OR, 2.026; 95% CI, 1.002–4.378; P= 0.001) and cholangitis (OR, 3.903; 95% CI, 1.001–10.038; P= 0.036). The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis (101 cases; 55.5%), benign bile duct strictures (46 cases; 25.3%), and malignant bile duct strictures (28 cases; 15.4%). Among them, 23 patients (12.6%) underwent balloon dilation and 79 patients (43.4%) underwent sphincterotomy. Of the patients with cirrhosis, delayed bleeding occurred in ten patients (5.5%), postoperative pancreatitis occurred in 80 patients (44.0%), and postoperative cholangitis occurred in 25 patients (13.7%). An additional multivariate analysis showed that the total bilirubin (TBIL) level (OR, 4.58; 95% CI, 2.37–6.70) and Child-Pugh score of C (OR, 3.11; 95% CI, 1.04–5.37) were risk factors for postoperative complications in patients with cirrhosis.

Compared with the general population of patients undergoing ERCP, patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis. TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.

Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.

PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells. Cell proliferation was assessed by CCK8 assays. Cell migration and invasion were assessed by Transwell assays. PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017. Tissue miR-485-3p and p21-activated kinase-1 (PAK1) expression was examined by real-time polymerase chain reaction (RT-PCR), and the relationship of the two was analyzed using Pearman’s product-moment correlation. The clinical significance of miR-485-3p was analyzed using the Chi-square test, Wilcoxon rank-sum test, and Fisher exact probability, respectively. The binding of miR-485-3p to PAK1 5^＇-untranslated region (5^＇-UTR) was examined by luciferase assay. PC cells were xenografted into nude mice as a PC metastasis model.

Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs. MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs, in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells. And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells, to inhibit PC cell migration and invasion. Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues (P < 0.05) and was negatively associated with lymphovascular invasion (P = 0.044). As a direct target of miR-485-3p, PAK1 was found to exert an inhibitory effect on PC cells, and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1 (r = -0.6525, P < 0.0001) in PC tissues. Moreover, miR-485-3p could suppress PC metastasis in vivo by targeting p21-activated kinase-1.

Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1. The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.

Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC).

We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage.

From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group (P < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298–0.726; P = 0.001) and 0.474 (0.314–0.717; P < 0.001) after adjusting for potential confounders, respectively.

ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.

Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients.

This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events.

At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated.

Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high.

ClinicalTrials.gov, NCT04214951.

根据现行指南，HBV DNA阳性但丙氨酸氨基转移酶（ALT）水平正常的慢性乙型肝炎病毒（HBV）感染患者目前不需要抗病毒治疗。^[1]然而，研究发现，即使是ALT正常的慢性HBV感染患者，也可能进展为肝硬化或肝细胞癌（HCC）。此外，发现几乎一半ALT水平正常的患者具有中度至重度炎症和/或显著纤维化。^[2]目前对ALT水平正常的慢性HBV患者的治疗研究很少，影响其病毒学应答（VR）的因素仍不清楚。越来越多的研究证明，血清HBV RNA可以作为预测VR的非侵入性指标。^[3]在这项研究中，我们探讨了HBV RNA在预测ALT正常的慢性HBV患者VR中的预测价值。

致编辑：氨甲环酸（TXA）最近在骨科手术中变得流行，因为它在减少失血、输血率和死亡率方面的功效而不增加深静脉血栓形成的风险。^[1]尽管TXA给药的理想剂量和途径仍不清楚，但它已成为围手术期血液保存策略中最重要的部分之一。然而，给心血管疾病患者开TXA处方仍然存在争议，因为它具有促血栓形成和促惊厥作用，可能会增加心血管风险。心房颤动（AF）是最常见的持续性心律失常，影响全球超过3300万人，并与中风风险增加五倍相关。^[2]对这些患者给予口服抗凝剂以预防中风和全身栓塞，抗凝治疗会增加全关节置换术期间的围手术期失血量。尽管先前的一项研究表明TXA对全髋关节置换术后心血管事件和死亡的风险没有有害影响，但该研究中调查的人群包括无心血管疾病的患者，这可能掩盖了这些患者术后心血管并发症的真实发生率，从而导致统计学偏倚。^[1]因此，回顾性队列研究旨在评估围手术期TXA给药对接受全关节置换术的房颤患者心血管闭塞事件和围手术期复苏的影响。

致编辑：预防溃疡性结肠炎（UC）相关的致癌作用越来越受到关注。肠道微生物群在维持肠道屏障和免疫功能方面发挥着重要作用。2015年5月从Sigma-Tau pharmaceuticals(De Simone制剂)购买的益生菌混合物VSL#3是以下的混合物：干酪乳杆菌、植物乳杆菌、嗜酸乳杆菌、德氏乳杆菌亚种。保加利亚菌、长双歧杆菌、短双歧杆菌、婴儿双歧杆菌和唾液链球菌并含有45亿个活细菌菌落。^[1]先前的研究表明，VSL#3可以帮助诱导和维持UC缓解。益生菌对UC相关癌变的影响在临床上很难观察到；因此，常采用小鼠模型研究本病。既往研究表明，偶氮甲烷（AOM）联合葡聚糖硫酸钠（DSS）可快速诱导UC相关致癌模型。使用小鼠模型的研究已经证明VSL#3抑制UC相关的致癌作用，但是结论仍然有争议。VSL#3预防UC相关致癌作用的确切机制仍不清楚。因此，我们利用AOM/DSS诱导UC相关癌变的小鼠模型验证了VSL#3预防UC相关癌变的作用，并探讨了具体的作用机制。考虑到小鼠和人类之间的差异，我们进一步探索了益生菌如何在人类细胞水平上影响Wnt/β-catenin通路。由于同时培养多种益生菌具有挑战性，我们使用双歧杆菌探讨VSL#3对小鼠和细胞癌变的影响和机制。

致编辑：胃癌（GC）对全球人类健康构成巨大威胁。N6-甲基腺苷（m6A）RNA甲基化是最丰富的转录后RNA修饰，在RNA剪接、输出、加工、翻译和衰变中起着至关重要的作用。^[1]肿瘤微环境(TME)是肿瘤细胞和周围肿瘤相关非肿瘤细胞的聚集，天生调节肿瘤进展。^[2]然而，m6A调节因子相关基因的预后价值及其与TME的关系尚未在GC中得到很大程度的探索。我们研究的目的是在癌症基因组图谱（TCGA）数据库中筛选胃癌患者中与m6A修饰相关的预后基因，建立用于预测临床结果的m6A调节因子相关特征，并验证在TCGA和基因表达综合（GEO）队列中的表现。还在GC中评估了m6A和免疫浸润之间的关系。随着潜在机制的揭示，m6A相关基因可能成为GC的预测生物标志物，并为TME和免疫治疗提供更深入的见解。

致编辑：体温过低被描述为患者的核心温度降低到等于或<36°，这是择期手术患者中常见且严重的并发症。^[1]研究报告称，体温过低与几种不良事件的风险增加相关，包括术后寒战、手术部位感染、失血增加和住院时间延长。^[2]已经发现在手术过程中主动加温>30分钟可降低围手术期体温过低的风险。因此，如何有效预防围手术期体温过低越来越受到重视，许多术中主动加温策略因此被应用于临床实践，如强制空气加温技术、麻醉前预热技术、电阻聚合物系统、循环水床垫、自暖毯等。

致编辑：冠状动脉计算机断层扫描血管造影（CCTA）已越来越广泛地用于诊断冠状动脉疾病。^[1]解剖诊断，即狭窄分级，仍是大多数CCTA检查提供的主要诊断指标。狭窄的后处理和解释是心血管影像专业人员从扫描完成到诊断结论需要执行的两个基本步骤，这是重复和耗时的，在中国平均每个病例需要30分钟，并成为瓶颈并逐渐造成供需失衡。随着近年来人工智能（AI）技术的快速发展，人们一直期望解决这些具体问题。我们开发了一个人工智能系统，使用深度学习算法自动进行CCTA数据的后处理和诊断报告，以建立一个新的日常使用的一键式工作流程，即CCTA-AI（图1).为了进一步评估其能力，本研究打算回答以下两个问题：它能在多大程度上提高后处理的效率？CCTA-AI能在多大程度上检测和计算每个动脉粥样硬化斑块导致的冠状动脉狭窄？

致编辑：永久性血管通路是血液透析依赖患者的维持生命的措施。通常，隧道套囊导管（TCC）被认为是动静脉瘘（AVF）或动静脉移植物（AVG）的桥接通路，指南不鼓励TCC作为永久性血管通路的首选，因为并发症风险较高，预期使用寿命较短。^[1]然而，值得注意的是，一个子集（<10%)的血液透析患者需要通过TCC进行永久通路，因为他们已经用尽了其他动静脉通路选择。^[2]

致编辑：非酒精性脂肪性肝病（NAFLD）在亚洲流行，据报道在中国的患病率为24%至36%。^[1]NAFLD的患病率及其相关的医疗负担可能被低估。NAFLD的诊断导致排除了包括“过量”酒精在内的其他慢性肝病，因此饮酒或患有其他肝病的人群可能会被忽视。2020年3月，国际专家共识提出了一个新概念，“代谢相关脂肪性肝病（MAFLD）”，并取代了早期的术语“NAFLD”。^[2]作为最普遍的女性恶性肿瘤，乳腺癌（BC）与MAFLD具有相似的危险因素。较高水平的肥胖和缺乏体育活动与BC密切相关，并且是BC患病率增加趋势的重要驱动力。一些BC幸存者可能接受化疗和内分泌治疗，据报道，这两种治疗都会增加肝脂肪变性（HS）的风险，而这是诊断MAFLD的基本标准。^[2]乳腺癌幸存者（BCS）中HS的患病率通常被肿瘤学家忽视，HS通常通过常规肝脏超声检查（US）诊断，而肝脏超声弹性成像（USE）由于其比US更高的敏感性和特异性而越来越多地使用。^[3]因此，在我们的研究中，使用来调查BC中HS和MAFLD的准确患病率。

致编辑：小脑-面-牙综合征（CFDS）是一种罕见的常染色体隐性（AR）神经发育疾病，以小脑发育不全和智力残疾、面部畸形、身材矮小、小头畸形和牙齿异常为特征。^[1]2015年，Borck等人观察到三对兄弟姐妹具有以前未描述的异常模式，并将CFD确立为临床实体。迄今为止，共报告了六个差价合约家族。^[1,2,3,4]报告患者的年龄范围从婴儿期到成年早期。由于CFD的罕见性，需要更多的研究来评估其自然史和临床特征。本文报道了一种新的纯合子BRF12例中国中年CFDS患者的基因突变，并总结其临床和遗传学特征，加强其致病性BRF1基因突变和扩大CFDS的表现范围。

致编辑：周围神经损伤（PNI）是指周围神经丛、神经干或其分支在外力作用下的损伤。骨骼肌来源的细胞具有很强的分泌功能，同时可以分化为雪旺细胞样细胞或其他细胞类型，因此可以有效地促进周围神经的再生。^[1]使用一些表面有轻度机械刺激的特定穴位，可以对神经修复产生积极作用。^[2]推拿有助于缓解神经损伤引起的肌肉痉挛和疼痛等症状。有三个穴位属于足太阳膀胱经(BL)和足少阳胆囊经(GB)，通常被选择进行推拿。根据解剖神经位置，阴门（BL37）在坐骨神经干上，承山（BL57）在胫神经上，阳陵泉（GB34）在腓总神经上；同时，这三个点在坐骨神经或其分支上。这三个点分别在股二头肌、腓肠肌和胫骨前肌上。推拿能促进坐骨神经损伤（SNI）大鼠痛觉知觉和后肢精细运动的恢复，并与背根神经节和神经损伤点的遗传改变有关；同时，差异表达基因（DEGs）在与肌细胞调节相关的生物学过程中富集。^[3]本研究探讨推拿对SNI大鼠后肢肌力变化的恢复及腓肠肌遗传变化的影响。

致编辑：血管性痴呆（Vascular dementia，VD）是一种由多种脑血管因素引起的以认知功能障碍和智力下降为特征的临床疾病。中老年人VD的高发已成为世界性的重大医学和社会问题。^[1]由于其具体发病机制尚未完全阐明，临床上仍以改善认知、对症治疗为主，如吡拉西坦、多奈哌齐等。^[2]另一方面，中药以其疗效高、副作用小的特点，引起了医学界的关注，成为医学研究领域的热点。