2023年 · 第136卷第07期

出版日期 2023-04-05电子版￥0.00元

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Review Article

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长非编码RNA JPX在恶性过程中的新作用及其在癌症中的潜在应用

Yuanyuan Wang, Huihui Bai, Meina Jiang, Chengwei Zhou, Zhaohui Gong

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002392

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选择性剪接在传染病中的作用：从宿主、病原体到它们的相互作用

Mengyuan Lyu, Hongli Lai, Yili Wang, Yanbing Zhou, Yi Chen, Dongsheng Wu, Jie Chen, Binwu Ying

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002621

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磁共振聚焦超声在帕金森病治疗中的应用现状

Haoxuan Lu, Xiaoyu Wang, Xin Lou

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002319

摘要

Meta Analysis

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普通人群和高危人群结直肠癌的化学预防：一项系统综述和网络荟萃分析

Ye Ma, Wen You, Yang Cao, Xuxia He, Jing Wang, Yuelun Zhang, Ji Li, Jingnan Li

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002514

摘要

Background: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents. Methods: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study. Results: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44–0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43–0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43–0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13–1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo. Conclusions: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence. Registration: PROSPERO, No. CRD42022296376

Original Article

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TRIM25通过促进HBx降解和RIG-I介导的pgRNA识别来抑制HBV复制

Hongxiao Song, Qingfei Xiao, Fengchao Xu, Qi Wei, Fei Wang, Guangyun Tan

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002617

摘要

Background: The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25. Methods: The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay. Results: We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process. Conclusions: The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.

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脑容量显著偏差的特发性神经发育迟缓患者的遗传背景

Xiang Chen, Yuxi Chen, Kai Yan, Huiyao Chen, Qian Qin, Lin Yang, Bo Liu, Guoqiang Cheng, Yun Cao, Bingbing Wu 等

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002297

摘要

Background: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). Methods: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. Results: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs. 75.0% [30/40], P= 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes (P = 1.656e-9). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. Conclusion: Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.

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急性髓系白血病患者显微移植后不匹配供体细胞输注相关综合征

Bo Cai, Xiaoyan Zou, Xin Ning, Tieqiang Liu, Bingxia Li, Yaqing Lei, Jianhui Qiao, Kaixun Hu, Yangyang Lei, Zhiqing Liu 等

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002611

摘要

Background: Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted. Methods: We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored. Results: Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2–5] loci vs. 5 [3–5] loci, P = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P = 0.024). On the other hand, those with decreased CD4+/CD8+ T-cell ratio developed more fever (0.8 [0.7–1.2] vs. 1.4 [1.1–2.2], P = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932–0.995, P = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859–0.975, P = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control. Conclusions: Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.

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中国57个新生儿重症监护病房24~31周胎龄婴儿产前皮质类固醇使用情况的横断面研究

Jing Zhao, Zongtai Feng, Yun Dai, Wanxian Zhang, Siyuan Jiang, Yanchen Wang, Xinyue Gu, Jianhua Sun, Yun Cao, Shoo K. Lee 等

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002266

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5-氟尿嘧啶和亚叶酸钙术中化疗对结直肠癌根治术后患者生存率的影响：一项回顾性队列研究

Xuhua Hu, Zhaoxu Zheng, Jing Han, Baokun Li, Ganlin Guo, Peiyuan Guo, Yang Yang, Daojuan Li, Yiwei Yan, Wenbo Niu 等

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002598

摘要

Background: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. Methods: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. Results: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients (P < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). Conclusions: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. Trial registration: chictr.org.cn, ChiCTR 2100043775.

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胆囊切除术与结直肠癌风险的关系：孟德尔随机化研究

Lanlan Chen, Zhongqi Fan, Xiaodong Sun, Wei Qiu, Wentao Mu, Kaiyuan Chai, Yannan Cao, Guangyi Wang, Guoyue Lv

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002612

摘要

Background: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. Methods: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level (P value <5 × 10-8) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. Results: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607–3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn’s disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164–0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096–52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010–1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002–1.125) after adjustment of cholecystectomy. Conclusions: The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.

Correspondence

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吡咯替尼与当前标准治疗晚期非小细胞肺癌患者二线/三线治疗的结果比较HER2突变

Shiqi Mao, Libo Luo, Shuo Yang, Yan Wang, Fei Zhou, Jia Yu, Bin Chen, Guanghui Gao, Xuefei Li, Chao Zhao 等

中华医学杂志英文版2023年 136卷 07期

DOI: 10.1097/CM9.0000000000002453

摘要