[摘 要] 可变剪接是转录后水平的基因表达调控机制，也是导致真核生物转录组和蛋白质组多样性的重要途径。然而，可变剪接的异常是驱动肿瘤进展的重要推手。在肿瘤微环境中，肿瘤细胞、免疫细胞及肿瘤中其他类型细胞中mRNA的异常剪接，不仅参与塑造肿瘤细胞的恶性生物学行为和免疫逃逸，还促进支持肿瘤进展的免疫抑制性微环境的形成。靶向肿瘤相关剪接体组分、剪接调控因子、可变剪接产生的蛋白异构体和mRNA变异体，以及异常可变剪接产生的肿瘤新抗原已成为肿瘤治疗的新策略，已有基于可变剪接的肿瘤生物治疗项目进入到Ⅰ期临床研究阶段。基于可变剪接的肿瘤治疗面临安全性、长读测序和算法优化、核酸类药物递送等许多尚待解决的科学和技术问题，这些挑战的解决将为精准筛选肿瘤相关靶点和高免疫原性新抗原，突破传统疗法耐药瓶颈，增强免疫检查点阻断和CAR-T细胞等疗效提供新策略，开辟新领域。

Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

Objective To summarize and explore the current state,hotspots,and trends in the field of surgical treatment for intracerebral hemorrhage(ICH)over the past decade through a bibliometric and visualization analysis of relevant literature.Methods Relevant Chinese and English literature on the surgical treatment of ICH,published from January 1,2014 to April 1,2024,was retrieved and screened from CNKI and Web of Science databases.Visualization analysis was conducted using CiteSpace,VOSviewer,and other software to analyze the number of published papers,authors,countries,institutions,etc.Social network analysis diagrams of authors,keyword clustering network analysis diagrams,keyword burst strength,and keyword timeline maps were also utilized.Results(1)A total of 3 456 relevant papers were included,with 2 173 in Chinese and 1 283 in English.From 2014 to 2021,the annual number of Chinese publications on ICH surgery was higher than that of English publications,but the number of Chinese publications began to decline from 2016.The number of English publications showed an overall increasing trend.(2)A total of 6 367 authors were identified from the English literature,with notable collaboration networks led by researchers such as Mocco J,Hanley DF,Ziai WC,You C,and Tang ZP.The Chinese literature included 6 522authors,with prominent collaboration networks led by Wang LK,Cai Q,Ku HB,Zhang S,and Zhu SQ.(3)Analysis of the countries involved in the English literature showed that 31 countries participated in research on ICH surgery,with China leading in the number of publications(505),followed by the United States(330)and Germany(106).The top three countries in centrality were the United States(0.32),China(0.16),and Canada(0.11).The top three institutions in English literature publications were Johns Hopkins University(51 papers),Ohio State University(39 papers),and Harvard University(38 papers).In China,Sichuan University(32 papers),Huazhong University of Science and Technology(30 papers),and Capital Medical University(27 papers)had multiple English publications;Wuhan University People's Hospital(15 papers),Affiliated Hospital of Guizhou Medical University(13 papers),and Affiliated Hospital of Yan'an University(13 papers)had multiple Chinese publications.There was close collaboration among research institutions in the English literature,whereas Chinese researchers often established research teams within their medical units with relatively less collaboration between teams.(4)Research on ICH surgery primarily focused on surgical methods,complications,and comprehensive perioperative treatment.Research hotspots included hypertensive ICH,minimally invasive surgical techniques,and perioperative management and treatment."neuroendoscopy"was the most recent emergent keyword in Chinese literature with high centrality and the strongest burst strength,while"randomized trial"had the highest burst strength in English literature.Research trends included the integration of artificial intelligence with minimally invasive techniques to optimize ICH surgery management and treatment strategies,analysis of risk factors,and evaluation of imaging value.Conclusions Over the past decade,the overall publication volume on the surgical treatment of ICH has been in a stable development phase,with research directions covering surgical techniques,diagnosis and treatment,evaluation,and management.Core research teams led by key authors were the main contributors to the publications.Future research hotspots and trends in ICH surgery may include the optimization of surgical techniques,complication management,large-scale multicenter clinical trials and integration of artificial intelligence with minimally invasive techniques.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective This study aims to investigate the sex difference in the hippocampus and parahippocampus in patients with bipolar disorder. Methods We acquired T1－weighted structural MRI from 133 bipolar type I patients (60 males) and 144 normal controls (81 males). The General Linear Model was used to examine the relationship between sex and brain volumes of the hippocampus and parahippocampus, with age and intracranial volume as covariates. Results Patients showed significantly smaller volumes of the bilateral hippocampus and parahippocampus (P＜0.01). There were sex－by－diagnosis interactions in the left parahippocampus gyrus (F=6.534, P=0.044). Male patients had significant smaller volumes of the left parahippocampus gyrus compared to the male normal controls (P＜0.001) whereas the volumes were not significantly different between female patients and female normal controls (P＞0.05). Conclusion The results suggest sex difference in the left parahippocampus gyrus volume in patients with bipolar type I disorder, which deserves further investigation in the future bipolar imaging researches.

AIM:To evaluate the effect of mycoplasma on the rRNA composition of mature ribosomes in human cell lines.METHODS:We isolated ribosome nascent-chain complex ( RNC) from multiple mycoplasma-positive-negative human cell lines.RNC-RNA was acquired from each cell line through RNA extraction, followed by agarose gel separation, fluorescent visualization and gray-scale value measurements on the rRNA bands.Western blot analysis was performed to in-vestigate the MAPK pathway alterations.RESULTS:In various human cell lines derived from different tissues, we found that as compared with mycoplasma-negative cells, mycoplasma-positive cells showed aberrant RNC-rRNA band patterns, featured by the decreases in 28S and 18S eukaryotic rRNAs and the increases in 16S and other unknown prokaryotic rRNAs.When cultured without ciprofloxacin, mycoplasma-negative HBE cells acquired mycoplasma contamination as ob-served with such characteristic abnormal rRNA bands.The ciprofloxacin treatment was able to recover the RNC-rRNA bands of the mycoplasma-contaminated cells to the normal pattern.The results of Western blot analysis on total and phos-phorylated proteins indicated that p38 pathway was significantly deactivated in mycoplasma-infected A549 cells, while ERK1/2 pathway was not significantly altered.CONCLUSION:Mycoplasma contamination severely alters the RNC-rRNA composition via p38 MAPK pathway, thus seriously impacting on the host cell translational behaviors.

Objective To analyze the clinical and pathologieal characteristics of IgA nephmlogy secondary to primary sj(o)gren's syndrome(pSS).Method The clinical and pathological data of 8 patients with pSS and IgA in Changzheng Hospital from 2004 to 2009 were analyzed.Results The average age of seven female and one male was (44±8) years old.Five patients presented with edema and proteinuria.Eight patients presented with microhematuria.The average 24-hour proteinuria was (3±4) g.Two patients had hypertension.Serum creatinine levels of two patients were higher than normal level,the others'were normal.Light microscopy examination showed three patients were mild mesangial proliferation with Lee's classification grade Ⅰ;five patients had global sclerosis with Lee's classification grade Ⅱ,Ⅲ and Ⅳ.Positive IgA was mainly found under immunofluorescence microscopy.Electronic microscopy showed no electron-dense deposits.Conclusion IgA nephrology secondary to pSS is different from primary IgA nephrology under immunofluorescence microscopy.