ObjectiveTo explore the effects of hypoxia on the migration ability of human oligodendrocyte precursor cells （hOPCs） and its regulatory mechanisms. MethodsBased on the variations in oxygen concentration within the culture system， three experimental groups were set up： the 21%O₂ group （normoxic control group）， the 5%O₂ group， and the 2%O₂ group. The migration ability of hOPCs under normoxia （21%O₂）， 5%O₂， and 2%O₂ conditions was detected through the Transwell migration assay. RT-qPCR， transcriptome sequencing， and flow cytometry were used to detect the expression changes of genes and proteins such as hypoxia-inducible factor 1 alpha （HIF-1α） and chemokine （C-X-C Motif） receptor 4 （CXCR4）. Bioinformatics analysis was combined to analyze the KEGG pathways related to migration， so as to explore the effects of different oxygen concentrations on the migration ability of hOPCs and their possible mechanisms. ResultsHypoxia treatments at concentrations of 5%O₂ and 2%O₂ could both promote the in vitro migration of hOPCs， and the promoting effect of migration was more significant at the 2%O₂ concentration （P<0.001）. After hypoxia treatment， the mRNA expression levels of HIF-1α， CXCR4， etc. in hOPCs significantly increased （P<0.001）. Compared with the 5%O₂ concentration， the expression of CXCR4 in cells was higher at the 2%O₂ concentration （P<0.000 1）. Flow cytometry analysis detection showed that the expression of CXCR4 increased significantly after hypoxia treatment （P<0.01）， and with the decrease of oxygen concentration， its expression level further increased （P<0.000 1）. Ordinary transcriptome sequencing analysis indicated that hypoxia treatment could activate the PI3K-Akt signaling pathway and the Axon guidance pathway. ConclusionHypoxia treatment can enhance the in vitro migration ability of hOPCs， and this effect is negatively correlated with the oxygen concentration. Its mechanism may be related to the up-regulation of the expression of genes such as HIF-1α and CXCR4， and the activation of the migration related signaling pathway including PI3K-Akt signaling pathway and axon guidance pathway.

To investigate the awareness of cognitive impairment disorders among residents of the Xizang Autonomous Region and its influencing factors, thereby providing a basis for targeted prevention and treatment efforts.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Objective:To examine the distribution of pathogens that cause postoperative nosocomial infections in patients with rectal cancer(RC)and to construct a predictive nomogram for nosocomial infection.Methods:The clinical data of 1537 RC patients admitted to Sir Run Run Shaw Hospital between January 2021 and December 2022 were collected.Patients were assigned 1∶1 by propensity score matching(PSM)to the infection group(n=83)and control group(n=83)based on the occurrence of nosocomial infection.The dis-tribution and drug resistance of bacteria in patients with nosocomial infection were analyzed.Risk factors for postoperative nosocomial infection were identified by least absolute shrinkage and selection operator(LASSO)regression,and a predictive nomogram was con-structed using multivariate logistics regression.The predictive performance of the model was evaluated by receiver operating character-istic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results:A total of 93 strains of pathogens were isolated from the 83 infected patients,including 62 strains of Gram-negative bacteria(66.67%;predominantly Escherichia coli and Pseudomonas ae-ruginosa),25 strains of Gram-positive bacteria(26.88%;mainly Enterococcus faecalis),and 6 strains of fungi(6.45%;all Candida albicans).LASSO and multivariate logistics regression showed that smoking(odds ratio[OR]=3.97,95%CI=1.27-12.43),the dwelling time of drainage tube(OR=1.19,95%CI=1.08-1.30),difference in preoperative and postoperative neutrophil counts(OR=1.23,95%CI=1.01-1.49),and difference between preoperative and postoperative C-reactive protein levels(OR=1.05,95%CI=1.03-1.07)were inde-pendent risk factors for postoperative nosocomial infection in RC patients.The area under the ROC curve of the nomogram constructed based on the above factors was 0.933(95%CI=0.896-0.969).The calibration curve showed that the predicted risk was in good agree-ment with the actual observed risk of infection.In addition,DCA demonstrated that the nomogram has good clinical utility and high net clinical benefits in predicting nosocomial infection.Conclusion:The nomogram constructed in this study has a good predictive perfor-mance in postoperative nosocomial infection in RC patients.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

BACKGROUND: Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC. METHODS: Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS. CONCLUSIONS ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.
Humans ; Female ; Breast Neoplasms/metabolism* ; Receptor, ErbB-2/metabolism* ; Progression-Free Survival ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease Progression ; Treatment Outcome

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*