OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.

Objective To explore the feasibility and safety of fastest recovery after surgery(FRAS)in laparoscopic surgery of gastrointestinal tumors.Methods The clinical data of patients undergoing laparoscopic surgery for gastrointestinal tumors under FRAS and enhanced recovery after surgery(ERAS)from Jan.2023 to May 2024 were collected,and perioperative safety and medical cost were analyzed.Results A total of 87 patients were enrolled,including 43 in the FRAS group and 44 in the ERAS group.Compared with the ERAS group,the FRAS group had significantly shorter surgical time(3.0[2.5,3.5]h vs 3.0[2.5,4.0]h),first postoperative movement time([2.85±4.29]h vs[20.18±6.13]h),first postoperative oral feeding time(2.0[2.0,3.0]h vs 24.0[15.0,48.0]h),postoperative hospital stay(24.0[20.0,40.0]h vs 192.0[150.0,216.0]h),lower hospitalization costs(50 515.61[46 650.44,56 827.12]yuan vs 65 555.09[58 683.21,86 239.02]yuan),and lower medication costs(2 671.09[2 063.31,3 127.09]yuan vs 7 326.90[5 104.66,10 674.26]yuan)(all P＜0.05).Conclusion It is safe and feasible to use FRAS during the perioperative period of laparoscopic radical gastrectomy for gastrointestinal tumors,and FRAS can also reduce the costs of hospitalization and medications.

Objective To investigate the effect of overexpression of LncRNA MEG3 on proliferation,migration and cisplatin sensitivity of hepatoma cells HepG2 and LM3 and explore the underlying and mechanism.Methods The expression of MEG3 in healthy individuals and patients with hepatocellular carcinoma(HCC)was analyzed by online bioinformatics analysis,and Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect MEG3 expression in different HCC cell lines.A MEG3-overexpresing plasmid was transfected in HepG2 and LM3 cells,and the changes in cell proliferation and migration were examined using CCK8 assay and scratch assay.CCK8 assay was used to determine the inhibitory rate of cisplatin on the transfected cells.A reactive oxygen species(ROS)fluorescence probe(DCFH-DA)and malondialdehyde(MDA)kit were used to assess the changes in ROS production and MDA level in the cells.Western blotting was performed to detect the expression levels of ferroptosis-related proteins glutathione peroxidase 4(GPX4)and ferritin heavy chain 1(FTH1).Results The expression of MEG3 was significantly lower in HCC cells than in LO2 cells,which was consistent with the results of bioinformatic analysis(P<0.05).Overexpression of MEG3 in the HCC cell lines significantly suppressed cell proliferation and migration(P<0.05),increased the cell inhibition rate of cisplatin(P<0.05),enhanced cellular ROS production and increased MDA levels in the cells(P<0.05).MEG3 overexpression significantly decreased the expressions of GPX4 and FTH1 in the HCC cell lines.Conclusion The expression of MEG3 is decreased in HCC cells,and its overexpression inhibits proliferation and migration and enhances cisplatin sensitivity of HCC cells by promoting ferroptosis of the cells.

Objective: To examine the mediating effect of positive coping style on health literacy and lifestyle among medical students, so as to provide the reference for health education and health promotion among medical students in universities. Methods: Medical students of six full-time medical colleges in Guizhou Province were sampled using a multi-stage stratified cluster random sampling method from April to June 2023, and their gender, age and educational level were investigated by questionnaires. The College Students' Healthy Lifestyle Scale, the Health Literacy Questionnaire and the Simplified Coping Style Scale were used to evaluate lifestyle, health literacy and coping style of students. The Process program was used to analyze the mediating effect of positive coping style on health literacy and lifestyle, and Bootstrap method was used to examine the significance of the mediating effect. Results: A total of 9 266 peoples were investigated, including 3 177 males (34.29%) and 6 089 females (65.71%), and had a mean age of (21.06±2.61) years. There were 2 775 junior college students (29.95%), 4 864 undergraduates (52.49%) and 1 627 master students (17.56%). The scores of lifestyle, health literacy and positive coping style among medical students were 118.34±19.06, 54.57±10.81 and 2.81±0.68, respectively. Health literacy had a direct positive effect on lifestyle (effect value=0.286, 95%CI: 0.257-0.316) and a indirect positive effect on lifestyle through positive coping style (effect value=0.215, 95%CI: 0.193-0.236), and the mediating effect contributed 42.91% to the total effect. Conclusion Health literacy could improve lifestyle indirectly through positive coping style among medical students.

Objective To investigate the effect of overexpression of LncRNA MEG3 on proliferation,migration and cisplatin sensitivity of hepatoma cells HepG2 and LM3 and explore the underlying and mechanism.Methods The expression of MEG3 in healthy individuals and patients with hepatocellular carcinoma(HCC)was analyzed by online bioinformatics analysis,and Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect MEG3 expression in different HCC cell lines.A MEG3-overexpresing plasmid was transfected in HepG2 and LM3 cells,and the changes in cell proliferation and migration were examined using CCK8 assay and scratch assay.CCK8 assay was used to determine the inhibitory rate of cisplatin on the transfected cells.A reactive oxygen species(ROS)fluorescence probe(DCFH-DA)and malondialdehyde(MDA)kit were used to assess the changes in ROS production and MDA level in the cells.Western blotting was performed to detect the expression levels of ferroptosis-related proteins glutathione peroxidase 4(GPX4)and ferritin heavy chain 1(FTH1).Results The expression of MEG3 was significantly lower in HCC cells than in LO2 cells,which was consistent with the results of bioinformatic analysis(P<0.05).Overexpression of MEG3 in the HCC cell lines significantly suppressed cell proliferation and migration(P<0.05),increased the cell inhibition rate of cisplatin(P<0.05),enhanced cellular ROS production and increased MDA levels in the cells(P<0.05).MEG3 overexpression significantly decreased the expressions of GPX4 and FTH1 in the HCC cell lines.Conclusion The expression of MEG3 is decreased in HCC cells,and its overexpression inhibits proliferation and migration and enhances cisplatin sensitivity of HCC cells by promoting ferroptosis of the cells.

Objective To explore the clinical characteristics of Kennedy's disease （KD）. Methods We reported three cases of KD confirmed by genetic testing admitted to the Department of Neurology of The First Affiliated Hospital of Henan University of Science and Technology. Based on their clinical manifestations， physical examination results， and auxiliary examination data as well as previous literature， we analyzed and summarized the clinical features of KD. Results The three male KD patients were aged 43-46 years. They mainly manifested with progressive slurred speech， limb weakness， tongue muscle atrophy with tremor， and breast development. Creatine kinase levels were increased and sex hormone levels were abnormal in all the patients. Electromyography showed extensive neurogenic damage with involvement of both motor and sensory nerves. Genetic testing detected over 40 CAG repeats in the androgen receptor gene in all the cases. Conclusion KD is a late-onset inherited motor neuron disease， which can involve multiple systems to cause various clinical manifestations. Genetic testing is needed for a definite diagnosis.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective:To investigate the feasibility and effectiveness of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery.Methods:The clinical data of 140 patients underwent gastrointestinal surgery from August 2021 to April 2022 in Shanghai Fourth People′s Hospital, School of Medicine, Tongji University were retrospectively analyzed. Among them, 70 patients were given routine postoperative analgesia (control group), and 70 patients were given incision subcutaneous porous catheter combined with ropivacaine analgesia on the basis of routine postoperative analgesia (observation group). The visual analogue score (VAS) 4, 24, 32, 48, 56 and 72 h after operation was evaluated; and the complications of subcutaneous catheterization, incision infection, postoperative nausea vomiting, neurological symptoms, time to extubation, patient satisfaction degree, recovery time of intestinal function and hospital stay were recorded.Results:The VAS 4, 24, 32, 48, 56 and 72 h after operation in observation group was significantly lower than that in control group: 1.000 (- 0.250, 2.250) scores vs. 1.000 (- 1.000, 3.000) scores, 2.000 (1.000, 3.000) scores vs. 4.000 (2.000, 6.000) scores, 1.000 (0.000, 2.000) scores vs. 3.000 (1.000, 5.000) scores, 2.000 (1.000, 3.000) scores vs. 3.000 (1.750, 4.250) scores, (1.100 ± 0.934) scores vs. (2.085 ± 0.943) scores and (0.985 ± 0.842) scores vs. (1.814 ± 0.921) scores, and there was statistical difference ( P<0.05 or <0.01). The recovery time of intestinal function and hospital stay in observation group were significantly shorter than that that in control group: (1.743 ± 0.557) d vs. (2.200 ± 0.714) d and (8.043 ± 1.160) d vs. (8.757 ± 1.221) d, and there were statistical difference ( P<0.01); there were no statistical differences in the rate of incision infection, incidence of postoperative nausea vomiting, time to extubation and patient dissatisfaction rate between two groups ( P>0.05); there were no the complications of subcutaneous catheterization and neurological symptoms in two groups. Conclusions:The incision subcutaneous porous catheter combined with ropivacaine analgesia after laparoscopic gastrointestinal surgery is a safe, effective and feasible method. Multimodal analgesia under enhanced recovery after surgery can increase the postoperative recovery after gastrointestinal operations and shorten the postoperative hospital stay.