Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

Objective:To analyze the significance of systemic immune inflammatory index (SII) combined with neutrophil lymphocyte ratio (NLR) in the treatment of advanced gastric cancer with PD-1/PD-L1 inhibitors.Methods:The clinical data of 90 patients with stage Ⅳ gastric adenocarcinoma who received immunotherapy from January 2020 to January 2023 were retrospectively analyzed, including 70 males and 20 females, aged from 36 to 80 years, with an average age of (53.76±15.58) years. The clinicopathological features and follow-up data were collected. SPSS 26.0 software was used to conduct statistical analysis. The critical values of NLR, SII, PLR and MLR were calculated, and the overall survival (OS) and progression free survival (PFS) of patients with different levels of markers were analyzed. The independent predictive factors of PFS and OS were determined, and the predictive value of risk factors for PFS and OS in patients with gastric cancer was evaluated.Results:The median follow-up time of all patients was 27.3 months, and the median PFS and OS were 10.0 months and 17.7 months, respectively. The area under the curve (AUC) of NLR and SII for predicting PFS and OS were>0.7, the critical values NLR were 4.75 and 3.85, and SII were 1154.67 and 887.90, respectively. PFS and OS in patients with high NLR, high MLR, high PLR and high SII were lower than those in patients with low levels. ECoG PS≥ 1, high NLR and high SII were independent influencing factors of disease progression or death. The AUC of the combination of NLR, ECoG PS and SII was 0.761, which was higher than that of any single factor. The fewer the number of risk factors, the longer the PFS and OS.Conclusions:NLR and SII are effective predictors of PFS and OS in patients with advanced gastric cancer receiving immunotherapy. Pre treatment detection of NLR and SII can provide reliable guidance for immunotherapy of advanced gastric cancer.

Objective To investigate the predictive value of urinary exosomal microRNA(miR)-29 c in the clinical outcome of organ-and non-organ-confined bladder urothelial carcinoma(BUC).Methods From January 2017 to March 2022,152 patients with BUC were recruited from the Department of Urology in our hospital as a validation set.In addition,126 non-cancer controls were selected from the physical examination center of our hospital.The expression level of urinary exosomal miR-29c was detected by real-time quantitative PCR.Results In the validation set,urinary exosomal miR-29c level in BUC patients was significantly lower than that in non-cancer control group(P＜0.05),while urinary exosomal miR-17-5p level and miR-590-5p level were not significantly different(P＞0.05).The area under ROC curve of urinary exosomal miR-29c for the diagnosis of BUC was 0.969(95％CI:0.953～0.986),and the corresponding sensitivity and specificity were 92.1％and 90.2％,respectively.In subtype analysis,urinary exosomal miR-29c levels were further reduced in patients with non-organ-confined BUC compared with patients with organ-confined BUC(P=0.009).Overall survival(OS),disease-free survival(DFS)and disease-specific survival(DSS)were longer in the urinary exosomal miR-29c high expression group(P＜0.05).Conclusion Low levels of urinary exosomal miR-29c are an adverse prognostic factor for survival in patients with BUC,and are promising as a predictor of adverse clinical outcomes of organ-and non-organ-confined BUC.

Objective This paper investigates the effect of a multi-physical field fusion intervention based on transcranial direct current stimulation(tDCS),transcranial magnetic stimulation(TMS)and music on mental fatigue.Methods After fatigue induction,10 subjects received blank group stimulation,music group stimulation and tDCS-TMS-Music stimulation,respectively.tDCS stimulation sites were located in the bilateral frontal regions of the subjects,and TMS stimulation sites were located in the bilateral occipital regions of the hindbrain.Heart rate variability and reaction performance were measured before and after each intervention to determine the elimination effect of different intervention programs on mental fatigue.Results Compared with the control group,the tDCS-TMS-Music group showed significantly greater improvements in subjective mental workload,response performance,and heart rate variability.Conclusion The results of this study support that tDCS-TMS-Music can effectively alleviate mental fatigue induced by long-term cognitive performance tasks,and the intervention effect is better than music intervention and resting-state relief at the same time.

Objective To investigate the clinical significance of the differential expression of CD44 in glioblastoma(GBM),and the enrichment of related pathways combined with U87 cell verification.Methods Differential ex-pression and Cox analysis were used to find potential differences in CD44 expression between tumor patients and healthy people as shown by pancancer transcriptome and hazard ratio(HR).Immunoinfiltration and stem-cell re-lated scores of GBM patients with high and low CD44 expression groups were compared and the differences be-tween immune cell subsets,and their correlation with CD44 were further analyzed.Pathway enrichment of differen-tially expressed genes in high and low CD44 expression groups for GBM patients was performed.Over-expression(OE),knockdown(KD)and knockout(KO)of CD44 in U87 cells was done by constructing and packaging lenti-virus and using the electroribonucleoprotein complex;CD44 immunofluorescence staining was performed on U87 and U87 CD44 OE cells.The activity and apoptosis of U87 cells were detected by knocking down CD44 and the mi-gration and invasion ability of U87 cells were detected by knocking down CD44.Results The expression of CD44 in GBM patients was higher than that in healthy people(P＜0.05)and HR＞1.GBM patients with high CD44 ex-pression had higher stromal cell and immunoinfiltration scores,and GBM patients with high and low CD44 expres-sion had significant differences in the ratio of dendritic cells,CD4+memory T cells and regulatory T cells,all posi-tively correlated with CD44 expression(P＜0.05).Differential gene enrichment in GBM patients with high and low CD44 expression was further associated with pathways related to cell migration and apoptosis(P＜0.05).Experi-ments using U87 cells showed that CD44 was normally localized in the cell membrane,but for CD44 OE it accumu-lated in the cytoplasm.CD44 KD can lead to a decrease in cell viability,increased in cell apoptosis,with the cell migration and invasion ability of CD44 KO also decreasing(P＜0.05).Conclusions Low expression of CD44 can decrease viability,migration and invasion of U87 cells and promote apoptosis rate of U87 cells,which leads to the deterioration of GBM and is a related factor potentially affecting the prognosis of GBM patients.

Purpose/Significance To investigate the effectiveness of experiential teaching in perinatal healthcare management contin-uing education.Method/Process The perinatal healthcare team of Peking Union Medical College Hospital holds a four-day experiential learning program for 30 maternity-related medical staffs from China.Through the self-administered experiential teaching questionnaire(ETQ)and satisfaction questionnaire,the researchers analyze the participants'post-teaching skill acquisition,clinical application abil-ity and educational needs,as well as their satisfaction with course content,course duration,teaching design,classroom atmosphere,and teaching format,which are quantified with Likert scale.Result/Conclusion The experiential teaching mode shows good teaching effects in perinatal healthcare management continuing education,and has higher application value.In the future,the researchers should combine it with theoretical teaching and carry out more comprehensive and structured periodic learning classes throughout the country,so as to im-prove both the theoretical foundation and practical ability of healthcare workers for better healthcare services for pregnant women.

Vascular stents are an essential tool in cardiovascular interventional therapy, and their demand is growing with the increasing incidence of cardiovascular diseases. Compared with permanent stents, which are prone to in-stent restenosis, and drug-eluting stents, which may cause late stent thrombosis, biodegradable stents offer advantages. After providing early radial support to prevent elastic recoil, biodegradable stents gradually degrade, allowing the vessel to regain its natural physiological contractility and undergo positive remodeling. A review of the current mainstream biodegradable metal stents, magnesium-based, iron-based, and zinc-based alloys, shows promising findings in both preclinical and clinical research. Magnesium-based stents exhibit good operability and low thrombosis rates, but their limitations include rapid degradation, hydrogen evolution, and significant pH changes in the microenvironment. Iron-based stents demonstrate excellent mechanical strength, formability, biocompatibility, and hemocompatibility, but their slow corrosion rate hampers broader clinical application; accelerating degradation remains key. Zinc-based alloys have a moderate degradation rate but relatively low mechanical strength; enhancing stent strength by alloying with other elements is the main improvement direction for zinc-based stents.
Humans ; Absorbable Implants ; Stents ; Alloys/chemistry* ; Magnesium/chemistry* ; Biocompatible Materials/chemistry* ; Zinc/chemistry* ; Drug-Eluting Stents ; Iron/chemistry* ; Metals/chemistry*

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.