Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective:To evaluate the efficacy and safety of telitacicept in the treatment of systemic lupus erythematosus (SLE) .Methods:The clinical data of 25 SLE patients who received standard therapy combined with telitacicept at the Department of Dermatology, Xiangya Second Hospital, Central South University, from 2021 to 2024 were retrospectively collected. Baseline demographic and clinical characteristics were analyzed. Changes in skin lesions, joint pain symptoms, complete blood count, and biochemical parameters at 4, 12, and 24 weeks of treatment were compared with baseline (week 0). The Wilcoxon signed-rank test was used to compare complement C3 and C4 levels before and after treatment, and univariate logistic regression analysis was performed to explore factors influencing the efficacy of telitacicept.Results:Among the 25 SLE patients, 3 were male (12.0%) and 22 were female (88.0%). Based on the SLE Disease Activity Index (SLEDAI) -2000 scores, 8 patients were mild, 13 were moderate, and 4 were severe. Of the 11 SLE patients with rashes before treatment, 6 achieved complete remission at 12 weeks. Among the 7 patients with joint pain before treatment, 4 experienced symptom resolution at 24 weeks. The proportion of patients with leukopenia at baseline and at 4, 12, and 24 weeks was 10/25 (40.0%), 0/24 (0), 1/22 (4.5%), and 2/19 (10.5%), respectively. The proportion of patients with thrombocytopenia was 6/25 (24.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively, and the proportion of patients with anemia was 7/25 (28.0%), 3/24 (12.5%), 1/22 (4.5%), and 1/19 (5.3%), respectively. At baseline, 11 out of 25 patients (44.0%) had proteinuria. At 12 weeks, the urinary protein quantification level (0.4 [0, 0.6] g/L) was significantly lower than at baseline (0.9 [0.8, 1.2] g/L). The SLE responder index-4 (SRI4) response rates at 4, 12, and 24 weeks were 14/18, 15/17, and 12/14, respectively. Complement C3 and C4 levels were significantly higher at 4, 12, and 24 weeks compared to baseline (all P < 0.001). Univariate logistic regression analysis showed that age, disease duration, glucocorticoid dosage, baseline complement C4 levels, antinuclear antibody titer, and SLEDAI-2K score did not significantly affect the efficacy of telitacicept (SRI4 response rate at 12 weeks) (all P > 0.05). No serious adverse reactions related to telitacicept were observed in patients. Conclusions:Telitacicept improved skin lesions, complement C3 and C4 levels, and anti-double-stranded DNA antibody levels in SLE patients. No association was found between the efficacy of telitacicept and baseline SLEDAI-2K scores, antinuclear antibody titers, or complement C4 levels, suggesting that telitacicept is an effective and safe treatment for SLE patients.

Type 2 diabetes(T2DM)was a chronic metabolic disease,vascular lesions was one of the common complications of T2DM,including microvascular and macrovascular lesions,which seriously threatens the health of patients and increases the risk of disability and death.Dyslipidemia was one of the pathogenesis of type 2 diabetes,the disorder of lipid metabolism was also closely related to various acute and chronic complications of diabetes,the cholesterol in the lipoproteins rich in triglycerides(TG)was known as residual cholesterol.Existing studies have shown that,residual cholesterol was closely related to the occurrence and development of vascular lesions in T2DM.Residual cholesterol may be involved in T2DM vascular lesions through mediating inflammatory response,participating in oxidative stress,lipid metabolism disorder and direct damage to vascular endothelial function.This study reviewed the association between residual cholesterol and T2DM vascular lesions and its mechanism of action in T2DM vascular lesions,aiming to provide solid theoretical support for the formulation of prevention and treatment strategies for T2DM vascular lesions.

Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.