Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Cardiovascular diseases are the leading cause of mortality, posing a significant threat to human health due to the high incidence rate. Atherosclerosis, a chronic inflammatory disease, serves as the primary pathological basis for most such conditions. The incidence of atherosclerosis continues to rise, but its pathogenesis has not been fully elucidated. As an important member of the small GTPase superfamily, Ras-association proximate 1 (Rap1) is an important molecular switch involved in the regulation of multiple physiological functions including cell differentiation, proliferation, and adhesion. Rap1 achieves the utility of the molecular switch by cycling between Rap1-GTP and Rap1-GDP. Rap1 may influence the occurrence and development of atherosclerosis in a cell-specific manner. This article summarizes the potential role and mechanism of Rap1 in the progression of atherosclerosis in different cells, aiming to provide new therapeutic targets and strategies for clinical intervention.
Humans ; Atherosclerosis/metabolism* ; rap1 GTP-Binding Proteins/physiology* ; Animals ; Cell Differentiation ; Cell Adhesion ; Cell Proliferation

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

Objective To study the compliance and correctness of hand hygiene(HH)of staff in intensive care units(ICUs)of a tertiary first-class hospital,and provide theoretical basis for HH intervention.Methods In April 2023,staff in 17 ICUs of this hospital were performed on-site survey by infection control staff,and monitoring forms about HH compliance and correctness were filled out.Results A total of 874 HH opportunities were ob-served with the concealed observation method,501 HH opportunities were implemented,the compliance rate was 57.32％,273 HH opportunities were correctly implemented,with an correct rate of 54.49％.The compliance and correct rate of HH among staff in different ICUs varied significantly.Compliance and correct rates of HH among staff with different jobs were statistically different:HH compliance rate of cleaners(31.97％)was lower than that of nurses(63.83％),doctors(58.77％)and other personnel(58.14％);HH correct rate of cleaners(30.77％)was lower than that of nurses(58.17％).The causes for not implementing HH among staff with different jobs and at different HH opportunities were statistically different:the rate of not implementing any HH measures after con-tact with patients(84.75％)was higher than before contact with patients(41.27％),before clean and sterile ma-nipulation(30.00％),as well as after contact with blood and body fluid(45.45％).The rate of not implementing any HH measures after contact with the patient's surrounding environment(66.67％)was higher than before con-tact with patient as well as before clean and sterile manipulation.The rates of incomplete HH steps and insufficient HH time among staff with different jobs were statistically different:The rates of incomplete HH steps of other per-sonnel(82.35％)was higher than that of doctors(52.63％).The rates of insufficient HH time of doctors(82.46％)and nurses(78.18％)were higher than that of cleaners(51.85％).Conclusion The implementation of HH among different occupational groups and at different HH implementation opportunities in ICU is significantly different,which should be intervened based on their characteristics.

AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM,and the mice were randomly divided into the control group,the model group,the pirfenidone group(0.3 g/kg)and the high,medium and low dose groups of Ophiopogonis Root Decoction(18,9,4.5 g/kg).HE and Masson staining,ELISA,flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung,the levels of Collagen I,HYP and TGF-β1,the proportion of PD-1+ CD4+T cells in plasma,and the expressions of p-STAT3,PD-1,PD-L1 and IL-17A in lung tissue,respectively.RESULTS Compared with the control group,the model group displayed significantly higher level of lung coefficients(P<0.01),more severe pulmonary inflammatory cell infiltration and collagen fiber deposition,and increased pulmonary fibrosis score(P<0.01),increased levels of Collagen I,HYP and TGF-β1(P<0.01),increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01),increased pulmonary expression of p-STAT3,PD-1,PD-L1 and IL-17A(P<0.01).Compared with the model group,the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05),less pulmonary inflammatory cell infiltration and collagen fiber deposition,decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I,HYP and TGF-β1(P<0.05),decreased proportion of PD-1+ CD4+T cells in plasma(P<0.05),and decreased pulmonary expression of p-STAT3,PD-1,PD-L1,and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM)deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.

Objective:To investigate the effects of oral probiotics on intestinal microbiota and cognitive dysfunction in breast cancer chemotherapy patients. Methods:Thirty breast cancer patients who received anthracycline chemotherapy between December 2021 and June 2022 in the Department of Oncology, the First Affiliated Hospital of Bengbu Medical University were included in this study. The patients were randomly divided into the observation and control groups (15 cases per group). During chemotherapy, the observation group was additionally given oral probiotics. The fecal microbiota compositions before and after chemotherapy were detected using 16S rDNA sequencing. The changes in patients' subjective and objective cognitive function levels were evaluated by Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog), respectively. Results:The microbiota diversity, as indicated by the Chao, Ace, Shannon and Simpson indices, showed no significant difference between two groups (P>0.05). As compared with the control group, the relative abundance of the genus Actinomyces in the feces was significantly higher than in the observation group (P<0.05). By contrast, the relative abundance of the genera Acetoanaerobium, Lachnospiracea_incertae_sedis, and unclassified_Frankineae bacteria was significantly lower in the observation group (P<0.05). The total scores of the objective and subjective cognitive function as well as the scores of each dimension in both groups were markedly decreased after chemotherapy (P<0.05). The scores in the observation group were higher than those in the control group after chemotherapy (P<0.05). During chemotherapy, the presence of the gastrointestinal adverse reactions (constipation, nausea and vomiting, diarrhea and abdominal distension) in the observation group were significantly lower than in control group (P<0.05). Conclusion:Oral probiotics could improve the cognitive impairment and reduce the presence of the gastrointestinal side effects in the breast cancer patients receiving chemotherapy, which may be caused by modulating the intestinal microbiota.