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.

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.

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.

italic>Salvia apiana Jepson, commonly known as white sage, is a perennial sub-shrub of the Salvia genus in the Lamiaceae family with a long medicinal history. In this study, the complete chloroplast genome of S. apiana was sequenced using PacBio HiFi third-generation sequencing technology. The physical map of the genome was constructed, and the sequence structure features, codon preference, and repetitive sequences were analyzed. Furthermore, a comparative analysis of the chloroplast genome and phylogenetic evolution with closely related species within the same genus was conducted. The chloroplast genome of S. apiana was found to have a length of 151 701 bp (GenBank accession number: OR389048), with a typical quadripartite structure and a GC content of 38.06%. A total of 132 genes were annotated, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Among them, 17 genes contained introns, and 18 genes were present in duplicate copies. Codon preference analysis revealed a preference for codons ending with A or U. Analysis of repetitive structures in the S. apiana chloroplast genome identified 170 simple sequence repeat (SSR) sites and 65 scattered repeat sequences, with the majority of SSR sites composed of A and T. Phylogenetic analysis of the complete chloroplast genomes of 21 species within the same genus showed that S. apiana is most closely related to Salvia hispanica Ettling. ex Willk. & Lange, Salvia leucantha Cav., and Salvia tiliifolia Vahl. Comparative analysis of the chloroplast genomes revealed slight contraction and expansion of the inverted repeat (IR) boundaries in S. apiana, as well as multiple highly variable regions in the chloroplast genome sequence. This study establishes a method for de novo assembling the chloroplast genome of S. apiana using third-generation sequencing data and provides a comprehensive analysis of its chloroplast genome, which can serve as a theoretical basis for studies on chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification.

AIM To investigate the clinical effects of Buyang Huanwu Decoction combined with Erlong Xizhu Acupuncture Method on elderly patients with stroke.METHODS Ninety-six patients were randomly assigned into control group(48 cases)for 1-month intervention of Erlong Xizhu Acupuncture Method,and observation group(48 cases)for 1-month intervention of both Buyang Huanwu Decoction and Erlong Xizhu Acupuncture Method.The changes in neurological function indices(NIHSS score,NDS score),Hcy,CysC,vascular endothelial function indices(ET-1,NO,vWF),intracranial hemodynamic indices(Vmean,R,DR),hemorheological indices(WBLSV,WBHSV,FIB,HCT,EAI)and prognosis assessment indices(mRS score,BI score)were detected.RESULTS After the treatment,the two groups displayed decreased neurological function indices,Hcy,CysC,ET-1,vWF,R,DR,hemorheological indices,mRS score(P＜0.05),and increased NO,Vmean,BI score(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the elderly patients with stroke,Buyang Huanwu Decoction combined with Erlong Xizhu Acupuncture Method can reduce serum Hcy,CysC levels,and improve vascular endothelial functions,intracranial hemodynamics,hemorheological indices,thus improve neurological functions and promote prognosis.

Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

Objective This study aims to establish a regional digitalized venous thromboembolism(VTE)prevention and control model with the support of the VTE Quality Control Center in Hangzhou to enhance the standardized prevention and re-gional treatment level.Methods The research was carried out from four aspects:constructing organizational structure,formula-ting implementation standards,promoting operational mechanisms,and building intelligent supervision platforms.A statistical a-nalysis was conducted to the data on the intelligent supervision platforms of three medical institutions.Results From January 2022 to June 2023,the VTE risk assessment of inpatients in the three medical institutions gradually became standardized,with an assessment rate exceeding 93％.The rates of VTE risk assessment within 24 hours of admission,dynamic assessment of VTE,and the proportion of VTE with moderate to high risk all showed significantly increasing trends.The standardized prevention rate of VTE remained around 60％.The incidence of relevant VTE within the hospital decreased from 1.82％to 0.41％,with a de-crease rate of over 70％.Conclusion The regional digitalized VTE prevention and control management model contributes to im-proving the standardized prevention and treatment level of VTE and reducing the incidence of hospital-related VTE in the region.

Objective·To establish the early symptom network of adult intensive care unit(ICU)patients after transfer(post-ICU patients),identify the core symptoms and bridge symptoms,compare the symptom networks of two subgroups,i.e.mixed ICU and coronary care unit(CCU),and analyze the occurrence of symptoms.Methods·From December 2022 to August 2023,a total of 328 adult patients transferred to wards from mixed ICU and CCU of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine were selected by convenience sampling.The general situation and clinical data questionnaire,and symptom questionnaires(including Hospital Anxiety and Depression Scale,Fatigue Severity Scale,Richards-Campbell Sleep Questionnaire,and Pain Numeric Rating Scale)were used.Based on Spearman correlation analysis and GLASSO algorithm,contemporaneous symptom network was built,and centrality indices and differences between subgroup symptom networks were computed.The edge accuracy and the stability of centrality indices of the network were tested.Results·A total of 302 valid questionnaires were collected,and the effective rate was 92.1％.The results of the centrality indices computations showed that in the early symptom network of post-ICU patients,the highest strength was"feel cheerful"(rs=1.145),the highest closeness was"enjoy something"(rC=1.851×10-3),and the highest expected influence was"(fatigue)interferes with physical function"(rE=1.143).The top three highest bridge strengths of symptoms were"worrying thoughts"(rb=10.392),"enjoy something"(rb=10.359),and pain(rb=10.221).There were no significant differences in network structure(M=0.289)and overall connection strength(GSmixedICU=13.876,GSCCU=13.838;S=0.039)of the early symptom networks between mixed ICU and CCU patients after being transferred to wards.When comparing the centrality indices,apart from the strength and expected influence of five symptoms showing statistically significant differences(all P＜0.05),other indices were not significantly different.The edge accuracy and the stability of centrality indices in the early symptom network of post-ICU patients were fine.Conclusion·Anxiety and depression are the core symptoms of adult post-ICU patients,and pain is one of the bridge symptoms.There is no significant difference in the incidence of early symptoms between mixed ICU and CCU patients after being transferred out.Medical care personnel should pay attention to the discomfort symptoms of post-ICU patients,and carry out targeted interventions to improve patients'comfort and promote the rehabilitation process.