Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

Objective:To investigate the efficacy of modified fire dragon moxibustion in patients with phlegm-dampness obesity and prediabetes.Methods:From April 2024 to March 2025, 62 patients with phlegm-dampness obesity and prediabetes who visited the Department of Endocrinology of Ningbo Hospital of Traditional Chinese Medicine were selected as study subjects using convenience sampling. The study subjects were divided into an intervention group and a control group using a random number table method, with 31 cases in each group. Control group received conventional medication, dietary and exercise management, while intervention group received modified fire dragon moxibustion in addition to conventional medication, dietary and exercise management. Both groups underwent the intervention for 60 days. Fasting blood glucose (FBG) , glycated hemoglobin (HbA1c) , triglycerides (TG) , body mass index, fasting insulin (FINS) , and homeostatic model assessment of insulin resistance (HOMA-IR) were compared between the two groups before and after intervention.Results:After intervention, the body mass index, FBG, HbA1c, FINS, and HOMA-IR of intervention group were lower than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified fire dragon moxibustion can reduce the body mass index, improve glucose metabolism indicators, and FINS and HOMA-IR levels in patients with phlegm-dampness obesity and prediabetes.

Objective:To investigate the efficacy of modified fire dragon moxibustion in patients with phlegm-dampness obesity and prediabetes.Methods:From April 2024 to March 2025, 62 patients with phlegm-dampness obesity and prediabetes who visited the Department of Endocrinology of Ningbo Hospital of Traditional Chinese Medicine were selected as study subjects using convenience sampling. The study subjects were divided into an intervention group and a control group using a random number table method, with 31 cases in each group. Control group received conventional medication, dietary and exercise management, while intervention group received modified fire dragon moxibustion in addition to conventional medication, dietary and exercise management. Both groups underwent the intervention for 60 days. Fasting blood glucose (FBG) , glycated hemoglobin (HbA1c) , triglycerides (TG) , body mass index, fasting insulin (FINS) , and homeostatic model assessment of insulin resistance (HOMA-IR) were compared between the two groups before and after intervention.Results:After intervention, the body mass index, FBG, HbA1c, FINS, and HOMA-IR of intervention group were lower than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified fire dragon moxibustion can reduce the body mass index, improve glucose metabolism indicators, and FINS and HOMA-IR levels in patients with phlegm-dampness obesity and prediabetes.

Objective To observe the ameliorative effect of inhibiting acetyl-CoA carboxylase 2(ACC2)on cardiac dysfunction in septic mice and investigate its underlying mechanism.Methods Mouse model of sepsis was established by cecal ligation and perforation.A total of 24 male C57BL/6 mice(aged 8 weeks,weighing 20～25 g)were divided into sham operation group,sepsis group and ND-630+sepsis group.The cardiac specific ACC2 knockout(ACC2△CM)mice were constructed by Cre-LoxP recombinase system,and ACC2flox/flox Myh6-Cre-(ACC2fl/fl)mice were used as control.Several genetically engineered mice(8 weeks old,20～25 g,male)were divided into ACC2fl/fl+sham operation group,ACC2fl/fl+sepsis group,ACC2△CM+sepsis group,ACC2△CM+Mal-CoA+sepsis group,and ACC2△CM+sham operation group according to the random number table method.The contractile function and myofilament calcium sensitivity of cardiomyocytes were measured by a cell microtensiometer.Western blotting was used to detect the expression level of ACC2,and ELISA was employed to measure the level of malonyl-CoA(Mal-CoA)in myocardial tissue.The survival of the mice in 36 h after sepsis was observed.Results Compared with the sham operation group,the contraction amplitude of cardiomyocytes in sepsis group was decreased markedly,and the calcium sensitivity decreased significantly as well(P＜0.05).Based on the ACC2fl/fl+sham operation group,the ACC2△CM+sepsis group showed significant improvement in myocardial contraction compared with the ACC2fl/fl+sepsis group,with the contraction amplitude of cardiomyocytes recovered by 48.1％,and significantly restored calcium sensitivity(P＜0.05).ACC2△CM+Mal-CoA+sepsis group showed a notable decrease in myocardial cell contraction amplitude and a significant decrease in calcium sensitivity when compared to the ACC2△CM+sepsis group(P＜0.05).Compared with the sepsis group,the contraction amplitude of cardiomyocytes in the ND-630+sepsis group increased significantly,and the calcium sensitivity of myofilament also increased(P＜0.05).The expression level of ACC2 protein in the myocardial tissue of mice in the sepsis group increased compared to the sham operation group(P＜0.05).The level of myocardial Mal-CoA in the sepsis group was higher than that in the sham operation group(P＜0.05);Mal-CoA level in the myocardium of ACC2△CM+sepsis group mice was lower than that of sepsis group(P＜0.05).The 36-hour survival rate of the ACC2△CM+sepsis group.mice was 37.5％higher than that of the ACC2fl/fl+sepsis group mice.(P＜0.05).Conclusion Inhibition of ACC2 exerts a protective effect on myocardial contractility and calcium sensitivity in septic mice by reducing Mal-CoA.

Autophagy is a crucial physiological process in cells and an important mechanism in the maintenance of cell homeostasis and regulation of cell survival.Idiopathic pulmonary fibrosis(IPF)is an interstitial lung disease of unknown etiology with a poor prognosis,characterized by alveolar epithelial cell damage and abnormal proliferation and activation of fibroblasts.IPF is accompanied by the excessive deposition of extracellular matrix(ECM),and its pathogenesis involves a complex interaction between cell types and signaling pathways.Defects in autophagy function have been shown to play a key role in the occurrence and development of IPF.This review aims to investigate the mechanism of autophagy in IPF and reveal its complexity and related signaling pathways.

Autophagy is a crucial physiological process in cells and an important mechanism in the maintenance of cell homeostasis and regulation of cell survival.Idiopathic pulmonary fibrosis(IPF)is an interstitial lung disease of unknown etiology with a poor prognosis,characterized by alveolar epithelial cell damage and abnormal proliferation and activation of fibroblasts.IPF is accompanied by the excessive deposition of extracellular matrix(ECM),and its pathogenesis involves a complex interaction between cell types and signaling pathways.Defects in autophagy function have been shown to play a key role in the occurrence and development of IPF.This review aims to investigate the mechanism of autophagy in IPF and reveal its complexity and related signaling pathways.

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

Objective To study the effects of main ingredients from microemulsion extract of Compound Longqincao in vitro on anti-influenza virus H1N1 activity; To analyze effects of main ingredients from microemulsion extract on influenza virus inhibition rate.Methods Uniform design was used to conduct the experiment. MTT method was used to detect the effect rate (ER) of anti-influenza virus H1N1 on A549 cells. Setting ER as the index, Minitab17 software was used to establish mathematical model to come up with regression equations of all factors. The effects of ingredients on ER were analyzed and the efficient composition ratio of the optimum anti-influenza virus H1N1 was chosen.ResultsIn the compound compatibility, baicalin showed the most obvious antivirus activity, and licorice glycosides had certain inhibition effects on pathological changes of cells. Five ingredients had coordinative or controlled relation with ER. When per milliliter liquids containing licorice glycosides, baicalin, leucine, aspartic acid, glutamic acid was 13.94μg, 49.44μg, 0.23 mg, 1.25 mg, and 2.50 mg, ER was the best. ER was 85.34%±4.72% after verification.ConclusionThe optimized combination of main ingredients from microemulsion extract of Compound Longqincaocan better play a role in anti-influenza virus H1N1.