ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×10⁹/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Objective To investigate the value of multi-phase MRI-based radiomics machine learning models in differentiating small renal cell carcinoma(sRCC)from fat-poor renal angiomyolipoma(fp-AML).Methods 79 cases of sRCCs and 35 cases of fp-AMLs(diameter≤4 cm)which were confirmed by pathology were retrospectively analyzed.The volume of interest(VOI)of the total tumor was manually delineated on the images of T2WI(T2),unenhanced phase(UP),corticomedullary phase(CMP)and nephrographic phase(NP)and then the radiomics of the VOIs were extracted respectively.The training set and the test set were set according to the ratio of 7∶3.The t-test,maximal relevance and minimal redundancy(mRMR)and the least absolute shrinkage and selection operator(LASSO)were used to select the radiomics features.The selected features were used to build classification models with logistic regression(LR)and support vector machine(SVM).The receiver operating characteristic(ROC)curve was used to evaluate the classification performances of the models.Results There were 4,12,3,11 and 15 optimal features obtained from T2、UP、CMP、NP and the combined four phases,respectively.The radiomics features based on NP or the combined four phases with LR model performed best,AUCs were respectively 0.956,0.986 in the training set and both were 0.881 in the test set.Conclusion The multi-phase MRI-based radiomics machine learning model has favorable diagnostic performance in differentiating sRCC from fp-AML.

Objective: To describe the prevalence of alcohol consumption and the burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in adults aged ≥20 years in 31 provinces in China from 2005 to 2018. Methods: Data from several national representative surveys was used to estimate provincial alcohol exposure level of adults aged ≥20 years from 2005 to 2018 by using kriging interpolation and locally weighted regression methods. Global disease burden research method and data, and China's death cause surveillance data were used to calculate the population attributable fraction (PAF) of hemorrhagic stroke and hypertensive heart disease and the deaths due to alcohol consumption in men and women aged ≥20 years in 31 provinces in China. China census data of 2010 were used to calculate the attributable standardized mortality rate. Results: In 2005 and 2018, the prevalence of alcohol consumption was 58.7% (95%CI: 57.8%-59.5%) and 58.4% (95%CI: 57.6%-59.3%), respectively, in men and 17.0% (95%CI: 16.6%-17.4%) and 18.7% (95%CI:18.1%-19.3%), respectively, in women. The daily alcohol intake was 24.6 (95%CI: 23.8-25.3) g and 27.7 (95%CI: 26.8-28.7) g, respectively, in men and 6.3 (95%CI: 6.0-6.5) g and 5.3 (95%CI: 5.0-5.6) g, respectively, in women. Alcohol exposure level was higher in the provinces in central and eastern China than in western provinces. The lowest exposure level was found in northwestern provinces. From 2005 to 2018, the PAF of hemorrhagic stroke death due to alcohol consumption increased from 5.5% to 6.8%, the attributable deaths increased from 50 200 to 59 100, while the PAF of hypertensive heart disease death due to alcohol consumption increased from 7.0% to 7.7%, the attributable deaths increased from 15 200 to 29 300. The PAF of hypertensive heart disease and hemorrhagic stroke was higher in men than in women, and in central and eastern provinces than in western provinces. In 2018, the standardized mortality rates of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption were 4.58/100 000 and 2.11/100 000, respectively. Conclusions: The prevalence of alcohol consumption in men and daily alcohol intake of drinkers were relatively high in China, especially in eastern provinces. Alcohol exposure level was lower in women than in men. Regional measures should be taken to reduce the alcohol intakes in men and current drinkers in order to reduce the health problems caused by alcohol consumption.
Adult ; Male ; Humans ; Female ; Hemorrhagic Stroke ; Hypertension/epidemiology* ; Alcohol Drinking/epidemiology* ; Heart Diseases/epidemiology* ; China/epidemiology*

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.
Humans ; Laparoscopy/methods* ; Colonic Neoplasms/pathology* ; Lymph Node Excision/methods* ; Colectomy/methods* ; Dissection

Objective:To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection.Methods:Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results:A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group ( P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [ OR, 2.667 ( CI: 1.389-5.122); P=0.003], increased CK [ OR, 2.544 ( CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] ( CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [ OR, 0.424 ( CI: 0.254-0.709); P=0.001]. Conclusion:Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

Objective: To study the underlying mechanism of cadmium-induced apoptosis of mouse spermatocytes (GC-2 spd) . Methods: In March 2021, GC-2 spd cells were exposed to different concentrations of CdCl(2) for 24 hours, namely 5 μmol/L CdCl(2) (low-dose) group and 10 μmol/L CdCl(2) (high-dose) group, and unexposed GC-2 spd cells were used as control group. Mitochondrial morphology was observed in the cells stained with Mito-Track Red CMXRos fluorescent probes by confocal microscopy and the mitochrondrial membrane potential was measured by flow cytometry with JC-1 fluorescent probes. Mitochrondrial proteins, cytosolic proteins and total cellular proteins of GC-2 spd cells were extracted using cell mitochondria isolation kit and RIPA buffer, respectively. The expression of mitochondrial homeostasis regulatory proteins (FIS1 and OPA1), and apoptosis-related proteins (Cytochrome c and cleaved Caspase-3) were examined by Western blot. Results: Compared with the cells in the control group, the relative ratio of JC-1 red/green fluorescence signal in the cells of the low-dose and high-dose CdCl(2) groups decreased significantly (0.740±0.071, 0.570±0.028), with a statistically significant difference (P=0.017, 0.004) ; The morphology of mitochondria changed from long tube to point, and the proportion of cells containing point mitochondria increased significantly (45.1%±3.7% and 25.7%±4.9%), the difference was statistically significant (P=0.005, 0.001) ; The relative expression level of mitochondrial FIS1 in cells of low and high dose CdCl(2) groups was significantly higher (1.271±0.120, 1.693±0.155), the difference was statistically significant (P=0.046, 0.000) ; The relative expression level of OPA1 decreased significantly (0.838±0.050, 0.682±0.040), and the difference was statistically significant (P=0.049, 0.001). Compared with the control group, the relative expression level of cytochrome c protein in the cytoplasm of cells in the low dose group of CdCl(2) was not significantly increased (1.249±0.151), and the difference was not statistically significant (P=0.075). However, the relative expression level in the cytoplasm of cells in the high dose group of CdCl(2) was significantly increased (2.355±0.110), and the difference was statistically significant (P=0.000) ; The relative expression level of Cytochrome c in mitochondria of low and high dose CdCl(2) groups decreased significantly (0.681±0.043, 0.619±0.114), with a statistically significant difference (P=0.004, 0.001) ; Moreover, the level of cleaved Caspase-3 protein in cells gradually increased (5.486±0.544, 11.493±1.739), the difference was statistically significant (P=0.004, 0.000) . Conclusion: Cadmium induced cleaved Caspase-3 mediated apoptosis of GC-2 spd cells via promoting mitochrondrial fission and the release of Cytochrome c from the mitochrondria to the cytosol.
Male ; Mice ; Animals ; Mitochondrial Dynamics ; Caspase 3/metabolism* ; Cadmium/toxicity* ; Cytochromes c/metabolism* ; Fluorescent Dyes ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism* ; Membrane Potential, Mitochondrial

Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments in vitro were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments in vitro confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.

A novel HPLC method with the quantitative analysis of multi-components by single marker( QAMS) combined with the dual-wavelength method was developed for simultaneous determination of six flavonoids in Dendrobium officinale stems from different producing areas,cultivation and processing methods to clarify the main factors contributing to the different composition of flavonoids.The separation of six flavonoids was performed on a Shiseido Capcell PAK MGⅡ C18 column( 4. 6 mm×250 mm,5 μm) using a linear gradient elution system of acetonitrile-0. 1% formic acid aqueous solution. Schaftoside,isoschaftoside,vicenin-2,and glucosylvitexin were simultaneously analyzed using rutin as a reference standard at detection wavelength of 340 nm,and naringenin was determined at290 nm. The credibility and feasibility of QAMS method were validated and the results demonstrated that no significant differences were observed as compared with the external standard method. Finally,a total of 82 batches of D. officinale samples were analyzed and principal component analysis( PCA) and discriminant analysis were applied to distinguish and compare D. officinale samples from different producing areas,cultivation and processing methods. The results showed that the total flavonoid content of D. officinale stems cultivated in the simulated wild( attached tree cultivation or attached stone cultivation) was significantly higher than that in greenhouse bed cultivation. The content of flavonoids in simulated-wild D. officinale stems was higher in Jiangxi,Guizhou,Zhejiang,and Fujian provinces,while that in greenhouse bed cultivation was higher in Fujian and Zhejiang provinces. The content of naringenin was positively correlated with processing temperature,and that of the other five flavonoids was negatively correlated with processing temperature. PCA showed that wild-simulated D. officinale and greenhouse bed-cultivated D. officinale could be roughly divided into two clusters. The samples cultivated in the greenhouse bed were divided into four categories according to the geographical habitats. Wild-simulated D. officinale samples from Guizhou gathered together,and there was no obvious rule in samples from other producing areas. The established method simplified the determination method of flavonoids in D. officinale,and could provide the basis for effective quality control,cultivation and processing of D. officinale.
Chromatography, High Pressure Liquid ; Dendrobium ; Drugs, Chinese Herbal ; Flavonoids ; Quality Control

ObjectiveTo investigate the role of PI3K/Akt/eNOS signaling pathway in the protective effect of hydrogen sulfide（H₂S） on endothelial cell senescence induced by hydrogen peroxide （H₂O₂）. MethodsSenescence in human umbilical vein endothelial cells （HUVEC） was induced by 60 μmol/L H₂O₂ for 1 h， and the effects of NaHS on the senescence were examined by the expression of plasminogen activator inhibitor 1 （PAI-1） and senescence-associated β-galactosidase （SA-β-Gal） staining. Meanwhile，the expression of protein kinase B（Akt）， Phospho protein kinase B（p-Akt）， and endothelial nitric oxide synthase （eNOS） were examined by western blot， and the senescence-related parameters. The content of the nitric oxide （NO） was measured by nitrate reduction method. ResultsCompared with the control group， after being treated with 60 μmol/L H₂O₂， the number of SA-β-gal positive cells and the expression of PAI-1 were significantly increased. However， after pretreatment of NaHS， the expression of PAI-1， the ratio of SA-β-gal positive cells was significantly decreased， but the expression of p-Akt， eNOS and the NO concentration increased. ConclusionNaHS could reverse HUVEC senescence induced by H₂O₂， and this may be highly associated with PI3K/Akt/eNOS signaling pathway.