Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Developing and implementing biosafety standards for pathogenic microbiology laboratories is essential to achieving scientific, efficient, and standardized management and operation. This article analyzes the current standardization construction in biosafety in pathogenic microbiology laboratories domestically and internationally. It proposes a framework for the biosafety standard system of pathogenic microbiology laboratories, which mainly includes four parts: basic standards, management standards, technical standards, and industry applications. It provides a reference for the standardization work of pathogenic microbiology laboratories and helps to standardize the biosafety industry in China.

Objective:To develop and evaluate the efficacy and safety of a three-dimensional (3D) digestive endoscope for gastric endoscopic submucosal dissection (ESD) through animal experiments.Methods:Two Dutch pigs were utilized from the Zhengzhou University Animal Experiment Center for the study. ESD procedures were performed by two senior endoscopists, one using 3D glasses and the other utilizing a 3D high-definition head display. The success of ESD was assessed based on predefined criteria, including completion of surgical steps, complete detachment of the presumptive lesion, and effective bleeding control during and after the surgery. The number of successful procedures and incidences of perforation were recorded. The stereoscopic experience of the endoscopists, including both the primary endoscopist and the assistant, was also evaluated. Furthermore, the assessment encompassed any reported symptoms of eye discomfort, such as eye fatigue, ocular pain, and blurred vision. Additionally, the confidence level of the endoscopists in the mechanical aspects of the operation, as well as encountered issues during the endoscopic procedures, were documented.Results:Two ESD were successful and no perforation occurred. Feedback from endoscopists suggested that 3D digestive endoscopy offered clear images with enhanced three-dimensionality during surgery, clear sense of distance and layering, allowing for a precise judgment of bleeding points, which surpassed 2D capabilities. No eye discomfort was experienced by endoscopists or assistants during or after the procedures. While endoscopists exhibited high confidence in 3D digestive endoscopy, they noted issues with image blurring when the camera was positioned less than 10 mm from the gastrointestinal tract wall.Conclusion:Preliminary results show that 3D digestive endoscopes can provide excellent stereo imaging, improved positioning accuracy, and safety during live animal stomach ESD procedures, without significantly increasing endoscopists' eye discomfort. Nevertheless, efforts are needed to address image blurring concerns when the camera is close to the gastrointestinal tract wall.

OBJECTIVE: To explore the role of endoplasmic reticulum ryanodine receptor 1 (RyR1) expression and phosphorylation in sepsis- induced diaphragm dysfunction. METHODS: Thirty SPF male SD rats were randomized equally into 5 groups, including a sham-operated group, 3 sepsis model groups observed at 6, 12, or 24 h following cecal ligation and perforation (CLP; CLP-6h, CLP-12h, and CLP-24h groups, respectively), and a CLP-24h group with a single intraperitoneal injection of KN- 93 immediately after the operation (CLP-24h+KN-93 group). At the indicated time points, diaphragm samples were collected for measurement of compound muscle action potential (CMAP), fatigue index of the isolated diaphragm and fitted frequencycontraction curves. The protein expression levels of CaMK Ⅱ, RyR1 and P-RyR1 in the diaphragm were detected using Western blotting. RESULTS: In the rat models of sepsis, the amplitude of diaphragm CMAP decreased and its duration increased with time following CLP, and the changes were the most obvious at 24 h and significantly attenuated by KN-93 treatment (P < 0.05). The diaphragm fatigue index increased progressively following CLP (P < 0.05) irrespective of KN- 93 treatment (P>0.05). The frequency-contraction curve of the diaphragm muscle decreased progressively following CLP, and was significantly lower in CLP-24 h group than in CLP-24 h+KN-93 group (P < 0.05). Compared with that in the sham-operated group, RyR1 expression level in the diaphragm was significantly lowered at 24 h (P < 0.05) but not at 6 or 12 following CLP, irrespective of KN-93 treatment; The expression level of P-RyR1 increased gradually with time after CLP, and was significantly lowered by KN-93 treatment at 24 h following CLP (P < 0.05). The expression level of CaMKⅡ increased significantly at 24 h following CLP, and was obviously lowered by KN-93 treatment (P < 0.05). CONCLUSION Sepsis causes diaphragmatic dysfunction by enhancing CaMK Ⅱ expression and RyR1 receptor phosphorylation in the endoplasmic reticulum of the diaphragm.
Rats ; Male ; Animals ; Diaphragm/metabolism* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Rats, Sprague-Dawley ; Phosphorylation ; Muscle Contraction/physiology* ; Endoplasmic Reticulum ; Sepsis/metabolism*

Objective:To evaluate the relationship between intestinal microbiota heterogeneity and acquired myasthenia in septic mice.Methods:Eighty SPF healthy male C57BL/6 mice, weighing 18-20 g, aged 6-8 weeks, were included. Forty mice were selected to prepare a sepsis model by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Sepsis-sensitive mice (state of dying or even death within 24 h after developing the model) and sepsis-resistant mice (survival for 7 days and recovery) were screened. The feces from donor mice were collected to make fecal bacteria fluid. Forty mice were selected and divided into 4 groups ( n=10 each) by the random number table method: control group (C group), antibiotic group (ABX group), resistant group (Res group), and sensitive group (Sen group). Group C received no treatment. In ABX group, compound antibiotics were given by intragastric gavage once a day for 5 consecutive days. In Res group, the fecal solution from sepsis-resistant mice 150 μl was given by gavage once a day for 3 consecutive days starting from 5 days after gavage administration of compound antibiotics, and then LPS 15 mg/kg was intraperitoneally injected. In Sen group, the fecal solution from sepsis-sensitive mice was given by gavage for 3 days (using the same method as previously described in Res group) starting from 5 days after gavage administration of compound antibiotics, and then LPS 15 mg/kg was intraperitoneally injected. The severity of sepsis was assessed and scored at 24 h after developing the model. The four limb grip strength was measured after fecal bacteria transplantation and at 24 h after developing the sepsis model. The Compound Muscle Action Potential (CMAP) of the gastrocnemius was measured at 24 h after developing the sepsis model. Then blood samples were collected for determination of the levels of interleukin-1 (IL-1), IL-6 and tumor necrosis factor α (TNF-α) in serum by enzyme-linked immunosorbent assay. The tissues of anterior tibial muscle and gastrocnemius muscle were obtained for determination of the expression of muscle-specific ring finger protein 1 (MuRF-1) and muscle atrophy box F protein (MAFbx) by Western blot. The diameter and cross-sectional area of gastrocnemius muscle fibers were measured after HE staining. The feces of mice were collected at 3 days after fecal bacteria transplantation, and DNA was extracted from mouse fecal samples for 16S rDNA sequencing and untargeted metabolomics analysis. Results:Compared with C group, the score for severity of sepsis was significantly increased, the four limb grip strength was decreased after developing the sepsis model, the serum IL-6 concentration was increased, and the diameter and cross-sectional area of gastnemius muscle fibers were decreased ( P<0.05), and no statistically significant changes were found in the other parameters in Res group, and no statistically significant changes were found in the indexes mentioned above in ABX group ( P>0.05). Compared with C group and Res group, the score for severity of sepsis was significantly increased, the four limb grip strength was decreased, the latency of CMAP was prolonged, and the amplitude of CMAP was decreased, the serum concentrations of IL-1, IL-6 and TNF-α were increased, the diameter and cross-sectional area of gastrocnemius muscle fibers were decreased, and the expression of MuRF-1 and MAFbx in anterior tibial muscle was up-regulated after developing the sepsis model in Sen group ( P<0.05). 16S rDNA sequencing of intestinal flora: Compared with Sen group, no significant change was found in Chao1 index, Good-coverage index and Simpson index in Res group ( P>0.05), Shannon index was increased ( P<0.05), and no significant change was found in β diversity in Res group ( P>0.05). LDA analysis showed that f_Akkermarisiaceae, o_Verrucomicrobiales, g_Akmansia, c_Verrucomicrobiae and p_Verrucomicrobiota were significantly enriched in Sen group, and g_Enterococcus and f_Enterococcaceae were significantly enriched in Res group ( P<0.05). Nontargeted metabolic analysis: The metabolite profiles in Res group and Sen group suggested that the model was well developed (R2Y>Q2Y). Compared with Sen group, 90 metabolites was significantly up-regulated and 88 down-regulated, significantly up-regulated metabolic substances including vitamin K1, gamma-tocopherol, and taurine in Res group ( P<0.05). The differential metabolite KEGG enrichment pathway included 2-oxocarboxylic acid metabolism and ubiquinone and other terpenoid-quinone biosynthesis ( P<0.05). Conclusions:Intestinal flora heterogeneity may be involved in the pathogenesis of acquired myasthenia in septic mice.

Objective To explore the diagnostic value of Young's modulus obtained by real-time shear wave elastography (SWE) for liver fibrosis in autoimmune hepatitis (AIH) patients. Methods A total of 75 AIH patients in the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2022 were retrospectively enrolled. Scheuer scoring system was used to evaluate degrees of liver fibrosis (S0-S4). By using pathological examination of liver tissues as the golden standard, the receiver operating characteristic curve (ROC) was plotted and the area under the curve (AUC) was used to evaluate the diagnostic value of SWE for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3), and liver cirrhosis (S4), respectively. Independent sample t test was used for comparison of continuous data with normal distribution between the two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and Bonferroni method was used for further comparison between two groups. The Spearman correlation coefficient was used for correlation analysis. The logistic regression analysis was used to predict the impact factors in diagnosis accuracy. Results The Young's modulus measured by SWE was statistically significant different among various fibrosis groups ( H =35.186, P < 0.001) although there was no statistical significance in patients' age and platelet, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and glutamyl transpeptidase levels (all P > 0.05). The Young's modulus measurement was positively correlated with liver fibrosis ( r =0.675, P < 0.05). The AUCs of SWE in the diagnosis of≥S2, ≥S3, and S4 were 0.839, 0.820 and 0.898, respectively and the corresponding optimum cut-off values were 9.2, 10.9, and 14.4 kPa, respectively. The overall concordance rate of the liver Young' s modulus measurements vs . fibrosis stages was 57.33%. Moreover, the alkaline phosphatase level was an independent predictor for diagnostic accuracy of SWE for stage 0-1 fibrosis ( OR =1.009, 95% CI : 1.001-1.018, P =0.029). Conclusion The SWE possessed a diagnosis value for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3) and liver cirrhosis (S4), although there was a low overall concordance rate in the liver Young's modulus measurements obtained using SWE vs. fibrosis stages.

Background and Objectives: Acute myocardial infarction (AMI) often occurs suddenly and leads to fatal consequences. Ferroptosis is closely related to the progression of AMI.However, the specific mechanism of ferroptosis in AMI remains unclear. Methods: We constructed a cell model of AMI using AC16 cells under oxygen and glucose deprivation (OGD) conditions and a mice model of AMI using the left anterior descending (LAD) ligation. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide was employed to determine cell viability. The levels of lactate dehydrogenase, creatine kinase, reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and iron were measured using corresponding kits. Dual luciferase reporter gene assay, RNAbinding protein immunoprecipitation, and RNA pull-down were performed to validate the correlations among AC005332.7, miR-331-3p, and cyclin D2 (CCND2). Hematoxylin and eosin staining was employed to evaluate myocardial damage. Results: AC005332.7 and CCND2 were lowly expressed, while miR-331-3p was highly expressed in vivo and in vitro models of AMI. AC005332.7 sufficiency reduced ROS, MDA, iron, and ACSL4 while boosting the GSH and GPX4, indicating that AC005332.7 sufficiency impeded ferroptosis to improve cardiomyocyte injury in AMI. Mechanistically, AC005332.7 interacted with miR-331-3p, and miR-331-3p targeted CCND2. Additionally, miR-331-3p overexpression or CCND2 depletion abolished the suppressive impact of AC005332.7 on ferroptosis in OGD-induced AC16 cells. Moreover, AC005332.7 overexpression suppressed ferroptosis in mice models of AMI. Conclusions AC005332.7 suppressed ferroptosis in OGD-induced AC16 cells and LAD ligation-operated mice through modulating miR-331-3p/CCND2 axis, thereby mitigating the cardiomyocyte injury in AMI, which proposed novel targets for AMI treatment.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

Effective therapy options for pneumoconiosis are lacking. Traditional Chinese medicine (TCM) presents a favorable prospect in the treatment of pneumoconiosis. A pilot study on TCM syndrome differentiation can evaluate the clinical efficacy and safety of TCM and lay a foundation for further clinical research. A double-blind, randomized, and placebo-controlled trial was conducted for 24 weeks, in which 96 patients with pneumoconiosis were randomly divided into the control and treatment groups. Symptomatic treatment was conducted for the two groups. The treatment group was treated with TCM syndrome differentiation, and the control group was treated with placebo. The primary outcomes were the six-minute walking distance (6MWD) and the St. George Respiratory Questionnaire (SGRQ) score. The secondary outcomes were the modified British Medical Research Council Dyspnea Scale (mMRC), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), Hospital Anxiety and Depression Scale (HADS), and pulmonary function. Only 83 patients from the 96 patients with pneumoconiosis finished the study. For the primary outcome, compared with the control groups, the treatment group showed a significantly increased 6MWD (407.90 m vs. 499.51 m; 95% confidence interval (CI) 47.25 to 135.97; P < 0.001) and improved SGRQ total score (44.48 vs. 25.67; 95% CI -27.87 to -9.74; P < 0.001). The treatment group also significantly improved compared with the control group on mMRC score (1.4 vs. 0.74; 95% CI -1.08 to -0.23; P =0.003), CAT score (18.40 vs. 14.65; 95% CI -7.07 to -0.43; P =0.027), and the total symptom score (7.90 vs. 5.14; 95% CI -4.40 to -1.12; P < 0.001). No serious adverse events occurred. This study showed that TCM syndrome differentiation and treatment had a favorable impact on the exercise endurance and quality of life of patients with pneumoconiosis.
Humans ; Medicine, Chinese Traditional/methods* ; Quality of Life ; Pilot Projects ; Drugs, Chinese Herbal/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Pneumoconiosis/drug therapy* ; Double-Blind Method ; Treatment Outcome ; Syndrome

Metastatic prostate cancer is one of the most malignancies and do harm to the health and life expectancy of men. The popularization and application of 68Gallium or 18Fluorine labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) benefit for the excellent diagnostic efficacy, unique value in the diagnosis of metastatic prostate cancer, clinical decision-making guidance, efficacy in monitoring and prognosis evaluation. 223Radium and 177Lu-PSMA radioligand therapy (RLT) could effectively alleviate bone pain, and prolong the overall survival time (OS) as wellas progression-free survival time (PFS) with good safety. In addition, survival of patients with metastatic prostate cancer is expected to be further improved with the advance in the combination therapies with PSMA RLT, androgen-deprivation therapy (ADT), chemotherapy, targeted therapy and immunotherapy.