Objectives To analyze the spatial and temporal aggregation of multidrug resistant pulmonary tuberculosis (MDR-TB) incidence in Nanning at the township / street scale from 2017 to 2021, to explore the spatial and temporal characteristics of the spread of MDR-TB in Nanning, and to provide a scientific reference basis for the health administrative departments to achieve the precise implementation of MDR-TB prevention and control. Methods Based on the data of MDR-TB cases in Nanning from 2017 to 2021, the spatial-temporal scanning analysis software SaTScan v9.7 was used to retrospectively detect and analyze the areas where MDR-TB cases gathered. Results Through simple spatial scanning analysis, it was found that there were three first-class aggregation areas (the aggregation center was Fujiayuan Street, Jiangnan District, 2017, Xinyang Street, Xixiangtang District, 2019, and Zhonghe Town, Yongning District, 2020), and one second-class aggregation area (the aggregation center was Jinchai Town, Mashan County, 2020). Simple time scanning showed that the clustering occurred from May 2019 to December 2020. Temporal and spatial aggregation analysis showed that Xinyang Street in Xixiangtang District was the center of the first-class aggregation area, Zhonghe Town in Yongning District was the center of the second-class aggregation area, and Jinchai Town in Mashan County was the center of the third-class aggregation area. Conclusion The multidrug resistant pulmonary tuberculosis epidemic in Nanning is distributed in an aggregated manner, especially in Xinyang Street, Xixiangtang District, which has the highest spatial and temporal aggregation. It is necessary to focus on and take regional prevention and control measures to control the epidemic.

Objective: To investigate the specificity of endogenous metabolic profile in plasma of patients with occupational acute methyl acetate poisoning using non-targeted metabolomics. Methods: A total of six patients with occupational acute methyl acetate poisoning were selected as the poisoning group, while 10 healthy workers without occupational exposure history of chemical hazards in the same industry were selected as the control group using the judgment sampling method. Metabolites in patient plasma of the two groups were detected using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analysis was performed. Principal component analysis and partial least squares discriminant analysis were used to identify differential metabolites and analyze their metabolic pathways. Results: There were significant differences in metabolite profiles in patient plasma between poisoning group and control group. A total of 195 differentially expressed metabolites were screened in plasma of patients in poisoning group, including 119 upregulated and 76 downregulated metabolites. Lipid substances (lipids and lipid-like molecules) accounted for the highest proportion (21.5%). The differential metabolites of poisoning group were related to folate biosynthesis, amino acid metabolism, pyrimidine metabolism, sphingolipid biosynthesis and other metabolic pathways in plasma compared with the control group (all P<0.05). Conclusion: Occupational acute methyl acetate poisoning affects metabolism of the body. The folic acid biosynthesis, amino acid and lipid metabolism and other pathways may be involved in the occurrence and development of poisoning.

Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups： control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.

Objective To detect and analyze the susceptibility genes of methyl acetate poisoning in patients by whole exome sequencing. Methods Two patients with occupational acute severe methyl acetate poisoning and their first-degree relatives who work in the same occupation and position with similar working hours were selected as the research subjects by judgment sampling method. Peripheral blood was collected for whole exome sequencing. The sequencing data was compared with the public genome database to screen the mutation sites and find out the gene sites related to methyl acetate poisoning. The suspected pathogenic mutation genes were annotated and interpreted. Results The results of whole exome sequencing showed that there were 40 differential genes between the patients with methyl acetate poisoning and their first-degree relatives, including 80 single nucleotide polymorphisms and eight Indel with specific marker sequence index. Among these, the genes with strong correlation were carboxyesterase 1 (CES1) and mucin (MUC) 5B. The CES1 gene loci c.248C>T (p.Ser83Leu) heterozygous mutations, MUC5B gene loci c.6635C>T (p.Thr2212Met) and c.7685C>T (p.Thr2562Met) heterozygous mutations in patients with methyl acetate poisoning were detected. They were missense mutations. By constructing a protein-protein interaction network, a total of 11 pairs of interactions with high levels of evidence were identified, involving genes such as lysine methyltransferase 2C, HECT and RLD domains containing E3 ubiquitin protein ligase 2, neutrophil cytoplasmic factor 1, nicotinamide adenine dinucleotide phosphate oxidase 3, C-terminal binding protein 2, zinc finger protein 717, FSHD region gene 2 family member C, FSHD region gene 1, MUC4, MUC6, MUC5B, and MUC12. Conclusion The polymorphism of CES1 and MUC5B genes may be related to the occurrence and development of methyl acetate poisoning in patients.

Objective:To investigate the application effect of case-based learning (CBL) combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals. Methods:The cluster random sampling method was used to select the class of 2019 in the eight-year program and the class of 2020 in the five-year program, with the major of stomatology in Air Force Medical University. The 24 students in the observation group received CBL combined flipped classroom, and the 37 students in the control group received traditional teaching. The two groups were compared in terms of theoretical assessment score, classroom assessment score, comprehensive ability, self-learning ability, and degree of satisfaction with teaching. SPSS 22.0 was used for the t-test. Results:The observation group had a significantly higher theoretical assessment score than the control group [(74.88±3.46) vs. (71.89±4.45), P<0.05]. The observation group had significantly better scores of practical skill assessment than the control group ( P<0.05). Compared with the control group, the observation group had significantly better scores of comprehensive ability and self-learning ability ( P<0.05). The observation group had significantly better scores of satisfaction with teaching than the control group ( P<0.05). Conclusion:The application of CBL combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals can improve theoretical knowledge, practical skills, comprehensive quality, and satisfaction with teaching among students, and therefore, it holds promise for application in teaching.

Objective:To explore the medication law and academic thought of Professor Hu Guohua in treating diminished ovarian reserve (DOR) based on data mining.Methods:Collecting the medical records of DOR patients treated by Prof. Hu from January 1, 2021 to March 31, 2022. The TCM symptoms, tongue and pulse conditions, as well as the frequency, taste, meridian tropism and efficacy categories of TCM were analyzed by using the Traditional Chinese Medicine Inheritance Computing Platform V3.0 software. Commonly used drug combination analysis, high-frequency drug network relationship analysis, association rule analysis based on Apriori algorithm, cluster analysis based on K-means clustering algorithm, and core prescriptions were summarized.Results:A total of 85 DOR patients were included, involving 76 TCM symptoms, 15 tongue images, 11 pulse images. A total of 415 prescriptions were included, involving 164 kinds of Chinese materia medica. High-frequency drugs included Ligustri Lucidi Fructus, Angelicae Sinensis Radix, Astragali Radix, Cuscutae Semen, Herba Leonuri and Rhizoma Atractylodis Macrocephalae. The medicines were mostly warm, mild and cold in property, and the tastes were mostly sweet, bitter and pungent, mainly belonging to the liver, spleen and kidney meridians. 42 high-frequency drug combinations and 6 core prescriptions were obtained.Conclusions:Professor Hu treats DOR with the principle of tonifying the kidney and spleen to regulate body constitution, conditioning Chong Vessel and Conception Vessel to regulate the menstruation, soothing the liver and tranquillizing the heart to regulate the spirit. Professor Hu selects the medicines which are simplified and condensed, and is good at using drugs. The prescriptions are persistent and flexible, concerning the balance.

Humans ; Brain Ischemia/therapy* ; Ischemic Stroke ; Receptors, N-Methyl-D-Aspartate ; TRPM Cation Channels

Humans ; Alzheimer Disease ; Amyloid beta-Peptides ; Neurons ; Lysosomes ; Hydrogen-Ion Concentration

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.