Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Fel Ursi(bear bile) has been used as medicine for a long history, with wide clinical applications and definite curative efficacy. Fel Ursi has good pharmacodynamic activities in the treatment of liver and gallbladder diseases, and cardiovascular and cerebrovascular diseases. According to the places of origin, traditional Fel Ursi is divided into "Dongdan" and "Nandan". According to the gallbladder properties, it is divided into "Jindan" "Tiedan" "Caihuadan", and "Youdan". With the development of bear bile drainage technology, Pulvis Fellis Ursi has entered the market and been used clinically instead of Fel Ursi. At present, obtaining artificial Pulvis Fellis Ursi by chemical compounding and biotransformation is the hotspot in medical research, which can solve the shortage problem of bear bile resources, and also protect endangered animals. The quality problem of Fel Ursi in the market is prominent, with counterfeit products prepared from sheep bile, cow bile, pig bile, and chicken bile. Due to the scarcity of bear bile resources, the related research contents are scattered, and there is a lack of systematic analysis and summary. This paper focused on the development of Fel Ursi to clarify the source and classification of traditional Fel Ursi, and summarized the harvesting, processing, identification, and use of Fel Ursi. Additionally, the paper also compared the quality standards of Fel Ursi, summarized the technological development process of Pulvis Fellis Ursi, and prospected the modern research and clinical application of Pulvis Fellis Ursi, which is expected to provided references for the collation of bear bile resources, the clinical application of Fel Ursi, the development of Fel Ursi drugs, and related research on artificial Pulvis Fellis Ursi.
Animals ; Bile ; Medicine, Chinese Traditional ; Ursidae

Animal medicine is an important part of traditional Chinese medicine(TCM). Bear bile is one of the rare animal-derived medicinal materials with the functions of clearing the liver, promoting bile secretion, calming the liver, relieving convulsions, clearing heat, and removing toxins. From the Jin Dynasty to the Tang Dynasty, bear bile was mainly used to treat internal diseases, surgical diseases, and pediatric diseases with limitations. At present, bear bile has been used to treat various diseases in pediatrics, gynecology, internal medicine, and surgery. Studies on the chemical constituents and pharmacological effects of bear bile mostly focused on bile acids. Although the non-bile acids also showed certain pharmacological effects, their mechanism of action was less investigated. At present, the source animals of bear bile are national second-class protected animals. Obtaining transformed bear bile powder through biotransformation is expected to alleviate the shortage of bear bile resources to a certain extent. Although related research on bear bile substitutes has protected bear bile resources, there are problems in functional quantification and modern interpretation. It is necessary to sort out the functions and indications of bear bile recorded in ancient books according to related modern research. This study firstly reviewed the evolution of bear bile functions and indications, analyzed the chemical components of bear bile, sorted out the relevant records of the efficacy and clinical application of bear bile in ancient books, and summarized the research progress in the safety of bear bile based on the modern pharmacological effects and clinical applications of bear bile, which is conducive to the clarification of modern efficacy and functional quantification of bear bile and the tentative exploration of the modern interpretation of bear bile.
Animals ; Bile/metabolism* ; Bile Acids and Salts ; Humans ; Medicine, Chinese Traditional ; Powders ; Ursidae/metabolism*

OBJECTIVE: To develop and test the health education knowledge assessment questionnaire for gout and to investigate the understanding degree of health education knowledge in patients with gout. METHODS: From June 2019 to June 2019, 150 cases of gout patients were enrolled.According to the literature review and the healthy education requirements of gout patients, the framework of education knowledge system was preliminarily formed.The pre-test questionnaire was obtained through two rounds of he Delphi technique.A survey of 150 patients with gout was carried out.The analysis and selection of the questionnaire were based on the coefficient of variation, the analysis of determination value, the correlation coefficient of the items and the total scores, and the exploratory factor analysis.In this study, we evaluated the reliability of internal consistency, semi-reliability.Validity test mainly included content validity and construct validity.In addition, a total of 150 patients with gout in our hospital and outpatient gout were selected to investigate the understanding degree of health education knowledge from June 2019 to December 2019. RESULTS: The significance of the first level index of the questionnaire was 3.83-5.00, the secondary index was 3.00-4.83, and the variation coefficient of each item was 0.31-1.23, and the critical ratio(CR) value of each item in this questionnaire was 3.168-8.333.The Pearson correlation coefficient of each item and the total score of this study was 0.319-0.544.After exploratory factor analysis, some topics were deleted in four dimensions, and there were 16 entries in the final questionnaire.Cronbach' s α coefficient of this questionnaire was 0.715, split-half reliability Spearman-Brown coefficient was 0.785, and retest reliability coefficient was 0.729. The correlation coefficient between each factor of this questionnaire and the total questionnaire was 0.300-0.701, and the correlation coefficient between each item of the questionnaire and each factor was 0.402-0.732, all P < 0.05. The results were statistically significant. By questionnaire investigation, the total score of questionnaire was (6.85±3.22), the score of disease-related knowledge was (2.03±1.24), the score of dietary guidance was (1.53± 1.06), the score of exercise guidance was (2.19±1.24), the score of medication guide was (1.24±1.22). CONCLUSION The Health Education Knowledge Assessment Questionnaire For Gout has a good reliability and validity for measuring related content, the compilation process is scientific and the content is comprehensive, which can be further applied in clinic.The understanding degree of health education knowledge is low in Chinese patients with gout, and knowledge of gout medicine is lacking especially.
Factor Analysis, Statistical ; Gout/diagnosis* ; Health Education ; Humans ; Psychometrics/methods* ; Reproducibility of Results ; Surveys and Questionnaires

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m²), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m²) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m²)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.
Cohort Studies ; Glomerulonephritis, IGA/pathology* ; Humans ; Kidney Failure, Chronic/therapy* ; Plasma Exchange ; Prognosis ; Retrospective Studies ; Steroids/therapeutic use*

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

OBJECTIVE: To investigate the effects of long-term and low dose ionizing radiation on ocular lens opacities of residents living in areas with high natural radiation background(HNRB) in Yangjiang City, China. METHODS: A total of 483 Han residents from Yangjiang City(HNRB area) and 517 from Enping City(control area) were selected as study subjects using a cluster random sampling method. Questionnaire survey and lens examination were carried out. The risk factors of lens opacity and its severity were analyzed by logistic regression analysis. RESULTS: The prevalence rates of lens opacity, cortical opacity and posterior subcapsular opacity in HNRB area were higher than those in control area(60.7% vs 51.6%, 53.4% vs 46.8%, 21.9% vs 9.3%, all P<0.05). There was no significant difference in karyotype turbidity between HNRB area and control area(52.4% vs 47.6%, P>0.05). After adjusting for confounding factors including age, gender, cardiovascular/metabolic diseases, smoking, alcohol drinking and tea drinking, the unconditional logistic regression analysis results showed that the risk of ocular opacity, cortical opacity and posterior subcapsular opacity in residents of HNRB area was higher than that in control area(all P<0.05). Multivariate disordered logistic regression analysis results showed that residents in the HNRB area had a higher risk of grade two karyotype turbidity than grade one karyotype turbidity(P<0.01). Ordered logistic regression analysis results showed that residents in HNRB area had an increased risk of developing severe cortical turbidity(P<0.01). CONCLUSION: Long-term and low dose ionizing radiation exposure may increase the risk of ocular lens opacity, especially cortical and posterior subcapsular cataract, and affect the severity of the disease.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Animals ; Apoptosis ; Brucea/chemistry* ; Glycogen Synthase Kinase 3 ; Humans ; Jurkat Cells ; Mice ; Phosphatidylinositol 3-Kinases/genetics* ; Plant Oils/pharmacology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Proto-Oncogene Proteins c-akt/genetics* ; Seeds/chemistry* ; Signal Transduction

Objective:The chemical differences of Lycii Fructus samples from Qinghai, Ningxia, Gansu, Xinjiang and Inner Mongolia provinces were compared based on proton nuclear magnetic resonance (¹H-NMR) plant metabolomics. Method:A total of 97 Lycii Fructus samples from five provinces were collected, including 61 samples in Qinghai, and extracted by 50% methanol for detecting. ¹H-NMR spectra were obtained and compared by multivariate statistical analysis for investigating the chemical differences of samples from Qinghai and other production areas. And the content of Lycii Fructus polysaccharides in all samples was determined with the wavelength of 490 nm (calculated by anhydrous glucose). Result:A total of 32 chemical components were detected in the Lycii Fructus extract by ¹H-NMR. The multivariate statistical analysis revealed that there was no significant difference among the samples from five provinces. The difference between Lycii Fructus from Qinghai and Ningxia, as well as the samples among the six regions of Qinghai province were relatively small. The similarity values of the majority of samples were >0.85. Univariate analysis showed that no significant difference was observed for the most metabolites in Lycii Fructus collected from five provinces, except for sucrose, glucose, proline and so on. There was no significant difference in the content of Lycii Fructus polysaccharides between Qinghai and other provinces. And the correlation coefficient between the content of Lycii Fructus polysaccharides and the small molecular compounds identified by ¹H-NMR was -0.2-0.4. Conclusion:In this study, chemical characteristics of Lycii Fructus in Qinghai province are analyzed from the holistic view by ¹H-NMR plant metabolomics, in combination of polysaccharide determination, and the results show that there is no significant difference between samples from Qinghai and other four provinces. The quality evaluation method based on ¹H-NMR established in this study can provide scientific basis for improving quality control level and selecting planting areas of Lycii Fructus.