Objective:To summarize the drug resistance characteristics of clinical pathogen isolates in a tuberculosis specialized hospital from 2017 to 2023，and understand the distribution characterisitics of pathogens and their resistance to antimicrobial agents.Methods:The isolates from January 2017 to December 2023 were identified and subjected to drug susceptibility tests using the VITEK 2-compact system. The susceptibilities of the isolates to antimicrobial agents were determined by the minimum inhibitory concentration（MIC）methods according to the CLSI（2023）guideline. The data of detection of different kinds of bacteria，specimen distribution and the detection rates of major drug-resistant gram-negative bacteria in hospital antimicrobial resistance were analyzed. Chi square test were performed to analyze one or more sets of data related to detection rate or drug resistance rate by SPSS 17.0.Results:A total of 9 993 isolates were detected，among which 9 079（90.9%）were gram-negative bacteria and 914（9.1%）were gram-positive bacteria. From 2017 to 2022，among all gram-negative isolates，the top three most frequently isolated pathogens were Klebsiella pneumonia，followed by Pseudomonas aeruginosa and Acinetobacter baumannii. The overall resistance rates to carbapenems in Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumonia，and Escherichia coli were 43.7%（495/1 133），19.4%（276/1 423），8.4%（279/3 304），3.6%（19/521），respectively. The overall detection rates of ceftriaxone/ciprofloxacin-resistant Klebsiella pneumonia（CTX/CRO-R-KPN），or Escherichia coli（CTX/CRO-R-ECO），and quinolone-resistant Escherichia coli（QNR-ECO）were 19.5%（644/3 304），57.6%（300/521），77.4%（403/521），respectively. The difference in resistance rates between imipenem-resistant and imipenem-susceptible Klebsiella pneumoniae was statistically significant（ P<0.05）. Except for CTX/CRO-R-ECO（ χ2=7.9 ，P>0.05），significant differences were observed in the detection rates of other major drug-resistant gram-negative bacteria in hospital（ P<0.05）. The detection of some drug-resistant strains showed an upward trend in recent years. Carbapenem-resistant Acinetobacter baumannii， Pseudomonas aeruginosa，and Escherichia coli exhibited higher resistance rate to other antibiotics. Conclusions:The detection rates of major drug-resistant gram-negative bacteria have increased in the past two years. Carbapenem-resistant strains exhibit relatively high resistance rate to cephalosporin and quinolone antibiotics. Although carbapenem antibiotics remain effective against Enterobacteriaceae，strengthened antimicrobial resistance monitoring and control of multidrug-resistant bacteria spread are necessary.

Objective To explore the effect of organizational climate on work alienation in psychiatric nurses,and the mediating role of psychological capital and positive coping styles between organizational climate and work alienation,in order to provide a reference for reducing work alienation among psychiatric nurses.Methods Convenience sampling method was used to select nurses working in 6 tertiary A psychiatric hospitals in Shandong Province from January to July 2024,and the general questionnaire,Nurses' Work Alienation Questionnaire,Organizational Climate Scale for Nursing,Psychological Capital Questionnaire,and Simple Coping Style Scale were used to conduct the survey and the mediation effect test.Results A total of 606 questionnaires were recovered,of which 572 were valid,and the validity rate of the questionnaires was 94.39％.Psychiatric nurses scored(89.58±13.69)for nursing organizational climate,(32.48±11.31)for work alienation,(97.28±19.12)for psychological capital,and(23.93±7.22)for positive coping styles.There was a direct effect of nursing organizational climate on work alienation(β=-0.681,95％CI=-0.824～-0.539).Psychological capital and positive coping styles acted as separate mediators and chain mediators in the effect of nursing organizational climate on work alienation(β=-0.116,-0.048,-0.019,95％CI=-0.182～-0.034,-0.086～-0.006,-0.042～-0.002).Conclusion There are multiple mediating effects of psychiatric nurses' psychological capital,positive coping styles between nursing organizational climate and work alienation.Nursing managers can enhance psychiatric nurses' psychological capital by creating a positive and healthy organizational climate,encouraging them to adopt positive coping styles to solve problems,and reducing work alienation.

Objective To explore the effect of organizational climate on work alienation in psychiatric nurses,and the mediating role of psychological capital and positive coping styles between organizational climate and work alienation,in order to provide a reference for reducing work alienation among psychiatric nurses.Methods Convenience sampling method was used to select nurses working in 6 tertiary A psychiatric hospitals in Shandong Province from January to July 2024,and the general questionnaire,Nurses' Work Alienation Questionnaire,Organizational Climate Scale for Nursing,Psychological Capital Questionnaire,and Simple Coping Style Scale were used to conduct the survey and the mediation effect test.Results A total of 606 questionnaires were recovered,of which 572 were valid,and the validity rate of the questionnaires was 94.39％.Psychiatric nurses scored(89.58±13.69)for nursing organizational climate,(32.48±11.31)for work alienation,(97.28±19.12)for psychological capital,and(23.93±7.22)for positive coping styles.There was a direct effect of nursing organizational climate on work alienation(β=-0.681,95％CI=-0.824～-0.539).Psychological capital and positive coping styles acted as separate mediators and chain mediators in the effect of nursing organizational climate on work alienation(β=-0.116,-0.048,-0.019,95％CI=-0.182～-0.034,-0.086～-0.006,-0.042～-0.002).Conclusion There are multiple mediating effects of psychiatric nurses' psychological capital,positive coping styles between nursing organizational climate and work alienation.Nursing managers can enhance psychiatric nurses' psychological capital by creating a positive and healthy organizational climate,encouraging them to adopt positive coping styles to solve problems,and reducing work alienation.

Objective:To summarize the drug resistance characteristics of clinical pathogen isolates in a tuberculosis specialized hospital from 2017 to 2023，and understand the distribution characterisitics of pathogens and their resistance to antimicrobial agents.Methods:The isolates from January 2017 to December 2023 were identified and subjected to drug susceptibility tests using the VITEK 2-compact system. The susceptibilities of the isolates to antimicrobial agents were determined by the minimum inhibitory concentration（MIC）methods according to the CLSI（2023）guideline. The data of detection of different kinds of bacteria，specimen distribution and the detection rates of major drug-resistant gram-negative bacteria in hospital antimicrobial resistance were analyzed. Chi square test were performed to analyze one or more sets of data related to detection rate or drug resistance rate by SPSS 17.0.Results:A total of 9 993 isolates were detected，among which 9 079（90.9%）were gram-negative bacteria and 914（9.1%）were gram-positive bacteria. From 2017 to 2022，among all gram-negative isolates，the top three most frequently isolated pathogens were Klebsiella pneumonia，followed by Pseudomonas aeruginosa and Acinetobacter baumannii. The overall resistance rates to carbapenems in Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumonia，and Escherichia coli were 43.7%（495/1 133），19.4%（276/1 423），8.4%（279/3 304），3.6%（19/521），respectively. The overall detection rates of ceftriaxone/ciprofloxacin-resistant Klebsiella pneumonia（CTX/CRO-R-KPN），or Escherichia coli（CTX/CRO-R-ECO），and quinolone-resistant Escherichia coli（QNR-ECO）were 19.5%（644/3 304），57.6%（300/521），77.4%（403/521），respectively. The difference in resistance rates between imipenem-resistant and imipenem-susceptible Klebsiella pneumoniae was statistically significant（ P<0.05）. Except for CTX/CRO-R-ECO（ χ2=7.9 ，P>0.05），significant differences were observed in the detection rates of other major drug-resistant gram-negative bacteria in hospital（ P<0.05）. The detection of some drug-resistant strains showed an upward trend in recent years. Carbapenem-resistant Acinetobacter baumannii， Pseudomonas aeruginosa，and Escherichia coli exhibited higher resistance rate to other antibiotics. Conclusions:The detection rates of major drug-resistant gram-negative bacteria have increased in the past two years. Carbapenem-resistant strains exhibit relatively high resistance rate to cephalosporin and quinolone antibiotics. Although carbapenem antibiotics remain effective against Enterobacteriaceae，strengthened antimicrobial resistance monitoring and control of multidrug-resistant bacteria spread are necessary.

Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

Objective To investigate the effects of tanreqing injection(TRQ)on lipopolysaccharides(LPS)-induced colon injury and intestinal flora in mice.Methods BALB/c mice were randomly divided into normal group,LPS-induced group,low-dose TRQ group(LPS+TRQ 4mg/kg)and high-dose TRQ group(LPS+TRQ 8mg/kg)by completely randomalized design.Body weight and liv-ing status of mice were recorded daily.The serum inflammatory cytokines interleukin-1(IL-1),IL-6 and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin staining was used to observe the path-ological changes of colon.16S rDNA sequencing was used to analyze the changes of intestinal flora in mice.Results High-dose TRQ had significant therapeutic effect on LPS-induced weight loss in mice(P＜0.05).Both low-dose and high-dose TRQ can inhibit the LPS-induced increase in serum IL-1,IL-6 and TNF-α levels(P＜0.01).Both low-dose and high-dose TRQ groups could sig-nificantly improve the colonic shortening(P＜0.01,P＜0.05)and pathological changes induced by LPS.High-dose TRQ could signifi-cantly increase the Simpson index of intestinal flora(P＜0.05)and improve Beta diversity.The abundance of a variety of intestinal flora changed significantly in the high-dose TRQ group.Conclusion TRQ may improve the intestinal function by inhibiting the release of in-flammatory cytokines and regulating the structure of intestinal flora,and play a protective role in LPS-induced inflammatory response and colon injury in mice.

Objective To investigate the effects of tanreqing injection(TRQ)on lipopolysaccharides(LPS)-induced colon injury and intestinal flora in mice.Methods BALB/c mice were randomly divided into normal group,LPS-induced group,low-dose TRQ group(LPS+TRQ 4mg/kg)and high-dose TRQ group(LPS+TRQ 8mg/kg)by completely randomalized design.Body weight and liv-ing status of mice were recorded daily.The serum inflammatory cytokines interleukin-1(IL-1),IL-6 and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin staining was used to observe the path-ological changes of colon.16S rDNA sequencing was used to analyze the changes of intestinal flora in mice.Results High-dose TRQ had significant therapeutic effect on LPS-induced weight loss in mice(P＜0.05).Both low-dose and high-dose TRQ can inhibit the LPS-induced increase in serum IL-1,IL-6 and TNF-α levels(P＜0.01).Both low-dose and high-dose TRQ groups could sig-nificantly improve the colonic shortening(P＜0.01,P＜0.05)and pathological changes induced by LPS.High-dose TRQ could signifi-cantly increase the Simpson index of intestinal flora(P＜0.05)and improve Beta diversity.The abundance of a variety of intestinal flora changed significantly in the high-dose TRQ group.Conclusion TRQ may improve the intestinal function by inhibiting the release of in-flammatory cytokines and regulating the structure of intestinal flora,and play a protective role in LPS-induced inflammatory response and colon injury in mice.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.