Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

Objective:To develop national standard materials for Streptococcus pneumoniae serotypes 12F,14,17F and 22F polysaccharides.Methods:According to the method recommended by the 2020 Chinese Pharmacopoeia,the relevant limit quality control of four different serotypes of polysaccharide candidate standards was conducted.The uniformity of subpackage and stability of the candidate standard products under different conditions were ana-lyzed.Furthermore,three laboratories were organized for collaborative calibration.Results:The results showed that the quality of serotypes 12F,14,17F and 22F polysaccharides candidate standards met the requirements of the quality standard of polysaccharide in the 2020 edition of the Chinese Pharmacopoeia.The RSD between polysaccha-ride content of different candidate standard samples were less than 5.0％,indicating that the uniformity of the poly-saccharide candidate standards was better.The results from stability analysis confirmed that the polysaccharide con-centration of serotypes 12F,14,17F and 22F polysaccharide candidate standard did not change significantly after being placed at 2-8 ℃,25 and 37℃for different times and after repeated freezing and thawing three times.Compared with the test results of each candidate standard product stored at-70 ℃ for a long time,the RSD were all within 5％.The collaborative results confirmed that the RSD of the polysaccharide content in different laborato-ries were less than 12％,of which assigned the concentration of four different serotype polysaccharide candidate standards.Conclusion:Serotypes 12F,14,17F and 22F polysaccharide standards have been developed,of which can be used for quality control of pneumococcal polysaccharide vaccines in the future.

OBJECTIVE To analyze the reasons for the outbreak of suspected carbapenem-resistant Acinetobacter baumannii(CRAB)infections in the neurosurgical intensive care unit to take comprehensive prevention and con-trol measures to control the spread of infections,and to provide a reference for the control of multidrug-resistant organisms(MDRO)infections in intensive care units.METHODS Epidemiological data were collected from five patients with CRAB infections in the neurosurgical intensive care unit of Gansu Provincial People's Hospital in Mar.2024,and environmental hygiene monitoring and comprehensive infection prevention and control measures were conducted.RESULTS A total of five cases of lower respiratory tract infections occurred,all of which were hospital-acquired infections,and all patients had consistent spatial-temporal distribution.A.baumannii was detec-ted in the sputum cultures of all patients,and all were resistant to carbapenems,aminoglycosides and some β-lac-tam drugs.Before the implementation of comprehensive prevention and control measures,a total of 25 samples from the surfaces and the hands of health workers were collected,with a pass rate of 52.00％;CRAB was detected on the surface of treatment carts and the wall of sputum suction bottles in the treatment room,with a detection rate of 8.00％.After the implementation,a total of 24 samples were collected,with a pass rate of 100.00％,and the difference was statistically significant when compared with the pre-implementation period(χ2=16.987,P<0.001).Through the implementation of comprehensive measures such as isolation,standardization of the ward cleaning and disinfection process,strengthening hand hygiene,standardization of sterile operations and personnel management,the indicators such as hand hygiene compliance rate,the execution rate of multi-drug-resistant bac-terial preventive and control measures and the fluorescent marker removal rate were all improved,and the suspec-ted CRAB infection outbreak was timely controlled.CONCLUSION This suspected CRAB hospital-acquired infec-tion outbreak may be related to a variety of factors,and timely environmental hygiene monitoring and comprehen-sive infection prevention and control measures can effectively control the spread of CRAB infection.

Objective To investigate the status quo,driving factors and clinical intervention measures of intrinsic capacity(IC)in elderly patients with cerebrovascular disease.Methods Clinical data of 206 elderly patients with cerebrovascular disease admitted to our hospital from January to December 2024 were retrospectively collected.According to the IC score,they were divided into a low IC group(123 cases,IC score＜4)and a good IC group(83 cases,IC score≥4).The IC scores were compared between the two groups,and the driving factors affecting the IC were analyzed.Results The low IC group exhibited significantly lower IC score than the good IC group(1.94±0.49 vs 4.52±0.15,P＜0.01).The age ≥80 years,dysfunctions,three or more chronic diseases,frailty,albumin ≤ 35 g/L,pre-albumin ≤280 mg/L,rehabilitation guidance and regular exercises were the influencing factors of IC in elderly patients with cerebrovascular disease(P＜0.05,P＜0.01).Conclusion The IC of elderly patients with cerebrovascular disease is associated with many factors,and corresponding clinical intervention measures should be implemented to promote the improvement of patient's IC.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Objective:To construct and validate the risk prediction model of osteoporosis (OP) in the middle-aged and elderly healthy physical examination population.Methods:In this cross-sectional study, 18 030 middle-aged and elderly people with bone mineral density tested in Health Management Center of Guangxi Zhuang Autonomous Region Hospital from January 2020 to December 2022 were selected. The general data, physical examination index and biochemical blood index were collected. The subjects were divided into training set (12 621 cases) and validation set (5 409 cases) in a ratio of 7∶3 with the simple random sampling method. The variables were screened with minimum LASSO regression and logistic regression and the corresponding nomogram prediction model for the risk of osteoporosis in the middle-aged and elderly health examination population was established. The performance of the nomogram model was evaluated with the area under the receiver operating characteristic curve (ROC AUC), specificity, sensitivity, calibration curve (CAL), and decision curve (DCA).Results:The results of LASSO regression and multivariate logistic regression in training set showed that gender, age, body mass index, hip circumference, waist circumference, systolic blood pressure, total cholesterol, glutamyl transpeptidase and albumin/globulin ratio were the independent best predictors of OP risk in the middle-aged and elderly health examination population (all P<0.05). The ROC AUC-value of the training set was 0.895 (95% CI: 0.886-0.904), with a sensitivity of 87.25% and a specificity of 85.01%. The ROC AUC value of the validation set was 0.892 (95% CI: 0.886-0.898), with a sensitivity of 83.74% and a specificity of 82.46%. The CAL showed a C-index value of 0.790 in the training set and a C-index value of 0.784 in validation set. The CALs all showed deviation correction and obvious curves similar to the ideal line. DCA showed that when the OP risk threshold probability of the training set was 45%-93%, and the OP risk threshold probability of the validation set was 45%-92%, the nomogram model had better efficacy in predicting OP risk in the middle-aged and elderly physical examination population, and the two results were still relatively consistent. Both CAL and DCA showed good performance. Conclusion:This study establishes a practical prediction model for osteoporosis risk in the middle-aged and elderly population, it can provide an early warning for the timely detection of OP risk for the middle-aged and elderly people.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To analyze the correlation between inflammation indicators(systemic inflammatory response syndrome and systemic immune-inflammation index)and adverse outcomes in patients with symptomatic stroke during hospitalization.Methods This study was a prospective cohort study including consecutive patients with symptomatic stroke who were hospitalized in Fuwai Hospital from January to September 2023.The past medical history,clinical symptoms and signs of the patients were collected.The neurological damage was evaluated with National Institute of Health Stroke Scale(NIHSS).Laboratory test results were recorded and the SIRI and SII in-dex were calculated.Patients were followed up for 90 days after the stroke,and their neurological outcomes were evaluated using the modified Rankin Scale.A score of 0-1 was classified as good outcome,and a score ≥2 was classified as poor outcome.The correlation between inflammatory response indicators and poor outcomes was as-sessed using multiple Logistic regression.Results A total of 97 patients with in-hospital symptomatic stroke were included with an average age of 61.8±12.7 years.Among them,there were 28 females(28.9％,28/97),9 with a history of prior stroke(9.3％,9/97),15 with atrial fibrillation(15.5％,15/97),16 with heart failure(16.5％,16/97),and 7 with myocardial infarction(7.2％,7/97).Correlation analysis showed that the NIHSS score at the time of stroke onset was significantly correlated with the patient's post-stroke SIRI(r=0.237,P＜0.05)and SII(r=0.234,P＜0.05).After 90 days of follow-up,41 cases(42.3％,41/97)had a poor outcome.Multiple Logistic regression analysis showed that post-stroke SIRI(Or=4.71,95％CI:1.24-17.90)and SII(Or=3.13,95％CI:0.88-11.06)were correlated with poor outcomes within 90 days after the stroke.Analysis using restricted cubic splines showed that as the levels of SIRI and SII increased,the risk of poor out-comes in patients with in-hospital symptomatic stroke increased.Conclusions SIRI is an independent risk factor for poor outcomes in patients with in-hospital symptomatic stroke,and the risk of poor neurological outcomes in-creases with high level of SIRI.