Objective To explore the causal relationships of anxiety,depression and neuroticism with recurrent spontaneous abortion(RSA).Methods Genome-wide association study(GWAS)data were used to extract single nucleotide polymorphisms(SNPs)closely related to anxiety,depression and neuroticism as instrumental variables(IVs).Inverse variance weighting(IVW),weighted median estimator(WME),weighted mode(WM)and Mendelian randomization(MR)-Egger regression were employed for MR analysis to evaluate the causal effects of anxiety,depression and neuroticism with RSA,and to analyze heterogeneity,gene pleiotropy and sensitivity.Results A total of 46 SNPs were extracted from GWAS data as IVs(5 anxiety SNPs,9 depression SNPs,and 32 neuroticism SNPs).IVW,WME,WM and MR-Egger regression analysis revealed that the odds ratio(OR)and 95%confidence interval(CI)of anxiety data were 1.07(0.86-1.32),1.10(0.85-1.43),1.14(0.81-1.59)and 1.18(0.53-2.61);those of depression data were 1.11(0.93-1.32),1.05(0.83-1.32),0.96(0.67-1.38)and 0.57(0.25-1.31);those of neuroticism data were 1.01(0.75-1.36),1.07(0.73-1.56),1.02(0.49-2.12)and 2.40(0.46-12.44),but none of the above causal analyses were statistically significant(all P>0.05).After reliability analysis,the Cochran's Q test for heterogeneity evaluation was not significant(P>0.05),the MR-Egger regression intercepts for gene pleiotropy evaluation were all close to 0(P>0.05),and the sensitivity evaluation"Leave-one-out"test also shows that the combined causal effect values are similar.Conclusion There dose not exist causal relationships of anxiety,depression and neuroticism with RSA.The reliability test shows that the results are relatively robust.

OBJECTIVE To analyze the epidemiological characteristics of hospital-associated infections(HAIs)in a large scale three-A hospital and assess the occurrence and development trends of HAIs before and after COVID-19 epidemic and during different stages of prevention and control strategies so as to provide scientific bases for HAIs management.METHODS The surveillance data were collected from the patients who were hospitalized in a large scale three-A hospital by nosocomial infection real-time surveillance system from Jan.2018 to Dec.2023.The prevalence trend,infection sites and distribution of pathogens were analyzed.The study period was divided into the pre-epidemic stage and the epidemic stage,the epidemic stage was divided into the strict infection prevention and control phase and the loose infection prevention and control phase.The epidemiological characteristics of HAIs were observed and compared.RESULTS From 2018 to 2023,the prevalence rate of HAIs was decreased from 3.39％to 2.21％,and there was significant difference in the prevalence rate of the infections among the years(x2=105.00,P＜0.001).During the six years,the prevalence rate of HAIs was highest in the internal medicine wards of critical care medicine department(54.91％),and the gram-negative bacteria(56.61％)were dominant among the pathogens.Lower respiratory tract(41.85％),bloodstream(20.93％)and urinary tract(20.50％)ranked the top 3 infection sites;the lower respiratory tract infection ranked the first place before the COVID-19 epidemic and the different stages of epidemic.The overall prevalence rate of HAIs was 3.26％during the epidemic period,remarkably lower than 3.91％before the COVID-19 epidemic(P＜0.001);the overall prevalence rate of HAIs was 2.21％in the loose prevention and control phase of 2023,remarkably lower than 3.78％in the strict prevention and control phase(P＜0.001).CONCLUSIONS The prevalence of HAIs generally shows a downward trend during the six years.The lower respiratory tract is the major infection site,and the gram-negative bacteria are dominant among the pathogens,especially Klebsiella pneumoniae.The prevention and control strategies for the COVID-19 epidemic may facilitate the reduction of incidence of HAIs,and the prevalence rate is remarkably reduced even in the loose prevention and control phase.It is necessary for the hospital to take targeted prevention and control measures based on the departments,carry out rigid surveillance of the major infection sites and patho-gens,and conduct multidisciplinary coordinated prevention and control so as to control the HAIs.

OBJECTIVE To analyze the epidemiological characteristics of hospital-associated infections(HAIs)in a large scale three-A hospital and assess the occurrence and development trends of HAIs before and after COVID-19 epidemic and during different stages of prevention and control strategies so as to provide scientific bases for HAIs management.METHODS The surveillance data were collected from the patients who were hospitalized in a large scale three-A hospital by nosocomial infection real-time surveillance system from Jan.2018 to Dec.2023.The prevalence trend,infection sites and distribution of pathogens were analyzed.The study period was divided into the pre-epidemic stage and the epidemic stage,the epidemic stage was divided into the strict infection prevention and control phase and the loose infection prevention and control phase.The epidemiological characteristics of HAIs were observed and compared.RESULTS From 2018 to 2023,the prevalence rate of HAIs was decreased from 3.39％to 2.21％,and there was significant difference in the prevalence rate of the infections among the years(x2=105.00,P＜0.001).During the six years,the prevalence rate of HAIs was highest in the internal medicine wards of critical care medicine department(54.91％),and the gram-negative bacteria(56.61％)were dominant among the pathogens.Lower respiratory tract(41.85％),bloodstream(20.93％)and urinary tract(20.50％)ranked the top 3 infection sites;the lower respiratory tract infection ranked the first place before the COVID-19 epidemic and the different stages of epidemic.The overall prevalence rate of HAIs was 3.26％during the epidemic period,remarkably lower than 3.91％before the COVID-19 epidemic(P＜0.001);the overall prevalence rate of HAIs was 2.21％in the loose prevention and control phase of 2023,remarkably lower than 3.78％in the strict prevention and control phase(P＜0.001).CONCLUSIONS The prevalence of HAIs generally shows a downward trend during the six years.The lower respiratory tract is the major infection site,and the gram-negative bacteria are dominant among the pathogens,especially Klebsiella pneumoniae.The prevention and control strategies for the COVID-19 epidemic may facilitate the reduction of incidence of HAIs,and the prevalence rate is remarkably reduced even in the loose prevention and control phase.It is necessary for the hospital to take targeted prevention and control measures based on the departments,carry out rigid surveillance of the major infection sites and patho-gens,and conduct multidisciplinary coordinated prevention and control so as to control the HAIs.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

Maintenance hemodialysis can improve many symptoms of patients with end-stage renal disease, but long-term dialysis can cause various physiological symptoms and psychological negative emotions. As a positive psychological change, post-traumatic growth plays a role in relieving patients' psychological pressure and reducing their pain. However, the post-traumatic growth of patients with maintenance hemodialysis needs to be improved. This article reviewed the status, influencing factors and interventions of post-traumatic growth in maintenance hemodialysis patients in order to provide reference for psychological care of such patients.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

A 46-year-old female patient was treated with Jingangteng capsules 2 g (4 capsules) thrice daily and Kangfuyan capsules 1.2 g (3 capsules) twice daily after hysterectomy. After 23 days of treatments, the patient developed gastrointestinal discomfort, and Jingangteng capsules and Kangfuyan capsules were stopped 2 days later. However, gastrointestinal discomfort gradually worsened and symptoms such as nausea, dark urine, and yellow staining of the skin and sclera appeared. After discontinuing the drug for 10 days, laboratory tests showed alanine aminotransferase (ALT) 366 U/L, aspartate aminotransferase (AST) 485 U/L, alkaline phosphatase (ALP) 145 U/L, gamma glutamyltransferase (γ-GT) 67 U/L, total bilirubin (TBil) 67.1 μmol/L, and direct bilirubin (DBil) 59.5 μmol/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination, and drug-induced liver injury was diagnosed. Oral liver-protective drugs and IV infusions of compound glycyrrhizin injection and polyene phosphatidylcholine injection were given successively, but jaundice continued to deepen with the peak TBil and DBil values of 189.7 μ mol/L and 159.4 μ mol/L, respectively. An IV infusion of ademetionine 1,4-butanedisulfonate for injection 1 g dissolved in 5% glucose injection 250 ml was given once daily. Three days later, the patient′s symptoms were improved and the jaundice subsided obviously; 9 days later, the liver function was improved obviously and laboratory tests showed ALT 29 U/L, AST 50 U/L, γ-GT 36 U/L, TBil 66.5 μmol/L, and DBil 53.2 μmol/L; 1 month later, her liver function returned to normal.

A 46-year-old female patient was treated with Jingangteng capsules 2 g (4 capsules) thrice daily and Kangfuyan capsules 1.2 g (3 capsules) twice daily after hysterectomy. After 23 days of treatments, the patient developed gastrointestinal discomfort, and Jingangteng capsules and Kangfuyan capsules were stopped 2 days later. However, gastrointestinal discomfort gradually worsened and symptoms such as nausea, dark urine, and yellow staining of the skin and sclera appeared. After discontinuing the drug for 10 days, laboratory tests showed alanine aminotransferase (ALT) 366 U/L, aspartate aminotransferase (AST) 485 U/L, alkaline phosphatase (ALP) 145 U/L, gamma glutamyltransferase (γ-GT) 67 U/L, total bilirubin (TBil) 67.1 μmol/L, and direct bilirubin (DBil) 59.5 μmol/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination, and drug-induced liver injury was diagnosed. Oral liver-protective drugs and IV infusions of compound glycyrrhizin injection and polyene phosphatidylcholine injection were given successively, but jaundice continued to deepen with the peak TBil and DBil values of 189.7 μ mol/L and 159.4 μ mol/L, respectively. An IV infusion of ademetionine 1,4-butanedisulfonate for injection 1 g dissolved in 5% glucose injection 250 ml was given once daily. Three days later, the patient′s symptoms were improved and the jaundice subsided obviously; 9 days later, the liver function was improved obviously and laboratory tests showed ALT 29 U/L, AST 50 U/L, γ-GT 36 U/L, TBil 66.5 μmol/L, and DBil 53.2 μmol/L; 1 month later, her liver function returned to normal.

Objective To investigate the effect of up-regulation of miR-132 on expressions of angiopoietin-1 (Ang-1)/endothelium-specific tyrosine kinase receptor 2 (Tie2) in focal cerebral ischemia reperfusion injury of rats.Methods Forty adult healthy SD rats were randomly divided into sham-operated group,cerebral ischemia group,miR-132 mimic group and negative control group (n=10).The models of middle cerebral artery occlusion in the later three groups were established by using modified Longa suture method.Rats in the miR-132 mimic group and negative control group were injected miR-132 mimic 15 μg and negative control 15 μg via paracele.Rats in each group were sacrificed 24 h after ischemia,and the brain tissues were collected;the total infarct volumes were calculated by TTC staining.The mRNA expressions ofmiR-132,Ang-1 and Tie2 in ischemic cerebral cortex tissues were detected by real-time fluorescence quantitative PCR.The protein expressions of Ang-1,Tie2,CD31 and vessel endothelial growth factor (VEGF) in ischemic cerebral cortex tissues were detected by Western blotting.Results The total infarct volume in the miR-132 mimic group was (27.92±3.05) mm3,which was significantly smaller than that in the cerebral ischemia group and negative control group ([51.34±2.86] mm3 and [50.46±2.57] mm3,P＜0.05).The relative mRNA expression levels of miR-132,A ng-1,Tie2,and the protein expression levels of Ang-1,Tie2,CD31,VEGF in the ischemic cerebral cortex tissues of the miR-132 mimic group were significantly higher than those in the negative control group,cerebral ischemia group and sham-operated group (P＜0.05);and those in the negative control group and cerebral ischemia group were significantly higher than those in the sham-operated group (P＜0.05).Conclusion Up-regulation ofmiR-132 expression could improve the ischemic states of ischemic stroke in rats,which might be related to Ang-1/Tie2 increased expressions to promote angiogenesis in ischemic brain tissues.