Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T⁺tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
Mice ; Animals ; NF-kappa B ; Myeloid Differentiation Factor 88/metabolism* ; Lipopolysaccharides/pharmacology* ; Toll-Like Receptor 4/metabolism* ; Autistic Disorder/metabolism* ; Signal Transduction/physiology*

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:The paper seeks to explore the characteristics of myeloid tumors with genetic DDX41 gene mutations,especially focusing on the understanding and treatment of acute myeloid leukemia with germline/somatic DDX41 mutation. Methods:One AML patient with germline/somatic DDX41 mutation who was diagnosed by using morphology,immunology,cytogenetics and molecular biology in Shanghai Shidong Hospital was retrospectively analyzed,and the patient was treated with lenalidomide combined with decitabine,and the literatures were reviewed. Results:The patient obtained complete remission after the therapy and there were no relevant adverse reactions to the treatment. Conclusion:The DDX41 gene mutations have effects on the prognosis and treatment of myeloid malignancies,and lenalidomide combined with decitabine is effective in acute myeloid leukemia with germline/somatic DDX41 mutation.The germline mutation status should be identified and confirmed early.

With the development of Internet technology and big data, artificial intelligence has been widely used in the field of clinical anesthesia. In the field of clinical teaching, artificial intelligence has also led to a series of innovations and changes in teaching model, contents, and evaluation. With reference to the current status of the application of artificial intelligence in the field of anesthesia, this article analyzes the possible impact of artificial intelligence on teaching model, teaching effect evaluation, teaching management, and ethical issues in clinical anesthesia teaching, so as to provide a theoretical basis for integrating artificial intelligence into clinical anesthesia teaching practice in the future.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective: To evaluate the relationships between admission fasting serum C-peptide concentration and cardiac function status in chronic heart failure (CHF) patients with or without diabetes. Methods: From July 2017 to December 2018, 262 CHF patients with or without diabetes in the Department of Cardiology of Pudong hospital in Shanghai were analyzed.Their cardiac function was classified as New York Heart Association (NYHA) grade Ⅱ to Ⅳ, and they were divided into diabetes group (80 cases) and non diabetes group (182 cases). At the same time, 62 subjects without diabetes and heart disease were randomly selected as the control group.To analyze the relationship between fasting serum C-peptide level and cardiac function in diabetic and nondiabetic CHF patients. Results: (1)The fasting plasma glucose and serum C-peptide concentrations of diabetes group paitents were(8.7±2.9) mmol/L and(0.78±0.67) nmol/L respectively, the nondiabetes group paitents were(5.8±1.67) mmol/L and(0.56±0.61)nmol/L respectively, the control group were(5.1±0.69) mmol/L and(0.16±0.12)nmol/L respectively.The difference in the three groups was statistically significant(all P<0.001). The levels of fasting blood glucose and serum C-peptide in diabetic group were significantly higher than those in non diabetic group and control group (all P<0.01). The levels of fasting blood glucose and serum C-peptide in non diabetic group were significantly higher than those in control group (P<0.05 or P<0.01). The left ventricular ejection fraction (LVEF) in diabetic group was(44.1±8.3)%, and those in non diabetic group and control group were(46.7±7.2)% and(64.8±3.8)%.The difference in the three groups was statistically significant(<0.001). The LVEF of diabetic group was significantly lower than that of non diabetic group and control group (all P<0.01), and the CRP of diabetic group was (1.39±0.91) mg/L, the N-terminal pro-B-type natriuretic peptide (pro-BNP) was (1 771.3±23.1) ng/L, the hemoglobin was (125.6±16.7) g/L in the diabetic group, and (1.22±0.73) mg/L, (1 659.2±19.3) ng/L, (126.1±16.5) g/L in the non diabetic group, respectively, and (0.85±0.72) mg/L, (87.2±17.2) ng/L, (136.4±15.2) g/L in the control group, respectively.The differences among the three groups were statistically significant (P<0.001). CRP and pro-BNP in the diabetic group and non diabetic group were significantly higher than those in the control group (all P<0.01), and hemoglobin levels were significantly lower than those in the control group(all P<0.01). There were no statistically significant differences in CRP, pro-BNP and hemoglobin between the diabetic group and non diabetic group (all P>0.05). (2) In all patients with heart failure, diabetes mellitus and non diabetes heart failure, the levels of serum C-peptide were (1.05±0.85), (1.17±0.82), (0.99±0.86) nmol/L in NYHA Ⅳ group, and (0.53±0.22), (0.52±0.20), (0.54±0.23) nmol/L in NYHA Ⅲ group, and (0.32±0.09), (0.32±0.11), (0.31±0.09) nmol/L in NYHA Ⅱ group.After adjustment of age, gender, smoking, insulin secretion and hypoglycemic drugs, body mass index, blood pressure, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine, blood glucose, blood lipid, white blood cell count (WBC) and hemoglobin level by covariance analysis, all patients with heart failure The level of serum C-peptide in NYHA Ⅳ group was significantly higher than that in Ⅲ group (all P<0.01) and Ⅱ group (all P<0.01). In all patients with heart failure and non diabetic heart failure, the level of serum C-peptide in NYHA Ⅲ group was significantly higher than that in Ⅱ group (all P<0.05). There was no significant difference in serum C-peptide between all patients with heart failure, diabetes mellitus and non diabetes heart failure (all P>0.05) (3) Using multiple linear regression analysis, the adjustment factors included age, gender, smoking, BMI, blood pressure, TBIL, alt, creatinine, blood glucose, blood lipid, WBC and hemoglobin levels.The results showed that the serum C-peptide level was positively correlated with pro-BNP in all patients with heart failure, diabetes and non diabetes heart failure (β: 0.006, 95%CI -0.016-0.028 , P=0.007; β: 0.117, 95%CI-0.042-0.277 , P=0.006; β: 0.411, 95%CI-0.149-0.971 , P=0.023), negatively correlated with LVEF(β: -0.122, 95%CI-0.285-0.041, P=0.004; β: -0.008, 95%CI-0.032-0.016, P=0.010; β: -0.065, 95%CI-0.139-0.011, P=0.036). Conclusion The level of fasting serum C-peptide was significantly increased in patients with CHF and non-diabetic patients, and was related to the severity of heart failure.

Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells.After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.

Objective To investigate the clinical efficacy of etoposide and levofloxacin in the treatment of chronic nonbacterial prostatitis(CNP)alone or in combination.Methods A total of 168 patients with CNP in our hospital from August 2014 to January 2016 were enrolled in this study.The patients were divided into A, B and C groups according to the random number table,56 cases in each group.Group A treatment alone, group B was treated with levofloxacin alone, group C was treated with Yongqing Tablet and levofloxacin, and the clinical efficacy and adverse hair loss were compared.Results After a course of treatment, there was no significant difference in the effective rate of treatment between group A and group B.The effective rate of treatment of group C was higher than that of group A and B, the difference was statistically significant (P<0.05).There was no significant differences in the incidence of adverse events between the three groups.Conclusion The clinical effect of Tongueqing and levofloxacin in the treatment of CNP is higher than that of single administration, and it will not increase the adverse reaction.It is worthy to be popularized and applied.