Objective To investigate the distribution and antibiotic resistance profiles of the bacterial strains isolated from urine samples in a tertiary Traditional Chinese Medicine hospital in Shanghai in the 12-year period from 2010 through 2021 for better empirical antibiotic use in clinical practice.Methods The clinical data of patients with urinary tract infection,including the species and antibiotic resistance of the bacterial strains isolated from urine samples from January 2010 to December 2021 were retrospectively analyzed.Results A total of 5 231 nondupliate bacterial strains were isolated,among which E.coli was the most common(52.8％),followed by Enterococcus spp(19.1％)and Klebsiella spp(11.1％).Most of the urinary isolates(76.0％)were isolated from the elderly aged 60-89,and only 3.1％of the strains were isolated from the young people aged under 44.Most of the bacterial strains were isolated from female patients(75.8％),however,more P.aeruginosa and A.baumannii were isolated from male patients compared to female patients(55.3％vs 44.7％and 67.7％vs 32.3％).About 13.7％of the strains were collected from the Department of Nephrology,more than the strains from any other clincial department.In intensive care unit(ICU),the proportion of E.coli was the lowest,while the proportion of Enterococcus spp was the highest.Enterobacterales showed lower resistance raets to carbapenems,cephamycin,amikacin,cefepime,and β-lactam/β-lactamase inhibitor combinations.P.aeruginosa showed higher susceptibility rates to carbapenems,aminoglycosides and β-lactam/β-lactamase inhibitor combinations compared to A.baumannii(≥54.6％vs≤39.8％).Gram-positive cocci were highly sensitive to glycopeptide antibiotics.No SS.aureus or E.faecalis isolates were found resistant to vancomycin.About 2.7％of the E.faecium isolates were resistant to vancomycin.The prevalence of drug-resistant bacteria was the highest in elderly patients,and in the strains isolated from ICU and emergency department.Conclusions Compared with general hospitals,a high proportion of elderly patients were treated in this hospital.It should be more cautious in the treatment of patients with urinary tract infection.The major bacterial species isolated from urine were E.coli,Enterococcus,and K.pneumoniae.Empirical treatment should be prescribed considering patient age and gender as well as the species and distribution of pathogenic bacteria.Urine culture and antibiotic susceptibility testing should be performed proactively.Appropriate antimicrobial agents should be selected according to the results of antimicrobial susceptibility testing.Antimicrobial ressitance surveillance should also be strengthened.

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*

OBJECTIVE: To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China. METHODS: Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm²·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes. RESULTS: The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity. CONCLUSION There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.
Humans ; Adolescent ; Child ; Overweight/etiology* ; Pediatric Obesity/etiology* ; Light Pollution ; Risk Factors ; China/epidemiology*

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Chromatography, Liquid ; Interleukin-6 ; Tandem Mass Spectrometry ; Acupuncture Points ; Arthritis, Rheumatoid/drug therapy*

AIM: To systematically evaluate the efficacy and safety of olopatadine combined with pranoprofen in the treatment of allergic conjunctivitis.METHODS: Using “olopatadine eye drops”, “pranoprofen eye drops” and “allergic conjunctivitis” as keywords, the controlled clinical trials of olopatadine combined with pranoprofen in the treatment of allergic conjunctivitis were searched from Embase, Cochrane library, PubMed, CNKI, Wanfang and VIP database, with an retrieval time from the establishment of the database to January 1, 2022; The Cochrane Risk of Bias Assessment Tool was used to assess the quality of the included studies, and the Egger's test was performed for publication bias of the included literatures. Meta-analysis was performed by using RevMan 5.3.RESULTS: A total of 24 eligible Chinese literatures were included, with 2 443 patients(2 547 eyes)in total. The test group was administrated olopatadine combined with pranoprofen, and the control group was treated with olopatadine monotherapy; The results of Meta-analysis showed that the clinical efficiency of the test group was better than that of the control group(OR=4.42, 95%CI:3.37-5.80,P<0.00001); There was no significant difference in the incidence of adverse reactions between the test group and the control group(OR=0.89, 95%CI: 0.45-1.75, P=0.73); Egger's test was conducted on the clinical efficiency and the incidence of adverse reactions, which showed that there was publication bias in the clinical efficiency, but the existed publication bias did not affected results through trim and fill method.CONCLUSIONS: The combination of olopatadine with pranoprofen may improve the clinical efficacy of allergic conjunctivitis. In the future, multicentered, randomized, double-blind studies can be conducted to improve the strength of the evidence.

ObjectiveTo predict the mechanism of Sinitang in treating myocardial ischemia-reperfusion injury （MI/RI） based on network pharmacology and verify the prediction results by cellular experiments. MethodThe traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） was employed for retrieval of the main components and potential targets of Sinitang. Online Mendelian Inheritance in Man （OMIM） and GeneCards were employed to obtain the targets of Sinitang in treating MI/RI. STRING was employed to construct the protein-protein interaction （PPI） network， and DAVID to perform gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Finally， cellular experiments were carried out to verify the predicted anti-MI/RI mechanism of Sinitang. ResultA total of 105 active ingredients and 234 targets of Sinitang were screened out， among which 116 targets were predicted to be involved in the treatment of MI/RI. The GO annotation gave 587 entries， including 417 biological process entries， 101 cell component entries， and 69 molecular function entries. The KEGG analysis enriched 125 signaling pathways， involving vascular endothelial growth factor （VEGF）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， forkhead box transcription factor O （FoxO）， hypoxia-inducible factor-1 （HIF-1） apoptosis and other signaling pathways. The results of cell viability assay showed that Sinitang increased the survival rate of H9C2 cells damaged by hypoxia/reoxygenation （H/R）. Sinitang decreased the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and creatine kinase-MB （CK-MB） in H9C2 cells damaged by H/R. The results of flow cytometry demonstrated that Sinitang decreased the apoptosis rate of H9C2 cells damaged by H/R. Western blot showed that Sinitang down-regulated the expression of Bcl-2 related X protein （Bax） and up-regulated that of B-cell lymphoma-2 （Bcl-2） in H/R-injured H9C2 cells. ConclusionSinitang treats MI/RI in a multi-target and multi-pathway manner， which involves the signaling pathways associated with apoptosis.

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.
4-Butyrolactone/chemistry* ; Animals ; Chromatography, Liquid ; Exosomes/chemistry* ; Hydroxybutyrates/chemistry* ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Oxybate/analysis* ; Tandem Mass Spectrometry/methods*

Circular RNAs (circRNAs),a kind of novel non-coding RNAs, have been shown to play animportant role in cellular redox reactions. In the previous study, we found that hsa_circ_0087354 wasclosely related to the cellular redox state by real-time PCR. After overexpression of hsa_circ_0087354, the relative expression of ROS1 were decreased significantly (P < 0. 01), while the levels of SOD1 wereincreased significantly (P < 0. 05) . The activities of SOD and Gpx as well as GSH concentration weresignificantly increased (P < 0. 01), and cell proliferation was promoted in cells (P < 0. 05) . Bioinformatics analysis predicted that there were binding sites between hsa-miR-199-3p and hsa_circ_0087354 as well as solute carrier family 7 member 11 (SLC7A11), which might have a targetedregulatory relationship. Dual luciferase reporter assay confirmed the targeted regulatory relationshipbetween hsa-miR-199-3p with hsa_circ_0087354, and SLC7A11. Overexpressed hsa_circ_0087354 plasmid and ctrl plasmid were constructed, hsa-miR-199a-3p, hsa-miR-199b-3p and hsa-miR-NC mimicswere synthesized. Real-time PCR analysis showed that the relative expression of hsa-miR-199-3p was observably decreased (P < 0.01), while the relative expression of SLC7A11 in cells was dramaticallyincreased after transfection of has_circ_0087354 plasmid (P < 0.05) . After transfection with hsa-miR-199-3p, the relative expressions of SLC7A11 were markedly decreased (P < 0.001) . The activities ofSOD and Gpx, GSH concentration (P<0.01), and cell proliferation rate (P < 0.05) were significantlyreduced. In conclusion, hsa_circ_0087354 could enhance the expression of SLC7A11, promote theproliferation of cells and reduce the oxidative stress by adsorption of hsa-miR-199-3p.

Objective:To validate the performance of cardiovascular risk prediction models based on the Sweden National Diabetes Register (NDR) and Diabetes Lifetime-perspective prediction (DIAL) model for assessing risks of 5-year and 10-year cardiovascular disease (CVD) among Chinese patients with type 2 diabetes.Methods:Based on the Chinese Electronic Health Records Research in Yinzhou study, 83 503 patients with type 2 diabetes aged 30-75 years without a history of CVD at baseline were included from January 1, 2010 to December 31, 2020. Recalibrated NDR model was used to estimate 5-year risk, while the recalibrated DIAL model was used to predict 5-year and 10-year risks. The competing events adjusted Kaplan-Meier analysis was used to obtain the observed cardiovascular events. Discrimination C statistics evaluated model accuracy, calibration χ2 value, and calibration plots. Results:Through a median follow-up of 7.0 years, 7 326 cardiovascular events, and 2 937 non-vascular deaths were identified among a total of 83 503 subjects. The recalibrated NDR model overestimated 5-year risk by 39.4% in men and 8.6% in women, whereas the overestimation for the recalibrated DIAL model was 14.6% in men and 50.1% in women. The DIAL model had a better discriminative ability ( C-statistic=0.681, 95% CI: 0.672-0.690) than NDR model ( C-statistic=0.667, 95% CI: 0.657-0.677) in 5-year risk prediction for men, and the models had a similar ability for women ( C-statistic=0.699, 95% CI: 0.690-0.708 for NDR and C-statistic=0.698, 95% CI: 0.689-0.706 for DIAL). The prediction accuracy of the DIAL model was improved in the 10-year risk, with the underestimation being 1.6% for men and the overestimation being 12.8% for women. Conclusions:Both recalibrated NDR and DIAL models overestimated 5-year cardiovascular risk in Chinese patients with type 2 diabetes, while the higher overestimation was shown using the DIAL model. However, the improvement was found in predicting 10-year CVD risk using the DIAL model, which suggested the value of lifetime risk prediction and indicated the need for research on the lifetime risk prediction model for cardiovascular risk assessment in Chinese patients with type 2 diabetes.