Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable sig-nificance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39％of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.
Anti-Inflammatory Agents/therapeutic use* ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Plant Extracts/therapeutic use* ; SARS-CoV-2/drug effects*

The metabolic syndrome(MS)is a pathological state in children and adolescents,which is mainly characterized by aggregation onset of overweight or obesity,hyperinsulinemia or insulin resistance,im-paired glucose tolerance or type 2 diabetes,hypertension,lipid metabolism disorder and atherosclerosis.The prev-alence rate of MS has increased year by year.Studies have confirmed that the risk factors of coronary heart dis-ease and other chronic diseases in adults and its pathological process existed in childhood,so it will be of great significance to early detection and prevention of chronic diseases.At present,many reports have showed that CD40-CD40L system is closely related to cardiovascular disease,diabetes and many kinds of risk factors of car-diovascular disease,diabetes mellitus.It also plays a very important role in the development and prognosis of dia-betes.In this paper,the research progress of the relationship between CD40-CD40L system and metabolic syn-drome is reviewed.Monitoring CD40-CD40L system may be helpful to early diagnose and further therapy.It'll provide a new approach for the diagnosis of metabolic syndrome,so as to better control the incidence of related chronic diseases.

OBJECTIVETo investigate the effects of ropivacaine on Gamma-aminobutyric acid(GABA)-activated currents in dorsal root ganglion (DRG) neurons in rats and discuss the analgesia mechanism of ropivacaine.

METHODSBy means of using whole-cell patch-clamp technique, to investigate the modulatory effects of ropivacaine on GABA-activated currents (I(GABA)) in acutely isolated dorsal root ganglion neurons.

RESULTS(1) In 48 out of 73DRG cells (65.7%, 48/73), to perfusion ropivacaine bromide (0.1 - 1 000 micromol/L) were sensitive. Which produce in 0 to 380 pA current. (2) The majority of the neurons examined (74.5%, 73/98) were sensitive to GABA. Concentration of 1 - 1 000 micromol/L GABA could activate a concentration-dependent inward current, which manifested obvious desensitization, and the inward currents could be blocked byGABA-receptor selective antagonist of bicuculline (100 micromol/L). (3) After the neurons were treated with ropivacaine (0.1 - 1000 micromol/L) prior to the application of GABA (100 micromol/L) 30 s, GABA currents were obviously increased. Ropivacaine could make dose-response curve of the GABA up, EC50 is 23.46 micromol/L. Ropivacaine shifted the GABA dose-response curve upward and increased the maximum response to the contrast about 153%.

CONCLUSIONThe enhancement of ropivacaine to DRG neurons activation of GABA current, can lead to enhancement of pre-synaptic inhibition at the spinal cord level. This may be one of the reasons for the anesthetic effect and analgesia for ropivacaine in epidural anesthesia.

Amides ; pharmacology ; Animals ; Ganglia, Spinal ; cytology ; physiology ; Membrane Potentials ; drug effects ; Neurons ; cytology ; drug effects ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology

Objective To describe the uncertainty in illness and social support of patients before percutaneous coronary intervention (PCI) and explore the correlation between them.Methods By descriptive and correlation study,sixty patients before PCI were recruited in the study and were investigated with Mishel Uncertainty in Illness Scale (MUIS) and social support rating scale (SSRS).Results The total score of uncertainty in illness of patients before PCI was(90.72 ± 13.97 ) and was in the medium range.Among the four dimensions,the average score of ambiguity (40.27 ±6.87) was the highest.The total score of social support was(44.35 ±7.65 )and was at middle or high level.The uncertainty in illness of patients was negatively related with their social support(r =- 0.31 P ＜ 0.05 ).Conclusions Nurses should pay attention to the patients' uncertainty in illness before PCI and take advantage of their social support adequately.In this way,patients' uncertainty in illness can be decreased.

OBJECTIVETo explore the biomarkers and mechanism of kidney toxicity induced by trimethyltin chloride (TMT-Cl) through analyzing the differences of protein expression profiles between vero cells and vero cells exposed to TMT-Cl.

METHODSThe differences of protein expression levels of three paired samples of vero cells and vero cells exposed to TMT-Cl were compared by two-dimensional gel electrophoresis (2-DE) and liquid chromatography-electrospray ionization-linear trap quadrupole (LC-ESI-LTQ). The differences of expression levels of Annexin A1 and α-Tubulin proteins were validated with western blot assay, and the differences of mRNA expression levels of Annexin A1 and α-Tubulin genes were detected with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).

RESULTSFifteen spots of differential expression in protein profiles between vero cells and vero cells exposed to TMT-Cl were found, and 9 of these spots were identified by LC-ESI-LTQ. The expression levels of 3 proteins (Annexin A1,similar to RAN protein and a hypothetical protein) increased and the expression levels of 6 proteins(growth factor receptor-bound protein 10, tubulin alpha 6, heterogeneous nuclear ribonucleoprotein, similar to elongation factor SIII p15 subunit, S-adenosylhomocysteine hydrolase and a hypothetical protein) reduced. The expression levels of α-Tubulin protein and mRNA significantly decreased in vero cells exposed to TMT-Cl, as compared with vero cells (P < 0.01). The expression of Annexin A1 protein in all exposure groups was significantly up-regulated, the expression of Annexin A1 mRNA in the groups exposed to 25 and 50 µmol/L TMT-Cl was significantly down-regulated, and The expression of Annexin A1 mRNA in the group exposed to 100 µmol/L TMT-Cl was significantly up-regulated (P < 0.01).

CONCLUSIONSThe results of present study suggest that 9 proteins with differential expression detected by LC-ESI-LTQ may be related to the kidney toxicity induced by TMT-Cl, which can serve as the biomarkers of early diagnosis and therapeutic effect for the kidney toxicity induced by TMT-Cl.

Animals ; Cercopithecus aethiops ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Profiling ; RNA, Messenger ; genetics ; Transcriptome ; Trimethyltin Compounds ; toxicity ; Tubulin ; genetics ; metabolism ; Vero Cells

OBJECTIVETo investigate the effects of CS(2) occupational exposure on thumbprint and intelligence.

METHODSAccording to the monitoring results of CS(2) concentration, which were got at various workplace in chymic fiber factory, the workers were divided into three groups including the low-concentration group (TWA < 5 mg/m(3)), the high-concentration group (TWA >or= 5 mg/m(3)) and the control group. The method of cluster sampling was used respectively. 139, 129 and 327 people were taken at random from three groups and they were given thumbprint and intelligence examinations through following three methods, including MMPI, SCL-90 and SPM.

RESULTSMMPI test showed that Hy, Pa, Pt, Sc positive rates in the low-concentration group were 7.19%, 2.16%, 26.62% and 10.07%, Hs, D, Hy, Pa, Pt, Sc, Ma, Si positive rates in the high-concentration group were 32.56%, 8.53%, 9.30%, 24.81%, 2.33%, 42.64%, 15.50%, 5.43% and 6.20%. There was a significant difference with the control group (Hs, D, Hy, Pd, Pa, Pt, Sc, Ma, Si was 14.07%, 2.14%, 2.14%, 14.07%, 0.00%, 17.74%, 3.67%, 1.22%, 1.22% respectively). The differences of Hs, Pt positive rates between high-concentration and low-concentration group were significantly. SCL-90 showed that the total positive rate in the low concentration and the high concentration groups was 15.8% and 20.2%. The positive rate of the basic factors were significantly different among the low-concentration group, the high concentration group and the control group while there was no significant difference in the positive rate between the high concentration and low concentration group. SPM test found that the positive rates of the intelligence in the low concentration group and the high concentration group were 35.1% and 35.7% respectively and the control group (15.1%) was significantly different from low-concentration and high concentration group. Moreover, there was no obvious difference between high-concentration and the low-concentration group. The intelligence damage was associated with the length of CS(2) occupational exposure and the correlation coefficient had statistical significance.

CONCLUSIONThe low-concentration CS(2) occupational exposure could affect personality and intelligence, and the degree of this influence is associated with the length of CS(2) occupational exposure.

Adolescent ; Adult ; Air Pollutants, Occupational ; adverse effects ; analysis ; Carbon Disulfide ; adverse effects ; analysis ; Chemical Industry ; Female ; Humans ; Intelligence ; drug effects ; Male ; Middle Aged ; Occupational Exposure ; Personality ; drug effects ; Surveys and Questionnaires ; Textile Industry ; Workplace ; Young Adult

Objective To explore the influencing factors of job satisfaction, social support and dimission intention of nursing staff. Methods Chose 295 cases of medical staff randomly in 2 provincial hospitals in Dalian. Collected data with self-designed questionnaire and analyze influencing factors. Results The influencing factors of job satisfaction included culture level, marriage status, working age, ideal commitment and emotional exhaustion; The influencing factors of social support included culture level, children, individual sense of achievement, standared commitment, economy commitment, society commitment and emotional estrangement;The influencing factors of dimission intention were ideal commitment, night-watch, emotional exhaustion and sentiment estrangement. Conclusions The influencing factors of job satisfaction, social support and dimission intention were defined, we should comprehensively improve physical and mental health of nursing staff aimed at these factors.

China ; Humans ; Occupational Health Services