OBJECTIVE To establish a method for simultaneously determining three anti-tuberculosis drugs in the plasma of patients with spinal tuberculosis and apply it in clinical practice. METHODS LC-MS/MS method was established for the quantitative determination of the concentrations of isoniazid， rifampicin and pyrazinamide in the plasma of patients with spinal tuberculosis， using diphenhydramine as the internal standard. The determination was carried out using Chemalink CM-C18T column， with mobile phase consisting of 0.1% formic acid-methanol solution （gradient elution）， at the flow rate of 0.4 mL/min and an injection volume of 2 μL. Multiple reaction monitoring was conducted using an electrospray ionization source in positive ion mode. The ion pairs used for quantitative analysis were m/z 138.0→121.0（ for isoniazid）， m/z 823.3→791.3（ for rifampicin）， m/z 124.1→ 79.0 （for pyrazinamide）， and m/z 256.0→167.0 （for diphenhydramine）. Fifty-three patients diagnosed with spinal tuberculosis in Qinghai Provincial People’s Hospital from January 2023 to June 2025 were selected， and the plasma concentrations of isoniazid， rifampicin and pyrazinamide in these patients were measured using the above method. RESULTS The linear ranges for isoniazid， rifampicin and pyrazinamide were 0.5-16， 2-64， and 2.5-80 μg/mL， respectively （r≥0.998 7）. The accuracy ranged from 90.20% to 108.64% （n＝5）. RSDs for intra-day precision were all less than 6.63% （n＝5）， while those for inter-day precision were all less than 8.42% （n＝3）. The matrix effects ranged from 88.60% to 115.41% （n＝5）. The relative deviations in the stability tests were all within the ±15% range， and the carry-over effect did not interfere with the determination. The results of clinical application showed that the mean plasma drug concentrations of isoniazid， rifampicin and pyrazinamide in patients with spinal tuberculosis were （3.62±2.80）， （8.55±4.57）， and （20.12±6.56） μg/mL， respectively. The incidences of plasma drug concentrations falling below the effective peak concentrations were 49.06%， 58.49% and 60.38%， respectively. CONCLUSIONS The method established in this study is rapid， accurate， and demonstrates good stability， making it suitable for clinical monitoring of the plasma concentrations of isoniazid， rifampicin and pyrazinamide in patients with spinal tuberculosis.

Objective To investigate the pathogenic distribution characteristics and drug resistance of opportunistic Candida in patients with pulmonary tuberculosis on the Qinghai-Tibet Plateau.Methods 3 012 hospitalized cases of pulmonary tuberculosis at Qinghai Province Fourth People's Hospital from March 1,2020 to December 31,2020 were analyzed,sputum samples were collected,Candida identification was carried by VITEK-32-YBC automatic bacterial analysis system,and the detected Candida was tested for drug sensitivity.Results Among the 3 012 cases of pulmonary tuberculosis in this investigation,283 cases of pulmonary tuberculosis patients with Candida infection,accounting for 9.40%.Among them,Candida albicans was the main type of Candida,accounting for 79.86%of the total.Conclusion The prevalence rate of pulmonary tuberculosis complicated with Candida infection was high in Qinghai-Tibet Plateau.Therefore,the selection of antimicrobial drugs should be based on a comprehensive analysis of the patient's condition,in order to select the best and most effective drugs for treatment.

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Cirrhotic portal hypertension could complicate impaired intestinal barrier function,small intestinal bacterial overgrowth and dysbiosis of intestinal microbiota,further exacerbate the severity of cirrhosis.TIPS might lead to hepatic encephalopathy(HE).The research progresses in correlations of cirrhotic portal hypertension,TIPS related HE and gut microbiota were reviewed in this article.

Objective:To explore the current status and correlation of occupational stress and burnout among pediatric nurses.Methods:From April 2023 to January 2024, convenience sampling was used to select 150 pediatric nurses from Taizhou Hospital of Zhejiang Province, East Campus of Taizhou Hospital of Zhejiang Province, and Taizhou Enze Medical Center as research subjects. The survey was conducted using the General Information Questionnaire, Chinese version of the Maslach Burnout Inventory General Survey, and Nurse Job Stressors Scale.Results:A total of 150 nurses were surveyed, and 149 valid questionnaires were collected, with a valid response rate of 99.33%. Pediatric nurses had high scores in emotional exhaustion and depersonalization dimensions in occupational burnout. The job stressors for pediatric nurses were ranked in order of their scores in each dimension, including workload and time management, work environment and resources, nursing profession and work, management and interpersonal relationships, and patient nursing. There were correlations between occupational burnout and occupational stress among pediatric nurses in multiple dimensions (all P<0.05) . Conclusions:Pediatric nurses have a relatively high level of occupational burnout and often face significant occupational stress. In the development of the healthcare system, attention should be paid to the occupational burnout and stress of pediatric nurses. The physical and mental health of pediatric nursing staff can be promoted and work efficiency can be improved by reducing the overloaded work of pediatric nurses, optimizing personnel allocation, and improving social support.

Objective:To investigate the predictive value of serum proenkephalin A 119-159 (penKid) on incidence and the 28-day mortality in patients with sepsis-associated acute kidney injury (SA-AKI).Methods:This study was a single center, observational cohort study. Sepsis/septic shock patients admitted to Department of Critical Care Medicine of Taizhou People's Hospital Affiliated to Nanjing Medical University from September 2021 to September 2022 were selected and divided into the SA-AKI group and the non-SA-AKI group according to whether acute kidney injury (AKI) occurred within 28 days. Patients in the SA-AKI group were subdivided into the death group and the survival group according to whether death occurred within 28 days. Baseline data and laboratory indicators such as penKid concentration were compared among different groups. COX regression analysis was used to explore the risk factors of death within 28 days in the SA-AKI patients, And Kaplan-Meier curve was used to analyze patient prognosis.Result:A total of 161 patients were included in this study, of whom 66 (41.0%) developed AKI. The baseline penKid concentration in the SA-AKI group was significantly higher than that in the non-SA-AKI group [(2.99 ± 0.68) μg/L vs. (1.86±0.75) μg/L, P<0.05]. Multivariate COX regression analysis showed that the baseline penKid ( HR=5.608, 95% CI: 3.507-8.967, P<0.001) and lactate (LA) ( HR=1.089, 95% CI: 1.003-1.183, P=0.043) were independent risk factors for AKI in sepsis/septic shock patients. Of the 66 SA-AKI patients, 27 (40.9%) died within 28 days, and the baseline penKid concentration in the death group was significantly higher than that in the survival group [ (3.55 ± 0.54) μg/L vs. (2.60±0.47) μg/L, P<0.05]. COX regression analysis showed that penKid ( HR=5.892, 95% CI: 2.457-14.132, P<0.001) was an independent risk factor for mortality in SA-AKI patients. Kaplan-Meier curve showed that the 28-day mortality of patients with baseline penKid ≥ 3.24 μg/L was significantly higher than that of patients with baseline penKid <3.24 μg/L ( P<0.001). Conclusions:In sepsis/septic shock patients, the penKid concentration measured on the first day in the SA-AKI group is significantly higher than that in the non-SA-AKI group. In SA-AKI patients, the penKid concentration measured in patients who survived within 28 days is significantly lower than that in the death group. PenKid is an independent risk factor for the occurrence and death of SA-AKI.

Objective To evaluate the effect of obstructive sleep apnea syndrome (OSAS) on the degree of bronchial asthma (BA) in adults, and to analyze the potential relationship between the two. Methods A retrospective study was used to collect 90 patients with BA patients who were admitted to Jiangsu Provincial Hospital of Traditional Chinese Medicine from January 2018 to June 2022. All patients received polysomnography (PSG) to calculate the apnea hypopnea index (AHI). Patients were divided into mild OSAS (AHI<15), moderate OSAS (1530) according to AHI value. In addition, BA related indicators of patients were measured, such as forced expiratory volume in the first second (FEV1), FEV1%, FEV1/forced vital capacity (FVC), exhaled nitric oxide (FeNO), total airway resistance (R5), central airway resistance (R20) and peripheral elastic resistance (X5). Analysis of variance was used to compare the differences in BA related indicators in patients with different degrees of OSAS, and Pearson linear correlation analysis was used to analyze the correlation between AHI and the measured values of BA indicators. Results There was 1 case (1.11%) in AHI<15, 41 cases (45.56%) in 1530. There was no difference in gender composition among different AHI groups, but the AHI value of BA patients aged 70 years and above was higher, and the age difference was statistically significant (P<0.05). The results of different AHI groups showed that the patients with moderate to severe OSAS received higher step-up treatment for asthma, most of which were in step 3 and step 4, with a statistically significant difference (2=90.085，P<0.001). The variance analysis results showed that the more severe the OSAS, the lower the ratio of FEV1/FVC (%) (F=2.600, P=0.011), and the higher the FeNO and R5 measurements values (F=-6.454 , F=-3.291, P<0.001). Pearson linear correlation analysis showed that AHI was negatively correlated with FEV1% (r=-0.356, P<0.05) and FEV1/FVC% (r=-0.289, P<0.001), but AHI was positively correlated with R5 (r=0.447, P<0.05). Conclusion BA patients with OSAS have significantly abnormal respiratory function-related indicators, and with the aggravation of OSAS, BA will further deteriorate

Objective:To explore the effect of job insecurity on work engagement, and examine the mediating role of job satisfaction and the moderating role of occupational proactive behavior.Methods:Using the convenient sampling method, nurses from Southern University of Science and Technology Hospital and Jiangyou Second People's Hospital were selected as the research objects in July 2022. General information questionnaire, Occupational Insecurity Scale, Occupational Satisfaction Scale, Work Engagement Scale and Occupational Proactive Behavior were used for questionnaire investigation. A total of 598 valid questionnaires were collected. Model 4 and Model 7 in the SPSS 22.0 Process were used to test the mediating effect and the moderated mediating effect respectively.Results:Occupational insecurity was negatively correlated with occupational satisfaction and work engagement ( r=-0.202, -0.165, P<0.01) , while occupational satisfaction was positively correlated with work engagement ( r=0.549, P<0.01) . Work satisfaction played a completely mediating role in the effect of job insecurity on work engagement (mediating effect value: -0.090 9, 95% confidence interval: -0.14 - -0.04) , accounting for 65.30% of the total effect. Occupational active behavior positively moderated the relationship between job insecurity and job satisfaction (β=0.07, P<0.01) . Conclusions:Nurses' work engagement is at a high level, but occupational insecurity will reduce nurses' job satisfaction and thus reduce their work engagement. Nurses with high occupational proactive behavior can alleviate the weakening of job insecurity on job satisfaction.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.