Objective:To establish a highly sensitive indirect competitive ELISA(icELISA)method for detecting ribavirin in chicken.Methods:Based on the obtained monoclonal antibodies against ribavirin,a chessboard test was employed to determine the optimal working concentration of artificial antigen and antibody,and then established an icELISA method.Furthermore,performance of the detection method was evaluated.Results:The established icELISA method has a linear range of 0.44～32.71 ng/ml,IC50 of which was 3.78 ng/ml,and the limit of detection(LOD)was 0.20 ng/ml.Except for specific reaction with ribavirin,there were no cross reactions with other antiviral drugs.Recovery rate of sample spiking was between 91.60%and 100.76%,and coefficient of variation was between 7.29%and 10.63%.Conclusion:A highly sensitive and specific icELISA method for detection of ribavirin has been estab-lished,which can be used to determine the residue of ribavirin in chicken.

Objectives:To assess the impact of intravascular ultrasound(IVUS)guidance for drug-eluting stent(DES)implantation on the long-term outcomes in coronary artery disease(CAD)patients with chronic kidney disease(CKD).Methods:A retrospective study was conducted on 1 800 CAD and CKD patients who underwent coronary DES implantation at Nanjing First Hospital from January 2018 to December 2022.Patients were divided into IVUS-guided group(IVUS group,n=333)and angiography-guided group(angiography group,n=1 467).Propensity score matching(PSM)was performed at a 1:2 ratio to adjust for differences in baseline clinical and angiographic characteristics between the two groups.Major adverse cardiovascular events(MACE),including cardiac death,target vessel myocardial infarction,and clinically driven target vessel revascularization,were evaluated over a 2-year follow-up.Cox proportional hazards regression was performed to identify independent predictors of MACE.Results:After propensity score matching,333 patients in the IVUS group were matched with 666 patients in the angiography group.Following matching,there were no significant differences in clinical characteristics and angiographic data between the two groups(all P>0.05).Regarding procedural data,IVUS group had a higher number of stents implanted,longer total stent length,larger average stent diameter,more frequent use of post-dilation balloons,larger post-dilation balloon diameter,and greater contrast agent usage(all P<0.05).MACE rate was significantly higher in the angiography group than that in the IVUS group(23.9%vs.18.0%,P=0.037).The difference was mainly attributed to a higher rate of cardiac death in the angiography group(16.1%vs.10.8%,P=0.013).Additionally,patients in angiography group had a significantly higher all-cause mortality rate compared to IVUS group(19.7%vs.13.8%,P=0.022).Multivariate cox regression analysis showed that IVUS guidance(HR=0.73,95%CI:0.55-0.99,P=0.042)was an independent protective factor,while hypertension(HR=1.60,95%CI:1.13-2.26,P=0.008),type 2 diabetes(HR=1.56,95%CI:1.19-2.05,P=0.001),acute coronary syndrome(HR=1.92,95%CI:1.12-3.30,P=0.018),and moderate to severe calcification(HR=1.55,95%CI:1.18-2.04,P=0.002)were independent risk factors for MACE at 2 years after DES implantation in CKD patients.Conclusions:Patients with CAD and CKD,IVUS-guided DES implantation is associated with a reduced risk of MACE and all-cause mortality at 2 years post-procedure compared to coronary angiography-guided implantation.

Objective:To analyze the prevalence of chronic diseases, the level of chronic disease prevention and control literacy and its influencing factors among middle-aged and elderly residents in Wenzhou from 2020 to 2023.Methods:Based on a cross-sectional research design, 19 528 usual residents aged 45-69 were retrospectively selected with a multi-stage stratified random sampling method from the health literacy monitoring survey in Wenzhou from 2020 to 2023. The χ2 tests and trend χ2 tests were employed to analyze chronic disease prevalence rates and health literacy possession rates across different population subgroups. Binary logistic regression models were used to identify determinants of chronic disease prevention health literacy among middle-aged and elderly residents in Wenzhou. The results were standardized using data from Wenzhou′s Seventh National Population Census. Results:The numbers of middle-aged and elderly respondents was 5 528, 4 822, 4 575 and 4 603 from 2020 to 2023, respectively, and the prevalence of self-rated chronic diseases was 39.56%, 37.33%, 41.29% and 39.00%, respectively (the standardized rate was 33.49%, 33.58%, 36.43% and 35.34%, respectively) in the each year, and the rates of chronic disease prevention and control literacy was 24.76%, 27.98%, 24.44% and 28.13%, respectively (the standardized rate was 27.95%, 30.11%, 27.57%, 29.78%, respectively). The rates of chronic disease prevention and control literacy was on an upward trend in middle-aged and elderly respondents in Wenzhou from 2020 to 2023 ( χ2trend=5.997, P=0.014). From 2020 to 2023, chronic disease prevention health literacy showed a positive educational gradient, with significantly higher levels observed among more educated populations (both P<0.05). Except for 2020, the residents with household income≥30 000 yuan had a higher chronic disease prevention and control literacy than those with household income less than 30 000 yuan (both P<0.05); in 2021 and 2022, the chronic disease prevention and control literacy in the people of 45-59 years was higher than that in the individuals of 60-69 years (both P<0.05); in 2020 and 2022, the rural residents had a higher chronic disease prevention and control literacy than the urban residents, and the rates of chronic disease prevention and control literacy of employees or retirees in government institutions/doctors/teachers were higher than that in the peasants (both P<0.05); in 2023, the chronic disease prevention and control literacy of the smokers was lower than that in the non-smokers ( P=0.014). Conclusions:The prevalence of chronic diseases among the middle-aged and elderly residents in Wenzhou is relatively low, people with chronic diseases, especially those with multiple chronic diseases, have a low level of chronic disease prevention and control literacy. To prevent and control chronic diseases among them, interventions should be differentiated by the chronic disease status, occupation and household income.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective:To explore the application of the O-PIRTAS flipped classroom in teaching the course of "developmental psychology".Methods:This study involved second-year undergraduate students majoring in clinical psychology. The 26 undergraduate students enrolled in 2023 who participated in the late adulthood section of the course were selected as the experimental group (O-PIRTAS teaching), while the 25 undergraduate enrolled in 2022 in the same course were selected as the control group (traditional teaching). Assessments were conducted through closed-book tests and questionnaires. The student questionnaire evaluated their theoretical knowledge, class assessment, and class engagement. The teacher questionnaire assessed the completeness of the lecture, logical flow, and student engagement. SPSS 22.0 was used for t test. Results:In the theoretical examination, the experimental group showed significantly higher scores compared to the control group in knowledge application [(13.09±1.59) vs. (10.54±0.77)] and practical problem-solving ability [(8.27±0.57) vs. (6.95±0.32)]. In the questionnaire survey, 24 (92.00%) students in the experimental group expressed recognition of the flipped classroom mode. Teachers reported greater improvement in satisfaction with the classroom performance of the experimental group compared to the control group.Conclusions:O-PIRTAS flipped classroom improves the quality of teaching "developmental psychology", enhances student learning outcomes, and stimulates learning motivation.

Cantharidin(CTD),a natural compound used to treat multiple tumors in the clinic setting,has been limited due to acute kidney injury(AKI).However,the major cause of AKI and its underlying mechanism remain to be elucidated.Serum creatinine(SCr)and blood urea nitrogen(BUN)were detected through pathological evaluation after CTD(1.5 mg/kg)oral gavage in mice in 3 days.Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to investigate lipids disorder after CTD exposure in mice.Then,spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI)was used to detect the kidney spatial distribution of lipids.Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro.The results showed that the levels of SCr and BUN were increased,and tubular necrosis was observed in mouse kidneys,resulting in acute tubular necrosis(ATN)in CTD-induced AKI.Then,lipidomics results revealed that after CTD exposure,232 differential lipid metabolites and 11 pathways including glycerophospholipid(GP)and sphingolipid(SL)metabolism were disrupted.Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed.Subsequently,integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla,whereas SL metabolism was inhibited in the renal cortex.Up-regulated lysophosphatidylcholine(LysoPC)(18∶2(9Z,12Z)),LysoPC(16∶0/0∶0),glycerophosphocholine,and down-regulated sphingomyelin(SM)(d18∶0/16:0),SM(d 18∶1/24:0),and SM(d42∶1)were key differential lipids.Among them,LysoPC(16∶0/0∶0)was increased in the CTD group at 1.1196 μg/mL,which aggravated CTD-induced ATN in human kidney-2(HK-2)cells.LysoPC acyltransferase was inhibited and choline phos-photransferase 1(CEPT1)was activated after CTD intervention in mice and in HK-2 cells.CTD induces ATN,resulting in AKI,by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla,LysoPC(16:0/0:0),LysoPC acyltransferase,and CEPT1 may be the therapeutic targets.

OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVES: To investigate the inhibitory effect of Fuzheng Huaji Decoction against non-small cell lung cancer (NSCLC) cells in vitro and explore the underlying mechanism. METHODS: The active ingredients and targets of Fuzheng Huaji Decoction were identified using TCMSP and SwissTargetPrediction databases. NSCLC-related targets from GeneCards and PharmGKB were intersected with the targets of the Decoction, and a protein-protein interaction (PPI) network was constructed to identify the core targets, which were analyzed with GO and KEGG pathway enrichment analysis. Cultured A549 cells were treated with different concentrations of Fuzheng Huaji Decoction-medicated serum, and the changes in cell proliferation, apoptosis, and protein expressions were examined using CCK-8 assay, annexin V-FITC/PI staining and Western blotting. RESULTS: Fuzheng Huaji Decoction contained 140 active ingredients, and 707 drug-disease intersecting targets were identified. Among these targets, TP53, AKT1, HIF1A, GAPDH, ALB, EGFR, CTNNB1, and TNF were identified as the core targets which were involved in the biological processes related to kinases and receptors and the PI3K-AKT, Ras, calcium, and MAPK pathways. Molecular docking studies indicated strong binding affinity of the active ingredients with TP53, AKT1, and HIF1A. In cultured A549 cells, treatment with 2.5%, 5%, and 10% Fuzheng Huaji Decoction-medicated serum significantly inhibited cell proliferation, promoted cell apoptosis, and downregulated the expression levels of HIF1A, p-AKT (Thr308), and TP53 proteins. CONCLUSIONS Fuzheng Huaji Decoction inhibits proliferation of NSCLC cells possibly by downregulating the expressions of HIF1A, p-AKT (Thr308), and TP53.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Lung Neoplasms/metabolism* ; A549 Cells ; Proto-Oncogene Proteins c-akt/metabolism* ; Protein Interaction Maps ; Signal Transduction/drug effects* ; Cell Line, Tumor

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.