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.

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

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 (d18:1/24:0), 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 phosphotransferase 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.

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 current self-compassion levels in hematologic malignant tumor patients and analyze the influencing factors, providing a basis for clinical interventions.Methods:A convenience sampling method was used to select 120 patients with hematologic malignant tumors treated at the First Affiliated Hospital of Wenzhou Medical University from January to December 2022. Clinical data, self-compassion levels, social support, and adult attachment status were assessed using general data questionnaires, the Self-Compassion Scale (SCS) , the Perceived Social Support Scale (PSSS) , and the Experiences in Close Relationship Scale-Short Form (ECR-S) . Pearson correlation analysis was performed to analyze the correlation between SCS scores and PSSS, ECR-S scores. Multiple linear regression analysis was conducted to explore the influencing factors of self-compassion levels.Results:A total of 120 questionnaires were distributed, and 114 valid questionnaires were returned, resulting in an effective response rate of 95.00%. The average SCS score of hematologic malignant tumor patients was (80.54±5.80) . Univariate analysis showed that self-compassion levels differed significantly among patients of different ages, education levels, per capita family monthly income, disease duration, and the first diagnosis or not of hematologic malignant tumors ( P<0.01) . Pearson correlation analysis revealed a positive correlation between SCS scores and PSSS scores ( r=0.659, P<0.001) , and a negative correlation with the attachment anxiety and avoidance dimensions of the ECR-S ( r=-0.152, -0.588, P<0.001) . Multiple linear regression analysis showed that education level, the first diagnosis or not, PSSS score, ECR-S attachment anxiety dimension, and ECR-S attachment avoidance dimension scores entered the regression equation. Conclusions:The influencing factors of self-compassion levels in hematologic malignant tumor patients include education level, the first diagnosis or not, social support level, and adult attachment status. Healthcare providers should strengthen psychological support for patients with low education, disease recurrence/treatment failure, and insecure attachment types, while also improving patients' social support levels to enhance their self-compassion status.

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.

Objective:To explore the causes of lack of compliance with life care in hematopoietic stem cell transplantation recipients while living alone in the transplant warehouse, and to provide a basis for developing targeted promotion measures.Methods:Using purposive sampling method, from June to December 2023, on-site observations were conducted on the voluntary completion of life care by hematopoietic stem cell transplant patients (with a 30 day observation period) admitted to the Blood Transplantation Center of the First Affiliated Hospital of Wenzhou Medical University. The compliance was calculated after the observation period. Patients with a compliance of less than 80% were selected, and semi-structured interviews were conducted with 17 of them after informed consent. The Colaizzi 7-step analysis method was applied to organize and analyze the interview data.Results:Three core themes on lack of compliance were distilled, namely physical factors impeding compliance (somatic specific symptoms leading to distraction, somatic non-specific symptoms leading to activity intolerance), psychological factors impeding compliance (negative emotions, comfort zone dilemmas, regression phenomena, constraints of personality psychological traits), and cognitive factors impeding compliance (subjective cognitive unperceived benefit, poor modeling resulting in cognitive biases, limited perceived attention) .Conclusions:The behavioral causes of lack of compliance with life care of hematopoietic stem cell transplant patients while living alone in the transplant warehouse are due to multiple factors of the body and mind, among which psychologically mediated mechanisms are key to compliance. Healthcare professionals should pay attention to both the physiological and psychological needs of patients, actively alleviate physical symptoms, appropriately provide psychological care to remove psychological barriers, help them actively seek family and social support, and promote cognitive improvement, thereby improving compliance.

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.