Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

Objective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.

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

Objective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.

BackgroundThe prevalence of depressive disorder in adolescents is on the rise. There have been studies on the pairwise relations between dysfunctional attitude， negative automatic thoughts， positive coping style and depressive symptoms in the past. However， the impact of the intrinsic relations among dysfunctional attitude， negative automatic thoughts and positive coping style on depressive symptoms is still unclear. ObjectiveTo explore the influence of dysfunctional attitude on adolescent depressive symptoms and examine the action path of negative automatic thoughts and positive coping style on it， in order to provide references for intervention for adolescent patients with depressisve disorder. MethodsThis study involved 162 adolescent patients with depressive disorder， who met the diagnostic criteria for depressive episodes in the International Classification of Diseases， 10th edition （ICD-10） and received treatment in Taiyuan Psychiatric Hospital from October 1， 2022 to October 31， 2023. These patients were evaluated using Self-rating Depression Scale （SDS）， Dysfunction Attitude Scale （DAS）， Positive Coping Style Subscale in Simplified Coping Style Questionnaire（SCSQ） and Automatic Thoughts Questionnaire （ATQ）. Pearson correlation analysis was adopted to examine the correlation among scores of scales above. Model 6 in Process 3.4.1 was adopted to test the acting path of negative automatic thoughts and positive coping style between dysfunctional attitude and adolescent depression symptoms. ResultsA total of 148 adolescent patients with depressive disorder completed an effective questionnaire survey， with a response rate of 91.36%. The direct effect value of dysfunctional attitude on depressive symptoms was 0.423 and the effect size was 63.32%. Negative automatic thoughts and positive coping style affected as acting path between dysfunctional attitude and depressive symptoms， with effect values of 0.156 （accounting for 23.35% of the total effect） and 0.045 （accounting for 6.74% of the total effect） respectively. Meanwhile， negative automatic thoughts and positive coping style affected as a chain reaction pathway between dysfunctional attitude and depressive symptoms， with an effect value of 0.044， accounting for 6.59% of the total effect. ConclusionDysfunctional attitude can not only directly affect the depressive symptoms of adolescent patients with depressive disorder， but also affect the depressive symptoms of adolescent patients with depressive disorder through the independent path or chain path of negative automatic thoughts and positive coping style.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective:To construct a core competence evaluation index system for Anesthesia Intensive Care Unit (AICU) nurses, and to provide reference for the career orientation, training and management of AICU nurses.Methods:The first draft of the core competence evaluation index system of AICU nurses was developed by literature evaluation, semi-structured interview and group discussion. Using the purposive sampling method, 26 experts were selected for 2 rounds of expert consultation from August to September 2021 to determine the evaluation index system of core competence of AICU nurses, and the weights of indicators at all levels were determined by analytic hierarchy process.Results:The effective recovery rates of the 2 rounds of expert letter consultation questionnaire were respectively 92.31% (24/26) and 91.67% (22/24) , the expert authority coefficients were respectively 0.93 and 0.93, and the Kendall's harmony coefficients were respectively 0.28 and 0.19 (all P<0.01) . The final evaluation index system of AICU nurses' core competence included 4 first-level indicators (theoretical knowledge, nursing practice, comprehensive ability, personal characteristics) , 14 second-level indicators and 52 third-level indicators. Conclusions:The constructed evaluation index system of core competence of AICU nurses is scientific and reliable, which can provide a reference for the career orientation, training and management of AICU nurses.

Objective:To survey the first-aid ability of general practitioners (GPs) and the emergency service capacity of primary health institutions in southern Zhejiang province.Methods:The questionnaire of first-aid ability of GPs in primary care institution was developed on the basis of the Delphi method during August to October 2018. The questionnaire was employed in a survey on the first-aid ability among 480 GPs from 169 community health service centers of three regions in southern Zhejiang province. The survey covered basic information and first-aid skills and emergency response ability of GPs, and the emergency facilities of primary health institutions.Results:A total of 480 questionnaires were distributed and 447 were retrieved with an recovery rate of 93. 1%(447/480). Among the 447 responders, 55.9% (250/447) were males, 70.9% (317/447) had bachelor′s degree or above, and 60.2% (269/447) had middle and senior professional titles. There were 99.6% (445/447), 86.6% (387/447), 76.1% (340/447) and 69.8% (312/447) responders considered cardiopulmonary resuscitation(CPR), electrical defibrillation, respiratory balloon and endotracheal intubation as important first-aid skills, and corresponding mastery rates were 84.3% (377/447), 32.0% (143/447), 55.2% (247/447) and 12.9% (58/447), respectively. The 92.4% (413/447) responders thought that the rescue ability of common emergency and critical illness was the most important, while only 32.4% (145/447) responders mastered it. Least responders [41.4%(185/447)] thought that ability of using bedside ultrasound was important, and the corresponding mastery rate was only 3.8%(17/447); 77.4%(346/447) of general practitioners believed that CPR machines was important, while the available rate of CPR machines in primary health care institutions was only 16.0%(27/169).Conclusion:The GPs in southern Zhejiang province have a good grasp of cardiopulmonary resuscitation skills, but have a low mastery rate of first-aid skills such as electrical defibrillation, tracheal intubation, and emergency rescue capabilities, which are quite different from their perceived importance evaluation.