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 explore the value of combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),neuron specific enolase(NSE)and S-100 calcium binding protein β(S-100β)in the diagnosis and prognosis evaluation of acute cerebral infarction(ACI)in patients with carbon monoxide poisoning(CMP).Methods A total of 102 patients with CMP complicated with ACI admitted to the hospital from Jan-uary 2020 to November 2021 were selected as the study group,meanwhile,102 patients with simple CMP were enrolled as the control group.Patients in the study group were followed up for 6 months after discharge,ac-cording to the follow-up results,they were grouped into good prognosis group(60 cases)and poor prognosis group(42 cases).The serum levels of Lp-PLA2,NSE and S-100β were detected by enzyme-linked immunosor-bent assay(ELISA).The receiver operating characteristic(ROC)curve was applied to analyze the value of the combination of serum Lp-PLA2,NSE and S-100β in the early diagnosis and prognosis evaluation of patients with CMP and ACI.Results Compared with the control group,the levels of Lp-PLA2,NSE and S-100β in the study group were obviously higher(P<0.05).The ROC curve analysis results showed that the area under the curve(AUC)of the combined detection of serum Lp-PLA2、NSE、S-100β for the diagnosis of CMP complicat-ed with ACI was greater than the AUC of single detection of each indicator(P<0.001).Compared with the good prognosis group,the levels of Lp-PLA2,NSE and S-100β in the poor prognosis group were obviously higher(P<0.05).The results of ROC curve analysis showed that the AUC of the combined detection of ser-um Lp-PLA2、NSE、S-100β for the prognosis of patients with CMP complicated with ACI was greater than the AUC of single detection of each indicator(P<0.05).Conclusion The expression of Lp-PLA2,NSE and S-100β in serum of patients with CMP complicated with ACI is high,and the combined detection of the three has certain value in the diagnosis and prognosis evaluation for patients with CMP complicated with ACI.

OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

COVID-19 associated Guillain-Barré syndrome (GBS) caused by peripheral nerve damage after SARS-CoV-2 infection is one of the most common COVID-19 related nervous system inflammatory diseases, with high incidence of respiratory failure and mortality. Positive SARS-CoV-2 RNA in cerebrospinal fluid of COVID-19 associated GBS patients has been rarely reported. This paper reports 4 patients with COVID-19 associated GBS in China who developed neurological symptoms 4-15 days after fever and were confirmed SARS-CoV-2 infection. All patients presented with progressive weakness of both lower limbs, 3 patients with autonomic dysfunction such as defecation and urination disorders, and 1 patient with polycranial neuritis and Miller-Fisher syndrome such as bilateral facial palsy, dysphagia, diplopia and ataxia. Nerve conduction velocity and F wave were abnormal in 3 patients, and motor conduction pathway was abnormal in 1 patient. Anti-ganglioside antibodies were tested in 3 patients, and GD1a-IgG was positive in 1 patient. All 4 patients underwent metagenomic next-generation sequencing examination in blood and cerebrospinal fluid. SARS-CoV-2 RNA was positive in blood and cerebrospinal fluid of 3 patients, and SARS-CoV-2 RNA was positive in cerebrospinal fluid of 1 patient.

Objective To explore the prognostic value of serum neutrophils/lymphocytes(NLR)for first-line treatment of patients with advanced gastric cancer using programmed cell death receptor 1(PD-1)inhibitors.Methods A total of 168 patients with advanced gastric cancer who were treated with immunotherapy combined with chemotherapy in the Fourth Hospital of Qinhuangdao from January 2018 to January 2021 were selected as study subjects,and the follow-up period was terminated at January 2023.The patients'data were collected,hematological and tumor markers before the combined treatment were analyzed,and the optimal cut-off value of NLR was calculated using X-tile software.The effect of NLR expression on the survival rate of patients with advanced gastric cancer was analysed by the Kaplan-Meier survival curve.Receiver operating curve(ROC)was used to analyze the predictive value of NLR in patients with advanced gastric cancer.The related factors affecting the disease progression of patients with advanced gastric cancer were screened combined with Cox proportional risk model.Results Among 168 patients,the optimal cut-off value of serum NLR before treatment was 2.41.Patients were divided into high NLR group(NLR＞2.41,n=93)and low NLR group(NLR＜2.41,n=75).NLR was related to tumor differentiation,distant metastasis,composite positive scores of PD-L1,carcinoembryonic antigen and cancer antigen 125(P＜0.05);the effective rate in the low NLR group was significantly higher than that in the high NLR group(P＜0.05);the median progression free survival(PFS)and the overall survival(OS)of patients in the low NLR group were both longer than those in the high NLR group(PFS:P=0.006;OS:P=0.023);ROC analysis showed that the area under the curve of NLR for the prognosis of advanced gastric cancer patients was 0.740,sensitivity was 81.50％,and specificity was 69.70％;in multivariate analysis,except initial NLR value,tumor differentiation degree and distant metastasis were also independent predictors of poor prognosis in patients with advanced gastric cancer(P＜0.05).Conclusion Among patients with advanced gastric cancer who received first-line immunotherapy combined with chemotherapy,pretreatment NLR is correlated with efficacy and PFS/OS,and has high value in predicting the prognosis of immunotherapy for advanced gastric cancer.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

With the increasing number of cancer patients in China, the lack of hospice communication between medical staff and cancer patients can easily cause doctor-patient conflicts. Facing the special group of cancer patients, by introducing the concept of hospice communication and comparing the current situation of hospice communication of cancer patients at home and abroad, this paper found the shortcomings of hospice communication between medical staff and cancer patients in China. This paper aimed to analyze the influencing factors of cancer patients’ hospice communication from three aspects of medical staff, cancer patients and social and cultural background, summarized the assessment tools and matters needing attention related to hospice communication, so as to provide reference for domestic medical staff to develop relevant tools for hospice communication with cancer patients, and help medical staff to implement more effective hospice communication with cancer patients in the context of tranquil care. It is also conducive to help patients open the topic of death from the perspective of doctors and build an open hospice communication environment that is more in line with national conditions of China.

Objective To observe the effects of Yiqi Jiedu Compound on TCM syndrome score and immune regulation of Th17/Treg cells in peripheral blood of patients with myasthenia gravis.Methods 63 patients with myasthenia gravis were randomly divided into the control group(n=31)and the treatment group(n=32).The control group was given the basic treatment of pyridostigmine bromide and glucocorticoid and so on,and the treatment group was given Yiqi Jiedu Compound based on the control group.The two groups were treated for 12 weeks.Clinical efficacy was observed,TCM syndrome scores were statistically analyzed,and the expression levels were detected,which Th17/Treg cells,Foxp3/RORγ t gene and IL-6 and IL-17 cytokines in peripheral blood of patients in both groups before and after treatment.Results After 12 weeks of treatment,compared with the control group,the TCM syndrome score of patients in the treatment group was significantly decreased(P<0.05),and the expression of Foxp3 and Treg genes in peripheral blood was promoted(P<0.05),and the expression of Th17 and Treg cells and IL-6 and IL-17 cytokines in peripheral blood was decreased(P<0.05).Conclusion Yiqi Jiedu Compound may regulate the immune balance of Th17/Treg cells by affecting the differentiation of Th17 and Treg cells in peripheral blood and the expression levels of transcription factors RORγ t and Foxp3 genes and related cytokines,thus achieving the effect of myasthenia gravis treatment.

Clinical comprehensive evaluation of drugs is an important technical tool for drug supply assurance decision - making，which requires evaluation subjects to use multiple evaluation methods and tools to carry out a comprehensive evaluation of multi-dimensional and multi -level evidence for drugs . Multi-criteria decision analysis （MCDA）is an important method for clinical comprehensive evaluation of drugs ，including weight assignment and comprehensive evaluation . Step-wise weight assessment ratio analysis（SWARA）is a weighting method for MCDA ，which can determine indicator weight concisely and accurately compared to other methods . This paper introduces the method of SWARA ，and systematically reviews the application of SWARA in the comprehensive clinical evaluation of drugs . Currently，the SWARA method is used in various research areas . Within the field of pharmaceuticals，researchers use the SWARA method to build MCDA models and calculate specific weight values for each drug evaluation criterion by consulting a team of experts . The advantage of SWARA is that it provides a brand -new way of assigning the weight of drug evaluation criterion by consulting experts ’opinions or judgments according to corresponding steps to solve the MCDA problem in the medical field ；however，it has certain subjectivity and uncertainty in solving complex decision -making problems，and there may also be problems such as insufficient screening of evaluation criterion and incomplete coverage of topics ， which should be paid attention to in application .