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 The prediction of the fatality rate of COVID-19 pandemic is of great significance for in-depth understanding of the severity of the new coronavirus,rational allocation of medical resources,and targeted epidemic prevention strategies.Methods This study divides the development of the epidemic into four periods based on the dominant strain of the new coronavirus variant.Six countries including the United States,India,Brazil,Mexico,Peru,China,and the global average case fatality rate were selected as study subjects.Six models including the Grey Model,Exponential Smoothing Model,ARIMA,SVM,Prophet and LSTM are used for fitting and forecasting,the advantages,disadvantages and applicability of each model are discussed,and the model with the best effect is selected to forecast the fatality rate in the world and key countries.Results Model comparison shows that various models have their own advantages and disadvantages.It is predicted that the growth rate of the cumulative number of confirmed cases and cumulative deaths in most countries has slowed down,and the development trend has gradually stabilized.Conclusion The study suggests that traditional time series model is suitable for the prediction of stable development trend and limited samples,and the machine learning model is more suitable for fluctuating data,which can be used for large sample predictions.Depending on the features of these models,application can be extended to other fields.

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 investigate the risk factors for inflammatory complications after radical gastrectomy for gastric cancer and construct a nomogram model for risk prediction. Methods The clinical data of 402 patients with primary gastric cancer who underwent radical gastrectomy were retrospectively analyzed. All patients underwent preoperative Nutritional Risk Screening 2002 (NRS2002) score, Patient-Generated Subjective Global Assessment (PG-SGA) grading, Lumbar 3 Skeletal Muscle Index (L3-SMI) assessment, and serological index testing. Univariate analysis was used to screen for influencing factors of postoperative inflammatory complications of gastric cancer, and multivariate Logistic regression analysis was conducted to determine independent risk factors. A nomogram model for predicting postoperative inflammatory complications after radical gastrectomy was constructed based on the results of multivariate Logistic regression analysis, and the predictive performance of the model was evaluated using the receiver operating characteristic (ROC) curve and calibration curve. Results Univariate analysis revealed that age, TNM stage, body mass index, preoperative hemoglobin, preoperative albumin, preoperative globulin, NRS2002 score, PG-SGA grade, and L3-SMI were influencing factors of postoperative inflammatory complications in patients undergoing radical gastrectomy (P < 0.05). Multivariate Logistic regression analysis showed that age ≤60 years, preoperative hemoglobin ≤130 g/L(male) or ≤115 g/L(female), TNM staging of Ⅳ stage, NRS2002 score≥3, and L3-SMI ≤52.4 cm²/m²(male) or ≤38.5 cm²/m²(female) were independent risk factors for postoperative inflammatory complications in gastric cancer patients (P < 0.05). A nomogram model was constructed based on age, preoperative hemoglobin, TNM stage, and NRS2002 score. The ROC curve showed that the area under the curve of the nomogram model was 0.930, with sensitivity and specificity of 93.2% and 89.2%, respectively. The calibration curve demonstrated good consistency between the predicted probability of inflammatory complications and the actual outcomes. Conclusion Age≤60 years, low preoperative hemoglobin, TNM staging of Ⅳ stage, NRS2002 score ≥3, and low L3-SMI are independent risk factors for postoperative inflammatory complications in gastric cancer patients. The nomogram model constructed based on age, preoperative hemoglobin, TNM stage, and NRS2002 score can accurately predict postoperative inflammatory complications after gastrectomy for gastric cancer.

Background::At present, a large number of chronic obstructive pulmonary disease (COPD) patients are undiagnosed in China. Thus, this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD.Methods::The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China. We stepwisely selected the predictors using logistic regression model. Then we tested the model validity through P-P graph, area under the receiver operating characteristic curve (AUROC), ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China.Results::The final prediction model involved 14 independent variables, including age, sex, location (urban/rural), region, educational background, smoking status, smoking amount (pack-years), years of exposure to air pollution by cooking fuel, family history of COPD, history of tuberculosis, body mass index, shortness of breath, sputum and wheeze. The model showed an area under curve (AUC) of 0.72 (95% confidence interval [CI]: 0.72-0.73) for detecting undiagnosed COPD patients, with the cutoff of predicted probability of COPD=0.22, presenting a sensitivity of 70.13% and a specificity of 62.25%. The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68 (95% CI: 0.66-0.69). Moreover, the ten-fold cross validation reported an AUC of 0.72 (95% CI: 0.71-0.73), and the external validation presented an AUC of 0.69 (95% CI: 0.68-0.71).Conclusion::This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.

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.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

ObjectiveTo compare the efficacy and safety of acupuncture combined with auricular acupoints patches and nicotine transdermal patch in treating moderate to severe nicotine dependence. MethodsIn a rando-mized controlled trial， 64 quit smoking voluntary subjects with moderate to severe nicotine dependence were randomly divided at a ratio of 1∶1 into a treatment group and a control group， with 32 cases in each group. The treatment group was given acupuncture combined with auricular acupoints patches， twice weekly， four weeks as a course for two courses. The control group was given nicotine transdermal patch， one patch per day for 24 hours， 8 weeks. The cure rate was assessed after treatment and at follow-up （the 16th week after treatment）.The daily smoking volume， exhaled carbon monoxide （CO） value， Nicotine Dependence Scale （FTND）， Minnesota Nicotine Withdrawal Symptoms Scale （MNWS）， and Pittsburgh Sleepiness Index Inventory （PSQI） were evaluated before and after treatment and at follow-up， and adverse effects were recorded. ResultsIn terms of the cure rate， there were both six cured cases （20%） after treatment and at follow-up in the treatment group， while in the control group， seven （23.3%） and five （16.7%） patients were cured after treatment and at follow-up， respectively， with no statistically significant differences between the two groups both after treatment and at follow-up （P＞0.05）. The daily smoking volume and exhaled CO value significantly decreased after treatment and at follow-up in both groups （P＜0.05）， but were not significantly different between the groups after treatment and at follow-up （P＞0.05）. After treatment and at follow-up， FTND， MNWS， and PSQI scores were significantly reduced in both groups compared with those before treatment （P＜0.05）. There was no statistically significant difference in the FTND scale scores between the two groups after treatment and at follow-up （P＞0.05）， while the MNWS and PSQI scale scores were lower in the treatment group than in the control group （P＜0.05）. ConclusionAcupuncture combined with auricular acupoint patches for moderate to severe nicotine dependence has comparable effect with the first-line drug nicotine patch in terms of increasing the cure rate and decreasing the degree of nicotine dependence， and is superior to nicotine patch in terms of relieving withdrawal symptoms and improving sleep， with stable long-term effect.

Objective:To investigate influences of ginsenoside Rg1 regulating miR-144-3p on neuroinflammation and blood-brain barrier damage in rats with experimental cerebral hemorrhage,and its regulation on formyl peptide receptor 2(FPR2)/p38 path-way.Methods:Ninety SD rats were randomly divided into control group,cerebral hemorrhage group,ginsenoside Rg1 low-dose group(10 mg/kg),ginsenoside Rg1 high-dose group(40 mg/kg),ginsenoside Rg1 high-dose+ago-miR-144-3p group(40 mg/kg ginseno-side Rg1+ago-miR-144-3p),with 18 mice in each group.Except for control group,experimental intracerebral hemorrhage rat model was constructed by injecting collagenase Ⅱ into right caudate nucleus,and then each group was given intraperitoneal administration and intracerebral injection as required.Neurological damage in rats was scored;rat brain water content was determined by dry-wet spe-cific gravity method;levels of TNF-α,IL-6 and IL-1β in rat brain tissues homogenate were determined by ELISA;ultrastructure around cerebral edema was observed by electron microscope;permeability of blood-brain barrier in rats was determined by Evans blue(EB)method;expressions of miR-144-3p/FPR2/p38 pathway were determined by qRT-PCR and Western blot.Results:Compared with control group,blood-brain barrier damage was aggravated in cerebral hemorrhage group,neurological function damage score,brain water content,miR-144-3p,TNF-α,IL-6,IL-1β,p38 mRNA,p-p38/p38 expressions in brain homogenate were increased(P<0.05),FPR2 mRNA and protein expressions were decreased(P<0.05);compared with cerebral hemorrhage group,blood-brain barrier damage was reduced in ginsenoside Rg1 low-dose group and ginsenoside Rg1 high-dose group,neurological function damage score,brain water content,miR-144-3p,TNF-α,IL-6,IL-1β,p38 mRNA,p-p38/p38 expressions in brain homogenate were decreased(P<0.05),FPR2 mRNA and protein expressions were increased(P<0.05);ago-miR-144-3p was able to reverse protective effects of gin-senoside Rg1 on blood-brain barrier and neuroinflammation in rats(P<0.05).Conclusion:Ginsenoside Rg1 may inhibit blood-brain barrier damage and neuroinflammation in rats by regulating miR-144-3p/FPR2/p38 axis.

Objective To investigate the predictive factors for acute kidney injury (AKI) in patients with acute liver failure (ALF), and to establish a new predictive model. Methods Clinical data were collected from 253 patients who were diagnosed with ALF in The First Affiliated Hospital of Zhengzhou University from January 2015 to October 2021, and according to the presence or absence of AKI, these patients were divided into non-AKI group with 170 patients and AKI group with 83 patients. Related clinical data and laboratory markers were collected. Non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between two groups; categorical data were expressed as cases (%), and the chi-square test was used for comparison between two groups. The binary logistic regression analysis was used to investigate the risk factors for AKI in ALF patients, and the receiver operating characteristic (ROC) curve was used to evaluate the performance of the indices obtained in predicting AKI in ALF patients. Results Compared with the non-AKI group, the AKI group had a significantly higher proportion of patients with hypertension, diabetes, hepatic encephalopathy, ascites, and pulmonary infection, significantly higher levels of white blood cell count (WBC), international normalized ratio (INR), C-reactive protein, procalcitonin (PCT), neutrophil-to-lymphocyte ratio, and Model for End-Stage Liver Disease (MELD) score, and significantly lower levels of platelet count, lymphocyte-to-monocyte ratio, and PNI (all P < 0.05). The multivariate logistic regression analysis showed that WBC (odds ratio [ OR ]=1.267, 95% confidence interval [ CI ]: 1.124-1.428, P < 0.001), INR ( OR =1.663, 95% CI : 1.205-2.293, P =0.002), PCT ( OR =1.416, 95% CI : 1.137-1.764, P =0.002), and MELD score ( OR =1.098, 95% CI : 1.029-1.172, P =0.005) were risk factors for the development of AKI in patients with ALF. The ROC curve analysis showed that the combination of WBC+INR+PCT+MELD had the largest area under the ROC curve (AUC) of 0.908 in predicting AKI in ALF patients, while WBC, INR, PCT, and MELD alone had an AUC of 0.776, 0.771, 0.746, and 0.780, respectively, in predicting AKI. Conclusion WBC, INR, PCT, and MELD score are independent influencing factors for AKI in patients with ALF, and the predictive model established based on these four indices has a relatively high predictive value.