OBJECTIVE To evaluate the cost-effectiveness of fluzoparib monotherapy versus combination with apatinib as second-line or later-line treatment for patients with germline BRCA1 / 2 -mutated human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， from the perspective of the Chinese healthcare system. METHODS Based on the FABULOUS trial， a partitioned survival model was developed to simulate disease progression， with a cycle length of 21 days and a time horizon of 10 years. A discount rate of 4.5% per annum was applied. Model outputs included total costs and quality-adjusted life years （QALYs）. Cost-utility analysis was conducted by comparing the incremental cost-effectiveness ratio （ICER） between the two regimens against a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product in 2025 （199 330 yuan/QALY）. Robustness of the base-case results was tested through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analyses. RESULTS For patients with germline BRCA1/2 -mutated HER2－ metastatic breast cancer， fluzoparib combination with apatinib provided greater health benefits （1.91 QALYs vs. 1.69 QALYs） and incurred lower total costs （1 634 119.3 yuan vs. 1 855 264.2 yuan） compared with fluzoparib monotherapy， thus representing a dominant strategy. One-way sensitivity and probabilistic sensitivity analyses confirmed the robustness of the base-case findings. Scenario analyses showed that the conclusion remained robust when the time horizon was shortened to 5 years or when the discount rate was changed to 3%； however， the results reversed when the extrapolation distribution model was altered. CONCLUSIONS Under the current WTP threshold， compared with fluzoparib monotherapy， the combination of fluzoparib and apatinib is more cost-effective as a second-line or later-line treatment for Chinese patients with germline BRCA1 / 2 -mutated HER2－ metastatic breast cancer.

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 characteristics of the cross-sectional area(CSA)of the vagus nerve in a healthy population in Qujing,Yunnan,and its correlation with demographic characteristics.Methods High-resolution nerve ultrasound examinations were conducted on the vagus nerve of 201 healthy volunteers from a hospital in Qujing,Yunnan from September 2022 to March 2023.The CSA was measured through transverse scans of the vagus nerve.The correlation of vagus nerve CSA with age,body mass index(BMI),and gender was assessed.Results The mean CSA of the bilateral VN were 1.9 mm2(right)and 1.3 mm2(left),respectively.The average CSA of the right vagus nerve was significantly greater than that of the left(P<0.001).In the high-age group(>50 years),the average CSA of the right vagus nerve was significantly higher than that of the low-age group(≤50 years)(P=0.0142).However,there was no statistically significant difference in the average CSA of the right vagus nerve between the BMI>24 kg/m2 group and the≤24 kg/m2 group(P=0.0852).The average CSA of the left vagus nerve showed no statistically significant differences across different age groups and BMI groups(P>0.05),but the average CSA of the bilateral vagus nerve in the male group was greater than that in the female group,with a statistically significant difference(P<0.05).Correlation analysis further confirmed a negative correlation between the average CSA of the right vagus nerve and age(r=-0.17,P=0.0139).Multiple linear regression models indicated that age(P=0.007)and gender(P=0.001)were independent influencing factors for the average CSA of the right vagus nerve.Conclusion In the healthy population of Qujing,Yunnan,the CSA of the right vagus nerve is significantly greater than that of the left,and males also exhibit a significantly greater CSA than females.With increasing age,the vagus nerve gradually becomes thinner.

Objective:To systematically evaluate the risk factors for dysphagia among community-dwelling older adults.Methods:A comprehensive literature search was conducted in databases, including China National Knowledge Infrastructure, Wanfang Data, VIP, PubMed, Medline, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Library, with the search ending on July 31, 2024. The quality of cross-sectional studies was assessed using the Agency for Healthcare Research and Quality (AHRQ) criteria, while cohort and case-control studies were evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using Stata 18.Results:A total of 26 studies were included. The prevalence of dysphagia in community-dwelling older adults ranged from 7.9% to 63.7%. The following were identified as the risk factors for dysphagia ( P<0.05) : advanced age [ OR=1.17, 95% CI (1.08, 1.28) ], history of coughing or choking [ OR=7.25, 95% CI (3.66, 14.33) ], poor oral health [ OR=1.99, 95% CI (1.63, 2.43) ], impaired tongue-lip motor function [ OR=3.41, 95% CI (1.48, 7.85) ], reduced tongue pressure [ OR=1.63, 95% CI (1.16, 2.32) ], chewing dysfunction [ OR=2.18, 95% CI (1.57, 3.04) ], medication use history [ OR=1.22, 95% CI (1.02, 1.47) ], malnutrition [ OR=1.92, 95% CI (1.04, 3.56) ], history of the comorbid disease [ OR=4.18, 95% CI (2.61, 6.71) ], history of stroke [ OR=3.27, 95% CI (1.69, 6.33) ], depression [ OR=3.18, 95% CI (2.18, 4.65) ], frailty [ OR=1.43, 95% CI (1.12, 1.82) ], and male gender [ OR=2.91, 95% CI (1.70, 4.96) ] . Conclusions:Medical staff should pay close attention to the above-mentioned risk factors and develop targeted prevention strategies to reduce the incidence of dysphagia in community-dwelling older adults.

Objective:To systematically evaluate the risk factors for dysphagia among community-dwelling older adults.Methods:A comprehensive literature search was conducted in databases, including China National Knowledge Infrastructure, Wanfang Data, VIP, PubMed, Medline, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Library, with the search ending on July 31, 2024. The quality of cross-sectional studies was assessed using the Agency for Healthcare Research and Quality (AHRQ) criteria, while cohort and case-control studies were evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using Stata 18.Results:A total of 26 studies were included. The prevalence of dysphagia in community-dwelling older adults ranged from 7.9% to 63.7%. The following were identified as the risk factors for dysphagia ( P<0.05) : advanced age [ OR=1.17, 95% CI (1.08, 1.28) ], history of coughing or choking [ OR=7.25, 95% CI (3.66, 14.33) ], poor oral health [ OR=1.99, 95% CI (1.63, 2.43) ], impaired tongue-lip motor function [ OR=3.41, 95% CI (1.48, 7.85) ], reduced tongue pressure [ OR=1.63, 95% CI (1.16, 2.32) ], chewing dysfunction [ OR=2.18, 95% CI (1.57, 3.04) ], medication use history [ OR=1.22, 95% CI (1.02, 1.47) ], malnutrition [ OR=1.92, 95% CI (1.04, 3.56) ], history of the comorbid disease [ OR=4.18, 95% CI (2.61, 6.71) ], history of stroke [ OR=3.27, 95% CI (1.69, 6.33) ], depression [ OR=3.18, 95% CI (2.18, 4.65) ], frailty [ OR=1.43, 95% CI (1.12, 1.82) ], and male gender [ OR=2.91, 95% CI (1.70, 4.96) ] . Conclusions:Medical staff should pay close attention to the above-mentioned risk factors and develop targeted prevention strategies to reduce the incidence of dysphagia in community-dwelling older adults.

To have better clinical understanding of Schimke immuno-osseous dysplasia(SIOD) through analyzing the clinical features, treatment, and prognosis of four patients with SIOD.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Objective To investigate the difference of matrix stiffness in different regions of tibial plateau in osteoarthritis (OA) and its effects on morphology of the cartilage and mitochondria. Methods The tibial plateau cartilage specimens of OA were obtained for nanoindentation test, transmission electron microscopy and histological analysis. The stiffness of cartilage matrix in different regions of OA tibial plateau was detected by nano-indentation. The morphology of cartilage mitochondria in different regions was observed by transmission electron microscopy, and the changes of mitochondrial plane area, shape and ridge volume density were quantitatively analyzed. Cartilage injury in different regions of OA tibial plateau was observed by histological staining. Results The cartilage of OA tibial plateau showed regional heterogeneity, and the cartilage and mitochondria on medial side of varus knee OA were more severe, and the matrix stiffness was higher. The OA scores were positively correlated with matrix stiffness. There was also a significant correlation between OA scores and mitochondrial morphology: the higher OA scores, the larger and rounder mitochondrial plane area, and the lower cristae volume density. Conclusions The differences of tibial plateau revealed the correlation between cartilage matrix stiffness, OA scores and mitochondrial morphological parameters. The increased cartilage matrix stiffness may be the main cause of chondrocyte mitochondrial injury, and further aggravate the progression of OA.

Objective:To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy.Methods:Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining.Results:Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction.Conclusion:Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

AIM To prepare the chrysin-phospholipid complex and to investigate its pharmacokinetic behaviors.METHODS Solvent evaporation method was used for preparing the complex.With preparation temperature,preparation time,chrysin concentration and drug-lipid ratio (chrysin-phospholipid) as influencing factors,together with recombination rate as an evaluation index,the preparation was optimized by orthogonal test.The obtained complex was analyzed by X-ray diffraction,differential scanning calorimetry,1H-NMR and 31P-NMR,whose solubility was examined as well.SD rats were intragastrically administered with chrysin and its phospholipid complex,respectively.The blood concentration of chrysin was detected by HPLC,after which the pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 40 ℃ for preparation temperature,2 h for preparation time,20 mg/mL for chrysin concentration,and 1 ∶ 2 for drug-lipid ratio,the recombination rate was close to 100％.Chrysin existed in an amorphous state in the phospholipid complex,which was a new phase rather than physical mixture (chrysin-phosphatidylcholine),and no new chemical bond was generated.Phospholipid complex could significantly increase chrysin's apparent solubility in water and n-octanol,the Cmax,AUC0-t and AUC0-∞ were also obviously increased as compared with raw medicine.CONCLUSION Phospholipid complex can improve both the solubility of chrysin and its oral bioavailability.