Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

OBJECTIVE To evaluate the cost-utility of switching to gemcitabine maintenance therapy for patients with unresectable malignant mesothelioma after first-line chemotherapy from the perspective of China’s healthcare system. METHODS A partitioned survival model was constructed based on data from the NVALT19 trial， with a cycle length of 21 days， a time horizon of 10 years， and a discount rate of 5%. Key model outputs included total costs， quality-adjusted life year （QALY）， incremental costs， and incremental cost-effectiveness ratio （ICER）， etc. Cost-utility analysis was conducted to evaluate the cost- effectiveness of gemcitabine maintenance therapy （gemcitabine group） plan versus best supportive care （supportive care group） plan for the patients with unresectable malignant mesothelioma after first-line chemotherapy. Sensitivity analyses were performed. RESULTS Compared with the supportive care group plan， the gemcitabine group plan had an ICER of 54 860.50 yuan/QALY， which was significantly lower than the willingness-to-pay （WTP） threshold （3 times China’s 2023 per capita gross domestic product， 268 077 yuan/QALY）， indicating that gemcitabine group plan was cost-effective. One-way sensitivity analysis revealed that end-of-life care costs and adverse event management costs in the gemcitabine group had the greatest impact on ICER. Probabilistic sensitivity analysis showed gemcitabine group plan was 100% cost-effective when WTP exceeded 270 000 yuan/QALY. CONCLUSIONS From the perspective of China’s healthcare system， switching to gemcitabine maintenance therapy after first-line chemotherapy is cost-effective for unresectable malignant mesothelioma.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

The pathogenesis and progression of myocardial fibrosis(MF)are modulated by diverse cytokines and signaling pathways.Studies in recent years have revealed an extremely close association between MF evolution and programmed cell death(PCD)modali-ties,including apoptosis,autophagy,pyroptosis,necrosis,ferroptosis,and cuproptosis.This article reviews the characteristics of MF and distinct PCD modalities,with particular emphasis on cutting-edge discoveries elucidating PCD in the field of MF,hoping to pro-vide a theoretical-level reference basis for the in-depth exploration and clinical intervention of MF.

Objective:To investigate the factors associated with chromosomal abnormalities in embryos of patients with recurrent miscarriage in the in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) population, and to establish a prediction model for chromosomal abnormalities. Methods:This was a retrospective case-control study, aborted tissues were collected from 349 patients who attended the Reproductive and Genetic Laboratory Sports New Town Ward of Dalian Women's and Children's Medical Center (Group) after IVF/ICSI from September 2019 to October 2024, and the samples were examined by copy number variation sequencing (CNV-seq) combined with short tandem repeat (STR) technology. According to the test results, the aborted tissues were divided into chromosome normal and chromosome abnormal groups. Factors affecting the occurrence of chromosomal abnormalities were analyzed by univariate analysis and multifactorial logistic regression.Results:1) By CNV-seq combined with STR method, a total of 252 cases (72.21%, 252/349) of chromosomal abnormalities were detected, while 97 cases had normal chromosomes. 2) The results of univariate analysis showed that the differences in female age, female body mass index (BMI), gestational week, number of miscarriages, progesterone level after 14 d post-transplantation, ovarian reserve function, male age, and male BMI were statistically significant between the chromosome normal group and the chromosome abnormal group (all P<0.05). 3) The results of the multifactorial logistic regression model showed that female age ( OR=1.261, 95% CI: 1.137-1.398, P<0.001), female BMI ( OR=1.121, 95% CI: 1.038-1.227, P=0.004), gestational week ( OR=1.406, 95% CI: 1.155-1.711, P=0.001), progesterone level 14 d after transplantation ( OR=1.016, 95% CI: 1.000-1.031, P=0.043), and BMI of the male partner ( OR=1.132, 95% CI: 1.050-1.220, P=0.001) were the independent risk factors of chromosomal abnormalities. 4) There were statistically significant differences in female age, female BMI, gestational week, progesterone level 14 d after transplantation, and male BMI between patients with normal chromosomes and those with trisomy chromosomes in aborted tissues (all P<0.05).Advanced female age was correlated with the occurrence of trisomy 22 ( P<0.05), and there was a correlation between advanced female age and increased male BMI and the occurrence of trisomy 16 (all P<0.05). Conclusion:The increase in maternal age, BMI, gestational age, progesterone levels 14 d after transplantation, and male BMI can all lead to an increase in the rate of chromosomal abnormalities and an increase in the incidence of trisomy. The advanced age of the female, can lead to the occurrence of trisomy 22. The age of the female and the BMI of the male are positively correlated with the abnormality rate of trisomy 16.

Objective:To investigate the factors associated with chromosomal abnormalities in embryos of patients with recurrent miscarriage in the in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) population, and to establish a prediction model for chromosomal abnormalities. Methods:This was a retrospective case-control study, aborted tissues were collected from 349 patients who attended the Reproductive and Genetic Laboratory Sports New Town Ward of Dalian Women's and Children's Medical Center (Group) after IVF/ICSI from September 2019 to October 2024, and the samples were examined by copy number variation sequencing (CNV-seq) combined with short tandem repeat (STR) technology. According to the test results, the aborted tissues were divided into chromosome normal and chromosome abnormal groups. Factors affecting the occurrence of chromosomal abnormalities were analyzed by univariate analysis and multifactorial logistic regression.Results:1) By CNV-seq combined with STR method, a total of 252 cases (72.21%, 252/349) of chromosomal abnormalities were detected, while 97 cases had normal chromosomes. 2) The results of univariate analysis showed that the differences in female age, female body mass index (BMI), gestational week, number of miscarriages, progesterone level after 14 d post-transplantation, ovarian reserve function, male age, and male BMI were statistically significant between the chromosome normal group and the chromosome abnormal group (all P<0.05). 3) The results of the multifactorial logistic regression model showed that female age ( OR=1.261, 95% CI: 1.137-1.398, P<0.001), female BMI ( OR=1.121, 95% CI: 1.038-1.227, P=0.004), gestational week ( OR=1.406, 95% CI: 1.155-1.711, P=0.001), progesterone level 14 d after transplantation ( OR=1.016, 95% CI: 1.000-1.031, P=0.043), and BMI of the male partner ( OR=1.132, 95% CI: 1.050-1.220, P=0.001) were the independent risk factors of chromosomal abnormalities. 4) There were statistically significant differences in female age, female BMI, gestational week, progesterone level 14 d after transplantation, and male BMI between patients with normal chromosomes and those with trisomy chromosomes in aborted tissues (all P<0.05).Advanced female age was correlated with the occurrence of trisomy 22 ( P<0.05), and there was a correlation between advanced female age and increased male BMI and the occurrence of trisomy 16 (all P<0.05). Conclusion:The increase in maternal age, BMI, gestational age, progesterone levels 14 d after transplantation, and male BMI can all lead to an increase in the rate of chromosomal abnormalities and an increase in the incidence of trisomy. The advanced age of the female, can lead to the occurrence of trisomy 22. The age of the female and the BMI of the male are positively correlated with the abnormality rate of trisomy 16.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Pharmacists are important members of the multidisciplinary team of anti-tumor therapy. With the transformation of pharmacists, the content of pharmaceutical care provided by oncology pharmacists continues to extend. Expanded services such as clinical comprehensive evaluation of anti-tumor drugs and management of off-label drug use are an important development trend of oncology pharmacy. The column named “Oncology Pharmacy Management and Services” is introduced, which discussed in depth from the two parts of “frontier progress of anti-tumor drugs” and “comprehensive clinical evaluation of anti-tumor drugs”, aiming to provide new ideas for the exploration of oncology pharmaceutical services, so as to further accelerate the transformation of oncology pharmaceutical care and promote the high-quality development of oncology pharmacy.

Third space fluid(TSF) is a common complication of advanced malignancies, including malignant pleural effusion, malignant ascites, intracranial effusion, and pelvic effusion, etc. The pharmacokinetics(PK) of anti-tumor drugs in vivo are influenced by various factors, and TSF is one of the potential factors that contributes to PK variations, which may consequently affect the efficacy and safety of anti-tumor drugs. This paper aimed to comprehensively investigate PK studies related to anti-tumor drugs in patients with malignant tumors accompanied by TSF. The paper summarized the PK characteristics of common cytotoxic drugs, small molecule targeted drugs, and monoclonal antibodies in both blood and TSF.