OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of serplulimab as a first-line treatment of small- cell lung cancer （SCLC）， and provide an evidence-based basis for drug selection in hospitals. METHODS Rapid health technology assessment was adopted； PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and official websites of domestic and international health technology assessment agencies were systematically searched from the inception to Oct. 2024. Two reviewers independently screened the literature， assessed the quality of included studies and carried out the qualitative analysis according to the inclusion and exclusion criteria. RESULTS A total of 13 systematic reviews/meta-analyses and 9 economic studies were included， and the literature quality was generally good. In terms of effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy significantly improved progression-free survival， overall survival， and objective response rate in patients with SCLC. In terms of safety， serplulimab combined with chemotherapy showed no significant difference in the incidence of ≥3 grade adverse events compared with chemotherapy alone in the treatment of SCLC， indicating a good safety profile； compared with combination therapies involving other immunosuppressive agents， the incidence rate of adverse events was also lower. In terms of cost-effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy is not cost- effective， which may be related to the high price of serplulimab. CONCLUSIONS Serplulimab is effective and safe in the treatment of SCLC， but has no obvious advantage in terms of cost-effectiveness.

OBJECTIVE To evaluate the cost-utiliby of capivasertib combined with fulvestrant for the second-line treatment of hormone receptor-positive/human epidermal growth factor receptor-2-negative （HR+/HER2－） advanced breast cancer from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed using clinical data from the CAPItello-291 trial. Costs and quality-adjusted life years （QALYs） were used as the output indicators of the model， and the incremental cost-effectiveness ratio （ICER） was used as the evaluation indicator of the model. Using three times the per capita gross domestic product （GDP） of China in 2024 as the willingness-to-pay threshold （WTP）， this study analyzed the cost-utility of capivasertib combined with fulvestrant versus fulvestrant monotherapy in the treatment of HR+/HER2－ advanced breast cancer， and conducted sensitivity analysis and scenario analysis under conditions where the price of capivasertib was reduced by 50%， 60%， 70% and 95%， respectively. RESULTS The results of the basic analysis showed that compared with the fulvestrant monotherapy regimen， the ICER of capivasertib combined with fulvestrant was 843 038.46 yuan/QALY， which was higher than the WTP（287 247 yuan/QALY）. The one-way sensitivity analysis revealed that the top three factors with the most substantial influence on ICER were the utility value in the progression disease state， the price of capivasertib， and the utility value inthe progression free survival state. Probabilistic sensitivity analysis demonstrated the robustness of the basic analysis results. Scenario analysis revealed that even if the price of capivasertib were reduced by 95%， capivasertib combined with fulvestrant did not exhibit cost-effectiveness at the current WTP. CONCLUSION At a WTP of three times China’s GDP per capita in 2024， compared to fulvestrant monotherapy， capivasertib combined with fulvestrant as the second-line treatment for HR+/ HER2－ advanced breast cancer is not cost-effective.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Objective:To construct a nomogram model for predicting stress urinary incontinence (SUI) in young and middle-aged women.Methods:Using a sampling survey method, 1 000 questionnaires were distributed to young and middle-aged women in 2 streets of Urumqi community from May 2021 to October 2023 to investigate their basic situation, lifestyle habits and gynecological related information. The International Urinary Incontinence Advisory Committee urinary incontinence questionnaire was used to diagnose SUI, and the patients were divided into SUI group and control group based on the results. Seven hundred and eighty-six questionnaires were collected. The survey results of the two groups were analyzed, and a nomogram model for predicting the occurrence of SUI in young and middle-aged women was constructed and validated.Results:Among the 786 young and middle-aged women, there were 147 cases in the SUI group and 639 cases in the control group. The age, body mass index (BMI), and the incidences of diabetes, chronic constipation, delivery history, macrosomia delivery history, pelvic floor dysfunction in SUI group were significantly higher than those in control group: (44.51 ± 8.20) years vs. (38.60 ± 12.35) years, (27.31 ± 4.53) kg/m 2 vs. (24.28 ± 4.38) kg/m 2, 13.61% (20/147) vs. 3.44% (22/639), 19.05% (28/147) vs. 5.01% (32/639), 90.48% (133/147) vs. 75.90% (485/639), 17.01% (25/147) vs. 3.44% (22/639) and 11.56% (17/147) vs. 3.29% (21/639), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that age>44 years, BMI≥30 kg/m 2, diabetes, chronic constipation, delivery history, macrosomia delivery history and pelvic floor dysfunction were independent risk factors for SUI in young and middle-aged women ( RR = 1.511, 2.543, 4.636, 4.293, 2.526, 6.220 and 5.834; 95% CI 1.007 to 2.268, 1.661 to 3.894, 2.281 to 9.422, 2.339 to 7.881, 1.374 to 4.643, 3.205 to 12.071 and 2.641 to 12.888; P<0.05 or <0.01). The age, BMI, diabetes, chronic constipation, delivery history, macrosomia delivery history and pelvic floor dysfunction were used as predictors to construct a nomogram model for predicting the SUI in young and middle-aged women. The 550 cases were randomly selected from the dataset as the training set and the remaining 236 cases as the validation set. The receiver operating characteristic curve was drawn, and the result showed that the area under the training set curve was 0.818 (95% CI 0.773 to 0.862), and the area under the validation set curve was 0.826 (95% CI 0.764 to 0.889); the Hosmer-Lemeshow goodness of fit test in validation set that result showed that the nomogram model had high reliability ( χ2 = 8.48, P>0.05). Conclusions:The incidence of SUI in young and middle-aged women is high. The age >44 years, BMI≥30 kg/m 2, diabetes, chronic constipation, delivery history, macrosomia delivery history and pelvic floor dysfunction are independent risk factors for SUI in young and middle-aged women. The nomogram model based on related risk factors has high predictive value and credibility.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Objective:To investigate the current situation of occurrence of social isolation in maintenance hemodialysis patients and analyze its influencing factors, in order to provide a theoretical basis for the implementation of targeted interventions.Methods:The study was a cross-sectional study. A total of 315 dialysis patients in three hemodialysis centers in Xinjiang were selected by simple sampling method from October 2021 to March 2022, who were investigated using the general information questionnaire, Lubben-6 social network scale, International Physical Activity Questionnaire (sedentary behavior section), Patient Health Questionnaire 9-item scale (PHQ-9) and Frail Scale. Univariate analysis and binary Logistic regression analysis were used to explore the influencing factors affecting the social isolation of dialysis patients.Results:Social isolation was present in 28.89% (91/315) of maintenance hemodialysis patients, and binary Logistic regression analysis revealed that age (45-59 years old: OR=4.815, 95% CI 1.362-17.017;≥60 years old: OR=8.968, 95% CI 2.349-34.236), dialysis age ( OR=2.788, 95% CI 1.334-5.826), sedentary behavior ( OR=2.504, 95% CI 1.406-4.461), depression ( OR=2.095, 95% CI 1.179-3.722), and debilitation ( OR=2.043, 95% CI=1.062-3.933) were influencing factors of social isolation in maintenance hemodialysis patients (all P<0.05). Conclusions:The occurrence of social isolation in maintenance hemodialysis patients was closely associated with advanced age, high dialysis age, sedentary behavior, debilitation, and depressive status, suggesting that medical staff in hemodialysis centers can implement targeted interventions to prevent or improve the level of social isolation in patients based on relevant influencing factors.

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

OBJECTIVE: To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT). METHODS: Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus. RESULTS: The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus. CONCLUSION Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.
Female ; Genetic Counseling ; Humans ; Karyotyping ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

Objective To investigate the clinical value of 2 dimension late Gadolinium enhancement MRI (LGE-MRI) technique for the evaluation of atrial myocardial fibrosis in patients with atrial fibrillation. Methods Forty-nine cases of atrial fibrillation in our hospital from March 2015 to December 2016 were retrospectively collected. The LGE-MR was acquired by the Siemens 3.0 T MR machine before the catheter ablation.The findings of LGE-MR were evaluated by two experienced doctors. The left atrium(LA)were manually segmented into 8 regions in axial view.All patients were classified into 4 stages based on the extent of enhancement, stage 0: absence of enhancement, stage Ⅰ: enhancement appeared in minimal two consecutive slices in single region,stageⅡ:enhancement in two regions,stageⅢ:enhancement in three or more regions. All electroanatomic maps were obtained after electrical conversion during catheter ablation. The Kappa test was used to assess the consistency of LGE-MRI left atrial myocardial fibrosis and CARTO system of the left atrial endocardial voltage reconstruction. Results Forty-nine cases of atrial fibrillation with LGE-MRI and CARTO were included. There were 17 cases of atrial fibrosis stage 0,10 cases of stageⅠ,11 cases of stageⅡ,11 cases of stageⅢaccording to LGE-MRI findings;There were 17 cases of atrial fibrosis stage 0,19 cases of stageⅠ,12 cases of stageⅡ,11 cases of stage Ⅲ with reference to CARTO findings. The diagnostic accuracy of the LGE-MRI atrial fibrosis was 81.6%(40/49),of which the correlation was good(Kappa= 0.751,P<0.001). Conclusions LGE-MRI can accurately assess the degree of left atrial myocardial fibrosis in patients with atrial fibrillation,help to select the proper candidate and strategy in catheter ablation.