OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective:To investigate the predictive value of maximum tumor diameter and the peripheral blood neutrophil to lymphocyte ratio (NLR) before radiotherapy for the occurrence of esophageal fistula after radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) .Methods:A total of 98 patients with ESCC who underwent radiotherapy in Hefei Cancer Hospital, Chinese Academy of Sciences from February 2017 to February 2021 were selected, and the patients were divided into esophageal fistula group (13 cases) and no esophageal fistula group (85 cases) according to whether esophageal fistula occurred during the follow-up process. The prognostic nutritional index (PNI) , NLR, and systemic inflammatory response index (SIRI) were calculated. Univariate and multivariate logistic regression were used to analyze the influencing factors of esophageal fistula, and the predictive value of each indicator was evaluated by using the receiver operator characteristic (ROC) curve.Results:There were no statistically significant differences in age, smoking history, diabetes mellitus history, gender, concurrent chemotherapy and alcohol history between the esophageal fistula group and the no esophageal fistula group (all P>0.05) , while there were statistically significant differences in PNI ( t=2.24, P=0.041) , NLR ( t=3.75, P=0.001) , SIRI ( t=2.68, P=0.015) . Univariate analysis showed that tumor length ( OR=1.16, 95% CI: 1.01-1.35, P=0.043) , maximum tumor diameter ( OR=1.63, 95% CI: 1.11-2.39, P=0.012) , PNI ( OR=0.83, 95% CI: 0.71-0.98, P=0.023) , NLR ( OR=1.94, 95% CI: 1.20-3.12, P=0.007) and SIRI ( OR=1.82, 95% CI: 1.03-3.24, P=0.041) were related to esophageal fistula. Multivariate analysis showed that maximum tumor diameter ( OR=2.17, 95% CI: 1.02-4.94, P=0.033) and NLR ( OR=2.40, 95% CI: 1.89-6.59, P=0.018) were independent influencing factors for the development of esophageal fistula in patients with ESCC after radiotherapy. ROC curve analysis showed that the area under the curve of maximum tumor diameter before radiotherapy combined with NLR for predicting esophageal fistula in patients with esophageal squamous cell carcinoma after radiotherapy was 0.83 (95% CI: 0.74-0.90) , which was greater than that of maximum tumor diameter before radiotherapy (0.71, 95% CI: 0.63-0.81, Z=1.80, P=0.039) and NLR (0.74, 95% CI: 0.67-0.85, Z=1.64, P=0.046) alone. Conclusions:The maximum tumor diameter before radiotherapy and NLR are closely related to the occurrence of esophageal fistula in ESCC after radiotherapy, and these factors are expected to serve as key predictors of the occurrence of esophageal fistula.

Breast cancer is one of the most common tumors worldwide.Despite significant pro-gress in diagnosis and treatment,the incidence and mortality rates remain high due to its highly inva-sive and metastatic characteristics.Trichorhinophalangeal syndrome type 1(TRPS1)is an atypical globin transcription factor-1(GATA).It plays an important role in regulating cell proliferation and differentiation and tissue growth.Studies have found that TRPS1 is significantly overexpressed in breast cancer and closely related to tumor invasion and metastasis.TRPS1 is specifically expressed in the ductal epithelial cells of breast tissue and closely associated with the differentiation of breast ducts.In recent years,scholars have mainly focused on the role and mechanisms of TRPS1 in the di-agnosis and treatment of breast cancer.This review summarized the research progress of TRPS1 in breast cancer,aiming to further analyze its clinical application value in the occurrence,development,diagnosis,and treatment of breast cancer.

Objective To compare the efficacy of tegoprazan and esomeprazole in treatment of reflux esophagitis(RE)and analyze the influencing factors for treatment failure.Methods A total of 120 RE patients were selected as study subjects and divided into control group(treated with esome-prazole)and observation group(treated with tegoprazan)using random number table method,with 60 cases in each group.The clinical efficacy and gastroscopic efficacy of the two groups were com-pared.Based on the gastroscopic assessment results,the patients were divided into failure group(26 cases)and success group(94 cases).The clinical data of the failure group and the success group were collected and compared.Multivariate Logistic regression analysis was used to screen the influen-cing factors for treatment failure in RE patients.Results The total clinical effective rate in the ob-servation group was 93.33％(56/60),which was higher than 76.67％(46/60)in the control group(P＜0.05).The total effective rate under gastroscopy in the observation group was 88.33％(53/60),which was higher than 68.33％(41/60)in the control group,and the difference was statistically significant(P＜0.05).The proportions of patients with body mass index(BMI)＞28 kg/m2,diabe-tes,a family history,Helicobacter pylori(Hp)infection,Los Angeles classification(LA classifica-tion)of gastroesophageal reflux disease(GERD)grade C to D,and treated with esomeprazole in the failure group were all higher than those in the success group,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that BMI＞28 kg/m2,con-comitant diabetes,LA classification grade C to D,and treatment with esomeprazole were all inde-pendent risk factors for treatment failure in RE patients(P＜0.05).Conclusion Tegoprazan has a significant clinical effect in treatment of RE,and its efficacy is superior to that of esomeprazole.BMI＞28 kg/m2,concomitant diabetes,LA classification grade C to D,and treatment with esome-prazole are all risk factors for treatment failure in RE patients.

Objective: To explore the expression of collagen type 1 alpha 2 (COL1A2) in cervical cancer and its correlation with immune infiltration. Methods: Bioinformatics techniques were used to analyze the expression of COL1A2 in cervical cancer. Western blot and RT-qPCR were used to detect the expression of COL1A2 in cervical cancer tissues and cell lines. The correlation between the expression of COL1A2 and tumor immune cell infiltration was analyzed by tumor immune estimation resource (TIMER2. 0) . Gene set enrichment analysis (GSEA) was used to analyze the possible mechanism of COL1A2 in cervical cancer. Jaspar database was used to predict the transcrip- tion factors of COL1A2. Western blot and RT-qPCR were used to detect the expression of transcription factors in cervical cancer tissues and cell lines. Results: The expression of COL1A2 was down-regulated in cervical cancer (P < 0. 05) . The expression of COL1A2 was positively correlated with the levels of macrophages and myeloid den- dritic cells (P < 0. 01) . The proportions of 22 types of immune cells were different in different cervical cancer pa- tients. In addition , compared with the high expression group of COL1A2 , the proportion of M0 macrophages , M2 macrophages and resting memory CD4 + T cells increased in the low expression group of COL1A2 , while the propor- tion of CD8 + T cells , activated memory CD4 + T cells , follicular helper T cells , activated NK cells and activated myeloid dendritic cells decreased (P < 0. 05) . GSEA analysis showed that COL1A2 was related to immune-related signaling pathways , including Notch signaling pathway , interleukin-6/janus kinase/signal transducer and activator of transcription 3 (IL6/JAK/STAT3) , Wnt/β-catenin signaling pathway , etc. (P < 0. 01) . Jaspar database pre- dicted that the transcription factor of COL1A2 was paired box protein 5 (PAX5) , and the expression of PAX5 de- creased in cervical cancer (P < 0. 05) . Conclusion COL1A2 is expected to become a potential diagnostic biomar- ker and immunotherapy target for cervical cancer.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective:To investigate the clinical and pathological characteristics and prognosis of children with lupus nephritis(LN)and thrombotic microangiopathy (TMA).Methods:In this retrospective case-control study, clinical and pathological data of LN children confirmed by renal biopsy from January 2008 to January 2023 in Xuzhou Children′s Hospital, Xuzhou Medical University were analyzed.There were 46 LN children complicated with TMA (LN-TMA group). With matched age, sex and pathology, 92 LN children (1∶2) without TMA were selected as the control group (LN group). The Kaplan-Meier method was used to evaluate the overall and renal survival rates of children with LN, and the Cox regression model was used to analyze the risk factors for the progression to end-stage renal disease (ESRD).Results:TMA was moderately associated with serum creatinine, serum C3, anti-C1q antibody (a-C1q), estimated glomerular filtration rate (eGFR), endocapillary proliferation, fibrinoid necrosis, and renal C1q deposition (all r>0.5). Serum a-C1q≥20 U/mL ( HR=8.724, 95% CI: 0.976-16.114, P=0.026) and eGFR≤60 mL/(min·1.73 m 2) ( HR=12.213, 95% CI: 1.147-25.048, P=0.038) were independent risk factors for TMA in children with LN.Glomerular sclerosis ( HR=7.228, 95% CI: 0.186-22.358, P=0.016), TMA ( HR=11.387, 95% CI: 3.426-42.554, P=0.009) and eGFR≤60 mL/(min·1.73 m 2) ( HR=3.116, 95% CI: 0.592-10.064, P=0.030) were independent risk factors for developing ESRD in LN children.The 5-year and 10-year renal survival rates in the LN-TMA group were lower than those in the LN group (97.44% vs.98.28%, 80.90% vs.87.27%, χ2=4.918, P=0.027). Conclusions:Children with LN-TMA present with severe symptoms and poor prognosis.TMA is an independent risk factor for progression to ESRD in children with LN, and the mechanism may be related to complement activation.