OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Congenital blood group chimerism refers to the coexistence of two or more distinct blood types within an individual, resulting from the presence of hematopoietic cell populations with different genotypes. Consequently, red blood cells in such individuals may express different blood group antigens. Based on the timing and mechanism of formation, blood group chimerism can be classified as either congenital or acquired. Although congenital blood group chimerism is rare and involves complex mechanisms, it holds significant implications in transfusion medicine, transplantation, and obstetrics. This article reviews the formation mechanisms, detection methods, and clinical significance of congenital blood group chimerism in transfusion medicine. Particular emphasis is placed on the principles, advantages, and limitations of various detection techniques. Furthermore, the potential applications of these technologies in clinical diagnosis are discussed, providing a technical foundation for the development of precise transfusion strategies.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus(CMV)infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT).METHODS A retrospective cohort study was conducted,enrolling patients who underwent allo-HSCT at the Department of Hematology,Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,from August 30,2022,to February 21,2024.Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group(99 cases),while those who did not initiate letermovir within this period were assigned to the control group(18 cases).The incidence and clinical characteristics of CMV infection(including the number of CMV infection cases,the number of cases progressing to CMV disease,recurrent CMV disease,onset time of CMV infection,and treatment duration),immune function recovery within 120 days post-transplantation,and the occurrence of transplantation-related complications(including CD4+and CD8+T-cell recovery,Epstein-Barr virus infection,acute graft-versus-host disease,human herpesvirus 6 infection,and posttransplant lymphoproliferative disorders)and adverse events were recorded.Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection.RESULTS A total of 117 patients were included,among whom 15 developed CMV infection,5 progressed to CMV disease,and 2 experienced recurrent CMV disease.The CMV infection rate in the experimental group was significantly lower than that in the control group(P＜0.001),and the onset time of CMV infection was significantly delayed(P=0.014).The proportion of patients with CD4+T-cell counts≥200 cells/μL in the experimental group was significantly lower than that in the control group(P=0.022).During the follow-up period,elevated creatinine levels were observed in 1 patient,and nausea and vomiting were observed in 2 patients.Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection(HR=6.230,95%CI of 1.255-30.926,P=0.025),while initiating letermovir within 28 days post-transplantation was a protective factor(HR=0.125,95%CI of 0.045-0.348,P＜0.001).CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection,with favorable short-term safety.

Objective To construct and evaluate a mouse model of renal fibrosis(RF)combined with Qi deficiency and dampness stasis,and investigate the changes in protein and metabolic pathways using multiomics.Methods Twenty-four C57BL/6J mice were divided randomly into normal(N),model(M),and RF and syndrome combined groups(BZ)(n=8/group).The experiment lasted 6 weeks.A mouse model of RF with Qi deficiency and dampness stasis was established by "cyclosporine A+high-fat diet+swimming exhaustion+constant temperature and humidity".The model was evaluated by detecting general signs,renal function,tongue RGB(red,green,blue)values,hemorheology indexes,blood lipids,and inflammation and oxidation indexes,combined with hematoxylin and eosin,Masson,periodic acid-Schiff,and Oil red O staining,terminal deoxynucleotidyl transferase dUTP nick end labeling apoptosis,and transforming growth factor-β immunofluorescence analysis of renal tissue.Differential proteins and metabolites were screened by renal proteomics combined with serum metabolomics and subjected to pathway enrichment analysis.Results Body mass of mice in the BZ group began to decline at week 3(P＜0.05)and decreased significantly at week 4(P＜0.01),while food and water consumption decreased,the fur became messy and less glossy,mood and activity decreased,and stools became watery.Serum creatinine,blood urea nitrogen,urine albumin-creatinine ratio,and N-acetyl-beta-glucosaminidase(NAG)were significantly higher in the BZ group compared with those in the N group(P＜0.05,P＜0.01),and serum creatinine and NAG levels were significantly different compared with those in the M group.The R value of tongue images was significantly lower in the BZ group compared with that in the N group(P＜0.01),while the B value was significantly higher(P＜0.05).The viscosity of the whole blood multi-shear rate and the hematocrit were higher in the BZ group compared with those in the N and M groups,and the platelet volume was higher than in the N group(P＜0.05,P＜0.01).Total cholesterol,low-density lipoprotein cholesterol,C-reactive protein,interleukin-6,and malondialdehyde levels were significantly increased in the BZ group compared with those in the N and M groups(P＜0.01),and superoxide dismutase activity was significantly decreased compared with that in the N group(P＜0.05).Renal tubule vacuolation,inflammatory cell infiltration,glomerular basement membrane thickening,collagen fiber hyperplasia,and lipid accumulation were evident,and renal cell apoptosis and transforming growth factor-β deposition were increased in the BZ group.There were 299 differential proteins in the BZ and N groups,including 180 up-regulated and 119 down-regulated proteins,and 323 differential metabolites,including 205 up-regulated and 118 down-regulated.Primary bile acid biosynthesis,taurine and hypotaurine metabolism,and biosynthesis of unsaturated fatty acids were co-enriched in differential proteins and differential metabolites,involving three differential proteins and nine differential metabolites.Among these,docosapentaenoic acid(22n-3),eicosapentaenoic acid,taurine,3-sulfinoalanine,taurocholic acid,Acnat1,Acnat2,and Hsd17b12 showed high prediction accuracy.Conclusions We successfully constructed an RF animal model of Qi deficiency and dampness stasis using the "cyclosporine A+high-fat diet+exhaustion of swimming+constant temperature and humidity" method.Biosynthesis of unsaturated fatty acids and taurine and hypotaurine metabolism may play important roles in this RF mouse model of Qi deficiency and dampness stasis.

Objective To construct and evaluate a mouse model of renal fibrosis(RF)combined with Qi deficiency and dampness stasis,and investigate the changes in protein and metabolic pathways using multiomics.Methods Twenty-four C57BL/6J mice were divided randomly into normal(N),model(M),and RF and syndrome combined groups(BZ)(n=8/group).The experiment lasted 6 weeks.A mouse model of RF with Qi deficiency and dampness stasis was established by "cyclosporine A+high-fat diet+swimming exhaustion+constant temperature and humidity".The model was evaluated by detecting general signs,renal function,tongue RGB(red,green,blue)values,hemorheology indexes,blood lipids,and inflammation and oxidation indexes,combined with hematoxylin and eosin,Masson,periodic acid-Schiff,and Oil red O staining,terminal deoxynucleotidyl transferase dUTP nick end labeling apoptosis,and transforming growth factor-β immunofluorescence analysis of renal tissue.Differential proteins and metabolites were screened by renal proteomics combined with serum metabolomics and subjected to pathway enrichment analysis.Results Body mass of mice in the BZ group began to decline at week 3(P＜0.05)and decreased significantly at week 4(P＜0.01),while food and water consumption decreased,the fur became messy and less glossy,mood and activity decreased,and stools became watery.Serum creatinine,blood urea nitrogen,urine albumin-creatinine ratio,and N-acetyl-beta-glucosaminidase(NAG)were significantly higher in the BZ group compared with those in the N group(P＜0.05,P＜0.01),and serum creatinine and NAG levels were significantly different compared with those in the M group.The R value of tongue images was significantly lower in the BZ group compared with that in the N group(P＜0.01),while the B value was significantly higher(P＜0.05).The viscosity of the whole blood multi-shear rate and the hematocrit were higher in the BZ group compared with those in the N and M groups,and the platelet volume was higher than in the N group(P＜0.05,P＜0.01).Total cholesterol,low-density lipoprotein cholesterol,C-reactive protein,interleukin-6,and malondialdehyde levels were significantly increased in the BZ group compared with those in the N and M groups(P＜0.01),and superoxide dismutase activity was significantly decreased compared with that in the N group(P＜0.05).Renal tubule vacuolation,inflammatory cell infiltration,glomerular basement membrane thickening,collagen fiber hyperplasia,and lipid accumulation were evident,and renal cell apoptosis and transforming growth factor-β deposition were increased in the BZ group.There were 299 differential proteins in the BZ and N groups,including 180 up-regulated and 119 down-regulated proteins,and 323 differential metabolites,including 205 up-regulated and 118 down-regulated.Primary bile acid biosynthesis,taurine and hypotaurine metabolism,and biosynthesis of unsaturated fatty acids were co-enriched in differential proteins and differential metabolites,involving three differential proteins and nine differential metabolites.Among these,docosapentaenoic acid(22n-3),eicosapentaenoic acid,taurine,3-sulfinoalanine,taurocholic acid,Acnat1,Acnat2,and Hsd17b12 showed high prediction accuracy.Conclusions We successfully constructed an RF animal model of Qi deficiency and dampness stasis using the "cyclosporine A+high-fat diet+exhaustion of swimming+constant temperature and humidity" method.Biosynthesis of unsaturated fatty acids and taurine and hypotaurine metabolism may play important roles in this RF mouse model of Qi deficiency and dampness stasis.

OBJECTIVE To evaluate the cost-effectiveness of capecitabine metronomic chemotherapy combined with aromatase inhibitor(AI)versus AI monotherapy as first-line treatment for hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-)metastatic breast cancer,thereby providing evidence-based support for clinical therapeutic decision-making and healthcare policy formulation.METHODS Based on the MECCA trial,a partitioned survival model was constructed using a 4-week cycle length to simulate outcomes over patients'lifetime.The model outputs included total costs,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).Sensitivity analyses were performed to validate the robustness of base-case results,while scenario analyses examined the cost-effectiveness of both treatment strategies under 10-year,20-year,and lifetime time horizons.RESULTS With the willingness-to-pay(WTP)threshold set at 1 times China's 2024 per capita gross domestic product(GDP)(95 749 yuan/QALY),patients receiving capecitabine metronomic chemotherapy combined with AI regimen gained incremental utility(0.66 QALYs)while incurring higher costs,with ICER of 27 684.85 yuan/QALY.Results of the one-way sensitivity analysis showed that factors with significant impacts on ICER included the cost discount rate,drug costs of the capecitabine metronomic chemotherapy combined with AI group,utility value in the progression-free survival state,follow-up costs,and treatment costs in the subsequent stable phase.Probabilistic sensitivity analysis indicated that when the WTP threshold≥49 250 yuan/QALY,the capecitabine metronomic chemotherapy combined with AI regimen had a 100%probability of being cost-effective.Scenario analysis results demonstrated that capecitabine metronomic chemotherapy combined with AI regimen was more cost-effective than the AI alone regimen across 10-year,20-year,and lifetime study horizons.CONCLUSIONS Under the premise that the WTP threshold is set at 1 times China's per capita GDP in 2024,capecitabine metronomic chemotherapy combined with AI regimen is more cost-effective than the AI alone regimen as the first-line treatment for HR+/HER2-metastatic breast cancer.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.

Objective:To determine the pathogens causing viral diarrhea in children under 5 years of age and the epidemiological patterns in Chengdu from 2021 to 2024.Methods:Fecal samples were collected from hospitalized children under 5 years of age with diarrhea in a sentinel surveillance hospital for viral diarrhea in Chengdu from 2021 to 2024. Norovirus（NoV），sapovirus（SaV），astrovirus（AstV），and enteric adenovirus（EAdV）were detected by real-time PCR or real-time RT-PCR. Group A rotavirus（RVA）was detected by enzyme-linked immunosorbent assay. The results were analyzed statistically by using SPSS 20.0 software.Results:RVA，NoV，SaV，AstV，and EAdV were detected in 329 fecal samples from 719 hospitalized children with diarrhea under 5 years of age. The total detection rate was 48.8%（329/719）. The detection rate of RVA，NoV，SaV，AstV，and EAdV was 17.0%（122/719），20.9%（150/719），4.0%（29/719），2.8%（20/719），8.6%（62/719），separately. The detection rate of mixed infection with multiple pathogens was 7.1%（51/719），among which RVA combined with NoV infection was the most common（2.2%，16/719）. Except for EAdV（ χ2=14.368， P=0.002），there was no significant difference in the detection rates of RVA，NoV，SaV，and AstV in different years. Except for SaV and EAdV，the detection rates of RVA（ χ2=11.106， P<0.001），NoV（ χ2=65.164， P<0.001）and AstV（ χ2=19.612， P<0.001）were statistically significant in different quarters. There was no statistically significant difference in the detection rates of the five pathogens between males and females. Except for NoV，there were statistically significant differences in the detection rates of RVA（ χ2=32.209， P<0.001），SaV（ χ2=13.983， P=0.002），AstV（ χ2=9.56， P=0.015）and EAdV，（ χ2=8.992， P=0.029）in children of different months of age. Conclusion:RVA and NoV are the main pathogens causing viral diarrhea in children under 5 years of age in Chengdu. The peak infection period of viral diarrhea tends to occur in winter and spring and occurs most frequently in 12-24 months old and 24-59 months old children.