Objective: To investigate the incidence of occult hepatitis B virus infection (OBI) in spouses of asymptomatic hepatitis B virus (HBV) infected individuals in Shenzhen, China, and to analyze their serological and molecular characteristics and possible transmission routes, so as to propose refined strategies for blood safety. Methods: After rapid screening for HBsAg at the blood collection sites, samples from HBsAg-positive blood donors and their concurrently donating spouses were collected. All samples were tested for hepatitis B serological markers by electrochemiluminescence immunoassay (ECLI). Simultaneously, HBV nucleic acid extractiona, nested PCR amplification, gene sequencing of S and BCP/PC regions and qPCR were conducted. Results: A total of 112 samples were collected, including 56 from HBsAg positive donors and 56 from their spouses. All donors were confirmed as HBsAg+/DNA+/anti-HBc+, indicative of asymptomatic chronic hepatitis (CHB) infection. Among their 56 spouses, 11 (19.6%) were identified as HBV DNA+. The prevalence was higher in males (23.1%) than in females (16.7%). Six spouses (10.8%) had OBI, three of whom (5.4%) were negative in routine blood screening tests. The residual risk of HBV were estimated as 1∶127 (95%CI, 1∶356 to 1∶66). Among infected couples, immune escape mutation (E164D) and glycosylation mutations (I126T and T131N/M133T) were identified. Furthermore, sequence analysis suggested partner-to-partner transmission in eight cases. Conclusion: A substantial proportion (19.6%) of spouses of asymptomatic HBV infected donors were HBV-positve, with an OBI prevalence of 10.9%. Among these, 5.4% were negative in routine tests. To ensure blood safety, we recommend that spouses of HBV infected individuals be deferred from blood donation.

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.

BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

Autoimmune liver diseases （AILD） are a group of chronic liver diseases caused by abnormal activation of the immune system， mainly including autoimmune hepatitis， primary biliary cholangitis， primary sclerosing cholangitis， IgG4-related sclerosing cholangitis， and overlap syndrome. Clinical studies have shown that patients with AILD are often comorbid with thyroid diseases， especially autoimmune thyroid diseases （AITD）， such as Graves’ disease and Hashimoto’s thyroiditis. This article systematically reviews the epidemiological association， potential shared pathogenesis， and overlapping features between AILD and thyroid diseases. A deeper understanding of the immunological links between AILD and AITD may provide a theoretical basis for precision medicine and future research.

Objective To understand the current status of blood pressure variability and dyslipidemia in young and middle-aged patients with ischemic stroke, and to explore their relationship with prognosis. Methods A total of 312 young and middle-aged patients with ischemic stroke who met the inclusion criteria in Beijing Pinggu District Hospital from January 2022 to January 2025 were selected. The prognosis status [modified Rankin scale (mRS)], blood pressure variability, and blood lipids [total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were analyzed. The correlation of blood pressure variability and blood lipids levels with prognosis was explored by logistic regression analysis. Results There were 206 patients with good prognosis and 106 patients with poor prognosis. The number of patients who received diversified health education in the good prognosis group was more than that in the poor prognosis group (P<0.05). The systolic blood pressure successive variation (SV) and average real variability (ARV), and diastolic blood pressure SV and ARV were lower in the good prognosis group than those in the poor prognosis group (P<0.05). Furthermore, compared with the poor prognosis group, the good prognosis group had lower levels of TC, TG and LDL-C, while the number of patients receiving diversified health education and the level of HDL-C were higher (P<0.05). After logistic regression analysis, it was found that the levels of TC, TG, LDL-C, systolic blood pressure SV and ARV, and diastolic blood pressure SV and ARV were risk factors for poor prognosis. Conversely, receiving diversified health education and HDL-C level were protective factors for poor prognosis (P<0.05). Conclusion High blood pressure fluctuation, dyslipidemia, and lack of health education will increase the risk of poor prognosis in young and middle-aged stroke patients.

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.

ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Acupuncture and moxibustion have their unique advantages in treating tumors,but the theoretical framework of acupuncture and moxibustion intervention in tumors needs to be improved,and the academic system still needs to be sorted out.In this paper,we try to describe the commonalities between Chinese medical theories and modern medical technologies in order to consolidate the theoretical foundation of acupuncture intervention in tumor.Specifically:① Acupuncture regulates immune function and energy metabolism,which is a specific form of tonifying the spleen and stomach to support positive qi.② Tumors belong to the broad definition of"sores and ulcers"in traditional Chinese medicine,which is a special kind of chronic inflammation,and acupuncture intervenes in tumors by intervening in inflammatory reactions from ulcers.③ Tumor is a"dynamic pseudo-organ"with yin and yang attributes and"life attributes".Acupuncture and moxibustion can regulate various cells and factors in the tumor environment in a multi-targeted way,so as to make it tend to the state of yin and yang equilibrium.④ Acupuncture and moxibustion have unique advantages in the reduction of toxicity,enhancement of efficacy,tonicity,rejuvenation,treatment of complications,etc.,which complement the allopathic therapies of modern medicine,and can help to realize survival with tumors.

Objective:To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma(MM)and develop a risk prediction model based on these factors.Methods:A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma(NDMM)patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020.The clinical,laboratory examination,and follow-up data of patients experiencing relapse/progression within 24 months after treatment(ER/EP24)were analyzed using univariate and multivariate analyses,and a nomogram prediction model was established.Results:Among the 187 patients,58(31.0％)experienced ER/EP24,with a median survival time of only 24 months.The results of multivariate logistic regression analysis showed that failure to achieve partial response(PR)or better after 3-4 cycles of chemotherapy and albumin(ALB)levels＜35 g/L were independent risk factors for ER/EP24(P＜0.05).These factors,along with other clinically relevant variables,were further incorporated into the nomogram prediction model.The model demonstrated a concordance index(C-index)of 0.784,indicating strong predictive accuracy.Conclusion:MM patients experiencing ER/EP24 exhibit poor outcome,and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients,providing a valuable tool for clinical risk assessment.

Objective·To explore the mechanism at the atomic level by which the KRASG12D/R68G mutation induces tumor cell resistance to MRTX1133.Methods·The crystal structure data of the KRASG12D-MRTX1133 complex were obtained from the RCSB Protein Data Bank(PDB).PyMOL software was used to mutate arginine at position 68 of KRAS to glycine(R68G),constructing the initial conformations of the KRASG12D-MRTX1133 and KRASG12D/R68G-MRTX1133 complexes.The LEaP module was used to build simulation systems under periodic boundary conditions.The ff19SB force field was applied to standard amino acids in KRAS,GAFF(general AMBER force field)to MRTX1133,and TIP3P(intermolecular potential three point)to water molecules.Energy minimization was performed using the Amber software suite.The systems were then heated to 300 K,followed by NVT(constant volume and temperature)equilibration and NPT(constant pressure and temperature)production.Root mean square deviation(RMSD),root mean square fluctuation(RMSF),principal component analysis(PCA)and solvent-accessible surface area(SASA)of MRTX1133 and GDP were analyzed using cpptraj.The number of hydrogen bonds between regions and the dynamic cross-correlation matrix(DCCM)of amino acid movements were also calculated.Results·RMSD analysis showed greater structural variation in KRAS in the KRASG12D/R68G system compared to the KRASG12D system.RMSF analysis revealed significantly higher fluctuations in the Switch Ⅰ and Switch Ⅱ regions of the KRASG12D/R68G system.PCA indicated that Switch Ⅰ and Switch Ⅱ in the KRASG12D/R68G system were more frequently in an open conformation.The distances between Switch Ⅰ and the P-loop,and between Switch Ⅱ and the P-loop,were larger in the KRASG12D/R68G system,indicating an expanded binding pocket for GDP and MRTX1133 compared to the KRASG12D system.SASA analysis indicated that both GDP and MRTX1133 had increased solvent exposure in the KRASG12D/R68G system.DCCM analysis revealed more decoupled movements among the Switch Ⅰ,Switch Ⅱ and P-loop regions in the KRASG12D/R68G system.Conclusion·The KRASG12D/R68G mutation disrupts the interactions between the Switch Ⅰ and Switch Ⅱregions,leading to their separation and the opening of the MRTX1133 binding pocket.This increases the solvent exposure of MRTX1133,accelerates its dissociation,and ultimately results in KRASG12D/R68G resistance to MRTX1133.