OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

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.

Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

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 construct a framework for risk identification and mechanistic explanation of conduct problems in adolescents, so as to provide a basis for formulating effective prevention strategies. Methods: In October 2025, a total of 2 126 junior and senior high school students from Zibo City in Shandong Province, Zhengzhou City in Henan Province, and Shenzhen City in Guangdong Province were selected as the study subjects using a combination of convenience sampling and random cluster sampling. The instruments included the Adolescent Conduct Problem Tendency Questionnaire, Barratt Impulsiveness Scale, Callous- Unemotional Traits Scale, Parenting Style Scale, Family Adaptation, Partnership, Growth, Affection, and Resolve Scale, Perceived School Climate Scale, and the School Context Subscale of the Multiple Violence Exposure Scale. Machine learning algorithms and response surface methodology (RSM) were employed to reveal the non linear interactive effects of risk factors on adolescent conduct problems. Results: Impulsive personality ranked first in feature importance, followed by neglectful parenting style and perceived school climate. Impulsive personality and neglectful parenting style both positively predicted rule breaking ( B =0.42, 0.16) and aggression tendencies( B =0.41,0.14), with the interaction effect between the two being significantly negative in both cases ( B =-0.19,-0.08); impulsive personality ( B =0.33) and perceived school climate ( B =0.47) positively predicted addiction tendency, with the interaction term being significantly negative ( B =-0.16)(all P <0.05). For rule breaking tendency, the congruence slope (0.58), congruence curvature (-0.16), incongruence slope (0.26), and incongruence curvature (0.22) all reached statistical significance (all P <0.05). For addiction tendency, the congruence slope (0.79), incongruence slope (-0.15), and incongruence curvature (0.34) all reached statistical significance (all P <0.05). For aggression tendency, the congruence slope (0.55), incongruence slope (0.26), and incongruence curvature (0.15) all reached statistical significance(all P <0.05). Conclusion Impulsive personality is the core driver of rule breaking and aggression tendencies, with neglectful parenting style playing a moderating role; perceived school climate is the core driver of addiction tendency and exhibits an interactive inhibition effect with impulsive personality.

OBJECTIVE To evaluate the cost-utility of benmelstobart combined with anlotinib and chemotherapy as first-line treatment for extensive-stage small cell lung cancer （ES-SCLC） from the perspective of China’s healthcare system. METHODS Based on the data from the ETER 701 study， a partitioned survival model was constructed with a cycle of 3 weeks to simulate the total cost， quality-adjusted life years （QALY）， and incremental cost-effectiveness ratio （ICER） over 10 years for patients with ES- SCLC treated with benmelstobart plus anlotinib and chemotherapy， or chemotherapy alone. One-way sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the simulation results. The willingness-to-pay （WTP） threshold was set at 3 times the per capita gross domestic product （GDP） of China in 2023， which amounted to 268 074 yuan/QALY. RESULTS Compared with chemotherapy alone， benmelstobart combined with anlotinib and chemotherapy gained 0.438 QALY more at the cost of 403 505.55 yuan more， with an ICER of 922 031.37 yuan/QALY， which was higher than the WTP threshold set in this study. One-way sensitivity analysis showed that benmelstobart’s cost and utility value of the progression-free survival state had a greater impact on the ICER value； probabilistic sensitivity analysis confirmed the robustness of the model； only when the price of benmelstobart was reduced by 75.4%， the combined regimen would be cost-effective. CONCLUSIONS The first-line treatment of ES-SCLC with benmelstobart combined with anlotinib and chemotherapy is not cost-effective from the perspective of China’s healthcare system at present.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

Objective:To develop a tool package that meets the routine statistical analysis requirements of population-based cancer registries in China based on R language, with the aim of improving data quality and efficiency, and promoting the nationwide scientific utilization of cancer registry data.Methods:The functional demands for statistical analysis of population-based cancer registry staff were collected through questionnaires or face-to-face interviews. Based on the concept of generic functions in R software's S3 object system, functions were developed by defining specific S3 classes for different data types, allowing the same function to perform diverse tasks depending on the class of input data. A stepwise development strategy was adopted to ensure logical coherence among functional modules, and all functions were systematically tested and validated in accordance with standard R package development guidelines.Results:Six categories of functions, including data reading, data manipulation, data processing, statistical calculation, visualization, and statistical reporting, were developed to support routine statistical analysis of population-based cancer registry data. Data reading functions support reading data formats required by the National Cancer Registry. Data manipulation functions empower conditional filtering of registry data and support regrouping, merging, or transforming the data based on registry attributes (such as urban/rural location) to accommodate different analytical needs. Data processing functions includes age grouping, International Classification of Diseases 10 th Revision (ICD-10) classification, childhood cancer classification, and population estimation. Statistical calculation functions permit the calculation of age-standardized rates, truncated rates, cumulative rates, cumulative risks, life tables, and expansion from abridged to complete life tables. Visualization functions can generate commonly used statistical charts, including population pyramids, bar charts, and line graphs. Statistical reporting functions can integrate key indicators, charts, and narrative descriptions into comprehensive cancer registry reports. Conclusion:An R package named Canregtools was developed based on the concept of S3 generic functions. This package is free of charge, open-source, and highly efficient. It can meet the diversified needs in cancer registry data analysis, visualization, and reporting through standardized data processing workflows, thereby enhancing the quality and efficiency of routine statistical analysis in population-based cancer registries in China.