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.

OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists （TPO-RAs） on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed， Web of Science， CNKI， Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials （RCTs） comparing oral non-peptidic TPO-RAs （intervention group） with placebo or conventional therapy （control group）. All databases were searched from their inception to June 2025. After literature screening， data extraction and quality assessment of the included studies， meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included， with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR＝1.24， 95%CI （0.77， 1.99）， P ＝0.37 ] ， the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR＝1.21， 95%CI （0.73， 1.99）， P ＝0.46 ] ， and the incidence of severe hepatic enzyme elevation[OR＝1.39， 95%CI（0.46， 4.20）， P ＝0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR＝1.57，95%CI（0.85，2.87）， P ＝0.15 ] ， avatrombopag[OR＝0.88，95%CI （0.09，8.46）， P ＝0.91 ] ， and hetrombopag[OR＝1.04，95%CI（0.30，3.65）， P ＝0.95 ] ， respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia， and show an overall favorable hepatic safety profile.

Objective: To investigate the factors influencing intraoperative blood transfusion in patients with hip fractures and to develop a machine learning (ML) model for predicting this risk. Methods: A total of 424 patients with hip fractures who underwent surgical treatment between November 2022 and March 2025 in our hospital were selected. Key feature variables of intraoperative blood transfusion risk were identified using the Boruta algorithm. Four different ML algorithms—support vector machine (SVM), linear discriminant analysis (LDA), mixed discriminant analysis (MDA), and extreme gradient boosting (XGBoost)—were used to develop predictive models for intraoperative blood transfusion risk. The predictive performance of the four ML models were evaluated using accuracy, precision, receiver operating characteristic (ROC) curves, precision-recall curves (PRC), precision-recall gain curves (PRGC), and F1 scores. Shapley additive interpretation (SHAP) was used to interpret the final model. Results: Among the 424 patients, 77(18.2%) received intraoperative blood transfusion. The Boruta algorithm identified albumin (ALB), activated partial thromboplastin time (APTT), types of anesthesia, types of fracture, and hemoglobin (Hb) as key feature variables for predicting intraoperative blood transfusion risk. In model evaluation, the SVM model outperforms the other three models across multiple metrics, including the area under the receiver operating characteristic curve (AUC), recall, recall gain, accuracy, precision, F1 score, and the area under the precision-recall curve (PRC-AUC). The SVM model, interpreted and visualized based on SHAP values, effectively predicted intraoperative blood transfusion risk in patients with hip fracture. A visual online application was developed based on the SVM model (https://pbo-nomogram.shinyapps.io/blood/). Conclusion: Preoperative low ALB and Hb levels, prolonged APTT, general anesthesia, and intertrochanteric fractures are risk factors for intraoperative blood transfusion in hip fracture patients. The risk prediction model for intraoperative blood transfusion constructed based on the SVM algorithm has optimal performance, which provides new ideas and methods for the clinical early identification of hip fracture patients with high transfusion risk and the implementation of targeted interventions.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

ObjectiveTo evaluate the clinical efficacy of Shenqi Yangxin decoction in the treatment of ischemic cardiomyopathy （ICM） with Qi and Yin deficiency and blood stasis syndrome and its effect on serum hydrogen sulfide （H₂S） and calcium ion （Ca²⁺）. MethodsA total of 64 ICM patients with Qi and Yin deficiency and blood stasis syndrome who met the inclusion criteria were randomly divided into a control group （n=32） and a treatment group （n=32）. All patients received conventional Western medicine treatment. The treatment group was additionally given Shenqi Yangxin decoction. The TCM syndrome score， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， 6-minute walk test （6MWT）， New York Heart Association （NYHA） cardiac function classification， and serum H₂S and Ca²⁺ levels were compared between the two groups pre- and post-treatment. ResultsTwo cases dropped out from each group during the study. Finally， 30 patients in each group were included in the analysis. There were no significant differences in age， gender， course of coronary heart disease， underlying diseases， and laboratory tests between the two groups. Compared with baseline， the TCM syndrome score， MLHFQ score， and NT-proBNP in both treatment group and control group decreased significantly （P<0.01）， LVEF， 6MWT， and H₂S increased significantly （P<0.01）， and serum Ca²⁺ increased （P<0.05）. Compared with the control group after treatment， the MLHFQ score and NT-proBNP in the treatment group decreased （P<0.05）， the TCM syndrome score decreased significantly （P<0.01）， LVEF， 6MWT， and serum Ca²⁺ increased （P<0.05）， and H₂S increased significantly （P<0.01）. The improvement degree of the NYHA cardiac function classification in the treatment group was higher than that in the control group， but there was no significant difference. ConclusionShenqi Yangxin decoction is effective in treating ICM patients with Qi and Yin deficiency and blood stasis， which could significantly improve cardiac function and quality of life， and its therapeutic effect may be related to the regulation of serum H₂S and Ca²⁺ levels.

BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

ObjectiveTo evaluate the clinical efficacy of Xu's Shenqiyizhu （SQYZ） decoction combined with chemotherapy in the treatment of cancer-related fatigue （CRF） of stagnated-toxin spleen deficiency type after gastric cancer surgery and explore its possible mechanism. MethodsFifty postoperative gastric cancer patients with CRF of stagnated-toxin spleen deficiency type were selected and randomly divided into an experimental group and a control group by using a random number table，with 25 cases in each group. The control group was treated with FLOT chemotherapy （50 mg·m^-2 docetaxel （iv drip on day 1） + 85 mg·m^-2 oxaliplatin （iv drip on day 1） + 200 mg·m^-2 calcium folinate （iv drip on day 1） + 2 600 mg·m^-2 fluorouracil （iv drip for 24 h on day 1），once every three weeks） and basic and symptomatic supportive treatment. The experimental group was treated with Xu's SQYZ decoction （decocted twice，200 mL taken orally twice a day） in addition to the treatment of the control group. One course of treatment lasted for three weeks，with a total of four courses conducted. Observation was performed on the piper fatigue scale （PFS） scores，karnofsky performance status （KPS） scores，European Organization for Research and Treatment of cancer quality of life questionnaire （EORTC QLQ-C30） scores，traditional Chinese medicine syndrome scores，and serum levels of tumor necrosis factor-α （TNF-α），interferon-γ （IFN-γ），and interleukin-6 （IL-6）detected via enzyme linked immunosorbent assay （ELISA） before and after treatment in the two groups. The safety test results before and after treatment for the two groups of patients，as well as the occurrence of adverse events during treatment， were recorded. Transcriptome sequencing data of peripheral blood samples from gastric adenocarcinoma patients and normal individuals were downloaded from the gene expression omnibus （GEO） database，and differentially expressed genes between the tumor and normal groups were identified. Differential gene enrichment analysis was made based on the Kyoto Encyclopedia of Genes and Genomes （KEGG） and Gene Ontology （GO）. The CRF relevance scores of genes were retrieved from the GeneCards database. Results① Compared with that before treatment，the total PFS score in the experimental group was significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced total PFS score （P<0.05）. ② Compared with that before treatment，the KPS score in the experimental group decreased significantly （P<0.05）. Compared with the control group after treatment，the experimental group exhibited a significantly decreased KPS score （P<0.05）. The experimental group demonstrated significantly increased functional scores （physical function，role function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，shortness of breath，loss of appetite，constipation，and diarrhea） of the EORTC QLQ-C30 scale after treatment compared with before treatment. Compared with the control group after treatment，the experimental group presented significantly increased functional scores （physical function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，nausea and vomiting，shortness of breath，loss of appetite，and diarrhea） of the EORTC QLQ-C30 scale （P<0.05）. Compared with those before treatment，the traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，postprandial bloating，abnormal bowel movements，lassitude and weakness，and total score） in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group had significantly reduced traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，nausea and vomiting，and sallow complexion） （P<0.05）， which indicated better efficacy in the experimental group than in the control group （χ²=7.996，P<0.05）. The serum levels of TNF-α，IL-6，and IFN-γ were significantly correlated with each other （P<0.01）. Compared with those before treatment，the levels of serum cytokines TNF-α，IL-6，and IFN-γ in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced serum levels of cytokines TNF-α，IL-6，and IFN-γ （P<0.05）. ③ There were no significant intra-group and inter-group differences in the safety test results of the two groups before and after treatment. During the treatment period，there was no significant difference in the incidence of adverse reactions between the two groups of patients. ④ Compared with the normal group，the tumor group exhibited a total of 328 significantly up-regulated genes in the peripheral blood （P<0.05），and KEGG and GO analyses showed that they were significantly enriched in signaling pathways such as TNF （P<0.05）. ⑤ TNF，IL6，IFNG， and other cytokine encoding genes may be key pathogenic genes for CRF. ConclusionXu's SQYZ decoction can alleviate symptoms such as fatigue in postoperative chemotherapy patients with gastric cancer and improve their functional status and quality of life. Its mechanism may be related to improving cytokine imbalance.

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor worldwide and also the main indication for liver transplantation in China. The refined classification of transplant recipients has driven the evolution of indications for liver transplantation in HCC and is key to achieving precise liver transplantation. Tumor number and size have always been important clinical parameters limiting the eligibility of transplant recipients. The development of single-cell and spatial transcriptomics has further revealed the spatiotemporal heterogeneity of HCC. The incorporation of molecular markers into the criteria for liver transplantation in HCC represents a milestone. A classification system based on dual molecular markers can expand the pool of suitable candidates for liver transplantation while ensuring therapeutic efficacy. In recent years, the comprehensive diagnosis and treatment model for HCC represented by immunotherapy has made significant progress. The pre-transplant downstaging treatment system has become increasingly mature, allowing more patients who were previously unsuitable for transplantation to become eligible. The rise of artificial intelligence technology has also provided new tools for patient screening, classification, prognostic evaluation, and personalized treatment, further promoting the precision of liver transplantation in HCC. Therefore, this article reviews the scientific evolution of indications for liver transplantation in HCC and the role of artificial intelligence in revolutionizing the outcomes of liver transplantation for HCC patients, with the aim of benefiting more patients with HCC.