OBJECTIVE To explore the influencing factors for immune-related endocrine toxicity in the treatment of malignant solid tumors with sintilimab， aiming to provide a reference for rational drug use. METHODS Case data were collected from patients with malignant solid tumors， who were treated with sintilimab at the First Affiliated Hospital of Jinzhou Medical University from January 1， 2020 to December 31， 2024， using the electronic medical record system. The patients were divided into an endocrine immune-related adverse events （irAEs） group and a non-endocrine irAEs group based on whether they developed immune-related endocrine toxicity after sintilimab administration. The statistical significance of predictive variables was examined through univariate and multivariate Logistic regression methods. RESULTS A total of 224 patients were enrolled， including 138 cases （61.6%） in the non-endocrine irAEs group and 86 cases （38.4%） in the endocrine irAEs group. After univariate and multivariate Logistic regression analysis， a treatment period of 1-12 cycles was identified as an independent influencing factor for immune-related endocrine toxicity [OR＝7.175， 95%CI （1.239， 41.563）， P ＜0.05 ] ， immune-related hyperglycemia [OR＝6.600， 95%CI （1.053， 41.359）， P ＜0.05 ] ， and immune-related subclinical hypothyroidism [OR＝20.200， 95%CI （3.224， 126.558）， P ＜0.05 ] . The combination with paclitaxel-based drugs was identified as an independent influencing factor for immune-related subclinical hyperthyroidism [OR＝6.410， 95%CI （1.790， 22.955）， P ＜0.05 ] . CONCLUSIONS Among patients treated with sintilimab， the treatment cycle is a risk factor for immune-related endocrine toxicity， immune-related hyperglycemia and immune-related subclinical hypothyroidism. The combination of paclitaxel-based drugs is a risk factor for immune-related subclinical hyperthyroidism. It is recommended that when applying sintilimab in clinical practice， especially during the first few treatment cycles， the relevant endocrine indicators should be dynamically monitored in a standardized manner. In addition， special attention should be paid to patients treated with the combination of paclitaxel-based drugs to be vigilant against the occurrence of endocrine adverse events.

Objective : To explore the mediating effect of self-efficacy on family health and health literacy among middle-aged and elderly chronic diseases patients in rural areas, so as to provide a basis for developing targeted health literacy improvement strategies. Methods: Based on the publicly available 2021 "Survey of Chinese Residents' Psychology and Behavior" database, rural chronic diseases patients aged >45 years were selected as the study subjects. Data on demographic information, family type, and chronic diseases comorbidities were collected. The Chinese simplified Family Health Scale, General Self-Efficacy Scale, and Health Literacy Scale were used to assess family health, self-efficacy, and health literacy, respectively. Correlation analysis was employed to explore the relationships between variables, and the 4.1 Process program was used to analyze the mediating effect of self-efficacy on family health and health literacy. The Bootstrap method was applied to test the significance of the mediating effect. Results: A total of 449 participants were included, of whom 241 were male (53.67%) and 208 were female (46.33%). The majority (205 cases, 45.66%) were aged 60-<76 years. There were 168 cases (37.42%) with chronic disease comorbidities. The total score for family health was (37.96±6.25) points. The self-efficacy score was (27.28±5.40) points, the health literacy index was (27.72±8.08) points, and the health literacy proficiency rate was only 14.90% (67 patierts). Mediating effect analysis showed that family health could directly and positively influence health literacy, with a direct effect value of 0.090 (95%CI: 0.001-0.179). It could also indirectly and positively influence health literacy through self-efficacy, with a mediating effect value of 0.164 (95%CI: 0.099-0.234). The mediating effect accounted for 64.31% of the total effect. Conclusion Self-efficacy plays a positive mediating role between family health and health literacy among middle-aged and elderly chronic diseases patients in rural areas.

ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

AIM To study the chemical constituents from Euphorbia humifusa Willd.and their in vitro anti-hepatoma activity.METHODS Silica gel,D101 macroporous adsorption resin and semi-preparative RP-HPLC were used for isolated and purified,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-hepatocellular carcinoma activity was determined by MTT mothod.RESULTS Eighteen compounds were isolated and identified as 22-O-angeloyl-R1-barrigenol(1),dimethyl 3,3'-[oxybis(4,1-phenylene)](2E,2'E)-diacrylate(2),N-(3-methoxy-1,3-dioxopropyl)-D-tryptophan methyl ester(3),N-acetyltryptophan methyl ester(4),N-(methoxycarbonyl)-tryptophan methyl ester(5),(3β,5α,17β)-4,4,8,14-tetramethyl-18-norandrostane-3,17-diol(6),3β,18,19β-trihydroxylupane(7),pregnenolone(8),3-hydroxy-5,6-epoxy-7-megastigmen-9-one(9),dehydrovomifoliol(10),loliolide(11),2,2'-oxybis(1,4-di-tert-butylbenzene)(12),dibutyl phthalate(13),4-methoxycinnamic acid(14),3,4-dimethoxycinnamic acid(15),methyl 4-hydroxybenzoate(16),kaempferol(17),quercetin(18).The IC50 values of compounds 1,7 and 8 on HepG2 cells were(17.27±0.92),(19.11±2.14)and(7.53±1.09)μmol/L,respectively.CONCLUSION Compounds 1-16 are first isolated from this plant.Compounds 1,7 and 8 have anti-hepatoma activity.

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.

AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

Objective Based on the US Food and Drug Administration(FDA)adverse event Reporting System(FAERS),to explore the signal of adverse events of basiliximab in solid organ transplantation,and to provide reference for its clinical safety.Methods The adverse drug event(ADE)signals of basiliximab in solid organ transplantation from the first quarter of 2004 to the second quarter of 2024 were retrospectively analyzed in the FAERS database of the FDA.The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were used for signal mining.Results A total of 1,581 ADE reports related to the use of basiliximab were obtained,involving 27 system/organ classifications.A total of 460 ADE signals were identified.The top 5 PT signals in terms of report frequency were mainly elevated serum creatinine,fever,cytomegalovirus infection,decreased hemoglobin,and decreased lymphocyte count.The top 5 PT signals in terms of signal intensity were mainly cytomegalovirus infection,elevated serum creatinine,decreased lymphocyte count,increased neutrophil count,and thrombotic microangiopathy.New ADE signals identified included decreased lymphocyte count,thrombotic microangiopathy,eye organ diseases,Kaposi's sarcoma,elevated blood lactate dehydrogenase,elevated transaminases,and shock.Conclusion Data mining using FAERS database is helpful to find new ADE signals of basiliximab in solid organ transplantation.Clinicians should focus on new severe ADE signals such as coagulation function,ocular organ diseases,elevated transaminase,shock and so on.