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.

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.

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

Objective: To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism． Methods: The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937，and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein．Cell morphology was observed using a microscope．Cell phenotypes were analyzed by CCK-8 assay，colony formation experiments，and flow cytometry． RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line．Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms．Western blot was used to detect the expression of downstream differentially expressed genes．The Cleavage Under Targets and Tagmentation ( CUT＆Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein，and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) ． Results: Compared with the control group，after knocking out IRF2BP2，the CCK-8 experiment showed that AML cell proliferation was inhibited ( P ＜0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P＜0. 05) ，and the proportion of G1 phase was prolonged ( P＜0. 05) ; in U937 cell lines，knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways，and the protein expression levels of pathway molecules MYC，cyclin-dependent kinase 4 ( CDK4) ，and cyclin － dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT＆Tag experiments，IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region． Conclusion IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC．

Objective: To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods: Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Results: Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .

Objective:To investigate the feasibility of ultra-low dose (ULD) CT pulmonary angiography (CTPA) combined with deep learning reconstruction (DLR) in the diagnosis of pulmonary embolism (PE).Methods:This cross-sectional study prospectively enrolled 100 patients with suspected PE who underwent CTPA examination in Zhongshan Hospital Fudan University, and Shanghai Geriatric Medical Center from April to July 2024, and were randomly divided into the routine dose (RD) group and ULD group according to block randomization. Effective dose (ED) were calculated. The noise index of RD group and ULD group was set to 10 and 20, respectively. Other scanning parameters and contrast agent injection protocol were the same. The CT images of RD group were reconstructed using hybrid iterative reconstruction (HIR), while ULD images were reconstructed with HIR and DLR (ULD-HIR subgroup and ULD-DLR subgroup). The image quality of the three groups of images was subjectively evaluated (overall image noise, pulmonary artery display) and objectively evaluated [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of the images] respectively. Finally, the diagnostic results of PE by the expert committee composed of three chief physicians were taken as the gold standard, and one physician with lower qualifications independently evaluated the diagnostic rate of PE in the three groups of images. Objective image quality parameters across the three groups were compared using ANOVA, with LSD post hoc test was used for multiple comparisons. Subjective scores among the three groups were analyzed using the Kruskal-Wallis H test, with Bonferroni corrected pairwise post hoc test was applied for multiple pairwise comparisons. Results:The ED in the RD group and ULD group were (2.7±0.5) mSv and (0.7±0.2) mSv, respectively, and the differences were statistically significant ( t=26.42, P<0.001). The overall differences in CT values of pulmonary arteries at all levels in the images of the RD group, the ULD-HIR subgroup, and the ULD-DLR subgroup were not statistically significant ( P>0.05).The RD group, ULD-HIR subgroup and ULD-DLR subgroup overall differences in SNR and CNR at all levels pulmonary arteries were statistically significant ( P<0.001), in which except for the differences in CNR and SNR values of the left pulmonary arterial trunk in the RD group and the ULD-HIR subgroup, and SNR values of basal segment pulmonary artery of the lower lobe of the left lung, which were not statistically significant ( P>0.05), the differences of the rest of the indexes in the pairwise comparisons between the groups were statistically significant ( P<0.05). The overall differences in the subjective scores of image pulmonary vascular display and image noise in the RD group, ULD-HIR subgroup and ULD-DLR subgroup were statistically significant ( P<0.001), except that the differences in the subjective scores of image pulmonary vascular display in the ULD-DLR subgroup were not statistically significant when compared with that of the RD group ( P>0.05) and that of the rest of the metrics in the between-groups two-by-two comparisons were all statistically significant ( P<0.05). The difference in diagnostic rates of PE in the pulmonary artery trunk, lobe and segmental levels in the images of the RD group, ULD-HIR subgroup and ULD-DLR subgroup was not statistically significant ( P>0.05). Conclusions:DLR can significantly reduce the radiation dose of CTPA examination. Even at ultra-low radiation dose, its image quality is still better than HIR reconstruction at conventional doses and preserve diagnostic accuracy of PE at the lobe level and segment level.

Objective:This study aimed to compare short-chain fatty acid (SCFA) levels in saliva between patients with laryngopharyngeal reflux disease (LPRD) and healthy controls, and to explore the relationship between these SCFAs and the salivary microbiota.Methods:A retrospective case-control study was conducted, enrolling 36 patients with laryngopharyngeal reflux disease (LPRD) who visited the Department of Otorhinolaryngology Head and Neck Surgery, the Eighth Medical Center, Chinese PLA General Hospital between February and November 2023. All patients were diagnosed via pharyngeal pH monitoring. The LPRD group included 30 males and 6 females, aged 20-53 years (30.61±7.83 years). In addition, 39 healthy volunteers were recruited as the control group, comprising 25 males and 14 females, aged 18–58 years (28.64±7.97 years). Unstimulated mixed saliva samples were collected from all participants. Concentrations of eight SCFAs (acetic acid, propionic acid, isobutyric acid, butyric acid, valeric acid, isovaleric acid, hexanoic acid, and heptanoic acid) in saliva were quantified using gas chromatography-mass spectrometry (GC-MS). Salivary DNA was extracted, followed by amplification and sequencing of the 16S rRNA gene to analyze the microbiota composition at the genus level. The SCFA concentrations and the differences in bacterial species between the LPRD and control groups were compared, and the correlation between SCFA concentrations and the relative abundance of different bacterial genera in the salivary microbiota was analyzed. All statistical analyses were performed using R version 3.6.1 and SPSS version 26.0, while, microbiome analyses were conducted using R language.Results:Salivary hexanoic acid concentration was significantly higher in the LPRD group than in the control group [(29.50±19.61) ng/ml vs. (10.15±3.65) ng/ml; t=-2.72, P<0.05]. Significant differences in the relative abundance of 17 bacterial genera were observed between the two groups ( P<0.05), including Prevotella, Butyrivibrio, Streptococcus, and Actinomyces. Correlation analysis revealed that hexanoic acid concentration was significantly positively correlated with the abundance of Butyrivibrio (γ=0.73, P<0.05) and Streptococcus (γ=0.78, P<0.05), while showing a significant negative correlation with Actinomyces (γ=-0.73, P<0.05). Conclusion:Elevated salivary hexanoic acid levels may be associated with the development of LPRD. Dysbiosis of the salivary microbiota might contribute to LPRD pathogenesis by altering the concentrations of SCFA, particularly hexanoic acid.