OBJECTIVE To investigate the mechanism of Shenling baizhu san （SLBZS） in ameliorating ulcerative colitis （UC）. METHODS Mice were randomly divided into normal group， model group， and low-， medium-， high-dose SLBZS groups （3， 6， 12 g/kg）， with 10 mice in each group. Except for the normal group， mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously， mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration， the histopathological morphology of colon tissues was observed； the serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-18 were detected； the total bile acid contents in liver， gallbladder and colon tissues were determined； the expression level of NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41（GPR41），GPR43，farnesoid X receptor （FXR）， G protein-coupled bile acid receptor 1 （TGR5）， flavin-containing monooxygenase 3 （FMO3）， cytochrome P450 family 27 subfamily A member 1 （CYP27A1）， CYP7A1] in liver or colon tissues， as well as the proteins related to Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3 inflammatory axis [TLR4， NF-κB， phosphorylated NF-κB （p-NF-κB）， myeloid differentiation factor 88 （MyD88）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1] in colon tissues were measured. RESULTS Compared with the model group， the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α， IL-1β and IL-18， total bile acid contents in liver and colon tissues， as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues， TLR4， p-NF-κB， NF-κB， MyD88， NLRP3， ASC and caspase-1 in colon tissues were significantly decreased （P＜0.05）. Meanwhile， the total bile acid content in gallbladder， the protein expression levels of GPR41 and GPR43 in colon tissues， along with CYP27A1， FXR and TGR5 in liver tissues were significantly increased （P＜0.05）. CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.

Objective: We employed Mendelian randomization (MR) to test the traditional Chinese medicine (TCM) theory of emotional pathogenesis concept and explore the causal relationship between negative emotions and chronic obstructive pulmonary disease (COPD). Methods: Data of negative emotions, bronchitis, emphysema, and C-reactive protein (CRP) levels were downloaded from genome-wide association study (GWAS) public database for a two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with negative emotions, bronchitis, and emphysema were selected as instrumental variables. Primary causal estimates were derived using inverse-variance weighting (IVW), supplemented by weighted median (WM), and simple mode (SM) methods. Sensitivity analyses included MR-Egger regression and MR-PRESSO to assess pleiotropy, Cochran’s Q test for heterogeneity, and multivariate MR to adjust for smoking. Mediation analysis evaluated the role of inflammatory markers. Reverse MR was tested for bidirectional causality. Weak instrument bias was mitigated via F-statistic thresholds (> 10). All analyses were conducted in RStudio. Results: MR analysis identified significant causal effects of several negative emotions on COPD. Genetically, the IVW analysis of seen doctors for nerves anxiety tension or depression [ORIVW = 1.006, 95% CI = (1.002, 1.010), P = 0.002], sensitivity/hurt feelings [ORIVW = 1.024, 95% CI = (1.004, 1.044), P = 0.017], and irritability [ORIVW = 1.019, 95% CI = (1.003, 1.035), P = 0.019 were robustly associated with increased risks of COPD. No heterogeneity was detected among the different instrumental variables (IVs) for depression (P = 0.655) and irritability (P = 0.163). MR-Egger regression intercepts for all emotional exposures were close to zero and statistically non-significant, indicating no evidence of directional pleiotropy. The horizontal pleiotropy results showed that except for worry (MR-PRESSO P = 0.006), other emotion exposures confirming no substantial pleiotropic bias. Multivariable MR demonstrated that anxiety remained independently associated with COPD after adjusting for smoking (P = 0.002), while associations with other negative emotions were attenuated post-adjustment. The mediation analysis revealed that CRP mediated 3.93% of the total effect of anxiety on COPD. However, reverse MR analysis found no evidence of reverse causality. Conclusion This study confirmed the causal effects of negative emotions on COPD through MR analysis and revealed that negative emotions may trigger CRP production, which plays an essential mediating role in this relationship. This study provides a reliable modern theoretical basis for emotion theory in TCM.

ObjectiveTo investigate the modifiable areal unit problem （MAUP） in the spatial pattern of Pseudostellaria heterophylla production regions and reveal the impact of statistical scales on the spatial distribution characteristics of this medicinal plant species. MethodsUsing multi-source data （literature records， field surveys， and statistical data）， we systematically analyzed the spatial patterns across three administrative levels （provincial， prefectural， and county scales）. Spatial autocorrelation （Moran's I） analysis， high-low clustering （Getis-Ord General G）， and hot/cold spot analysis （Getis-Ord Gi*） were employed. ResultsThe literature-based analysis showed that the production regions of P. heterophylla presented random distribution on the provincial scale and significant aggregation on the prefectural scale. The field survey data showed that the production regions displayed random distribution on the provincial scale but significant aggregation on both prefectural and county scales. The statistical data revealed that the production regions lacked spatial autocorrelation on the provincial scale but demonstrated significant aggregation on prefectural and county scales. ConclusionMAUP effects have substantive implications for understanding and decision-making in the arrangement of medicinal plant production regions. The county scale proves to be the most sensitive and explanatory level for analyzing the spatial pattern of P. heterophylla production regions， providing a critical foundation for habitat modeling， suitability evaluation， and ecological cultivation planning of medicinal plants.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To analyze the application effects of artificial intelligence (AI) software and Mimics software in preoperative three-dimensional (3D) reconstruction for thoracoscopic anatomical pulmonary segmentectomy. Methods A retrospective analysis was conducted on patients who underwent thoracoscopic pulmonary segmentectomy at the Second People's Hospital of Huai'an from October 2019 to March 2024. Patients who underwent AI 3D reconstruction were included in the AI group, those who underwent Mimics 3D reconstruction were included in the Mimics group, and those who did not undergo 3D reconstruction were included in the control group. Perioperative related indicators of each group were compared. Results A total of 168 patients were included, including 73 males and 95 females, aged 25-81 (61.61±10.55) years. There were 79 patients in the AI group, 53 patients in the Mimics group, and 36 patients in the control group. There were no statistical differences in gender, age, smoking history, nodule size, number of lymph node dissection groups, postoperative pathological results, or postoperative complications among the three groups (P>0.05). There were statistical differences in operation time (P<0.001), extubation time (P<0.001), drainage volume (P<0.001), bleeding volume (P<0.001), and postoperative hospital stay (P=0.001) among the three groups. There were no statistical differences in operation time, extubation time, bleeding volume, or postoperative hospital stay between the AI group and the Mimics group (P>0.05). There was no statistical difference in drainage volume between the AI group and the control group (P=0.494), while there were statistical differences in operation time, drainage tube retention time, bleeding volume, and postoperative hospital stay (P<0.05). Conclusion For patients requiring thoracoscopic anatomical pulmonary segmentectomy, preoperative 3D reconstruction and preoperative planning based on 3D images can shorten the operation time, postoperative extubation time and hospital stay, and reduce intraoperative bleeding and postoperative drainage volume compared with reading CT images only. The use of AI software for 3D reconstruction is not inferior to Mimics manual 3D reconstruction in terms of surgical guidance and postoperative recovery, which can reduce the workload of clinicians and is worth promoting.

Objective:To establish an accurate, stable, and convenient Taka amylase enzymolysis ion-selective electrode method for determination of trace fluoride in Mongolian milk tea powder.Methods:The samples of instant Mongolian milk tea powder were heated and dried at 50 ℃, 1.0 g of the sample was accurately weighed and dissolved in pure water. The sample solution, Taka amylase, and total ion strength buffer solution were mixed and enzymatically hydrolyzed in a 55 ℃ water bath for 60 minutes. After cooling, filtration was carried out. The clarified liquid was collected and the fluoride content was detected by the ion-selective electrode method, and the method validation test was conducted.Results:When the standard linear concentration range was 0.2 to 5.0 mg/L, the correlation coefficient ranged from 0.999 5 to 0.999 9. The detection limit of the method was 0.006 mg/kg. The relative standard deviations ( RSD) for detecting high, medium, and low concentration samples were 0.8%, 1.9%, and 2.1%, respectively. The recovery rates ranged from 98% to 101%, 95% to 101%, and 101% to 107%, respectively. This method simultaneously measured the same batch of samples with the second method of the "National Food Safety Standard - Determination of Fluorine in Foods" (GB 5009.18-2025) - the ion-selective electrode method. The results were (23.1 ± 7.7) and (22.5 ± 7.6) mg/kg, respectively. There was no statistically significant difference between the two methods ( t = 2.01, P = 0.066). Conclusion:The Taka amylase enzymolysis ion-selective electrode method has good reproducibility and high accuracy, making it suitable for determination of trace fluoride in Mongolian milk tea powder.

Objective:To investigate the feasibility of ductus arteriosus (DA) stent placement through femoral artery approach without guiding catheter.Methods:In this retrospective case study, the birth weight, intervention age, preoperative echocardiography, intraoperative angiography and other clinical data, as well as the follow-up status (Nakata index and final circulatory status, etc.) of 15 patients with congenital heart disease who are dependent on the DA for pulmonary circulation at Women and Children′s Hospital, Qingdao University between January 2018 to June 2023 were collected. All pediatric patients underwent placement of a DA stent without a guiding catheter, the efficacy and safety of this approach were analyzed.Results:Among all 15 cases, there were 9 males and 6 females, with the birth weight of (3.3±0.3) kg and the intervention age of (15.0±0.1) d. Of which, there were 9 cases of pulmonary atresia with intact ventricular septum (PA-IVS), and 6 cases of critical pulmonary stenosis (CPS) with intact ventricular septum. The tricuspid annulus diameter before intervention was (8.8±0.8) mm, and the tricuspid annulus Z-score was -0.7±0.9. There were 3 cases of mild right ventricular dysplasia, 9 cases of moderate dysplasia, and 3 cases of severe dysplasia. All patients successfully completed the intervention without major complications. The narrowest diameter of the DA was (2.2±0.1) mm, the diameter of the DA stent was (3.9±0.3) mm, the preoperative percutaneous oxygen saturation (SpO 2) was 0.83±0.03, and the postoperative SpO 2 was 0.96±0.02. The follow-up time was (7.0±0.5) months. The Nakata index was (163±30) mm 2/m 2 before intervention, and was (173±34) mm 2/m 2 at the last follow-up. Biventricular circulation was successfully achieved in 14 patients, and the other one patient currently under close observation. Conclusion:The placement of a ductus arteriosus stent through femoral artery retrogradely without guiding catheter could serve as an effective and safe plan for neonates with PA-IVS or CPS accompanied by hypoplastic right heart syndrome.

Objective:To analyze the current status and factors influencing clinician participation in remote patient management in China.Methods:In December 2023, a structured electronic questionnaire was administered to 7 980 clinicians, including 930 cardiologists. The survey assessed clinicians′ participation in online doctor-patient interactions; differences in hospital support across city tiers, hospital grades, professional titles, and departments; and factors influencing the willingness of clinicians to invest time in remote patient management.Results:Among the 7 980 surveyed clinicians, online consultations had the highest participation rate (72.2%). Among cardiologists, participation rates for online consultations, health education, and post-consultation management were 73.3%, 66.9%, and 38.5%, respectively, which were relatively higher than those of other specialties. Hospital-based support for physicians in remote patient management showed significant variations across specialties and regions. Among cardiologists, 68.4% received "encouraging" policies, with the majority falling under "encouragement without incentive policies" (42.6%). In tier 3 cities, the proportion of physicians receiving "encouragement without incentive policies" was the highest (47.9%), while the proportion in the "cautious, requiring reporting" category was the lowest (3.9%). During remote patient management, the proportions of clinicians receiving support from professional teams were highest among those in tier 3 cities (29.6%) and cardiologists (30.5%). A significant interaction effect was observed between hospital policy and specialty (cardiologists vs. all clinicians) regarding physicians′ willingness to invest time in remote patient management ( F=5.95, P<0.001). Among cardiologists, those working in institutions with "encouraging, with incentives" policies reported a significantly longer median weekly investment time (10.0 h) compared to those under "neutral, unrestricted" policies (7.0 h, P<0.001). Cardiologists with team support reported a significant increase in the time they were willing to invest (10 h/week) than those without team support (7.0 h/week, P<0.001), although no significant interaction effect was found when compared with all clinicians ( P=0.186). Cardiologists with a high online income (>5 000 Yuan/month) reported a significantly longer weekly investment time in remote management (25.0 h) compared to those with lower income (<200 yuan/month; 8.0 h, P<0.001). However, whether the income met their personal expectations had no significant effect on their time commitment ( P=0.638). Conclusions:Clinicians from tertiary hospitals and tier 3 cities demonstrated a higher level of engagement in remote patient management. Strengthening hospital policy support, enhancing team-based collaborations, and increasing online income levels may help promote the broader adoption of telemedicine.

Objective:To investigate the current awareness of large language models (LLM) among Chinese clinical physicians and analyze the application needs of cardiovascular specialists.Methods:This is a cross-sectional study utilized convenience sampling. In December 2023, a self-designed questionnaire was distributed to 7 980 clinical physicians, including 930 cardiologists. The survey collected demographic information, including work city (categorized as first-tier, new first-tier, second-tier, third-tier, and fourth-tier and below), hospital level, professional title, and department. And the awareness of LLM, and their application demands in clinical decision-making support, information filtering, and scientific research work were also collected. Differences in awareness and application requirements across geographic regions, hospital tiers, professional ranks, and medical departments were analyzed. Besides, specific demands of cardiovascular specialists were further examined.Results:Among the 7 980 clinical physicians, the awareness rate of LLM was 76.3% (6 088/7 980), and the utilization rate was 11.8% (942/7 980). For the 930 cardiologists, the awareness rate was 78.5% (730/930) and the utilization rate was 11.4% (106/930). Significant differences in awareness and utilization rates were observed across city tiers, hospital grades, and departments (all P<0.05). No significant difference was found among professional titles ( P=0.053). Among the 6 088 physicians aware of LLM, demand rates for clinical information filtering, clinical decision support, and research assistance were 87.3% (5 312/6 088), 78.4% (4 774/6 088), and 75.8% (4 616/6 088), respectively. For the 730 cardiologists aware of LLM, these rates were 91.0% (664/730), 79.2% (578/730), and 75.9% (554/730), respectively. Significant differences in demands for clinical information filtering and research assistance were observed across city tiers, hospital grades, professional titles, and departments (all P<0.05), while no significant difference was noted for decision support demands across hospital grades ( P=0.085). In clinical information screening and acquisition, cardiologists from different city tiers exhibited statistically significant differences in the demand for literature interpretation. Similarly, variations in the demand for conference summaries, expert biographies, healthcare policies, and social news were noted among cardiologists with different professional titles, while disparities in patient education and science popularization needs were identified across city tiers and hospital grades (all P<0.05). In clinical decision-making support, cardiologists from diverse city tiers and professional titles demonstrated distinct differences in guideline and consensus inquiries, and those from various city tiers showed varied demands for pharmaceutical and medical device-related content (all P<0.05). For research support, cardiologists across city tiers and professional titles exhibited statistically significant differences in trial protocol design requirements, while those from varying city tiers differed in literature search/analysis and research application procedures. Additionally, physicians from different hospital grades displayed divergent needs for data collection (all P<0.05). Conclusions:The adoption of LLM is significantly influenced by regional disparities, institutional resources, and professional backgrounds. Implementing targeted interventions, such as enhancing technical training, optimizing LLM functionalities, and improving accessibility across diverse healthcare settings, could encourage widespread integration of LLM into clinical practice. Such measures could ultimately enhance the quality and efficiency of medical services in China and foster innovations in healthcare delivery.

In order to delve into the molecular mechanism underlying the increased pathogenicity of the recombinant Muscovy duck parvovirus(rMDPV)towards Muscovy ducklings,two sub-genom-ic fragments of the rMDPV strain ZW were cloned into the plasmid pBluescript Ⅱ(SK)to gener-ate the recombinant plasmid pZW.A single nucleotide mutation was engineered in the VP3 gene of pZW to discriminate from the parental strain ZW.pZW plasmid-lipid complex was transfected into the chorioallantoic membrane of 11-day-old embryonated Muscovy duck embryos,resulting in res-cue of infectious virus,rZW,carrying the genetic marker.The rescued virus was passaged in 12-day-old embryonated Muscovy duck embryos and exhibited the similar medium embryo lethal dose(ELD50)value and growth curve compared to the parental strain ZW.Both rZW and strain ZW led to 100％mortality in the infection tests performed with 3-day-old Muscovy duckling.Postmortem necropsy revealed a characteristic intestine embolism formed in the rZW-infected ducklings.Taken together,the generation of the infectious clone pZW lays a solid foundation for deciphering the pathogenesis of rMDPV.