In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

ObjectiveTo develop a standardized living will manual suitable for promotion in China， combining existing literature and the current implementation status of living will both domestically and internationally as well as the characteristics of modern medicine. MethodsA pool of manual entries was constructed through hospital interviews and literature retrieval. A Delphi method expert correspondence was conducted to modify and supplement the manual entry settings. The results of the correspondence were statistically analyzed to verify the reliability and scientific validity of the manual and the correspondence. ResultsThis study constructed a pool of manual entries by conducting interviews in four hospitals in Beijing and retrieving and including 155 pieces of literature，and developed a preliminary version of the manual with a total of 40 entries in four sections， namely medicine， psychology， society， and farewell. The manual items were revised through two rounds of the Delphi method correspondence with a total of 88 experts. The expert response rates in the two rounds of the correspondence questionnaires were 100% and 90%， respectively； the expert authority coefficients were 0.84 and 0.865， respectively； and Kcndall W was 0.141 and 0.077， respectively. In terms of the reliability test， the Cronbach’s α coefficients of the two rounds of correspondence were 0.941 and 0.969， respectively， and the Guttman coefficients were 0.862 and 0.857， respectively. As for the validity test， the Pearson correlation coefficient for 39 entries was R>0.4 in the first round of correspondence， and for 41 entries was R>0.4 in the second round of correspondence； a total of 20 entries in the first round of correspondence had an I-CVI ≥ 0.780， and the scale’s S-CVI was 0.786； a total of 31 entries in the second round of correspondence had an I-CVI ≥ 0.780， and the scale’s S-CVI was 0.846. Meanwhile， this study developed a legal instrument section of the manual including personal information， effective time， modification and revocation， witnesses， and other contents by reviewing relevant laws and regulations both domestically and internationally. ConclusionThe standardized living will manual is comprehensive， reliable， and scientific， which makes it suitable for promotion and further improvement.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To analyze the influencing factors of severe dengue fever patients in the early stage, construct a early prediction model for severe dengue fever, and evaluate it.Methods:A retrospective analysis was conducted to collect early clinical data of dengue fever patients admitted to the People's Hospital of Mengla County and the Third People's Hospital of Kunming in Yunnan Province from July to December 2023. The multifactor logistic regression was used to analyze the factors affecting the severe dengue fever patients, and Nomogram prediction model was used for visualization. Receiver operating characteristic (ROC) curve and calibration curve analysis were used to evaluate the model.Results:A total of 534 dengue fever patients were included, including 291 males and 243 females, aged (39.95 ± 15.69) years. Among them, there were 59 cases (11.05%) of severe dengue fever. The results of multifactor logistic regression analysis showed that age ( OR = 1.05, 95% CI: 1.02 - 1.08, P < 0.001), cardiovascular disease ( OR = 5.28, 95% CI: 2.08 - 13.40, P < 0.001), serous effusion ( OR = 4.34, 95% CI: 1.63 - 11.57, P = 0.003), aspartate aminotransferase ( OR = 1.03, 95% CI: 1.02 - 1.04, P < 0.001), lactate dehydrogenase ( OR = 1.00, 95% CI: 1.00 - 1.01, P = 0.001), and fibrinogen ( OR = 0.46, 95% CI: 0.28 - 0.76, P = 0.003) were independent influencing factors in the early stage of severe dengue fever. The area under the ROC curve of the Nomogram prediction model constructed from the above six variables was 0.96 (0.93 - 0.98). The calibration curve analysis results showed that the mean absolute error between the predicted values of the Nomogram prediction model and the actual observed values was 0.014. Conclusions:Age, cardiovascular disease, serous effusion, aspartate aminotransferase, lactate dehydrogenase, and fibrinogen are independent influencing factors in the early stage of severe dengue fever. The Nomogram prediction model established based on these variables has good predictive ability for severe dengue fever.

Objective:To investigate the utilization of inpatient service and influencing factors among pneumoconiosis patients in Chongqing within one year, and to provide a reference basis for the formulation of relevant policies by health management departments.Methods:From October 2020 to October 2023, a multi-stage cluster random sampling method was adopted to select 2002 patients with confirmed pneumoconiosis as the research subjects. A questionnaire survey was conducted on their basic information, inpatient service utilization within one year, treatment for pneumoconiosis-related symptoms, and choice of medical service institutions. Chi-square test and logistic regression were used for statistical analysis.Results:All 2002 pneumoconiosis patients were male, with 40.16% (804/2002) aged 46-55 years old, and 83.32% (1668/2002) currently residing in rural areas. The monthly income of the patients was 833 (167, 2000) yuan, and 22.03% (441/2002) had no income. 30.97% (620/2002) of the patients spent more than 5001 yuan per year on treatment for pneumoconiosis, and 14.64% (293/2002) had debts of more than 5001 yuan. 42.06% (842/2002) had no work-related injury insurance. 21.68% (434/2002) of the patients self-assessed their health status as very poor or poor. The one-year inpatient rate of the patients was 51.25% (1026/2002), and the total inpatient time within one year was 18 (10, 51) days. The inpatient expenses were 6000 (1000, 16625) yuan. Through univariate analysis, the one-year inpatient rates of pneumoconiosis patients were statistically significantly different among different age groups, current employment status, annual household income levels, types of pneumoconiosis, stages of pneumoconiosis, presence or absence of work-related injury insurance, whether receiving minimum living allowances and social assistance related to pneumoconiosis, and different segments of self-assessed health status ( P<0.05). Patients with stage Ⅲ pneumoconiosis, those who received social assistance and minimum living allowances related to pneumoconiosis had higher one-year inpatient rates ( P<0.05), with OR values of 3.893, 1.859, and 2.589, respectively. Conclusion:The utilization of inpatient service by pneumoconiosis patients is influenced by demographic characteristics, social support, and disease factors. It is necessary to enhance the occupational disease diagnosis and treatment capabilities of primary health institutions, build a multi-level social support network, and ensure that patients can conveniently access medical services.

Objective:To analyze the influencing factors of severe dengue fever patients in the early stage, construct a early prediction model for severe dengue fever, and evaluate it.Methods:A retrospective analysis was conducted to collect early clinical data of dengue fever patients admitted to the People's Hospital of Mengla County and the Third People's Hospital of Kunming in Yunnan Province from July to December 2023. The multifactor logistic regression was used to analyze the factors affecting the severe dengue fever patients, and Nomogram prediction model was used for visualization. Receiver operating characteristic (ROC) curve and calibration curve analysis were used to evaluate the model.Results:A total of 534 dengue fever patients were included, including 291 males and 243 females, aged (39.95 ± 15.69) years. Among them, there were 59 cases (11.05%) of severe dengue fever. The results of multifactor logistic regression analysis showed that age ( OR = 1.05, 95% CI: 1.02 - 1.08, P < 0.001), cardiovascular disease ( OR = 5.28, 95% CI: 2.08 - 13.40, P < 0.001), serous effusion ( OR = 4.34, 95% CI: 1.63 - 11.57, P = 0.003), aspartate aminotransferase ( OR = 1.03, 95% CI: 1.02 - 1.04, P < 0.001), lactate dehydrogenase ( OR = 1.00, 95% CI: 1.00 - 1.01, P = 0.001), and fibrinogen ( OR = 0.46, 95% CI: 0.28 - 0.76, P = 0.003) were independent influencing factors in the early stage of severe dengue fever. The area under the ROC curve of the Nomogram prediction model constructed from the above six variables was 0.96 (0.93 - 0.98). The calibration curve analysis results showed that the mean absolute error between the predicted values of the Nomogram prediction model and the actual observed values was 0.014. Conclusions:Age, cardiovascular disease, serous effusion, aspartate aminotransferase, lactate dehydrogenase, and fibrinogen are independent influencing factors in the early stage of severe dengue fever. The Nomogram prediction model established based on these variables has good predictive ability for severe dengue fever.

Objective:To investigate the utilization of inpatient service and influencing factors among pneumoconiosis patients in Chongqing within one year, and to provide a reference basis for the formulation of relevant policies by health management departments.Methods:From October 2020 to October 2023, a multi-stage cluster random sampling method was adopted to select 2002 patients with confirmed pneumoconiosis as the research subjects. A questionnaire survey was conducted on their basic information, inpatient service utilization within one year, treatment for pneumoconiosis-related symptoms, and choice of medical service institutions. Chi-square test and logistic regression were used for statistical analysis.Results:All 2002 pneumoconiosis patients were male, with 40.16% (804/2002) aged 46-55 years old, and 83.32% (1668/2002) currently residing in rural areas. The monthly income of the patients was 833 (167, 2000) yuan, and 22.03% (441/2002) had no income. 30.97% (620/2002) of the patients spent more than 5001 yuan per year on treatment for pneumoconiosis, and 14.64% (293/2002) had debts of more than 5001 yuan. 42.06% (842/2002) had no work-related injury insurance. 21.68% (434/2002) of the patients self-assessed their health status as very poor or poor. The one-year inpatient rate of the patients was 51.25% (1026/2002), and the total inpatient time within one year was 18 (10, 51) days. The inpatient expenses were 6000 (1000, 16625) yuan. Through univariate analysis, the one-year inpatient rates of pneumoconiosis patients were statistically significantly different among different age groups, current employment status, annual household income levels, types of pneumoconiosis, stages of pneumoconiosis, presence or absence of work-related injury insurance, whether receiving minimum living allowances and social assistance related to pneumoconiosis, and different segments of self-assessed health status ( P<0.05). Patients with stage Ⅲ pneumoconiosis, those who received social assistance and minimum living allowances related to pneumoconiosis had higher one-year inpatient rates ( P<0.05), with OR values of 3.893, 1.859, and 2.589, respectively. Conclusion:The utilization of inpatient service by pneumoconiosis patients is influenced by demographic characteristics, social support, and disease factors. It is necessary to enhance the occupational disease diagnosis and treatment capabilities of primary health institutions, build a multi-level social support network, and ensure that patients can conveniently access medical services.

Objective:To investigate the efficacy of negative pressure wound therapy (NPWT) combined with a retrograde sural neurovascular flap for the repair of foot and ankle wounds.Methods:Eighty-eight patients with foot and ankle wounds who received treatment in Shandong Wendeng Osteopathic Hospital from July 2019 to January 2020 were included in this study. They were randomly assigned to undergo either NPWT combined with retrograde sural neurovascular flap repair (observation group, n = 44) or retrograde sural neurovascular flap repair alone (control group, n = 44). Clinical efficacy, flap survival, wound healing, and postoperative ankle function scores were compared between the two groups. Results:Total response rate was significantly higher in the observation group than in the control group [97.73% (43/44) vs. 81.82% (36/44), χ2 = 6.07, P = 0.014]. Flap survival rate was significantly higher in the observation group than in the control group [100.00% (44/44) vs. 86.36% (38/44), χ2 = 4.47, P = 0.034]. Wound healing rate was significantly higher in the observation group than in the control group [97.73% (43/44) vs. 79.55% (35/44), χ2 = 7.22, P = 0.007]. Half a year after surgery, pain score, gait score, foot and ankle swelling score, range of motion of the tibiotalar joint, range of motion of the ankle joint were (1.81 ± 0.45) points, (1.40 ± 0.41) points, (1.98 ± 0.38) points, (0.41 ± 0.35) points, and (0.84 ± 0.51) points, respectively in the observation group, which were significantly lower than those in the control group ( t = 2.63, 2.62, 2.15, 2.09, 2.02, all P < 0.05). Conclusion:NPWT combined with a retrograde sural neurovascular flap greatly increases flap survival rate and wound healing rate and improves the ankle function of patients with foot and ankle wounds.