OBJECTIVE To optimize the extraction process of Shenye buyi formula. METHODS Based on the quality by design （QbD） concept， the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin，and glycyrrhizic acid ammonium salt， as well as the extract yield， were selected as the critical quality attributes （CQAs） for the extraction process of Shenye buyi formula. The fishbone diagram combined with the failure model and effect analysis method was adopted to determine the water addition， extraction time and extraction times as critical process parameters （CPPs）. High-performance liquid chromatography was employed to detect the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin， and glycyrrhizic acid ammonium salt. The analytic hierarchy process-entropy weight method was used to comprehensively assign weights to the content of the five components including rutin and the extract yield. The Box-Behnken response surface method was employed to fit the mathematical model between CQAs and CPPs， screen the operational space of the extraction process， and validate it. RESULTS The optimal operational space of the extraction process was 9.5 to 12 times the amount of water added， the extraction time was 1 to 1.7 hours， and the extraction times were 3. Upon verification，the comprehensive scores of the optimal extraction process within the operational space were 89.79 and 84.93， respectively. CONCLUSIONS The extraction process of the Shenye buyi formula can be applied to the development and production of its granule preparations.

Objective To construct and compare logistic regression and decision tree models for predicting systemic inflammatory response syndrome (SIRS) in patients with type B aortic dissection (TBAD) after interventional surgery. Methods A retrospective analysis was conducted on clinical data of TBAD patients at Peking University Shenzhen Hospital from 2020 to 2024. The patients were divided into a SIRS group and a non SIRS group based on whether SIRS occurred within 24 hours after surgery. Multivariate logistic regression was used to analyze the influencing factors of SIRS occurrence in TBAD intervention patients, and a decision tree model was constructed using SPSS Modeler to compare the predictive performance of the two models. Results A total of 742 patients with TBAD were included, including 579 males and 163 females, aged 27-97 (58.85±10.79) years. Within 24 hours after intervention, a total of 506 patients developed SIRS, with an incidence rate of 68.19%. Logistic regression analysis showed that the extensive involvement of the dissection, the surgical time≥2 hours, PET coated stents implanted, serum creatinine, white blood cell count, C-reactive protein, monocyte (MONO), neutrophil count levels elevated, estimated glomerular filtration rate and decreased albumin levels were independent risk factors for SIRS (P<0.05). The decision tree model selected a total of 10 explanatory variables and 6 layers with 37 nodes, among which MONO was the most important predictor. The area under the decision tree model curve was 0.829 [95%CI (0.800, 0.856)], which was better than the logistic regression model's 0.690 [95%CI (0.655, 0.723)], and the difference was statistically significant (P<0.001). Conclusion The incidence of SIRS after TBAD intervention is high, and the decision tree model has better predictive performance than logistic regression. It can identify high-risk patients with higher accuracy and provide a practical tool for early clinical intervention.

BACKGROUND:Meningeal lymphatic vessels can drain cerebral spinal fluid and amyloid β-protein,promoting T lymphocyte to transport and home to deep cervical lymph nodes.A simple,quick and definite method of dural separation and accurate localization of deep cervical lymph nodes can provide strong support for the study of neurodegenerative diseases.OBJECTIVE:To establish a convenient and practical method for exfoliating dural and deep cervical lymph nodes.METHODS:ICR mice,3 months old,were taken,anesthetized and injected with Evans blue and tracer in the occipital pool for localizing deep cervical lymph nodes.A midline incision of about 3 cm in length was made about 5 mm above the clavicle,the superficial fat and fascia were bluntly separated,and the lateral sternocleidomastoid muscle was pulled to expose the deep cervical lymph nodes,which were removed under a stereomicroscope and frozen at-80℃.Subsequently,the mouse head was cut and the skin and muscles of the head were separated to expose the entire skull structure.The skull and brain tissue were separated from the foramen magnum along the lower parietal bone with scissors,and the complete skull top was obtained.The skull was sequentially fixed in 40 g/L paraformaldehyde solution for 24 hours,120 g/L paraformaldehyde for 24 hours,and 120 g/L paraformaldehyde for 10,20,30,and 40 minutes,and the dural structure was stripped.The drainage capacity of meningeal lymphatic vessels and deep cervical lymphatic vessels was verified by tracer,and the meningeal lymphatic vessels were identified by the lymphatic vessel endothelial hyaluronan receptor 1 using the immunofluorescence method.RESULTS AND CONCLUSION:(1)Obvious blue staining was observed in deep cervical lymph nodes 15 minutes after Evans blue staining.(2)The skull was sampled and fixed in 120 g/L paraformaldehyde for 24 hours,resulting in a less tight connection between the dura mater and the skull,and easier stripping of the dural structures with an intact shape.The dura mater fixed at 120 g/L concentration was more resilient and remained more intact during peeling compared with the conventional 40 g/L concentration;120 g/L paraformaldehyde fixed meninges for a short time,and 30-40 minutes was preferred.(3)The frozen section of deep cervical lymph nodes showed the presence of the tracer,complete meningeal lymphatic vessels were visible in the dura mater,and the tracer was observed at the tail of lymphatic vessels.Immunofluorescence staining for endothelial hyaluronan receptor 1 was positive in the deep cervical lymph nodes and dural lymphatics.In summary,the best peeling concentration and time is 120 g/L paraformaldehyde fixed for 24 hours.At this concentration,the dura mater has a stretched morphology,a better toughness,and is more intact after peeling,which is conducive to later use.Verified by Evans blue,tracers and immunofluorescence,deep cervical lymph nodes are located accurately,which can be used as a basis for the study of various neurodegenerative diseases.

Sodium glucose cotransporter(SGLT)2 inhibitors,initially developed as antihyperglycemic agents,have demonstrated remarkable cardioprotective effects in numerous clinical trials and are now utilized in the treat-ment of heart failure across a range of ejection fractions.SGLT2 is predominantly expressed in the renal proximal tubules,brain,and epicardial adipose tissue within the human body.Research indicates that the protective effects of SGLT2 inhibi-tors in heart failure are linked to their direct modulation of SGLT2 receptors in both the kidneys and epicardial adipose tis-sue.Furthermore,SGLT is also present in the brain,and recent studies have revealed that SGLT2 inhibitors can enhance sympathetic activity in patients with metabolic syndrome,suggesting a potential neuroregulatory role.Given that excessive activation of the sympathetic nervous system can contribute to the onset and progression of heart failure,this paper reviews the neural regulatory mechanisms of SGLT2 inhibitors to provide insights for a deeper understanding of heart failure and to optimize their clinical application.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective:To analyze the differences in clinicopathological features between non-elderly and elderly patients with melanoma, and to identify risk factors for prognosis in elderly patients with melanoma.Methods:A retrospective analysis was conducted on clinical and pathological data collected from non-elderly (aged < 60 years) and elderly (aged ≥ 60 years) patients with melanoma, who were confirmedly diagnosed according to clinical manifestations and histopathological findings at the People's Hospital of Xinjiang Uygur Autonomous Region from January 2008 to December 2023. The differences in clinical and pathological characteristics between the two groups were analyzed using the chi-square test and Wilcoxon rank-sum test. Survival curves were estimated using the Kaplan-Meier method and log-rank test. The relationship between clinicopathological variables and overall survival was analyzed using a Cox regression model.Results:A total of 233 patients with cutaneous melanoma were included, with the age being 60.3 ± 14.7 years, and the number of patients was highest in the age group of 60 - 69 years. There were 102 cases (43.8%) in the < 60 years old group and 131 cases (56.2%) in the ≥ 60 years old group. Compared with the < 60 years old group, the ≥ 60 years old group showed a significant increase in the proportion of patients with active tumor-infiltrating lymphocytes ( P = 0.040), proportion of those with Ki-67 index ≥ 30% ( P = 0.010), and Charlson comorbidity index ( P = 0.002), but a significant decrease in the proportion of patients with BRAF/KIT/NRAS mutations ( P = 0.003), proportion of those receiving surgical treatment ( P = 0.034), and proportion of those receiving adjuvant therapy ( P = 0.042). There was a significant difference in the overall survival between the two groups (log-rank test, χ2 = 6.10, P = 0.014). The gender, metastasis status, presence or absence of ulceration, distant metastasis status, American Joint Committee on Cancer staging, Charlson comorbidity index, and Breslow thickness were important prognostic indicators affecting the overall survival in the elderly patients with melanoma. Multivariate Cox regression analysis showed that males ( P = 0.015, HR = 4.622, 95% CI: 1.352 - 15.798), presence of distant metastasis ( P = 0.013, HR = 9.844, 95% CI: 4.621 - 59.763), and Charlson comorbidity index ≥ 3 ( P = 0.038, HR = 3.149, 95% CI: 1.067 - 9.294) were independent risk factors affecting the overall survival in the elderly patients with melanoma. Conclusions:Compared with the non-elderly patients with melanoma, a higher Ki-67 index, a higher Charlson comorbidity index, less surgical treatment, and less adjuvant therapy were more common in the elderly patients with melanoma. Males, the presence of distant metastasis, and Charlson comorbidity index ≥ 3 appeared to be independent risk factors affecting the overall survival in the elderly patients with melanoma.

Objective:To evaluate the role of tumor necrosis factor-α-induced protein 8-like molecule-2 (TIPE2) in the endogenous protective mechanism against acute lung injury in septic mice and the relationship with ferroptosis.Methods:Twenty SPF healthy wild-type male C57BL/6N mice and 20 TIPE2 gene knockout C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were assigned to wild-type sham operation group (WT-Sham group), wild-type sepsis group (WT-SEP group), TIPE2 knockout sham operation group (KO-Sham group), and TIPE2 knockout sepsis group (KO-SEP group) using a random number table method, with 10 mice in each group. Acute lung injury was induced by cecal ligation and perforation in anesthetized mice. The animals were sacrificed after anesthesia at 24 h after operation and lung tissues were obtained for examination of the morphological results of lung tissues (with a light microscope) and for determination of wet to dry lung weight (W/D) ratio, contents of ferrous ions (Fe 2+ ), glutathione (GSH) and malondialdehyde (MDA) and expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot). Results:Compared with WT-Sham group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in KO-SEP group ( P<0.05). Conclusions:TIPE2 is involved in the endogenous protective mechanism against acute lung injury, which may be related to the inhibition of ferroptosis in lung tissues of septic mice.

Objective:To investigate the effectiveness of the 5A (Ask, Assess, Advise, Assist, Arrange follow-up) management model based on personalized health education records in community patients with type 2 diabetes mellitus.Methods:A convenience sampling method was used to select patients with type 2 diabetes mellitus who were enrolled with family doctors in Yuxin Community, Haidian District, Beijing, from January 2022 to May 2023. Using a random number table method, the patients were divided into an observation group ( n=68) and a control group ( n=68). The control group received routine community management, while the observation group received management based on the 5A model and personalized health education records. Differences in metabolic indicators, including glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, body mass index (BMI), and waist circumference, as well as self-management behaviors were compared between the two groups at 3, 6, and 12 months of intervention. Results:During the entire intervention period, four cases were lost in the observation group and eight cases were lost in the control group. Finally, data from 124 patients were included in the analysis, including 64 cases in the observation group and 60 cases in the control group. Repeated measures analysis of variance showed interaction effects between time points and groups for HbA1c, BMI, waist circumference, and self-management behavior scores among patients with diabetes, with statistically significant differences ( P<0.05) . Conclusions:The 5A management model based on personalized health education records has a positive impact on improving metabolic indicators and self-management behaviors in community patients with type 2 diabetes mellitus.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.