ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

[Objective]To investigate LI Dongyuan's theory of"any deficiency of spleen and stomach is a disease of the blood"and provide reference for modern clinical practice.[Methods]Taking Discussion on Internal and External Injuries,Treatise on Spleen and Stomach,Orchid Chamber of Secrets and Invention of Medicine as references,it starts from the connotation of"any deficiency of spleen and stomach is a disease of the blood",and explores the etiology and pathogenesis of the diseases,the theoretical construction and the clinical application respectively.[Results]Taking Inner Canon of Yellow Emperor and Zhongjing's academic thought as the source,absorbing CHENGs' and ZHU Xi's ideas of science.Being inspired by his teacher ZHANG Yuansu,and driven by his own clinical practice,LI Dongyuan put forward the academic thought of"any deficiency of spleen and stomach is a disease of the blood".From the Treatise on Spleen and Stomach-Treatise on the Prosperity and Decline of Spleen and Stomach,"any deficiency of spleen and stomach is a disease of the blood",which is a pathological state caused by the deficiency of spleen and stomach Qi and the weakness of elevation due to the disorders of emotions and moods,overwork and overdose,and uncontrolled diets,there fore causes insufficient blood production and too much blood consumption,and then leads to the deficiency of blood and Yin,and the essence of which is the disordered ascending,descending,floating and sinking of the human body's Qi.In treatment,LI Dongyuan always based on regulating blood,to restore the body's Qi,and harmonize Qi and blood as the goal,with"blood replenishment must have Yang Qi,Qi and blood double tonic""rising Yang must be in response to the time of the day,and make good use of the wind herbs""relieving heat must protect the Yin and blood,moderation in attacking and destroying".[Conclusion]Exploring this theory can help to view the relationship between Qi and blood from a new perspective,better grasp LI Dongyuan's academic thinking,and provide reference for the treatment of spleen and stomach diseases and blood diseases.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

Objective:To evaluate the role of uncoupling protein 2 in dexmedetomidine-induced alleviation of myocardial ischemia-reperfusion (I/R) injury in diabetic mice.Methods:SPF C57BL/6 male mice, aged 6-8 weeks, weighing 20-25 g, in which the model of type 2 diabetes mellitus was established by high-fat feeding combined with intraperitoneal injection of streptozotocin, were used in this study. Ninety diabetic mice were divided into 5 groups ( n=18 each) by a random number table method: sham operation group (S group), myocardial I/R group, myocardial I/R+ UCP2 inhibitor genipin group (I/R+ G group), myocardial I/R+ dexmedetomidine group (I/R+ D group) and myocardial I/R+ dexmedetomidine+ UCP2 inhibitor genipin group (I/R+ DG group). Myocardial I/R injury model was established by ligating the left anterior descending coronary artery of diabetic mice for 60 min followed by 120 min of reperfusion. Dexmedetomidine 20 μg/kg was intraperitoneally injected at 5 min prior to reperfusion in I/R+ D group. Genipin 100 mg/kg was intraperitoneally injected at 14 h prior to ischemia, and dexmedetomidine 20 μg/kg was intraperitoneally injected at 5 min prior to reperfusion in I/R+ D+ G group. The concentrations of cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in serum were detected by enzyme-linked immunosorbent assay at 120 min of reperfusion. The myocardial tissue was obtained for determination of the myocardial infarct size, the level of reactive oxygen species (ROS) (by flow cytometry), and the expression of UCP2, nuclear factor kappa B (NF-κB) inhibitory protein α (IκBα), phosphorylated IκBα (p-IκBα), NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for observation of the morphological structure of the myocardial tissue. The cardiac function was evaluated by echocardiography at 24 h of reperfusion. Results:Compared with group S, the percentage of myocardial infarct size and level of ROS were significantly increased, the concentrations of cTnI, TNF-α, IL-6 and IL-10 were increased, the expression of UCP2 was up-regulated, the p-IκBα/IκBα ratio and p-NF-κB p65/NF-κB p65 ratio were increased, the stroke volume (SV), ejection fraction (EF), and left ventricular fractional shortening (FS) were decreased ( P<0.05), and the myocardial structure was severely damaged in group I/R. Compared with group I/R, the percentage of myocardial infarct size and level of ROS were significantly decreased, the concentrations of cTnI, TNF-α and IL-6 were decreased, the concentration of IL-10 was increased, the expression of UCP2 was up-regulated, the p-IκBα/IκBα ratio and p-NF-κB p65/NF-κB p65 ratio were decreased, the SV, EF and FS were increased ( P<0.05), and the pathological damage was significantly attenuated in group I/R+ D. Compared with group I/R+ D, the percentage of myocardial infarct size and level of ROS were significantly increased, the concentrations of cTnI, TNF-α and IL-6 were increased, the concentration of IL-10 was decreased, the expression of UCP2 was down-regulated, the p-IκBα/IκBα ratio and p-NF-κB p65/NF-κB p65 ratio were increased, the SV, EF and FS were decreased ( P<0.05), and the pathological damage was aggravated in group I/R+ D+ G. Conclusions:Dexmedetomidine may ameliorate myocardial I/R injury by up-regulating UCP2 expression in the myocardium and inhibiting mitochondrial ROS-mediated inflammatory responses in diabetic mice.