Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

ObjectiveTo investigate the independent risk factors for decompensation in patients with liver cirrhosis， to construct a nomogram-based risk assessment model， and to assess its risk assessment performance and clinical value by comparing it with Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， and MELD 3.0 scoring system. MethodsA retrospective analysis was performed for 514 patients with liver cirrhosis who attended The First Hospital of Shanxi Medical University from January 2020 to May 2025， and related data were collected， including demographic data and laboratory markers. According to the presence or absence of decompensation， the patients were divided into compensation group with 275 patients and decompensation group with 239 patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator regression analysis was used for screening of variables， and the multivariate logistic regression analysis was used to identify independent risk factors for decompensated liver cirrhosis and construct a nomogram model. The receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis were used to assess the discriminatory ability， calibration， and net clinical benefit of the model. ResultsThe multivariate logistic regression analysis showed that low hemoglobin （odds ratio ［OR］=0.984， 95% confidence interval ［CI］： 0.969　—　0.999， P<0.05）， low lymphocytes （OR=0.564， 95%CI： 0.383　—　0.830， P<0.05）， high international normalized ratio （OR=3.131， 95%CI： 1.242　—　7.891， P<0.05）， and low serum sodium （OR=0.922， 95%CI： 0.872　—　0.975， P<0.05） were independent risk factors for decompensation events in patients with liver cirrhosis. Construct the prediction model equation： Logit（P）=intercept value－0.016×hemoglobin－0.573×lymphocytes+1.141×INR－0.081×serum sodium. The nomogram constructed based on these factors had a good discriminatory ability， with an area under the ROC curve （AUC） of 0.787， a specificity of 77.8%， and a sensitivity of 67.4%， and it had significantly better predictive performance than MELD score （AUC=0.718）， MELD-Na score （AUC=0.719）， and MELD 3.0 score （AUC=0.725）. The calibration curve showed good consistency between the probability of risk assessed by the model and the observed probability. The decision curve analysis showed that compared with the MELD-based scores， this model provided higher net clinical benefit across a wide range of risk thresholds. ConclusionThis study successfully constructed and validated a nomogram risk assessment model incorporating hemoglobin， international normalized ratio， lymphocytes， and serum sodium. This model has good clinical practicability and can help to achieve early identification of high-risk patients with decompensated liver cirrhosis and optimize intervention strategies in clinical practice.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

Objective To establish a stable and reproducible animal model of abdominal intestinal firearm penetrating injury in a cold high-altitude environment.Methods Twenty landrace pigs were randomly and equally assigned to a low-altitude normal temperature(LN)group and a high-altitude cold(HC)group.The HC group was placed in a cold environment at high altitudes,and the LN group was placed in a normal-temperature environment at low altitudes.They were raised for 48 hours respectively.After anesthesia,they were suspended on the shooting range,and the right lower abdomen of the experimental pigs was shot with a gun.After injury,they were simply bandaged and transported back to the laboratory for observation in the normal temperature environment of the low altitudes.The vital signs and injuries at 0,2,4,8,12 and 24 h and 24 h survival rates of experimental pigs were compared.Laparotomy was immediately performed on the dead pigs and the experimental pigs still alive at 24 h to explore the injuries and observe the pathology of the small intestine and colon.Results The 24 h survival rate of the HC group was 70％,with no statistically significant difference compared to the LN group's 90％(P＞0.05).After the injury,the body temperature of both groups gradually increased.The body temperature of the HC group was significantly higher than the LN group at 0,2,4 and 8 h time points(P＜0.001),and the LN group exceeded the HC group at 24 h(P＜0.05).Both groups showed an initial increase followed by a decrease in heart rate,with the HC group significantly higher than the LN group only at 0 h(P＜0.01),and no statistically significant differences were observed at other time points(P＞0.05).Both groups showed an early increase and later decrease in respiratory rate,with the HC group higher than the LN group at 0,4,8,12 and 24 h(P＜0.05 or P＜0.001).There was no statistically significant difference(P＞0.05)between the HC group and the LN group in small intestine rupture,small intestine contusion,mesenteric injury,colon rupture and wound diameter.The pathology of the small intestine and colon in the HC group showed extensive necrosis and shedding of the mucosa layer,severe congestion and edema of the submucosa,and extensive lymphocyte infiltration.The LN group also showed similar symptoms but to a lesser extent.Conclusion This study established a pig model of abdominal firearm intestinal perforation injury in a cold environment at high-altitudes.The model has strong operability and stable damage,which can provide a reference for subsequent research.