OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

Abstract Short form video applications provide a new mode of online participation for college students, but also bring some problematic issues, especially short form video addiction among college students. The article expounds the definition, influencing factors and adverse impacts on physical and mental health of short form video addiction among college student users by systematically reviewing the existing domestic and foreign literature regarding college students short form addiction. Awareness should be raised among families, schools and society regarding college students addiction to short form video, and healthy usage of short form video are encouraged among college students to reduce the risk of addiction to short form video.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Abstract Cyberchondria is a growing mental health concern in the digital age, significantly impacting college students physical and psychological wellbeing as well as their daily functioning. The paper systematically reviews existing domestic and international literature to synthesize key aspects of cyberchondria among college students, including its conceptualization, measurement tools, prevalence, contributing factors, consequences, and intervention approaches. Building on the foundation, the study identifies critical gaps and proposes future research directions. By establishing a comprehensive theoretical framework, the work aims to inform subsequent studies and targeted interventions, ultimately supporting the promotion of mental and physical health among college students affected by cyberchondria.

ObjectiveTo investigate the expression of C1q tumor necrosis factor-related protein 3 （C1QTNF3） in liver cancer tissue， its association with the clinicopathological features of patients， and its potential value in predicting the prognosis of liver cancer. MethodsRelated data were collected from TIMER， UALCAN， TNMplot， and GEO databases， and the bioinformatics methods were used to measure the expression level of C1QTNF3 in pan-cancer， normal tissue/liver cancer tissue， and cancerous tissue/paracancerous tissue. Cancerous and paracancerous tissue samples were collected from 90 patients with liver cancer， and related clinical data were collected， including age， sex， tumor diameter， and tumor number. The independent-samples t test or the paired t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used to investigate the association between the expression level of C1QTNF3 and the survival of patients with liver cancer. The Cox regression model was used to identify the risk factors for the prognosis of patients with liver cancer， and the receiver operating characteristic （ROC） curve was used to analyze the ability of C1QTNF3 expression at different time points for predicting the prognosis of patients with liver cancer. ResultsThe bioinformatics analysis showed that the expression of C1QTNF3 was upregulated in various malignant tumors， especially in liver cancer tissue （P<0.001）， and the expression level of C1QTNF3 in liver cancer tissue was significantly higher than that in normal tissue and paracancerous tissues （all P<0.01）. The immunohistochemical staining results of 90 patients with liver cancer showed that C1QTNF3 was mainly expressed in cytoplasm， with a small amount in nucleus， and it had negative expression in paracancerous tissue and positive expression in liver cancer tissue. The positive expression rate and strong positive expression rate of C1QTNF3 protein in liver cancer tissue were significantly higher than those in paracancerous tissue （positive expression rate： 76.67% vs 33.33%， χ²=34.141， P<0.01； strong positive expression rate： 54.44% vs 5.56%， χ²=51.217， P<0.01）. The liver cancer patients with a tumor diameter of ≥5 cm， an advanced stage， the presence of liver cirrhosis， negative HBsAg， and gamma-glutamyl transpeptidase （GGT）≥50 U/L had a significantly higher strong positive expression rate of C1QTNF3 protein than those with a tumor diameter of <5 cm， an early stage， the absence of liver cirrhosis， positive HBsAg， and GGT<50 U/L （all P<0.05）. The univariate Cox regression analysis showed that tumor diameter， recurrence， and C1QTNF3 expression were influencing factors for the prognosis of patients with liver cancer （all P<0.05）， and the multivariate Cox regression analysis showed that the expression level of C1QTNF3 and recurrence were independent risk factors for the survival of patients with liver cancer （both P<0.05）. The survival curve analysis showed that for all patients with liver cancer， the patients with high （strong positive） expression of C1QTNF3 had significantly lower overall survival rate and disease-free survival rate than those with low expression （χ²=17.010 and 13.647， both P<0.001）； for liver cancer patients with a tumor diameter of ≥5 cm， an early/advanced stage， recurrence， the presence of liver cirrhosis， positive HBsAg， alanine aminotransferase （ALT） <40 U/L， ALT≥40 U/L， and GGT≥50 U/L， the patients with high expression of C1QTNF3 had a significant reduction in overall survival rate （χ²=11.086， 5.578， 5.295， 19.159， 16.391， 13.774， 10.119， 8.152， and 12.035， all P<0.05）. The ROC curve analysis showed that C1QTNF3 expression had the strongest predictive potential at 5 years， with an area under the ROC curve of 0.77. ConclusionC1QTNF3 is highly expressed in liver cancer tissue， and the expression level of C1QTNF3 and recurrence are closely associated with the survival of patients with liver cancer. Patients with high expression of C1QTNF3 protein tend to have a lower survival rate.

Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ²_trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ² = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ² = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ² = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ² = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ² = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ²_trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ² = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ² = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.

Objective: To compare the intervention effects of sitagliptin combined with metformin and insulin aspart combined with metformin among patients with type 2 diabetes mellitus (T2DM), so as to provide the reference for optimizing blood glucose control strategies among patients with T2DM. Methods: T2DM patients admitted to the department of endocrinology of Jinhua Central Hospital from January 2018 to December 2024 were selected as the research objects. According to the propensity score matching, T2DM patients were divided into sitagliptin combined with metformin group and insulin aspart combined with metformin group at a ratio of 1∶1. The basic information, capillary blood glucose, glycosylated hemoglobin blood glucose (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were collected by questionnaire survey, physical examination and laboratory test. The generalized estimating equation was used to analyze the changes of various indicators before and after treatment between the two groups of patients, and the intervention effect was compared. Results: There were 69 cases in the sitagliptin combined with metformin group. Among these 42 cases were males, accounting for 60.87%, and 27 cases were females, accounting for 39.13%.Forty-two cases were younger than 60 years, accounting for 60.87%. There were 69 cases in the insulin aspart combined with metformin group. Among these 47 cases were males, accounting for 68.12%, and 22 cases were females, accounting for 31.88%. Forty-five cases were younger than 60 years, accounting for 65.22%. There were no statistically significant differences in gender, age, education level, smoking, drinking, vegetable and fruit intake, and disease duration between the two groups (all P>0.05). After 6 months of treatment, there was an interaction between group and time in capillary blood glucose and HbA1c in the two groups (all P<0.05), and the reduction of capillary blood glucose and HbA1c in the sitagliptin combined with metformin group was greater than that in the insulin aspart combined with metformin group. There were no statistically significant differences between groups and time in TC, HDL-C, TG, BMI, SBP, and DBP, and no interaction effect was found between groups and time (all P>0.05). Conclusion Sitagliptin combined with metformin is more effective than insulin aspart combined with metformin in controlling blood glucose among patients with T2DM.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.