Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

On the occasion of the 110th Anniversary of the establishment of the Chinese Medical Association, the third conference of the Fourth Editorial Board of Chinese Journal of Digestive Surgery, and the Second Elite Group of Chinese Journal of Digestive Surgery, was successfully held in Kunming on July 4, 2025. This conference systematically summarizes the development experience of the journal over the past 20 years from three aspects: the role of ecological construction of thought in the discipline construction of digestive surgery, the display of the latest academic achievements in the field of digestive surgery, the development difficulties, and breakthrough paths of the discipline, and strategically plans the path of discipline construction in the new era.

Vitamin D is a fat-soluble vitamin primarily synthesized through skin exposure to ultraviolet B irradiation and dietary intake.Its biological effects are not limited to the regulation of calcium and phosphorus metabolism but also involve a variety of physiological functions such as immune modulation,anti-inflammation,and anti-tumor.In recent years,as research deepens,the role of the vitamin D signaling pathway in various diseases has been gradually revealed,and its regulatory mechanisms are complex and diverse.This paper systematically reviews the molecular mechanisms underlying the vitamin D signaling pathway,including the two-step hydroxylation activation process of vitamin D,the regulation of gene transcription mediated by the vitamin D receptor(VDR),the homeostatic regulation involving vitamin D-binding protein and metabolic enzymes such as 1α-hydroxylase and 24-hydroxylase,and interactions with other signaling pathways,including NF-κB,Wnt,and Hedgehog.This study highlights the role of vitamin D in various multi-system diseases such as inflammatory bowel disease,diabetes and its complications,obesity,cardiovascular disease,colorectal cancer,breast cancer,among others.The systematic cognitive framework for understanding the vitamin D signaling pathway was conducted,providing a theoretical basis for precision treatment strategies targeting VDR.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective To explore the alterations in the numbers of cortical neurons and synapses in type 1 diabetic rats and their correlation with cognitive dysfunction.Methods A type 1 diabetes model was induced by intraperitoneal injection of streptozotocin(STZ).Four-month-old specific pathogen-free(SPF)-grade Sprague-Dawley(SD)rats were randomly allocated into a control group and a diabetic group,with five rats in each group.After three months of continuous feeding,optical fractionator stereology was employed to quantitatively analyze the volume of the cerebral cortex,the number of neurons,and the number of synapses.Results In comparison with the control group,the volume of the cerebral cortex in the diabetic group decreased by 6.00%,and the number of neurons decreased by 14.09%.However,these differences were not statistically significant(P>0.05).Never the-less,the density of synapses significantly decreased by 70.14%(P<0.05),and there was a significant difference in the number of Spinophilin/Neurabin-positive synaptic boutons per neuron in the cortex(P<0.05).Conclusion Although early-stage type 1 diabetes does not lead to a significant loss of cortical neurons,the substantial reduction in synaptic numbers might be a crucial pathological basis for cognitive dysfunction.

Objective To design a precision nutrition information management system to improve clinical nutrition diagnosis and treatment.Methods A precision nutrition information management system was developed with such technologies as Internet,big data and remote diagnosis and treatment,which was composed of a hardware system and a software system.The hardware system consisted of a Web and interface server,a database server,a front-end server,a personal digital assistant,a barcode scanner and a label printer;the software system with B/S architecture encapsulated business functions into reusable and easily expandable modular components based on.NET technology stack,which was made up of three subsystems for outpatient nutrition diagnosis and treatment,inpatient nutrition diagnosis and treatment and nutrition stocking management.Results The system developed realized data sharing and interaction among multi information systems,and contributed to implementing rational,normalized and efficient outpatient nutrition diagnosis and treatment,inpatient nutrition support and nutrition stocking management.Conclusion The system developed meets the requirements for clinical nutrition diagnosis and treatment and enhances clinical nutrition service.[Chinese Medical Equipment Journal,2025,46(10):41-48]

On the occasion of the 110th Anniversary of the establishment of the Chinese Medical Association, the third conference of the Fourth Editorial Board of Chinese Journal of Digestive Surgery, and the Second Elite Group of Chinese Journal of Digestive Surgery, was successfully held in Kunming on July 4, 2025. This conference systematically summarizes the development experience of the journal over the past 20 years from three aspects: the role of ecological construction of thought in the discipline construction of digestive surgery, the display of the latest academic achievements in the field of digestive surgery, the development difficulties, and breakthrough paths of the discipline, and strategically plans the path of discipline construction in the new era.