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.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

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.

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]

OBJECTIVE To evaluate the status of microbial contamination in the environment of respiratory tract specimens sampling rooms and observe the association of the factors such as design and layouts of the sampling rooms with the potential risk of infections in the environment so as to provide scientific bases for optimizing the construction standards of fever clinics of the medical institutions.METHODS The sampling rooms of fever clinic were chosen from 10 tertiary or above medical institutions of Hangzhou,and the samples were collected from the key sites such as air,object surfaces and hands of health care workers.The respiratory tract pathogens in the sam-ples were detected by FilmArray full-automatic medical PCR analysis system,and the pathogens in the samples were detected by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF MS).The data including the areas,windows,mechanical ventilation facilities,physical partitions,frequencies and modes of disinfection and daily amounts of diagnosis and treatment of the 10 sampling rooms were investigated,and the univariate analysis was performed for their association with the microbial contamination of environment.RESULTS The isolation rate of respiratory tract pathogens was 10.00％(4/40),respiratory syn-cytial virus,human rhinovirus and adenovirus were dominant among the respiratory tract pathogens.The isolation rate of bacteria was 71.88％(23/32),Staphylococcus ho minis and Staphylococcus epidermidis were the major species of opportunistic pathogens isolated.The result of univariate analysis indicated that both the presence of windows(P=0.012)and mechanical ventilation facilities(P=0.047)were associated with the potential risk of infections in the environment(P＜0.05);while the factors such as the areas of sampling rooms,physical parti-tions,disinfection modes and daily amounts of diagnosis and treatment were not remarkably associated with the potential risk of infections in the environment.CONCLUSION It is an effective way to physically separate the air-flow from other areas or fix the mechanical ventilation facilities to create proper airflow during the construction of fever clinic sampling rooms so as to reduce the potential risk of infections in the environment of sampling rooms.

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 investigate the predictive value of morphology,immunology,and cytogenetics for isocitrate dehydrogenase 1 and 2(IDH1/2)gene mutation in newly diagnosed acute myeloid leukemia(AML)patients.Methods:The clinical data of 186 newly diagnosed AML patients(except M3 subtype)in the First People's Hospital of Changzhou were retrospectively analyzed,and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model.The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model,and receiver operating characteristic(ROC)curve was used to evaluate the predictive performance of the model.Results:A total of 60 AML patients had IDH1/2 mutation at initial diagnosis.LASSO regression screened 9 predictive variables associated with IDH1/2 mutation,including CD7,CD56,CD11b,CD15,CD64,HLA-DR,platelet count ≥ 50 × 109/L,isolated+8 and normal karyotype.The nomogram and ROC curve were plotted based on the above 9 variables.The area under the ROC curve(AUC)of the training set and the validation set were 0.871 and 0.806,respectively.Internal validation showed that the nomogram had good predictive ability.Conclusion:The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.

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.