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.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

Objective:To investigate the effect of early high-sucrose diet (eHSD) on cognitive function and its regulatory mechanism in 3×Tg-AD mice.Methods:(1) Eighteen specific-pathogen-free (SPF)-grade 2-month-old wide-type (WT) mice were randomly divided into a WT+normal chow diet (NCD) group and a WT+eHSD group, with 9 mice in each group; and 18 SPF-grade 2-month-old 3×Tg-AD mice were randomly divided into a 3×Tg-AD+NCD group and a 3×Tg-AD+eHSD group, with 9 mice in each group. At 2-5 months old, mice in the 4 groups received standard laboratory food+purified water or 30% sucrose water, followed by standard feed for all groups. At 8 months old, cognitive function was assessed by Morris water maze test; fluorescent intensity of AT8 (phosphorylated [p]-tau) and T22 (tau oligomers) in the hippocampal tissues was detected by immunofluorescent staining; concentrations of β-amyloid protein (Aβ) 42 and Aβ 40 were detected by enzyme-linked immunosorbent assay (ELISA); protein expressions of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), p-TBK1, and CCAAT/enhancer-binding protein β (C/EBPβ) were detected by Western blotting; activity of C/EBPβ transcription factor was detected by activity assay; mitochondrial DNA (mtDNA) content in the cytoplasm of cell was detected by real-time quantitative PCR (qPCR). (2) Eighteen SPF-grade 2-month-old 3×Tg-AD mice were randomized into a 3×Tg-AD+eHSD+H-151 group and a 3×Tg-AD+eHSD+dimethyl sulfoxide (DMSO) group, with 9 mice in each group. Mice at 2-5 months old were given standard laboratory food+30% sucrose water; they were, respectively, injected intraperitoneally with STING pathway inhibitor H-151 or DMSO at 5 months old, and continually injected until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, Western blotting and C/EBPβ transcription factor activity experiments were repeated as before. (3) After crossing C/EBPβ heterozygous knockout (C/EBPβ +/-) mice with 3×Tg-AD mice, 3×Tg-AD/C/EBPβ +/- mice were obtained, and 3×Tg-AD mice were used as controls; they were named 3×Tg-AD/C/EBPβ +/-+eHSD group and 3×Tg-AD+eHSD group, with 9 mice in each group. Both groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old, followed by standard feed until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. (4) C/EBPβ transgenic mice (C/EBPβTg) were crossed with 3×Tg-AD mice to obtain C/EBPβTg/3×Tg-AD mice, and Non-Tg/3×Tg-AD mice were used as controls; they were, respectively, named as C/EBPβTg/3×Tg-AD+eHSD+H-151 group, Non-Tg/3×Tg-AD+eHSD+H-151 group, and Non-Tg/3×Tg-AD+eHSD+DMSO group, with 9 mice in each group. All 3 groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old; at 5-8 months old, mice in the C/EBPβTg/3×Tg-AD+eHSD+H-151 group and Non-Tg/3×Tg-AD+eHSD+H-151 group were intraperitoneally injected with H-151, while mice in the Non-Tg/3×Tg-AD+eHSD+DMSO group were injected with DMSO; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. Results:(1) Compared with those in the WT+NCD group and WT+eHSD group, area under the latency curve of 3×Tg-AD+eHSD mice was significantly increased, and proportion of time spending in the targeted quadrant of mice in the 3×Tg-AD+NCD group and 3×Tg-AD+eHSD group was significantly decreased ( P<0.05); compared with that in the 3×Tg-AD+NCD group, proportion of time spending in the targeted quadrant in mice of the 3×Tg-AD+eHSD group was significantly reduced ( P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.076 vs. 2.902±0.399; T22 fluorescent intensity: 1.000±0.145 vs. 2.495±0.273; Aβ 42: 1.000±0.167 vs.1.956±0.132; Aβ 40: 1.000±0.226 vs.1.900±0.116), significantly increased C/EBPβ protein expression and C/EBPβ transcription factor activity (1.000±0.164 vs. 1.804±0.112; 1.000±0.216 vs. 2.743±0.301), and statistically increased mtDNA level detected by D-loop1 and D-loop3 (1.000±0.234 vs. 2.800±0.210; 1.000±0.155 vs. 2.952±0.078; P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.192 vs. 2.093±0.081; p-TBK1/TBK1: 1.000±0.148 vs. 1.561±0.112, P<0.05). (2) Compared with the 3×Tg-AD+eHSD+DMSO group, the 3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers expressions, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.142 vs. 0.538±0.057; T22 fluorescent intensity: 1.000±0.104 vs. 0.665±0.088; Aβ 42: 1.000±0.084 vs. 0.600±0.007; Aβ 40: 1.000±0.138 vs. 0.476±0.083), significantly decreased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.054 vs. 0.468±0.111; p-TBK1/TBK1: 1.000±0.057 vs. 0.598±0.090), and significantly decreased C/EBPβ transcription factor activity (1.000±0.097 vs. 0.445±0.106; P<0.05). (3) Compared with the 3×Tg-AD+eHSD group, the 3×Tg-AD/C/EBPβ +/-+eHSD group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.160 vs. 0.506±0.065; T22 fluorescent intensity: 1.000±0.127 vs. 0.346±0.048; Aβ 42: 1.000±0.017 vs. 0.510±0.101; Aβ 40: 1.000±0.098 vs. 0.586±0.153), and significantly decreased C/EBPβ protein expression (1.000±0.101 vs. 0.568±0.094; P<0.05). (4) Compared with the Non-Tg/3×Tg-AD+eHSD+DMSO group, the Non-Tg/3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, and significantly decreased p-tau and tau oligomers expressions, Aβ 40 concentration in the hippocampus, and the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly decreased STING protein expression and p-TBK1/TBK1 ratio in the hippocampus ( P<0.05). Compared with the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly increased area under the latency curve, significantly decreased proportion of time spending in the targeted quadrant, and significantly increased p-tau and tau oligomers expressions, Aβ 40 and Aβ 42 concentration in the hippocampus ( P<0.05). Conclusion:The eHSD aggravates cognitive impairment in 3×Tg-AD mice through activating cGAS-STING-C/EBPβ pathway.

Background When discussing the new concept of"pancreas spleen integration"in the early stage,we proposed that dampness heat stagnation in the spleen and deficiency due to stagnation are the traditional Chinese medicine(TCM)pathogenesis elements of pancreatitis-induced pancreatic ductal adenocarcinoma,among which dampness heat is the soil of pancreatitis deteriorates into pancreatic cancer.Objective Based on the TCM pathogenesis elements of pancreatitis to cancer with"damp heat"as the main factor,data mining technology was used to analyze the properties,channel conversion and active ingredients of heat-clearing Chinese medicines with anti-inflammatory and anti-tumor effects,and to summarize the drug characteristics of these Chinese medicines.To prospectively predict the use of drugs in the transformation process of pancreatitis to pancreatic cancer.Methods Taking Traditional Chinese Medicine(10th Edition of China Traditional Chinese Medicine Press)as the drug data source,66 heat-clearing herbs were searched in the literature database of CNKI and PubMed of inflammation * TCM or(inflammation+tumor)* TCM.The active ingredients were analyzed in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Results Among the 66 heat-clearing drugs(excluding adjunct drugs),58 herbs had anti-inflammatory effects,53 herbs had anti-tumor effects,and 48 herbs had both anti-inflammatory and anti-tumor effects.The three groups of drugs were mainly bitter,sweet and pungent in five flavors,and were mainly liver,stomach,lung,heart and large intestine in meridian affinity.Five flavors and meridian affinity were highly similar.In the TCMSP,the"five principles of drug class"were used to screen the active ingredients of anti-inflammatory and anti-tumor drugs.A total of 1041 active ingredient data were screened,and 798 active ingredient data were screened after duplicate items were deleted.Top three active ingredients were Luteolin,Kaempferol and Acacetin.Conclusion Based on the analysis of five flavors,meridian affinity and active ingredients of heat-clearing medicine,this study found that the anti-inflammatory and anti-tumor effects of these Chinese herbs are highly overlapping,it has important guiding significance for the drug research and clinical prescription of pancreatitis-induced pancreatic ductal adenocarcinoma.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.