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.

Acquired paralytic strabismus is a common neuromuscular disorder in adults,characterized by diplopia, visual confusion, impaired ocular motility, and ocular deviation, which severely affects the patient's quality of life and overall health. The disease has a complex etiology, encompassing multiple pathological mechanisms such as vascular pathologies, trauma, inflammation, neoplasms, and immune-related disorders. Treatment primarily focuses on addressing the underlying cause. While conventional Western approaches, such as medication and surgery, can alleviate symptoms, some carry the risk of adverse effects, and their long-term recurrence rates warrant careful consideration. Traditional Chinese medicine utilizes distinctive therapies such as herbal medicine, acupuncture, and other adjunctive therapies, which have shown promising therapeutic effects but are constrained by a lack of high-quality evidence from large-scale randomized controlled trials. This review systematically summarizes recent advances in the etiological classification and traditional Chinese and Western medical treatments of acquired paralytic strabismus. It innovatively summarizes the clinical features associated with different causes, analyzes current therapeutic strategies and research landscape, aiming to inform clinical practice and suggest future research directions.

Objective To evaluate the impact of incorporating two doses of varicella vaccine into the immunization program in Shanghai on the incidence of varicella, age-specific incidence, and varicella outbreaks in kindergartens and schools in Jinshan District, and to assess its prevention and control effects. Methods Descriptive epidemiological methods were used to analyze and compare the population distribution characteristics and the occurrence of varicella outbreaks before (2013-2017) and after (2018-2024) the implementation of the strategy. Interrupted time series (ITS) design and its segmented regression model were used to analyze the changes in the incidence of varicella in the two stages before and after the implementation of the vaccination of two doses of varicella vaccine, and to evaluate the short-term and long-term preventive and control effects of the strategy. Results After the incorporation of two doses of varicella vaccine into the immunization program, the average annual incidence of varicella in Jinshan District decreased from 82.19/100 000 (2013-2017) to 53.51/100 000 (2018-2024). The interrupted time series analysis showed that after the implementation of the strategy, the slope change in the incidence of varicella was -10.20/100 000 (t=-2.38, P=0.04), and the overall trend was downward (slope β₁+β₃= -8.34/100 000). Except for the 30-49 years old group, the incidence rates in all other age groups decreased to varying degrees. Among them, the 5-9 years old group had a better vaccine efficacy (VE) of 52.23% (95% CI: 49.07-60.65), followed by the 10-14 years old group. The number of potential varicella outbreaks and cluster outbreaks in nurseries, kindergartens, and schools across the district dropped significantly. Conclusion Incorporating two doses of varicella vaccine into the immunization program can effectively reduce the incidence of varicella and the number of varicella outbreaks in kindergartens and schools, which is of great significance for the prevention and control of varicella.

Objective To investigate the biological behavior of EMP1 in pancreatic cancer cells and the molecular mechanism of EMP1 in promoting tumor progression.Methods A stable EMP1 knockdown cell line was obtained by lentivirus transfection.The effect of EMP1 on the proliferation of cancer cells was determined by CCK-8 and clonal formation assay.The effect of EMP1 on the migration and invasion of cancer cells was detected by scratch test and Transwell test.The influence of EMP1 on downstream signaling pathways was investigated by Western blot.Results The results of qRT-PCR and Western blot showed that EMP1 was highly expressed in pancreatic cancer cells.The results of CCK-8,colony formation,scratch,and Transwell assays indicated that EMP1 promoted the proliferation,migration,and invasion of pancreatic cancer cells.Western blot results revealed that EMP1 might promote tumor progression through the PI3K/AKT signaling pathway.Conclusion This study suggested that EMP1 may activate the PI3K/AKT signaling pathway to promote the proliferation,migration,and invasion of pancreatic cancer cells,thereby positively regulating tumor progression.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Objective:To compare the clinical characteristics of neovascular age-related macular degeneration (nAMD) patients with or without secondary subretinal fibrosis (SF).Methods:A retrospective case-control study. A total of 88 patients (92 eyes) diagnosed with nAMD at Department of Ophthalmology, Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2020 to January 2024 were enrolled in this study. All eyes underwent best-corrected visual acuity (BCVA), color fundus photography, and optical coherence tomography (OCT) examinations. BCVA was measured using the international standard visual acuity chart and converted to logarithm of the minimum angle of resolution for statistical analysis. SF area was measured on color fundus images. OCT was used to assess the presence of shallow irregular retinal pigment epithelial (RPE) elevation, RPE detachment, ellipsoid zone/external limiting membrane disruption, subretinal fluid and/or intraretinal fluid, thinning of the inner nuclear layer or inner plexiform layer, complete RPE and outer retinal atrophy (cRORA), epiretinal membrane, and suprachoroidal fluid. Device-integrated software measured central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and the height and width of subfoveal fibrosis in SF eyes. Based on the presence of SF, patients were divided into the SF group (47 eyes) and the non-SF (NSF) group (45 eyes). Baseline characteristics, OCT, and color fundus photography imaging features were compared between groups. Independent samples t tests were used for intergroup comparisons, and multiple linear regression was performed to analyze potential factors influencing SF height. Results:Compared with the NSF group, the SF group had a longer disease duration, longer symptom onset to initial treatment interval to receiving anti-vascular endothelial growth factor (VEGF) drug treatment, a lower proportion of patients receiving 3 anti-VEGF drug injections within 6 months, worse BCVA, thicker SFCT, higher rates of pigment epithelial detachment and inner nuclear layer or inner plexiform layer thinning, and a lower rate of subretinal fluid ( P<0.05). No significant differences were observed in CRT or the proportions of irregular retinal pigment epithelia, ellipsoid zone/external limiting membrane disruption, cRORA, suprachoroidal fluid, or epiretinal membrane between the two groups ( P>0.05). Conclusion:nAMD eyes with secondary SF exhibit distinct OCT imaging features compared to NSF eyes.