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 To investigate the epidemiological characteristics of imported malaria cases in Shanghai Municipality from 2020 to 2024, so as to provide insights into dynamic adjustment of imported malaria control strategies. Methods All data pertaining to malaria cases reported in Shanghai Municipality from 2020 to 2024 were collected from Infectious Diseases Reporting Information Management System and Parasitic Diseases Prevention and Control Information Management System of Chinese Center for Disease Control and Prevention, and epidemiological investigation reports of malaria cases. The type of malaria cases, source of acquiring infections, temporal, spatial and population distributions of malaria cases, type of initial diagnosis institutions, accuracy of initial diagnosis, time interval from disease onset to initial diagnosis, and the time interval from initial diagnosis to diagnosis were statistically analyzed. The monthly distribution of malaria cases was analyzed using a circular distribution method. Results A total of 124 malaria cases were reported in Shanghai Municipality from 2020 to 2024, with 14, 52, 22, 8 and 28 cases annually, respectively, and all cases were overseas imported cases. Plasmodium falciparum malaria was the predominant type, accounting for 82.26% (102/124) of all malaria cases, while P. ovale, P. vivax and P. malariae malaria accounted for 8.06% (10/124), 7.26% (9/124) and 2.42% (3/124) of reported cases, respectively. Malaria cases acquired infections from 28 countries in 4 continents, with African countries as a major source of acquiring infections (96.77%, 120/124). Malaria cases were reported across all 16 districts in Shanghai Municipality. There were peaks in numbers of reported malaria cases in May 2021 (9 cases) and November 2021 (9 cases); however, there was no concentration trend in the reporting time of malaria cases from 2020 to 2024 (Z = 2.45, P > 0.05). The reported malaria cases included 116 males and 8 females, with a male-to-female ratio of 14.5∶1.0, and had a median age of 39 (17) years. Worker was the primary occupation of reported malaria cases, accounting for 48.39% (60/124) of all reported cases. City-level medical institutions were the predominant initial diagnosis institutions (75.81%, 94/124). The overall accuracy of initial diagnosis was 74.19% (92/124), and the median time interval from disease onset to initial diagnosis was 0 (2) day (healthcare seeking on the day of disease onset), with 72.58% (90/124) of malaria cases seeking healthcare services within one day. The median time interval from initial diagnosis to diagnosis was 2 (3) days, with 41.94% (52/124) of malaria cases that were definitively diagnosed within one day following initial diagnosis. There were significant differences in the accuracy of initial malaria diagnosis (χ² = 15.01, P < 0.05), the time interval from disease onset to initial diagnosis (H = 29.30, P < 0.001), and the time interval from initial diagnosis to diagnosis (H = 22.92, P < 0.001) among years from 2020 to 2024, and the time interval from disease onset to initial diagnosis (Z = -5.09, P < 0.001) and the time interval from initial diagnosis to diagnosis (Z = -4.14, P < 0.001) were both shorter during the period from 2020 to 2022 than those recorded from 2023 to 2024. In addition, a total of 2 malaria deaths were reported in Shanghai Municipality during the period from 2020 to 2024, both caused by P. falciparum malaria. Conclusions The numbers of malaria cases fluctuated continuously in Shanghai Municipality from 2020 to 2024. It is recommended to continuously strengthen surveillance and response measures, improve malaria diagnosis and treatment capabilities, and conduct targeted health education activities among high-risk populations, such as labors going to overseas malaria hyper-endemic areas, so as to prevent re-establishment of imported malaria.

To address the challenges of fragmented data, inconsistent standards, and delayed feedback in the full-cycle competency development process at teaching hospitals, this paper proposes the LEADS data governance system for Precision Medical Education (LEADS-PME), drawing on the practical experience of building the integrated medical education management platform at Zhongshan Hospital, Fudan University. The LEADS-PME framework comprises five interconnected core components: Longitudinal foundation, Evidence-chain generation, Analytics and profiling, Decision-support and prediction, and Simulation and digital-twin governance. Currently, Zhongshan Hospital has established a full-cycle educational data infrastructure and achieved multi-system data integration and competency-based profiling and evaluation, while the prediction and simulation modules are still in the prototype exploration phase. A mixed-methods evaluation will be subsequently conducted from the perspectives of data quality, management effectiveness, and predictive intervention. As a locally adapted framework, LEADS-PME can transform operational data derived from clinical practice, teaching, assessment, and management processes into traceable, interpretable, and reusable evidence of competency development. It is expected to facilitate the transformation of medical education management from a outcome-oriented approach to process monitoring, evidence-driven decision-making, and precision governance, thereby providing both a theoretical framework and practical reference for precision medical education in Chinese teaching hospitals.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Objective To explore the risk factors for 28-day mortality of sepsis-associated acute kidney injury(SA-AKI)patients and to develop a nomogram risk prediction model.Methods A retrospective cohort study was conducted,involving 184 patients with SA-AKI admitted to the intensive care unit(ICU)of the 940th Hospital of Joint Logistic Support Force of PLA between January 2017 and December 2022.Patients were categorized into survival(n=135)and non-survival(n=49)groups based on 28-day mortality.Clinical data were collected,and statistically significant risk factors were preliminarily screened.Multivariate stepwise logistic regression analysis was performed to identify independent risk factors for 28-day mortality of SA-AKI patients.A nomogram predictive model was constructed using these factors,and internally validated with the Bootstrap method.The receiver operating characteristic curve(ROC curve)was drawn,and the area under the ROC curve(AUC)was calculated to verify the predictive value and accuracy of the model.Results The 28-day mortality rate among 184 SA-AKI patients was 26.6％(49/184).Multivariate stepwise logistic regression analysis identified multiple organ dysfunction syndrome(MODS)(OR=16.393,95％CI 4.317-62.254,P＜0.001),high acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(OR=1.097,95％CI 1.036-1.161,P=0.002),low oxygenation index(OR=0.992,95％CI 0.986-0.998,P=0.015),low neutrophil count(OR=0.912,95％CI 0.860-0.968,P=0.002)and low fibrinogen concentration(OR=0.733,95％CI 0.549-0.978,P=0.034)as independent risk factors.The prediction model equation was P=1/1+e-logit(P),logit(P)=-1.626+2.797×MODS+0.092×AP ACHE Ⅱ+(-0.311)×fibrinogen+(-0.092)×neutrophil count+(-0.008)×oxygenation index.Internal validation with 1000 Bootstrap resamples showed high consistency between predicted and actual values.ROC analysis showed an AUC of 0.911(95％CI 0.868-0.955,P＜0.05)for the model,with 93.9％sensitivity and 78.5％specificity at a cut-off of 0.194.The Hosmer-Lemeshow test confirmed good calibration(P=0.62),and decision-making curve analysis demonstrated clinical utility within the high-risk threshold range(0.1-0.9).Conclusions MODS,high APACHE Ⅱ score,low oxygenation index,low neutrophil count,and low fibrinogen concentration are independent risk factors for 28-day mortality in SA-AKI patients.The developed nomogram risk prediction model may provide important guidance for predicting 28-day mortality in SA-AKI patients.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of "X-ray-free" technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 ( v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.