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: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE: To compare the clinical efficacy and complication rates of staged open reduction internal fixation (ORIF) and external fixation combined with limited internal fixation (EFLIF) in the treatment of high-energy Pilon fractures. METHODS: A retrospective selection was conducted on 78 patients diagnosed with high-energy tibial Pilon fractures who received treatment between January 2021 and October 2023. These patients were categorized into the staged ORIF group and the EFLIF group according to their respective treatment protocols. The staged ORIF group comprised 48 patients, including 29 males and 19 females, aged from 33 to 53 years old with a mean age of (43.25±4.67) years old. The time from injury to treatment averaged (6.54±2.21) hours. All patients received staged ORIF treatment. The EFLIF Group consisted of 30 patients, including 18 males and 12 females, aged from 36 to 54 years old with a mean age of (43.37±3.24) years old. The time from injury to treatment averaged (6.87±1.96) hours. All patients received EFLIF treatment. The recovery of ankle joint function, fracture reduction quality, fracture healing time, and surgical-related indicators between two groups were observed and compared six months after surgery. Additionally, the postoperative complications of the two groups were recorded. RESULTS: Both groups of patients were followed up and the duration ranged from 6 to 12 months, with an average of (8.97±1.26) months. At 6-month postoperative follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) score in the ORIF group was (83.15±20.93), which did not show a statistically significant difference compared to the EFLIF group (81.88±20.67), P>0.05. The excellent and good rate of fracture reduction in the staged ORIF group was 33.33% (16/48), which did not show a statistically significant difference compared to the EFLIF group (30.00%, 9/30), P>0.05. The hospitalization duration and fracture healing time in the staged ORIF group were (16.57±1.25) days and (12.14±1.15) weeks, respectively. When compared to the EFLIF group, which demonstrated a hospitalization duration of (15.97±2.16 ) days and a fracture healing time of (12.36±1.17) weeks, no statistically significant differences were observed (P>0.05). The intraoperative blood loss in the staged ORIF group was (76.54±11.65) ml, which was significantly higher than that in the EFLIF group (70.15±10.29) ml, and the difference was statistically significant (P<0.05). The incidence of superficial tissue infection was 2.08%(1/48), which was significantly lower than that observed in the EFLIF group at 16.67% (5/30), and this difference was statistically significant (P<0.05). CONCLUSION Both staged ORIF and EFLIF were effective treatment options for high-energy closed Pilon fractures of the tibia. However, regarding the prevention of superficial tissue infection, staged ORIF demonstrates superior risk control compared to EFLIF.
Humans ; Male ; Female ; Middle Aged ; Adult ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; External Fixators ; Open Fracture Reduction/methods* ; Treatment Outcome

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.