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 efficacy of rigid ureteroscopic laser lithotripsy combined with N-trap(RULL+N-trap),which is scoop-shaped,in the treatment of ureteral stones with a maximum diameter ≥1.5 cm.Methods:This retrospective cohort study included patients diagnosed with ureteral calculi who underwent rigid ureteroscopic lithotripsy(RULL)combined with N-Trap stone entrapment system at the Department of Urology,Peking University Third Hospital,by the same surgical team between June 2021 and September 2024.A total of 364 patients were initially enrolled.After excluding 21 patients due to missing critical outcome variables,two distinct cohorts were established:38 patients with ureteral stones measuring ≥1.5 cm in maximum diameter,and 305 patients with stones＜1.5 cm in maximum diameter.To minimize selection bias and control for confounding variables,propensity score matching(PSM)was employed.This resulted in two well-balanced groups:31 patients with stones 1.5 cm in maximum diameter and 31 patients with stones＜1.5 cm in maximum diameter,matched on baseline demographic and clinical characteristics.The primary outcomes assessed between the two groups included stone clearance.Secondary outcomes included changes in renal function indicators,specifically serum creatinine(SCr)and estimated glomerular filtration rate(GFR),and other factors like postopera-tive hospital stay and operative time.Results:In the matched cohort,the patients with stones ≥1.5 cm in maximum diameter had significantly longer operative time compared with those with smaller stones:(85.8±28.8)min vs.(62.4±24.6)min(P＜0.05).Postoperative length of hospital stay showed no significant difference:(2.26±1.79)d vs.(2.03±0.80)d(P＞0.05).The stone clearance on postoperative day one was 90.3％in the study group vs.100.0％in the control group(P＞0.05).One month postoperatively,the stone clearance was 93.5％vs.100.0％,respectively(P＞0.05).Changes in SCr were(-6.58±16.10)μmol/L vs.(-13.70±12.50)μmol/L,and changes in GFR were(5.92±14.90)mL/(min·1.73 m2)vs.(7.47±11.20)m L/(min·1.73 m2),with no statistically significant differences observed between the two groups for either renal function marker(P＞0.05).Conclusion:Ureteroscopic lithotripsy combined with N-trap is an optional method for treating ureteral stones with a maximum diameter ≥1.5 cm.The overall therapeutic efficacy is comparable,with the added benefit of significantly reducing the economic burden on patients.

Objective:To explore the mediating effect of work engagement between growth mindset and prone ventilation knowledge, beliefs, and practices among neonatal intensive care unit (NICU) nurses.Methods:A convenience sampling method was used to select 360 NICU nurses from 13 tertiary hospitals in Shandong Province between August and December 2023. The study used General Information Surveys, Growth Mindset Assessment Scales, a simplified Work Engagement Scale, and an ICU Staff Acute Respiratory Distress Syndrome Prone Ventilation Knowledge, Beliefs, and Practices Questionnaire. Pearson correlation analysis was used to explore the relationship between growth mindset, work engagement, and prone ventilation knowledge, beliefs, and practices. The mediating model was constructed using the PROCESS plugin for SPSS software.Results:A total of 370 questionnaires were distributed, and 360 valid questionnaires were collected, with an effective response rate of 97.3% (360/370). Statistical analysis showed that NICU nurses' growth mindset positively predicted work engagement ( β=0.357, P<0.01) and prone ventilation knowledge, beliefs, and practices ( β=0.736, P<0.01). Work engagement positively predicted prone ventilation knowledge, beliefs, and practices ( β=0.107, P<0.01). Growth mindset had a positive indirect effect on prone ventilation knowledge, beliefs, and practices through work engagement, with an indirect effect of 0.039. Conclusions:NICU nurses' growth mindset positively predicts their prone ventilation knowledge, beliefs, and practices, and can also have an indirect effect through work engagement. Nursing managers should improve NICU nurses' growth mindset using management strategies, optimize resource allocation, and enhance work engagement to improve NICU nurses' prone ventilation knowledge, beliefs, and practices.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To investigate the efficacy of rigid ureteroscopic laser lithotripsy combined with N-trap(RULL+N-trap),which is scoop-shaped,in the treatment of ureteral stones with a maximum diameter ≥1.5 cm.Methods:This retrospective cohort study included patients diagnosed with ureteral calculi who underwent rigid ureteroscopic lithotripsy(RULL)combined with N-Trap stone entrapment system at the Department of Urology,Peking University Third Hospital,by the same surgical team between June 2021 and September 2024.A total of 364 patients were initially enrolled.After excluding 21 patients due to missing critical outcome variables,two distinct cohorts were established:38 patients with ureteral stones measuring ≥1.5 cm in maximum diameter,and 305 patients with stones＜1.5 cm in maximum diameter.To minimize selection bias and control for confounding variables,propensity score matching(PSM)was employed.This resulted in two well-balanced groups:31 patients with stones 1.5 cm in maximum diameter and 31 patients with stones＜1.5 cm in maximum diameter,matched on baseline demographic and clinical characteristics.The primary outcomes assessed between the two groups included stone clearance.Secondary outcomes included changes in renal function indicators,specifically serum creatinine(SCr)and estimated glomerular filtration rate(GFR),and other factors like postopera-tive hospital stay and operative time.Results:In the matched cohort,the patients with stones ≥1.5 cm in maximum diameter had significantly longer operative time compared with those with smaller stones:(85.8±28.8)min vs.(62.4±24.6)min(P＜0.05).Postoperative length of hospital stay showed no significant difference:(2.26±1.79)d vs.(2.03±0.80)d(P＞0.05).The stone clearance on postoperative day one was 90.3％in the study group vs.100.0％in the control group(P＞0.05).One month postoperatively,the stone clearance was 93.5％vs.100.0％,respectively(P＞0.05).Changes in SCr were(-6.58±16.10)μmol/L vs.(-13.70±12.50)μmol/L,and changes in GFR were(5.92±14.90)mL/(min·1.73 m2)vs.(7.47±11.20)m L/(min·1.73 m2),with no statistically significant differences observed between the two groups for either renal function marker(P＞0.05).Conclusion:Ureteroscopic lithotripsy combined with N-trap is an optional method for treating ureteral stones with a maximum diameter ≥1.5 cm.The overall therapeutic efficacy is comparable,with the added benefit of significantly reducing the economic burden on patients.

Objective:To explore the mediating effect of work engagement between growth mindset and prone ventilation knowledge, beliefs, and practices among neonatal intensive care unit (NICU) nurses.Methods:A convenience sampling method was used to select 360 NICU nurses from 13 tertiary hospitals in Shandong Province between August and December 2023. The study used General Information Surveys, Growth Mindset Assessment Scales, a simplified Work Engagement Scale, and an ICU Staff Acute Respiratory Distress Syndrome Prone Ventilation Knowledge, Beliefs, and Practices Questionnaire. Pearson correlation analysis was used to explore the relationship between growth mindset, work engagement, and prone ventilation knowledge, beliefs, and practices. The mediating model was constructed using the PROCESS plugin for SPSS software.Results:A total of 370 questionnaires were distributed, and 360 valid questionnaires were collected, with an effective response rate of 97.3% (360/370). Statistical analysis showed that NICU nurses' growth mindset positively predicted work engagement ( β=0.357, P<0.01) and prone ventilation knowledge, beliefs, and practices ( β=0.736, P<0.01). Work engagement positively predicted prone ventilation knowledge, beliefs, and practices ( β=0.107, P<0.01). Growth mindset had a positive indirect effect on prone ventilation knowledge, beliefs, and practices through work engagement, with an indirect effect of 0.039. Conclusions:NICU nurses' growth mindset positively predicts their prone ventilation knowledge, beliefs, and practices, and can also have an indirect effect through work engagement. Nursing managers should improve NICU nurses' growth mindset using management strategies, optimize resource allocation, and enhance work engagement to improve NICU nurses' prone ventilation knowledge, beliefs, and practices.

Background and purpose:Urothelial carcinoma(UC)is a prevalent malignant tumor of the urinary system,and early diagnosis is crucial for improving patient prognosis.This study evaluated the diagnostic efficacy of fluorescence in situ hybridization(FISH),urine cytology and their combination for UC,as well as for its different subtypes.Methods:This study included patients who underwent transurethral resection of bladder tumor(TURBT)from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center,No.:050432-4-2307E)that met the inclusion and exclusion criteria.We collected TURBT pathological results and pre-procedure FISH and cytology results.Diagnostic accuracy,sensitivity and specificity of FISH,cytology and their combination were analyzed and compared for urothelial carcinoma.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist and Standards for Reporting of Diagnostic Accuracy(STARD)were followed for this study.Results:A total of 283 patients were enrolled in this study,136 were diagnosed with UC,and 147 were not.Of the 136 UC cases,79(58.09%)were invasive and 57(41.91%)were non-invasive.In terms of malignancy grade,112(82.35%)were high-grade UC and 24(17.65%)were low-grade UC.Using histopathology as the gold standard,the accuracy of FISH,cytology and their combination in diagnosing UC was 79.51%,72.08%and 77.39%,respectively;sensitivity was 72.06%,58.82%and 78.68%,respectively;specificity was 86.39%,84.35%and 76.19%,respectively.The area under the curve(AUC)for FISH and the combination was similar but higher than that for cytology(0.792 vs 0.716,P=0.006;0.774 vs 0.716,P=0.004);the Net Reclassification Improvement(NRI)for FISH compared to cytology was 15.28%(P=0.006).In the 79 cases of invasive UC,FISH had higher accuracy than cytology(86.28%vs 78.32%,P=0.011).The sensitivity of FISH and the combination was higher than that of cytology(86.08%vs 67.09%,P=0.004;91.14%vs 67.09%,P＜0.001),and the AUC values were also higher(0.808 vs 0.713,P=0.004;0.784 vs 0.713,P=0.007).The NRI for FISH compared to cytology was 21.03%(P=0.003).In the 57 cases of non-invasive UC,the AUC values for all three methods were low(AUC＜0.700).Among the 112 cases of high-grade UC,FISH had higher accuracy(84.94%vs 76.45%,P=0.005),and the combination had higher sensitivity(89.29%vs 66.07%,P＜0.001)compared to cytology.The AUC values for FISH and the combination were also superior to that for cytology(0.847 vs 0.752,P=0.002;0.827 vs 0.752,P=0.001).The NRI for FISH compared to cytology was 19.01%(P=0.003).In the 24 cases of low-grade UC,the AUC values for all three methods were low(AUC＜0.600).Conclusion:For UC,particularly invasive and high-grade subtypes,FISH shows superior diagnostic efficacy compared to cytology.FISH alone offers accuracy and sensitivity comparable to the combination test,with higher specificity.In cases of non-invasive or low-grade UC,however,all three diagnostic methods demonstrate relatively low efficacy.