Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

The incidence rate of thyroid cancer has been rising in recent years. How to accurately distinguish malignant and benign thyroid nodules before surgery has become an important research direction. Ultrasound, as a non-invasive and fast examination method, has been widely used in clinical practice. Some typical ultrasound features, such as calcification, unclear boundaries, multiple lesions, low echo, and aspect ratio>1, can indicate the occurrence of thyroid cancer before surgery. Further analysis of these ultrasound features is still a focus of current research. This article will review the expression and distribution of calcification, a typical ultrasound feature, in benign and malignant thyroid nodules, in order to provide a basis for predicting the malignancy of thyroid nodules based on the characteristics of calcification under preoperative ultrasound.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Background and Aims:Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation,specifically BRAFV600E,is a specific biomarker for papillary thyroid carcinoma (PTC). However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAFV600E mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAFV600E mutations were analyzed. Using postoperative pathology as the gold standard,the diagnostic performance of BRAFV600E mutation testing in FNA benign nodules was assessed. Results:Among the 84 FNA benign thyroid nodules,44 (52.4％) tested positive for the BRAFV600E mutation. Patients with BRAFV600E-positive nodules were more likely to be younger than 45 years (56.8％ vs. 35.0％,P=0.045),and their nodules had a smaller median long diameter compared to the BRAFV600E-negative group (0.49 cm vs. 0.61 cm,P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm,P=0.004) and a higher proportion of nodules<1 cm (95.2％ vs. 71.4％,P=0.007),with a higher BRAFV600E mutation rate (68.3％ vs. 4.8％,P<0.001). In terms of the ultrasound characteristics of thyroid nodules,BRAFV600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4％ vs. 60.0％,P=0.006). Similarly,PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0％ vs. 52.4％,P=0.010). Multivariate Logistic regression analysis indicated that BRAFV600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAFV600E-negative nodules (P=0.001),with BRAFV600E mutation being an independent risk factor for PTC diagnosis. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of BRAFV600E mutation testing for PTC diagnosis were 69.3％,95.2％,97.7％,50.0％,and 75.0％,respectively. Conclusion:BRAFV600E mutation testing demonstrates high positive predictive value and accuracy,and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAFV600E mutation testing.