Objective To explore the regulatory mechanism of methyltransferase like protein 3 (METTL3)–mediated m⁶A methylation in promoting pri-microRNA 150 (miR-150) maturation in esophageal squamous cell carcinoma (ESCC). Methods Quantitative real-time PCR and Western blot analysis were used to detect the expression of METTL3, pri-miR-150, miR-150, and MYB in ESCC cell lines, and lentiviral transfection and cell proliferation assays were applied to explore the role of METTL3 in ESCC cell proliferation. RNA immunoprecipitation and co-immunoprecipitation assays were used to confirm that METTL3 binds DGCR8 and regulates pri-miR-150 processing and maturation in an m⁶A methylation–dependent manner. Luciferase reporter assays were utilized to map the direct binding sites between miR-150 and MYB. Colony formation and CCK-8 assays confirmed that miR-150 functions in METTL3-induced ESCC cell proliferation. Results METTL3 expression was substantially upregulated in ESCC tissues and corresponding cell lines. ESCC cell proliferation was suppressed by METTL3 knockdown or enhanced by METTL3 overexpression. METTL3 mediates miR-150 processing and maturation via DGCR8, and miR-150 rescues METTL3-induced ESCC cell proliferation by targeting the MYB transcription factor. Conclusion This study demonstrates that METTL3 promotes pri-miR-150 processing and maturation in an m⁶A methylation–dependent manner by interacting with DGCR8, thereby enhancing ESCC cell proliferation and providing novel insights into ESCC diagnosis and treatment.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To observe the effect of the supine-posture ripple wood training in preventing motion sickness caused by linear acceleration.Methods Totally 61 motion sickness sensitive males were screened by a vertical oscillation simulator and divided into mildly sensitive group(Graybiel score 1-15,n=28)and severely sensitive group(Graybiel score 16,n=33).The participants in the 2 groups received 5-d ripple wood training,30 min/d.The movement frequency of the ripper wood was maintained at 0.25-0.35 Hz,with an acceleration of 0.15-0.25 g.Graybiel score during the training period was recorded.The static balance function test was conducted before and after training on the 1st and 5th day.Results During the training period,the Graybiel scores and motion sickness incidence in the severely sensitive group were decreased with the increase of training days,and all participants achieved complete acclimatization on the 4th day.The Graybiel scores of the mildly sensitive group were low during the whole period,and the complete acclimatization period was 2 d.There was no significant difference in the sway area of the severely sensitive group in static balance function test before and after training(P＞0.05).The mean velocity of the severely sensitive group in static balance function test was significantly increased after training versus before training on the 1st day(P＜0.01),and there was no significant difference before and after training on the 5th day(P＞0.05).There were no significant differences in the sway area or mean velocity of the mildly sensitive group during the whole training period(all P＞0.05).The validation experiment showed that the motion sickness incidence and the symptom severity were significantly decreased in both groups;the motion sickness incidence of the mildly sensitive group decreased from 100.00％(28/28)to 35.71％(10/28);the incidence of severe symptoms in the severely sensitive group decreased from 100.00％(33/33)to 6.06％(2/33)and the vomiting incidence decreased from 96.97％(32/33)to 6.06％(2/33).Conclusion The supine-posture ripple wood training has great effect in preventing motion sickness,with widespread use and simple operation.

Objective:To analyze the clinical characteristics of patients of chronic active Epstein-Barr virus infection (CAEBV) with intestinal involvement misdiagnosed as inflammatory bowel disease (IBD).Methods:A retrospective analysis was conducted on the clinical characteristics, laboratory results, digestive endoscopic findings, histological results, treatment and prognosis of 10 patients with CAEBV intestinal involvement who were misdiagnosed as IBD and treated at the Department of Hematology, Beijing Friendship Hospital, Capital Medical University from February 2019 to November 2022. Epstein-Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Results:Among the 10 patients with CAEBV, eight were males and two were females. Seven patients had been misdiagnosed as ulcerative colitis and three misdiagnosed as Crohn′s disease. The median age of onset was 36 years (ranged from 26 to 52 years), and the median time from onset to CAEBV diagnosis was 18.5 months (ranged from 2.0 to 96.0 months). The main clinical characteristics of these patients included fever >38.5 ℃ in 10 cases, diarrhea in seven cases, abdominal pain in seven cases, abdominal lymph node enlargement in six cases and hematochezia in seven cases. Six patients primarily presented with gastrointestinal symptoms, and seven patients had involvement of extraintestinal organs, three patients developed hemorrhagic shock due to gastrointestinal bleeding. The laboratory findings included anemia in seven cases, elevated erythrocyte sedimentation rate in six cases, decreased natural killer cell activity in five cases, and elevated ferritin in three cases. Epstein-Barr virus (EBV) DNA were detected in the peripheral blood mononuclear cells (PBMCs) of nine patients, with a median viral load of 23 000 copies/mL. Seven patients were tested positive for anti-EBV viral capsid antigen IgG and nuclear antigen 1 IgG. The main endoscopy findings were hyperemia, edema of the affected intestinal wall mucosa, which could be accompanied by erosion, multiple scattered shallow ulcers with varying sizes. There were six patients with total colon involvement. The rectum was involved in three patients, and the esophagus, gastric antrum, duodenum and small intestine were each involved in one patient. Seven patients underwent follow-up colonoscopy after diagnosis, and four cases progressed. All 10 patients showed active chronic inflammation in the histopathological examinations of their intestinal tissue, with crypt changes in four cases and granulomatous changes in one cases. The intestinal tissues of eight patients were positive for EBER staining, and EBER positive cells≥50 cells/high-power field in seven patients. Seven patients were treated with 5-aminosalicylic acid before the correct diagnosis. Five patients had not improved or progressed upon the follow-up colonoscopy. Two patients died of uncontrolled massive hemorrhage of digestive tract.Conclusions:The clinical, endoscopic and pathological findings of patients with CAEBV intestinal involvement lack specificity. For IBD patients initially diagnosed accompanied by fever and evidence of extraintestinal organ involvement, it is recommended to simultaneously detect EBV DNA in PBMCs and blood plasma, EBER in intestinal tissue, and identify the main EBV-infected cells in peripheral blood and/or tissue, to distinguish CAEBV.

Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

BACKGROUND:Electrical stimulation is a physical method that can be used to induce various cellular activities such as cell proliferation,differentiation,and apoptosis.The induction of osteogenic differentiation of stem cells will be beneficial in the field of bone regeneration. OBJECTIVE:To observe whether micro-current field can promote the proliferation and osteogenic differentiation of human umbilical cord mesenchymal stem cells. METHODS:The fresh human umbilical cord tissue was cut to obtain umbilical cord mesenchymal stem cells,which were inoculated into a 6-well plate after cell culture and passage to the third generation.After 24 hours,the cells were cultured under a stimulation of 0,50,and 100 mV/mm micro-electric field,at a frequency of 1 hour per day for 3 continuous days.The growth and morphological changes of human umbilical cord mesenchymal stem cells were observed by a microscope.The cell proliferation was detected by CCK-8 assay and EdU staining.Alizarin red staining was used to detect the osteogenic differentiation ability of cells.Western blot assay was used to determine the expression of ERK signal pathway proteins. RESULTS AND CONCLUSION:(1)The optical density value and the number of proliferating cells in 50 and 100 mV/mm groups were significantly higher than those of the unstimulated group(P<0.05).(2)Human umbilical cord mesenchymal stem cells could be induced to differentiate into osteocytes before and after micro-electric field stimulation,but the differentiation rate of 50 and 100 mV/mm groups was faster than that of unstimulated groups.(3)The protein expression of p-ERK1/2 in the 50 and 100 mV/mm groups was higher than that in the unstimulated group,and significant difference was detected between the 100 mV/mm group and the unstimulated group(P<0.05).(4)Micro-electric field can promote the proliferation of human umbilical cord mesenchymal stem cells,and the mechanism may be achieved by promoting the phosphorylation of ERK.

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-a and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/b-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt b-catenin pathways.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.
Humans ; Vocal Cords/pathology* ; Retrospective Studies ; Laryngopharyngeal Reflux/complications* ; Prospective Studies ; Precancerous Conditions/pathology* ; Risk Factors