Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons.Methods Fifty-two C57BL/6J mice were randomized into control group(n= 12),MPTP group(n=14),MPTP+resveratrol(30 mg/kg)group(n=13),and MPTP+resveratrol(90 mg/kg)group(n=13),and mouse models were established by intraperitoneal MPTP(30 mg/kg)injection for 7 days in the latter 3 groups.Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice.Western blotting was used to detect the expression of TH,α-syn,ZO-1,Claudin-1,TLR4,MyD88,and NF-κB in the brain tissues of the mice.Immunohistochemistry,immunofluorescence,ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier.Results Compared with those in the normal control group,the mice in MPTP group showed significant changes in motor function,number of dopaminergic neurons,neuroinflammation,levels of LPS and LBP,and expressions of tight junction proteins in the intestinal barrier.Resveratrol treatment significantly improved motor function of the PD mice(P<0.01),increased the number of neurons and TH protein expression(P<0.05),down-regulated the expressions of GFAP,Iba-1,and TLR4,lowered fecal and plasma levels of LPS and LBP(P<0.05),restored the expression levels of ZO-1 and Claudin-1(P<0.01),and down-regulated the expressions of TLR4,MyD88,and NF-κB in the colon tissue(P<0.05).The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi.Conclusion Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response,thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

【Objective】 To construct a nomogram survival prediction model for patients with locally advanced renal cell carcinoma based on SEER database (n=7893), so as to provide reference for future prognosis study. 【Methods】 Case data were downloaded from the SEER database, and divided into the experimental group and validation group with a ratio of 7∶3 by simple randomization.The clinical information was analyzed, independent risk factors influencing prognosis were screened, and the overall survival (OS) and tumor-specific survival (CSS) were mapped.Model performance was evaluated using consistency index, area under the receiver operating characteristic curve (AUC), internal and external validation, and calibration curves. 【Results】 Patients’ age, tumor size, disease progression tpye, TNM stage, number of positive lymph nodes, marital status and pathological type were significantly correlated with OS and CSS (P<0.01).Based on the above predictors, the internal verification AUC of the 1-, 3- and 5- year OS nomogram model was 0.809, 0.721 and 0.715, respectively.The internal validation AUC of the nomogram model for 1-, 3- and 5- year CSS was 0.802, 0.745 and 0.735, respectively.The external validation AUC of the OS nomogram model was 0.792, 0.628 and 0.620 at 1, 3 and 5 years, respectively, and the external validation AUC of CSS was 0.943, 0.803 and 0.737 at 1.3 and 5 years, respectively, showing good model differentiation and accuracy. 【Conclusion】 The prediction performance of the nomogram model is good, and it can provide reference for individualized treatment.

Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Objective:To compare the postoperative recurrence rates between Thulium laser en bloc resection of bladder tumor (ERBT) and traditional transurethral resection of bladder tumor (TURBT) in treating patients with non-muscle invasive bladder cancer (NMIBC).Methods:A retrospective analysis was conducted on the clinical data of 1 439 patients with NMIBC who underwent either Thulium laser ERBT or TURBT in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 2010 and March 2024. Among them, 201 patients received Thulium laser ERBT, while 1 238 patients underwent TURBT. Propensity score matching (PSM) was employed in a 1∶1 ratio to eliminate selection bias due to non-random assignment, ensuring the comparability of clinical baseline data such as gender, age, pathological diagnosis, T stage, tumor grade, tumor size, and tumor number between the two groups. Kaplan-Meier method was used to generate recurrence-free survival curves for the matched groups, and the log-rank test was conducted to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting postoperative recurrence.Results:After PSM matching, 193 patients were included in each group. There were no statistically significant differences between the two groups in terms of gender ( P=0.317), age ( P=0.207), pathological type ( P=0.756), T stage ( P=0.402), tumor grade ( P=0.965), tumor size ( P=0.821), or number of tumors ( P=0.421). The median follow-up time was 16.2(8.0, 33.9) months. Excluding patients with non-urothelial tumors such as adenocarcinoma and squamous cell carcinoma, there were 180 cases in the Thulium laser ERBT group and 184 cases in the TURBT group. Survival analysis showed that the postoperative recurrence rate of urothelial carcinoma patients in the Thulium laser ERBT group was lower than that in the TURBT group [20.0%(36/180) vs. 38.6%(71/184), P<0.001]. Stratified survival analysis indicated that in patients with tumor diameters ≤30 mm [22.3%(29/130) vs. 33.6%(45/134), P=0.017] or >30 mm [14.0%(7/50) vs. 52.0%(26/50), P=0.002], the Thulium laser ERBT group had lower postoperative recurrence rate compared to the TURBT group.Among patients with single tumor, the recurrence rate in the Thulium laser ERBT group was lower than in the TURBT group[10.5%(11/105) vs. 31.5%(35/111), P<0.001]. However, among patients with multiple tumors, there was no statistically significant difference in recurrence rates between the Thulium laser ERBT group and the TURBT group [35.7%(25/70) vs. 47.9%(34/71), P=0.061]. Univariate and multivariate Cox regression analyses indicated that Thulium laser ERBT treatment was an independent protective factor against postoperative recurrence in NMIBC patients ( HR=0.44, 95% CI 0.30-0.66, P<0.001). Patients with adenocarcinoma ( HR=5.85, 95% CI 2.07-16.51, P<0.001), squamous cell carcinoma ( HR=2.98, 95% CI 1.04-8.55, P=0.042), or other types of tumors ( HR=2.98, 95% CI 1.14-7.75, P=0.026) had higher risks of recurrence. High-grade tumor patients faced increased risks of postoperative recurrence ( HR=1.84, 95% CI 1.21-2.79, P=0.004). Additionally, tumors >30 mm had increased risks of postoperative recurrence compared to those ≤30 mm ( HR=2.00, 95% CI1.31-3.05, P=0.001). Patients with single tumor had significantly reduced risks of postoperative recurrence compared to those with multiple tumors ( HR=0.50, 95% CI 0.34-0.73, P<0.001). Conclusions:Regardless of tumor diameter (≤30 mm or >30 mm), Thulium laser ERBT significantly reduces the postoperative recurrence rate in patients with urothelial carcinoma compared to TURBT, with the advantage being more pronounced in patients with single bladder tumor. Additionally, patients with high-grade tumors, tumor diameters >30 mm, or multiple bladder tumors have higher risk of postoperative recurrence.

Objective:To evaluate the effects of biorhythm factors on the occurrence of acute kidney injury (AKI) after cardiac surgery using cardiopulmonary bypass.Methods:This was a retrospective cohort study. Data from patients undergoing heart surgery involving cardiopulmonary bypass from June 2018 to December 2019 were collected and divided into 2 groups ( n=125 each) based on the time of anesthesia operation: morning rhythm group (group Ⅰ) and afternoon rhythm group (group Ⅱ). Anesthesia operation was performed from 8: 00 to 12: 00 in group Ⅰ. Anesthesia was performed from 14: 00 to 18: 00 in group Ⅱ. The occurrence of postoperative AKI and other postoperative complications (pulmonary infection, sepsis, cerebral infarction) was recorded. Results:Compared with group Ⅱ, the incidence of postoperative AKI was significantly increased, the relative risk was 3.2 (95% confidence interval 1.31-7.70), and no significant change was found in the incidence of pulmonary infection, sepsis and cerebral infarction in group Ⅰ ( P>0.05). Conclusions:Biorhythm factors affect the development of AKI after cardiac surgery using cardiopulmonary bypass, and performing surgeries in the afternoon rather than the morning helps reduce the risk of postoperative AKI.

Objective To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons.Methods Fifty-two C57BL/6J mice were randomized into control group(n= 12),MPTP group(n=14),MPTP+resveratrol(30 mg/kg)group(n=13),and MPTP+resveratrol(90 mg/kg)group(n=13),and mouse models were established by intraperitoneal MPTP(30 mg/kg)injection for 7 days in the latter 3 groups.Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice.Western blotting was used to detect the expression of TH,α-syn,ZO-1,Claudin-1,TLR4,MyD88,and NF-κB in the brain tissues of the mice.Immunohistochemistry,immunofluorescence,ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier.Results Compared with those in the normal control group,the mice in MPTP group showed significant changes in motor function,number of dopaminergic neurons,neuroinflammation,levels of LPS and LBP,and expressions of tight junction proteins in the intestinal barrier.Resveratrol treatment significantly improved motor function of the PD mice(P<0.01),increased the number of neurons and TH protein expression(P<0.05),down-regulated the expressions of GFAP,Iba-1,and TLR4,lowered fecal and plasma levels of LPS and LBP(P<0.05),restored the expression levels of ZO-1 and Claudin-1(P<0.01),and down-regulated the expressions of TLR4,MyD88,and NF-κB in the colon tissue(P<0.05).The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi.Conclusion Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response,thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

Objective To investigate the effects of ethanol extract of Akebia trifoliate(Thunb.)Koidz(EEATK)on the proliferation and apoptosis of human hepatocellular carcinoma Hep3B and Huh-7 cells and to explore its underlying mechanism.Methods Human Hep3B cells and Huh-7 cells were cultured in vitro and separated into control group,Sorafenib group(5 μmol/L),and EEATK groups(0.10 mg/mL,0.15 mg/mL,0.20 mg/mL,0.3 mg/mL)and given the corresponding drug interventions.A CCK-8 assay was used to measure the impact of the different interventions on the proliferation of Hep3B cells and Huh-7 cells to screen the optimal action-inducing concentrations for subsequent experiments.EdU staining assay and colony formation assay were used to explore the effect of EEATK on proliferation,and Annexin V-FITC/PI double-staining assay was applied for apoptotic rate analysis.Transcriptome sequencing(RNA-seq)technology was used to analyze differentially expressed genes(DEGs)related to cell proliferation and apoptosis in the control group and EEATK(0.15 mg/mL)groups of Hep3B cells.DEGs were analyzed for function with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The Comparative Toxicogenomics Database(CTD)was used to validate the expression of key proteins related to cell proliferation and apoptosis,and the findings were verified by qRT-PCR.Results Compared with the control group,different concentration of EEATK significantly inhibited the activity of Hep3B and Huh-7 cells(P＜0.01).Hep3B cells were treated with 0.15 mg/mL EEATK,the EdU-positive cell rate and clone formation rate significantly decreased(all P＜0.01).At the same time,the apoptotic rate of the EEATK group significantly increased(P＜0.01).Transcriptome sequencing of Hep3B cells showed that EEATK induced significant changes in the expression of 1577 genes(P＜0.01),of which 942 were up-regulated and 635 were down-regulated compared with the control group.GO functional enrichment analysis revealed that the DEGs were mainly enriched for cholesterol synthesis,inflammation,and extracellular matrix.KEGG pathway analysis showed that EEATK plays an anti-tumor role,mainly through the TFG-β and NF-κB signaling pathways.CTD and qRT-PCR analysis showed that EEATK significantly down-regulated the expression of apoptosis-related genes such as BIRC5 and CDK1(P＜0.01)and significantly upregulated the expression of CDKN1A and EGLN3(P＜0.01).At the same time,EEATK caused the significant downregulation of cell-proliferation-related genes such as FAM83D and MKI-67(P＜0.01),and significantly upregulated the expression of MYC and FOXC1(P＜0.01).Conclusions EEATK can inhibit cell proliferation and induce apoptosis in a manner that may be related to the regulation of TGF-β and NF-κB signal pathway-related gene expression.