Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Objective:To study the effects of parenteral nutrition containing ω-3 fish oil fat emulsion on the inflammatory status of patients with intestinal fistula at the early stage.Methods:A retrospective analysis was conducted on 28 patients with intestinal fistula who were admitted to the Sixth Department of General Surgery of Anhui Provincial Second People's Hospital from November 2023 to May 2024.The patients were either divided into control group(n=15,parenteral nutrition alone group)or study group(n=13,parenteral nutrition plus ω-3 fish oil fat emulsion)according to whether ω-3 fish oil fat emulsion was added to parenteral nutrition.Both groups of patients received parenteral nutrition support treatment,and the study group was given ω-3 fish oil fat emulsion during treatment.The general information,inflammatory factors in the blood,nutrition,and immune status of two groups of patients were collected and compared.The feces samples on the first and 14th day of admission were collected and analyzed by 16S rRNA high-throughput sequencing of gut microbiota.Results:There was no statistically significant difference in the general information,inflammation,nutrition,immune status,and gut microbiota between the two groups of patients on the first day of admission(P>0.05),indicating comparability between the two groups.After two weeks of parenteral nutrition support,the counts of red blood cells,white blood cells,platelets,lymphocytes,and levels of C-reactive protein,glutamate-pyruvate transaminase,aspartate aminotransferase,total bilirubin,direct bilirubin,total protein,albumin,and creatinine in the research group were similar to those in the control group without statistically significant differences(P>0.05).However,the counts of neutrophils and levels of blood urea nitrogen in the study group were significantly lower than those in the control group(P=0.03 and P=0.01).In addition,the abundance of intestinal flora in the study group was significantly higher than that in the control group(P<0.05).At the genus level,the abundance of Bacteroides_uniformis,Parabacteroides_merdae,Alistipes_finegoldii,Streptococcus_constellatus,Christensenella_minuta were different between the two groups after two weeks of treatment(P<0.05).Conclusion:Parenteral nutrition containing ω-3 fish oil fat emulsion can reduce the counts of neutrophils,which may alleviate inflammatory responses for patients with intestinal fistula at the early stage.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Myopia has become a serious public health problem, but its pathogenesis is still unclear, and effective interventions are relatively scarce.It is recognized that myopia is influenced by both genetic and environmental factors, in which epigenetics may play a key role.Epigenetics refers to the changes in gene expression and function that do not involve DNA sequence variation.Mainly including DNA methylation, non-coding RNA (microRNA, long non-coding RNA and circular RNA, etc.), histone modification and mRNA modification, epigenetic modifications interact to form a complex regulatory network in the pathophysiological process of myopia.By controlling the process of scleral matrix remodeling, eye cell proliferation and retinal development, the morphological characteristics of the eye are jointly regulated, ultimately affecting the onset and development of myopia.Epigenetics has provided new targets of myopia intervention and has become a hotspot in the field.In this paper, we reviewed the current findings of myopia epigenetics to provide a reference for related research.

Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

BACKGROUND: The prognostic benefit of complete revascularization in elderly patients (aged over 75 years) with multi-vessel disease and acute coronary syndrome (ACS) is currently unclear. This study aimed to determine the long-term prognostic impact of complete revascularization in this population. METHODS: We conducted this study using data obtained from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry, which was carried out from 2003 to 2014. The objective was to categorize older patients diagnosed with ACS into two groups: those who underwent complete revascularization and those who did not. Propensity score matching and the Kaplan-Meier analysis were employed to examine differences in one-year clinical outcomes. The primary endpoint was major adverse cardiovascular event (MACE), which encompassed a combination of all-cause mortality and myocardial infarction. RESULTS: Out of 1263 patients evaluated, 445 patients (35.2%) received complete revascularization. Patients who underwent complete revascularization had a higher prevalence of hypertension and prior percutaneous coronary intervention compared to those who did not. During the one-year follow-up period, complete revascularization was associated with a significantly decreased risk of MACE [13.7% vs. 20.5%, hazard ratio (HR) = 0.63, 95% CI: 0.45-0.88, P = 0.007] and a lower risk of myocardial infarction (5.9% vs. 9.9%, HR = 0.55, 95% CI: 0.33-0.92, P = 0.02). However, it was not linked to a lower risk of all-cause death (9.5% vs. 13.5%, HR = 0.68, 95% CI: 0.45-1.02, P = 0.06). Similar results were observed in the subgroup analysis. CONCLUSIONS Long-term clinical improvements were observed in ACS patients aged over 75 years with multi-vessel disease who achieved complete revascularization. Therefore, adhering to guidelines for complete revascularization should be recommended for elderly patients.

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ² test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.
Adolescent ; China/epidemiology* ; Electronic Nicotine Delivery Systems ; Humans ; Prevalence ; Students ; Tobacco ; Tobacco Smoke Pollution

Objective To investigate the genes involved in Wolbachia-induced cytoplasmic incompatibility among three natural populations of Culex pipiens pallens in eastern China, so as to provide insights into the development of preventive and control measures for mosquito-borne diseases based on Wolbachia. Methods The cytoplasmic incompatibility was tested among three natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province and Tangkou of Shandong Province using reciprocal crosses. Wolbachia infection was detected in C. pipiens pallens using a PCR assay, and the expression of Wolbachia wsp and WD0513 genes was quantified using a fluorescent quantitative real-time PCR (qPCR) assay. Results Bidirectional compatibility was found between the natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province (t = 0.57 and 0.15, both P values > 0.05), while bidirectional incompatibility was seen between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Wuxi of Jiangsu Province (t = 63.81 and 43.51, both P values < 0.01), and between the natural populations of C. pipiens pallens collected from Nanjing of Jiangsu Province and Tangkou of Shandong Province (t = 39.62 and 43.12, both P values < 0.01). Wolbachia wsp gene was amplified in all three natural populations of C. pipiens pallens, and qPCR assay detected no significant difference in the Wolbachia wsp gene expression among the three natural populations of C. pipiens pallens (F = 2.15, P > 0.05). In addition, there was no significant difference in the WD0513 gene expression between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Nanjing of Jiangsu Province (q = 8.42, P < 0.05) or between the natural populations of C. pipiens pallens collected from Tangkou of Shandong Province and Wuxi of Jiangsu Province (q = 7.84, P < 0.05); however, there was a significant difference detected in the WD0513 gene expression between the natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province (q = 0.40, P > 0.05). Conclusions Different Wolbachia numbers are detected in natural populations of C. pipiens pallens collected from Nanjing and Wuxi of Jiangsu Province and Tangkou of Shandong Province, and WD0513 gene may be involved in the Wolbachia-induced cytoplasmic incompatibility among three natural populations of C. pipiens pallens.

Objective To evaluate the 1-year follow-up effect of smoking cessation contest among government functionaries in Shanghai in 2015, providing evidence and basis for the effective intervention of smoking cessation. Methods A case-control study design was used for those who had quit smoking periodically, and their 1-year smoking cessation situation was investigated. Results At the 1-year follow-up after the contest, the relapse rate was 19.70%, of which 79.49% occurred within 2 months after quitting smoking.The main causes of relapse were the peer pressure and attack of smoking addiction. Conclusion After the smoking cessation contest, the 1-year follow-up relapse rate is at a low level, which indicates the contest among government functionaries in Shanghai in 2015 is effective.Education level is found to be a risk factor for relapse.