AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

Objective To analyze the colorectal cancer screening of community residents in Pudong New Area in Shanghai and provide reference for the promotion and strategy optimization of colorectal cancer screening programs. Methods Residents aged 50-74 years in the colorectal cancer screening project of Pudong New Area in Shanghai from 2013 to 2023 were recruited in this analysis. The situation of primary screening and colonoscopy in the community was described, and results of different age groups in primary screening and colonoscopy surveys were evaluated. Chi-square test was used to determine differences between groups. Results From 2013 to 2023, 907 030 residents were screened in Pudong New Area, of which 183 724 residents were positive, and the positive rate was 20.3%. The positive rate was the lowest in the 50-54 age group and the highest in the 70-74 age group. The positive rate was higher in men than in women. The overall colonoscopy rate was 27.1%, with the highest rates in the 50-54 age group in men and the 55-59 age group in women, respectively. The participation rate of colonoscopy increased with the increase of the year. A total of 19 094 cases of intestinal lesions were found by colonoscopy. Among these lesions, 1 147 cases were colorectal cancer, accounting for 6.0%, and the population detection rate was 126.5/100 000. In addition, 4 751 cases of precancerous lesions were found, accounting for 24.9%, and the detection rate was 523.8/100 000. Conclusion Colorectal cancer screening improves the detection rate of precancerous lesions and early cancer and is of great significance for reducing the incidence and mortality of colon cancer. Measures should be taken to optimize the screening strategy based on age differences and increase the participation rate of primary screening and colonoscopy to achieve the best effect of local colorectal cancer prevention and treatment.

A large number of data show that the prevalence rate of alcoholic liver injury （ALI） is increasing year by year， and it has become one of the main causes of death due to chronic liver diseases such as liver cancer and liver cirrhosis. Quitting drinking is the main method for the prevention of ALI in modern medicine， and the main treatment methods include Western medicine with antioxidant and anti－fibrotic effects and nutritional support. However， Western medicine tends to have an unsatisfactory treatment effect and can only alleviate initial symptoms， and severe ALI still requires surgical treatment. Studies have shown that the monomers extracted from natural drugs and foods have obvious preventive and therapeutic effects on ALI， with high safety and easy access. Therefore， this article systematically summarizes the main natural drug and food monomers used for the prevention and treatment of ALI and proposes the idea of the combination of drug and food for the prevention and treatment of ALI from the perspective of paying attention to the whole process of health， in order to explore more effective prevention， health care， and treatment methods and provide ideas for research on the prevention and control of ALI.

Background: Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway. Methods: We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole. Results: 1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group. Conclusion We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.

Objective:To analyze the results of polysomnography(PSG) in 523 children, and explore the sleep monitoring results and related influencing factors of obstructive sleep apnea hypopnea syndrome(OSAHS).Methods:The PSG monitoring results of children with OSAHS and non-OSAHS were analyzed for children aging from 0 to 16 years old, who were monitored at Sleep Medicine Center of Gansu Maternal and Child Health Hospital from January 2014 to December 2019.Results:A total of 523 children underwent PSG monitoring during the past 5 years.The male to female ratio was 1∶0.47, of which 66.9%(350/523)were children with OSAHS.The average proportion of rapid eye movement sleep was 1.95%(7.7/394). The height of non-OSAHS group was significantly higher than that of OSAHS group[(108.72±16.39)cm vs.(104.80±16.60)cm, P=0.016]. The incidence of OSAHS decreased with age( P=0.038). The apnea index, hypopnea index, apnea hypopnea index, obstructive apnea index, microarousal index, oxygen desaturation index, mean apnea time, and longest apnea time in the OSAHS group were higher than those in the non-OSAHS group( P<0.05). And the lowest oxygen saturation and the mean oxygen saturation during sleep were lower than those in the non-OSAHS group( P<0.05). Logistic regression analysis on the clinical data of OSAHS children showed that open mouth breathing and snoring at night had significant effects on children′s OSAHS, and the differences were statistically significant( P<0.05). Conclusion:PSG is of great significance for the diagnosis of OSAHS.The more severe the degree of OSAHS, the worse severe the night sleep hypoxemia.PSG should be recommended before taking any treatment for children with sleep disorders.

Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients. Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis. Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2% vs. 90.1% (P=0.001), 96.7% vs. 90.1% (P=0.028), 98.4% vs. 90.1% (P=0.005) and 98.4% vs. 100% (P > 0.05), respectively. EBV DNA is negatively correlated with the ratio of CD19⁺ B cells before treatment (r=-0.138, P=0.040), and there was no significant correlation between EBV DNA and other circulating immune supgroups (P > 0.05). ROC analysis showed that the cut-off value of CD19⁺B cell ratio before treatment related to the 3-year OS was 8.33% (P=0.02). The 3-year OS, PFS, DMFS and LRFS of patients with CD19⁺B cells ratio ≤8.33% and CD19⁺B cells ratio > 8.33% were respectively 90.4% vs. 99.2% (P=0.003), 89.2% vs. 97.5% (P=0.008), 90.4% vs. 98.3% (P=0.008) and 98.8% vs. 99.2% (P > 0.05). However, ROC analysis showed that there was no significant correlation between OS and other peripheral immune cells (including the proportion of CD3⁺T, CD3⁺CD4⁺T, CD3⁺CD8⁺T and CD56⁺NK cells and CD4⁺/CD8⁺ ratio). Multivariate analysis showed that EBV DNA load was an independent prognostic factor of 3-year PFS of NPC patients, and the ratio of CD19⁺B cells was an independent prognostic factor of 3-year PFS, MFS and OS of NPC patients. Conclusion Before treatment, there is a negative correlation between plasma EBV DNA and the proportion of CD19⁺B cells in peripheral blood. Both can be used as the predictors of 3-year OS, PFS and DMFS of NPC patients.

Objective To understand the distribution characteristics of death causes and potential life loss of residents in Pudong New Area from 2009 to 2018, assess the disease burden caused by different diseases, and provide a basis for formulating regional prevention and control strategies. Methods The mortality data of residents in Pudong New Area of Shanghai from 2009 to 2018 were collected. The death causes were classified by International Classification of Diseases (ICD-10). The crude mortality rate, standardized mortality rate, potential years of life lost (PYLL), potential years of life lost rate (PYLLR), and average years of life lost (AYLL) were calculated. Results The crude mortality and standardized mortality of residents in Pudong New Area between 2009 and 2018 were 7.55‰ and 3.65‰, respectively. The top five causes of death in Pudong New Area residents were circulatory system diseases, tumors, respiratory diseases, endocrine nutrition and metabolic diseases, and injury and poisoning, accounting for 87.85% of the total deaths. The PYLL was 687 729 person-years, the PYLLR was 24.11‰ and the AYLL was 3.19 years per person. The top 5 causes of life loss of residents in Pudong New Area was tumor, circulatory system disease, injury and poisoning, endocrine nutrition and metabolism illness, and congenital anomalies, accounting for 82.08% of total life loss of residents. Conclusion Chronic non-infectious diseases, including circulatory diseases, tumors, and endocrine nutritional metabolism diseases, were the main causes of death of residents in Pudong New Area, and caused a heavy disease burden, which should be the focus of prevention and control in the future. Comprehensive preventive and control measures should be taken to protect the residents from the harm due to chronic non-communicable diseases and improve the health condition of the residents in Pudong New Area.

Objective To investigate the clinical outcomes of patients with locally advanced uterine cervical cancer (UCC) treated by 3-dimensional high dose rate-intracavitary brachytherapy (3D HDR-ICBT) combined with complementary applicator-guided external beam radiotherapy (EBRT).Methods A total of 120 patients pathologically diagnosed with locally advanced UCC (tumors with a maximum diameter≥6 cm or ≥5 cm complicated with eccentric tumor growth) treated with concurrent chemoradiotherapy (CCRT) from June 2010 to June 2015 were recruited.Five fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were performed.The prescribed dose for HR-CTV and IR-CTV was 7 Gy (D9o) and 5-6 Gy (D90).The rectum,sigmoid colon,bladder and adjacent small intestine were delineated as the organs at risk.Intensity-modulated radiation therapy (IMRT) was used for EBRT (45 Gy/ 25f) combined with cisplatin-based chemotherapy every three weeks (75 mg/m2).Results The median follow-up time was 46 months (14-96 months).The 5-year local control rate (LCR),disease-free survival (DFS),and overall survival (OS) were 92.8％,76.6％ and 81.0％,respectively.The incidence rate of grade Ⅰ-Ⅱ genitourinary and gastrointestinal acute toxicities were 57.8％ and 14.6％,whereas 8.1％ and 2.9％ for grade Ⅲ toxicities.The incidence rate of later grade Ⅰ-Ⅱ genitourinary and gastrointestinal toxicities were 8.4％ and 5.3％,and 0.97％ and 1.3％ for grade Ⅲ late toxicities.Conclusions The combination of HDR-ICBT with an applicator-guided IMRT (ICBT+IMRT) yields low incidence of severe adverse events,relatively high LC and OS rate for locally advanced UCC.It is an efficacious comprehensive treatment of locally advanced bulky UCC.