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.

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.

Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).
Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve Insufficiency ; Diffusion Magnetic Resonance Imaging ; Aortic Valve Stenosis ; Stroke

OBJECTIVE: To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. METHODS: A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. RESULTS: Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. CONCLUSION SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.
Humans ; Infant, Newborn ; Amino Acid Metabolism, Inborn Errors/genetics* ; Carnitine ; Neonatal Screening/methods*

Covalent organic nanospheres(CONs)were explored as a fiber coating for solid-phase microextraction of genotoxic impurities(GTIs)from active ingredients(AIs).CONs were synthesized by an easy solution-phase procedure at 25℃.The obtained nanospheres exhibited a high specific surface area,good ther-mostability,high acid and alkali resistance,and favorable crystallinity and porosity.Two types of GTIs,alkyl halides(1-iodooctane,1-chlorobenzene,1-bromododecane,1,2-dichlorobenzene,1-bromooctane,1-chlorohexane,and 1,8-dibromooctane)and sulfonate esters(methyl p-toluenesulfonate and ethyl p-toluenesulfonate),were chosen as target molecules for assessing the performance of the coating.The prepared coating achieved high enhancement factors(5097-9799)for the selected GTIs.The strong affinity between CONs and GTIs was tentatively attributed to T-T and hydrophobicity interactions,large surface area of the CONs,and size-matching of the materials.Combined with gas chromatography-mass spectrometry(GC-MS),the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range(0.2-200 ng/g)with a low detection limit(0.04-2.0 ng/g),satisfactory recovery(80.03％-109.5％),and high repeatability(6.20％-14.8％)and reproducibility(6.20％-14.1％).Therefore,the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.

Objective To explore the epidemiological characteristics and the potential years of life lost of gynecological malignant tumors among female residents in Pudong New Area of Shanghai between 2002 and 2019. Methods Crude mortality rate (CMR), age-standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL) and annual percent change (APC) of the cervical cancer，uterine cancer and ovarian cancer deaths were calculated to analyze the mortality situation of gynecological malignant tumors among female residents in Pudong New Area. Results The crude mortality rate were 2.65/100 000, 2.44/100 000 , 4.55/100 000, and age-standardized mortality rate were 1.33/100 000, 1.06/100 000, 2.26/100 000, respectively, among female residents in Pudong New Area during 2002 to 2019. In the study period, both the crude mortality rate and the age-standardized mortality rate of cervical cancer rose over the years; Both the crude mortality rate and the age-standardized mortality rate of uterine cancer kept stable; The crude mortality rate of ovarian cancer showed an upward trend, and the age-standardized mortality rate kept stable. The PYLL of cervical cancer was 7335 years, the PYLL rate was 0.30‰, and the AYLL was 11.20 years per person; The PYLL of uterine cancer was 3556 years, the PYLL rate was 0.14‰, and the AYLL was 5.90 years per person; The PYLL of uterine cancer was 10017 years, the PYLL rate was 0.41‰, and the AYLL was 8.91 years per person. Conclusion The mortality rate of cervical cancer and ovarian cancer rose over years, and the mortality of uterine cancer kept stable among female residents in Pudong New Area during 2002 to 2019. The gynecological malignant tumors caused severe disease burden.

Objective To explore the death characteristics and the potential years of life lost from chronic obstructive pulmonary disease (COPD) among residents in Pudong New Area of Shanghai from 2002 to 2019, so as to provide a reference for formulating corresponding prevention and control strategies for chronic obstructive pulmonary disease. Methods The death data of chronic obstructive pulmonary disease was extracted from the Pudong New Area's death surveillance system. Crude mortality, age-standardized mortality, potential years of life lost (PYLL), average years of life lost (AYLL) and annual percent change (APC) of chronic obstructive pulmonary disease deaths were calculated to analyze the situation of COPD death in Pudong New Area. Results The crude mortality and age-standardized mortality of chronic obstructive pulmonary disease among residents in Pudong New Area between 2002 and 2019 were 64.94/100,000 and 21.04/100 000, respectively. The chronic obstructive pulmonary disease showed a downward trend (APC=-2.05%, Z=- 5.342, P<0.001), and the standardized mortality rate decreased year by year (APC=-6.23%, Z=-13.052, P<0.001). The crude mortality and age-standardized rates in male residents were both higher than those in females (Z-crude mortality=46.471, P<0.001, Z-standardized mortality=-48.961, P<0.001). The PYLL of chronic obstructive pulmonary disease was 16,997 years, the PYLL rate was 0.34‰, and the AYLL was 0.53 years per person. Conclusion From 2002 to 2019, the mortality of chronic obstructive pulmonary disease among residents in Pudong New Area was relatively high and caused serious life loss. Both crude mortality and age-standardized rate showed a downward trend during the study period. Comprehensive prevention and control measures should be further developed.

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 evaluate the optical coherence tomograghy (OCT) morphological parameters for predicting anatomical outcomes and postoperative visual acuity in idiopathic macular hole (IMH) after pars plana vitrectomy (PPV).Methods A retrospective study.A total of 26 eyes in 23 IMH patients underwent PPV,internal limiting membrane (ILM) peeling and gas filling surgery were included in this study.The patients included 8 eyes of 7 males and 18 eyes of 16 females,with the mean age of (63.9 ± 9.4).All patients received the best corrected visual acuity (BCVA),slit lamp microscope,indirect ophthalmoscopy and three-dimensional optical coherence tomography (3D OCT) examinations.The BCVA was measured using the international standard visual acuity chart,and the results were converted to the logarithm of the minimum angle of resolution visual acuity.According to the standard classification system of International Vitreomacular Traction Study (IVTS) Group,8 eyes were medium full-thickness macular hole (FTMH) and 18 eyes were large FTMH,none of which were with vitreomacular traction (VMT).The minimum diameter (MIN),base diameter (BASE),height (H),left and right arm length (LAL and RAL),diameter of ellipsoid zone absence (DEZA) were measured.Macular hole index (MHI),hole form factor (HFF),tractional hole index (THI),diameter hole index (DHI) were calculated.The average follow-up period were (9.2 ± 9.7) months.The postoperative DEZA were measure at the last time.Anatomical outcomes were divided into 3 groups.The multiple factors related with predicting anatomical outcome and visual acuity were analyzed.Results In the 26 eyes,the hole was closed in 16 eyes of type 1,7 eyes of type 2,3 eyes of type 3.The mean pre-and post-operative logMAR BCVA were 0.9 ± 0.3,0.7 ± 0.3 respectively.The MIN,BASE,H were (533 ± 176),(1 035 ±270),(462 ± 138) μm respectively.The MHI,HFF,THI,DHI were 0.46 ±0.15,0.72 ±0.19,0.95 ±0.37,0.52 ±0.11 respectively.The mean preand post-operative DEZA were (1 775 ± 486),(960 ± 138) μm respectively.Postoperative logMAR BCVA were correlated significantly with MHI,THI (all P ≤ 0.01),correlated weakly with MIN,BASE,HFF (all P ≤ 0.05),but not correlated with age,sex,DHI,pre-and post-operative DEZA (all P ＞ 0.05).Anatomical prognosis types were significantly correlated with MHI,HFF,THI (all P ≤ 0.01),weakly correlated with MIN,DHI (all P ≤ 0.05),but not correlated with age,sex,BASE,pre-and post-operative DEZA (all P ＞ 0.05).Conclusions For medium and large FTMH in IVTS classification system,MHI,THI have the best correlation with postoperative BCVA and can be considered as key indicators for predicting postoperative BCVA.MHI,HFF,THI have the best correlation with anatomical outcomes and can be considered as key indicators for predicting anatomical outcomes of IMH.