Objective To analyze the characteristics of viral hepatitis mortality and life loss among residents in Pudong New Area from 2003 to 2023, and to provide a basis for related prevention and control work. Methods Viral hepatitis mortality data were obtained from the Pudong New Area mortality monitoring system. The crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), and standardized potential years of life lost (SPYLL) were calculated to analyze viral hepatitis deaths. The average annual change (AAPC) and annual percentage change (APC) of the mortality rate were calculated by Joinpoint regression analysis to analyze the trend of mortality. Results The CMR and SMR of viral hepatitis among residents in Pudong New Area from 2003 to 2023 were 3.89/100000 and 1.98/100000, respectively. Both CMR and SMR of viral hepatitis showed a decreasing trend over time (CMR:APC=-5.476, t=-13.581, P<0.001; SMR:APC=- 7.624, t= -21.253, P<0.001). The CMR for males was 4.75/100000 and the SMR for males was 2.65/100000; the CMR for females was 3.04/100000 and the SMR for females was 1.32/100000, with a higher mortality rate for males than for females（Z_CME=12.094，P<0.001; Z_SMR=-14.718，P<0.001). Deaths were concentrated in the age groups of 45-64 years old and 65 years old and above, accounting for 91.62% of the total deaths. The PYLL of deaths due to viral hepatitis among residents in Pudong New Area from 2003 to 2023 was 26912 person-years, with a PYLLR of 0.45% and an AYLL of 8.88 years per person. Conclusion The mortality rate of viral hepatitis among the residents of Pudong New Area in 2003-2023 shows a decreasing trend over time. The mortality rate of males is higher than that of females, and the deaths of middle-aged and elderly people account for a large proportion of the total deaths. Chronic hepatitis B is the main cause of death.

Objective:To investigate the effects of pulsed electric field (PEF) combined with gemcitabine (GEM) on the viability and stemness of HCCC-9810 cholangiocarcinoma stem cells.Methods:HCCC-9810 cholangiocarcinoma stem cells were established in serum-free, cytokine-rich medium and divided into four groups: the control group, GEM group, PEF group, and the pulsed electric field combined with gemcitabine (PEF+ GEM) group. Cell proliferation was detected using the Cell Counting Kit-8 (CCK8) assay. Cell viability and apoptosis rate were measured by flow cytometry. Cell invasion ability was assessed using the Transwell assay. The expression of stemness marker proteins CD133 and Octamer-binding transcription factor 4 (OCT4), as well as the expression of β-catenin, was detected by Western blotting.Results:Regarding cell viability, the GEM, PEF, and PEF+ GEM groups showed significantly lower cell viability and higher apoptosis rate than the control group at 24 h, 48 h, and 72 h (all P<0.05). At 48 h and 72 h, the PEF+ GEM group showed significantly lower cell viability (7.2%±0.3% and 5.9%±0.8%, respectively) than the GEM group (50.7%±0.6% and 31.0%±1.2%, respectively) and the PEF group (12.2%±0.2% and 12.8%±0.2%, respectively) (all P<0.05). Regarding stemness inhibition, the PEF+ GEM groups showed significantly lower expression levels of CD133 and OCT4 at 24 h, 48 h, and 72 h compared with the control group (all P<0.05). Notably, at 48 h, the PEF+ GEM group showed a significantly lower expression level of the OCT4 (0.61±0.02) than the GEM group (0.87±0.08) and the PEF group (1.00±0.10) ( P<0.01). Furthermore, at 24 h and 48 h, the GEM, PEF, and PEF+ GEM groups showed significantly lower expression levels of β-catenin compared with the control group (all P<0.05). Conclusion:Pulsed electric field combined with gemcitabine therapy demonstrated more effective anti-proliferation and cancer stemness inhibition effects on HCCC-9810 cholangiocarcinoma stem cells compared with either monotherapy.

[Purpose]To analyze the trends in pancreatic cancer mortality and disease burden among residents in Shanghai Pudong New Area from 2002 to 2022,and to investigate the effects of age,period,and birth cohort on mortality risk.[Methods]Data on pancreatic cancer deaths among residents of Pudong New Area from 2002 to 2022 were collected through the Shanghai Population Cause of Death Registration System.The crude mortality rate,age-standardized mortality rate by Chinese standard population(ASMRC),potential years of life lost(PYLL),potential years of life lost rate(PYLLR),and average years of life lost(AYLL)were calculated.Joinpoint regression was applied to calculate the average annual percentage change(AAPC)for analyzing the changing trend of the mortality rate of pancreatic cancer.The age-period-cohort model was applied with R 4.4.1 to analyze the age,period,and cohort effects on the mortality risk of pancreatic cancer.[Results]The crude mortality rate of pancreatic cancer among residents in Pudong New Area increased from 10.42/105 in 2002 to 18.73/105 in 2022,showing a significant upward trend(AAPC=2.90％,P＜0.001);the ASMRC was generally stable(AAPC=-0.05％,P=0.775).The crude mortality rate of males(17.09/105)was higher than that of females(13.75/105),and both showed an upward trend(AAPC=3.05％and 2.75％respectively,both P＜0.001).After the age of 40,the mortality rate of pancreatic cancer increased significantly with the growth of age in both sexes.The PYLL was 31 347 person-years,showing an upward trend(AAPC=1.83％,P＜0.001),and the AYLL was 3.59 years,showing a downward trend(AAPC=-2.45％,P＜0.001).The age effect showed that the mortality risk of pan-creatic cancer was increased with age;the period effect showed that the mortality risk decreased from 2002 to 2016 and then increased;the cohort effect showed that the mortality risk increased with the advancement of the birth cohort.[Conclusion]From 2002 to 2022,the crude mortality rate of pancreatic cancer in Pudong New Area showed an upward trend,and the mortality rate of males was higher than that of females.The mortality risk of pancreatic cancer increases with age,and the later the birth year of the residents,the higher the mortality risk.Early screening should be strengthened for men and the elderly,environmental and lifestyle risk factors should be paid attention to in combination with the characteristics of cohort effect,and the prevention and control strategy for the whole population should be optimized.

Objective:To summarize the clinical, pathological, and molecular genetic features of dermatofibrosarcoma protuberans (DFSP) in children.Methods:A retrospective analysis was conducted on clinical data from 8 children with DFSP in the Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2024. General information, clinical manifestations, pathological examinations, molecular genetic examinations, and treatments were analyzed, and clinical features and prognosis were summarized.Results:All the 8 cases were females, with ages at onset ( M[ Q1, Q3]) of 1.3 (0.3, 2.6) years, including 2 congenital cases; their ages at diagnosis were 5.1 (3.7, 7.4) years. Skin lesions manifested as solitary dark red patches, plaques, or nodules, and were located on the trunk in 5 cases (3 on the back, 1 on the abdomen, and 1 on the chest) and on the lower limbs in 3 cases. Histopathological examinations of all the 8 cases showed tumor cells diffusely infiltrating the dermis and subcutaneous tissue without epidermal involvement. Immunohistochemical staining showed that all the cases were strongly positive for CD34 and negative for soluble 100 protein; the Ki-67 labeling index ( M[ Q1, Q3]) was 9.0% (8.0%, 17.5%). Fluorescence in situ hybridization revealed the COL1A1-PDGFB fusion gene or PDGFB gene rearrangement in all 8 cases. All the patients underwent surgical excision of the primary skin lesions, including 3 treated with wide local excision, 2 with traditional Mohs surgery, and 3 with modified slow Mohs surgery, and all achieved negative margins. During the follow up of 6 months to 7 years, no tumor recurrence was observed. Conclusions:DFSP often occurred at a relatively young age in children, and mostly presented as atrophic patches or plaques. PDGFB gene alterations were commonly observed, and prognosis after surgical treatment was generally favorable.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective:To prepare novel dental composite resins using zinc(Zn)-and nitrogen(N)-modified titanium dioxide(TiO?)nanoparticles(NPs)and mesoporous alumina(Al?O?,r type,20 mm)NPs as reinforcing fillers,systematically evaluating their antibacterial activity,mechanical strength,basic performance,and biosafety to obtain the dental composite resins with excellent antibacterial activity and mechanical strength.Methods:Zn-N-TiO? NPs and mesoporous Al?O? NPs were added into a resin matrix at varying mass ratios to prepare five composite resins:control group(no filler),group 0(Zn-N-TiO?∶Al?O?=1∶0),group 1(Zn-N-TiO?∶Al?O?=1∶1),group 2(Zn-N-TiO?∶Al?O?=1∶2),and group 3(Zn-N-TiO?∶Al?O?=1∶3).Plate colony counting method was used to detect the number of adhered bacteria on composite resin surfaces in various groups and calculate the antibacterial rate;scanning electron microscope(SEM)was used to observe the morphology of adhered bacteria in various groups;universal testing machine was used to measure flexural strength(FS)and elastic modulus(EM)of composite resins in various groups;SEM was used to observe fracture surface morphology of composite resins in various groups;microhardness tester was used to determine Vickers microhardness of the composite resins in various groups;Fourier transform infrared spectroscope was used to detect double bond conversion rate(DC)after 20 s photocuring and calculate curing depth;water contact angle meter was used to measure water contact angle(WCA),water sorption property(WSP),and water solubility level(WSL)of composite resins in various groups;cell counting kit-8(CCK-8)method was used to evaluate relative growth rate(RGR)of the mouse fibroblast L-929 cells cultured in composite resin extracts on days 1,3,and 5 and determine in vitro cytotoxicity grade.Results:The plate colony counting results showed that compared with control group,the colony counts on agar plates in the other groups were significantly reduced,with group 1 showing the lowest count.The SEM images results showed densely distributed and morphologically intact Streptococcus mutans in control group;small clusters of bacteria with depressed cell membranes in group 0 and group 3;sparsely distributed bacteria with obvious membrane shrinkage and cytoplasmic leakage in group 1 and group 2.No statistically significant difference in colony counts was found between group 1 and group 2(P>0.05),but both were lower than the other groups(P<0.05).All the composite resins in experimental groups exhibited>85%antibacterial rates,with group 1 and group 2 exceeding 99%.The composite resins in group 0 showed the lowest FS.With addition of mesoporous Al?O?,the FS of the composite resin in group 1 and group 2 were significantly increased,with the composite resin in group 2 showing the highest FS among all groups.Although the FS of the composite resin in group 3 was lower than that in group 2,but it remained higher than other groups(P<0.05).The SEM images results showed that in control group,the smooth-surfaced sillicon dioxide(SiO?)particles exhibited clear fracture interfaces with resin matrix,with>50%particle exposure;the composite resin in group 0 showed similar morphology and large Zn-N-TiO? agglomerates with tight filler-matrix bonding;the composite resin in group 1,2,and 3 showed resin adhesion to SiO? surfaces(<50%particle exposure)and uneven fracture surfaces.Fractured SiO? spheres were observed in group 2.Filler distribution was uniform in group 1 and group 2,while the minor NP agglomeration occurred in group 3.The composite resin in control group showed the lowest EM.The EM was significantly improved in experimental groups,with group 3 having the highest value.Group 0 exhibited the lowest Vickers microhardness,showing statistically significant differences among other groups(P<0.05).The Vickers microhardness of the composite resion was gradually increased with the rising of Al?O? content.The resins in group 2 and group 3 achieved>45 HV hardness,representing increases of 29.73%and 33.82%compared with control group,and 51.34%and 56.28%compared with group 0.No significant differences in DC of the composite resin were found among groups(P>0.05).The depth of cure for all composite resin groups exceeded 4 mm,with no significance differences observed between various groups(P>0.05).The composite resin in group 0 showed the smallest WCA.The hydrophobicity of the composite resion was increased with the rising of Al?O? content,but all the WCA values remained<80°.The composite resin in group 3 had the largest WCA without statistical significance compared with group 2(P>0.05).Filler incorporation reduced the water sorption/solubility.The composite resin in the CCK-8 assay results showed the composite resins in all groups had RGR>75%,meeting in vitro safety standards.Conclusion:Reinforcing fillers impart superior antibacterial activity and mechanical properties to composite resins.Under experimental conditions,group 2 composite resin achieves optimal comprehensive performance in antibacterial efficacy and mechanical strength,demonstrating promising clinical application potential.

Objective:To investigate the influence of inner cell mass and trophectoderm cytoplasmic strings during blastocyst expan-sion on embryonic development and pregnancy outcome.Methods:A retrospective cohort analysis was performed for the clinical data of patients who received pre-implantation genetic testing for aneuploidy(PGT-A)and underwent single blastocyst transplantation in our hospital from June 2019 to December 2021.A total of 530 patients were enrolled,and genetic testing was performed for 2132 blasto-cysts.According to the presence or absence of cytoplasmic strings during blastocyst expansion,the blastocysts were divided into cyto-plasmic strings(+)group with 534 blastocysts and cytoplasmic strings(-)group with 1598 blastocysts,and quality and PGT-A results were compared between the two groups.After the transfer of euploid blastocysts,pregnancy outcome was compared between the 115 blastocysts with cytoplasmic strings and the 415 blastocysts without cytoplasmic strings.Results:The rates of cytoplasmic strings(+)in the high-,average-,and low-quality blastocyst groups were 30.19%,24.62%,and 12.63%,respectively.The correlation analysis showed a correlation coefficient of-0.115(P<0.001)between embryo quality and the rate of cytoplasmic strings(+).There was no sig-nificant difference in euploidy rate between the two groups(45.3%vs.44.6%).There were no significant differences between the euploid blastocysts with cytoplasmic strings and those without cytoplasmic strings in implantation rate(72.17%vs.66.02%,P=0.213),miscarriage rate(14.46%vs.12.77%,P=0.691),and live birth rate(61.74%vs.57.59%,P=0.424).Conclusion:The presence of cyto-plasmic strings is associated with the morphological quality of blas-tocysts,while it has no impact on embryo ploidy or clinical outcome after euploid embryo transfer.Further research is needed to confirm the impact of cytoplasmic strings on embryonic development.

Objective To establish a stable in vitro model of CD8+T cell exhaustion.Methods CD8+T cells were isolated and purified from the spleens of ovalbumin-specific CD8+T cell receptor(OT-I)transgenic mice and subjected to chronic antigen stimulation to induce exhaustion in vitro.Flow cytometry was employed to evaluate the expressions of exhaustion markers,secretion of effector cytokines,and transcription factor profiles in CD8+T cells.Exhausted and effector(non-exhausted)CD8+T cells were co-cultured with tumor cells before tumor cell viability was measured to assess the cytotoxic potential of CD8+T cells.Additionally,N-acetyl-L-cysteine(N-AC)was used as a positive control during exhaustion induction to validate the model.Results Chronic stimulation resulted in a significant upregulation of inhibitory receptors,including programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifdomain(TIGIT),and lymphocyte activation gene 3(LAG-3).Concurrently,the secretion of key effector cytokines such as tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)was markedly reduced.Exhausted CD8+T cells exhibited diminished cytotoxicity against tumor cells compared to effector CD8+T cells.Notably,treatment with N-AC effectively restored the function of exhausted CD8+T cells and enhanced their anti-tumor activity.Conclusion This study has established an effective in vitro model for CD8+T cell exhaustion.The use of N-AC demonstrates its potential to restore functionality in exhausted CD8+T cells,underscoring the reliability and utility of this model for investigating the anti-tumor potential of exhausted T cells.

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.