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 mine and analyze adverse event signals associated with inebilizumab， and to provide reference for safe and rational clinical use. METHODS Reports of adverse event related to inebilizumab were collected from the FDA adverse event reporting system （FAERS） database， from Q2 2020 to Q4 2024. Adverse events were standardized and categorized according to the preferred term （PT） and system organ class （SOC） of the Medical Dictionary for Regulatory Activities （MedDRA） version 26.0. Signals were mined using the reporting odds ratio （ROR） method and the Bayesian confidence propagation neural network （BCPNN） method. RESULTS A total of 783 adverse event reports with inebilizumab as the primary suspected drug were identified， involving 297 patients. Most reports originated from the United States and Japan， with physicians being the primary reporters. Female patients outnumbered males， and the most common age group was 45-64 years. Using the ROR method and BCPNN method， a total of 29 valid adverse event signals were detected， involving 12 SOCs and comprising 225 adverse event reports. The five most frequently reported PTs were headache， nausea， fatigue， infectious pneumonia and arthralgia. The five PTs with the strongest signal intensity were： B-cell recovery， decreased blood immunoglobulin G， spinal compression fracture， COVID-19 and acute respiratory distress syndrome. Among the 29 valid signals for adverse event， 19 were not documented in the drug package inserts， involving 10 SOCs and comprising 107 adverse event reports. These encompassed nervous system disorders， general disorders and administration site conditions， eye disorders， among others. CONCLUSIONS Inebilizumab treatment not only causes adverse events documented in the product information， such as infections， immunoglobulin reduction and infusion-related reactions but also leads to potential signals， including B-cell recovery， spinal compression fracture. When using this drug in clinical practice， the patient’s risk of infection and baseline immune status should be assessed， relevant indicators should be closely monitored， and targeted preventive measures should be considered when necessary.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

Objective: To investigate the association between uric acid level and elevated blood pressure among children and adolescents in Guangzhou, so as to provide a scientific basis for prevention and control of hypertension in the pediatric population. Methods: From March to December 2019, using stratified cluster random sampling, 3 626 children and adolescents aged 6-17 years without elevated blood pressure at baseline were recruited from 6 primary and secondary schools in Guangzhou. Serum uric acid levels were measured at baseline, and divided into four groups ( Q1-Q 4) based on age and sex specific quartiles for analyses. Two waves of follow up were carried out from October 2020 to May 2021 and from October 2021 to May 2022, respectively. Multilevel robust Poisson regression was used to evaluate the association between uric acid level and elevated blood pressure among children and adolescents. The additive interaction between high uric acid level and sugar sweetened beverage (SSB) intake on elevated blood pressure was assessed by stratification analysis and calculation of the relative excess risk due to interaction (RERI). Results: A total of 1 131 new cases of elevated blood pressure were identified during the two follow ups, with an incidence density of 130.5 cases 1 000 person years. Multilevel robust Poisson regression analysis showed that after adjusting for confounders such as gender, age and annual family income, compared with those in the uric acid Q 1 level, the risk of elevated blood pressure in individuals in the Q 4 level increased by 25% ( RR=1.25, 95%CI =1.08-1.44), and the risk of elevated systolic blood pressure increased by 20% ( RR=1.20, 95%CI =1.05-1.36) (both P <0.05); no statistical association was observed between uric acid and elevated diastolic blood pressure (all P >0.05). In the stratified analysis, the statistical associations of uric acid Q 4 level with elevated blood pressure ( RR=1.34, 95%CI =1.13-1.58) and elevated systolic blood pressure ( RR=1.33, 95%CI =1.14-1.55) were only observed in the group with SSB intake ≥ 250 mL/week (both P <0.05). The RERI values for the effect of uric acid Q 4 and Q 3 levels with SSB intake ≥ 250 mL/week on elevated systolic and diastolic blood pressure were 0.29 and 0.44 (both P <0.05). Conclusions High uric acid level is a risk factor for elevated blood pressure among children and adolescents, with a predominant effect on systolic blood pressure. High uric acid level and SSB intake synergistically promote the increase of blood pressure of children and adolescents.

Objective To investigated the effects of occupational exposure to N,N-dimethylformamide (DMF) on sterol regulatory element-binding protein (SREBP) and iron metabolism among workers. Methods A total of 20 workers occupationally exposed to DMF were selected as the exposure group, and 15 healthy workers without DMF exposure from the same factory were selected as the control group using the purposive sampling method. DMF exposure levels were assessed in individual samples of the workers. The urinary N-methylformamide (NMF) levels were measured by gas chromatography. The mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood was measured by real-time quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to detect serum transferrin, soluble transferrin receptor (sTfR), and ferritin levels. Results The DMF exposure levels among the workers in the control group were below the detection limit, and urinary NMF was undetectable. The median DMF exposure level was 13.30 mg/m³, and the mean urinary NMF level was (9.72±1.78) mg/g Cr among the workers in the exposure group. Compared with the control group, the relative mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood of workers in the exposure group increased (all P<0.05), while the levels of transferrin and sTfR decreased (both P<0.01). However, there was no statistically significant difference in serum ferritin levels between the two groups (P>0.05). In the exposure group, urinary NMF level of workers was negatively correlated with the relative mRNA expression level of SREBP-1c in blood [correlation coefficient (r)=-0.50, P=0.03], and positively correlated with the levels of serum transferrin, sTfR, and ferritin (r = 0.63, 0.58, and 0.52, respectively; all P<0.05). Conclusion Occupational exposure to DMF can upregulate the expression of the SREBP family and disrupt iron metabolism, with a potential association between these effects.

Background The crude mortality rate of sudden death has shown a steady upward trend. Pudong New Area, Shanghai, is a highly urbanized and densely populated district that is substantially affected by the urban heat island effect and has experienced frequent extreme temperature events in recent years. However, evidence on the association between ambient temperatures and sudden death among local residents remains limited. Objective To examine the association between daily mean temperature and sudden death in Pudong New Area, and to provide evidence for reducing temperature-related risks of sudden death. Methods Data on sudden death, meteorological factors (daily average temperature, daily average relative humidity, and daily average air pressure), and air pollutants [inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), and nitrogen dioxide (NO₂)] in Pudong New Area from 2016 to 2021 were collected. A distributed lag non-linear model was used to examine the associations of daily mean temperature with total sudden death and sudden death due to cardiovascular and cerebrovascular diseases, including lagged and cumulative effects (lag0, 0-3, 0-7, 0-14, and 0-21 d). Stratified analyses were performed by sex, age, and education level to identify vulnerable populations. The temperature attributable burden of sudden death was assessed by calculating attributable number (AN) and attribute fraction (AF). Results A total of 19458 sudden deaths were reported in Pudong New Area from 2016 to 2021, of which 11082 (56.95%) were due to cardiovascular and cerebrovascular diseases. Both low (P₅, 4.6 ℃) and high (P₉₅, 30.2 ℃) temperatures were associated with increased risks of sudden death. The cumulative risks associated with low temperature peaked at lag 0-21 d for both total sudden death and sudden death due to cardiovascular and cerebrovascular diseases. In contrast, the cumulative risks associated with high temperature peaked at lag 0-7 d for total sudden death and at lag 0-3 d for sudden death due to cardiovascular and cerebrovascular diseases. Stratified analyses showed that females, individuals aged ≥65 years, and those with primary school education or below were more sensitive to low temperature; whereas females, individuals aged <65 years, and those with secondary school education or above were more sensitive to high temperature. Using 21.5 ℃ as the minimum mortality temperature, the AN of total sudden deaths attributable to non-optimal temperature was 3791 (95%CI: 1853, 5587), with an AF of 20.41% (95%CI: 9.47%, 28.94%); the AN attributable to low temperature was 3358 (95%CI: 1087, 5062), with an AF of 17.26% (95%CI: 5.89%, 26.01%), whereas the AN attributable to high temperature was 225 (95%CI: −274, 655), with an AF of 2.03% (95%CI: −2.53%, 5.78%). For sudden deaths due to cardiovascular and cerebrovascular diseases, the AN attributable to non-optimal temperature was 2721 (95%CI: 1747, 5575), with an AF of 24.55% (95%CI: 9.59%, 28.65%); the AN attributable to low temperature was 2496 (95%CI: 988, 3562), with an AF of 22.53% (95%CI: 8.97%, 32.41%), whereas the AN attributable to high temperature was 614 (95%CI: −15, 1176), with an AF of 3.15% (95%CI: −0.08%, 6.02%). Conclusions Both low (P₅, 4.6 ℃) and high (P₉₅, 30.2 ℃) temperatures are associated with increased risks of sudden death in Pudong New Area, Shanghai. High temperature shows a relative short-term effect, whereas low temperature shows a stronger cumulative effect. Females, people ≥65 years, and individuals with primary school educational attainment or below are more vulnerable to low temperature, while females, people <65 years, and those with secondary school educational attainment or above are more vulnerable to high temperature. The attributable burden of low temperature is greater than that of high temperature. Targeted health protection measures should be strengthened for vulnerable populations during extreme temperature events.

ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT （DLCT） parameters in predicting lymph node metastasis （LNM） of non-functional pancreatic neuroendocrine neoplasms （NF-pNENs）. MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest （ROIs） were manually delineated on three representative slices of the solid component of the lesion， and the mean values were recorded. Conventional CT parameters， monochromatic energy images （40 keV， 70 keV， 100 keV）， iodine concentration maps， and effective atomic number （Z_eff） maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters， including clinical characteristics， imaging features， conventional CT and DLCT quantitative parameters， were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator （LASSO） regression. Receiver operating characteristic （ROC） curves were generated for each predictive model， and the area under the curve （AUC） was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled， including 37 males and 45 females， with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression， LASSO regression and multivariate stepwise logistic regression analyses， body mass index （BMI）， organ invasion， normalized CT value in the portal venous phase （nCTv） and normalized iodine concentration in the portal venous phase （nICv） were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model （BMI+organ invasion）， conventional CT model （nCTv）， DLCT model （nICv） and comprehensive model （organ invasion+nICv） were 0.815 （0.719， 0.910）， 0.750 （0.642， 0.858）， 0.829 （0.733， 0.925） and 0.865 （0.879， 0.953）， respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs， enabling non-invasive preoperative prediction and assisting clinical decision-making.

ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT （DLCT） parameters in predicting lymph node metastasis （LNM） of non-functional pancreatic neuroendocrine neoplasms （NF-pNENs）. MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest （ROIs） were manually delineated on three representative slices of the solid component of the lesion， and the mean values were recorded. Conventional CT parameters， monochromatic energy images （40 keV， 70 keV， 100 keV）， iodine concentration maps， and effective atomic number （Z_eff） maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters， including clinical characteristics， imaging features， conventional CT and DLCT quantitative parameters， were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator （LASSO） regression. Receiver operating characteristic （ROC） curves were generated for each predictive model， and the area under the curve （AUC） was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled， including 37 males and 45 females， with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression， LASSO regression and multivariate stepwise logistic regression analyses， body mass index （BMI）， organ invasion， normalized CT value in the portal venous phase （nCTv） and normalized iodine concentration in the portal venous phase （nICv） were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model （BMI+organ invasion）， conventional CT model （nCTv）， DLCT model （nICv） and comprehensive model （organ invasion+nICv） were 0.815 （0.719， 0.910）， 0.750 （0.642， 0.858）， 0.829 （0.733， 0.925） and 0.865 （0.879， 0.953）， respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs， enabling non-invasive preoperative prediction and assisting clinical decision-making.

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.