OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

To investigate the impact and underlying mechanism of NOP2/Sun RNA methyltransferase 2 (NSUN2) on gastric cancer progression, TCGA database was used and revealed a significant upregulation of NSUN2 expression in gastric cancer tissues. Western blot analysis revealed that NSUN2 was upregulated in gastric cancer cells compared with gastric mucosal epithelial cells. Colony formation assays demonstrated an enhanced colony-forming capacity in NSUN2-overexpressing cells. Furthermore, Transwell assays showed a marked increase in cell migration and invasion upon high NSUN2 expression. Moreover, TCGA database analysis suggested ARMC9 as a potential downstream target of NSUN2. Subsequently, MeRIP-qPCR analysis revealed that NSUN2 overexpression could increase m5C modification of ARMC9 mRNA, and reduce its degradation rate, thus enhancing protein expression. Additionally, ARMC9 overexpression augmented cellular colony formation and migratory and invasive capabilities. These findings indicate that NSUN2 promotes gastric cancer progression by elevating m5C modification of ARMC9 mRNA, increasing its stability and enhancing its expression, therefore, NSUN2 and ARMC9 may serve as potential therapeutic targets for gastric cancer.

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

The National Institute for Health and Care Excellence(NICE)first updated its 2013 Health Technology Evaluations Guidelines in 2022,followed by further minor adjustments in 2023.This round of updates primarily focuses on five key areas:mea-suring the value of health technologies,understanding and improving the evidence base,structured decision-making,addressing challenging diseases and technologies,and ensuring consistency in methods across evaluation and review projects.It outlines the up-date process and major changes,providing an analysis of these key points with the aim of offering valuable insights and methodologi-cal references for health technology assessment in China.

Objective:To understand the current status of health management cognition and healthcare behaviors of community residents in Shanghai, and to analyze their related influencing factors, in order to promote the optimization of proactive health-oriented health management strategies.Methods:This study was a cross-sectional survey. From February to May 2023, 1-4 community health service centers were randomly selected from each administrative district in Shanghai by stratified random sampling using the random number table method. Ultimately, 28 community health service centers were selected as research sites. The research team then used convenience sampling method to select at least 50 patients as research subjects from those visiting each selected center. A total of 1 436 community residents were included in this study in the form of on-site completion of questionnaire stars, and the study covered the residents′ level of health management cognition, chronic disease management, intention to seek medical care, physical examination behavior, and handling of abnormal values. Multiple regression analysis was used to assess the correlation between health management cognition and medical consultation behavior and their influencing factors.Results:The results of the health management awareness survey showed that 827 residents (57.6%) had a relatively high level of awareness. Among the 755 residents (52.6%) with chronic diseases, the proportion of self-assessed stable control was significantly higher in the high-cognition group (318 (76.0%)) than that in the low-cognition group (223 (66.2%)), and the difference was statistically significant ( χ2=9.01, P=0.003). Multiple regression analysis showed that females ( OR=1.293, 95% CI: 1.028-1.627),≤44 years old and 45-59 years old ( OR=2.328, 95% CI: 1.648-2.328; OR=1.351, 95% CI: 1.035-1.763), bachelor′s degree or above ( OR=1.784, 95% CI: 1.256-2.534), living in suburban area ( OR=1.577, 95% CI: 1.235-2.014), use of employee health insurance and resident health insurance ( OR=2.294, 95% CI: 1.629-3.232; OR=1.628, 95% CI: 1.149-2.306), suffering from a chronic disease ( OR=3.110, 95% CI: 1.918-5.042), and having a contracted family doctor ( OR=1.870, 95% CI: 1.431-2.442) were all positive correlation with health management perception(all P<0.05). In terms of health care behavior, 908 (63.2%) residents showed a high active intention to seek medical care, and 906 (63.1%) and 796 (55.4%) residents showed active participation in medical check-ups and timely handling of medical check-up abnormal values, respectively. Residents in the high awareness group were significantly better than those in the low awareness group in terms of intention to seek medical care ( χ2=33.26), mode of medical checkups ( χ2=110.71), frequency of medical checkups ( χ2=45.37), and the way of dealing with abnormal values after medical checkups ( χ2=93.14), with the difference being statistically significant(all P<0.05). The results of linear regression analysis of the factors influencing the medical behavior of community residents showed that age≤44 and 45-59 ( B=0.479, 0.167), high school and specialist versus bachelor′s degree and above ( B=0.465, 0.739), use of employee medical insurance and residents′ health insurance ( B=0.604, 0.420), the number of current chronic diseases 1 ( B=0.919) and contracted family doctor ( B=0.134) of community residents′ health care behaviors are better (all P<0.05). Conclusions:The level of community residents′ health management cognition needs to be improved, and high health management cognition can significantly promote proactive healthcare-seeking behavior. However, residents′ medical behavior is still influenced by multidimensional factors. Signing a contract with a family doctor is significantly associated with high cognition and quality healthcare behaviors.

Environmental damage affects many aspects of healthcare, from extreme weather events to evolving population disease. Singapore's healthcare sector has the world's second highest healthcare emissions per capita, hampering the nation's pledge to reduce emissions by 2030 and achieve net zero emissions by 2050. In this review, we provide an overview of the impact environmental damage has on healthcare, including facilities, supply chain and human health, and examine measures to address healthcare's impact on the environment. Utilising the 'R's of sustainability - rethinking, reducing/refusing, reusing/repurposing/reprocessing, repairing, recycling and research - we have summarised the opportunities and challenges across medical disciplines. Awareness and advocacy to adopt strategies at institutional and individual levels is needed to revolutionise our environmental footprint and improve healthcare sustainability. By leveraging evidence from ongoing trials and integrating sustainable practices, our healthcare system can remain resilient against environment-driven challenges and evolving healthcare demands while minimising further impacts of environmental destruction.
Humans ; Climate Change ; Delivery of Health Care ; Singapore ; Conservation of Natural Resources ; Sustainable Development ; Environment

Objective:To understand the current status of health management cognition and healthcare behaviors of community residents in Shanghai, and to analyze their related influencing factors, in order to promote the optimization of proactive health-oriented health management strategies.Methods:This study was a cross-sectional survey. From February to May 2023, 1-4 community health service centers were randomly selected from each administrative district in Shanghai by stratified random sampling using the random number table method. Ultimately, 28 community health service centers were selected as research sites. The research team then used convenience sampling method to select at least 50 patients as research subjects from those visiting each selected center. A total of 1 436 community residents were included in this study in the form of on-site completion of questionnaire stars, and the study covered the residents′ level of health management cognition, chronic disease management, intention to seek medical care, physical examination behavior, and handling of abnormal values. Multiple regression analysis was used to assess the correlation between health management cognition and medical consultation behavior and their influencing factors.Results:The results of the health management awareness survey showed that 827 residents (57.6%) had a relatively high level of awareness. Among the 755 residents (52.6%) with chronic diseases, the proportion of self-assessed stable control was significantly higher in the high-cognition group (318 (76.0%)) than that in the low-cognition group (223 (66.2%)), and the difference was statistically significant ( χ2=9.01, P=0.003). Multiple regression analysis showed that females ( OR=1.293, 95% CI: 1.028-1.627),≤44 years old and 45-59 years old ( OR=2.328, 95% CI: 1.648-2.328; OR=1.351, 95% CI: 1.035-1.763), bachelor′s degree or above ( OR=1.784, 95% CI: 1.256-2.534), living in suburban area ( OR=1.577, 95% CI: 1.235-2.014), use of employee health insurance and resident health insurance ( OR=2.294, 95% CI: 1.629-3.232; OR=1.628, 95% CI: 1.149-2.306), suffering from a chronic disease ( OR=3.110, 95% CI: 1.918-5.042), and having a contracted family doctor ( OR=1.870, 95% CI: 1.431-2.442) were all positive correlation with health management perception(all P<0.05). In terms of health care behavior, 908 (63.2%) residents showed a high active intention to seek medical care, and 906 (63.1%) and 796 (55.4%) residents showed active participation in medical check-ups and timely handling of medical check-up abnormal values, respectively. Residents in the high awareness group were significantly better than those in the low awareness group in terms of intention to seek medical care ( χ2=33.26), mode of medical checkups ( χ2=110.71), frequency of medical checkups ( χ2=45.37), and the way of dealing with abnormal values after medical checkups ( χ2=93.14), with the difference being statistically significant(all P<0.05). The results of linear regression analysis of the factors influencing the medical behavior of community residents showed that age≤44 and 45-59 ( B=0.479, 0.167), high school and specialist versus bachelor′s degree and above ( B=0.465, 0.739), use of employee medical insurance and residents′ health insurance ( B=0.604, 0.420), the number of current chronic diseases 1 ( B=0.919) and contracted family doctor ( B=0.134) of community residents′ health care behaviors are better (all P<0.05). Conclusions:The level of community residents′ health management cognition needs to be improved, and high health management cognition can significantly promote proactive healthcare-seeking behavior. However, residents′ medical behavior is still influenced by multidimensional factors. Signing a contract with a family doctor is significantly associated with high cognition and quality healthcare behaviors.

The National Institute for Health and Care Excellence(NICE)first updated its 2013 Health Technology Evaluations Guidelines in 2022,followed by further minor adjustments in 2023.This round of updates primarily focuses on five key areas:mea-suring the value of health technologies,understanding and improving the evidence base,structured decision-making,addressing challenging diseases and technologies,and ensuring consistency in methods across evaluation and review projects.It outlines the up-date process and major changes,providing an analysis of these key points with the aim of offering valuable insights and methodologi-cal references for health technology assessment in China.

OBJECTIVE:To review the development trend,target population,setting and construction process of osteoporosis-specific quality of life measures both domestically and internationally.METHODS:All of the currently available publicly available osteoporosis-specific quality-of-life scales were found by searching the PubMed,Embase,CNKI,and WanFang Data.The search period included the time from database construction to August 2024.The basic information,development trend,target population,and the setting of the scale's dimensions,entries,and levels were taken from the original research and development literature that included the scale.The content of the dimensions and the scale's construction process were then compiled and examined.RESULTS:A total of 20 osteoporosis-specific quality of life scales were included in the study,and the literature on the development of 34 scales was traced.The number of dimensions of the included scales ranged from 2-7 dimensions,all of which included physiological dimensions;the number of entries of the scales ranged from 10-84 entries,while the number of levels set under the entries was mostly focused on four or five levels.There are three main ways of constructing the scales,of which the construction of a pool of entries and the screening of the entries according to classical measurement theory and item response theory is an approach that has emerged in recent years.CONCLUSION:According to the specific target population and diversified measurement objectives,the content of osteoporosis-specific quality of life scales has become increasingly streamlined,with fewer dimensions and entries overall;and its building procedure is gradually becoming more standardized.