The impact of China's universal two-child policy on total, preterm, and multiple births: a nationwide interrupted time-series analysis.

BACKGROUND: Although years have passed since the implementation of China's universal two-child policy, the effectiveness of this policy remains unclear. To address this knowledge gap, we, here, assessed the impact of the two-child policy on total live births, preterm births, and multiple live births. METHODS: Data identifying pregnancies resulting in at least one live birth between April 1 2013 and December 31 2018 were collected from the Hospital Quality Monitoring System database. Using an interrupted time-series analysis, we estimated immediate level changes and long-term trends in total, preterm (birth before 37 weeks' gestation), and multiple live births that had occurred after July 2016, when the universal two-child policy had taken effect. RESULTS: A total of 8,273,622 live births were reported during the study time frame. The number of live births (p = 0.277), preterm births (p = 0.052), and multiple births (p = 0.856) per month slightly increased immediately after July 2016, but these increases did not meet statistical significance. Further, all three outcomes showed a significant downward trend that lasted until the end of 2018 (p < 0.0001 for all). Among all live births, the percentage of preterm births remained stable (p = 0.101), while the percentage of multiple live births that were preterm significantly increased (trend change = 0.21% per month, 95% CI 0.14 to 0.28, p < 0.0001). The percentage of live multiple births among all live births significantly decreased (p for trend = 0.0039). CONCLUSIONS: Overall, our data reveal a transient baby boom, as well as an increase in the proportion of live multiple births that were preterm, after China's two-child policy took effect. The latter should be noted by healthcare professionals due to the high risk of complications and special medical care required by preterm babies.

Exploring the therapeutic mechanisms of resveratrol for treating arecoline-induced malignant transformation in oral epithelial cells: insights into hub targets.

BACKGROUND: Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer. METHODS: Data mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments. RESULTS: Sixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis. CONCLUSION: Resveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry.

[Cardiovascular safety of sitagliptin added to metformin in real world patients with type 2 diabetes].

OBJECTIVE: To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM). METHODS: Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1, 2017 to December 31, 2022. According to drug prescription records, the patients were divided into metformin plus sitagliptin group (combination group) and metformin monotherapy group(monotherapy group). A series of retrospective cohorts were constructed according to the index date.Finally, full retrospective cohorts were constructed according to propensity score model, including baseline covariates that might be related to outcomes, to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics. The participants were followed up from the index date until the first occurrence of the following events: Diagnosis of outcomes, death, or the end of the study period (December 31, 2022). Cox proportional risk model was used to estimate the hazard ratio(HR)and 95% confidence interval (CI) of sitagliptin added to metformin on 3-point major adverse cardiovascular events (3P-MACE) combination outcome and secondary cardiovascular outcomes. RESULTS: Before propensity score matching, the proportion of the patients in combination group using insulin, α glucosidase inhibitors, sodium-glucose transporter 2 inhibitors (SGLT-2I) and glienides at baseline was higher than that in monotherapy group, and the baseline fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in combination group were higher than those in monotherapy group. After propensity score matching, 5 416 subjects were included in the combination group and the monotherapy group, and baseline characteristics were effectively balanced between the groups. The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years, respectively. Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy (HR=1.00, 95% CI: 0.91-1.10). In secondary outcomes analysis, the incidence of cardiovascular death was lower in the combination group than in the monotherapy group (HR=0.59, 95% CI: 0.41-0.85), and no association was found between sitagliptin and the risk of myocardial infarction and stroke (HR=1.12, 95% CI: 0.89-1.41; HR=0.99, 95% CI: 0.91-1.12). CONCLUSION: In T2DM patients in Yinzhou district of Ningbo, compared with metformin alone, sitagliptin added to metformin may reduce the risk of cardiovascular death, and do not increase the incidence of overall cardiovascular events. The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.

MYO1B as a prognostic biomarker and a therapeutic target in Arecoline-associated oral carcinoma.

BACKGROUND: Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline-induced oral cancer and further verify their expressions and roles. METHODS: This study included a data-mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels. RESULTS: MYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline-transformed oral cells and oral cancer cells. CONCLUSION: This study revealed MYO1B as a key gene in Arecoline-induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.

Association between Mobile Phone Use and Incidence of Dementia: A Prospective Cohort Study Using the UK Biobank.

INTRODUCTION: The rapid growth in mobile phone use has led to public concern about its potential effects on the risk of dementia. This study aimed to investigate the association between mobile phone use in daily life and the risk of dementia incidence in community-dwelling adults based on the data from the UK Biobank. METHODS: Participants in the UK Biobank aged 60 years or older with no diagnosis of dementia at the time of recruitment were included in this prospective cohort study. A Cox regression model adjusted for sociodemographic characteristics, general health factors, mental health, lifestyle factors, comorbidities, and medication use was used to estimate the hazard ratio (HR) and confidence interval (CI) of the association between mobile phone use and dementia risk. RESULTS: The final analyses included 213,181 participants. During a median follow-up period of 12.4 years, 6,344 cases of incident dementia occurred. Mobile phone use displayed a modest association with lower risk of dementia incidence, with HRs of 0.85 (95% CI: 0.79-0.91), 0.85 (95% CI: 0.80-0.91), 0.78 (95% CI: 0.71-0.86), 0.86 (95% CI: 0.77-0.96), and 0.83 (95% CI: 0.70-0.98) for participants who reported phone call usage of fewer than 5 min, 5-29 min, 30-59 min, 1-3 h, and more than 3 h per week, respectively, compared with nonusers. In addition, the proportions of the association medicated by family/friend visits and other leisure/social activities were 2.62% (95% CI: -0.64-6.51) and 2.22% (95% CI: 1.12-4.12), respectively. CONCLUSIONS: Daily mobile phone use is significantly associated with a reduced risk of incident dementia in community-dwelling adults in the UK Biobank population. This association seems to be mediated by improved social and mental activities.

Global burden of influenza lower respiratory tract infections in older people from 1990 to 2019.

BACKGROUND: Infections with influenza viruses cause severe illness, substantial number of hospitalization and death, especially in older adults. However, few studies have focused on the burden of influenza lower respiratory tract infections (LRTIs) solely in older adults, particularly in low-resource settings. AIMS: We aimed to estimate the mortality and DALYs of influenza LRTIs for people aged 55 years and older in 204 countries and territories from 1990 to 2019. METHODS: The Global Burden of Disease (GBD) 2019 study was used to obtain data on mortality and DALYs of influenza LRTIs at the global, regional, and country levels. RESULTS: In 2019, the global rates for mortality and DALYs of influenza LRTIs were 6.46 per 100,000 [95% uncertainty interval (UI): 2.37-12.62] and 97.39 per 100,000 (95% UI: 34.70-187.03). Although the rates for mortality and DALYs in people aged 55 years and older decreased from 1990 to 2019, the absolute numbers for both increased by 85.84% and 66.56%, respectively. Both the absolute numbers and rates of deaths and DALYs of influenza LRTIs were higher in male than in female in all age groups. Although low-socio-demographic index (SDI) regions experienced the largest declines for the rates of mortality and DALYs of influenza LRTIs over the past three decades, they still had the highest rates for mortality and DALYs in all age groups. Moreover, the absolute numbers and rates of deaths and DALYs of influenza LRTIs showed an increasing trend with age, reaching the peak in the people over 85 years old. DISCUSSION: Burden of influenza LRTIs in older adults is still high and could continue to grow along with global aging. CONCLUSION: Efforts to improve vaccination for influenza are needed for preparedness of another influenza pandemic, especially in low-SDI regions.

Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL-17 pathway.

Cisplatin (DDP) resistance is a bottleneck in the treatment of head and neck cancer (HNC), leading to poor prognosis. Fisetin, a dietary flavonoid, has low toxicity and high antitumor activity with unclear mechanisms. We intended to predict the targets of fisetin for reversing DDP-resistance and further verify their expressions and roles. A network pharmacology approach was applied to explore the target genes. The hub genes were screened out and subjected to molecular docking and experimental verification (in vivo and in vitro). Thirty-two genes common to fisetin and DDP-resistance were screened, including three hub genes, namely HSP90AA1, PPIA, and PTPRS. Molecular docking suggested that fisetin and the candidate proteins could bind tightly. HSP90AA1 was identified as the key gene. Administration of fisetin increased the sensitivity of chemoresistant cells (Cal27/DDP and FaDu/DDP) to DDP, accompanied by the downregulation of HSP90AA1 and IL-17. HSP90AA1 silencing increases the sensitivity of DDP-resistant cells to DDP, which was mediated by IL-17. In summary, fisetin might inhibit the chemoresistance of HNC cells to DDP by targeting the HSP90AA1/IL-17 pathway. Several hub genes might be the targets of fisetin for reversing DDP-resistance in HNC cells and might also serve as prognostic factors and therapeutic targets for HNC.

Overexpression of KITLG predicts unfavorable clinical outcomes and promotes lymph node metastasis via the JAK/STAT pathway in nasopharyngeal carcinoma.

Lymph node metastasis (LNM) is an early clinical sign and a contributor to the treatment failure in patients with nasopharyngeal carcinoma (NPC). The molecular mechanisms of LNM in NPC remain unclear. We aimed to identify and validate the possible key genes that play a crucial role in the LNM of NPC. The study included a discovery and validation phase. In the discovery phase, the key gene was identified by bioinformatics analysis. In the validation phase, the mRNA and protein expression of the key gene was detected by RT-PCR in NPC cells and by immunohistochemistry in a tissue microarray. Then, the effect of the key gene expression on cell invasion and migration was explored in vitro and in vivo. As a result, KITLG was identified as the key gene. The overexpression of KITLG was detected in NPC cells, which was correlated with neck lymph node metastasis and poor prognosis in patients with NPC. The suppression of KITLG inhibited the proliferation, invasion, and metastasis of NPC cells in vitro and in vivo. JAK/STAT signaling pathway might mediate the enhancement of cell invasion and metastasis caused by KITLG. In summary, the overexpression of KITLG in NPC cells might play a crucial role in the LNM of NPC, raising the possibility of KITLG as a prognostic factor and a potential target for NPC treatment.

SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is an important cause leading to recurrence and development of head and neck carcinoma (HNC), with the precise mechanisms unclear. Thus, we aimed to identify the key genes involved in LNM and further evaluate their expressions and roles. METHODS: A cohort of HNC in the TCGA was analyzed. The study involved three phases (one screening and two validation phases). First, the differentially expressed genes regarding LNM were screened, from which a key gene was identified by a series of data mining approaches. Then, the expressions and roles of the key gene were validated in HNC through bioinformatics. Afterward, the expression of the key gene was detected by qPCR, western blot, and Immunohistochemistry based on a cell model and a tissue microarray. Further, colony formation and transwell migration and invasion assays were used to evaluate the roles of the key gene. RESULTS: SPP1 was overexpressed in HNC tissues and was identified as the key gene. Overexpression of SPP1 in HNC was correlated with advanced pathological stages and T-stage, as well as the presence of LNM, which predicted poor prognosis. The expression of SPP1 was closely associated with the infiltration of immune cells in HNC, especially M2 macrophages. Lab experiments confirmed that SPP1 silence in HNC cells resulted in weakened invasive and metastatic abilities. CONCLUSION: This study reveals that SPP1 may be a key gene associated with LNM in HNC, raising the possibility of SPP1 as a target for HNC prevention and treatment.

The expression and clinical significance of an Epithelial-Mesenchymal Transition inducer, SNAI1, in head and neck carcinoma.

BACKGROUND: SNAI1 is an epithelial-mesenchymal transition (EMT) inducer, which has been indicated to play a role in the progression of cancers. We aimed to evaluate the expression and prognostic roles of SNAI1 in head and neck carcinoma (HNC). METHODS: The study involved two major phases. In the in silico phase, the SNAI1 expression and its association with clinical features as well as its prognostic values were assessed; then, the target genes of SNAI1 were predicted and the relationship between SNAI1 expression and immune cell infiltration was evaluated. In the validation phase, a cohort of a tissue microarray (47 cases) and a cohort of HNC patients (68 cases) were enrolled. SNAI1 was detected by using an immunochemistry assay. RESULTS: The in silico analysis showed that overexpression of SNAI1 in HNC tissues may be correlated with metastatic lymph node numbers and may predict poor outcomes. Six genes, including CREB3L1, MITF, KLF9, RARA, KLF7, and ETV1, were predicted to be the target genes of SNAI1. The expression of SNAI1 was negatively correlated with tumor purity of HNC, while it was positively correlated with the infiltration of diverse immune cells, such as B cells and macrophages. In the validation phase, the relationships of SNAI1 expression with lymph node metastasis and poor prognosis were verified. CONCLUSION: Overexpression of SNAI1 might promote lymph node metastasis through complex molecular mechanisms and act as a prognostic indicator in HNC. SNAI1 expression may have a correlation with immune cell infiltrates. Future studies are needed to address these points.

TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis.

BACKGROUND: Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches. METHODS: High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool. RESULTS: The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells. CONCLUSION: The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.

Advances in methodologies of negative controls: a scoping review.

OBJECTIVES: Negative controls are considered an important tool to mitigate biases in observational studies. The aim of this scoping review was to summarize current methodologies of negative controls (both negative control exposure [NCE] and negative control outcome [NCO]). STUDY DESIGN AND SETTING: We searched PubMed, Web of Science, Embase, and Cochrane Library (up to March 9, 2023) for articles on methodologies of negative controls. Two reviewers selected eligible studies and collected relevant data independently and in duplicate. We reported total numbers and percentages, and summarized methodologies narratively. RESULTS: A total of 37 relevant methodological articles were included in our review. These publications covered NCE (n = 11, 29.8%), NCO (n = 13, 35.1%), or both (n = 13, 35.1%), with most focused on bias detection (n = 14, 37.8%), bias correction (n = 16, 43.3%), and P value or confidence interval (CI) calibration (n = 5, 13.5%). For the two remaining articles (5.4%), one discussed bias detection and P value or CI calibration and the other covered all the three functions. For bias detection, the existence of an association between the NCE (NCO) and outcome (exposure) variables of interest simply indicates that results may suffer from confounding bias, selection bias and/or information bias. For bias correction, however, the algorithms of negative control methods need more stringent assumptions such as rank preservation, monotonicity, and linearity. CONCLUSION: Negative controls can be leveraged for bias detection, P value or CI calibration, and bias correction, among which bias correction has been the most studied methodologically. The current available methods need some stringent assumptions to detect or remove bias. More methodological research is needed to optimize the use of negative controls.

Immunohistochemical Expression and Clinical Significance of WWP1 Protein in Nasopharyngeal Cancer.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Its pathogenesis is complicated and needs further investigation. The aim of this study was to investigate the expression and clinical significance of WWP1 in NPC. Bioinformatics approaches were used to evaluate the expression and functions of WWP1 in NPC. WWP1 protein expression was then detected by immunohistochemistry on a tissue microarray in an NPC cohort and its association with clinical features and prognosis was determined. In addition, WWP1 expression was knocked down in NPC cells using RNA interference, and their colony formation and invasion abilities were assessed. A total of 25 genes closely related to WWP1, which may be enriched in different pathways, were filtered out. WWP1 expression was significantly higher in NPC cells than in normal controls. High WWP1 expression was correlated with lymph node metastasis, tumor recurrence, clinical stage and poor prognosis. Knockdown of WWP1 resulted in attenuated proliferation and invasion of NPC cells. The results suggest that WWP1 may serve as a novel biomarker and prognostic factor for NPC and a potential therapeutic target worthy of further investigation.

Association of outpatient fluoroquinolone prescribing with the National Medical Products Administration announcements of label changes in China.

BACKGROUND: In 2017 and 2021, the National Medical Products Administration (NMPA) announced to revise the drug label of fluoroquinolones. We aimed to evaluate the association of fluoroquinolone prescribing with the NMPA announcements of label changes. RESEARCH DESIGN AND METHODS: Monthly prevalence of fluoroquinolone prescriptions for uncomplicated urinary tract infections (uUTI), acute exacerbation of chronic bronchitis (AECB), and acute sinusitis (AS) between 2016 and 2022 was calculated, and interrupted time series analysis was applied to assess the impacts of NMPA label changes on fluoroquinolone use. RESULTS: Prevalence of fluoroquinolone prescriptions decreased by 2.39% (95% CI, -4.72% to -0.07%) for uUTI but increased by 3.02% (95% CI, 1.71% to 4.34%) for AS immediately after the 2017 label change. Moreover, after the 2021 label change, fluoroquinolone use decreased shortly in all the three indications. However, a significant increasing trend was observed in fluoroquinolone use for AECB episodes, and fluoroquinolons were used for 61.4% of treated uUTI, 31.6% of treated AECB, and 5.42% of treated AS at the end of 2022, respectively. CONCLUSIONS: The label changes issued by the NMPA had no substantial impacts on fluoroquinolone prescribing in the study region in China. Fluoroquinolone prescribing was still highly prevalent for uUTI and AECB and thus requiring further antimicrobial stewardship.

Risk of type 2 diabetes and long-term antibiotic use in childhood: Evidence from the UK Biobank.

AIMS: This study aimed to investigate the association between long-term use of antibiotics during childhood and the risk of type 2 diabetes mellitus (T2DM) using a prospective cohort from the UK Biobank. METHODS: Participants in the UK Biobank who completed the online survey for digestive health were included in this prospective cohort study. A Cox regression model adjusted for sociodemographic characteristics, general health factors, mental health, lifestyle factors, comorbidities, and medication use was used to estimate the hazard ratio (HR) and confidence interval (CI) of the association between long-term use of antibiotics in the childhood and incident T2DM. RESULTS: The final analyses included 152,992 participants and 22,133 of them received long-term/recurrent antibiotics as children or teenagers. During the follow-up, 3370 and 681 incident T2DM cases occurred in the non-exposed and exposed groups respectively. Long-term use of antibiotics in childhood was associated with an increased risk of T2DM, with an HR of 1.16 (95 % CI, 1.07-1.27) after adjusting for potential confounders. Results in the subgroup analyses and sensitivity analyses were highly consistent with the primary analyses. CONCLUSIONS: Long-term use of antibiotics in childhood is associated with the risk of T2DM in middle and old age in the UK Biobank population.

Prospective cohort study evaluating the association between influenza vaccination and neurodegenerative diseases.

The effect of influenza vaccination (FluVac) on the risk of neurodegenerative diseases has not been well evaluated in prospective populations. We aimed to assess the association between FluVac and the risk of dementia and Parkinson's disease (PD) in people aged 60 years or older through a prospective population-based cohort from the UK Biobank. A time-varying Cox regression model adjusted for baseline and repeatedly measured covariates was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between influenza vaccination and risk of dementia/PD. We took into account 70,938 participants in the cohort, including 38,328 participants who got vaccinated. During a median follow-up period of 12.2 years, 2087 incident dementia cases occurred, including 281 cases who received FluVac and 1806 cases who were not vaccinated. In addition, 742 incident PD cases occurred, among whom 131 cases received FluVac and 611 PD cases did not receive FluVac. FluVac was associated with reduced dementia risk with an HR of 0.83 (95% CI, 0.72-0.95) but was not associated with PD incidence (HR = 1.07; 95% CI, 0.87-1.32) after controlling baseline and repeatedly measured covariates. Further, among all dementia cases, there were 733 Alzheimer's disease (AD) (94 vaccinated cases and 639 non-vaccinated cases), 307 vascular dementia (VD) (34 vaccinated cases and 273 non-vaccinated cases), and 1047 cases with other dementias (OD) (153 vaccinated cases and 894 non-vaccinated cases). The HRs for the associations between FluVac and AD, VD, and OD were 0.79 (95% CI, 0.63-1.00), 0.58 (95% CI, 0.39-0.86), and 0.94 (95% CI, 0.78-1.14) respectively. A dose-response relationship was found in the association between FluVac and dementia but not in the association with PD. A major limitation of the study is the low accuracy in the diagnosis of dementia subtypes, namely AD, VD, and OD. However, Results of sensitivity analyses were consistent with the primary analyses. In conclusion, influenza vaccination is significantly associated with a reduced risk of incident dementia but not PD in community-dwelling adults in the UK Biobank population.

Recent Progress of Bioinspired Cell Membrane in Cancer Immunotherapy.

By modifying immune cells, immunotherapy can activate immune response to establish long-term immune memory and prevent tumor recurrence. However, their effectiveness is largely constricted by the poor immunogenicity, immune escape, and immune tolerance of the tumor. This is related to the characteristics of the tumor itself, such as genome instability and mutation. The combination of various nanocarriers with tumor immunotherapy is beneficial for overcoming the shortcomings of traditional immunotherapy. Nanocarriers coated by cell membranes can extend blood circulation time, improve ability to evade immune clearance, and enhance targeting, thus significantly enhancing the efficacy of immunotherapy and showing great potential in tumor immunotherapy. This article reviews the application research progress of different types of cell membrane-modified nanocarriers in tumor immunotherapy, immunotherapy combination therapy, and tumor vaccines, and provides prospects for future research.

Associations Between Thiazolidinediones Use and Incidence of Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study.

OBJECTIVE: Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population-based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. RESULTS: The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person-years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59-0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35-0.88) and 0.74 (95% CI 0.57-0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. CONCLUSION: Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM.

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia.

Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Hyperbaric oxygen preconditioning rescues prolonged underwater exercise-induced hippocampal dysfunction by regulating microglia activation and polarization.

Underwater exercise is becoming increasingly prevalent, during which brain function is necessary but is also at risk. However, no study has explored how prolonged exercise affect the brain in underwater environment. Previous studies have indicated that excessive exercise in common environment causes brain dysfunction but have failed to provide appropriate interventions. Numerous evidence has indicated the neuroprotective effect of hyperbaric oxygen preconditioning (HBO-PC). The objective of this study was to investigate the cognitive effect of prolonged underwater exercise (PUE) and to explore the potential neuroprotective effect of HBO-PC in underwater environment. Rats swimming for 3 h in a simulated hyperbaric chamber (2.0 ATA) was used to establish the PUE animal model and HBO-PC (2.5 ATA for 1, 3,5 times respectively) was administrated before PUE. The results demonstrated that PUE triggers anxiety-like behaviors, cognitive impairment accompanied by hippocampal dysfunction, microglia activation and neuroinflammation. Conversely, 3 HBO-PC rescued anxiety-like behaviors and cognitive impairment. Mechanistically, 3 HBO-PC reduced microglia activation and switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. These findings illustrated that PUE induces anxiety-like behaviors and cognitive impairment and HBO-PC of proper frequency may provide an appropriate and less invasive intervention for protecting the brain in underwater exercise.