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[This corrects the article DOI: 10.1039/D0RA00184H.].
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OBJECTIVE: This study investigated the correlation between uncertainty stress (US) and depression among healthcare professionals (HCPs) in China. DESIGN, SETTINGS AND PARTICIPANTS: A cross-sectional online survey was conducted by recruiting HCPs from three provinces in China (central, eastern and western) through purposive sampling between 29 September 2022 and 18 January 2023. US was measured using the Life Stress Questionnaire and depression was measured using the Patient Health Questionnaire-9. In total, 2976 questionnaires were deemed valid. PRIMARY AND SECONDARY OUTCOME: This study examined the prevalence of US and depression among HCPs in China; the correlating sociodemographic traits; and the correlation between US and depression. RESULTS: The prevalence of US and depression among HCPs in China was 26.54% (790 out of 2976) and 71.63% (2132 out of 2976). Binary logistic analysis revealed that individuals with graduate degrees (OR: 1.83; 95% CI 1.07 to 3.11; p<0.05), central China (OR: 1.75; 95% CI 1.36 to 2.24; p<0.01), primary medical institutes (OR: 1.33; 95% CI 1.03 to 1.72; p<0.05), secondary medical institutes (OR: 1.30; 95% CI 1.01 to 1.68; p<0.05), an annual income of less than ¥50 000 (OR: 1.85; 95% CI 1.26 to 2.73; p<0.01) and an income range of ¥50 000-¥99 999 (OR: 1.49; 95% CI 1.10 to 2.03; p<0.05) were associated with a higher likelihood of US. The adjusted logistic regression model demonstrated that HCPs with higher US had a greater likelihood of depression (adjusted OR: 5.02; 95% CI 3.88 to 6.50; p<0.01). The increase in the US score was paralleled by an increased depression score (beta (B): 1.32; 95% CI 1.25 to 1.39; p<0.01). CONCLUSION: These findings reveal a significant correlation between US and depression among HCPs and suggest that improving the management of US may help reduce the prevalence of depression among HCPs.
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Depressão , Pessoal de Saúde , Humanos , Estudos Transversais , China/epidemiologia , Feminino , Masculino , Adulto , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Incerteza , Depressão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Estresse Psicológico/epidemiologia , Adulto Jovem , Modelos LogísticosRESUMO
NIR-II fluorescent photosensitizers as phototheranostic agents hold considerable promise in the application of mild photothermal therapy (MPTT) for tumors, as the reactive oxygen species generated during photodynamic therapy can effectively disrupt heat shock proteins. Nevertheless, the exclusive utilization of these photosensitizers to significantly augment the MPTT efficacy has rarely been substantiated, primarily due to their insufficient photodynamic performance. Herein, the utilization of high-performance NIR-II fluorescent type I/II photosensitizer (AS21:4) is presented as a simple but effective nanoplatform derived from molecule AS2 to enhance the MPTT efficacy of tumors without any additional therapeutic components. By taking advantage of heavy atom effect, AS21:4 as a type I/II photosensitizer demonstrates superior efficacy in producing 1O2 (1O2 quantum yield = 12.4%) and O2 â¢- among currently available NIR-II fluorescent photosensitizers with absorption exceeding 800 nm. In vitro and in vivo findings demonstrate that the 1O2 and O2 â¢- generated from AS21:4 induce a substantial reduction in the expression of HSP90, thereby improving the MPTT efficacy. The remarkable phototheranostic performance, substantial tumor accumulation, and prolonged tumor retention of AS21:4, establish it as a simple but superior phototheranostic agent for NIR-II fluorescence imaging-guided MPTT of tumors.
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Most fouling organisms have planktonic larval and benthic adult stages. Larval settlement, the planktonic-benthic transition, is the critical point when biofouling begins. However, our understanding of the molecular mechanisms of larval settlement is limited. In our previous studies, we identified that the AMP-activated protein kinase-silk gland factor 1 (AMPK-SGF1) pathway was involved in triggering the larval settlement in the fouling mussel M. sallei. In this study, to further confirm the pivotal role of SGF1, multiple targeted binding compounds of SGF1 were obtained using high-throughput virtual screening. It was found that the targeted binding compounds, such as NAD+ and atorvastatin, could significantly induce and inhibit the larval settlement, respectively. Furthermore, the qRT-PCR showed that the expression of the foot proteins' genes was significantly increased after the exposure to 10 µM NAD+, while the gene expression was significantly suppressed after the exposure to 10 µM atorvastatin. Additionally, the production of the byssus threads of the adults was significantly increased after the exposure to 10-20 µM of NAD+, while the production of the byssus threads was significantly decreased after the exposure to 10-50 µM of atorvastatin. This work will deepen our understanding of SGF1 in triggering the larval settlement in mussels and will provide insights into the potential targets for developing novel antifouling agents.
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Hypertension and diabetes are two common metabolic disorders that often coexist in the same individual. Their concurrence increases the risk of cardiovascular disease, renal dysfunction, and other complications. Cardiovascular disease is the primary cause of morbidity and mortality in individuals with diabetes, and hypertension further aggravates this condition. Interestingly, hypertension and diabetes share several common pathophysiological mechanisms including insulin resistance, vascular inflammation, endothelial dysfunction, obesity, and oxidative stress suggesting a cross-talk between these two conditions that could potentially contribute to the development of other human diseases. Effective management of diabetes should include a multifaceted approach that addresses not only glycemic control but also blood pressure (BP) and lipid control. Treatment plans should be individualized to each patient's needs and should involve a combination of lifestyle modifications and medications to achieve optimal control. With the availability of newer antidiabetic medications such as SGLT inhibitors and GLP1 receptor agonists, it is crucial to consider their potential to reduce BP, enhance kidney function, and lower the risk of cardiovascular diseases when initiating treatment for glycemic control. A more profound comprehension of the shared underlying mechanisms between these conditions could pave the way for the development of innovative therapeutic approaches to tackle them. Our review offers an in-depth analysis of the literature, providing a holistic view of the mechanisms underlying diabetes-hypertension comorbidity and its implications on heart and kidney diseases. The present article concludes by discussing current approaches for managing hypertensive diabetic patients to create a set of comprehensive individualized recommendations.
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BACKGROUND: Medications for opioid use disorders (MOUDs) are effective, but most people with opioid use disorder (OUD) do not receive treatment. Prior research has explored patients' structural barriers to access and perceptions of MOUD. Little research has considered treatment knowledge and perceptions outside of the patient population. Members of the public without OUD themselves (eg, family, friends) can significantly influence treatment decisions of persons with OUD. Considering these gaps, we conducted an original survey with a diverse sample of US adults to explore knowledge and preferences toward OUD treatments. METHODS: We conducted an online survey with 1505 White, Black, and Latino/a Americans including a small percentage (8.5%) with self-reported lifetime OUD. The survey used vignettes to describe hypothetical patients with OUD, provide basic treatment information (ie, methadone, buprenorphine, naltrexone, nonmedication treatment), and then assessed treatment preferences. Using multivariable logistic regression, we examined associations between covariates of interest (eg, perceived access, knowledge, demographics) and preference for MOUD versus nonmedication treatment. RESULTS: There were 523 White, 502 Black, and 480 Latino/a respondents. Across racial/ethnic subsamples, respondents had the greatest knowledge of nonmedication treatments, with Black (72.7%) and Latino/a (70.2%) respondents having significantly greater knowledge compared to White respondents (61.8%). However, after viewing the vignette, a greater proportion of respondents chose methadone (35.8%) or buprenorphine (34.8%) as their first-choice treatment for hypothetical patients. Multivariable logistic regression suggested that among Black respondents, those with knowledge of nonmedication treatment were more likely to choose MOUD than those without knowledge (odds ratio = 2.41, 95% confidence interval = 1.34-4.34). Perceived treatment access did not affect treatment choice. CONCLUSIONS: Across racial groups, knowledge and perceived access to nonmedication treatment was greater than for MOUD, but many still selected MOUD as a first-choice treatment. Significant findings emphasized the importance of treatment knowledge around decision-making, highlighting opportunities for tailored education efforts to improve uptake of evidence-based treatment.
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BACKGROUND: Obesity is an important risk factor for kidney stones(KS). Chinese Visceral Adiposity Index (CVAI), as a specific indicator for visceral obesity in the Chinese population, can more accurately assess the visceral fat content in Chinese individuals compared to Visceral Adiposity Index (VAI). However, the association between CVAI and risk for KS has not been studied. METHODS: A total of 97,645 participants from a health screening cohort underwent ultrasound examinations for the diagnosis of kidney stones, along with measurements of their CVAI. Logistic regressions were utilized to determine the relationship between different quartiles of CVAI and the incidence of kidney stones. Simultaneously, subgroup analysis and the computation of dose-response curves were employed to pinpoint susceptible populations. RESULTS: Among the participants, 2,888 individuals (3.0%) were diagnosed with kidney stones. The mean CVAI values ± standard deviation for the four groups were: Q1 (18.42 ± 19.64), Q2 (65.24 ± 10.39), Q3 (98.20 ± 9.11), and Q4 (140.40 ± 21.73). In the fully adjusted multivariable model, CVAI was positively correlated with urolithiasis (OR = 1.001; 95% CI = 1.000, 1.002). Compared with the first quartile of CVAI, the population in the fourth quartile of CVAI had a higher prevalence of kidney stones (OR = 1.231; 95% CI = 1.066, 1.415). Through subgroup analysis, a positive correlation between CVAI and the risk of kidney stones was found in non-smokers (OR = 1.001, 95%CI:1.000, 1.002), non-drinkers (OR = 1.001, 95%CI:1.000, 1.002), non-hypertensive subgroups (OR = 1.003, 95%CI:1.002, 1.003), and non-diabetes subgroups (OR = 1.001, 95%CI:1.000, 1.002). CONCLUSION: The findings suggest that CVAI could be a reliable and effective biomarker for assessing the potential risk of kidney stone prevalence, with significant implications for the primary prevention of kidney stones and public health.
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Gordura Intra-Abdominal , Cálculos Renais , Obesidade Abdominal , Ultrassonografia , Humanos , Masculino , Feminino , Cálculos Renais/epidemiologia , Cálculos Renais/diagnóstico por imagem , Estudos Transversais , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/diagnóstico por imagem , Fatores de Risco , Programas de Rastreamento/métodos , Adiposidade , Idoso , População do Leste AsiáticoRESUMO
INTRODUCTION: Medications for opioid use disorder (MOUD) including methadone (MMT), buprenorphine (BUP), and naltrexone (NTX) are safe and effective. However, there are significant negative perceptions surrounding MOUD, creating barriers to uptake. While research on MOUD stigma has largely focused on provider and patient experiences, fewer studies have explored MOUD perceptions among the general public. Given that MOUD stigma expressed by social ties surrounding individuals with OUD can influence treatment choices, we assessed MOUD perceptions among U.S. adults to determine how beliefs impacted treatment preference. We further explored how MOUD perceptions may be amplified among racialized groups with histories of experiencing drug-related discrimination. METHODS: The study collected survey data from a diverse sample of U.S. adults (n = 1508) between October 2020 and January 2021. The survey measured knowledge of MOUD and non-medication treatments, relative agreement with common MOUD perceptions, and treatment preferences. Multinomial logistic regression analysis tested associations with treatment preference, stratified by race/ethnicity. RESULTS: Descriptive results indicated that across groups, many respondents (66.8 %) had knowledge of MOUD, but believed MOUD was a "substitute" for opioids and had some degree of concern about misuse. Multivariable results showed knowledge of non-medication treatments was positively associated with MOUD preference among White (MMT OR = 3.16, 95 % CI = 1.35-7.39; BUP OR = 2.69, CI = 1.11-6.47), Black (MMT OR = 3.91, CI = 1.58-9.69), and Latino/a (MMT OR = 5.12, CI = 1.99-13.2; BUP OR = 3.85, CI = 1.5-9.87; NTX OR = 4.51, CI = 1.44-14.06) respondents. Among White respondents, we identified positive associations between MOUD experience and buprenorphine preference (OR = 4.33, CI = 1.17-16.06); non-medication treatment experience and preference for buprenorphine (OR = 2.86, CI = 1.03-7.94) and naltrexone (OR = 3.17, CI = 1.08-9.28). Concerns around misuse of methadone were negatively associated with methadone preference among White (OR = 0.65, CI = 0.43-0.98) and Latino/a (OR = 0.49, CI = 0.34-0.7), and concerns around misuse of buprenorphine was negatively associated with preference for MOUD among White (MMT OR = 0.62, CI = 0.39-0.99; BUP OR = 0.48, CI = 0.3-0.77; NTX OR = 0.6, CI = 0.36-0.99) and Latino/a (BUP OR = 0.59, CI = 0.39-0.89) respondents. CONCLUSIONS: This analysis offers critical insights into treatment perceptions beyond the patient population, finding that negative beliefs around MOUD are common and negatively associated with preferences for medication-based treatment. These findings highlight implications for public support of evidence-based treatment and lay the groundwork for future interventions addressing public stigma toward MOUD.
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Buprenorfina , Metadona , Naltrexona , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/psicologia , Feminino , Adulto , Estados Unidos/epidemiologia , Metadona/uso terapêutico , Naltrexona/uso terapêutico , Buprenorfina/uso terapêutico , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , Estigma Social , Analgésicos Opioides/uso terapêutico , Adulto Jovem , Preferência do Paciente/psicologia , Preferência do Paciente/estatística & dados numéricos , Inquéritos e Questionários , Etnicidade/psicologia , Antagonistas de Entorpecentes/uso terapêuticoRESUMO
PURPOSE: Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS: We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. RESULTS: A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION: Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.
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Derivações do Líquido Cefalorraquidiano , Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Ventriculostomia , Humanos , Hidrocefalia/cirurgia , Ventriculostomia/métodos , Masculino , Feminino , Taiwan/epidemiologia , Pré-Escolar , Criança , Lactente , Estudos Retrospectivos , Terceiro Ventrículo/cirurgia , Adolescente , Derivações do Líquido Cefalorraquidiano/métodos , Neuroendoscopia/métodos , Reoperação/estatística & dados numéricos , Estudos de Coortes , Recém-Nascido , Resultado do Tratamento , Adulto JovemRESUMO
Aurora kinase A, as a pro-carcinogenic in gastric cancer and glioma kinase, is enhanced in several human tumors. However, it's regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear. Thus, this study aimed to investigate the expression status, functional roles, and molecular mechanisms of AURKA in ESCC development. AURKA expression was analyzed by the screening of the GEO database and detected using an immunohistochemical method. The biological function of AURKA on ESCC was evaluated in vitro and in vivo. Western blot assay, malondialdehyde (MDA), iron, and glutathione (GSH) kits were utilized to assess changes in ferroptosis. Database analysis results showed that AURKA was a differential gene in ESCC and was highly expressed in human ESCC tissues. Functionally, AURKA knockdown decreased ESCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Moreover, when AURKA was knockdown, cells were more correctly blocked in the G2/M phase, and the ferroptosis-related MDA and Fe increased, whereas the GSH reduced. Consistently, Glutathione peroxidase 4 (GPX4) and solute carrier family 7a member 11 (SLC7A11) expression were downregulated by AURKA knockdown. However, ferroptosis inhibitor partially restore ESCC cell proliferation, invasion, and metastasis caused by AURKA knockdown. AURKA knockdown enhances ferroptosis and acts against cancer progression in ESCC. AURKA acts as a tumor-promoting gene and may serve as potential target for ESCC treatment.
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Research on the microbiota associated with marine invertebrates is important for understanding host physiology and the relationship between the host and the environment. In this study, the microbiota of the green mussel Perna viridis was characterized at the tissue scale using 16S rRNA gene high-throughput sequencing and compared with the microbiota of the surrounding environment. Different mussel tissues were sampled, along with two environmental samples (the mussel's attachment substratum and seawater). The results showed that the phyla Proteobacteria, Bacteroidetes, and Spirochaetae were dominant in mussel tissues. The bacterial community composition at the family level varied among the tissues of P. viridis. Although the microbiota of P. viridis clearly differed from that of the surrounding seawater, the composition and diversity of the microbial community of the foot and outer shell surface were similar to those of the substratum, indicating their close relationship with the substratum. KEGG prediction analysis indicated that the bacteria harbored by P. viridis were enriched in the degradation of aromatic compounds, osmoregulation, and carbohydrate oxidation and fermentation, processes that may be important in P. viridis physiology. Our study provides new insights into the tissue-scale characteristics of mussel microbiomes and the intricate connection between mussels and their environment.
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Barnacles are the only sessile lineages among crustaceans, and their sessile life begins with the settlement of swimming larvae (cyprids) and the formation of protective shells. These processes are crucial for adaptation to a sessile lifestyle, but the underlying molecular mechanisms remain poorly understood. While investigating these mechanisms in the acorn barnacle, Amphibalanus amphitrite, we discovered a new gene, bcs-6, which is involved in the energy metabolism of cyprid settlement and originated from a transposon by acquiring the promoter and cis-regulatory element. Unlike mollusks, the barnacle shell comprises alternate layers of chitin and calcite and requires another new gene, bsf, which generates silk-like fibers that efficiently bind chitin and aggregate calcite in the aquatic environment. Our findings highlight the importance of exploring new genes in unique adaptative scenarios, and the results will provide important insights into gene origin and material development.
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Thoracica , Animais , Thoracica/genética , Adaptação Fisiológica/genética , Larva/genética , Quitina/metabolismo , Filogenia , Carbonato de Cálcio , Elementos de DNA Transponíveis/genética , Metabolismo Energético/genética , Evolução MolecularRESUMO
PURPOSE: Helicobacter pylori (H. pylori) infection has been reported to be associated with multiple metabolic diseases. However, the connection between H. pylori infection and gout has not been explored previously. Our study aimed to investigate the association of gout and H. pylori infection in hyperuricemia population in China. PATIENTS AND METHODS: This cross-sectional study was performed among the subjects who underwent health checkup in our health promotion center from January 1, 2020 to December 31, 2021. A total of 53,629 subjects with a mean age of 44.2 years were included in this study. H. pylori infection was defined as a positive [13]C-urea breath test. The effect of H. pylori infection on gout was assessed by multiple logistic regression analysis. RESULTS: 720 subjects with gout and 15,077 subjects with asymptomatic hyperuricemia (> 420 µmol/L in male and > 360 µmol/L in female) were enrolled. The prevalence rates of H. pylori infection, hyperuricemia and gout were 26.3%, 29.5%, 1.3%, respectively. The prevalence rate of H. pylori infection was significantly higher in subjects with gout than in those with asymptomatic hyperuricemia (35.0% vs. 27.2%; P<0.001). Multiple logistic regression analysis showed that H. pylori infection was associated with an increased risk of gout independent of serum uric acid level in hyperuricemia population (odds ratio [OR]: 1.320, 95% confidence interval [CI]: 1.124-1.550, P = 0.001). CONCLUSION: H. pylori infection is positively associated with higher risk of gout in hyperuricemia population. The causal relationship and potential mechanism between H. pylori infection and gout warrants further investigation.
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Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316â882 women with surgical treatment for ectopic pregnancy and 3â168â820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.
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Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Gravidez Ectópica , Salpingectomia , Humanos , Feminino , Gravidez , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/epidemiologia , Adulto , Taiwan/epidemiologia , Gravidez Ectópica/epidemiologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/epidemiologia , Incidência , Estudos de Casos e Controles , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Urinary incontinence is a common disease among middle-aged and elderly women, which not only affects the physical and mental health of patients, but also brings a great medical burden to society. Obesity is a known risk factor for urinary incontinence and is the most common secondary cause of hyperlipidemia. Most obese patients also suffer from hyperlipidemia in the clinic. However, few studies have explored the role of hyperlipidemia in women with urinary incontinence. Using data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), we aimed to evaluated the independent associations of high body mass index and hyperlipidemia with urinary incontinence in Americans by conducting a weighted multivariate logistic regression model. Additive interactions were also assessed using the relative excess risk due to interaction (RERI), attributed proportion of interaction (AP) and synergy index (S). This study demonstrated that hyperlipidemia was associated with a higher risk of stress urinary incontinence among women with obesity (OR = 1.52, 95% CI = 1.03-2.25), and there was a significant synergistic effect of hyperlipidemia and obesity on stress urinary incontinence(adjusted RERI: 3.75, 95% CI 0.30-7.20; adjusted AP: 0.67, 95% CI 0.54-0.80; adjusted S: 5.49, 95% CI 4.15-7.27). Moreover, fasting serum triglyceride lipids were the most relevant blood lipid indicator for the risk of stress urinary incontinence, especially among obese women younger than 50 years old, which contributes to the development of more refined lipid control protocols for patients with urinary incontinence in different age groups.
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Hiperlipidemias , Incontinência Urinária por Estresse , Incontinência Urinária , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Estados Unidos/epidemiologia , Incontinência Urinária por Estresse/etiologia , Inquéritos Nutricionais , Hiperlipidemias/complicações , Fatores de Risco , Obesidade/complicações , Incontinência Urinária/etiologia , Incontinência Urinária/complicações , LipídeosRESUMO
BACKGROUND: DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors, the loss of which is attributed to the development of various types of cancers. Although well characterized, MMR factors remain to be identified. As a 3'-5' exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways. However, the role of MRE11A in MMR is unclear. METHODS: Initially, short-term and long-term survival assays were used to measure the cells' sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Meanwhile, the level of apoptosis was also determined by flow cytometry after MNNG treatment. Western blotting and immunofluorescence assays were used to evaluate the DNA damage within one cell cycle after MNNG treatment. Next, a GFP-heteroduplex repair assay and microsatellite stability test were used to measure the MMR activities in cells. To investigate the mechanisms, western blotting, the GFP-heteroduplex repair assay, and chromatin immunoprecipitation were used. RESULTS: We show that knockdown of MRE11A increased the sensitivity of HeLa cells to MNNG treatment, as well as the MNNG-induced DNA damage and apoptosis, implying a potential role of MRE11 in MMR. Moreover, we found that MRE11A was largely recruited to chromatin and negatively regulated the DNA damage signals within the first cell cycle after MNNG treatment. We also showed that knockdown of MRE11A increased, while overexpressing MRE11A decreased, MMR activity in HeLa cells, suggesting that MRE11A negatively regulates MMR activity. Furthermore, we show that recruitment of MRE11A to chromatin requires MLH1 and that MRE11A competes with PMS2 for binding to MLH1. This decreases PMS2 levels in whole cells and on chromatin, and consequently comprises MMR activity. CONCLUSIONS: Our findings reveal that MRE11A is a negative regulator of human MMR.
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Reparo de Erro de Pareamento de DNA , Metilnitronitrosoguanidina , Humanos , Cromatina , Células HeLa , Metilnitronitrosoguanidina/farmacologia , Endonuclease PMS2 de Reparo de Erro de PareamentoRESUMO
BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication of stroke with a high incidence of underdiagnosis. The relationship between dyslipidemia and VTE remains uncertain. Therefore, this study aimed to explore this connection in acute stroke patients to enhance diagnostic and preventative strategies. METHODS: Retrospective data from 7854 acute stroke patients admitted to Dongyang Hospital, Affiliated with Wenzhou Medical University, between 2010 and 2020 were extracted. Differential tests were compared among various blood lipid parameters and the presence or absence of venous thrombosis. Logistic regression analysis was employed to estimate associations. RESULTS: The prevalences of DVT and PE were 3.9 % and 1.1 %, respectively. Additionally, 43 cases (0.5 %) exhibited combined DVT and PE. A high triglyceride (TG) level was associated with a decreased risk of VTE (adjusted odd ratio [aOR] = 0.69, 95 % confidence interval [CI]: 0.54-0.89, P = 0.004), whereas a high low-density lipoprotein cholesterol (LDL-C) level was associated with an increased risk of VTE (aOR = 1.51, 95 % CI: 1.16-1.97, P = 0.002), after adjusting for confounding factors. No significant associations were observed for high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) levels with VTE risk. Subgroup analyses revealed that these associations were significant in ischemic stroke patients. CONCLUSION: Low TG levels and high LDL-C levels were found to be associated with an increased risk of VTE in acute stroke patients, offering valuable insights for the early identification and management of high-risk individuals.
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Embolia Pulmonar , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , LDL-Colesterol , Fatores de Risco , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , LipídeosRESUMO
Purpose: To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Methods: Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). Results: A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Conclusion: Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.
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BACKGROUND: Whether perceived stress is associated with loneliness and depressive symptoms in general adults, and to what extent sleep quality mediates the associations, remains unknown. The aim of this study was to estimate the associations of perceived stress with loneliness and depressive symptoms, and the mediating role of sleep quality in these associations. METHODS: Cross-sectional data on 734 participants (aged 18-87 years) were analyzed. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10; range 0-40). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; range 0-21). Loneliness was assessed using the three-item short form of the Revised University of California, Los Angeles (UCLA) loneliness scale (range 3-9). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CESD-10) Scale (range 0-30). General linear regression models, multivariable logistic regression models, and formal mediation analysis were performed. RESULTS: After adjustment for age and sex, we found that with each 1-point increment in the perceived stress score, both the loneliness score (ß = 0.07; 95% confidence interval [CI]: 0.06, 0.08) and depression score (ß = 0.45; 95% CI: 0.40, 0.49) increased significantly. Robust results were observed when adjusting for more confounders. Furthermore, sleep quality mediated 5.3% (95% CI: 1.3%, 10.0%; P = 0.014) and 9.7% (95% CI: 6.2%, 14.0%; P < 0.001) of the associations of perceived stress score with loneliness score and depression score, respectively. CONCLUSIONS: In general Chinese adults, perceived stress was positively associated with loneliness and depressive symptoms, and sleep quality partially mediated these associations. The findings reveal a potential pathway from perceived stress to mental health through sleep behaviors, and highlight the importance of implementing sleep intervention programs for promoting mental health among those who feel highly stressed.