Activation of parkin by a molecular glue.

Mutations in parkin and PINK1 cause early-onset Parkinson's disease (EOPD). The ubiquitin ligase parkin is recruited to damaged mitochondria and activated by PINK1, a kinase that phosphorylates ubiquitin and the ubiquitin-like domain of parkin. Activated phospho-parkin then ubiquitinates mitochondrial proteins to target the damaged organelle for degradation. Here, we present the mechanism of activation of a new class of small molecule allosteric modulators that enhance parkin activity. The compounds act as molecular glues to enhance the ability of phospho-ubiquitin (pUb) to activate parkin. Ubiquitination assays and isothermal titration calorimetry with the most active compound (BIO-2007817) identify the mechanism of action. We present the crystal structure of a closely related compound (BIO-1975900) bound to a complex of parkin and two pUb molecules. The compound binds next to pUb on RING0 and contacts both proteins. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) experiments confirm that activation occurs through release of the catalytic Rcat domain. In organello and mitophagy assays demonstrate that BIO-2007817 partially rescues the activity of parkin EOPD mutants, R42P and V56E, offering a basis for the design of activators as therapeutics for Parkinson's disease.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China.

BACKGROUND: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. METHODS: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. RESULTS: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. CONCLUSIONS: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

HPV integration: a precise biomarker for detection of residual/recurrent disease after treatment of CIN2-3.

BACKGROUND: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. METHODS: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. RESULTS: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. CONCLUSIONS: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

Analysis of Related Factors Influencing Hypertension Classification among Centenarians in Hainan, China.

Background: As a population ages, blood pressure levels gradually increase, leading to a higher incidence of hypertension and increased cardiovascular diseases risk. This study examines factors affecting hypertension grading among centenarians in the Hainan Province. Methods: Data from 2014 to 2016 were accessed from the cross-sectional database "Hypertension Levels and Epidemiological Characteristics of the Elderly and Centenarians in Hainan province of China". This study included 690 centenarians with hypertension. Hypertension grading was the dependent variable, analyzed against independent variables including demographic information (sex, age, ethnicity, education level, marital status, cohabitation, and regional distribution), lifestyle factors (smoking, alcohol consumption, and physical activity), body mass index (BMI), and comorbid conditions (diabetes and hyperlipidemia). Logistic regression models, adjusted for these factors, were used to assess the determinants of hypertension grading among the participants. Results: Multivariate regression analysis, after adjusting for other variables, revealed significant associations between BMI, low-density lipoprotein (LDL) levels, and hypertension grades. Individuals with BMI below 18.5 kg/m 2 had a 0.614-fold lower risk of developing grade III hypertension (odds ratio [OR]: 0.614, 95% confidence interval [CI]: 0.390-0.966, p = 0.0350) and a 0.586-fold lower risk for grade II hypertension (OR: 0.586, 95% CI: 0.402-0.852, p = 0.0052). Furthermore, individuals with elevated LDL levels had a 6.087-fold greater risk of progressing from grade I to grade III hypertension (OR: 6.087, 95% CI: 1.635-22.660, p = 0.0071) and a 4.356-fold greater risk of progressing from grade II to grade III hypertension (OR: 4.356, 95% CI: 1.052-18.033, p = 0.0423). Additionally, individuals of Li ethnicity had 1.823-fold greater risk of progressing from grade I to grade II hypertension compared to those of Han ethnicity (OR: 1.823, 95% CI: 1.033-3.218, p = 0.0383). Conclusions: A BMI below 18.5 kg/m 2 , elevated LDL, and ethnicity emerged the primary factors associated with hypertension grading in centenarians. To reduce the risk of hypertension, it is crucial for centenarians to maintain a healthy weight, normal LDL levels, and adopt dietary habits including a low-cholesterol and low-fat diet.

Comparative evaluation of two clinical sampling techniques for HPV detection in male genital sites: a randomized controlled study.

AIMS: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection. METHODS AND RESULTS: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (ß-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites. CONCLUSIONS: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity.

Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.

BACKGROUND: Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs. METHODS: CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time. FINDINGS: Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE. CONCLUSIONS: There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials. FUNDING: This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).

The diabetes mellitus multimorbidity network in hospitalized patients over 50 years of age in China: data mining of medical records.

OBJECTIVE: Many diabetes mellitus (DM) patients suffer from multimorbidity. Understanding the DM multimorbidity network should be given priority. The purpose of this study is characterize the DM multimorbidity network in people over 50 years. METHODS: Data on 75 non-communicable diseases (NCDs) were extracted from electronic medical records of 309,843 hospitalized patients older than 50 years who had at least one NCD. The association rules analysis was used as a novel classification method and combined with the Chi-square tests to identify associations between NCDs and DM. RESULT: A total of 12 NCDs were closely related to DM, {cholelithiasis, DM} was an unexpected combination. {dyslipidemia, DM} and {gout, DM} had the largest lift in the male and female groups, respectively. The negative related group included 7 NCDs. There were 9 NCDs included in the strong association rules. Most combinations were different by age and sex. In males, the strongest rule was {peripheral vascular disease (PVD), dyslipidemia, DM}, while {hypertension, dyslipidemia, chronic liver disease (CLD), DM} was the strongest in females. In patients younger than 70 years, hypertension, CLD, and dyslipidemia were the most dominant NCDs in the DM multimorbidity network. In patients 70 years or older, chronic kidney disease (CKD), CVD, CHD, and heart disease (HD) frequently co-occurred with DM. CONCLUSION: Future primary healthcare policies for DM should be formulated based on age and sex. In patients younger than 70 years, more attention to hypertension, CLD, and dyslipidemia is required, while attention to CKD, CVD, CHD and HD is needed in patients older than 70 years.

A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest Drosophila suzukii.

CRISPR-based gene drives offer promising prospects for controlling disease-transmitting vectors and agricultural pests. A significant challenge for successful suppression-type drive is the rapid evolution of resistance alleles. One approach to mitigate the development of resistance involves targeting functionally constrained regions using multiple gRNAs. In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility gene Tyrosine decarboxylase 2 (Tdc2) in Drosophila suzukii, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects in Tdc2 mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system in Drosophila melanogaster and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genetic polymorphisms in wild populations may limit the spread of gene drive alleles, and the position effect profoundly influences Cas9 activity. Furthermore, this study highlights the potential of conditionally rescuing the female infertility caused by the gene drive, offering a valuable tool for the industrial-scale production of gene drive transgenic insects.

Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Development of a Mass Spectrometry-Based Method for Quantification of Total Cashew Protein in Roasting Oil.

BACKGROUND: Food allergen cross-contact during food preparation and production is one of the causes of unintentional allergen presence in packaged foods. However, little is known about allergen cross-contact in shared frying or roasting oil, which prevents the establishment of effective allergen controls and may put allergic individuals at risk. To better understand the quantity of allergen transferred to frying oil and subsequent products, an analytical method is needed for quantifying protein in oil that has been exposed to frying/roasting conditions. OBJECTIVE: The goal of this study was to develop a parallel reaction monitoring LC-MS/MS method to quantify the amount of cashew protein in shared roasting oil. METHODS: The sample preparation method was evaluated to improve protein extractability and peptide performance. Four quantitative peptides representing cashew 2S and 11S proteins were selected as targets based on their sensitivity, heat stability, and specificity. A calibration strategy was developed to quantify the amount of total cashew protein in oil. Method performance was evaluated using a heated cashew-in-oil model system. RESULTS: The method showed high recovery in oil samples spiked with 100 or 10 parts per million (ppm) total cashew protein heated at 138 or 166°C for 2-30 min. Samples (100 ppm total cashew protein) heated for 30 min had more than 90% recovery when treated at 138°C and more than 50% when heated at 166°C. CONCLUSION: The method is fit-for-purpose for the analysis of cashew allergen cross-contact in oil. HIGHLIGHTS: A novel MS-based method was developed that can accurately quantify the amount of cashew protein present in heated oil.

Rapamycin inhibits B16 melanoma cell viability invitro and invivo by inducing autophagy and inhibiting the mTOR/p70­S6k pathway.

Rapamycin is an immunosuppressant that has been shown to prevent tumor growth following organ transplantation. However, its exact mode of antitumor action remains unknown. The present study used the B16-F10 (B16) murine melanoma model to explore the antitumor mechanism of rapamycin, and it was revealed that rapamycin reduced B16 cell viability in vitro and in vivo. In addition, in vitro and in vivo, the results of western blotting showed that rapamycin reduced Bcl2 expression, and enhanced the protein expression levels of cleaved caspase 3 and Bax, indicating that it can induce the apoptosis of B16 melanoma cells. Furthermore, the results of cell cycle analysis and western blotting showed that rapamycin induced B16 cell cycle arrest in the G1 phase, based on the reduction in the protein expression levels of CDK1, cyclin D1 and CDK4, as well as the increase in the percentage of cells in G1 phase. Rapamycin also significantly increased the number of autophagosomes in B16 melanoma cells, as determined by transmission electron microscopy. Furthermore, the results of RT-qPCR and western blotting showed that rapamycin upregulated the protein expression levels of microtubule-associated protein light chain 3 (LC3) and Beclin-1, while downregulating the expression of p62 in vitro and in vivo, thus indicating that rapamycin could trigger cellular autophagy. The present study revealed that rapamycin in combination with chloroquine (CQ) further increased LC3 expression compared with that in the CQ group, suggesting that rapamycin induced an increase in autophagy in B16 cells. Furthermore, the results of western blotting showed that rapamycin blocked the phosphorylation of p70 ribosomal S6 kinase (p70-S6k) and mammalian target of rapamycin (mTOR) proteins in vitro and in vivo, thus suggesting that rapamycin may exert its antitumor effect by inhibiting the phosphorylation of the mTOR/p70-S6k pathway. In conclusion, rapamycin may inhibit tumor growth by inducing cellular G1 phase arrest and apoptosis. In addition, rapamycin may exert its antitumor effects by inducing the autophagy of B16 melanoma cells in vitro and in vivo, and the mTOR/p70-S6k signaling pathway may be involved in this process.

Cardiometabolic diseases and early cognitive decline: Mitigated by integrated active lifestyle for brain health.

BACKGROUND: Cardiometabolic diseases (CMDs) increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. METHODS: This prospective study used the baseline and 2-year follow-up data of 2537 dementia-free elderly ≥60 from PINDEC Project. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking, and alcohol consumption) were collected and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, ≤3 score; intermediate, 4 score; and active, ≥5). Logistic regression was used in data analysis. RESULTS: 35.2 % participants had 5-6 healthy components, while only 5.4 % had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95 % confidence interval) of early cognitive decline was 1.223 (0.799-1.871) and 1.832 (1.140-2.943) for participants with only one CMD and any two or more CMDs, respectively. An inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend = 0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95%CI: 0.302-2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR = 3.422, 95%CI: 1.764-6.638). LIMITATIONS: Our research lacks information about nutrition. CONCLUSIONS: A dose-response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.

Multistate structures in a hydrogen-bonded polycatenation non-covalent organic framework with diverse resistive switching behaviors.

The inherent structural flexibility and reversibility of non-covalent organic frameworks have enabled them to exhibit switchable multistate structures under external stimuli, providing great potential in the field of resistive switching (RS), but not well explored yet. Herein, we report the 0D+1D hydrogen-bonded polycatenation non-covalent organic framework (HOF-FJU-52), exhibiting diverse and reversible RS behaviors with the high performance. Triggered by the external stimulus of electrical field E at room temperature, HOF-FJU-52 has excellent resistive random-access memory (RRAM) behaviors, comparable to the state-of-the-art materials. When cooling down below 200 K, it was transferred to write-once-read-many-times memory (WORM) behaviors. The two memory behaviors exhibit reversibility on a single crystal device through the temperature changes. The RS mechanism of this non-covalent organic framework has been deciphered at the atomic level by the detailed single-crystal X-ray diffraction analyses, demonstrating that the structural dual-flexibility both in the asymmetric hydrogen bonded dimers within the 0D loops and in the infinite π-π stacking column between the loops and chains contribute to reversible structure transformations between multi-states and thus to its dual RS behaviors.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Testing for viral DNA integration among HPV-positive women to detect cervical precancer: An observational cohort study.

OBJECTIVE: Human papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV-positive women. DESIGN: An observational cohort study. SETTING: A cervical cancer screening programme in China. POPULATION: 1393 HPV-positive women aged 25-65 years undergoing routine cervical cancer screening and HPV integration testing with 1-year follow-up. METHODS: The sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared. MAIN OUTCOME MEASURES: Cervical intraepithelial neoplasia grade 3 or more severe (CIN3+). RESULTS: Among 1393 HPV-positive patients, 138 (9.9% [8.3-11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0-41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3-95.8%] versus 63.8% [61.2-66.4%]) and equivalent sensitivity (70.5% [61.4-79.7%] versus 70.5% [61.4-79.7%]) for detection of CIN3+. HPV integration-negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1-year follow-up, the progression rate in the HPV integration-positive women was higher than in the HPV integration-negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6-11.9). In 10 conservatively managed integration-negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1-year follow-up. CONCLUSION: The HPV integration test may be a precise risk stratification tool for HPV-positive women and could avoid excessive use of invasive biopsies.

Association of Sleep Status With Cognitive Functions in Centenarians: Evidence From Hainan Centenarian Cohort.

OBJECTIVES: This study aimed to analyze the association between sleep quality, sleep duration, and cognitive functions among centenarians. METHODS: The baseline data of the China Hainan Centenarians Cohort Study served as the foundation for this study. Logistic regression was utilized to demonstrate the relationship between sleep status and cognitive impairment. Moreover, a canonical correlation analysis was performed to analyze the correlation between these variables. RESULTS: A total of 994 centenarians were included. After adjustment, poor sleep quality centenarians had an odds ratio of 1.77 (95% confidence interval [CI]: 1.00-3.09) for cognitive impairment when compared to centenarians with normal sleep quality. Centenarians who slept for more than 9 hr had a stronger association with severe cognitive impairment, indicated by an odds ratio of 1.41 (95% CI: 1.02-1.96), compared to those who slept for 7-9 hr. Additionally, the canonical correlation analysis results revealed that the linear combination of sleep quality V1, primarily determined by sleep latency, daytime dysfunction, and subjective sleep quality, was associated with cognitive function; the linear combination of cognitive function W1, mainly determined by orientation, attention and calculation, and memory. DISCUSSION: There exists a correlation between poor sleep quality and cognitive impairment in centenarians, as well as a correlation between sleep duration >9 hr at night and severe cognitive impairment. The primary cognitive domains associated with sleep quality are orientation, calculation, and memory. It is imperative to monitor and safeguard the cognitive functions linked to poor sleep quality in the older individuals, with attention to orientation, calculation, and memory.

The relationship between sleep status and activity of daily living: based on China Hainan centenarians cohort study.

OBJECTIVE: This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions. METHOD: The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability. RESULTS: A total of 994 centenarians were included in this study with the age range 100-116 years old. Compared with the centenarians who sleep 6-9 h at night and < 2 h in the daytime, the adjusted OR between sleep > 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02-8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56-4.83). Compared with centenarians who sleep for 7-9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54-9.00). CONCLUSION: Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.