ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex.

53BP1 is primarily known as a key regulator in DNA double-strand break (DSB) repair. However, the mechanism of DSB-triggered cohesin modification-modulated chromatin structure on the recruitment of 53BP1 remains largely elusive. Here, we identified acetyltransferase ESCO2 as a regulator for DSB-induced cohesin-dependent chromatin structure dynamics, which promotes 53BP1 recruitment. Mechanistically, in response to DNA damage, ATM phosphorylates ESCO2 S196 and T233. MDC1 recognizes phosphorylated ESCO2 and recruits ESCO2 to DSB sites. ESCO2-mediated acetylation of SMC3 stabilizes cohesin complex conformation and regulates the chromatin structure at DSB breaks, which is essential for the recruitment of 53BP1 and the formation of 53BP1 microdomains. Furthermore, depletion of ESCO2 in both colorectal cancer cells and xenografted nude mice sensitizes cancer cells to chemotherapeutic drugs. Collectively, our results reveal a molecular mechanism for the ATM-ESCO2-SMC3 axis in DSB repair and genome integrity maintenance with a vital role in chemotherapy response in colorectal cancer.

Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. METHODS: PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger's and Begg's test were used to evaluate publication bias. RESULTS: A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22-18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68-3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16-2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15-2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37-3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45-5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71-5.46, P = 0.19). CONCLUSIONS: The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib.

Age-specific association of stage of hypertension at diagnosis with cardiovascular and all-cause mortality among elderly patients with hypertension: a cohort study.

BACKGROUND: Hypertension affects 31.1% of adults worldwide, with higher prevalence of great than 60% in elderly. Advanced hypertension stage was associated with the higher risk of mortality. However, little is known about the age-specific association of stage of hypertension at diagnosis on cardiovascular mortality or all-cause mortality. Therefore, we aim to explore this age-specific association among the hypertensive elderly through stratified and interaction analyses. METHODS: This cohort study included 125,978 elderly hypertensive patients aged 60+ years from Shanghai of China. Cox regression was used to estimate the independent and joint effect of hypertension stage and age at diagnosis on cardiovascular and all-cause mortality. Interactions were evaluated both additively and multiplicatively. Multiplicative interaction was examined by the Wald test of the interaction term. Additive interaction was assessed by relative excess risk due to interaction (RERI). All analyses were performed stratified by sex. RESULTS: 28,250 patients died during the follow-up up to 8.85 years, and 13,164 died of cardiovascular events. Older age and advanced hypertension stage were risk factors of cardiovascular mortality and all-cause mortality. Besides, smoking, rarely exercise, BMI < 18.5 and diabetes were also the risk factors. When we compared stage 3 hypertension with stage 1 hypertension, hazard ratios (95% confidence interval) of cardiovascular mortality and all-cause mortality were 1.56(1.41-1.72) and 1.29(1.21-1.37) for males aged 60-69 years, 1.25(1.14-1.36) and 1.13(1.06-1.20) for males aged 70-85 years, 1.48(1.32-1.67) and 1.29(1.19-1.40) for females aged 60-69 years, and 1.19(1.10-1.29) and 1.08(1.01-1.15) for females aged 70-85 years, respectively. Negative multiplicative interaction and positive additive interaction between age at diagnosis and stage of hypertension at diagnosis on cardiovascular mortality were observed in males (HR: 0.81, 95% CI: 0.71-0.93 RERI: 0.59, 95% CI: 0.09-1.07) and females (HR: 0.81, 95% CI: 0.70-0.93 RERI: 0.66, 95% CI: 0.10-1.23). CONCLUSIONS: Diagnosed with stage 3 hypertension was associated with higher risks of cardiovascular mortality and all-cause mortality, which were stronger among patients with age at diagnosis of 60-69 years compared with those with age at diagnosis of 70-85 years. Therefore, for the younger part of the elderly, the Department of Health should pay more attention to treating patients with stage 3 hypertension.

Incidence, associated factors, and outcomes of delirium in critically ill children in china: a prospective cohort study.

BACKGROUND: Delirium occurs frequently in critically ill children and has been reported in many countries, but delirium is not well-characterized in China. The aim of this study was to represent the incidence of delirium in critically ill children in China, its associated factors, and the influence of delirium on in-hospital outcomes. METHODS: This observational prospective cohort study was set up in a large academic medical center with a 57-bed PICU in southwestern China. Critically ill children who required PICU stays over 24 h and were admitted between November 2019 and February 2022 were included in this study. The Cornell Assessment of Pediatric Delirium was used twice daily for delirium evaluation by bedside nurses, and twenty-four clinical features were collected from medical and nursing records during hospitalization. RESULTS: The incidence of delirium was 26.0% (n = 410/1576). Multivariate analysis revealed that seven independent risk factors including days of mechanical ventilation and physical restraints, admission diagnosis (neurologic disorder), sleep deprivation, use of benzodiazepines and dexmedetomidine, liver failure/liver dysfunction associated with delirium in critically ill children. One potentially protective factor was the watching television /listening to music/playing with toys. Children with delirium had longer lengths of stay in the PICU (median 11 vs. 10 days, p < 0.001) and hospital (median 18 vs. 15 days, p < 0.001) compared to those without delirium. Additionally, the in-hospital mortality rates were 4.63% and 0.77% in patients with and without delirium (p < 0.05). CONCLUSIONS: Delirium is common in critically ill children in China and related to poor outcomes. Interventional studies are warranted to determine the best practices to reduce delirium exposure in at-risk children.

A Novel Technique for Reduction and Fixation of Severe Extracapsular Condylar Fracture.

Introducing a novel surgical technique that uses 2 screws and 3 titanium plates to reduce and fix an extracapsular condylar fracture. This technique has been used on 18 sides of extracapsular condylar fracture over the last 3 years in the Department of Oral and Cranio-Maxillofacial Science of Shanghai Ninth People's Hospital without severe complications in clinical practice. Applying this technique, the dislocated condylar segment can be reduced accurately and fixed efficiently.

Efficient enzymatic synthesis of d-allulose using a novel d-allulose-3-epimerase from Caballeronia insecticola.

BACKGROUND: Rare sugars have become promising 'sugar alternatives' because of their low calories and unique physiological functions. Among the family of rare sugars, d-allulose is one of the sugars attracting interest. Ketose 3-epimerases (KEase), including d-tagatose 3-epimerase (DTEase) and d-allulose 3-epimerase (DAEase), are mainly used for d-allulose production. RESULTS: In this study, a putative xylose isomerase from Caballeronia insecticola was characterized and identified as a novel DAEase. Caballeronia insecticola DAEase displayed prominent enzymatic properties, and 150 g L-1 d-allulose was produced from 500 g L-1 d-fructose in 45 min with a conversion rate of 30% and high productivity of 200 g L-1 h-1 . Furthermore, DAEase was employed in a phosphorylation-dephosphorylation cascade reaction, which significantly increased the conversion rate of d-allulose. Under optimized conditions, the conversion rate of d-allulose was approximately 100% when the concentration of d-fructose was 50 mmol L-1 . CONCLUSION: This research described a very beneficial and facile approach for d-allulose production based on C. insecticola DAEase. © 2022 Society of Chemical Industry.

Time-varying association between body mass index and all-cause mortality in patients with hypertension.

BACKGROUND: Relationship between BMI and all-cause mortality in patients with hypertension remains controversial. This study aimed to evaluate the time-varying association between BMI in patients with hypertension and all-cause mortality. METHODS: This population-based cohort study included 212,394 Chinese adults with hypertension from 2007 to 2015 and was followed up until death, loss-to-follow-up, or December 31, 2018. According to the World Health Organization criteria for Asians, BMI was categorized into five groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), class I obesity (25-29.9 kg/m2) and class II obesity (BMI ≥ 30 kg/m2). Cox model was used to estimate the time-varying association of BMI on the risk of mortality by including the interaction term between BMI and time using restricted cubic spline. RESULTS: Compared with normal weight, underweight and class II obesity were associated with higher mortality (Hazard ratio [HRs] at 1 and 10 years of follow-up: 1.51 [95% CI: 1.39-1.65], and 1.27 (1.15-1.41) for underweight, respectively; 1.08 (0.96-1.21), and 1.16 (1.03-1.30) for class II obesity, respectively). However, overweight and class I obesity were associated with lower mortality, although the protective effects gradually attenuated over time (HRs at 1 and 10 years of follow-up: 0.85 (0.81-0.90), and 0.96 (0.91-1.02) for overweight, respectively; 0.80 (0.76-0.84), and 1.04 (0.99-1.10) for class I obesity, respectively). CONCLUSIONS: We found increased mortality among hypertensive patients with underweight and class II obesity while decreased mortality with overweight and class I obesity was observed during the first 5 years of follow-up. Management efforts for hypertension may target controlling body weight in a reasonable range for patients, and probably more attention should be given to underweight patients.

Choline deficiency-related multi-omics characteristics are susceptible factors for chemotherapy-induced thrombocytopenia.

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Differentially expressed features (DEFs) from each uni-omics analysis were then subjected to integrative analysis using Multi-Omics Factor Analysis (MOFA). Choline-deficiency in plasma and CRT was found as the most critical TCP-related feature. Based on bioinformatic analysis and literature research, we further concluded that choline-deficiency was the possible reason for most of the other TCP-related multi-omics DEFs, including metabolites representing reduced sphingolipid de novo synthesis and elevated solute carrier-mediated transmembrane transportation in CRT and plasma, DNA hypermethylation and elevated expression of genes involved in neuronal system genes. In terms of thrombocytopoiesis, these TCP-related DEFs may cause atypical maintenance and differentiation of megakaryocyte, resulting a suppressed ability of thrombocytopoiesis, making patients more susceptible to chemotherapy-induced TCP. At last, prediction models were developed and validated with reasonably good discrimination. The area under curves (AUCs) of training sets were all > 0.9, while validation sets had AUCs between 0.778 and 0.926. In conclusion, our results produced reliable marker systems for predicting TCP and promising target for developing precision treatment to prevent TCP.

Separate and combined effect of visit-to-visit glycaemic variability and mean fasting blood glucose level on all-cause mortality in patients with type 2 diabetes: A population-based cohort study.

AIMS: To assess the independent and combined impacts of visit-to-visit fasting blood glucose variability (VVV-FBG) and mean fasting blood glucose level (M-FBG) on all-cause mortality. MATERIALS AND METHODS: This prospective cohort study included 48 843 Chinese patients with type 2 diabetes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association of VVV-FBG and M-FBG with all-cause mortality. The potential nonlinear associations were examined using restricted cubic splines, and additive interaction was evaluated using relative excess risk due to interaction (RERI). Cox generalized additive models (CGAMs) and bivariate response surface models were further used to assess the combined effects of VVV-FBG and M-FBG. RESULTS: A total of 4087 deaths were observed during a median follow-up of 6.99 years. Compared with patients with values at the 5th percentile of average real variability (ARV) and M-FBG, we observed a 23% and 38% increased risk of premature deaths among those with values at the 95th percentile of ARV (HR 1.23, 95% CI 1.10, 1.37) and M-FBG (HR 1.38, 95% CI 1.26, 1.51), respectively. The interaction between glycaemic variability (ARV) and M-FBG was significant on both the additive scale (RERI 0.80 [0.29, 1.32]) and the multiplicative scale (HR 1.90 [1.10, 3.28]). High VVV-FBG and high M-FBG conferred the highest risk of all-cause mortality (HR 1.89, 95% CI 1.64, 2.17), compared to low VVV-FBG and low M-FBG. The CGAMs showed significant synergistic effects between glycaemic variability and M-FBG (P < 0.05). Moreover, a bivariate surface plot showed that risk of death increased more rapidly in type 2 diabetes patients with lower M-FBG combined with lower VVV-FBG. CONCLUSIONS: The coexistence of high glycaemic variability and high glucose level might exacerbate the independent risk of premature mortality in type 2 diabetes patients, highlighting the importance of achieving normal and stable glucose levels simultaneously in the management of glucose.

Environmental tobacco smoke and cancer risk, a prospective cohort study in a Chinese population.

Few prospective cohort studies have investigated associations between environmental tobacco smoke (ETS) and other cancer sites, in addition to lung cancer. We assessed these associations in a population-based prospective cohort study started from 2008 to 2011 with average of 9.1 years of follow-up, in Minhang district, Shanghai, China. The study included a total of 23,415 participants (8388 men, 15,027 women) and 205,515 person-years. Epidemiological data were collected by a standardized questionnaire including ETS exposure. Newly diagnosed patients with primary cancers and deaths were identified by record linkage system with the Shanghai Cancer Registry and Shanghai Vital Statistics. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models, adjusting for potential confounders. During the study period, a total of 1462 patients with diagnoses of primary cancers were identified. Among all participants and non-smokers, ETS was associated with an increased risk of all smoking-related cancers (all: adjusted HR: 1.23, 95% CI: 1.05-1.43 and non-smokers: 1.24, 1.02-1.49), lung cancer (1.29, 0.98-1.71 and 1.27, 0.91-1.77), and stomach cancer (1.86, 1.21-2.85 and 1.75, 1.05-2.91), respectively. Furthermore, associations for lung and stomach cancers were the strongest among non-smoking females. The joint effects of both ETS and active smoking were strongest for all cancers, all smoking-related cancers, lung cancer, and stomach cancer. No clear interactions were observed. These results suggest that ETS exposure may increase the risk of smoking-related cancers in a Chinese population. Further studies on the relationship between ETS exposure and specific cancer sites are warranted to replicate our findings.

The Postoperative Speech Intelligibility Evaluation of Modified Z-Plasty Palatoplasty.

The aim of the present study is to test the feasibility of modified Z-plasty palatoplasty for cleft palate repair in surgeries and provide a new surgical method. Forty cleft palate patients were selected as participants and divided into 2 groups in random. Twenty patients in the experiment group were treated by modified Z-plasty palatoplasty while the other 20 patients in the control group by double opposing Z-plasty and Sommerlad palatoplasty. By evaluating and observing postoperative velopharyngeal movement, speech intelligibility, nasal leaking, analysis of CSL (Computer Structure Language) and X-ray velopharyngeal lateral radiographs, Modified Z-plasty palatoplasty achieved better results than traditional operation. Satisfactory linguistic effects on incomplete cleft palate can be observed after modified Z-plasty palatoplasty treatment. So this method may be used as a clinical choice.

Body mass index and cancer risk among Chinese patients with type 2 diabetes mellitus.

BACKGROUND: Obesity and diabetes are two risk factors for cancer. To evaluate the association of body mass index (BMI) with cancer risk in diabetic patients may improve current understanding of potential mechanisms. METHODS: A retrospective cohort study was conducted in 51,004 newly diagnosed T2DM patients derived from an electronic health record (EHR) database of Minhang district in Shanghai, China. Incident cancer cases and all-cause deaths occurred before September 30, 2015 were identified by linking with the Shanghai Cancer Registry and the Shanghai Vital Statistics. To examine the potential non-linear and linear relationships of BMI and cancer risk, Cox proportional hazard models with and without restricted cubic spline functions were used, respectively. RESULTS: A non-linear association was observed between BMI and overall cancer incidence in men younger than 60 years old (p for non-linearity = 0.009). Compared with those having BMI of 25.0 kg/m2, the cancer risk increased in those with either lower or higher BMI. In women older than 60 years old, linear dose-response relationships were observed between BMI and the risk of both overall cancer and breast cancer. As each unit increase in BMI, the overall cancer risks elevated by 3% (95%CI: 1-5%) and the breast cancer risks increased by 7% (95%CI: 1-13%). No significant association was observed between BMI and other common cancer sites. CONCLUSIONS: Our results show that the effect of BMI on cancer risk in Chinese patients with T2DM may vary by gender, age and cancer subtypes, suggesting different underlying biological mechanisms.

Clinical validation of a novel urine-based metabolomic test for the detection of colonic polyps on Chinese population.

PURPOSE: Colorectal cancer is the fifth leading cause of cancer-related deaths in China. When detected early, with the removal of adenomatous polyps, precursors of colorectal cancer, it is preventable. The aim of this study was to evaluate a novel urine-based metabolomic diagnostic test for the detection of adenomatous polyps, PolypDx™, that was originally developed and validated using 1000 samples from Canadian Cohort, on Chinese population. METHODS: Prospective urine samples were collected from 1000 participants undergoing colonoscopy examination, from March 2013 to July 2014 at Minhang District, Shanghai Centre for Disease Control and Prevention. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to determine the concentrations of three key metabolites used in PolypDx™. The predicted results were then compared to the gold standard for colorectal cancer diagnostic, colonoscopy. Area under curve (AUC) was calculated specifically for the Chinese population and compared with the Canadian dataset. Sensitivity and specificity of this urine-based metabolomic diagnostic test were also compared with three commercially available fecal-based tests. RESULTS: An AUC of 0.717 for PolypDx™ was calculated on Chinese dataset which is slightly lower than the AUC on the Canadian dataset. A sensitivity of 82.6% and a specificity of 42.4% were achieved on Chinese dataset. CONCLUSIONS: Here, we validated a novel urine-based metabolomic diagnostic test for the detection of adenomatous polyps, PolypDx™, on Chinese population through a sample size of 1000 participants with a greater level of sensitivity than fecal-based tests.

Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to investigate the risk of common cancers in Chinese patients with T2DM. METHODS: A population-based retrospective cohort study including 36,379 T2DM patients was conducted in Minhang District of Shanghai, China, during 2004 to 2010. All T2DM patients were enrolled from the standardized management system based on local electronic information system. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. Standardized incidence ratios (SIR) and 95% confidence interval (CI) were used to estimate the risk of cancers among T2DM patients. RESULTS: Overall crude incidence rate (CIR) of cancers was 955.21 per 105 person-years in men and 829.57 per 105 person-years in women. Increased risk of cancer was found in both gender, with an SIR being 1.28 (95% CI = 1.17-1.38) in men and 1.44 (95% CI =1.32-1.55) in women. Increased risk of colon (SIR = 1.97; 95% CI = 1.49 to 2.46), rectum (1.72; 1.23 to 2.21), prostate (2.87; 2.19 to 3.56), and bladder cancers (1.98, 1.28 to 2.68) were observed in men and elevated risk of colon (1.67; 1.25 to 2.08), breast (1.66; 1.38 to 1.95), and corpus uteri cancers (2.87; 2.03 to 3.71) were observed in women. CONCLUSIONS: Our results indicate that Chinese patients with T2DM may have an increased risk of some cancers, and the increase may vary by sub-sites of cancers.

Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

BACKGROUND: Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. METHODS: We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. RESULTS: Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. CONCLUSION: This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.

Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity < 0.01), and the RRs (95 % CI) of type 2 diabetes were 0.98 (0.90-1.06), 0.97 (0.87-1.07), 0.89 (0.80-0.99), 0.76 (0.65-0.88), and 0.66 (0.53-0.82) for 15, 20, 25, 30, and 35 g/day. The departure from nonlinear relationship was not significant (P for nonlinearity = 0.72), and the risk of type 2 diabetes decreased by 6 % (RR 0.94, 95 % CI 0.93-0.96) for 2 g/day increment in cereal fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

LincRNA-EPS inhibits caspase-11 and NLRP3 inflammasomes in gingival fibroblasts to alleviate periodontal inflammation.

To investigate the effects of long intergenic noncoding RNA-erythroid prosurvival (lincRNA-EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA-EPS-/- ) and WT (lincRNA-EPS+/+ ) mice to compare the periodontal bone loss and inflammation by using micro-computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate-specific proteinase-11 (caspase-11) and NOD-like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor-kappa B (NF-κB) activation in mouse gingival fibroblasts (MGFs), were measured by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA-EPS. RNA pull-down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA-EPS. LincRNA-EPS-expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA-EPS increased bone loss and expression of myeloperoxidase, interleukin-1α (IL-1α) and IL-1ß in the inflammatory periodontium. LincRNA-EPS KO MGFs exhibited increased expression and activation of caspase-11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA-EPS overexpressed MGFs. Mechanistically, lincRNA-EPS directly bound to transactive response DNA-binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF-κB activation and the inflammasomes as lincRNA-EPS overexpression. Locally injecting lincRNA-EPS-expressing lentivirus weakened the periodontal damage. LincRNA-EPS inhibits the LPS-induced production and activation of caspase-11 and NLRP3 inflammasomes by suppressing the activation of the NF-κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis.

Measuring Interactions Between Proteins and Small Molecules or Nucleic Acids.

Interactions between proteins and small molecules or nucleic acids play a pivotal role in numerous biological processes critical for human health and are fundamental for advancing our understanding of biological systems. Proteins are the workhorses of the cell, executing various functions ranging from catalyzing biochemical reactions to transmitting signals within the body. Small molecules, including drugs and metabolites, can modulate protein activity, thereby impacting cellular processes and disease pathways. Similarly, nucleic acids, such as DNA and RNA, regulate protein synthesis and function through intricate interactions. Understanding these interactions is crucial for drug discovery and development and can shed light on gene regulation, transcriptional control, and RNA processing, providing insights into genetic diseases and developmental disorders. Moreover, studying protein-small molecule and protein-nucleic acid interactions enhances our comprehension of fundamental biological mechanisms. A wide array of methods to study these interactions range in cost, sensitivity, materials usage, throughput, and complexity. Notably in the last decade, new techniques have been developed that enhance our understanding of these interactions. In this review, we aim to summarize the new state-of-the-art methods for detecting interactions between proteins and small molecules or nucleic acids, as well as discuss older methods that still hold value today. © 2024 Wiley Periodicals LLC.

Interaction between body mass index and family history of cancer on the risk of female breast cancer.

Both body mass index (BMI) and family history of cancer are established risk factors for female breast cancer. However, few studies explored the potential interaction between both factors. We assessed the association of BMI and its interaction with family cancer history on the risk of female breast cancer in Shanghai, China. Based on a population-based prospective cohort study started from 2008 to 2012 with 15,055 Chinese female participants in Minhang district, Shanghai. Cox regression models were used to estimate the association of BMI and its interaction with a family history of cancer on breast cancer risk. The additive interaction was evaluated by the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP), and the multiplicative interaction was assessed by the product term (BMI* family history of cancer) in the Cox regression model. Compared with BMI of < 24 kg/m2 and no family history of cancer, women with BMI of ≥ 24 kg/m2 and a family history of cancer had a higher risk for breast cancer with HR 2.06 (95% CI 1.39, 3.06). There was an additive interaction between BMI and family history of cancer on breast cancer incidence, with the RERI being 0.29 (95% CI 0.08, 0.51) and the AP being 0.37 (95% CI 0.08, 0.66). The coexistence of obesity and cancer family history may exacerbate breast cancer incidence risk, highlighting the importance of weight management in women with a family history of cancer.

[Effectiveness Evaluation of Low-dose Spiral Computed Tomography 
for Lung Cancer Screening in Minhang District of Shanghai].

BACKGROUND: Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013. METHODS: A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases. RESULTS: The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases. CONCLUSIONS: The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.