Association between exposure to per- and polyfluoroalkyl substance and liver injury in American adults.

Epidemiological data is scarce regarding the association between exposure to mixtures of per- and polyfluoroalkyl substances (PFASs) and liver injury in the general populace. The current research used data from the National Health and Nutrition Examination Survey (2009-2018). The PFAS exposure levels were defined by the serum concentrations of PFASs with > 70% detection in samples, namely perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDeA), and perfluorooctane sulfonic acid (PFOS). Liver injury was assessed from two aspects: first, the degree of liver inflammation was determined based on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), and total bilirubin (TBIL) levels; second, the degree of liver fibrosis was determined based on fibrosis-4 (FIB-4) index. We assessed the associations between individual or total PFAS exposure and these outcomes using multivariable linear regression models and logistic regression models, restricted cubic splines, and weighted quantile sum regression. Among the samples of 7484 American adults, the median concentration of PFOS was the highest, followed by PFOA and PFHxS. Using multivariable linear regression, a positive correlation was observed between all PFASs and liver enzymes such as ALT, AST, and TBIL. Additionally, the weighted quantile sum model indicated an overall positive association between the five PFASs and liver injury indicators. For liver function biomarkers and liver fibrosis, PFNA and PFOS were the most heavily weighting chemicals, respectively. Our findings provide new epidemiological evidence indicating a potential association between PFAS exposure and adverse effects on liver injury biomarkers, highlighting the potentially harmful effects of PFAS exposure on liver health.

Comparison of Clinical Characteristics and Outcomes of MAFLD and NAFLD in Chinese Health Examination Populations.

Background and Aims: The recently proposed concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has remained controversial. We aimed to describe the features and associated outcomes to examine the diagnostic ability of MAFLD for identifying high-risk individuals. Methods: In this retrospective cohort study, we enrolled 72,392 Chinese participants between 2014 and 2015. Participants were classified as MAFLD, nonalcoholic fatty liver disease (NAFLD), non-MAFLD-NAFLD, and a normal control group. The primary outcomes were liver-related and cardiovascular disease (CVD) events. Person-years of follow-up were calculated from enrolment to the diagnosis of the event, or the last date of data (June, 2020). Results: Of the 72,392 participants, 31.54% (22,835) and 28.33% (20,507) qualified the criteria for NAFLD or MAFLD, respectively. Compared with NAFLD, MAFLD patients were more likely to be male, overweight, and have higher biochemical indices including liver enzyme levels. Lean MAFLD diagnosed with ≥2 or ≥3 metabolic abnormalities presented similar clinical manifestations. During the median follow-up of 5.22 years, 919 incident cases of severe liver disease and 2,073 CVD cases were recorded. Compared with the normal control group, the NAFLD and MAFLD groups had a higher cumulative risk of liver failure and cardiac-cerebral vascular diseases. There were no significant differences in risk between the non-MAFLD-NAFLD and normal group. Diabetes-MAFLD group had the highest incidence of liver-related and cardiac-cerebral vascular diseases, lean MAFLD came second, and obese-MAFLD had the lowest incidence. Conclusions: This real-world study provided evidence for rationally assessing the benefit and practicability of the change in terminology from NAFLD to MAFLD. MAFLD may be better than NAFLD in identifying fatty liver with worse clinical features and risk profile.

One-Pot Self-Assembly of Core-Shell Nanoparticles within Fibers by Coaxial Electrospinning for Intestine-Targeted Delivery of Curcumin.

Nanotechniques for curcumin (Cur) encapsulation provided a potential capability to avoid limitations and improve biological activities in food and pharmaceutics. Different from multi-step encapsulation systems, in this study, zein-curcumin (Z-Cur) core-shell nanoparticles could be self-assembled within Eudragit S100 (ES100) fibers through one-pot coaxial electrospinning with Cur at an encapsulation efficiency (EE) of 96% for ES100-zein-Cur (ES100-Z-Cur) and EE of 67% for self-assembled Z-Cur. The resulting structure realized the double protection of Cur by ES100 and zein, which provided both pH responsiveness and sustained release performances. The self-assembled Z-Cur nanoparticles released from fibermats were spherical (diameter 328 nm) and had a relatively uniform distribution (polydispersity index 0.62). The spherical structures of Z-Cur nanoparticles and Z-Cur nanoparticles loaded in ES100 fibermats could be observed by transmission electron microscopy (TEM). Fourier transform infrared spectra (FTIR) and X-ray diffractometer (XRD) revealed that hydrophobic interactions occurred between the encapsulated Cur and zein, while Cur was amorphous (rather than in crystalline form). Loading in the fibermat could significantly enhance the photothermal stability of Cur. This novel one-pot system much more easily and efficiently combined nanoparticles and fibers together, offering inherent advantages such as step economy, operational simplicity, and synthetic efficiency. These core-shell biopolymer fibermats which incorporate Cur can be applied in pharmaceutical products toward the goals of sustainable and controllable intestine-targeted drug delivery.

Behavioural activity pattern, genetic factors, and the risk of nonalcoholic fatty liver disease: A prospective study in the UK Biobank.

BACKGROUND & AIMS: Physical activity, sedentary behaviour, and genetic variants have been associated with the nonalcoholic fatty liver disease (NAFLD). However, whether and how the degree of healthy activity patterns may modify the impact of genetic susceptibility on NAFLD remains unknown. METHODS: Behaviour activity factors were determined according to total physical activity (TPA) and sedentary time. The polygenic risk score (PRS) was calculated by variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Cox regression was used to analyse the associations of genetic and behaviour activity factors with incident NAFLD in the UK Biobank (N = 338 087). RESULTS: During a median follow-up of 12.4 years, 3201 incident NAFLD cases were ascertained. Analyses of TPA and sedentary time simultaneously showed a dose-response association with the risk of NAFLD (ptrend < .001). The association of behaviour activity patterns with NAFLD varied by genetic variants. Of the subjects with high genetic risk, we observed a null protective effect of moderate or high TPA on NAFLD risk, while sitting less than three hours a day significantly decreased the risk of NAFLD (p = 3.50 × 10-4 ). The high genetic risk of NAFLD can also be offset by the combination of moderate physical activity and shorter sedentary time. Moreover, the high genetic risk group has the greatest reduction of 10-year absolute risk (6.95 per 1000 person-years) if reaching both healthy activities. CONCLUSIONS: Moderate-to-high physical activity and favourable sedentary behaviour may be lifestyle modifications in preventing NAFLD, which could offset the harmful effect of predisposing genetic factors.

RG-I Domain Matters to the In Vitro Fermentation Characteristics of Pectic Polysaccharides Recycled from Citrus Canning Processing Water.

Canned citrus is a major citrus product that is popular around the world. However, the canning process discharges large amounts of high-chemical oxygen demand wastewater, which contains many functional polysaccharides. Herein, we recovered three different pectic polysaccharides from citrus canning processing water and evaluated their prebiotic potential as well as the relationship between the RG-I domain and fermentation characteristics using an in vitro human fecal batch fermentation model. Structural analysis showed a large difference among the three pectic polysaccharides in the proportion of the rhamnogalacturonan-I (RG-I) domain. Additionally, the fermentation results showed that the RG-I domain was significantly related to pectic polysaccharides' fermentation characteristics, especially in terms of short-chain fatty acid generation and modulation of gut microbiota. The pectins with a high proportion of the RG-I domain performed better in acetate, propionate, and butyrate production. It was also found that Bacteroides, Phascolarctobacterium, and Bifidobacterium are the main bacteria participating in their degradation. Furthermore, the relative abundance of Eubacterium_eligens_group and Monoglobus was positively correlated with the proportion of the RG-I domain. This study emphasizes the beneficial effects of pectic polysaccharides recovered from citrus processing and the roles of the RG-I domain in their fermentation characteristics. This study also provides a strategy for food factories to realize green production and value addition.

Goji berry leaf exerts a comparable effect against colitis and microbiota dysbiosis to its fruit in dextran-sulfate-sodium-treated mice.

Goji berry and mulberry are both popular berries with anti-colitis effects, but their leaves have received less attention. In this study, the anti-colitis effects of goji berry leaf and mulberry leaf were investigated in dextran-sulfate-sodium-induced colitis C57BL/6N mice compared with their fruits. Goji berry leaf and goji berry reduced colitic symptoms and ameliorated tissue damage, while mulberry leaf did not. ELISA and western blotting analysis suggested that goji berry showed the best performance in inhibiting the overproduction of pro-inflammatory cytokines (TNF-α, IL-6 and IL-10) and improving damaged colonic barrier (occludin and claudin-1). Besides, goji berry leaf and goji berry reversed the gut microbiota dysbiosis by increasing the abundance of beneficial bacteria like Bifidobacterium and Muribaculaceae, and decreasing the abundance of harmful bacteria like Bilophila and Lachnoclostridium. Goji berry, mulberry and goji berry leaf could restore acetate, propionate, butyrate and valerate to ameliorate inflammation, while mulberry leaf could not restore butyrate. To the best of our knowledge, this is the first report on the comparison of the anti-colitis effects of goji berry leaf, mulberry leaf and their fruits, which is meaningful for the rational utilization of goji berry leaf as a functional food.

RGI-Type Pectic Polysaccharides Modulate Gut Microbiota in a Molecular Weight-Dependent Manner In Vitro.

In this study, the fermentation characteristics of high rhamnogalacturonan I pectic polysaccharides (RGI) and free-radical degraded RGI (DRGI) were evaluated by a human fecal batch-fermentation model, and their structural properties were also investigated. As a result, the Mw of RGI decreased from 246.8 to 11.6 kDa, and the branches were broken dramatically. Fermentation showed that RGI degraded faster and produced more acetate and propionate than DRGI. Both of them reduced the Firmicutes/Bacteroidetes ratio and promoted the development of Bacteroides, Bifidobacterium, and Lactobacillus, bringing benefits to the gut ecosystem. However, the composition and metabolic pathways of the microbiota in RGI and DRGI were different. Most of the dominant bacteria of RGI (such as [Eubacterium]_eligens_group) participated in carbohydrate utilization, leading to better performance in glucolipid metabolism and energy metabolism. This work elucidated that large molecular weight matters in the gut microbiota modulatory effect of RGI-type pectic polysaccharides in vitro.

Diet and Risk of Non-Alcoholic Fatty Liver Disease, Cirrhosis, and Liver Cancer: A Large Prospective Cohort Study in UK Biobank.

Background and Aims: Epidemiological evidence has shown the association between nutritional habits and liver disease. However, results remain conflicting. This study investigated the influence of dietary factors on the risk of incident non-alcoholic fatty liver disease (NAFLD), cirrhosis, and liver cancer. Methods: Data from the UK Biobank database were analyzed (n = 372,492). According to baseline data from the food frequency questionnaire, two main dietary patterns (Western and prudent) were identified using principal component analysis. We used cox proportional hazards models to explore the associations of individual food groups and dietary patterns with NAFLD, cirrhosis, and liver cancer. Results: During a median follow-up of 12 years, 3527 hospitalized NAFLD, 1643 cirrhosis, and 669 liver cancer cases were recorded among 372,492 participants without prior history of cancer or chronic liver diseases at baseline. In multivariable adjusted analysis, participants in the high tertile of Western dietary pattern score had an 18% (95%CI = 1.09−1.29), 21% (95%CI = 1.07−1.37), and 24% (95%CI = 1.02−1.50) higher risk of incident NAFLD, liver cirrhosis, and liver cancer, respectively, compared with the low tertile. Participants in the high tertile of prudent scores had a 15% (95%CI = 0.75−0.96) lower risk of cirrhosis, as compared with those in the low tertile. In addition, the higher consumption of red meat and the lower consumption of fruit, cereal, tea, and dietary fiber were significantly associated with a higher risk of NAFLD, cirrhosis, and liver cancer (ptrend < 0.05). Conclusions: This large prospective cohort study showed that an increased intake of food from the Western dietary pattern could be correlated with an increased risk of chronic liver diseases, while the prudent pattern was only correlated with a reduced liver cirrhosis risk. These data may provide new insights into lifestyle interventions for the prevention of chronical liver diseases.

Healthy Lifestyle Is Associated with Reduced Mortality in Patients with Non-Alcoholic Fatty Liver Disease.

Background and Aims: It is unclear whether a healthy lifestyle impacts mortality in the presence of non-alcoholic fatty liver disease (NAFLD). The present study aimed to examine the joint association of several modifiable lifestyle factors with mortality risk for NAFLD patients. Methods: We collected lifestyle behavior data form the National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and follow-up data form NHANES III-linked mortality data through 2015. We estimated joint association between four healthy lifestyle factors (non-smoking, non-drinking, regular physical activity, a healthy diet) after NAFLD diagnosis and mortality using Cox proportional hazards regression models. Results: During a median of 22.83 years of follow-up, 2932 deaths occurred. The risk of all-cause mortality decreased significantly with the healthy lifestyle scores increasing (p < 0.001). NAFLD patients with a favorable lifestyle (3 or 4 healthy lifestyle factors) reduced 36% of all-cause mortality and 43% of cardiovascular disease (CVD) mortality compared with those with an unfavorable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.64 [95% CI, 0.50−0.81], 0.57 [95% CI, 0.37−0.88]). Compared with the non-NAFLD group, the number of NAFLD patients required to adhere to a favorable lifestyle to prevent one cardiovascular disease death in 20 years was fewer (77 vs. 125). Conclusions: For the NAFLD patients, adopting a healthy lifestyle could significantly reduce their risk of death.

Weight Change across Adulthood in Relation to Non-Alcoholic Fatty Liver Disease among Non-Obese Individuals.

BACKGROUND: To investigate the associations of weight change patterns across adulthood with the risk of non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle, we performed a retrospective cohort study with 2212 non-obese participants aged 36 years old over. Weight change patterns were categorized as "stable non-obese", "early adulthood weight gain", "middle and late adulthood weight gain" and "revert to non-obese" according to the body mass index (BMI) at age 25, 10 years prior and at baseline. Vibration-controlled transient elastography (VCTE) was performed to diagnose NAFLD. Modified Poisson regression was used to quantify the associations of weight change patterns with NAFLD. RESULTS: Compared with participants in the "stable non-obese" group, those who gained weight at early or middle and late adulthood had an increased risk of NAFLD, with an adjusted rate ratio (RR) of 2.19 (95% CI 1.64-2.91) and 1.92 (95% CI 1.40-2.62), respectively. The risk of NAFLD in "revert to the non-obese" group showed no significant difference with the stable non-obese group. If the association of weight change and NAFLD was causal, we estimated that 73.09% (95% CI 55.62-82.93%) of incident NAFLD would be prevented if the total population had a normal BMI across adulthood. CONCLUSIONS: Weight gain to obese at early or middle and late adulthood was associated with an evaluated risk of NAFLD. A large proportion would have been prevented with effective weight intervention.

The prevalence of nonalcoholic fatty liver disease in Chinese adults screened by vibration controlled transient elastography and its diagnostic discrepancy compared with ultrasound.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques. METHODS: We collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound. RESULTS: Among the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P < 0.001), were obese (45.09% vs. 1.79%, P < 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter. CONCLUSIONS: More than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.

Structure and In Vitro Fermentation Characteristics of Polysaccharides Sequentially Extracted from Goji Berry (Lycium barbarum) Leaves.

Herein, the chelating agent-soluble fraction (CA), sodium carbonate-soluble fraction (SC), and sodium hydroxide-soluble fraction (SH) were sequentially extracted from the cell wall of goji berry (Lycium barbarum) leaves. Furthermore, SC was purified with Q-Sepharose fast flow resin to obtain the neutral sugar fraction (SC-I) and acid sugar fraction (SC-II). Physicochemical properties of polysaccharides were characterized by high-performance anion-exchange chromatography with pulsed amperometry detection, size exclusion chromatography-multi-angle laser light scattering, Fourier transform infrared spectroscopy, nuclear magnetic resonance, and atomic force microscopy analysis. Additionally, the impact of polysaccharides on modulating human gut microbiota was investigated by in vitro fermentation. A high amount of galacturonic acid (GalA) in CA showed that it was an aggregation of linear homogalacturonan. SC was the main pectic polysaccharide fraction and rich in neutral sugars. SC-I was the neutral sugar fraction with an extremely high molecular weight (2.055 × 106 Da), while SC-II was the acid sugar fraction with a low molecular weight (1.766 × 105 Da). SH seemed like a mixture of pectin and hemicellulose. All the five polysaccharides significantly (P < 0.05) increased the abundance of Bacteroides, Bifidobacteria, and Lactobacilli. To the best of our knowledge, this is the first report on the structure and fermentation characteristics of goji berry leaf polysaccharides, which is meaningful to provide a structural basis for further bioactivity research.

Enzyme-extracted raspberry pectin exhibits a high-branched structure and enhanced anti-inflammatory properties than hot acid-extracted pectin.

To characterize the structure of purified raspberry pectin and discuss the impact of different extraction methods on the pectin structure, raspberry pectin was extracted by hot-acid and enzyme method and purified by stepwise ethanol precipitation and ion-exchange chromatography isolation. Enzyme-extracted raspberry pectin (RPE50%-3) presented relatively intact structure with molecular weight of 5 × 104 g/mol and the degree of methylation was 39%. The 1D/2D NMR analysis demonstrated RPE50%-3 was a high-branched pectin mainly containing 50% homogalacturonan, 16% branched α-1,5-arabinan and α-1,3-arabinan, 18% ß-1,4-galactan and ß-1,6-galactan. Acid-extracted raspberry pectin (RPA50%-3) contained less arabinan than RPE50%-3. Moreover, RPE50%-3 inhibited the nitric oxide (NO), TNF-α, IL-6 production of lipopolysaccharide-induced macrophages by 67%, 22% and 46% at the dosage of 200 ug/mL, while the inhibitory rate of RPA50%-3 were 33%, 9%, and 1%, respectively. These results suggested that enzyme-extracted raspberry pectin contained more arabinan sidechains and exhibited better immunomodulatory effect.

Adherence to Healthy Lifestyle and Liver cancer in Chinese: a prospective cohort study of 0.5 million people.

BACKGROUND: Little prospective evidence exists about whether a combination of healthy lifestyle factors is related to a considerable reduction of liver cancer risk. METHODS: Based on the prospective China Kadoorie Biobank (CKB) cohort with a total of 492,640 Chinese adults, we examined the associations of five lifestyle factors with risk of liver cancer. Low-risk lifestyle factors were defined as non-smoking, non-drinking, median or higher level of physical activity, a healthy diet, and waist-to-hip ratio (WHR) < 0.90 for men and <0.85 for women. RESULTS: During a median of 10.12 years of follow-up, 2529 liver cancer events were observed. There was a significant decrease in liver cancer risk with the increasing of the healthy lifestyle index scores (P < 0.001). Participants with a favourable lifestyle (4 or 5 healthy lifestyle factors) had a 43% reduced liver cancer risk compared with those with an unfavourable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.57 [95% CI, 0.47-0.68]). The cumulative protective effect of a healthy lifestyle on liver cancer appeared to be more dramatic for patients with hepatitis B surface antigen (HBsAg) positive, the individuals at high risk of liver cancer. CONCLUSIONS: Individuals adhering to a favourable lifestyle was associated with a considerable absolute risk reduction of liver cancer.

Effect of Smoking on Lung Function Decline in a Retrospective Study of a Health Examination Population in Chinese Males.

Objective: China has established a goal of reducing adult smoking prevalence from 27.7% to 20% by 2030. Understanding the possible ongoing impairment in lung function in smokers, is critically important to encourage the populations to change their smoking behavior. Methods: A total of 14,273 males joined the health examination at Huadong Sanatorium from Jan 2012 to Dec 2019 were included. In cross-sectional analysis, we used multiple linear regression to evaluate the association between baseline lung function and smoking status. Then, 3,558 males who received ≥2 spirometry exams were analyzed in longitudinal study. Annual lung function decline was compared using mixed linear models adjusted for confounders. Results: In cross-sectional analysis, compared with never-smokers, decreases of -133.56 mL (95% CI: -167.27, -99.85) and -51.44 mL (-69.62, -33.26) in FEV1, -1.48% (-1.94, -1.02) and -1.29% (-1.53, -1.04) in FEV1/FVC were observed in former and current smokers. In longitudinal analysis, significant declines were observed in FEV1 [5.04 (2.30, 7.78) mL] and FEV1/FVC [0.09 (0.05, 0.13) %] in current smokers but not observed in former smokers after adjustment. Participants with long duration of smoking cessation had decelerate lung function than short duration. The annual decline rate of current smokers with high smoking intensity (≥30 cigarettes per day) was 13.80 and 14.17 times greater than that of never-smokers in FEV1 and FVC. Thus, early smoking cessation can slow down lung function decline trend for current smokers. Conclusions: The harms of current smoking on lung function emphasize the necessity of smoking cessation, especially for those with comorbidities.

Maternal mortality ratio in Jiangsu Province, China: recent trends and associated factors.

BACKGROUND: In recent years, births to older mothers and multiparous mothers have increased rapidly with the change of birth policy in China. And mothers of advanced age are more likely to have maternal complications and poor birth outcomes. We aimed to estimate the recent trends and underlying risk factors of maternal mortality. METHODS: In this systematic assessment, we used data from the National Maternal and Child Health Routine Reporting System (2013-2018), Jiangsu Provincial Maternal Mortality Surveillance System (2017-2018), the Integrated National Mortality Surveillance System (2018), City Statistical Yearbooks (2018), City Health Statistical Yearbooks (2018). The factors associated with maternal mortality ratio (MMR) were explored using the stepwise regression analysis and cluster analysis. RESULTS: The MMR maintained at low levels between 2013 and 2016 and there was a slight increase in maternal mortality after 2016 in Jiangsu province. With the implementation of the China's universal two child policies, the percentage of multiparous mothers ascended from 34.2% (95% confidence interval (CI) = 34.1-34.3%) in 2013 to 51.4% (95% CI = 51.3-51.6%) in 2018 (beta = 3.88, P < 0.001). Consistently, the percentage of advanced maternal age (≥ 35) increased from 8.4% (95% CI = 8.4-8.5%) in 2013 to 10.4% (95% CI = 10.3-10.4%) in 2018 (beta = 0.50, P = 0.012). And we found that the percentage of multiparous mothers and advanced maternal age among maternal deaths were higher than all pregnant women (P < 0.001). In the stepwise regression analysis, four risk factors were significantly associated with maternal mortality ratio (primary industry of gross domestic product (GDP), rate of delivery in maternal and child health hospital, rate of cesarean section and rate of low birth weight). As the results derived from cluster analysis, the relatively developed regions had lower preventable maternal mortality ratio (43.5% (95% CI = 31.2-56.7%) vs. 62.6% (95% CI = 52.3-72.0%), P = 0.027). CONCLUSIONS: Since the universal two child policy has been associated with changes in health related birth characteristics: women giving birth have been more likely to be multiparous, and more likely to be aged 35 and over. This somewhat magnifies the impact of differences in economic development and obstetric services on MMR. The findings based on prefecture level data suggest that interventions must target economic development, the health system and maternal risk factors in synergy. These approaches will be of great benefit to control or diminish environmental factors associated with preventable deaths and will effectively reduce MMR and narrow the gap among the different regions.

Prediction and clinical utility of a liver cancer risk model in Chinese adults: A prospective cohort study of 0.5 million people.

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up-to-date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10-year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person-years of follow-up. Excellent discrimination of the model was observed in both development and validation datasets, with c-statistics (95% CI) of 0.80 (0.79-0.81) and 0.80 (0.78-0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10-year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB-PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high-risk groups among the general population.

Dietary pectic substances enhance gut health by its polycomponent: A review.

Pectic substances, one of the cell wall polysaccharides, exist widespread in vegetables and fruits. A surge of recent research has revealed that pectic substances can inhibit gut inflammation and relieve inflammatory bowel disease symptoms. However, physiological functions of pectins are strongly structure dependent. Pectic substances are essentially heteropolysaccharides composed of homogalacturonan and rhamnogalacturonan backbones substituted by various neutral sugar sidechains. Subtle changes in the architecture of pectic substances may remarkably influence the nutritional function of gut microbiota and the host homeostasis of immune system. In this context, developing a structure-function understanding of how pectic substances have an impact on an inflammatory bowel is of primary importance for diet therapy and new drugs. Therefore, the present review has summarized the polycomponent nature of pectic substances, the activities of different pectic polymers, the effects of molecular characteristics and the underlying mechanisms of pectic substances. The immunomodulated property of pectic substances depends on not only the chemical composition but also the physical structure characteristics, such as molecular weight (Mw ) and chain conformation. The potential mechanisms by which pectic substances exert their protective effects are mainly reversing the disordered gut microbiota, regulating immune cells, enhancing barrier function, and inhibiting pathogen adhesion. The manipulation of pectic substances on gut health is sophisticated, and the link between structural specificity of pectins and selective regulation needs further exploration.

Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population.

BRCA1 and BRCA2 as important DNA repair genes have been thoroughly investigated in abundant studies. The potential relationships of BRCA1/2 pathogenic variants between multicancers have been verified in Caucasians but few in Chinese. In this study, we performed a two-stage study to screen BRCA1/2 pathogenic variants or variants of uncertain significance (VUS) with 7580 cancer cases and 4874 cancer-free controls, consisting of a discovery stage with 70 familial breast cancer cases and a subsequent validation stage with 7510 cases (3217 breast cancer, 1133 cervical cancer, 2044 hepatocellular carcinoma, and 1116 colorectal cancer). 48 variants were obtained from 70 familial breast cancer cases after BRCA1/2 exon detection, and finally, 20 pathogenic variants or VUS were selected for subsequent validation. Four recurrent variants in sporadic cases (BRCA1 c.4801A>T, BRCA1 c.3257del, BRCA1 c.440del, and BRCA2 c.7409dup) were identified and three of them were labeled Class 5 by ENIGMA. Two variants (BRCA1 c.3257del and c.440del) were specific in breast cancer cases, while BRCA2 c.7409dup and c.4307T>C were detected in two hepatocellular carcinoma patients and the BRCA1 c.4801A>T variant in one cervical cancer patient, respectively. Moreover, BRCA1 c.3257del was the most frequent variant observed in Chinese sporadic breast cancer and showed increased proliferation of BRCA1 c.3257del-overexpressing triple-negative breast cancer cell lines (MDA-MB-231) in vitro. In addition to the known founder deleterious mutations, our findings highlight that the recurrently pathogenic variants in breast cancer cases could be taken as candidate genetic screening loci for a more efficient genetic screening of the Chinese population.