FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.

Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell RNA sequencing was carried out on 38 MB tissues, followed by expression enrichment assays. Fanconi anemia group D2 gene (FANCD2) expression was evaluated in MB samples and public MB databases. The function of FANCD2 in MB cells was examined using cell counting assays (CCK-8), clone formation, lactate dehydrogenase activity, and in mouse orthotopic models. The FANCD2-related signaling pathway was investigated using assays of peroxidation, a malondialdehyde assay, a reduced glutathione assay, and using FerroOrange to assess intracellular iron ions (Fe2+ ). Here, we report that FANCD2 was highly expressed in the malignant sonic hedgehog (SHH) MB subtype (SHH-MB). FANCD2 played an oncogenic role and predicted worse prognosis in SHH-MB patients. Moreover, FANCD2 knockdown markedly suppressed viability, mobility, and growth of SHH-MB cells and sensitized SHH-MB cells to irradiation. Mechanistically, FANCD2 deficiency led to an accumulation of Fe2+ due to increased divalent metal transporter 1 expression and impaired glutathione peroxidase 4 activity, which further activated ferroptosis and reduced proliferation of SHH-MB cells. Using an orthotopic mouse model, we observed that radiotherapy combined with silencing FANCD2 significantly inhibited the growth of SHH-MB cell-derived tumors in vivo. Our study revealed FANCD2 as a potential therapeutic target in SHH-MB and silencing FANCD2 could sensitize SHH-MB cells to radiotherapy via inducing ferroptosis. © 2024 The Pathological Society of Great Britain and Ireland.

Factors affecting long-term myopic regression after corneal refractive surgery for civilian pilots in southwest China.

BACKGROUND: The purpose of this study was to analyze myopic regression after corneal refractive surgery (CRS) in civilian pilots and to explore the factors that may cause long-term myopic regression. METHODS: We included civilian pilots who had undergone CRS to correct their myopia and who had at least 5 years of follow-up. We collected retrospective data and completed eye examinations and a questionnaire to assess their eye habits. RESULTS: A total of 236 eyes were evaluated in this study. 211 eyes had Intrastromal ablations (167 eyes had laser in situ keratomileusis, LASIK, 44 eyes had small incision lenticule extraction, SMILE) and 25 eyes had subepithelial ablations (15 eyes had laser epithelial keratomileusis, LASEK and 10 eyes had photorefractive keratectomy, PRK). The mean preoperative spherical equivalent (SE) was - 2.92 ± 1.11 D (range from - 1.00 to -5.00 D). A total of 56 eyes (23.6%) suffered from myopic regression after CRS. Comparisons of individual and eye characteristics between the regression and non-regression groups revealed statistically significant differences in age, cumulative flight time, postoperative SE (at 6 months and current), uncorrected visual acuity (UCVA), accommodative amplitude (AA), positive relative accommodation (PRA), postoperative period, types of CRS and eye habits. Generalized propensity score weighting (GPSW) was used to balance the distribution of covariates among different age levels, types of CRS, cumulative flying time, postoperative period and continuous near-work time. The results of GPS weighted logistic regression demonstrated that the associations between age and myopic regression, types of CRS and myopic regression, continuous near-work time and myopic regression were significant. Cumulative flying time and myopic regression, postoperative period and myopic regression were no significant. Specifically, the odds ratio (OR) for age was 1.151 (P = 0.022), and the OR for type of CRS was 2.769 (P < 0.001). The OR for continuous near-work time was 0.635 with a P value of 0.038. CONCLUSIONS: This is the first report to analyze myopic regression after CRS in civilian pilots. Our study found that for each year increase in age, the risk of civilian pilots experiencing myopic regression was increased. Intrastromal ablations had a lower risk of long-term myopia regression than subepithelial ablations. There is a higher risk of myopic progression with continuous near-work time > 45 min and poor accommodative function may be related factors in this specific population.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

White matter changes in young and middle-aged males with chronic prostatitis/chronic pelvic pain syndrome: Tract-based spatial statistics analysis.

The supraspinal mechanism plays a key role in developing and maintaining chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, it is not clear how white matter changes in young and middle-aged males with CP/CPPS. In this cross-sectional study, 23 CP/CPPS patients and 22 healthy controls (HCs) were recruited. Tract-based spatial statistics was applied to investigate the differences in diffusion tensor imaging metrics, including fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD) and axial diffusion (AD), between CP/CPPS patients and HCs. The study also examined the association between white matter alterations and clinical variables in patients using correlation analysis. Compared with HCs, patients showed decreased FA, MD, RD and AD in the body and genu of the corpus callosum and right anterior corona radiata. In addition, they showed increased FA along with decreased MD, RD and AD in the left posterior limb of the internal capsule (PLIC-L), left external capsule and left cerebral peduncle. The FA of PLIC-L was negatively correlated with disease duration (r = -.54, corrected p = .017), while MD and RD were positively correlated (r = .45, corrected p = .042; r = .57, corrected p = .017). These results suggest that CP/CPPS is associated with extensive changes in white matter tracts, which are involved in pain processing. In particular, the FA, MD and RD values in the PLIC-L were correlated with the disease duration, indicating that the long-term course of CP/CPPS may have effects on the white matter microstructure of the pain perception pathways.

CA916798 predicts poor prognosis and promotes Gefitinib resistance for lung adenocarcinoma.

BACKGROUND: Our previous studies have identified CA916798 as a chemotherapy resistance-associated gene in lung cancer. However, the histopathological relevance and biological function of CA916798 in lung adenocarcinoma (LUAD) remains to be delineated. In this study, we further investigated and explored the clinical and biological significance of CA916798 in LUAD. METHODS: The relationship between CA916798 and clinical features of LUAD was analyzed by tissue array and online database. CCK8 and flow cytometry were used to measure cell proliferation and cell cycle of LUAD after knockdown of CA916798 gene. qRT-PCR and western blotting were used to detect the changes of cell cycle-related genes after knockdown or overexpression of CA916798. The tumorigenesis of LUAD cells was evaluated with or without engineering manipulation of CA916798 gene expression. Response to Gefitinib was evaluated using LUAD cells with forced expression or knockdown of CA916798. RESULTS: The analysis on LUAD samples showed that high expression of CA916798 was tightly correlated with pathological progression and poor prognosis of LUAD patients. A critical methylation site in promoter region of CA916798 gene was identified to be related with CA916798 gene expression. Forced expression of CA916798 relieved the inhibitory effects of WEE1 on CDK1 and facilitated cell cycle progression from G2 phase to M phase. However, knockdown of CA916798 enhanced WEE1 function and resulted in G2/M phase arrest. Consistently, chemical suppression of CDK1 dramatically inhibited G2/M phase transition in LUAD cells with high expression of CA916798. Finally, we found that CA916798 was highly expressed in Gefitinib-resistant LUAD cells. Exogenous expression of CA916798 was sufficient to endow Gefitinib resistance with tumor cells, but interference of CA916798 expression largely rescued response of tumor cells to Gefitinib. CONCLUSIONS: CA916798 played oncogenic roles and was correlated with the development of Gefitinib resistance in LUAD cells. Therefore, CA916798 could be considered as a promising prognostic marker and a therapeutic target for LUAD.

Dauer larva-derived extracellular vesicles extend the life of Caenorhabditis elegans.

There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that Dauer (C. elegans), known as "ageless" nematodes, can also secrete extracellular vesicles and influence the lifespan of C. elegans. Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type C. elegans were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of C. elegans as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity.

Systematic Comprehensive Evaluation of the Mindray CX-9000 Coagulation Analyzer Performance.

BACKGROUND: The aim of the study was to conduct a comprehensive performance evaluation of the Mindray CX-9000 fully automated coagulation analyzer for the detection of the seven coagulation items. METHODS: The performance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), fibrinogen degradation product (FDP), and antithrombin Ⅲ (AT) was validated for precision, linear range, carryover contamination rate, reference interval validation, inter-method agreement, and anti-interference ability. RESULTS: The intra- and inter-precision (coefficient of variation, CV%) of all seven items was less than the target CV%; the carryover contamination rates for different concentrations and between items were < 10%. The slope of the linear regression equation for the theoretical and measured values of the linear range was within 1 ± 0.05 and R ≥ 0.975. The reference interval quoted from the manufacturer's reference interval passed ≥ 95%. The CX-9000 was compared with the results of the reference instrument STAGO R MAX (STA-R MAX) and the p-values for all items ranged from 0.822 to 0.987. Within the concentration range claimed by the manufacturer, the interference errors produced by all items met the manufacturer's claimed criteria, except for triglycerides which produced interference errors > 10% for the FIB, D-D, FDP, and bilirubin which produced interference errors for the FIB and D-D assays. CONCLUSIONS: The CX-9000 automatic coagulation analyzer has good stability and repeatability, a wide linear range of detection, low carryover contamination rate, and high resistance to interference, making it suitable for the testing of clinical specimens.

Potential therapeutic effects of milk-derived exosomes on intestinal diseases.

Exosomes are extracellular vesicles with the diameter of 30 ~ 150 nm, and are widely involved in intercellular communication, disease diagnosis and drug delivery carriers for targeted disease therapy. Therapeutic application of exosomes as drug carriers is limited due to the lack of sources and methods for obtaining adequate exosomes. Milk contains abundant exosomes, several studies have shown that milk-derived exosomes play crucial roles in preventing and treating intestinal diseases. In this review, we summarized the biogenesis, secretion and structure, current novel methods used for the extraction and identification of exosomes, as well as discussed the role of milk-derived exosomes in treating intestinal diseases, such as inflammatory bowel disease, necrotizing enterocolitis, colorectal cancer, and intestinal ischemia and reperfusion injury by regulating intestinal immune homeostasis, restoring gut microbiota composition and improving intestinal structure and integrity, alleviating conditions such as oxidative stress, cell apoptosis and inflammation, and reducing mitochondrial reactive oxygen species (ROS) and lysosome accumulation in both humans and animals. In addition, we discussed future prospects for the standardization of milk exosome production platform to obtain higher concentration and purity, and complete exosomes derived from milk. Several in vivo clinical studies are needed to establish milk-derived exosomes as an effective and efficient drug delivery system, and promote its application in the treatment of various diseases in both humans and animals.

LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.

Integrated analysis of transcriptome profiling of lncRNAs and mRNAs in livers of type 2 diabetes mellitus.

Long noncoding RNAs (lncRNAs) influence the progression of almost all human diseases, but the participation of lncRNAs in type 2 diabetes mellitus (T2DM) has not been fully elucidated. This study aimed to systematically compare the transcriptome profiling of lncRNAs and mRNAs in livers between patients with T2DM and controls, to identify key genes associated with T2DM pathogenesis, and to predict the underlying molecular mechanisms. As a result, a total of 1,512 differentially expressed (DE) lncRNAs and 1,923 DE mRNAs were identified through microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that multiple metabolic processes were dysregulated such as small molecule, organic acid, lipid, and branched chain amino acid metabolism. Protein-protein interaction network was constructed, and 10 hub mRNAs were identified, including EHHADH, ATM, ACOX1, PIK3R1, EGFR, UQCRFS1, HMGCL, UQCRC2, NDUFS3, and F2. RT-qPCR was conducted to verify the validity of microarray results. Then, coding-noncoding co-expression network and competing endogenous RNA (ceRNA) network were analyzed to predict the lncRNA-mRNA and lncRNA-miRNA-mRNA regulatory patterns. Subsequently, 10 key intermediating miRNAs in ceRNA networks with a node degree >80 were identified, including hsa-miR-5692a, hsa-miR-12136, hsa-miR-5680, hsa-miR-1305, hsa-miR-6833-5p, hsa-miR-7159-5p, hsa-miR-548as-3p, hsa-miR-6873-3p, hsa-miR-1290, and hsa-miR-4768-5p. In conclusion, this study evaluated the transcriptome profiling of lncRNAs and mRNAs in livers from patients with T2DM, with a value for understanding the molecular mechanism of disease pathogenesis and identifying effective biomarkers in clinical diagnosis.

Dietary fat quantity and quality in early pregnancy and risk of gestational diabetes mellitus in Chinese women: a prospective cohort study.

We aimed to examine the association between the quantity and quality of dietary fat in early pregnancy and gestational diabetes mellitus (GDM) risk. In total, 1477 singleton pregnant women were included from Sichuan Provincial Hospital for Women and Children, Southwest China. Dietary information was collected by a 3-d 24-h dietary recall. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to estimate relative risks (RR) and 95% CI. The results showed that total fat intake was positively associated with GDM risk (Q4 v. Q1: RR = 1·40; 95 % CI 1·11, 1·76; Ptrend = 0·001). This association was also observed for the intakes of animal fat and vegetable fat. After stratified by total fat intake (< 30 %E v. ≥ 30 %E), the higher animal fat intake was associated with higher GDM risk in the high-fat group, but the moderate animal fat intake was associated with reduced risk of GDM (T2 v. T1: RR = 0·65; 95 % CI 0·45, 0·96) in the normal-fat group. Vegetable fat intake was positively associated with GDM risk in the high-fat group but not in the normal-fat group. No association between fatty acids intakes and GDM risk was found. In conclusion, total fat, animal and vegetable fat intakes were positively associated with GDM risk, respectively. Whereas when total fat intake was not excessive, higher intakes of animal and vegetable fat were likely irrelevant with increased GDM risk, even the moderate animal fat intake could be linked to lower GDM risk.

Dietary cholesterol and egg intake are associated with the risk of gestational diabetes: a prospective study from Southwest China.

BACKGROUND: An increasing body of evidence suggests that cholesterol intake increases during pregnancy and may influence the risk of gestational diabetes mellitus (GDM). However, existing evidence remains controversial and limited. The present study aimed to determine the relation among dietary cholesterol, specifically egg consumption, in pregnant Chinese women and their risk of GDM. METHODS: A population-based study that included 1617 pregnant women was conducted in 2017. At baseline, dietary information was collected by 24-hour dietary recalls over three days. GDM was diagnosed by a 75 g 2-hr oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Logistic regression models were used to examine the associations of dietary cholesterol and egg intake with GDM. In addition, path analysis including cholesterol intake, plasma lipid profiles and GDM risk was conducted. RESULTS: The average total cholesterol intake was 340.8 mg/d, and cholesterol from eggs accounted for 59.2%. The odds ratio (OR) of GDM risk was 1.48 for the highest quartile of total cholesterol intake compared to the lowest quartile (95% CI 1.10-2.00; P trend = 0.015) after adjustment for potential risk factors for GDM. Moreover, cholesterol from eggs rather than from other foods was positively associated with incident GDM (OR=1.09, 95% CI 1.03-1.17). Each additional egg consumed per day was positively correlated with a higher risk of GDM (OR=1.32, 95% CI 1.11-1.58). Path analysis indicated that cholesterol intake not only increased the risk of GDM by elevating plasma total cholesterol (TC), but also increased the risk of GDM through other non hyperlipidemia pathways. CONCLUSIONS: Maternal dietary cholesterol intake was significantly associated with incident GDM, and egg consumption was a major driver of the association in this population. More studies are needed to substantiate these findings and to explore the underlying mechanisms.

Induction of PDCD4 by albumin in proximal tubule epithelial cells potentiates proteinuria-induced dysfunctional autophagy by negatively targeting Atg5.

Autophagy dysfunction is a hallmark of type 1 diabetes. However, the precise molecular mechanism of proteinuria-induced dysfunctional autophagy remains unclear. Herein, we investigated the role of programmed cell death 4 (PDCD4) in the regulation of autophagy in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro. RT-qPCR, immunohistochemistry (IHC), and western blotting demonstrated an upregulation of Pdcd4 mRNA and protein in streptozotocin (STZ)-induced DKD rats, as compared to the control. In addition, IHC and western blotting of a unilateral ureteral obstruction mouse model showed an upregulation of PDCD4 in the disease group, as compared to their respective controls. IHC analysis of kidney biopsy samples of human DKD patients showed an upregulation of PDCD4 compared to the control. Western blotting of the STZ-induced DKD rat tissues displayed a low microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, as compared to the control. It was found that albumin overload in cultured PTECs upregulated the expression of PDCD4 and p62 and decreased the expression of LC3-II and autophagy-related 5 (Atg5) proteins. The knockout of Pdcd4 in cultured PTECs could reduce albumin-induced dysfunctional autophagy, as evidenced by the recovery of Atg5 and LC3-II protein. The forced expression of PDCD4 could further suppress the expression of the crucial autophagy-related gene Atg5. Evidence suggests that endogenous PDCD4 promotes proteinuria-induced dysfunctional autophagy by negatively regulating Atg5. Therefore, PDCD4 may be a potential therapeutic target in DKD.

Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36.

Hematoma size after intracerebral hemorrhage (ICH) significantly affects patient outcome. However, our knowledge of endogenous mechanisms that underlie hematoma clearance and the potential role of the anti-inflammatory cytokine interleukin-10 (IL-10) is limited. Using organotypic hippocampal slice cultures and a collagenase-induced ICH mouse model, we investigated the role of microglial IL-10 in phagocytosis ex vivo and hematoma clearance in vivo. In slice culture, exposure to hemoglobin induced IL-10 expression in microglia and enhanced phagocytosis that depended on IL-10-regulated expression of CD36. Following ICH, IL-10-deficient mice had more severe neuroinflammation, brain edema, iron deposition, and neurologic deficits associated with delayed hematoma clearance. Intranasal administration of recombinant IL-10 accelerated hematoma clearance and improved neurologic function. Additionally, IL-10-deficient mice had weakened in vivo phagocytic ability owing to decreased expression of microglial CD36. Moreover, loss of IL-10 significantly increased monocyte-derived macrophage infiltration and enhanced brain inflammation in vivo. These results indicate that IL-10 regulates microglial phagocytosis and monocyte-derived macrophage infiltration after ICH and that CD36 is a key phagocytosis effector regulated by IL-10. Leveraging the innate immune response to ICH by augmenting IL-10 signaling may provide a useful strategy for accelerating hematoma clearance and improving neurologic outcome in clinical translation studies.

A low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of gestational diabetes mellitus in Chinese women: a prospective cohort study.

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.

Association of gestational weight gain with cesarean section: a prospective birth cohort study in Southwest China.

BACKGROUND: Cesarean section (CS) is a rising public health issue globally, and is particularly serious in China. Numerous studies have suggested that gestational weight gain (GWG) control may be an effective way to reduce the rate of CS. However, rare study has examined the association between GWG and CS among women in Southwest China. We proposed to examine their association based on a prospective birth cohort, and further to explore the optimal GWG range. METHODS: We retrieved data from a prospective birth cohort from Sichuan Provincial Hospital for Women and Children, Southwest China. Unconditional multivariable logistic regression was used to examine the association between GWG and CS by adjusting for potential confounders. In one analysis, we incorporated the GWG as a categorical variable according to the Institute of Medicine (IOM) recommendation, similar to the method used in the majority of previous studies. In the other analysis, we directly incorporated GWG as a continuous variable and natural cubic splines were used to characterize the potential nonlinear exposure-response relationship, aiming to identify the optimal GWG. We further stratified the above analysis by pre-pregnancy BMI and GDM, and then a heterogeneity test based on a multivariate meta-analysis was conducted to examine whether the stratum specific estimations agreed with each other. RESULTS: A total of 1363 participants were included. By adopting the IOM recommendation, the adjusted OR of CS was 0.63 (0.47, 0.84) for insufficient GWG and 1.42 (1.06, 1.88) for excessive GWG. After stratification by pre-pregnancy BMI, we found a higher risk of CS in associated with excessive GWG in the stratum of underweight compared with the other strata, which implied that pre-pregnancy BMI may be an effect modifier. By applying a flexible spline regression, the optimal GWG levels in terms of reducing the CS rate based on our data were more stringent than those of IOM recommendation, which were 9-12 kg for underweight women, < 19 kg for normal weight women and < 10 kg for overweight/obese women. CONCLUSIONS: These results suggested that a more stringent recommendation should be applied in Southwest China, and that more attention should be given to underweight women.

Specific fruit but not total fruit intake during early pregnancy is inversely associated with gestational diabetes mellitus risk: a prospective cohort study.

OBJECTIVES: Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk. DESIGN: A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI. SETTING: Southwest China. PARTICIPANTS: Totally, 1453 healthy pregnant women in 2017. RESULTS: Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk. CONCLUSIONS: In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.

Associations between Maternal Lipid Profiles and Pregnancy Complications: A Prospective Population-Based Study.

OBJECTIVE: To investigate whether plasma lipid profiles are independently associated with pregnancy complications including gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), and intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: A prospective study was conducted among 1,704 pregnant women at three medical institutions in Chengdu, China. The concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at gestational weeks 12 ± 1, 24 ± 1, and 34 ± 1. Logistic regression models were used to estimate the association between lipid profiles and pregnancy complications. Receiver operating characteristic analysis was performed to determine the value of lipid profiles to predict GDM and HDCP. RESULTS: After adjusting for potential confounders, TG, TC, and LDL-C in the first trimester were independently associated with GDM (TG: odds ratio [OR] =2.00, 95% confidence interval [CI]: 1.57-2.56; TC: OR = 1.38, 95% CI: 1.16-1.64; LDL-C: OR = 1.43, 95% CI: 1.14-1.79) and HDCP (TG: OR = 2.42, 95% CI: 1.56-3.78, TC: OR = 1.64, 95% CI: 1.04-2.57; LDL-C: OR = 1.87, 95% CI: 1.07-3.25). The TC concentration during the whole pregnancy (first trimester: OR = 1.53, 95% CI: 1.13-2.08; second trimester: OR = 1.31, 95% CI: 1.06-1.61; third trimester: OR = 1.39, 95% CI: 1.17-2.04) and LDL-C in the last two trimesters (second trimester: OR = 1.62, 95% CI: 1.30-2.04; third trimester: OR = 1.56, 95% CI: 1.29-1.88) were positively associated with ICP. HDL-C in the third trimester was negatively associated with the risk of ICP (OR = 0.46, 95% CI: 0.22-0.98). Combining lipid profiles in the first trimester with the other common predictors to predict GDM or HDCP owned stronger predictive power with the largest area under the curve (GDM: 0.643 [95% CI: 0.613-0.673], HDCP: 0.707 [95% CI: 0.610-0.804]) than either indicator alone. CONCLUSION: Maternal lipid profiles during the whole pregnancy are significantly associated with GDM, HDCP, and ICP. Combining lipid profiles in the first trimester with the other common predictors could effectively improve the power of predicting GDM and HDCP.

[Prospective study of red meat intake in the first and second trimesters and the risk of gestational diabetes mellitus in Chengdu in 2017].

OBJECTIVE: To evaluate the red meat intake of pregnant women in Chengdu area and explore the effect of red meat intake in the first and second trimesters on gestational diabetes mellitus(GDM). METHODS: From February to July 2017, a prospective study was conducted among healthy singleton pregnant women within 8-14 weeks of gestation in a prenatal clinic of maternal-and-child medical institution in Chengdu City through purposive sampling. Data on maternal demographic characteristics was collected through questionnaire in early pregnancy. 3-day 24 hour dietary recall was used to collect dietary intake information in the first and second trimesters. The 75 g oral glucose tolerance test(OGTT)was conducted at 24 to 28 weeks of gestation, and GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression model was used to explore the association between tertiles of red meat intake and the risk of GDM in the first and second trimesters. RESULTS: A total of 985 valid samples were followed up. The mean intake of total meat and red meat in middle pregnancy(102. 9 g/d and 74. 6 g/d) was higher than that in early pregnancy(70. 7 g/d and 52. 0 g/d). The difference was statistically significant(P<0. 05). Red meat accounted for 73. 6% and 72. 5% of total meat intake in early and middle pregnancy, respectively. After adjusting the confounding factors, multivariate unconditional Logistic regression analysis showed the risk of GDM was 1. 499 times(95%CI 1. 028-2. 185) in the highest red meat intake(>86 g/d)women compared with the lowest red meat intake(<44 g/d) women in the second trimester. No association was found between red meat intake in the first trimester and the occurrence of GDM(OR=1. 029, 95%CI 0. 716-1. 481). CONCLUSION: Pregnant women in Chengdu area have excessive intake of red meat in the second trimester. Higher intake of red meat in the second trimester(>86 g/d) may increase the risk of gestational diabetes.

Endocytosis Is a Key Mode of Interaction between Extracellular ß-Amyloid and the Cell Membrane.

Interactions between amyloid-ß peptide (Aß) and the cell membrane include interaction with membrane lipids and binding to membrane receptors, both of which are considered to be the toxicity mechanisms of Aß. However, it is unclear whether both mechanisms lead to cytotoxicity. Thus, we aimed to analyze these two mechanisms of Aß42 interaction with cell membranes under different Aß aggregation states. To this end, model membrane experiments were conducted. Quantitative analysis of Aß42 monomers or oligomers bound to the membrane of neuro-2a cells was also performed, and laser confocal microscopy was employed to assess endocytosis of FITC-Aß42 monomers or oligomers by neuro-2a cells. We found that the binding capacity of Aß42 to membrane lipids was weak and that the amount of Aß42 bound to membrane lipids was low. Moreover, clathrin-mediated endocytosis of Aß42 oligomers by neuro-2a cells was observed. Endocytosis serves as a key mode of interaction between extracellular Aß42 and neurons. These findings provide insights into the mechanisms underlying Aß oligomer metabolism.