Maternal glycemic status during pregnancy and mid-childhood plasma amino acid profiles: findings from a multi-ethnic Asian birth cohort.

BACKGROUND: Increasing maternal glycaemia across the continuum during pregnancy may predispose offspring to subsequent cardiometabolic risk later in life. However, evidence of long-term impacts of maternal glycemic status on offspring amino acid (AA) profiles is scarce. We aimed to investigate the association between maternal antenatal glycaemia and offspring mid-childhood amino acid (AA) profiles, which are emerging cardiometabolic biomarkers. METHODS: Data were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, a multi-ethnic Asian birth cohort. A subset of 422 mother-child dyads from the GUSTO study, who was followed from early pregnancy to mid-childhood, was included. Mothers underwent an oral glucose tolerance test (OGTT) at 26-28 weeks gestation, with fasting and 2-h plasma glucose concentrations measured and gestational diabetes mellitus (GDM) diagnosed per WHO 1999 guidelines. Offspring fasting plasma samples were collected at mean age 6.1 years, from which AA profiles of nine AAs, alanine, glutamine, glycine, histidine, isoleucine, leucine, valine, phenylalanine, and tyrosine were measured. Total branched-chain amino acids (BCAAs) were calculated as the sum of isoleucine, leucine, and valine concentrations. Multi-variable linear regression was used to estimate the association of maternal glycemic status and offspring mid-childhood AA profiles adjusting for maternal age, ethnicity, maternal education, parity, family history of diabetes, ppBMI, child sex, age and BMI z-scores. RESULTS: Approximately 20% of mothers were diagnosed with GDM. Increasing maternal fasting glucose was significantly associated with higher offspring plasma valine and total BCAAs, whereas higher 2-h glucose was significantly associated with higher histidine, isoleucine, valine, and total BCAAs. Offspring born to mothers with GDM had higher valine (standardized mean difference 0.27 SD; 95% CI: 0.01, 0.52), leucine (0.28 SD; 0.02, 0.53), and total BCAAs (0.26 SD; 0.01, 0.52) than their counterparts. Inconsistent associations were found between maternal GDM and other amino acids among offspring during mid-childhood. CONCLUSIONS: Increasing maternal fasting and post-OGTT glucose concentrations at 26-28 weeks gestation were significantly associated with mid-childhood individual and total BCAAs concentrations. The findings suggest that elevated maternal glycaemia throughout pregnancy, especially GDM, may have persistent programming effects on offspring AA metabolism which were strongly associated with adverse cardiometabolic profiles at mid-childhood.

Mediterranean diet and female reproductive health over lifespan: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course. DATA SOURCES: We searched PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to identify eligible studies published till February 2022. Eligible references from identified studies and review articles were also considered. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, prospective cohort studies, or nested case-control studies examining Mediterranean diet and major female reproductive outcomes over the lifespan, including clinical outcomes from childhood to adulthood (menarche, polycystic ovary syndrome, endometriosis, and outcomes related to fertility, pregnancy, and menopause), were included for review. METHODS: Two independent reviewers screened and performed data extraction and risk-of-bias assessment. We performed random-effects meta-analysis to obtain summary relative risks and 95% confidence intervals for major female reproductive outcomes. Subgroup analyses were performed for several pregnancy outcomes according to timing of the interventions for randomized controlled trials and timing of the dietary assessment for observational studies. RESULTS: Thirty-two studies (9 randomized controlled trials, 22 prospective cohort studies, and 1 nested case-control study) involving 103,204 predominantly White women (>95%) were included. The pooled relative risk (95% confidence interval) comparing randomization to Mediterranean diet vs a control diet based on 7 randomized controlled trials was 0.74 (0.55-0.99) for gestational diabetes mellitus, 0.45 (0.26-0.76) for preterm birth, 0.71 (0.51-1.00) for gestational hypertension, and 0.82 (0.54-1.22) for preeclampsia; the effect sizes for preterm birth were greater in randomized controlled trials that initiated the interventions in first trimester vs after first trimester (P heterogeneity=.02). We observed inverse associations for all the above-mentioned pregnancy outcomes based on 9 cohort studies. There was suggestive evidence of favorable associations between Mediterranean diet adherence with fertility and gestational weight management. Limited studies suggested associations between higher Mediterranean diet adherence and later time to menarche and fewer vasomotor menopausal symptoms, null associations for polycystic ovary syndrome-like phenotype and pregnancy loss, and positive associations for luteal phase deficiency. CONCLUSION: Adherence to Mediterranean diet may lower risks of adverse pregnancy outcomes among predominantly White populations. For fertility-related outcomes, available evidence supporting potential beneficial effects is suggestive yet limited. For other reproductive outcomes across the lifespan, data remains sparse.

Ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry coupled with three-step data post-processing techniques for comprehensive profiling of the multiple components in Fufang Xianzhuli Ye.

INTRODUCTION: Fufang Xianzhuli (FXZL) Ye, a classical formula of traditional Chinese medicine, is composed of Succus Bambusae, Houttuyniae herba, Pinelliae Rhizoma, Zingiberis Rhizoma Recens, Eriobotryae Folium, Platycodonis Radix, and peppermint oil. For many years, FXZL has been primarily utilised in China to treat cough and phlegm. The chemical composition of FXZL has not been reported, which seriously affects the safety of the clinical application. OBJECTIVE: To establish a systematic method for rapidly classifying and recognising the chemical constituents in the FXZL for the safety of the clinical application. METHODS: An ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry coupled with a three-step data post-processing strategy was developed to screen the chemical constituents of FXZL. RESULTS: In this experiment, the diagnostic ions in FXZL were classified into six main compounds. A total of 106 compounds were unambiguously identified in FXZL based on their retention times, accurate masses, and tandem mass spectrometry data. These include 11 chlorogenic acids, three flavonoids, eight sesquiterpenoids, six organic acids, 65 triterpenoid saponins, and 13 other compounds. CONCLUSION: The chemical composition of FXZL was identified and summarised, providing useful information for quality control and a basis for further exploration of its active ingredients in vivo.

Plasma folate levels in relation to cognitive impairment: a community-based cohort of older adults in China.

PURPOSE: Lower plasma level of folate has been associated with an increased risk of age-related cognitive impairment. However, studies that examined this relation have yielded mixed results. We aimed to examine the prospective association of plasma folate level with risk of cognitive impairment in a community-based prospective cohort of older adults in China. METHODS: This study included 615 participants (mean age: 76.3 years) without baseline cognitive impairment from the Rugao Longevity and Ageing Study (RuLAS). We used logistic regression to examine the prospective association between baseline plasma folate and risk of cognitive impairment in the next two years. Fasting blood samples were collected and assayed for plasma folate level at baseline. Cognitive impairment was defined as Hasegawa Dementia Scale (HDS) score ≤ 21.5 points. RESULTS: During two years' follow-up, 20.7% of the participants developed cognitive impairment. After controlled for age, gender, and plasma homocysteine, a higher level of plasma folate was associated with lower odds of cognitive impairment. The corresponding odds ratio (OR) with 95% confidence interval was 0.41 (0.19-0.89) comparing participants at extreme quintiles of plasma folate (median level 17.2 vs. 6.3 nmol/L). The associations were similar after further adjustment for major demographic and lifestyle factors (OR = 0.42, 0.18-0.98). Moreover, the inverse association was particularly stronger among males (OR = 0.12, 0.03-0.52) but was non-significant among females. CONCLUSION: Our findings support a potential beneficial role of higher plasma folate levels in cognitive function in older Chinese adults, particularly among males. Future studies with larger sample size and longer follow-up are warranted to confirm these findings and to identify the optimal plasma folate level for cognitive function.

Gestational weight gain during the second and third trimesters and adverse pregnancy outcomes, results from a prospective pregnancy cohort in urban Tanzania.

BACKGROUND: Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort. METHODS: We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women's gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated. RESULTS: According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36-0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95-1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03-3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03-2.44). CONCLUSIONS: A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings. TRIAL REGISTRATION: This trial was registered as "Prenatal Iron Supplements: Safety and Efficacy in Tanzania" (NCT01119612; http://clinicaltrials.gov/show/NCT01119612 ).

Pregnancy is a critical lifetime event for both mother and the offspring, with implications in short-term and long-term health consequences. Gestational weight gain (GWG) is an important modifiable factor for pregnancy outcomes related to infant body size and weight and prematurity. Countries in sub-Saharan Africa (SSA) have long had poor rates of insufficient GWG and pregnancy complications associated with insufficient GWG. Nevertheless, some SSA countries are experiencing economic transitions accompanied with changes in lifestyle and nutrition, which might impact pregnancy experiences, including GWG and pregnancy outcomes. This study aimed to characterize recent GWG patterns and the associations of both inadequate and excessive GWG with adverse pregnancy outcomes, using an urban pregnancy cohort in Tanzania. This study found that 42.0%. 22.0%, and 36.0% of women had insufficient, adequate, and excessive GWG, respectively. Insufficient GWG was associated with higher risks of small infant size and low infant body weight, and excessive GWG was associated with higher risk of preterm birth, particularly among women with body mass index 18.5­25.0 kg/m². Results from the present study highlight that both insufficient and excessive GWG are of potential public health concerns in urban centers of SSA, concerning upward trends in obesity and possibly obesity-related pregnancy consequences. Local public health practitioners should continue to advocate longitudinal GWG monitoring and care among African pregnant women, and optimal GWG with feasible and effective clinical guidelines should be developed to prevent both over- and under-gaining of maternal weight during pregnancy.

Dietary diversity and diet quality with gestational weight gain and adverse birth outcomes, results from a prospective pregnancy cohort study in urban Tanzania.

Healthy maternal diets during pregnancy are an important protective factor for pregnancy-related outcomes, including gestational weight gain (GWG) and birth outcomes. We prospectively examined the associations of maternal dietary diversity and diet quality, using Minimum Dietary Diversity for Women (MDD-W) and Prime Diet Quality Score (PDQS), with GWG and birth outcomes among women enrolled in a trial in Tanzania (n = 1190). MDD-W and PDQS were derived from a baseline food frequency questionnaire. Women were monthly followed until delivery, during which weight was measured. GWG was classified based on the 2009 Institute of Medicine guidelines. Adverse birth outcomes were classified as low birth weight (LBW), small for gestational age, large for gestational age, and preterm birth. 46.2% participants had MDD-W ≥ 5. Mean score of PDQS was 23.3. Maternal intakes of nuts, poultry, and eggs were low, whereas intakes of sugar-sweetened beverages and refined grains were high. MDD-W was not associated with GWG or birth outcomes. For PDQS, compared to the lowest tertile, women in the highest tertile had lower risk of inappropriate GWG (risk ratio [RR] = 0.93, 95% confidence interval [CI]: 0.87-1.00). Women in the middle tertile group of PDQS (RR = 0.72, 95% CI: 0.51-1.00) had lower risk of preterm birth. After excluding women with prior complications, higher PDQS was associated with lower risk of LBW (middle tertile: RR = 0.55, 95% CI: 0.31-0.99, highest tertile: RR = 0.52, 95% CI: 0.29-0.94; continuous per SD: RR = 0.77, 95% CI: 0.60-0.99). Our findings support continuing efforts to improve maternal diet quality for optimal GWG and infant outcomes among Tanzanian women.

Intrauterine device use and risk of ovarian cancer: Results from the New England Case-Control study and Nurses' Health Studies.

Results of studies assessing intrauterine device (IUD) use and ovarian cancer risk are inconsistent. We examined the association between IUD use, including duration, type and timing of use, and ovarian cancer risk using three population-based studies. Data from the New England Case-Control Study (NEC) and two prospective cohort studies, the Nurses' Health Studies (NHS/NHSII), were included in the analysis. Information on IUD use was collected by in-person interview in NEC and by biennial questionnaire in NHS/NHSII. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) in NEC and Cox regression to calculate hazard ratios (HR) and 95% CI in NHS/NHSII. We used meta-analysis to combine the NEC and the pooled NHS/NHSII results. Overall, IUD use was not associated with epithelial ovarian cancer risk (OR = 0.96, 95% CI: 0.81-1.14 in NEC; HR = 0.89, 95% CI: 0.69-1.15 in NHS/NHSII; combined RR = 0.94, 95% CI: 0.81-1.08). Among IUD users, older age at first use was associated with increased ovarian cancer risk (P-trend = .03). We did not observe significant associations by IUD type or duration of use. In conclusion, IUD use was not associated with ovarian cancer risk in our study.

Methodological approaches to imputing early-pregnancy weight based on weight measures collected during pregnancy.

BACKGROUND: Early pregnancy weights are needed to quantify gestational weight gain accurately. Different methods have been used in previous studies to impute early-pregnancy weights. However, no studies have systematically compared imputed weight accuracy across different imputation techniques. This study aimed to compare four methodological approaches to imputing early-pregnancy weight, using repeated measures of pregnancy weights collected from two pregnancy cohorts in Tanzania. METHODS: The mean gestational ages at enrollment were 17.8 weeks for Study I and 10.0 weeks for Study II. Given the gestational age distributions at enrollment, early-pregnancy weights were extrapolated for Study I and interpolated for Study II. The four imputation approaches included: (i) simple imputation based on the nearest measure, (ii) simple arithmetic imputation based on the nearest two measures, (iii) mixed-effects models, and (iv) marginal models with generalized estimating equations. For the mixed-effects model and the marginal model with generalized estimating equation methods, imputation accuracy was further compared across varying degrees of model flexibility by fitting splines and polynomial terms. Additional analyses included dropping third-trimester weights, adding covariate to the models, and log-transforming weight before imputation. Mean absolute error was used to quantify imputation accuracy. RESULTS: Study I included 1472 women with 6272 weight measures; Study II included 2131 individuals with 11,775 weight measures. Among the four imputation approaches, mixed-effects models had the highest accuracy (smallest mean absolute error: 1.99 kg and 1.60 kg for Studies I and II, respectively), while the other three approaches showed similar degrees of accuracy. Depending on the underlying data structure, allowing appropriate degree of model flexibility and dropping remote pregnancy weight measures may further improve the imputation performance. CONCLUSIONS: Mixed-effects models had superior performance in imputing early-pregnancy weight compared to other commonly used strategies.

Association between body mass index, its change and cognitive impairment among Chinese older adults: a community-based, 9-year prospective cohort study.

To examine the association of baseline body mass index (BMI) and BMI change with cognitive impairment among older adults in China. The study included data from the Chinese Longitudinal Healthy Longevity Study, a national community-based prospective cohort study from 2002 to 2018. Baseline BMI and BMI change were available for 12,027 adults aged older than 65 years. Cognitive impairment was defined as Chinese version of the Mini Mental State Examination score lower than 18. Multivariable Cox proportional hazard model was used. Among 12,027 participants (mean age was 81.23 years old and 47.48% were male), the proportion of underweight, normal, overweight and obese at baseline was 33.87%, 51.39%, 11.39% and 3.34%, respectively. During an average of 5.9 years' follow-up, 3086 participants (4.35 per 100 person-years) with incident cognitive impairment were identified. Compared with normal weight group, adjusted hazard ratio (AHR) for cognitive impairment was 0.86 (95% CI 0.75-0.99) among overweight group, whereas corresponding AHR was 1.02 (95% CI 0.94-1.10) in underweight and 1.01 (95% CI 0.80-1.28) in obese participants. Large weight loss (< -10%) was significantly associated with an increased risk of cognitive impairment (AHR, 1.42, 95% CI 1.29-1.56), compared to stable weight status group (-5% ~ 5%). In the restricted cubic spline models, BMI change showed a reverse J-shaped association with cognitive impairment. BMI-defined overweight, but not obesity, was associated with a lower risk of cognitive impairment among elderly Chinese adults, while large weight loss was associated with an increased risk. These findings are consistent with weight loss in the prodromal phase of dementia.

Using Cervical Dilation to Predict Labor Onset: A Tool for Elective Labor Induction Counseling.

OBJECTIVE: To evaluate whether cervical dilation predicts the timing and likelihood of spontaneous labor at term. STUDY DESIGN: This was a retrospective cohort of nulliparous women with singleton pregnancies who delivered at term from 2013 to 2015. Outpatient cervical examinations performed after 37 weeks and prior to labor onset were collected. Survival analysis was used to analyze time to spontaneous labor with cervical dilation as the primary predictor, modeled as continuous and categorical variables (<1 cm, 1 cm, >1 cm). RESULTS: Our cohort included 726 women; 407 (56%) spontaneously labored, 263 (36%) were induced, and 56 (8%) had an unlabored cesarean delivery. Women with >1-cm dilation were three times more likely to spontaneously labor (adjusted hazard ratio [aHR]: 3.1; 95% confidence interval [CI]: 2.4-4) than those with <1-cm dilation. At 39 weeks, 60% of women with >1-cm dilation went into spontaneous labor as compared with only 28% of those with <1-cm dilation (aHR: 2.9; 95% CI: 2-4.4). CONCLUSION: In our cohort of nulliparous women at term, those with cervical dilation > 1 cm were significantly more likely to go into labor in the following week. This information can aid in counseling about elective induction of labor.

Oleuropein induced apoptosis in HeLa cells via a mitochondrial apoptotic cascade associated with activation of the c-Jun NH2-terminal kinase.

Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell lines. In this study, we investigate how oleuropein strongly induces apoptotic cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells apoptosis as demonstrated by induction of a sub-G(1) peak in flow cytometry and apoptosis-related morphological changes observed by fluorescence microscopy after being stained by Hoechst 33324. The results also showed that 150 - 200 µM oleuropein–treated HeLa cells were arrested at the G(2)/M phase. Western blot analysis revealed that the phosphorylated ATF-2, c-Jun NH(2)-terminal kinase (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm significantly increased in a dose-dependent manner after treatment of oleuropein for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK signaling, which formed mitochondrial membrane channels, accounted for releasing of cytochrome c and activation of caspase-9 and -3. SP600125 (20 µM), a JNK(1/2) inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by oleuropein at 200 µM. Thus, oleuropein-induced apoptosis was activated by the JNK/SPAK signal pathway. The result shows that oleuropein holds promise as a potential chemotherapeutic agent for the treatment of HeLa cells.

TLDA: A transfer learning based dual-augmentation strategy for traditional Chinese Medicine syndrome differentiation in rare disease.

The Traditional Chinese Medicine (TCM) has demonstrated its significant medical value over the decades, particularly during the COVID-19 pandemic. TCM-AI interdisciplinary models have been proposed to model TCM knowledge, diagnosis, and treatment experiments in clinical practice. Among them, numerous models have been developed to simulate the syndrome differentiation process of human TCM doctors for automatic syndrome diagnosis. However, these models are designed for normal scenarios and trained using a supervised learning paradigm which needs tens of thousands of training samples. They fail to effectively differentiate syndromes in rare disease scenarios where the available TCM electronic medical records (EMRs) are very limited for each unique syndrome. To address the challenge of rare diseases, this study proposes a simple yet effective method called Transfer Learning based Dual-Augmentation (TLDA). TLDA aims to augment the limited EMRs at both the sample-level and feature-level, enriching the pathological and medical information during training. Extended experiments involving 11 comparison models, including the state-of-the-art model, demonstrate the effectiveness of TLDA. TLDA outperforms all comparison models by a significant margin. Furthermore, TLDA can also be extended to other medical tasks when the EMRs for diagnosis are limited in samples.

Universal, minute-scale synthesis of transition metal compound nanocatalysts via graphene-microwave system for enhancing sulfur kinetics in lithium-sulfur batteries.

The application of Li-S batteries on large scale is held back by the sluggish sulfur kinetics and low synthesis efficiency of sulfur host. In addition, the preparation of catalysts that promote polysulfide redox kinetics is complex and time-consuming, reducing the cost of raw materials in Li-S. Here, a universal synthetic strategy for rapid fabrication of sulfur cathode and metal compounds nanocatalysts is reported based on microwave heating of graphene. Heat-sensitive materials can achieve rapid heating due to graphene reaching 500 ℃ within 4 s via microwave irradiation. The MoP-MoS2/rGO catalyst demonstrated in this work was synthesized within 60 s. When used for catalysts for Li-S batteries whose graphene/sulfur cathodes were also synthesized by microwave heating, enhanced catalytic effect for sulfur redox reaction was verified via experimental and DFT theoretical results. Benefiting from fast redox reaction (MoP), smooth Li+ diffusion pathways (MoS2), and large conductive network (rGO), the assembled Li-S battery with MoP-MoS2/rGO-Add@CS displays a remarkable initial specific capacity, stable lithium anode and good cycle stability (in pouch cells) using this two-pronged strategy. The work provides a practical strategy for advanced Li-S batteries toward a wide range of applications.

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis.

Introduction: Jinteng Qingbi granules (JTQBG), a traditional Chinese medicine formulation, are widely used for the treatment of rheumatoid arthritis (RA) due to their satisfactory therapeutic efficacy. However, the underlying mechanism of action remains unclear. This study aims to investigate the protective effects of JTQBG against RA and elucidates its potential molecular mechanisms. Methods: A collagen-induced arthritis (CIA) rat model was utilized, and JTQBG (1.25, 2.5, 5 g/kg/day) or methotrexate (MTX, 1 mg/kg/week) was orally administered. The rats' weight, arthritis index (AI), and paw volume were measured weekly. Synovial hyperplasia of the joints was detected using a small animal ultrasound imaging system. Joint destruction was assessed using an X-ray imaging system. Histopathological examinations were performed using hematoxylin-eosin (H&E), Saffron-O and fast green staining. Serum inflammatory cytokines were detected using ELISA. Furthermore, 4D label-free quantitative proteomics of synovial tissues and non-targeted metabolomics of blood serum were conducted to analyze the molecular mechanisms. Results: JTQBG exerted a significant therapeutic effect on CIA rats by reducing inflammatory cell infiltration, synovial hyperplasia, cartilage erosion, and bone destruction. It also decreased the spleen index, inhibited hyperplasia of the white pulp, and decreased the serum levels of IL-1ß and IL-18. Proteomics analysis identified 367 differentially expressed proteins (DEPs) between the Model and Normal groups, and 71 DEPs between the JTQBG and Model groups. These DEPs were significantly enriched in the NF-κB pathway. 11 DEPs were significantly reversed after treatment with JTQBG. Western blot results further validated the expression levels of Nfkb1, Pdk1, and Pecam1, and analyzed the expression levels of p-IKK, p-IκBα, and IκBα. The therapeutic efficacy of JTQBG was partly attributed to the suppression of the NF-κB pathway in synovial tissues. Serum metabolomics identified 17 potential biomarkers for JTQBG treatment of CIA rats, which were closely related to Alanine, aspartate and glutamate metabolism, Tryptophan metabolism, Ascorbate and aldarate metabolism, Arginine metabolism, and Inositol phosphate metabolism. Conclusion: Our findings demonstrated that JTQBG was effective against RA by alleviating synovial inflammation, synovial hyperplasia, and joint destruction. The anti-RA properties of JTQBG were likely attributed to the inhibition of the NF-κB pathway and the regulation of serum metabolite disorders.

Lifetime Duration of Breastfeeding and Cardiovascular Risk in Women With Type 2 Diabetes or a History of Gestational Diabetes: Findings From Two Large Prospective Cohorts.

OBJECTIVE: Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes mellitus (GDM) is unclear. RESEARCH DESIGN AND METHODS: We included 15,146 parous women with type 2 diabetes from the Nurses' Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD) (myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS: We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during 188,874 person-years of follow-up and 132 incident CVD cases among women with a GDM history during 100,218 person-years of follow-up. Longer lifetime duration of breastfeeding was significantly associated with lower CVD risk among women with type 2 diabetes, with pooled aHR of 0.68 (95% CI 0.54-0.85) for >18 months versus 0 months and 0.94 (0.91-0.98) per 6-month increment in breastfeeding. Similar associations were observed with CHD (pooled aHR 0.93 [0.88-0.97]) but not with stroke (0.96 [0.91-1.02]) per 6-month increment in breastfeeding. Among women with GDM history, >18 months versus 0 months of breastfeeding was associated with an aHR of 0.49 (0.28-0.86) for total CVD. CONCLUSIONS: Longer duration of breastfeeding was associated with lower risk of CVD in women with type 2 diabetes or GDM.

Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort.

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.

Comparison of prognosis after partial and total surgical resection for parathyroid carcinoma: an inverse probability of treatment weighting analysis of the SEER database.

Background: Complete resection of the tumor and the ipsilateral thyroid lobe at the primary surgery is the "gold standard" for the treatment of parathyroid carcinoma (PC). However, differences in the overall survival (OS) of patients with PC who underwent partial and total surgical resection remain to be determined. Methods: Data on patients with PC who underwent partial and total surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database (2000-2018). The X-tile software (https://medicine.yale.edu/lab/rimm/research/software/) was used to define the optimal cut-off values for continuous variables. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare the OS of patients with PC in the partial and total surgical resection groups. Results: A total of 334 patients with PC were included in this study (183 and 151 in the partial and total surgical resection groups, respectively). The optimal cut-off values for age at diagnosis were 53 and 73 years, respectively, while that for tumor size was 34 mm. In both the Kaplan-Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, the difference in OS between the partial and total surgical resection groups was not statistically significant (p>0.05). These findings were confirmed in the IPTW-adjusted Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis (p>0.05). Subgroup analysis revealed that total surgical resection was beneficial for OS only in the subgroup with unknown tumor size. Conclusion: There was no significant difference in the prognosis of patients who underwent partial and total surgical resection. This finding may provide a useful reference for the treatment of PC.

Assessing future heat stress across China: combined effects of heat and relative humidity on mortality.

This study utilizes China's records of non-accidental mortality along with twenty-five simulations from the NASA Earth Exchange Global Daily Downscaled Projections to evaluate forthcoming heat stress and heat-related mortality across China across four distinct scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The findings demonstrate a projected escalation in the heat stress index (HSI) throughout China from 2031 to 2100. The most substantial increments compared to the baseline (1995-2014) are observed under SSP5-8.5, indicating a rise of 7.96°C by the year 2100, while under SSP1-2.6, the increase is relatively modest at 1.54°C. Disparities in HSI growth are evident among different subregions, with South China encountering the most significant elevation, whereas Northwest China exhibits the lowest increment. Projected future temperatures align closely with HSI patterns, while relative humidity is anticipated to decrease across the majority of areas. The study's projections indicate that China's heat-related mortality is poised to surpass present levels over the forthcoming decades, spanning a range from 215% to 380% from 2031 to 2100. Notably, higher emission scenarios correspond to heightened heat-related mortality. Additionally, the investigation delves into the respective contributions of humidity and temperature to shifts in heat-related mortality. At present, humidity exerts a greater impact on fluctuations in heat-related mortality within China and its subregions. However, with the projected increase in emissions and global warming, temperature is expected to assume a dominant role in shaping these outcomes. In summary, this study underscores the anticipated escalation of heat stress and heat-related mortality across China in the future. It highlights the imperative of emission reduction as a means to mitigate these risks and underscores the variances in susceptibility to heat stress across different regions.

Metabolomic biomarkers of the mediterranean diet in pregnant individuals: A prospective study.

BACKGROUND AND AIMS: Metabolomic profiling is a systematic approach to identifying biomarkers for dietary patterns. Yet, metabolomic markers for dietary patterns in pregnant individuals have not been investigated. The aim of this study was to identify plasma metabolomic markers and metabolite panels that are associated with the Mediterranean diet in pregnant individuals. METHODS: This is a prospective study of 186 pregnant individuals who had both dietary intake and metabolomic profiles measured from the Fetal Growth Studies-Singletons cohort. Dietary intakes during the peri-conception/1st trimester and the second trimester were accessed at 8-13 and 16-22 weeks of gestation, respectively. Adherence to the Mediterranean diet was measured by the alternate Mediterranean Diet (aMED) score. Fasting plasma samples were collected at 16-22 weeks and untargeted metabolomics profiling was performed using the mass spectrometry-based platforms. Metabolites individually or jointly associated with aMED scores were identified using linear regression and least absolute shrinkage and selection operator (LASSO) regression models with adjustment for potential confounders, respectively. RESULTS: Among 459 annotated metabolites, 64 and 41 were individually associated with the aMED scores of the diet during the peri-conception/1st trimester and during the second trimester, respectively. Fourteen metabolites were associated with the Mediterranean diet in both time windows. Most Mediterranean diet-related metabolites were lipids (e.g., acylcarnitine, cholesteryl esters (CEs), linoleic acid, long-chain triglycerides (TGs), and phosphatidylcholines (PCs), amino acids, and sugar alcohols. LASSO regressions also identified a 10 metabolite-panel that were jointly associated with aMED score of the diet during the peri-conception/1st trimester (AUC: 0.74; 95% CI: 0.57, 0.91) and a 3 metabolites-panel in the 2nd trimester (AUC: 0.68; 95% CI: 0.50, 0.86). CONCLUSION: We identified plasma metabolomic markers for the Mediterranean diet among pregnant individuals. Some of them have also been reported in previous studies among non-pregnant populations, whereas others are novel. The results from our study warrant replication in pregnant individuals by future studies. CLINICAL TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov.

Association of Type 2 Diabetes Mellitus with Cognitive Function in Adults: A Prospective Cohort Study.

BACKGROUND: The Cognitive role of untreated type 2 diabetes mellitus (T2DM) has been less well substantiated. OBJECTIVE: We sought to explore the prospective association of T2DM and untreated T2DM with cognitive function among middle-aged and older Chinese adults. METHODS: Data of 7,230 participants without baseline brain damage/mental retardation, or memory-related diseases in China Health and Retirement Longitudinal Study (CHARLS) from 2011- 2012 to 2015, were analyzed. Fasting plasma glucose and self-reported information on T2DM diagnosis and treatment were assessed. Participants were categorized into normoglycemia, impaired fasting glucose (IFG), and T2DM (including untreated and treated T2DM) groups. Episodic memory and executive function were assessed by modified Telephone Interview for Cognitive Status every two years. We used generalized estimating equation model to examine the association of baseline T2DM status with cognitive function in succeedingyears. RESULTS: Compared to those with normoglycemia, T2DM was associated with worse overall cognitive function after controlling for demographic variables, lifestyles, follow-up time, major clinical factors, and baseline cognitive function, although the associations were statistically non-significant (ß= -0.19, 95% CI: -0.39, 0.00). However, a significant association was mainly observed for those with untreated T2DM (ß= -0.26, 95% CI: -0.47, -0.04), especially in the domain of executive function (ß= -0.19, 95% CI: -0.35, -0.03). In general, IFG and treated T2DM individuals had similar levels of cognitive function with normoglycemia participants. CONCLUSION: Our findings supported a detrimental role of untreated T2DM on cognitive function among middle-aged and older adults. Screening and early treatment for T2DM are warranted for maintaining better cognitive function in later life.