Association Between Serum Glycated Hemoglobin Levels at Early Gestation and the Risk of Subsequent Pregnancy Loss in Pregnant Women Without Diabetes Mellitus: Prospective Cohort Study.

BACKGROUND: As a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. OBJECTIVE: This study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. METHODS: This prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital's early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. RESULTS: In total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P<.001). CONCLUSIONS: Higher HbA1c levels in early pregnant women without diabetes are associated with an increased SPL risk in a dose-response manner. Pregnant women with an HbA1c level above 5.6% at early gestation need attention for its potentially increased risk for SPL. Our findings support the need to monitor HbA1c levels to identify individuals at high risk of subsequent SPL in the general population of pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737644; https://clinicaltrials.gov/study/NCT02737644.

Functional modification of gelatin-based biodegradable composite films: a review.

As one of the raw materials of biodegradable food packaging, gelatin is an environmentally friendly substitute for traditional plastic packaging. In this review both sources and extraction methods of gelatin are introduced, together with recent modification methods and applications of using plant sources instead of synthetic substances to endow gelatin film with functionality. Gelatin is extracted from mammals, marine organisms, and poultry. Different extraction methods (acid, alkali, enzyme treatment) can affect the molecular weight and amino acid composition of gelatin, thus affecting the molecular structure, physical properties, chemical and functional properties of gelatin. Gelatin serves as a good substrate, but its disadvantage is that it is very brittle. However, the addition of plasticizers can improve the flexibility of the film by reducing chain interactions during the dehydration process. Compared with other plasticizers, glycerol and sorbitol have better effects on adjusting the mechanical properties of gelatin films. Gelatin is combined with active substances such as essential oils, plant extracts, and nanoparticles to prepare gelatin based composite films with good mechanical properties and antibacterial and antioxidant properties. Gelatin-based composite films can effectively inhibit the growth and reproduction of microorganisms and lipid oxidation in food. Applying it to food packaging can improve the quality of fresh food and extend its shelf life.

Low-intensity red-light therapy in slowing myopic progression and the rebound effect after its cessation in Chinese children: a randomized controlled trial.

PURPOSE: To investigate the effect of low-intensity red-light (LRL) therapy on myopic control and the response after its cessation. METHODS: A prospective clinical trial. One hundred two children aged 6 to 13 with myopia were included in the LRL group (n = 51) and the single-focus spectacles (SFS) group (n = 51). In LRL group, subjects wore SFS and received LRL therapy provided by a laser device that emitted red-light of 635 nm and power of 0.35 ± 0.02 mW. One year after the control trial, LRL therapy was stopped for 3 months. The outcomes mainly included axial length (AL), spherical equivalent refraction (SER), subfoveal choroidal thickness (SFCT), and accommodative function. RESULTS: After 12 months of therapy, 46 children in the LRL group and 40 children in the SFS group completed the trial. AL elongation and myopic progression were 0.01 mm (95%CI: - 0.05 to 0.07 mm) and 0.05 D (95%CI: - 0 .08 to 0.19 D) in the LRL group, which were less than 0.39 mm (95%CI: 0.33 to 0.45 mm) and - 0.64 D (95%CI: - 0.78 to - 0.51 D) in the SFS group (p < 0.05). The change of SFCT in the LRL group was greater than that in the SFS group (p < 0.05). Accommodative response and positive relative accommodation in the LRL group were more negative than those in the SFS group (p < 0.05). Forty-two subjects completed the observation of LRL cessation, AL and SER increased by 0.16 mm (95%CI: 0.11 to 0.22 mm) and - 0.20 D (95%CI: - 0.26 to - 0.14 D) during the cessation (p < 0.05), and SFCT returned to baseline (p > 0.05). CONCLUSIONS: LRL is an effective measure for preventing and controlling myopia, and it may also have the ability to improve the accommodative function. There may be a slight myopic rebound after its cessation. The effect of long-term LRL therapy needs to be further explored. TRIAL REGISTRATION: Chinese Clinical Trial Registry: Chinese Clinical Trails registry: ChiCTR2100045250. Registered 9 April 2021; retrospectively registered. http://www.chictr.org.cn/showproj.aspx?proj=124250.

Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study.

BACKGROUND: Gestational diabetes mellitus (GDM) may lead to many adverse effects on women and their offspring. METHOD: 24,429 pregnant women were enrolled during early pregnancy from January 2018 to December 2021. The self-reported intake of folic acid supplements was assessed via a questionnaire. Oral glucose tolerance tests were used for the diagnosis of GDM. The association between intake or not, dose, and duration of folic acid and GDM risk was assessed. RESULTS: 6396 (26.18%) women were diagnosed with GDM. In the univariate models, folic acid was found to be correlated with total GDM risk (OR = 0.82, 95% CI: 0.70~0.95, p = 0.009). After adjusting for potential confounders, the association with total GDM risk was not significant, but the association of folic acid with 2-h PBG diagnosed GDM risk was consistently significant (OR = 0.75, 95% CI: 0.63~0.90, p = 0.002). No significant association between the dose and duration of folic acid supplementation and GDM risk was observed in the analyses. CONCLUSION: Folic acid supplementation might be a protective factor for the risk of GDM caused by the high level of postprandial blood glucose, but the dose or duration-related association between folic acid supplementation and GDM risk is not clear.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence.

Background: Management of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia. Methods: Network pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research. Results: Based on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF's regulation of the ERK1/2 and PI3K/AKT signaling pathways. Conclusion: This study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS.

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration. Methods: Young and middle-aged adults (18-65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction. Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (-9.9 vs -9.9 mmHg, P > 0.05) or daytime (-11.5 vs. -10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (-10.8 vs. -10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups. Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

Natural DNA-assisted RuP2 on highly graphitic N,P-codoped carbon for pH-wide hydrogen evolution.

Natural DNA was employed for the first time as a phosphorization agent and carbon source to controllably synthesize a RuP2/N,P-codoped carbon composite by a simple "mix-and-pyrolyze" strategy, which displays higher activity for alkaline and acidic HER and neutral activity compared to Pt/C together with outstanding durability.

Desmin Correlated with Cx43 May Facilitate Intercellular Electrical Coupling during Chronic Heart Failure.

Desmin is one of five major intermediate filament proteins in cardiomyocytes. Desmin contributes to the maintenance of healthy muscle. The desmin content in cardiomyocytes directly affects the long-term prognosis of patients with heart failure, and lack of desmin leads to myocyte contractile dysfunction. However, the mechanism is elusive. In this study, we measured desmin expression using western blotting and qPCR in the failed hearts of human patients and rats. Our results showed that desmin content was reduced at the protein level in failed hearts and isolated cardiomyocytes. The association of desmin and the gap junction proteins connexin 43 (Cx43) and zonula occludens-1 (ZO-1) was also investigated. Immunoprecipitation assay showed that desmin was associated with Cx43 in cardiomyocytes. To compare the electrical integration of skeletal myoblasts in cocultures with cardiac myocytes, familial amyloid polyneuropathy (FAP) activation rate was found in 33% desmin overexpressing skeletal myoblasts. Desmin not only affected Cx43 and ZO-1 expression but also facilitated the complex of Cx43 and ZO-1 in skeletal myoblasts, which enhanced cell-to-cell electrical coupling of skeletal myoblasts with cardiac myocytes. Desmin has potential as a novel therapeutic target for heart failure. Preservation of desmin may attenuate heart failure.

Delphinidin-3-sambubioside from Hibiscus sabdariffa. L attenuates hyperlipidemia in high fat diet-induced obese rats and oleic acid-induced steatosis in HepG2 cells.

Hibiscus sabdariffa. L is folk medicine that is often used for its hypolipidemic and antihypertensive effects; however, the active compound responsible for its anti-obesity effect is presently unknown. Delphinidin-3-sambubioside (Dp3-Sam) is an anthocyanin, was extracted from Hibiscus sabdariffa L. The present research aimed to investigate the role of Dp3-Sam in the prevention of hyperlipidemia in vivo and in vitro. Rats were fed with a standard chow diet (Control group) or high-fat diet (HFD and DP group) for eight weeks. Besides, HepG2 cells were stimulated with 0.2 mM oleic acid, with or without Dp3-Sam (100-200 µg/ml). Lipid profiles were measured by commercial kits. Oil Red O staining was performed to measure the hepatic and intracellular lipid levels. The key genes of lipid metabolism were measured by RT-PCR. In HFD-fed rats, Dp3-Sam reduced the body weight gain, visceral fat, and abdominal fat and decreased hepatic lipid deposits. Dp3-Sam decreased intracellular TG levels and lipid accumulation in oleic acid-treated HepG2 cells. Besides, Dp3-Sam downregulated the mRNA expression of HMG-CoA reductase (HMGCR), sterol regulatory element-binding protein-1 c (SREBP-1 C), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) and upregulated the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1), carnitine palmitoyltransferase1 (CPT1), acyl-coenzyme A oxidase (ACOX), and peroxisome proliferator-activated receptor alpha (PPARα). Dp3-Sam up-regulated the expression of phosphorylation of AMP-activated protein kinase (pAMPK) in HFD-fed rats. Our findings indicated that Dp3-Sam possesses the potential to improve lipid metabolism dysfunction and our results offered evidence for the use of Dp3-Sam as therapy for the prevention of obesity and dyslipidemia.

Association of Maternal Folate and Vitamin B12 in Early Pregnancy With Gestational Diabetes Mellitus: A Prospective Cohort Study.

OBJECTIVE: To investigate the association of folate and vitamin B12 in early pregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: The data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks' gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association. RESULTS: A total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19-2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03-2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (P trend = 0.021). Vitamin B12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B12 with GDM was observed. CONCLUSIONS: Higher maternal RBC folate and vitamin B12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B12 is not significantly associated with GDM.

[Change laws of water absorption in Chinese herbal pieces and prediction model of relative density for Chinese medicine decoction].

This study aims to explore the change laws of water absorption in Chinese herbal pieces and establish the prediction model of relative density for Chinese medicine compound decoction. Firstly, fitted equations of water absorption and decocting time was established by observing the change laws of water absorption in 36 kinds of Chinese herbal pieces in 12 groups(according to the drug-parts) with decocting time. The r value of the mineral group and other type group was 0.691 2 and 0.663 3, respectively. The r value of the remaining 10 groups was 0.802 2-0.925 4. All P values were less than 0.05(n=21). The formula of the amount of water added was optimized by combining the fitted equations with determined water absorption, and the liquid yield could be controlled in a range of 100%±10%. Secondly, it was determined that the liquid density tester could be used for the rapid determination of relative density of Chinese medicine decoction after methodological study and comparison with the pycnometer method. The linear regression equation between the corrected relative density(y) and extraction ratio(%, x) was built by measuring and analyzing the related parameters such as liquid yield, relative density and extraction ratio in 46 kinds of Chinese herbal pieces. The established equation was y=0.041 3x+1.003 7, r=0.930 9(P <0.01, n=46), with linear range of 1.94%-65.75%. Based on this, the prototype model for predicting relative density of Chinese medicine decoction was established, and the relative densities of 8 Chinese medicine decoctions were within the prediction interval of this model in verification. This study lays a foundation for database construction of Chinese medicine decoction, implementation of personalized decocting mode and rapid quality control of Chinese medicine decoction.

[Analysis of research hotspot and frontier of severe coronavirus disease 2019: visual analysis based on CiteSpace].

OBJECTIVE: To analyze the research hotspot and frontier of severe coronavirus disease 2019 (COVID-19) in China and abroad. METHODS: The CiteSpace software was used to visually analyze the relevant research of severe COVID-19 published by CNKI and Web of Science databases from January 30th to April 20th in 2020. The analysis content included the author of the literature, the publishing institutions, and high-frequency keywords. RESULTS: There were 389 Chinese literatures and 59 English literatures included. Analysis using CiteSpace software showed that there were four large teams in China currently concerning about the research on severe COVID-19. The co-authoring of each team was relatively close, but the teams were lack of cooperation. The main issuing institutions were affiliated hospitals of colleges and universities, but colleges and enterprises had less participation. The authors of English-language publications mainly had five research teams, some of whom had co-authored relationships. The country with the most enormous volume of English-language publications was China, followed by the United States and Canada. The Chinese keyword co-occurrence, clustering and highlighted words analysis showed that the main research areas of severe COVID-19 included clinical features, traditional Chinese medicine treatment, medical imaging, integrated traditional Chinese and Western medicine treatment and so on; nucleic acid detection, clinical features and diagnosis, plague theory and etiology mechanism, traditional Chinese medicine and integrated Chinese and Western medicine treatment, severe COVID-19 combined with diabetes and prognosis research will become future research trends; keyword cluster analysis showed that severe COVID-19, combined chronic underlying diseases, CT imaging characteristics will also become new trends in the field of research. Co-occurrence analysis of keywords in English literatures showed that the main research areas of severe COVID-19 included the names of novel coronavirus, pandemic diseases, infectious diseases, medical supplies distribution, and indicators related to myocardial damage. CONCLUSIONS: Researchers in China and abroad have different concerns about severe COVID-19. Domestic research focuses on the diagnosis and treatment of severe cases, while foreign countries attach importance to epidemic response and prevention.

Guanxintai Exerts Protective Effects on Ischemic Cardiomyocytes by Mitigating Oxidative Stress.

Oxidative stress participates in numerous myocardial pathophysiological processes and is considered a therapeutic target for myocardial ischemia and heart failure. Guanxintai (GXT), a traditional Chinese medicine, is commonly used to treat cardiovascular disease on account of its numerous beneficial physiological activities, such as dilating coronary arteries, inhibiting platelet aggregation, and reducing the serum lipid content. However, the antioxidative properties of GXT and potential underlying mechanisms remain to be established. In the present study, we investigated the protective effects of GXT on ischemic cardiomyocytes and the associated antioxidative mechanisms, both in vivo and in vitro. Notably, GXT treatment reduced the degree of cardiomyocyte injury, myocardial apoptosis, and fibrosis and partially improved cardiac function after myocardial infarction. Furthermore, GXT suppressed the level of ROS as well as expression of NADPH oxidase (NOX) and phospho-p38 mitogen-activated protein kinase (MAPK) proteins. Our results collectively suggest that the protective effects of GXT on ischemic cardiomyocytes are exerted through its antioxidative activity of NOX inhibition.

Glutamine Ameliorates Mucosal Damage Caused by Immune Responses to Duck Plague Virus.

The immune-releasing effects of L-glutamine (Gln) supplementation in duck plague virus (DPV)-infected ducklings were evaluated in 120 seven-day-old ducklings that were divided into 8 groups. The ducklings in control and DPV, 0.5Gln and DPV + 0.5Gln, 1.0Gln and DPV + 1.0Gln, and 2.0Gln and DPV + 2.0Gln received 0, 0.5, 1.0, and 2.0 g of Gln/kg feed/d by gastric perfusion, respectively. Then, the ducklings in control to 2.0Gln were injected with 0.2 mL of phosphate-buffered saline, while those in DPV to DPV + 2.0Gln were injected with DPV at 0.2 mL of 2000 TCID50 (50% tissue culture infection dose) 30 minutes after gavage with Gln, sampled at 12 hours and days 1, 2, 4, and 6. Glutamine supplementation under physiological conditions enhanced immune function and toll-like receptor 4 (TLR4) expressions in a dose-dependent manner. An increase in Gln supplementation under DPV-infected conditions enhanced growth performance, decreased immunoglobulin (Ig) release in plasma and secretory IgA in the duodenum, ameliorated plasma cytokine levels, and suppressed overexpressions of the TLR4 pathway in the duodenum. The positive effects of Gln on the humoral immunity- and intestinal inflammation-related damage should be considered a mechanism by which immunonutrition can assist in the recovery from DPV infection.

L-Glutamine Supplementation Alleviates Constipation during Late Gestation of Mini Sows by Modifying the Microbiota Composition in Feces.

Constipation occurs frequently in both sows and humans, particularly, during late gestation. The microbial community of the porcine gut, the enteric microbiota, plays a critical role in functions that sustain intestinal health. Hence, microbial regulation during pregnancy may be important to prevent host constipation. The present study was conducted to determine whether L-glutamine (Gln) supplementation improved intestinal function and alleviated constipation by regulation of enteric microbiota. 16S rRNA sequences obtained from fecal samples from 9 constipated sows (3 in the constipation group and 6 in the 1.0% Gln group) were assessed from gestational day 70 to 84. Comparative analysis showed that the abundance of intestinal-friendly microbiota, that is, Bacteroidetes (P = 0.007) and Actinobacteria (P = 0.037), was comparatively increased in the 1.0% Gln group, while the abundance of pernicious bacteria, Oscillospira (P < 0.001) and Treponema (P = 0.011), was decreased. Dietary supplementation with 1.0% Gln may ameliorate constipation of sows by regulated endogenous gut microbiota.

Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network.

Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain.

Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity.

Diosgenin, a naturally occurring steroidal saponin, possess tumor therapeutic potential. However, the effect of diosgenin on cancer metastasis remains poorly understood. In this study, we performed in vitro experiments to investigate the inhibitory activity of diosgenin on human breast cancer MDA-MB-231 cell migration, and reveal the possible mechanism. Diosgenin caused a marked inhibition of cell migration in MDA-MB-231 cell by transwell assay. In addition, diosgenin significantly impacted MDA-MB-231 cell migratory behavior under real-time observation. We also found diosgenin significantly inhibited actin polymerization, Vav2 phosphorylation and Cdc42 activation, which might be, at least in part, attributed to the anti-metastatic potential of diosgenin. These findings reveal a new therapeutic potential of diosgenin for human breast cancer metastasis therapy.

Hypothalamus-related resting brain network underlying short-term acupuncture treatment in primary hypertension.

The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male) were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM) as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP) and heart rate (HR) decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005) decreased and vitality (P = 0.036) increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.