Objective: To investigate the effects of thyroid stimulating hormone (TSH) and thyroid peroxidase antibody(TPOAb) on pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Methods: The patients who underwent IVF-ET at the Reproductive Medicine Center of Hefei Maternal and Child Health Care Hospital from December 2019 to November 2023, and had normal free thyroxine and 0.3-<10 mIU/L TSH levels were selected as subjects. The patients were divided into three groups based on TSH levels: 0.3-<2.5 mIU/L, 2.5-4 mIU/L, and >4-<10 mIU/L, and the patients with normal free thyroxine and TSH levels were further divided into TPOAb-positive and TPOAb-negative groups. The biochemical pregnancy rate, clinical pregnancy rate and miscarriage rate were compared among patients with different TSH and TPOAb groups. Results: A total of 3 876 patients were recruited, including 830 patients with fresh embryo transfer cycles and 3 046 patients with frozen-thawed embryo transfer cycles. In the patients with fresh embryo transfer cycles, the biochemical pregnancy rate, clinical pregnancy rate and miscarriage rate were 59.16%, 52.77% and 19.41%, respectively. In the patients with frozen-thawed embryo transfer cycles, these rates were 55.52%, 46.98% and 20.27%, respectively. For both groups, there were no statistically significant differences in biochemical pregnancy rate, clinical pregnancy rate and miscarriage rate between TPOAb-positive and TPOAb-negative patients or among the patients with different TSH groups (all P>0.05). Additionally, a follow-up study of 150 patients who had successfully delivered after IVF-ET from 2020 to 2022 with TSH levels of >4-<10 mIU/L showed that no intellectual developmental issues or tendencies toward intellectual developmental disorders were found in their offsprings. Conclusion In the context of normal free thyroxine levels, this study did not find any impacts of mildly elevated TSH levels or isolated TPOAb positivity on the pregnancy outcomes of IVF-ET.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.

Eutrophils are the first innate immune cells to reach the site of inflammation. Neutrophils produce neutrophil extracellular traps (NETs) that can quickly capture and limit the spread of pathogens, facilitating the removal of pathogens and their debris. Neutrophils in the oral cavity are specifically transformed from circulating neutrophils in the blood, and the number of NETs released by oral neutrophils is much higher than that of circulating neutrophils, thus better maintaining the balance of the oral microenvironment. As a bimorphic fungus, only the mycelium phase of Candida albicans can induce NETs, which is related to the neutrophils' ability to sense the size of pathogenic microorganisms through neutrophil elastase. However, spherical Staphylococcus aureus are much smaller than Candida albicans, and they can still induce NETs. Porphyromonas gingivalis, as one of the microorganisms in the periodontitis complex, induces fewer NETs than Streptococcus oralis and Actinomycetes, which are two common oral microorganisms, and there may be a mechanism allowing them to escape neutrophilic immunity in the early stage of periodontitis. Although the two main pathways of NET production have been studied in detail, the mechanisms involved in the induction of NETs by different microorganisms, especially from oral neutrophils, are not well understood. This review describes the mechanism of the immune effects of pathogenic microorganisms on neutrophil NETs in the oral cavity, providing a reference for the search for therapeutic targets and the development of key drugs for treating oral infectious diseases.

Human oral cavity is colonized by various microbial communities which play an important role in the initiation and progression of periodontitis. However, it is still not clear how these microbial communities mediate the disease. With the rise of metagenomics research, polymicrobial synergy and dysbiosis (PSD) model, a new periodontitis pathogenesis mechanism, was proposed. The importance of the microbial communities acting as a whole system in the development of periodontitis is gradually recognized. Host susceptibility, as another key factor in the initiation of the disease, is vital in PSD model. This article reviews the mechanisms of the PSD model and its research progress in periodontitis as well as some other diseases and briefly highlights the positive significance in terms of prevention and treatment of periodontitis in order to provide insights and perspectives for the future periodontal researches.

Epigallocatechin-3-gallate (EGCG) has antibacterial, anti-inflammatory, antitumor, and other functions. EGCG and its anticancer mechanism are hot research topics in the prevention and treatment of oral cancer. In this paper, the prevention and treatment effects of EGCG on oral cancer and its anticancer mechanism are reviewed. The results show that EGCG can regulate multiple cell metabolic signaling pathways, such as the G protein coupled receptor signaling pathway, mitogen-activated protein kinase (MAPK), and the Wnt signaling pathway, and it can regulate DNA methylation and act on RNA of oral cancer cells directly or indirectly through the oral cancer cell signal transduction network to inhibit the development of oral precancerous lesions and oral cancer. EGCG combined with 5-fluorouracil can enhance the curative effect and reduce adverse effects and is expected to be a new drug for the prevention and treatment of oral cancer.

Objective:To investigate the association of the difference between 2-hour postprandial blood glucose and fasting blood glucose with non-alcoholic fatty liver disease(NAFLD)in elderly patients with type 2 diabetes(T2DM).Methods:A total of 953 patients aged≥65 years with T2DM hospitalized in the Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital from January 2007 to June 2009, with complete clinical data, were selected in this retrospective study.The absolute value of the difference between 2-hour postprandial blood glucose and fasting blood glucose was recorded as the blood glucose difference.According to the tertiles of the blood glucose difference, patients were divided into three groups including the first tertile(n=317, blood glucose difference<4.12 mmol/L), the second tertile(n=320, blood glucose difference between 4.12-7.69 mmol/L), and the third tertile(n=316, blood glucose difference≥7.69 mmol/L). Detailed clinical data of the patients were collected, and clinical characteristics and the prevalence of NAFLD were compared among the three groups.The correlation between the blood glucose difference and NAFLD was analyzed.Results:From the first tertile to the third tertile, there appeared to be increased proportions of patients using metformin( χ2=9.581, P=0.008), higher waist-to-hip ratios( F=3.663, P=0.026), increased 24 h uric acid excretion( χ2=6.241, P=0.044), increased alanine aminotransferase levels( χ2=22.361, P<0.001), increased γ-glutamyl transpeptidase levels( χ2=17.681, P<0.001)and increased 2h postprandial blood glucose levels( χ2=579.315, P<0.001), with significant statistical differences in the waist circumference( F=4.723, P=0.009), body mass index( F=5.811, P=0.003), fasting C-peptide levels( χ2=9.442, P=0.009), 2h postprandial C-peptide levels( χ2=17.599, P<0.001)and glycosylated hemoglobin A1c( F=30.836, P<0.001)between the three groups and the prevalence of NAFLD also grew steadily(24.0%, n=76 vs. 33.1%, n=107 vs. 36.7%, n=116, χ2=12.712, P<0.01). After adjusting for other variables, multivariate logistic regression analysis showed that the blood glucose difference was correlated with NAFLD in elderly patients with T2DM( OR=1.396, Wald χ2=0.002, P<0.01). Conclusions:Elderly T2DM patients with greater blood glucose differences have more severe metabolic disorders and a higher prevalence of NAFLD.An increase in blood glucose differences is an independent risk factor for NAFLD in elderly T2DM patients.

The oral microbiota is associated with oral diseases and digestive systemic diseases. Nevertheless, the causal relationship between them has not been completely elucidated, and colonisation of the gut by oral bacteria is not clear due to the limitations of existing research models. The aim of this study was to develop a human oral microbiota-associated (HOMA) mouse model and to investigate the ecological invasion into the gut. By transplanting human saliva into germ-free (GF) mice, a HOMA mouse model was first constructed. 16S rRNA gene sequencing was used to reveal the biogeography of oral bacteria along the cephalocaudal axis of the digestive tract. In the HOMA mice, 84.78% of the detected genus-level taxa were specific to the donor. Principal component analysis (PCA) revealed that the donor oral microbiota clustered with those of the HOMA mice and were distinct from those of specific pathogen-free (SPF) mice. In HOMA mice, OTU counts decreased from the stomach and small intestine to the distal gut. The distal gut was dominated by Streptococcus, Veillonella, Haemophilus, Fusobacterium, Trichococcus and Actinomyces. HOMA mice and human microbiota-associated (HMA) mice along with the GF mice were then cohoused. Microbial communities of cohoused mice clustered together and were significantly separated from those of HOMA mice and HMA mice. The Source Tracker analysis and network analysis revealed more significant ecological invasion from oral bacteria in the small intestines, compared to the distal gut, of cohoused mice. In conclusion, a HOMA mouse model was successfully established. By overcoming the physical and microbial barrier, oral bacteria colonised the gut and profiled the gut microbiota, especially in the small intestine.
Animals ; Bacteria ; Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Microbiota ; RNA, Ribosomal, 16S

D-alanine is a chiral molecule of L-alanine that participates in the formation and regulation of cell wall peptidoglycans, phosphoteichoic acid, spore germination and respiratory metabolism in individual bacteria. D-alanine participates in the formation and regulation of biofilm in bacterial communities. The function and metabolism of D-alanine in bacteria are specific, and the enzymes and genes in its metabolic pathway can be used as drug targeting sites. In this paper, the synthesis, metabolism and function of D-alanine in bacteria were reviewed, and the relationship between D-alanine and pathogenicity of Streptococcus mutans was discussed to provide a theoretical basis for candidate targeting sites of anti-caries drugs. According to existing research results, the enzymes and related genes involved in D-alanine metabolism play important roles in the growth and biofilm formation of Streptococcus mutans, and D-alanine is expected to be a target for the design of anti-caries drugs.

The hyphal development of Candida albicans (C. albicans) has been considered as an essential virulent factor for host cell damage. However, the missing link between hyphae and virulence of C. albicans is also been discovered. Here, we identified that the null mutants of ERG3 and ERG11, two key genes in ergosterol biosynthesis pathway, can form typical hyphae but failed to cause the oral mucosal infection in vitro and in vivo for the first time. In particular, the erg3Δ/Δ and erg11Δ/Δ strains co-cultured with epithelial cells significantly reduced the adhesion, damage, and cytokine (interleukin-1α (IL-1α)) production, whereas the invasion was not affected in vitro. Importantly, they were incapable of extensive hyphal invasion, formation of micro-abscesses, and tongue epithelium damage compared to wild type due to the decrease of the colonization and epithelial infection area in a murine oropharyngeal candidiasis model. The fluconazole (FLC), an antifungal targeted at ergosterol biosynthesis, relieved the epithelial infection of C. albicansin vitro and in vivo even under non-growth inhibitory dosage confirming the virulent contribution of ergosterol biosynthesis pathway. The erg3Δ/Δ and erg11Δ/Δ strains were cleared by macrophages similar to wild type, whereas their virulence factors including agglutinin-like sequence 1 (Als1), secreted aspartyl proteinase 6 (Sap6), and hyphal wall protein-1 (Hwp1) were significantly reduced indicated that the non-toxicity might not result from the change on immune tolerance but the defective virulence. The incapacity of erg3Δ/Δ and erg11Δ/Δ in epithelial infection highlights the contribution of ergosterol biosynthesis pathway to C. albicans pathogenesis and fluconazole can not only eliminate the fungal pathogens but also reduced their virulence even at low dosage.
Animals ; Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; genetics ; pathogenicity ; Candidiasis, Oral ; drug therapy ; genetics ; microbiology ; Fluconazole ; pharmacology ; Genes, Fungal ; genetics ; Mice ; Microscopy, Electron, Scanning ; Potassium Channels ; genetics ; Virulence