The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

AIM: To determine the effects of valsartan on calcium channel and sodium-calcium exchanger current in isolated ventricular myocytes of congestive heart failure (CHF) rats. METHODS: Eight weeks after coronary ligation, the rats with heart failure were confirmed by measuring the hemodynamic parameters and divided randomly into the group treating with valsartan (CHF-T, 20 mg/kg) and placebo (CHF-C). Sham-operated group rats served as negative controls (PS). Twelve weeks later, 6 rats were selected randomly for the study of ion channel. Single ventricular myocytes of rats were isolated by enzymatic dissociation. The whole-cell patch-clamp recording technique was used to record calcium channel current and sodium-calcium exchanger current. RESULTS: (1) In the hemodynamic variables, HR and blood pressure were not significantly different in three groups. Compared CHF-C with PS group, LVEDP and Cm increased, LVSP and ?d p /d t max decreased ( P 0 05). (4) Na +-Ca 2+ exchanger current in CHF-C group increased significantly. Na +-Ca 2+ exchanger current in CHF-T group was smaller significantly than that in CHF-C group. However, CHF-T group and PS group were not significantly different. CONCLUSION: Administration of valsartan is effective in preventing from cardiac function deterioration, increases calcium channel current and decreases Na +-Ca 2+ exchanger current in ventricular myocytes of heat failure rats.

OBJECTIVETo study the relativity between Streptococcus sanguis group (SSG) and coronary heart disease (CHD).

METHODS41 individuals were diagnosed with CHD and 18 normals served as controls. All of them had undergone coronary angiography. Their social class (including education and wages), smoking, drinking, blood lipids and oral health were also recorded. SSG in saliva and subgingival plaque were cultivated in NAYS-B agar plates and counted. SSG were identified into species with routine biochemical reaction and AP-PCR.

RESULTSIn the multiple step regression analysis, the amount of SSG in saliva and subgingival plaque were positively associated with severe coronary atheromatosis after adjusting the classical risk factors of CHD. The average amount of SSG in saliva was (435 +/- 422) x 10(8) CFU/L in CHD group and (358 +/- 540) x 10(8) CFU/L in control group, F = 2.72, P = 0.08; the average amount of SSG in incisor was (331 +/- 484) x 10(7) CFU/L in CHD group and (98 +/- 164) x 10(7) CFU/L in control group, F = 5.54, P = 0.02; the average amount of SSG in molar was (352 +/- 381) x 10(7) CFU/L in CHD group and (185 +/- 232) x 10(7) CFU/L in control group, F = 2.86, P = 0.10. S. sanguis and S. gordonii were more in CHD group than in control group (P < 0.05), whereas S. mitis and S. oralis were the same in two groups (P > 0.05).

CONCLUSIONThe increase of SSG in oral floras may play an important role in the occurrence of CHD.

Aged ; Coronary Disease ; complications ; Dental Plaque ; microbiology ; Educational Status ; Gingiva ; microbiology ; Humans ; Middle Aged ; Molar ; microbiology ; Risk Factors ; Saliva ; microbiology ; Smoking ; Socioeconomic Factors ; Statistics as Topic ; Streptococcal Infections ; complications ; microbiology ; Streptococcus sanguis ; isolation & purification

Objective To investigate the relationship between the marrow edema and general clinical index,quadriceps muscle area,and the meniscus grade of knee osteoarthritis(OA).Methods 72 patients were collected with knee OA in our hospital, underwent X-ray and routine MRI examination of knee, and the same X-ray and MRI were reviewed at 12 months later in different time point.The K-L grading, bone marrow edema score, meniscal grading and VAS score of each knee joint were evaluated.The t-test and Rank-sum test were used to compare the two groups of general data, Spearman was used to perform bivariate correlation analysis.Results The age and VAS score of bone marrow edema group at the initial follow-up were significantly lower than those without edema group(P<0.05),the degree of marrow edema was moderately correlated with age and VAS score, and was not significantly correlated with other indexes.12 months later, BMI and the area of quadriceps femoris in the group with marrow edema were different from those in the group without bone marrow edema(P<0.05), the degree of marrow edema was moderately correlated with age, quadriceps area and VAS.Conclusion The range of marrow edema was related to age, quadriceps area, BMI index and VAS score in MRI.The MRI measurement could reflect the progression of knee OA more than that of X-ray.It also revealed some factors related to the progression of knee OA.

We integrate web-based learning with team based learning,which is called WTBL method (Web-based and team-based Learning). WTBL method is constructed and applied to the teaching practice of core curriculum group courses of clinical medicine. We build some small private online courses. The students can preview online and do the case discussions by teamwork in class. The application of WTBL teaching method has realized the flipping of classroom, and helps to enhance students' self-learning ability and teamwork ability.

Objective:To detect the serum level of chitinase-3-like protein 1 (YKL-40) in patients with pemphigus vulgaris, and to analyze its correlation with the severity of pemphigus vulgaris.Methods:From January 2017 to May 2018, serum samples were collected from 38 patients with pemphigus vulgaris in Department of Dermatology, the Affiliated Hospital of Southwest Medical University, and those collected from 14 age-, gender- and body mass index-matched healthy volunteers served as controls. Serum levels of YKL-40 and Th1/Th2/Th17-related cytokines were detected by using Luminex ? 200 TM system. Mann-Whitney U test was used to compare serum levels of cytokines between the patient group and control group; binary logistic regression was used to investigate factors independently related to the severity of pemphigus vulgaris; a receiver operating characteristic (ROC) curve was drawn, and the area under the curve, sensitivity and specificity were calculated to evaluate the ability of YKL-40 to predict the severity of pemphigus vulgaris. Results:Compared with the control group, the patient group showed significantly increased serum levels of YKL-40 (expressed as median[ Q1, Q3]: 15.22 [14.19, 15.93] vs. 13.64 [13.21, 14.63]μg/L, z=-3.88, P < 0.05) , interleukin (IL) -6 (2.05 [1.49, 4.21] vs. 1.57[1.38, 1.75]ng/L, z=-2.44, P < 0.05) , IL-7 (7.45[5.63, 11.63] vs. 3.77[2.21, 5.97]ng/L, z=-3.26, P < 0.05], IL-8 (6.59[3.60, 14.73] vs. 4.36[2.96, 6.53]ng/L, z=-1.96, P < 0.05) , IL-2R-α (509.08 [386.36, 757.67] vs. 336.44[309.86, 458.71]ng/L, z=-2.35, P < 0.05) , and C5a (100.35 [78.31, 140.84] vs. 72.08 [37.23, 82.08] ng/L, z = -3.04, P < 0.05) . The concentration of serum YKL-40 gradually decreased along with the reduction of lesion areas ( r = 0.63, P < 0.001) , and YKL-40 was independently correlated with the severity of pemphigus vulgaris ( P = 0.025, OR = 46.54, 95% CI: 1.61, 1 347.19) . The area under the curve of YKL-40 was 0.783 (95% CI: 0.613, 0.953) for distinguishing between patients with severe to extremely severe pemphigus vulgaris and those with mild to moderate pemphigus vulgaris. Conclusion:The serum level of YKL-40 is strongly correlated with the severity of pemphigus vulgaris, and has a potential value in predicting the severity of this disease.

Background Previous research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. Objective To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. Methods We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. Results The average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL⁻¹. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL⁻¹), perfluorooctanoic acid (PFOA, 4.55 ng·mL⁻¹), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL⁻¹), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL⁻¹), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL⁻¹), perfluorobutanoic acid (PFBA, 1.81 ng·mL⁻¹), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL⁻¹), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL⁻¹) were higher than 1.00 ng·mL⁻¹. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L⁻¹ and 0.24 (95%CI: 0.18, 0.30) mmol·L⁻¹, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50^th to the 75^th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L⁻¹, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. Conclusion PFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

Periapical periodontitis arises from the interaction between microbial factors and the inflammatory response of the host's periapical tissues. In this process, bacteria and their byproducts serve as the primary drivers for the initiation, progression, and spread of the disease. Pulp infections and periapical lesions are primarily dominated by gram-negative bacteria. The endotoxin lipopolysaccharide component of these bacteria plays a crucial role in pulp infection, triggering clinical symptoms, inflammatory reactions, and bone tissue resorption. Similarly, lipoteichoic acid and lipopolysaccharide from gram-positive bacteria exhibit similar pathogenic characteristics, causing damage to pulp and periapical tissues. The aim of this review is to delve deeper into the distribution patterns and pathogenesis of periapical microorganisms in chronic periapical periodontitis.

OBJECTIVES: The study aimed at identifying salivary microbiota in caries-free Chinese preschool children using high-throughput sequencing. METHODS: Saliva samples were obtained from 35 caries-free preschool children (18 boys and 17 girls) with primary dentition, and 16S ribosomal DNA (rDNA) V3-V4 hypervariable regions of the microorganisms were analyzed using Illumina MiSeq. RESULTS: At 97% similarity level, all of these reads were clustered into 334 operational taxonomic units (OTUs). Among these, five phyla (Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Candidate division TM7) and 13 genera ( CONCLUSIONS Our results revealed the diversity and composition of salivary microbiota in caries-free preschool children, with little difference between male and female subjects. Identity of the core microbiome, coupled with prediction of gene function, deepens our understanding of oral microbiota in caries-free populations and provides basic information for associating salivary microecology and oral health.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health