OBJECTIVETo evaluate the effect of SMU.2055 gene on acid resistance of Streptococcus mutans.

METHODSA SMU.2055-dificient mutant strain of S. mutans was constructed using homologous recombination technique. The growth of the wild-type and mutant strains was monitored in both normal and acidic conditions. The lethal pH level, glycolysis, proton permeability, cell permeability and biofilm formation of the two strains were compared.

RESULTSPCR and sequence analyses verified the successful construction of the SMU.2055-dificient mutant strain. The growth and biofilm formation capacity of the mutant strain were obviously lowered in both normal and acidic conditions. The mutant strain also showed increased lethal pH level, proton permeability, and cell permeability with impaired H-ATPase activity in acidic conditions, but its minimum glycolytic pH remained unaffected.

CONCLUSIONThe SMU.2055-deficient S. mutans mutant exhibits a lowered acid resistance, which affects the growth, lethal pH, proton permeability, H-ATPase activity, cell permeability and biofilm formation but not the minimum glycolytic pH of the mutant strain.

OBJECTIVETo investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in myocardial ischemia-reperfusion (IR) injury in isolated perfused rat heart and explore the underlying mechanisms.

METHODSAn ischemia-reperfusion (IR) model was prepared using isolated rat hearts perfused with Krebs-Henseleit solution were randomly divided into control group, 2.5 µmol/L KN-93 group, IR (induced by ischemia for 45 min followed by reperfusion for 120 min) group and KN-93+IR group. The myocardial performance was evaluated by assessing the left ventricular pressure. Lactate dehydrogenase (LDH) activity and cTnI content in the coronary flow and the infarct size were determined to evaluate the myocardial injury. The phosphorylation of CaMKII (p-CaMKII) and PLN (p-PLN) and oxidation of CaMKII (ox--CaMKII) were measured with Western blotting. The activity of mitochondrial superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using ELISA.

RESULTSCompared with the control group, KN-93 treatment at 2.5 µmol/L produced no significant effects on cardiac function or performance in rat hearts without IR injury. Myocardial IR injury significantly decreased myocardial performance and mitochondrial SOD activity in the perfused hearts (P<0.01) and caused significantly increased infarct size, LDH activity, cTnI content, expressions of p-CaMKII, ox-CaMKII and p-PLN, and also increased mitochondrial MDA content (P<0.01). KN-93 treatment at 2.5 µmol/L administered before ischemia and before reperfusion markedly attenuated such changes induced by ischemia and reperfusion (P<0.01).

CONCLUSIONCaMKII participates in myocardial IR injury in isolated rat heart, and inhibiting CaMKII can alleviate myocardial injury by relieving mitochondrial oxidation stress.

OBJECTIVETo investigate the association between SCN1A rs3812718 polymorphism and generalized epilepsy with febrile seizures plus (GEFS+), and to provide potential molecular targets for the diagnosis and treatment of GEFS+.

METHODSThe iPLEX technique in the MassARRAY system was used to determine SCN1A rs3812718 polymorphism, genotype frequency, and allele frequency in 50 patients with GEFS+ and 50 healthy controls.

RESULTSAs for the frequencies of CC, CT, and TT genotypes in SCN1A rs3812718, there was a significant difference in the frequency of TT genotype between the GEFS+ group and the control group (P<0.05). There was also a significant difference in the frequency of T allele between the two groups (P<0.05). Compared with those carrying CC genotype or C allele, the individuals with CT genotype , TT genotype or T allele had a higher risk of developing GEFS+ (CT/CC: OR=4.05, 95%CI: 1.04-15.69; TT/CC: OR=30.60, 95%CI: 6.46-144.85; T/C: OR=4.64, 95%CI: 2.54-8.48).

CONCLUSIONSSCN1A rs3812718 polymorphism is a risk factor for GEFS+, and the population carrying T allele may have an increased risk of GEFS.

OBJECTIVETo study the influence of cow's milk protein allergy (CMPA) on the diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV standard in infants and young children.

METHODSA total of 84 children aged 1 month to 3 years who were diagnosed with CMPA were enrolled as the case group, and 84 infants and young children who underwent physical examination and had no CMPA were enrolled as the control group. The pediatricians specializing in gastroenterology asked parents using a questionnaire for the diagnosis of FGID based on the Rome IV standard to assess clinical symptoms and to diagnose FGID.

RESULTSThe case group had a significantly higher incidence rate of a family history of allergies than the control group (P<0.05). In the case group, 38 (45%) met the Rome IV standard for the diagnosis of FGID, while in the control group, 13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID, the case group had significantly higher diagnostic rates of reflex, functional diarrhea, difficult defecation, and functional constipation than the control group (P<0.05). The children who were diagnosed with FIGD in the control group were given conventional treatment, and those in the case group were asked to avoid the intake of cow's milk protein in addition to the conventional treatment. After 3 months of treatment, the case group had a significantly higher response rate to the treatment than the control group (P<0.05).

CONCLUSIONSIn infants and young children, CMPA has great influence on the diagnosis of FGID based on the Rome IV standard. The possibility of CMPA should be considered during the diagnosis of FGID.

OBJECTIVETo study the burden of pediatric cancer in Jiangxi, China, in 2010 and 2015 and its changes from 2010 to 2015.

METHODSThe data of pediatric cancer in Jiangxi in 2010 and 2015 were collected from the Global Burden of Disease Study 2015 in China, including number of cases, number of deaths, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). The standardized incidence rate, mortality rate, and DALY rate were calculated with the national census data in 2010 as the standard population, in order to evaluate the changes in incidence, mortality, and disease burden of pediatric cancer in Jiangxi.

RESULTSIn both 2010 and 2015, boys had higher numbers of cases, deaths, and DALY than girls, and the 5-14 years group had higher numbers than the 0-4 years group; boys had higher incidence rate, mortality rate, and DALY rate than girls, and the 0-4 years group had higher rates than the 5-14 years group. In 2015, the standardized incidence rate of pediatric cancer was reduced by 6.66% in the 0-4 years group and 17.56% in the 5-14 years group; the standardized mortality rate was reduced by 11.34% in the 0-4 years group and 21.78% in the 5-14 years group; the standardized DALY rate was reduced by 11.27% in the 0-4 years group and 21.67% in the 5-14 years group. Among the different types of pediatric cancer, leukemia had the highest standardized DALY rate in 2010 and 2015, followed by brain cancer and non-Hodgkin's lymphoma.

CONCLUSIONSThere was a certain reduction in the burden of pediatric cancer in Jiangxi from 2010 to 2015. Leukemia, brain cancer, and non-Hodgkin's lymphoma are the focus of prevention and treatment, and children aged less than 5 years and boys should be closely monitored.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

No abstract available.
Lower Extremity* ; Lymph Nodes* ; Lymphedema*

BACKGROUND AND PURPOSE: Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 0.5 million Chinese adults. METHODS: Information about FHS was self-reported. The median follow-up time was 7.16 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system. Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests. RESULTS: Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number of first degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively, P(trend) <0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for sibling history and parental history, respectively. Similar associations with offspring stroke risk were observed between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49, 95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking). CONCLUSIONS: FHS is an independent risk factor for stroke in Chinese. The more first degree relatives are affected by stroke, the higher are individuals’ risk of suffering from stroke. The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS.
Adult ; Asian Continental Ancestry Group ; China* ; Cohort Studies* ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Parents ; Proportional Hazards Models ; Risk Factors ; Siblings ; Smoke ; Smoking ; Stroke*