Traffic-related air pollution, chronic stress, and changes in exhaled nitric oxide and lung function among a panel of children with asthma living in an underresourced community.

We examined associations between short-term exposure to traffic-related air pollutants (TRAP) and airway inflammation and lung function in children with asthma, and whether these associations are modified by chronic psychological stress. Residents of underresourced port-adjacent communities in New Jersey were concerned about the cumulative impacts of exposure to TRAP, particularly diesel-engine truck emissions, and stress on exacerbation of asthma among children. Children with asthma aged 9-14 (n = 35) were recruited from non-smoking households. We measured each participant's (1) continuous personal exposure to black carbon (BC, a surrogate of TRAP) at 1-min intervals, (2) 24-h integrated personal exposure to nitrogen dioxide (NO2), (3) daily fractional exhaled nitric oxide (FeNO), and (4) lung function for up to 30 consecutive days. Personal BC was recorded by micro-aethalometers. We measured daily FeNO using the NIOX MINO, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) using Easy One Frontline spirometers. Chronic stress was measured with the UCLA Life Stress Interview for Children. The association was examined using linear mixed-effect models. In the fully adjusted model, an interquartile range (IQR) increase in BC at lag 0-6 h before the FeNO measurement was associated with 8 % (95 % CI: 3 % - 12 %) increase in FeNO, whereas an IQR increase in BC at lag 7-12 h and lag 0-24 h were associated with 6 % (95 % CI: 2 % - 11 %) and 7 % (2 % - 12 %) FeNO increases, respectively. There were no significant lung function changes per IQR increase in BC. No interactions were observed between chronic stress and BC on FeNO. Chronic stress was negatively associated with individual average FeNO levels. Our findings suggest that higher levels of BC exposure within the prior 24 h increased airway inflammation levels in children with asthma, with the strongest effect observed within the first 6 h.

[Proximal tibial aspect ratio and matching of tibial component in total knee arthroplasty: a narrative review].

Proximal tibial aspect ratio (PTAR) is closely related to age, disease status and cutting parameters with considerable inter-individual variation independent of gender and race, nevertheless the aspect ratio of tibial components from different manufacturers remains relatively constant from smallest to largest size. As a result, component mismatching is an unavoidable dilemma during tibia preparation in total knee arthroplasty (TKA). Various prosthesis systems all can achieve more than 80% coverage on proximal tibia, whereas their optimal fit rates are generally not more than 50%. It is difficult for symmetrical components to avoid anteroposterior mismatch, internal malrotation tends to occur when maximum coverage is pursued on the resected surface with a medial dominant plateau or lower PTAR. Although it is easier to achieve a balance of rotation and coverage with anatomical components, significant anteromedial overhang tends to appear on the resected surface with a symmetrical or lateral dominant plateau. Further researches should focus on the law of inter-individual variability of proximal tibial morphology, the quantitative definition of "ideal matching" safety zone of key morphological parameters on different areas of proximal tibia and the methodology of realizing"ideal matching"in the majority patients with the least amount of component sizes. In addition, with the rapid development of additive manufacturing and digital orthopedic technology, individual customized implant is expected to become a breakthrough point in the field of TKA component fitting.

Comparison of laparoscopic hysteropectopexy and vaginal hysterectomy in women with pelvic organ prolapse.

BACKGROUND: To study whether laparoscopic hysteropectopexy (LHP) can be substituted for vaginal hysterectomy (VH) in patients with pelvic organ prolapse (POP), we compared VH with the relatively new procedure, LHP. METHODS: This retrospective study included 176 women who underwent LHP (N.=54) or VH (N.=122) for a Pelvic Organ Prolapse Quantification (POP-Q) System stage 2 or higher pelvic organ prolapse between January 2011 and December 2019. We compared the surgical outcomes and overall rate of complications between the two groups. RESULTS: The average length of hospitalization was 5.28 days for the LHP group and 7.08 days for the VH group. EBL (mL) in the LHP group was 32.2, whereas it was 47.7 in the VH group. The average operation time (min) was 68.2 in the LHP group and 98.9 in the VH group. Twenty-seven patients (22.1%) in the VH group had postoperative voiding difficulty compared with 2 patients (3.7%) in the LHP group. The overall number of intraoperative complications was 6 (11%) in the LHP group and 34 (27.9%) in the VH group. CONCLUSIONS: This study demonstrated that LHP is more effective than VH in patients with POP. However, since the number of cases was small and retrospective studies are limited, we recommend a randomized controlled trial to be conducted in the future to confirm our results.

[Study on the willingness to quit smoking and its influencing factors among current smokers in rural areas in China].

Objective: To study the willingness of current smokers to quit smoking in rural areas and related factors to provide a reference for tobacco control. Methods: The data were collected from the China Chronic Disease and Risk Factor Surveillance in 2018. A multi-stage stratified cluster sampling was used to select 184 509 residents (≥18 years old); among the residents, 10 241 current smokers in rural areas were included in the study. χ2/F test was used to analyze the factors such as willingness to quit smoking and demographic information, tobacco use, cognition of tobacco-related hazard knowledge, the prevalence of chronic diseases, and other factors. Unconditional multifactor logistic regression analysis was used in multivariate analysis. Results: A total of 3 453 (37.46%) considered quitting smoking in the next 12 months. Logistic regression analysis showed that occasional smokers were more willing to quit smoking than daily smokers (OR=0.693, 95%CI: 0.494-0.971), and those who smoked less than 1 pack per day were more willing to quit than those who smoked 1 pack or more per day (OR=0.628,95%CI: 0.511-0.771), those who had quit smoking within 12 months were more willing to quit than those who had not quit within 12 months (OR=0.438, 95%CI: 0.357-0.537), and those with high awareness of tobacco hazards were more willing to quit smoking (OR=1.056, 95%CI: 1.028-1.086). The differences were statistically significant (P<0.05). Conclusions: The willingness of current smokers in rural areas to quit smoking is related to the smoking situation, smoking intensity, previous smoking cession experience, and knowledge of the specific health effects of smoking. It suggests that health education should be strengthened through more efficient health communication methods in rural areas and provide brief smoking cessation interventions to improve rural smokers' willingness to quit smoking.

[Rotational alignment of the tibial component in total knee arthroplasty:a narrative review].

Component malrotation is one of the major causes of failure in total knee arthroplasty.Based on previous researches,Insall line has excessive external rotation tendency.Although Akagi line is the most recognized anatomical axis at present,it still has a certain tendency of internal rotation.The tibial posterior condylar axis is not suitable for symmetrical component and yet the Curve-on-Curve technique is not suitable for anatomic component.In addition,reference to any fixed anatomical markers cannot ensure the rotation consistency of tibiofemoral component in extension position.Although range of motion technique is beneficial to tibiofemoral rotation synchronization,its clinical effect seems to be unstable.Nevertheless,Patients can obtain good postoperative results with all major techniques.Before the recognized "gold standard" is defined,orthopedic surgeons can determine the rotation alignment of tibial component according to their most accustomed surgical method.With a deeper understanding of knee anatomy,biomechanics and kinematics,digital assistive technology may be expected to become a breakthrough in the tibial rotational alignment.

[24 hours urinary sodium and potassium excretion and association with blood pressure among people aged 18-75 years old in six Chinese provinces].

Objective: To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces. Methods: From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted. Results: A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95%CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95%CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95%CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95%CI:-2.05, -0.48). Conclusion: The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.

ORAOV1-B Promotes OSCC Metastasis via the NF-κB-TNFα Loop.

Metastasis, a powerful prognostic indicator of oral squamous cell carcinoma (OSCC), is chiefly responsible for poor cancer outcomes. Despite an increasing number of studies examining the mechanisms underlying poor outcomes, the development of potent strategies is hindered by insufficient characterization of the crucial regulators. Long noncoding RNAs (lncRNAs) have recently been gaining interest as significant modulators of OSCC metastasis; however, the detailed mechanisms underlying lncRNA-mediated OSCC metastasis remain relatively uncharacterized. Here, we identified a novel alternative splice variant of oral cancer overexpressed 1 (ORAOV1), named as ORAOV1-B, which was subsequently validated as an lncRNA and correlated with OSCC lymph node metastasis; significantly increased invasion and migration were observed in ORAOV1-B-overexpressing OSCC cells. RNA pulldown and mass spectrometry identified Hsp90 as a direct target of ORAOV1-B, and cDNA microarrays suggested TNFα as a potential downstream target of ORAOV1-B. ORAOV1-B was shown to directly bind to and stabilize Hsp90, which maintains the function of client proteins, receptor-interaction protein, and IκB kinase beta, thus activating the NF-κB pathway and inducing TNFα. Additionally, TNFα reciprocally enhanced p-NF-κB-p65 and the downstream epithelial-mesenchymal transition. ORAOV1-B effects were reversed by a TNFα inhibitor, demonstrating that TNFα is essential for ORAOV1-B-regulated metastatic ability. Consistent epithelial-mesenchymal transition in the ORAOV1-B group was demonstrated via an orthotopic model. In the metastatic model, ORAOV1-B significantly contributed to OSCC-related lung metastasis. In summary, the novel splice variant ORAOV1-B is an lncRNA, which significantly potentiates OSCC invasion and metastasis by binding to Hsp90 and activating the NF-κB-TNFα loop. These findings demonstrate the versatile role of ORAOV1 family members and the significance of genes located within 11q13 in promoting OSCC. ORAOV1-B might serve as an attractive OSCC metastasis intervention target.

Exposure to traffic-related air pollution and changes in exhaled nitric oxide and DNA methylation in arginase and nitric oxide synthase in children with asthma.

BACKGROUND: Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma. METHODS: We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level. RESULTS: Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0-6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13-24 h and lag 0-24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed. CONCLUSIONS: Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

[Burden of disease attributable to alcohol use and its counter measure in China].

Harmful drinking causes serious consequences to social security as well as physical and mental health of the general public. The Global Burden of Disease Study (2017) showed that the number of alcohol-related deaths in China in 2017 was 1.82 times higher than that in 1990, and the population attributable fraction increased by 44.13%. The burden of disease caused by drinking alcohol had been increasing. By comparing with the comprehensive intervention strategy of restricting harmful drinking put forward by the World Health Organization, we suggest that the current interventions that need to be improved in China should include several aspects below: (1) strengthening the control of alcohol production, marketing and circulation, (2) restricting the availability of alcohol products for minors through enterprise self-discipline, laws and regulations, parents and school health education, (3) bridging gaps in appropriate techniques and services for alcohol restriction/abstinence in the health care system, (4) providing services such as rapid screening of alcohol dependence and short abstinence interventions, (5) strengthening restrictions on alcohol advertising especially in new media (e.g., online and social media) marketing practices for alcohol products, (6) conducting scientific research and evaluation on alcohol tax-related issues, and (7) regularly reviewing alcohol prices related to inflation and income levels.

GPR39 Overexpression in OSCC Promotes YAP-Sustained Malignant Progression.

The clinical outcome of oral squamous cell carcinoma (OSCC) has not improved in recent years, mainly due to the limited effective targeted therapy that has been applied. Recently, a transcriptional coactivator, YAP, has been shown to have a key regulatory role in malignant progression in multiple cancers, including OSCC. But pharmacologically targeting YAP or the Hippo pathway, which is the main signaling pathway regulating YAP, has been proven to be challenging. Therefore, uncovering YAP upstream regulators in cancer would identify novel therapeutic targets for treatment of YAP-sustained cancers. Here, we showed that YAP was overactivated in OSCC and that high YAP activity in patients with OSCC was associated with malignant progression and poor survival. We uncovered that GPR39 (a G protein-coupled receptor) was overexpressed in OSCC, that the expression level of GPR39 was correlated with the activity level of YAP, and that the high GPR39 expression was associated with malignant progression and poor survival in patients with OSCC. Moreover, we found that GPR39 regulated YAP through a Gαq/11-RhoA-dependent signaling pathway. Importantly, inhibition of GPR39 resulted in YAP-sustained OSCC growth inhibition. Our findings suggest that GPR39 is a potential therapeutic target for OSCC treatment with itself as a biomarker.

[Disease burden on uterine fibroids in China, 1990 and 2016].

Objective: To assess the disease burden on uterine fibroids in China in 1990 and 2016. Methods: Data were extracted from the Global Burden of Disease Study 2016. Burdens of uterine fibrosis among different age groups and provinces were measured in 1990 and 2016, with key indicators including number of cases, prevalence rates, disability-adjusted life year (DALY) and the rates of DALY. The WHO world standard population, 2010-2035 was used to calculate the age- standardized rates. Results: In 1990 and 2016, there were 13 695 567 and 27 169 312 women aged 15 years and older, suffered from uterine fibrosis respectively, with prevalence rate as 2.48% and 4.10%, DALY as 146 045.05 life years and 281 976.67 life years, and the DALY rate as 26.40/100 000 and 42.50/100 000, in 1990 and 2016 respectively. Both the prevalence rate and the DALY rate increased with age, reaching the peak on the 45-49 years-old, in both 1990 and 2016. Women aged 40-54 years accounted for 55.60% (1990) and 66.74% (2016) of the total cases while 48.37% (1990) and 60.65% (2016) of the total DALY. The first three provinces with highest DALYs were Shandong (1990: 12 574.67 life year; 2016: 22 728.12 life year), Henan (1990: 10 849.29 life year; 2016: 18 454.32 life year) and Jiangsu (1990: 10 501.55 life year; 2016: 18 274.10 life year), while the three provinces with leading standardized DALY rates were Heilongjiang (1990: 48.20/100 000; 2016: 47.00/100 000), Shanxi (1990: 44.50/100 000; 2016: 47.70/100 000) and Tianjin (1990: 43.80/100 000; 2016: 46.40/100 000) in both 1990 and 2016. Compared with 1990, the number of cases with uterine fibroids increased by 13 473 745 (with rate of change as: 98.38%), standardized prevalence rate increased by 1.88%, DALY value increased by 135 931.62 life years (with the rate of change as 93.08%) and standardized DALY rate increased by 5.92% among Chinese women, in 2016. Conclusion: Menopausal women were the ones hard hit by uterine fibrosis. Compared with data from 1990, the disease burden of uterine fibrosis increased rapidly in China, in 2016.

[Disease burden of diabetes attributable to high body mass index in China,1990-2016].

Objective: To analyze the burden of disease (BOD) on diabetes attributable to high BMI in China from 1990 to 2016. Methods: Data based on population of the 2016 Global Burden of Disease Study for China were used to analyze the attributable fractions (PAF) of BOD for diabetes attributable to high BMI. Measurements for attributable BOD of diabetes included disability adjusted life years (DALY), years of lost life (YLL), years living with disability (YLD), death number and mortality rate. The average world population from 2010 to 2035 was used as a reference. Results: In 2016, death number of diabetes attributable to high BMI was 40 310, which was significantly higher than that in 1990 (15 008). Age-standardized death rate of diabetes attributable to high BMI increased from 2.01/100 000 in 1990 to 2.60/100 000 in 2016, which showed a more significant increasing trend in both males and people aged 15-49 years. DALYs of diabetes attributable to high BMI increased from 1.09 million person years to 3.30 million person years. YLL and YLD also showed increasing trends. The highest increasing rate of YLD was in people aged 15-49 years. High BMI was responsible for 26.01% of the diabetes deaths in 2016 in China, an increase of 39.39% compared with that in 1990 (18.66%). Most provinces in China experienced a sharp increase of DALY of diabetes attributable to high BMI from 1990 to 2016. Inner Mongolia, Xinjiang, Zhejiang, Macao SAR, Sichuan and Qinghai had the most significant increase tendency in terms of DALY rate during this period. Conclusions: There was a rapid increase of the deaths and mortality rate of diabetes attributable to high BMI, causing a heavy disease burden, in China from 1990 to 2016. The BOD varied in both different age and gender groups. More attention should be paid to males and people aged 15-49 years in the prevention and control programs of diabetes.

Hemoglobin A1c predicts hemorrhagic transformation and poor outcomes after acute anterior stroke.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a major complication of acute ischaemic stroke that is potentially related to clinical deterioration. The objective of this study was to assess whether chronic hyperglycemia is a predictive factor of HT in patients with acute anterior stroke. METHODS: Patients with acute anterior stroke were included in this study. Hemoglobin A1c (HbA1c) was measured in the morning after hospitalization. HT was detected by computed tomography scans or gradient echo magnetic resonance imaging performed 4 (±2) days after onset. Univariate and multivariate logistic regression analyses were used to assess the risks for HT and short-term outcomes. RESULTS: Of the 426 patients included, 93 (21.8%) had HT: 61 (14.3%) presented with hemorrhagic infarction and 32 (7.5%) presented with parenchymal hematoma. A total of 54 patients received thrombolytic treatment and 18 (33.3%) were found to have HT. In the multivariate analysis, HbA1c [odds ratio (OR), 1.294; 95% confidence interval (CI), 1.097-1.528], infarction size (OR, 3.358; 95% CI, 1.748-6.449) and thrombolytic therapy (OR, 3.469; 95% CI, 1.757-6.847) were predictors of HT. The predictive effect of HbA1c on HT was still observed in both groups when patients were stratified according to the levels of fasting blood glucose. HbA1c was found to be a predictor of poor outcomes in the multilogistic regression analysis (OR, 1.482; 95% CI, 1.228-1.788). CONCLUSIONS: Higher HbA1c was independently related to HT and poor neurological outcomes in patients with ischaemic stroke. These findings have significant implications for the treatment of diabetes and glucose management in patients with diabetes mellitus and/or acute ischaemic stroke.

[Disease burden for gynecological disease in China, 2016].

Objective: To assess the disease burden for gynecological disease in China in 2016. Methods: Data were extracted from the global burden of disease study 2016 (GBD 2016) . The burden of gynecological disease among age groups and provinces groups was assessed by prevalence rate, mortality rate, years lived with disability (YLD) , years of life lost due to premature mortality (YLL) and disability-adjusted life years (DALY) . An average world population age-structure for the period 2010-2035 was adopted to calculate age-standardized rates. Results: In 2016, the prevalence rate of gynecological disease in women aged 15 years and above in China was 24.94%, of which was 36.71% to women of childbearing age. The number of DALY from gynecological disease was 2 727 637.82 life years in 2016, with the DALY rate was 411.12/100 000 and standardized DALY rate was 341.80/100 000. The first three gynecological diseases with highest DALY and DALY rate among Chinese women aged ≥15 years were premenstrual syndrome (815 004.64 life years, 122.84/100 000) , uterine fibroids (281 976.67 life years, 42.5/100 000) and endometriosis (154 792.89 life years, 23.33/100 000) . The DALY caused by gynecological disease in Guangdong (220 871.19 life years) , Shandong (190 968.72 life years) , Henan (171 273.92 life years) , Jiangsu (168 404.27 life years) and Sichuan (144 358.5 life years) were higher than other provinces. The standardized DALY rate attributable to gynecological disease were highest in Xinjiang Uygur Autonomous Region (404.00/100 000) , Shanghai (394.90/100 000) , Heilongjiang (382.00/100 000) , Beijing (365.70/100 000) and Jiangsu (357.50/100 000). Conclusions: Gynecological disease is a great threat to women's reproductive health. Effective measures should be taken to address the issue, especially to women of childbearing age.

[Effect of lifestyle intervention among high risk group of chronic diseases in Shenzhen Futian district].

Objective: To evaluate the effect of lifestyle intervention among high risk group of chronic diseases in Shenzhen Futian district. Methods: 12 out of 115 communities were randomly selected in Futian district of Shenzhen city from October to November, 2013, and 1 923 cases were screened by multiple ways as high risk groups of chronic diseases. High risk groups of chronic diseases were divided into intervention group (1 338 cases, from five residential communities and three villages within city) and control group (585 cases, from four residential communities). The intervention group received group based health education activities as well as lifestyle intervention. The intervention group was provided with health management which was mainly lifestyle intervention. No intervention was implemented in the control group. All participants were followed up over two years. 1 563 participants (1 002 in intervention group and 561 in control group) were followed up from October to November, 2015. The changes of lifestyle related outcome indicators were analyzed to examine the effect of intervention. Results: In the intervention group, 21.8% (219 persons) in high risk groups of chronic diseases became healthy individuals and 15.2% (152 persons) became patients with chronic diseases. In the control group, 9.6% (54 persons) in high risk groups of chronic diseases became healthy individuals and 20.5% (115 persons) became patients with chronic diseases. The outcome of the intervention group was better than that of the control group and the difference was statistically significant (χ2=-5.67, P<0.001). The proportion of people who knew how to correctly use of oil control pot in the intervention group increased from 61.00% (61/100) to 80.00% (280/350). The proportion of people who took oil control measures in the intervention group increased from 36.43% (365/1 002) to 56.99%(571/1 002). The changes in the intervention group were statistically different (P<0.001), but there was no statistical difference in the control group over the years (P>0.05). The proportion of people who knew how to correctly use of the salt restriction spoon increased from 81.95% (109/133) to 97.99% (342/349). The proportion of people who took salt control measures increased from 45.61% (457/1 002) to 62.67% (628/1 002) in the intervention group. The changes in the intervention group were statistically different (P<0.001). There was no statistical difference in the control group over the years (P>0.05). Conclusion: The proportion of people who adopted healthy lifestyles has increased after 2 years intervention and the lifestyle intervention demonstrated good effect.

25-Hydroxyvitamin D3 -enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D3 (25VD3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis. MATERIAL AND METHODS: Porphyromonas gingivalis-infected db/db mice were treated with 25VD3 . Their fasting blood glucose and body weight were monitored every other week, and the levels of alveolar bone loss and serum inflammatory cytokines (tumor necrosis factor-α, interferon-γ and interleukin-6) were determined at the time of killing. The effect of PTPN2 on human OKF6-TERT2 oral keratinocytes was examined through the knockout of PTPN2 using the CRISPR/Cas9 knockout plasmid. The expression levels of the PTPN2, vitamin D receptor and JAK1/STAT3 signaling proteins in the gingival epithelium and OKF6-TERT2 cells were determined through western blot and immunohistochemical analyses. RESULTS: After 25VD3 treatment, db/db mice exhibited alleviated serum inflammatory cytokines and alveolar bone loss, and 25VD3 -enhanced PTPN2 expression decreased the expression of the JAK1/STAT3 signaling proteins in the gingival epithelium. Analyses of human oral keratinocytes showed that 25VD3 increased the expression of PTPN2, which dephosphorylates protein substrates in the JAK1/STAT3 signaling pathway. CONCLUSION: PTPN2 contributed to a decrease in periodontal inflammation in type 2 diabetes mellitus via dephosphorylate protein substrates in the JAK1/STAT3 signaling pathway after 25VD3 treatment in human oral keratinocytes and a mouse model of type 2 diabetes mellitus. A thorough understanding of PTPN2 and its involvement in inhibiting inflammation might provide alternative therapeutic approaches for the pathogenesis and treatment of diabetes mellitus-associated periodontitis.

Discovery and characterization of selective small molecule inhibitors of the mammalian mitochondrial division dynamin, DRP1.

Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential. Here we describe the discovery of novel small molecules that directly and selectively inhibit assembly-stimulated GTPase activity of the division dynamin, DRP1. In addition, these small molecules restore wild type mtDNA copy number in MFN1 knockout mouse embryonic fibroblast cells, a phenotype linked to deficient mitochondrial fusion activity. Thus, these compounds are unique tools to explore the roles of mitochondrial division in cells, and to assess the potential therapeutic efficacy of rebalancing mitochondrial dynamics in pathologies associated with excessive mitochondrial division.

[Deaths attributable to alcohol use and its impact on life expectancy in China, 2013].

Objective: To analyze the deaths attributable to alcohol use and its impact on people's life expectancy in China in 2013. Methods: The mortality data from the Disease Surveillance Points System and alcohol use data from China Chronic Disease Surveillance (2013) were used. The deaths attributed to alcohol use and its impact on the life expectancy of Chinese residents were estimated based on the principle of comparative risk assessment by calculating population attributable fraction. Results: In 2013, alcohol use resulted in 381 200 deaths, including 97 100 hemorrhagic stroke deaths, 88 200 liver cancer deaths, 61 400 liver cirrhosis deaths and 48 700 esophageal cancer deaths, and prevented 76 500 deaths, including 68 500, 4 900 and 3 100 deaths which might be caused by ischemic heart disease, hemorrhagic stroke and diabetes respectively. If risk factor of alcohol use is removed, the people's life expectancy would rise by an average of 0.43 years, especially in western China by 0.52 years, which was 0.12 years higher than that in eastern and central China, and the life expectancy of the population in rural and urban areas would rise by 0.48 years and 0.31 years respectively. Conclusions: Although alcohol has a protective effect on reducing ischemic heart disease, stroke and diabetes deaths, alcohol use is still a risk factor influencing the mortality and life expectancy of residents in China. It is necessary to take targeted measures to reduce the health problems caused by harmful use of alcohol.