Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway.

OBJECTIVE: To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization. METHODS: The ability of emodin to target vascular endothelial growth factor receptor 2 (VEGFR2) was predicted by molecular docking. The effects of emodin on the invasion, migration, and proliferation of human umbilical vein endothelial cells (HUVEC) were determined by cell counting kit-8, Transwell, and tube formation assays. Analysis of apoptosis was performed by flow cytometry. CD31 levels were examined by immunofluorescence. The abundance and phosphorylation state of VEGFR2, protein kinase B (Akt), signal transducer and activator of transcription 3 (STAT3), and P38 were examined by immunoblot analysis. Corneal alkali burn was performed on 40 mice. Animals were divided randomly into two groups, and the alkali-burned eyes were then treated with drops of either 10 µM emodin or phosphate buffered saline (PBS) four times a day. Slit-lamp microscopy was used to evaluate inflammation and corneal neovascularization (CNV) in all eyes on Days 0, 7, 10, and 14. The mice were killed humanely 14 d after the alkali burn, and their corneas were removed and preserved at －80 ℃ until histological study or protein extraction. RESULTS: Molecular docking confirmed that emodin was able to target VEGFR2. The findings revealed that emodin decreased the invasion, migration, angiogenesis, and proliferation of HUVEC in a dose-dependent manner. In mice, emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn. Compared to those of the PBS-treated group, lower VEGFR2 expression and CD31 levels were found in the emodin-treated group. Emodin dramatically decreased the expression of VEGFR2, p-VEGFR2, p-Akt, p-STAT3, and p-P38 in VEGF-treated HUVEC. CONCLUSION: This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization. Emodin might be a promising new therapeutic option for corneal alkali burns.

The association between blood glucose levels of children with type 1 diabetes mellitus and parental educational levels based on mobile health APP / 中国医师杂志

Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.

Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus

Background@#Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. @*Methods@#We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). @*Results@#Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05). @*Conclusion@#Although the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.

KLF2 is a therapeutic target for COVID-19 induced endothelial dysfunction

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1{beta} and TNF-, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.

Decline of SARS-CoV-2 specific IgG, IgM and IgA in convalescent COVID-19 patients within 100 days after hospital discharge

Monitoring the levels of SARS-CoV-2 specific antibodies such as IgG, M and A in COVID-19 patient is an alternative method for diagnosing SARS-CoV-2 infection and an simple way to monitor immune responses in convalescent patients and after vaccination. Here, we assessed the levels of SARS-CoV-2 RBD specific antibodies in twenty-seven COVID-19 convalescent patients over 28-99 days after hospital discharge. Almost all patient who had severe or moderate COVID-19 symptoms and a high-level of IgG during the hospitalization showed a significant reduction at revisit. The remaining patients who had a low-level IgG during hospitalization stayed low at revisit. As expected, IgM levels in almost all convalescent patients reduced significantly or stayed low at revisit. The RBD-specific IgA levels were also reduced significantly at revisit. We also attempted to estimate decline rates of virus-specific antibodies using a previously established exponential decay model of antibody kinetics after infection. The predicted days when convalescent patients RBD-specific IgG reaches to an undetectable level are approximately 273 days after hospital discharge, while the predicted decay times are 150 days and 108 days for IgM and IgA, respectively. This investigation and report will aid current and future studies to develope SARS-CoV-2 vaccines that are potent and long-lasting.

Association of Personal Protective Equipment Use with Successful Protection Against COVID-19 Infection Among Health Care Workers

The coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. In order to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs, we conducted a molecular epidemiological study among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. Nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) detection were performed to confirm SARS-CoV-2 infection among those HCWs. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 15, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. These HCWs were provided with adequate supply of PPE as committed by their original institutions or provinces. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. In conclusion, our findings indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection.

Association of Population Migration and Coronavirus Disease 2019 Epidemic Control

Background and ObjectiveTo analyze the impact of different patterns of migration flow in two cities, Hefei and Shenzhen, on the epidemic and disease control of Coronavirus Disease 2019 (COVID-19), in order to provide insight for making differentiated controlling policies. MethodsWe collected demographic and epidemiological information of confirmed COVID-19 cases in Hefei and Shenzhen between January 19 and February 11, 2020, from data officially published by the provincial and municipal Centers for Disease Control and Prevention (CDC). From these data we calculated basic reproduction number R0 to reflect the rate of spread of COVID-19 in these cities. Aggregated data of population migration during the same period was extracted from Baidu Migration. The change of R0 in the two cites were analyzed and compared. Spearman correlation analysis between R0 and population inflow from epidemic focus were performed. ResultsA total of 157 confirmed cases was identified in Hefei by 24:00 February 11, 2020, with an average age of 44.4{+/-}15.6 years, 74 female (47.1%) and 386 confirmed cases were identified in Shenzhen, with an average age of 45.15{+/-}17.99 years, 202 female (52.3%). Significant difference in the proportion of imported cases between the two cities was observed (Hefei vs Shenzhen, 24.2% vs 74.9%, p=0.000). Before January 31 2020, during the initial stage of the Level 1 Response to Major Public Health Emergencies, there was no significant association observed in Shenzhen between R0 and the proportion of population inflow from the epidemic focus (P =0.260, r=-0.452); meanwhile in Hefei, such association was strong (P =0.000, r=1.0). However, after the initial stage of response, the situation reversed. A weak association was observed in Shenzhen between be R0 and the proportion of population inflow from the epidemic focus (P=0.073, r=0.536) but not in Hefei (P =0.498, r=0.217). ConclusionFollowing Level 1 Response, consistent decline of R0 of COVID-19 was observed in both Hefei and Shenzhen. Different patterns of disease spread were observed in the two cities, driven by different patterns of population migration. This indicated that population migration should be taken into consideration when we set controlling policy of a novel infectious disease.

The validity and reliability of the revised Chinese version of diabetes self-management scales for adult type 1 diabetes patients / 中华内分泌代谢杂志

Objective In this study, we aimed to translate and revise the Summary of Diabetes Self-Care Activities( SDSCA) and the Confidence In Diabetes Self-care( CIDS) scales, to test the reliability and validity of the two scales in Chinese adult type 1 diabetes( T1D) patients. Methods In the first step, Chinese versions( C-SDSCA and C-CIDS) were developed conceptually equivalent to the English versions. And the investigation was conducted in 100 patients from Guangdong T1D Translational Medicine Study. 15 of them were randomly chosen to be retested 4 weeks later. Cronbach's α were used to assess reliability, and factor analysis to its validity. The relationship between scores of C-SDSCA and C-CIDS were analyzed using Spearman correlation analysis. Results The overall Cronbach's α of C-SDSCA was 0.72 and the retest reliability was 0.95( sub-scale:0.67-1.00) . 4 common factors were extracted by factor analysis, and the cumulative contribution was 87.39％. As for C-CIDS, the general Cronbach's α was 0.84 and the retest reliability was 0. 70 ( sub-scale: 0. 49-0. 86 ) . 6 common factors were extracted and the cumulative contribution was 75.41％. The score of the two scales was positively related(r=0.61, P<0.01). Conclusion The revised C-CIDS and C-SDSCA scales turn out to have good reliability and validity, and can be used as instruments to assess diabetes self-management efficacy and self-care activities of Chinese adult T1D patients.

The effect of mobile application based interactive peer support on glycemic control in patients with type 1 diabetes mellitus / 中华内科杂志

Objective@#To evaluate the effect of mobile application (APP) based interactive peer support on glycemic control in patients with type 1 diabetes mellitus (T1DM).@*Methods@#The data of the present study were from the largest mobile APP platform for patients with T1DM in China, Tangtangquan. Patients with T1DM who has registered in the APP for at least 1 year and had completed data entry were recruited. According to the monthly interaction index during the first year of APP registration (including four indicators: praise, comment, posting and collection), the eligible patients were divided into the high-interaction group and the low-interaction group. The changes from baseline of self-blood glucose monitoring frequency (SMBG), glycosylated hemoglobin (HbA1c), incidence of hyperglycemia and incidence of hypoglycemia were compared between the two groups after one year of using the APP.@*Results@#A total of 238 patients with T1DM with an age of (27±8) years were included. Among them, 77.3% (184/238) were female. The baseline SMBG [the low-interaction group (1.71±1.14) times/day vs. the high-interaction group (1.82±1.15) times/day] and HbA1c [the low-interaction group (6.72±0.99)% vs. the high-interaction group (6.76±1.04)%] were comparable between the two groups. After one year use of the APP, the frequency of SMBG in the high-interaction group was significantly higher than that in the low-interaction group [ΔSMBG (0.59+2.06) times/d vs. (0.08+1.69) times/d, t=4.280, P=0.04), and the reduction of HbA1c was more obvious in the high-interaction group [ΔHbA1c (-0.40+1.10)% vs. (-0.06+1.13)%, t=5.651, P=0.018] than in the lower-interaction group. The incidence of hyperglycemia in the high-interaction group was significantly lower than that in the low-interaction group [13.19(6.22,23.19)% vs. 17.69(10.56,30.49)%, Z=2.850, P=0.005]. There was no significant difference in the incidence of hypoglycemia between the two groups [4.62(2.14, 8.03)% vs. 4.83(2.06, 8.87)%, Z=1.276, P=0.204]. The correlation analysis showed that interaction index was significantly associated with the reduction of HbA1c and incidence of hyperglycemia.@*Conclusion@#Participation in interactive peer education via mobile APP may be beneficent for glycemic control in patients with T1DM.