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Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.

The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

Background The aim of this study is to quantify the effects of the SARS-CoV-2 pandemic on health services utilization in China using over four years of routine health information system data. Methods We conducted a retrospective observational cohort study of health services utilization from health facilities at all levels in all provinces of mainland China. We analyzed monthly all-cause health facility visits and inpatient volume in health facilities before and during the SARS-CoV-2 outbreak using nationwide routine health information system data from January 2016 to June 2020. We used interrupted time series analyses and segmented negative binomial regression to examine changes in healthcare utilization attributable to the pandemic. Stratified analyses by facility type and by provincial Human Development Index (HDI) – an area-level measure of socioeconomic status – were conducted to assess potential heterogeneity in effects. Findings In the months before the SARS-CoV-2 outbreak, a positive secular trend in patterns of healthcare utilization was observed. After the SARS-CoV-2 outbreak, we noted statistically significant decreases in all indicators, with all indicators achieving their nadir in February 2020. The magnitude of decline in February ranged from 63% (95% CI 61–65%; p <0•0001) in all-cause visits at hospitals in regions with high HDI and 71% (95% CI 70–72%; p <0•0001) in all-cause visits at primary care clinics to 33% (95% CI 24–42%; p <0•0001) in inpatient volume and 10% (95% CI 3–17%; p = 0•0076) in all-cause visits at township health centers (THC) in regions with low HDI. The reduction in health facility visits was greater than that in the number of outpatients discharged (51% versus 48%; p <0•0079). The reductions in both health facility visits and inpatient volume were greater in hospitals than in primary health care facilities ( p <0•0001) and greater in developed regions than in underdeveloped regions ( p <0•0001). Following the nadir of health services utilization in February 2020, all indicators showed statistically significant increases. However, even by June 2020, nearly all indicators except outpatient and inpatient volume in regions with low HDI and inpatient volume in private hospitals had not achieved their pre-SARS-COV-2 forecasted levels. In total, we estimated cumulative losses of 1020.5 (95% CI 951.2- 1089.4; P <0.0001) million or 23.9% (95% CI 22.5–25.2%; P <0.0001) health facility visits, and 28.9 (95% CI 26.1–31.6; P <0.0001) million or 21.6% (95% CI 19.7–23.4%; P <0.0001) inpatients as of June 2020. Interpretation Inpatient and outpatient health services utilization in China declined sig...

Abstract Background. The COVID-19 outbreak required the significantly increased working time and intensity for health professionals in China, which may cause stress signs. Methods. From March 2–13 of 2020, 4,618 health professionals in China were included in an anonymous, self-rated online survey regarding their concerns on exposure to the COVID-19 outbreak. The questionnaires consisted of five parts: basic demographic information and epidemiological exposure; occupational and psychological impact; concerns during the episode; coping strategies; and the Huaxi Emotional-Distress Index (HEI). Results. About 24.2% of respondents experienced high levels of anxiety or/and depressive symptoms since the COVID-19 outbreak. Respondents who worried about their physical health and those who had COVID-19 infected friends or close relatives were more likely to have high HEI levels, than those without these characteristics. Further, family relationship was found to have an independent protective effect against high HEI levels. Their main concerns were that their families would not be cared for and that they would not be able to work properly. Compared to respondents with clear emotional problems, those with somewhat hidden emotional issues adopted more positive coping measures. Conclusions. About a quarter of medical staff experienced psychological problems during the pandemic of COVID-19. The psychological impact of stressful events was related to worrying about their physical health, having close COVID-19 infected acquaintances and family relationship issues. Therefore, the psychological supprot for medical staff fighting in the COVID-19 pandemic may be needed.

PurposeTo explore regional variation of the macular microvasculature in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), also to detect the association between retinal macular microvascular parameters and the progress of preclinical AD.MethodsProspective study of healthy controls, patients with MCI and patients with AD by using Optical coherence tomography angiography (OCT‐A). We quantified foveal avascular zone (FAZ) areas, densities of the superficial retinal capillary plexuses (SRCP) and deep retinal capillary plexuses (DRCP). The SRCP and DRCP were divided into inner (3 mm) and external (6 mm) annular rings, each containing four quadrants (SI, II, TI, NI, SE, IE, TE and NE). The data were analysed statistically by using SPSS 22 software.ResultsTotally, 60 subjects including 21 HC (33 eyes), 21 patients with MCI (32 eyes) and 18 AD patients (28 eyes) were recruited. The microvascular densities of DRCP at all quadrants of the parafovea and perifovea were significantly lower in AD patients compared to HC group (p < 0.05). Compared to the HCs, MCI patients showed significant microvascular loss in most sectors of the parafovea and the SE sector of the DRCP (p < 0.05), but not in the parafovea (p = 0.829) or perifovea (p = 0.824) of the SRCP. No significant difference was found in microvascular density of SRCP among the groups, except at SI between the AD and HC groups (p = 0.048).ConclusionOur findings demonstrated the macular microvascular attenuation in MCI and AD patients. Both AD and MCI patients showed retinal microvascular density loss, which is more significant in the deep retinal capillary plexuses. Optical coherence tomography angiography (OCT‐A) can be used to identify early microvascular abnormalities in AD and MCI. Quantified microvascular density in the DRCP might serve as potential biomarkers of early sign of AD then contribute to forestall the progression of preclinical AD.

Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.

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