Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

[Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China].

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.

Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives.

A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent.

Synthesis and Biological Evaluation of Curcuminoid Derivatives.

Many curcuminoid derivatives have been reported to have multiple biological activities. The aim of this study was to improve the biological activity of curcuminoids by synthesizing 16 new derivatives which combined cinnamic acids with curcuminoids, and we also analyzed the structure-activity relationship of the new compounds. Almost all the new compounds showed encouraging activity, especially compound 7g. It had much better antioxidant activity than curcuminoids and Vitamin C (VC), and also had the most significant antibacterial activity, which was 5-folder better than ampicillin (one of the best marketed antibiotics) with a minimum inhibitory concentration (MIC) of 0.5 µg/mL against Gram-positive cocci (Staphylococcus aureus and Streptococcus viridans) as well as Escherichia coli and 0.6 µg/mL against Enterobacter cloacae. Compound 7g also showed the greatest anticancer activity with a much lower IC50, which was 0.51 µM against MCF-7, 0.58 µM against HepG-2, 0.63 µM against LX-2, and 0.79 µM against 3T3. The results suggest that these compounds have promising potential as candidates for the treatment of cancer and thus further studies are warranted.

[Expression of microRNA-203 and P63 in human epidermal stem cells and keratinocytes].

OBJECTIVE: To observe the changes in expression of microRNA-203 and P63 in human epidermal stem cells and KCs, and to investigate their effects and significance in the epidermal proliferation and differentiation. METHODS: (1) Five normal foreskin tissue specimens were collected from 5 patients by circumcision in Department of Urinary Surgery of the First Affiliated Hospital of Nanchang University from March to June in 2013. Then single cell suspension was obtained by separating epidermis with trypsin digestion method. The cells were divided into quick adherent cells and non-quick adherent cells by type IV collagen differential adherent method. The biological characteristics of cells were observed by inverted phase contrast microscope immediately after isolation and on post culture day (PCD) 3. The expression of CD29, keratin 19, keratin 1, and keratin 10 was identified by immunocytochemical staining. The expression of microRNA-203 and mRNA of P63 was determined by real-time fluorescent quantitative RT-PCR. The protein expression of P63 was determined by Western blotting. Data were processed with t test and Pearson correlation analysis. RESULTS: (1) Immediately after isolation, quick adherent cells were small, round, and dispersed uniformly. On PCD 3, the cells adhered firmly, and they grew in clones. Immediately after isolation, non-quick adherent cells appeared in different shapes and sizes, and dispersed unevenly. On PCD 3, the cells adhered precariously and did not show clonal growth. Quick adherent cells showed positive expression of CD29 and keratin 19, while non-quick adherent cells showed positive expression of keratin 1 and keratin 10. Quick adherent cells were identified as epidermal stem cells, and non-quick adherent cells were identified as KCs. (2)The expression level of microRNA-203 in epidermal stem cells (0.74 ± 0.20) was lower than that in KCs (3.66 ± 0.34, t =16.582, P <0.001). The mRNA expression level of P63 in epidermal stem cells (4. 16 ± 0.28) was higher than that in KCs (2.90 ± 0.39, t =5. 850, P =0.001). The protein expression level of P63 in epidermal stem cells (1.42 ± 0.05) was higher than that in KCs (0.73 ± 0.03, t =26.460, P <0. 001). (3) The expression level of microRNA-203 was in significantly negative correlation with the expression levels of mRNA and protein of P63 (with r values respectively - 0. 94 and -0.98 , P values below 0.05). CONCLUSIONS: The expression levels of microRNA-203 and P63 in human epidermal stem cells and KCs were significantly different, which might be related to the different characteristics of proliferation and differentiation of the cells.

Synthesis and biological evaluation of novel curcuminoid derivatives.

Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive cocci (S. aureus and S. viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 µM.

[Quality of life of inpatients with coal workers' pneumoconiosis and its influential factors].

OBJECTIVE: To investigate the quality of life ( QOL) of inpatients with coal workers' pneumoconiosis( CWP) and analyse its influential factors, and to provide a theoretical basis for effective control measures. METHODS: Eighty-eight CWP patients in a hospital were included in the study. A questionnaire survey was conducted in them using a self-designed QOL scale. A database was established by software EpiData3.1, and the obtained data were statistically analyzed by software SPSS 16.0. RESULTS: Of the 88 patients, 73( 82.9%) had middle-level QOL, with a mean QOL loss rate of 36.2%; the loss rates of physical function and somatic sensation were the highest ( 44.2% and 41.5%). The patients with stage II CWP had significantly lower physical function than those with stage I and III CWP; the physical function and social function of patients significantly decreased with age; the personal income, household income, and housing condition of the patients had a marked impact on their physical and psychological functions, and the housing condition and education level had a marked impact on their social function. The multivariate analysis showed that old age, low income,and poor housing condition were the main adverse factors for the QOL of inpatients with CWP. CONCLUSION: The QOL of inpatients with CWP declines significantly, and their QOL is related to the age, income, and satisfaction with housing condition.

Study of Astragalus mongholicus polysaccharides on endothelial cells permeability induced by HMGB1.

Astragalus mongholicus polysaccharide (APS) shows various biological activities. Here, we explored the effect of APS on high mobility group protein 1 (HMGB1) -induced endothelial cell permeability. The results indicated APS pretreatment effectively inhibited HMGB1-induced increased permeability in endothelial cells (ECs). Signal transduction studies showed APS inhibited not only the activation of small guanylate Rho and its downstream effector Rho kinase (ROCK), but also the subsequent phosphorylation of myosin light chain (MLC) in ECs. In conclusion, our investigations suggested that APS inhibited HMGB1-induced increased permeability in ECs, regulated by Rho/ROCK signal pathways.

[Annexin A5 gene polymorphism (-1C/T) and the susceptibility to pneumoconiosis in coal works].

OBJECTIVE: To explore the role of -1C/T single nucleotide polymorphism within Annexin A5 gene in the genetic susceptibility to coal worker's pneumoconiosis (CWP). METHODS: Four hundred and seventy CWP Han chinese patients and 428 Han chinese controls were enclosed in present case-control study. All subjects were exposed to coal dusts. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the -1C/T SNP in Annexin A5 gene for all subjects. The relationship between the -1C/T SNP in Annexin A5 gene and CWP was analyzed. RESULTS: CT/TT genotype in -1C/T SNP was associated with a significantly decreased risk of CWP, as compared with the CC genotype among subgroups exposed to coal dusts for ≥ 27 years (adjusted OR = 0.65, 95%CI: 0.44 - 0.98, P = 0.039) and patients with CWP at stage II (adjusted OR = 0.55, 95%CI: 0.34 - 0.90, P = 0.028). CONCLUSION: The results of present study suggest that the Annexin A5 -1C/T polymorphism may be involved in the development of CWP in Han Chinese coal miners.

[Analysis on the incidence of coal workers' pneumoconiosis from 2003 to 2008 in a coal mining group].

OBJECTIVE: Analyzed associations among the incidence of coal workers' pneumoconiosis from 2003 to 2008, jobs, exposure years and cumulative total dust exposure levels (CTE) and found the current characteristics of the mine incidence of pneumoconiosis disease. METHODS: collected the health care information of the new diagnosed pneumoconiosis of underground mine workers from 2003 to 2008 and the dust monitoring data of underground mine from 1949 and estimated the personnel cumulative total dust exposure levels (CTE); analyzed the incidence features of the new diagnosed pneumoconiosis. RESULTS: The rates of health surveillance of workers were gradually improved from 2003 to 2008 and 296 new coal workers pneumoconiosis were diagnosed. The total incidence was 0.57%, and the average annual rate was 0.32%. Among the new diagnosed cases, phase I accounted for 90.5% and the 87.2% from coal mine drillers. The shortest exposure period was 3 years and the longest was 38 years, and the cumulative total dose of dust was varied between 86.1 and 4926 mg/m(3) per year. The total dust accumulated limited dose was calculated by the percentile method to prevent 99% of miners from pneumoconiosis, which was 120.6 mg/m(3) per year, so we suggested that the exposure years should be shorter than 13 years under the current working conditions. CONCLUSIONS: Preventive coal workers' pneumoconiosis should be focused on mine drillers and their limited exposure years should be within 13 years.

[Polymorphisms in Fas pathway genes and risk of coal worker pneumoconiosis].

OBJECTIVE: To explore the possible association between six single nucleotide polymorphisms (SNPs) of Fas pathway genes and the risks of coal worker pneumoconiosis (GWP). METHODS: This case-control study consisted of 511 male patients with CWP and 530 male controls from the same coal mines. Five SNPs of Fas pathway genes were detected by restriction fragment length polymorphisms (PCR-RFLP) and CASP3 (rs6948) was genotyped by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: There were no differences of genotype frequencies of 6 SNPs between cases with CWP and controls. A significant increased risk of CWP was found in subjects with CASP8-652DD genotype as compared to subjects with CASP8-652II genotype (P < 0.05), and the further stratification analysis showed that smoking cases with CWP stage I, long exposure time and CASP8-652DD genotype had high risk of CWP (P < 0.05). The analysis of gene-gene interactions indicated that the carriers with FAS-1377GG/CASP8-652DD, FAS-670AG/CASP8-652DD and FASL-844CT/CASP8-652DD had the increased risk of CWP, and the carriers with FAS-1377GA/CASP8-652ID had the reduced risk of CWP. There were no significant differences of exposure times among the cases with CWP stage I and 3 genotypes of CASP8-652. CONCLUSION: CASP8-652 6N DD genotype may play a role in CWP development and interact with SNPs of FAS-1377, FAS-670 and FASL-844.

[Relationship between FAS/FASL gene polymorphisms and susceptibility of coal worker's pneumoconiosis].

OBJECTIVE: To investigate the effects of FAS and FASL gene polymorphisms on genetic susceptibility of coal worker's pneumoconiosis and their relationship to the pulmonary fibrosis. METHODS: 340 with coal worker's pneumoconiosis (CWP) and 312 coal mine workers (controls) exposed to the coal dusts were selected. FAS-1377G > A, FAS-670A > G and FASL-844T > C gene polymorphisms were analyzed by PCR-RFLP techniques. RESULTS: The distribution frequencies of genotypes of FAS-1377, FAS-670, FASL-844 genotypes in CWP had no significant differences compared to the control. Compared to CWP patients with exposure year > or = 25, the risk of pneumoconiosis with FAS-1377 GA/AA genotype was significantly higher than those with FAS-1377GG in the patients working age < 25 years (P = 0.098, 95% CI: 0.932 approximately 2.298); the risk of CWP in those with FAS-670AG genotype was higher than those with FAS-670GG genotype (P = 0.098, 95% CI: 0.928 approximately 2.404) the risks of CWP in those with FASL-844TT genotype and FASL-844TC genotype were respectively higher than those with FASL-844CC genotype (P = 0.039, 95% CI: 1.088 approximately 27.358, P = 0.089, 95% CI: 0.852 approximately 2.101). The frequencies of genotypes of FASL-844T > C were significantly different between CWP patients with exposure year > or = 25 and < 25. The risk of CWP with FASL-844TT genotype was significantly higher than that of FASL-844TT + TC (P = 0.054, 95% CI: 0.971 approximately 23.833). The risk of CWP patients with FASL-844TT/CT + FAS-1377GA genotype was 1.810-fold than the patients with FASL-844CC + FAS-1377GG genotype. The risk of CWP patients with FASL-844TT/CT + FAS-670AG genotype was 2.117-fold than the patients with FASL-844CC + FAS-670AA genotype. The risk of CWP patients with FASL-844TT/TC + FAS-1377GA/AA + FAS-670AG/GG genotype was 2.043-fold than the patients with FASL-844CC + FAS-1377GG+FAS-670AA genotype. CONCLUSION: FAS-1377G > A, FAS-670A > G and FASL-844T > C gene polymorphisms may not be associated with the susceptibility of CWP in Han nationality, but these three gene polymorphisms and their joint actions may influence on the progression of CWP.

[Experimental study of glucocorticoid in the treatment of acute respiratory distress syndrome induced by E.coli].

OBJECTIVE: To evaluate the effect of glucocorticoid (GC) in the treatment of septic acute respiratory distress syndrome (ARDS). METHODS: ARDS model was reproduced by intraperitoneal injection of E.coli in piglets. Nine male piglets were randomly divided into control (C group), early (GC1) and middle (GC2) stage treatment groups. In the latter two groups methylprednisolone 20 mg was intravenously,given every 12 hours (4 mg(-1)xkg(-1)xd(-1)). All of the clinical data and survival time during 72 hours were collected and analyzed, including the collection of bronchioalveolar lavage fluid (BALF) for the determination of total protein (TP), total phospholipids (TPL), disaturated phosphatidyl choline (DSPC), and measurement of alveolar tension. Ratio of pulmonary wet and dry(W/D) weight was determined routinely, and pathological changes and their severity were evaluated by optical microscope and Smith scores. RESULTS: ARDS model was reproduced at (8.3+/-8.5) hours, and survival time of three groups was (11.0+/-6.6) hours, (35.3+/-12.5) hours and (52.5+/-13.8) hours respectively. Animals in GC1 and GC2 survived longer than those in C group, but there was no statistically significant difference among them (both P>0.05).Oxygen index (PaO(2)/FiO(2)) and mean arterial pressure (MAP) were improved in GC1 much better than those of controls (both P<0.05), and the same was true in GC2 as compared that before GC treatment (P<0.05 or P<0.01). There were no significant differences among TPL, DSPC, white blood cell count (WBC) of BALF in each group, so were lung surface tension and W/D (all P>0.05). TP of BALF was significantly higher in GC1 than that in GC2. Compared with C group, alveolar and interstitial edema, inflammation and hemorrhage were more severe in GC1 (all P<0.01), hyaline membrane was less(P<0.01) and no difference in atelectasis (P>0.05). The alveolar and interstitial edema and inflammation in GC2 were more severe than in C group(all P<0.01), and there was no difference in hemorrhage and hyaline membrane formation (both P>0.05). CONCLUSION: GC might improve hypoxemia and septic shock as a result of septic ARDS. But the treatment has no influence on pulmonary surfactant (PS), surface tension and lung pathology of ARDS in piglets challenged with intraperitoneal E.coli.

[Evaluation of glucocorticoid in treatment for patients with acute respiratory distress syndrome as a result of serious community-acquired pneumonia].

OBJECTIVE: To evaluate the usage of glucocorticoid (GC) in treatment for patients with acute respiratory distress syndrome (ARDS) resulting from serious community-acquired pneumonia (SCAP). METHODS: The clinical data from all patients with ARDS resulting from SCAP in medical ICU (MICU) from May 2000 to Feb. 2003 were collected. Their age, sex, acute physiology and chronic health evaluation (APACHE II) score, PaO(2)/FiO(2) and Qs/Qt, the severity of SCAP, mechanical ventilation (MV) and the level of positive end-expiratory pressure (PEEP), time of stay in ICU, improvement of SCAP and oxygenation, as well as mortality and reasons of death were analyzed, respectively. So was did the influence of administration of GC on hypoxemia, septic shock, and their prognosis. RESULTS: There were 24 cases totally, among them 7 patients had not taken GC, and 5 patients were cured (71.4 percent), and the other 2 cases died (28.6 percent) Their direct cause of death were multiple organ dysfunction syndrome (MODS) and ARDS, respectively In 17 cases GC was given because hypoxemia and septic shock could not be alleviated with ordinary therapy, including MV Among them only 5 patients (29.4 percent) were cured, and all others (12 cases, 70.6 percent) died, and the major direct cause of death was MODS (6 cases, 75.0 percent). A few of them died of ARDS and septic shock (1 case, 12.5 percent, respectively). The severity of SCAP, as well as other clinical data of the survivors, showed no significant difference compared with the nonsurvivors (P>0.05). But except for their PaO2/FiO2, Qs/Qt and shock, their pulmonary infection was better controlled than deaths (P<0.001). CONCLUSION: Refractory hypoxemia and septic shock of patients with pulmonary ARDS might be alleviated by GC when they are treated with routine methods, including MV, thus it enabled to win the time for other effective treatments.

[Evaluation of glucocorticoid in treatment for patients with acute respiratory distress syndrome].

OBJECTIVE: To value of glucocorticoid (GC) in treatment for patients with acute respiratory distress syndrome (ARDS) was evaluated. METHODS: The clinical data from all patients with ARDS in medical ICU (MICU) during May 2000 to Aug. 2002 were collected. They were divided into two groups, GC and non-GC groups, in order to compare their age, sex, acute physiology and chronic health evaluation II (APACHE II) score, PaO2/FiO2, Qs/Qt, level of positive end-expiratory pressure(PEEP), mortality and dead reason of death, depending on whether GC was given or not. In cases with administration of GC, the dosage, as well as duration of treatment was analyzed in terms of the overcome. RESULTS: There were 77 cases totally, among them 60 cases were of GC group and 17 of non -GC. Their age, sex, APACHE II score, PaO2/FiO2, Qs/Qt, use of artificial ventilation and its duration, level of PEEP, and the extent of relief from hypoxemia showed no significant differences between two groups (P>0.05). Even the mortality for patients who were treated with GC was higher than those without (71.7% vs. 52.9%), though there was no statistically significant difference (P>0.05). The percentage of patients died primarily of ARDS was low in both groups (7.0% and 11.1%). The age, APACHE II score and underlying diseases for non-survivors were older and higher than survivors (P<0.001 or P<0.005) and their duration of staying in ICU was shorter than the latter (P<0.05). The mortality of patients who were given GC before or during 24 hours of the establishment of the diagnosis of ARDS (66.7% and 68.2%) was lower than those who were given GC 24 hours after the diagnosis of ARDS (90.0%). CONCLUSION: GC could be one of effective treatments for ARDS, and it should be given without hesitation when refractory hypoxemia and shock were found.

[Evaluation of mechanical ventilation for patients with acute respiratory distress syndrome as a result of interstitial pneumonia after renal transplantation].

OBJECTIVE: To evaluate the clinical value of mechanical ventilation for patients with acute respiratory distress syndrome(ARDS) as a result of interstitial pneumonia after renal transplantation in the intensive care unit (ICU). METHODS: All the clinical data (totally 16 cases) were collected, including the improvement of hypoxemia before and after mechanical ventilation. RESULTS: Different levels of positive end-expiratory pressure (PEEP) 4-15 cm H2O (1 cm H2O=0.098 kPa) were applied in the patients in whom mechanical ventilation was instituted. The time for different mechanical ventilation was different [1-87 days, (15.4+/-21.1) days] and duration of survival was different [1-1 945 days, (154.4+/-497.1) days]. Only one of them was survived (6.7%), and the others died (93.3%). The causes of death were analyzed. Among the patients who received the mechanical ventilation, 3 patients were alive less than 3 days and their dire ct cause of death was not respiratory (circulation and central). Only one of them did not receive artificial ventilation and the cause of death was hypoxemia. The successful experience for one survivor among the patients who received the ventilator was that hypoxemia was improved by the mechanical ventilation, winning the time for the treatment of the original disease. CONCLUSION: The major value of mechanical ventilation was to correct the hypoxemia in order to win the time to cure the interstitial pneumonia and ARDS. The survival rate was still low for such a group of patients because the pathogenesis was not identified, and therefore the disease could not be controlled, even the mechanical ventilation is instituted in time.