Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Objective:To observe the epidemiological characteristics and transmission chain of COVID-19 in Harbin, and to provide epidemiological evidence for improving the COVID-19 preventive measures and optimizing prevention and control strategies.Methods:The epidemic situation of COVID-19 in Harbin in January 2021 was analyzed by using the Infectious Disease Report Information Management System and the Public Health Emergency Management Information System of the China Disease Prevention and Control Information System, the epidemic situation information publicly released by the Heilongjiang Provincial Health Commission, and the epidemiological report of Heilongjiang Province Certer for Disease Control and Prevention and Harbin Center for Disease Control and Prevention. The main transmission chains were sorted out through combination of epidemiological field investigation, serological testing, gene sequencing, big data and other means.Results:From January 12 to February 4, 2021, 295 cases of COVID-19 infection (including confirmed cases and asymptomatic infections) were reported in Harbin, which affected 6 districts of Harbin and were concentrated in 41 of the 274 townships in the city. The sex ratio of male to female was 1.00∶1.12 (139∶156); the age ranged from 1 to 86 years old, and the median age was 45 years old. The proportion of confirmed cases and asymptomatic infection was 1.00 ∶ 1.02 (146 ∶ 149), and there was a significant difference in the distribution of different ages between them ( P = 0.042). The cases were mainly found through the health screening of the centralized isolation personnel (178 cases, 60.3%). Other detection methods included active screening (87 cases, 29.5%), screening of the home isolation personnel (26 cases, 8.8%), and medical treatment in medical institutions (4 cases, 1.4%). The main transmission chain of the outbreak was the case associated with a food processing enterprise, with a total of 259 cases, accounting for 87.8% of the total cases. The gene sequencing results showed that the case sequence was homologous with that of Wangkui County, Suihua City, Heilongjiang Province. Conclusions:A food processing enterprise is involved in the main transmission chain, which indicates that the epidemic prevention and control measures needs to be further optimized. Specifically, the supervision and management of food processing enterprises, cold chain storage companies and other enterprises should be strengthened. High attention should be paid to the hidden dangers of COVID-19 in large and medium sized enterprises with hermetic space in Harbin.

According to the general goal of long term development of basic science from 2021 to 2035 and the "14th Five-Year Plan" in China, starting from the reasearch characteristics and the basic situation of endemiology, this study discusses the strategic position, development law, development trend, development status and layout, development goals and realization ways of endemiology, combined with the strategic needs of the discipline, the important interdisciplinary research areas of endemiology are put forward. The purpose of this study is to promote the rapid development of basic research on endemic diseases, to provide reference for the scientific and technological layout and policy formulation of the endemiology, to provide reference for the "14th Five-Year Plan" in China, and to provide guarantee for the people in the sick area to seek health.

Based on the general goal of the medium and long term development of basic science from 2021 to 2035 and the "14th Five-Year Plan" in China, combined with the national strategic needs, this paper discusses the five priority development areas of endemiology according to the development trends and characteristics of endemiology in the next 5 - 15 years. The five areas are study on the pathogenesis and prevention measures of endemic fluorosis; study on risk assessment, pathogenic mechanism and control strategy of environmental arsenic exposure; research on the basis and application transformation of the pathogenesis of iodine nutrition-related diseases; molecular mechanism and targeted intervention of cartilage injury in Kashin-Beck disease; precise prevention and treatment, preservation of biological samples and etiology study of Keshan disease. Combined with the scientific significance and national strategic needs of various field, the authors analyze its main study directions and core scientific issues.

【Objective】 To analyze the cause of single-ELISA reactive of four blood screening items in 18 blood stations in Henan, so as to provide the basis for improving the quality of blood screening. 【Methods】 The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP of 18 blood station laboratories in Henan throughout 2019 was calculated, and the causes were analyzed according to different ELISA reagent combinations and gray area settings in each laboratory. 【Results】 The overall single-ELISA reactive rates of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP were 1.740(2 154/1 237 789), 0.564‰(698/1 237 789), 1.421‰(1 759/1 237 789) and 1.561‰(1 932/1 237 789), respectively, showing significant differences by detection items (P <0.05). Person correlation analysis showed that the single-ELISA reactive rate was independent of the gray area settings.but dependent on laboratories and reagent combinations. The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP in D laboratory was the highest and higher than that in other labs using the same reagent.The laboratories with high HBsAg single-ELISA reactive rate were mostly those using a combination of imported reagents and domestic reagents, including the top 6 laboratories. The laboratories with high anti-HCV single-ELISA reactive rate were mostly those using certain domestic reagents. No obvious rules was noticed by single-ELISA reactive for anti-HIV. Laboratories with high anti-TP single-ELISA reactive rate were mostly those using combination 4. 【Conclusion】 The HBsAg single-ELISA reactive rate was the highest in the four blood screening items of blood station laboratories in Henan. The single-ELISA reactive rate is related to the laboratory itself and the reagent manufacturer, suggesting that laboratory quality control should be strengthened and proper reagent combination should be selected to reduce the waste of blood.

Objective:To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning.Methods:select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP.Results:4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group ( P<0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission ( P<0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group ( P<0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission ( P<0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission ( P<0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores ( R=0.634, 0.723, P<0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion:sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.

Objective:To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning.Methods:select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP.Results:4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group ( P<0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission ( P<0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group ( P<0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission ( P<0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission ( P<0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores ( R=0.634, 0.723, P<0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion:sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.

A 65-year-old female patient with chronic renal failure undergoing continuous hemodialysis received an IV infusion of cefmenoxime 1 g twice daily for acute pancreatitis. The values of prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) were within the normal range before treatment. After 11 days of treatment, the patient developed multiple ecchymoses on the skin and bleeding from the venipuncture site which was not easily stopped. The reexamination of coagulation function showed PT 127 s, INR 10.72, and APTT 86 s. Coagulation dysfunction was considered and an IV infusion of leukocyte-reduced fresh-frozen plasma 150 ml was given. Examination of coagulation function next day showed PT 101 s, INR 8.49, and APTT 65 s. Mixing study for evaluation of abnormal coagulation testing showed that PT and APTT could be corrected, suggesting coagulation factor deficiency. Blood coagulation disorders caused by cefmenoxime was considered. Then the drug was discontinued and switched to amoxicillin sodium and clavulanate potassium, and a subcutaneous injection of vitamin K 1 10 mg was given once daily. Three days after the drug withdrawal, her coagulation function returned to within the normal range (PT 15 s, INR 1.19, APTT 36 s).

A 65-year-old female patient with chronic renal failure undergoing continuous hemodialysis received an IV infusion of cefmenoxime 1 g twice daily for acute pancreatitis. The values of prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) were within the normal range before treatment. After 11 days of treatment, the patient developed multiple ecchymoses on the skin and bleeding from the venipuncture site which was not easily stopped. The reexamination of coagulation function showed PT 127 s, INR 10.72, and APTT 86 s. Coagulation dysfunction was considered and an IV infusion of leukocyte-reduced fresh-frozen plasma 150 ml was given. Examination of coagulation function next day showed PT 101 s, INR 8.49, and APTT 65 s. Mixing study for evaluation of abnormal coagulation testing showed that PT and APTT could be corrected, suggesting coagulation factor deficiency. Blood coagulation disorders caused by cefmenoxime was considered. Then the drug was discontinued and switched to amoxicillin sodium and clavulanate potassium, and a subcutaneous injection of vitamin K 1 10 mg was given once daily. Three days after the drug withdrawal, her coagulation function returned to within the normal range (PT 15 s, INR 1.19, APTT 36 s).

Objective To observe the changes of the totle nitric oxide synthase (NOS) activity in brain tissue,the metabolism of arsenic speciations in urine and the totle contents in blood,brain after rats drinking water containing different doses of arsenic.Methods Forty SD rats were divided into 4 groups according to random number table,10 rats in each group:control group,5 mg/L NaAsO2 group,10 mg/L NaAsO2 group and 50 mg/L NaAsO2 group.The animals were allowed free access to water and food.Body mass was weighted once a week.Expose to arsenic was continued for three months,then the animals were put to death and their blood,urine and brain tissues were collected.Determination of four kinds of speciations of arsenic (3 valence inorganic arsenic,iAs3+;5 valence inorganic arsenic,iAs5+;monomethylated arsenic,MMA;dimethylated arsenic,DMA) in urine was carried out by high performance liquid chromatography-hydride atomic fluorescence spectrometry.Total arsenic concentration in blood and brain tissue was detected by Atomic Fluorescence Spectrometry.The activity of total NOS in blood and brain tissue was detected using the spectrophotometer method.Results ①Weight:at the 5th-12th week after arsenic exposure,compared with the weight of control group [(420.93 ± 21.13),(441.52 ± 28.85),(462.45 ± 30.57),(470.16 ± 31.17),(484.92 ± 32.93),(483.79 ± 29.63),(482.02 ± 29.14),(483.89 ± 29.31) g],weight of rats in 50 mg/L NaAsO2 group [(391.66 ± 32.88),(410.17 ± 33.47),(426.96 ± 33.49),(427.15 ± 32.20),(441.78 ± 33.69),(438.27 ± 33.05),(440.98 ± 33.33),(441.46 ± 32.45) g] was significantly lighter (all P ＜ 0.05).② Urine arsenic:the medians of iAs3+ content (0.00,57.30,236.33,857.80 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =31.982,P ＜ 0.01);the medians of iAs5+ content (0.00,0.00,80.75,162.90 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =24.206,P ＜ 0.01);the medians of DMA content (12.83,1 711.13,l0 386.20,37 038.90 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =34.338,P ＜ 0.01).③Blood arsenic:total arsenic content in serum of rats [(5.04 ± 1.57),(25.40 ± 7.33),(32.28 ± 7.75),(56.11 ± 19.87) mg/L] was compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (F =27.78,P ＜ 0.05).④Brain arsenic:total arsenic content in brain tissue of 5,10 and 50 mg/L NaAsO2 groups [(0.57 ± 0.20),(1.56 ± 0.52),(3.63 ± 0.48) μg/g] was respectively compared with that of control group [(0.11 ± 0.06) μg/g],the differences were statistically significant (all P ＜ 0.05).⑤NOS activity:compared with control group [(27.69 ± 5.56) kU/L],total NOS activity [(33.63 ± 2.26),(34.19 ± 2.55) kU/L] in serum of rats in 10 mg/L NaAsO2 group and 50 mg/L NaAsO2 group increased significantly (all P ＜ 0.05);compared with control group [(1.79 ± 0.79) U/(mg·prot)],total NOS activity [(2.63 ± 0.60)U/(mg ·prot)] in brain tissue of 50 mg/L NaAsO2 group increased significantly (P ＜ 0.05).Conclusions A high dose of arsenic exposure can increase totle contents of arsenic in blood,brain and the activity of total NOS in rat brain tissue.