Abstract: Objective To analyze the epidemiological characteristics of viral hepatitis E in Fujian Province from 2012-2021, and to provide scientific evidence for the prevention and control of hepatitis E in the future. Methods Descriptive epidemiological method was used to analyze hepatitis E cases in Fujian Province from 2012 to 2021. Results From 2012 to 2021, a total of 8 877 cases of hepatitis E were reported in Fujian Province from 2012-2021. The overall incidence rate showed a decreasing trend (χ2trend =458.14, P<0.001), with the lowest incidence rate of 1.32/100 000 in 2020 and an annual average incidence rate of 2.29/100 000 per year. The incidence was higher in winter and spring, with the months of March and April having the highest number of reported cases (2 146, 24.17%) and the fewest cases were reported in September (571, 6.43%). The difference in reported incidence rates between cities was statistically significant (χ2=1 877.75, P<0.01). The comprehensive experimental zone of Pingtan had the highest average reported incidence rate of 6.03/100 000, while Zhangzhou had the lowest at 0.94/100 000. The number of male cases was higher than the number of female cases, with a male to female ratio of 2.04∶1. The disease was most prevalent among middle-aged and elderly individuals, with the age group of 40-<65 years having the highest number of reported cases, accounting for 57.44% (5 099/8 877) of all cases. The age group of 50-<55 years had the highest reported incidence, with the number of reported cases increasing with age below 50 years, but decreasing with age over 50 years. As for occupational distribution, peasants had the highest proportion of the disease, accounting for 34.49% (3 062 cases) of the total cases. Conclusions The reported incidence rate of hepatitis E in Fujian showed a downward from 2012 to 2021. Due to the impact of COVID-19, incidence of the lowest was 2020, but it did not reflect the true situation of the disease, which may have affected trend of hepatitis E. In order to control and reduce the incidence of hepatitis E, efforts should be made to increase publicity and education on health knowledge and vaccination among key areas and populations, strengthen monitoring and diagnostic capability, and implement comprehensive prevention and control measures.

Objective To explore the recurrent epidemiological characteristics of hand,foot and mouth disease (HFMD) among children aged <4 years to provide evidence for HFMD prevention and control. Methods Principles on historical cohort study were followed when analyzing data related to HFMD surveillance in Fujian province. All the research objects were restricted to patients aged<4,with HFMD and who were permanent residents in Fujian province. Characteristics of the study objects were extracted as potential factors when the patients first showed symptoms of HFMD. These factors might cause the recurrence of HFMD and were filtered by the logistic stepwise regression with SAS 9.0. Results A total of 82 949 children were included. Among them,2 612 had repetitiously suffered from HFMD (occupied 3.15%),including 2 510 who had the histories of suffering twice,98 suffering three times,3 suffering four times,and 1 even suffering five times. Comparing with the objects who had the first onset at the age of 3,also with the risk increased to 4.39 (95%CI:3.80-5.07)times,when compared to those who had the first onset at the age below 2. Again, the risk among children whose first onset was at the age of 2 had increased to 2.73 (95%CI:2.35-3.18)times. According to the current residents areas,the morbidities of patients under 6 years old were below 2%when the symptoms first started,but the risk of the objects whose morbidities were higher than 4%,had increased 2.15(95%CI:1.88-2.45) times. Again,risk of the objects whose morbidities were between 3%and 4%had increased to 2.10(95%CI:1.85-2.38)times. Among those whose specific morbidities were between 2% and 3%,the risk had increased to 1.65(95%CI:1.44-1.89) times. Comparing with the objects who never visited any maternal/child care settings when started the first onset,the risk among the ones who had been to the maternal/child care settings, had increased to 1.64(95%CI:1.51-1.78)times. Boys had the risk 1.34(95%CI:1.23-1.46)times increase than girls. The preponderant pathogen causing HFMD recurrence was EV71 (33/60). Recurrence might cause more severe symptoms or signs (8/2 612). Pathogens causing the initial infection and recurrence might both belonged to the same-EV71(3/6). Conclusion Recurrence of the disease were closely related to the opportunities of contacting the pathogens. Interventions should be imposed on patients in time as soon as the disease initiated,especially at the younger age.

Objective To analyze the epidemiological characteristics and spatial distribution of human brucellosis in Fujian province during 2011-2016,and provide evidence for the prevention and control of the disease.Methods The surveillance data of human brucellosis in Fujian during 2011-2016 was analyzed with software R 3.3.1,ArcGIS 10.3.1,GeoDa 1.8.8 and SaTScan 9.4.3.Results During 2011-2016,a total of 319 human brucellosis cases were reported,the incidence increased year by year (F=11.838,P=0.026) with the annual incidence of 0.14/100 000.The male to female rate ratio of the incidence was 2.50 ∶ 1.Farmers and herdsmen accounted for 57.37％.The incidence was 0.40/100 000 in Zhangzhou and 0.32/100 000 in Nanping,which were higher than other areas.The number of affected counties (district) increased from 12 in 2011 to 28 in 2016,showing a significant increase (F=13.447,P=0.021).The Moran' s I of brucellosis in Fujian between January 2011 and December 2016 was 0.045,indicating the presence of a high value or low value clustering areas.Local spatial autocorrelation analysis showed that,high-high clustering area (hot spots) were distributed in Zhangpu,Longhai,Longwen,etc,while high-low clustering areas were distributed in Nan' an and Jiaocheng,etc.Temporal scanning showed that there were three clustering areas in areas with high incidence,the most possible clustering,occurring during January 1,2013-December 31,2015,covered 6 counties,including Yunxiao,Pinghe,Longhai,etc,and Zhangpu was the center,(RR =7.96,LLR=92.62,P＜0.001).Conclusions The epidemic of human brucellosis in Fujian is becoming serious,and has spread to general population and non-epidemic areas.It is necessary to strengthen the prevention and control of human brucellosis in areas at high risk.

OBJECTIVETo explore the recurrent epidemiological characteristics of hand, foot and mouth disease (HFMD) among children aged <4 years to provide evidence for HFMD prevention and control.

METHODSPrinciples on historical cohort study were followed when analyzing data related to HFMD surveillance in Fujian province. All the research objects were restricted to patients aged <4, with HFMD and who were permanent residents in Fujian province. Characteristics of the study objects were extracted as potential factors when the patients first showed symptoms of HFMD. These factors might cause the recurrence of HFMD and were filtered by the logistic stepwise regression with SAS 9.0.

RESULTSA total of 82 949 children were included. Among them, 2 612 had repetitiously suffered from HFMD(occupied 3.15%), including 2 510 who had the histories of suffering twice, 98 suffering three times, 3 suffering four times, and 1 even suffering five times. Comparing with the objects who had the first onset at the age of 3, also with the risk increased to 4.39 (95%CI:3.80-5.07) times, when compared to those who had the first onset at the age below 2. Again, the risk among children whose first onset was at the age of 2 had increased to 2.73 (95% CI: 2.35-3.18) times. According to the current residents areas, the morbidities of patients under 6 years old were below 2% when the symptoms first started, but the risk of the objects whose morbidities were higher than 4% , had increased 2.15(95% CI:1.88-2.45)times. Again, risk of the objects whose morbidities were between 3% and 4% had increased to 2.10 (95%CI:1.85-2.38) times. Among those whose specific morbidities were between 2% and 3% , the risk had increased to 1.65 (95% CI: 1.44-1.89) times. Comparing with the objects who never visited any maternal/child care settings when started the first onset, the risk among the ones who had been to the maternal/child care settings, had increased to 1.64 (95% CI:1.51-1.78) times. Boys had the risk 1.34 (95% CI:1.23-1.46)times increase than girls. The preponderant pathogen causing HFMD recurrence was EV71 (33/60). Recurrence might cause more severe symptoms or signs (8/2 612). Pathogens causing the initial infection and recurrence might both belonged to the same-EV71 (3/6).

CONCLUSIONRecurrence of the disease were closely related to the opportunities of contacting the pathogens. Interventions should be imposed on patients in time as soon as the disease initiated, especially at the younger age.

Child, Preschool ; China ; epidemiology ; Cohort Studies ; Epidemics ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; Humans ; Infant ; Logistic Models ; Male ; Recurrence ; Risk Factors

ObjectiveTo establish a rat model of diabetic wound by feeding on a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin （STZ） and surgical preparation of full-thickness skin defects， observe the effect of cinnamaldehyde on the wound healing of diabetes rats， and explore the therapeutic mechanism of cinnamaldehyde in improving wound healing of diabetes rats based on the PTEN-induced putative kinase （PINK1）/Parkin pathway-mediated mitochondrial autophagy. MethodForty-eight male SD rats were randomly divided into blank group （n=12） and diabetes group （n=36）. The diabetes group was further randomly divided into model group， cinnamaldehyde group， and Beifuxin group， with 12 rats in each group. The blank group and the model group received routine disinfection with physiological saline after creating the wounds， while the cinnamaldehyde group received topical application of polyethylene glycol 400 （PEG 400） gel containing 4 μmol·L^-1 cinnamaldehyde， and the Beifuxin group received topical application of Beifuxin gel. Dressings were changed once daily. The wound healing rate of each group was observed. On the 7th and 14th days after intervention， the wound tissues of the rats were collected. Hematoxylin and eosin （HE） staining was performed to observe the pathological changes in the local tissues. Immunohistochemistry （IHC） was used to detect the expression of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， vascular endothelial growth factor （VEGF）， and collagen fibers. Immunofluorescence （IF） and Real-time polymerase chain reaction （Real-time PCR） were used to detect the protein， and mRNA expression of PINK1， Parkin， microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. ResultAfter intraperitoneal injection of STZ， compared with the blank group， the random blood glucose values of rats in the diabetic group increased significantly （P<0.01）， all higher than 16.7 mmol·L^-1， and persistently hyperglycemic for some time after modeling. Compared with the blank group， the model group showed poor growth and healing of granulation tissue in the wounds， and the wound healing rate decreased （P<0.01）. On the 7^th day after intervention， the blank group had squamous epithelial coverage on the wounds. Compared with the blank group， the model group only had a small amount of scab at the wound edges， with a large number of infiltrating inflammatory cells in the wounds. The protein expression levels of IL-6 and TNF-α in the tissues increased （P<0.01）， and the protein and mRNA levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. On the 14^th day after the intervention， the granulation tissue in the wounds of the blank group was mature and well-healed. Compared with the blank group， the model group still had infiltrating inflammatory cells and red blood cell exudation. The protein expression levels of VEGF and collagen fibers in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. Compared with the model group， the cinnamaldehyde group and the Beifuxin group showed better wound healing， with increased wound healing rates （P<0.01）. On the 7th day after intervention， the protein expression levels of IL-6 and TNF-α in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. On the 14th day after intervention， the protein expression levels of VEGF and collagen fibers in the tissues increased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. ConclusionCinnamaldehyde can promote the wound healing of diabetes rats by increasing the wound healing rate， reducing the levels of inflammatory factors IL-6 and TNF-α， and increasing the levels of VEGF and collagen fibers. Its mechanism may be related to the regulation of the PINK1/Parkin signaling pathway， activation of mitochondrial autophagy， inhibition of inflammatory responses， and promotion of angiogenesis and collagen synthesis， thereby promoting the wound healing of diabetes rats.

Objective: To study the influence of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Xiamen, Fujian province, and provide scientific evidence for the early warning, prediction, prevention and control of HFMD. Methods: Correlation analysis and distribution lag nonlinear models (DLNM) analysis of meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours and the incidence of HFMD in Xiamen during 2013 to 2017 were conducted by using R3.4.3 software. Results: A total of 36 464 cases of HFMD were reported in Xiamen during 2013-2017, and the incidence showed an upward trend (F=40.359, P=0.008). The daily average relative humidity, daily average temperature and sunshine hours were positively correlated with the incidence of HFMD (r>0), and the daily average site pressure was negatively correlated with the incidence of HFMD (r<0). In the case of a lag of 0-5 days, when the daily average pressure of the station was higher than 1 005 hPa, the risk of HFMD gradually increased with the increase of air pressure, and the risk of disease decreased with the increase of lag days. The risk was highest when air pressure was 1 017 hPa and at the lag of 0 day (RR=1.14, 95%CI: 0.67-1.94). When the relative humidity was higher than 95%, the risk of HFMD gradually increased with the increase of relative humidity, and the lag time ranged from 0 day to 10 days, which was most obvious on the 4^th and 5^th days. The risk was highest when relative humidity was 100% and at the lag of 5 days (RR=1.32, 95%CI: 1.02-1.71). When the air temperature was >28 ℃ and <8 ℃, the risk of HFMD existed, but the lag time was inconsistent. The relative risk was highest during 15-20 days at low air temperature, and the lag time at high air temperature was mainly during 5-15 days. The risk was highest when air temperature was 28 ℃ and at the lag of 4 days (RR=1.10, 95%CI: 0.94-1.29). The sunshine time was >12 h and lag of 0-3 days was a risk factor for the incidence of HFMD. The risk was highest when sunshine time was 13 h and the lag of 0 day (RR=1.20, 95%CI: 1.05-1.36). Conclusion Meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours were associated with the incidence of HFMD with certain lag in Xiamen. So, it is suggested to use these data in the early warning system of HFMD.

Objective : To explore the mechanism of Wenyang Shengji Ointment (温阳生肌膏, WYSJO) in the treatment of diabetic wounds from the perspective of network pharmacology, and to verify it by animal experiments. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature were used to screen active compounds in WYSJO and their corresponding targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), DrugBank, PharmGkb, and Therapeutic Target Database (TTD) databases were employed to identify the targets associated with diabetic wounds. Cytoscape 3.9.0 was used to map the active ingredients in WYSJO, which was the diabetic wound target network. Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) platform was utilized to construct protein-protein interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) andGene Ontology (GO) enrichment analyses were performed to identify signaling pathways between WYSJO and diabetic wounds. AutoDock 1.5.6 was used for molecular docking of core components in WYSJO to their targets. Eighteen rats were randomly divided into control, model, and WYSJO groups (n = 6). The model and WYSJO groups were used to prepare the model of refractory wounds in diabetes rats. The wound healing was observed on day 0, 5, 9, and 14 after treatment, and the wound tissue morphology was observed by hematoxylin-eosin(HE) staining. The expression levels of core genes were detected by quantitative real-timepolymerase chain reaction (qPCR). Result: A total of 76 active compounds in WYSJO, 206 WYSJO drug targets, 3 797 diabetic wound targets, and 167 diabetic wound associated WYSJO targets were screened out through network pharmacology. With the use of WYSJO-diabetic wound target network, core targets of seven active compounds encompassing quercetin, daidzein, kaempferol, rhamnetin, rhamnocitrin, strictosamide, and diisobutyl phthalate (DIBP) in WYSJO were found. GO enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve lipopolysaccharide, bacteria-derived molecules, metal ions, foreign stimuli, chemical stress, nutrient level, hypoxia, and oxidative stress in the biological processes. KEGG enrichment analysis showed that the treatment of diabetes wounds with WYSJO may involve advanced glycation end products (AGE-RAGE), p53, interleukin (IL)-17, tumor necrosis factor (TNF),hypoxia inducible factor-1 (HIF-1), apoptosis, lipid, atherosclerosis, etc. The results of animal experiments showed that WYSJO could significantly accelerate the healing process of diabetic wounds (P < 0.05), alleviate inflammatory response, promote the growth of granulation tissues, and down-regulate the expression levels of eight core genes [histone crotonyltransferase p300 (EP300), protoc gene-oncogene c-Jun (JUN), myelocytomatosis (MYC), hypoxia inducible factor 1A (HIF1A), mitogen-activated protein kinase 14 (MAPK14), specificity protein 1 (SP1), tumor protein p53 (TP53), and estrogen receptor 1 (ESR1)] predicted by the network pharmacology (P < 0.05). Conclusion The mechanism of WYSJO in treating diabetes wounds may be closely related to AGE-RAGE, p53, HIF-1, and other pathways. This study can provide new ideas for the pharmacological research of WYSJO, and provide a basis for its further transformation and application.