BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective: To evaluate the effectiveness for the construction of "mosquito-free village" in Xuejia Village, Pujiang County, Zhejiang Province, so as to provide the guidance for the construction of "mosquito-free village" in other rural areas. Methods: Density of adult mosquitoes in Xuejia Village was investigated using light trap method and density of larval mosquitoes was investigated using larval straw method from April to November each year. Totally 30 households of villagers were randomly selected, and their awareness rates of mosquito control knowledge, mosquito control behavior forming rates and satisfaction rates were surveyed through questionnaires. Investment during construction (from August 2016 to December 2018) and maintenance period (from 2019 to 2023) of "mosquito-free village" were investigated through data review and interviews. Long-term effects of "mosquito-free village" construction in Xuejia Village were evaluated in terms of mosquito density from 2016 to 2023, effectiveness of health education for villagers, satisfaction and investment. Results: Compared with the year 2016, the densities of adult and larval mosquitoes in Xuejia Village were significantly decreased from 2017 to 2023. The average monthly density of adult mosquitoes in 2023 decreased by 98.34%, and the average monthly 100 household index of larval mosquitoes decreased by 98.45% compared to 2016. The average monthly density of adult mosquitoes from 2019 to 2023 was less than or equal to one mosquito per light trap in a night, and the average monthly 100 household index of larval mosquitoes was less than or equal to five places per 100 households. The awareness rate of mosquito control knowledge was 93.33%, the behavior forming rate was 86.67%, and the satisfaction rate was 90.00%. By December 2023, the total investment during construction and maintenance period was 450 thousand Yuan, with an average annual investment of 60.7 thousand Yuan and average annual investment of 206.61 Yuan per household. The average annual investment during maintenance period was 36.2 thousand Yuan, and the average annual investment per household was 109.70 Yuan. Conclusion The mosquito density, effectiveness of health education for villagers and satisfaction of "mosquito-free village" in Xuejia Village all meet the evaluation criteria of "mosquito-free village", and the investment is reasonable, making it suitable for promotion to other rural areas.

Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.

Objective:To systematically evaluate the effect of cognitive behavior therapy for insomnia on sleep quality of pregnant women.Methods:The PubMed, Cochrane Library, Embase, Web of Science, CNKI, CBM, VIP and Wanfang databases were searched from the establishment of the database to August 2021 for relevant studies on the impact of cognitive behavior therapy for insomnia on the sleep quality of pregnant women. Relevant randomized controlled trials were included. The data were analyzed by RevMan5.3 software inthisstudy.Results:A total of 8randomized controlled trials were included. The results indicated that cognitive behavior therapy for insomniacould improve the sleep quality of pregnant women ( SMD = -0.75, 95% CI -1.20 - -0.30, P<0.05). Face-to-facecognitive behavior therapy for insomniasignificantly improved sleep quality ( SMD = -1.14, 95% CI -1.85 - -0.42, P<0.05). Conclusions:Existing evidence indicates that cognitive behavior therapy for insomnia can enhance the sleep quality of pregnant women. Face-to-face cognitive behavior therapy for insomniahas better effect.

Objective:To investigate the epidemic characteristics and current situation of animal plague in Zhejiang Province, in order to provide data support for prevention and control of the plague in the whole province.Methods:A retrospective study was carried out to collect surveillance data of animal plague in Zhejiang Province from 2006 to 2020 from the "Pubonic Plague Control Management Information System". Descriptive epidemiological methods were used to analyze the density of domestic and wild rodents, the distribution of rodent species and flea species, and the serological and pathogenic test results of host animals.Results:From 2006 to 2020, the annual average density of domestic rodent in Zhejiang Province was 3.99%, which was lower than that in 2006, 2007, 2008, 2009, 2019 and 2020. The annual average density of wild rodents was 4.52%, which was lower than that in 2013, 2016, 2017, 2018, 2019 and 2020. From 2006 to 2020, a total of 173 432 rodents were captured, belonging to 3 orders, 5 families, 12 genera and 17 species; in the composition of rodent species, Rattus norvegicus was the most, accounting for 32.15% (55 765/173 432). A total of 107 736 rodents were examined, the number of flea-infected rodent was 3 885, and the flea-infested rate was 3.61%; the total number of flea collected was 9 039 and the total flea index was 0.083 9. A total of 172 235 serological samples were tested at various monitoring sites in Zhejiang Province, and 10 positive samples were detected, there were 7 copies of Apodemus agrarianus, 2 copies of Smelly Shrew and 1 copy of Rattus norvegicus, with titers ranging from 1 ∶ 40 - 1 ∶ 320; a total of 163 618 copies of rodent liver and spleen organs were cultured, and no Yersinia pestis was isolated. Conclusions:Positive host animals have been detected in Zhejiang Province for many years. It is necessary to further standardize plague surveillance and make emergency preparations to prevent relapse and import of the epidemics.

Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hemorrhagic fever with renal syndrome (HFRS) in Zhejiang province from 2005 to 2020, and provide scientific information for the precise prevention and control of HFRS.Methods:Data on HFRS cases in Zhejiang province during 2005-2020 were collected from the China National Notifiable Infectious Disease Reporting Information System (NNDS) for a descriptive analysis, and software ArcGIS 10.2 was used for global autocorrelation and local autocorrelation analyses. Spatiotemporal clusters were scanned with SaTScan 9.4.4 and visualized with ArcGIS 10.2.Results:A total of 7 724 HFRS cases were reported in Zhejiang province from 2005 to 2020, including 25 deaths. There were two incidence peaks each year, in late spring and early summer (May-June) and in winter (November-January). The top three areas with high cumulative cases were Ningbo (1 875, 24.27%), Taizhou (1 642, 21.25%), and Shaoxing (1 123, 14.54%). Among the reported cases, with a male to female ratio of 2.73∶1(5 656∶2 068). The majority of HFRS cases were middle-aged and elderly people, with cases aged 41-70 years accounting for 60.95%. Most HFRS cases were farmers, accounting for 69.89% (5 398/7 724). The spatial distribution of HFRS in most years was correlated. SaTScan was used for retrospective spatiotemporal scanning and three clusters were detected: the first type clusters were in 21 counties in eastern Zhejiang province and central Zhejiang province, among which 4 were in Ningbo, Shaoxing and Jinhua, 8 were in Taizhou, and 1 was in Lishui ( RR=13.69, LLR=5 522.60, P<0.001); the second type clusters were in Longquan and Qingyuan counties ( RR=31.20, LLR=1 232.46, P<0.001); the third types of clusters were in Changxing and Anji counties of Huzhou in northern Zhejiang province ( RR=3.42, LLR=23.93, P<0.001). Conclusions:HFRS mainly occurred in middle-aged,elderly and male farmers in Zhejiang province. The incidence was high in late spring, early summer and winter in eastern Zhejiang province. Precise prevention and control measures are needed for populations at high risk before the epidemic season.

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

Objective:Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province.Methods:The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared.Results:A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M( P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant ( P=0.003). Conclusion:COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.

Objective:Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province.Methods:The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared.Results:A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M( P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant ( P=0.003). Conclusion:COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.