Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective:To analyze the monitoring results of human brucellosis prevention and control project in Gansu Province, in order to provide reference for the next revision of prevention and control plans.Methods:The data from the "China Disease Prevention and Control Information System" in Gansu Province from 2016 to 2022 and the annual data of human brucellosis cases reported by the active monitoring reports in various project counties (districts) were input into Excel 2016 software and a database was established. The epidemiological situation of brucellosis, the coverage of brucellosis prevention and control projects, the number of detected cases and health education were analyzed and compared by descriptive epidemiological method.Results:From 2016 to 2022, 70 to 82 out of 86 counties (districts) in Gansu Province were found to have human outbreaks of brucellosis, with brucellosis prevention and control projects covering 17 to 43 counties (districts). A total of 19 855 cases of human brucellosis were reported online in the province, with an average annual incidence of 11.07/100 000 and an annual incidence ranging from 6.03/100 000 to 20.89/100 000. There was a statistically significant difference in incidence among years (χ 2 = 5 264.84, P < 0.001). Through active monitoring, a total of 433 303 cases of brucellosis (tiger red plate agglutination test, RBT) were initially screened in project counties (districts) throughout the province, with 13 277 positive cases and a positive rate of 3.06% (13 277/433 303). Then the laboratory confirmed test (test-tube agglutination test, SAT) for brucellosis was carried out, with 9 967 positive cases and a positive rate of 2.30% (9 967/433 303). The infection rate of brucellosis in the population (SAT positive) was compared between different years, and the difference was statistically significant (χ 2 = 600.12, P < 0.001). In the project counties (districts), 7 481 confirmed cases of brucellosis were detected by active surveillance, and 15 794 cases were reported online, accounting for 47.37% (7 481/15 794) of the total number of cases reported online. The average awareness rate of brucellosis knowledge among medical personnel increased from 70.49% before training to 88.89% after training. The average awareness rate of brucellosis prevention and control knowledge among high-risk groups increased from 63.49% before health education to 89.05% after health education, and the behavior formation rate increased from 62.84% to 86.04%. Conclusions:From 2016 to 2022, the epidemic scope of human brucellosis in Gansu Province has been expanding year by year, and the coverage of prevention and control project is relatively small. The proportion of cases detected through active screening is relatively low. It is necessary to increase special funding investment, expand project coverage, strengthen high-risk group screening, education and behavioral intervention, and follow-up management of acute stage patient, so as to identify patients as early as possible and curb the upward trend of the epidemic.

Objective:To study the epidemiological characteristics of human brucellosis in high incidence areas of brucellosis in Gansu Province, and provide a guidance for precise prevention and control of brucellosis in the areas with high incidence of the disease.Methods:Using a retrospective research method, human brucellosis monitoring data from five high incidence counties of brucellosis in Gansu Province from 2018 to 2020, including Huan County (eastern), Guazhou County (western), Zhangjiachuan County (southern), Gaotai County (northern), and Jingtai County (central), were collected from monitoring database of the Central Transfer Payment Project. The epidemic characteristics of brucellosis in high incidence areas were described and analyzed.Results:From 2018 to 2020, there were a total of 787 laboratory confirmed cases of brucellosis in high incidence areas of brucellosis in Gansu Province, with a prevalence rate of 3.64%. The incidence rates for each year were 2.63% (205/7 780), 4.60% (327/7 111), and 3.78% (255/6 746), with statistically significant differences between different years (χ 2 = 41.44, P < 0.001). The prevalence rates of brucellosis in Huan County, Guazhou County, Zhangjiachuan County, Gaotai County, and Jingtai County were 0.02% (1/4 263), 3.67% (140/3 817), 4.32% (182/4 209), 4.89% (237/4 847), and 5.04% (227/4 501), respectively. There was a statistically significant difference in comparison between different regions (χ 2 = 211.59, P < 0.001). In 2018, the incidence rate was highest in Jingtai County in the central region, and scattered to Zhangjiachuan County in the south and Gaotai County in the north in 2019 and 2020. There were statistically significant differences in the prevalence rates among different genders, ages, ethnicities, educational levels, and occupational groups (χ 2 = 111.95, 212.76, 35.32, 89.59, 97.93, P < 0.001). From 2018 to 2020, the incidence of brucellosis in the < 20 (0.78%, 6.36%, 10.00%), 40 - 50 age groups (5.15%, 7.03%, 8.00%), students and young children (0.58%, 9.20%, 13.64%), and cadres (2.86%, 4.55%, 10.53%) showed an increasing trend year by year (χ 2trend = 21.55, 7.00, 30.63, 2.01, P < 0.001). Conclusions:The brucellosis in Gansu Province is still in a high level of growth stage, and the epidemic area is gradually dispersing; the cases are gradually becoming younger, and key occupational personnel are shifting from farmers and herdsmen to social workers. It is recommended to increase the scope of monitoring, increase publicity efforts, and enhance the self-protection and control awareness of key populations.

Objective:To learn about the epidemic dynamics and spatial epidemic characteristics of human brucellosis in Gansu Province.Methods:Data on human brucellosis in Gansu Province reported by China Disease Control and Prevention Information System from January 2016 to December 2020 were collected and analyzed by descriptive epidemiology and spatial clustering analysis.Results:A total of 10 025 cases of human brucellosis were reported in Gansu Province from 2016 to 2020, with a statistically significant difference in incidence rate between years (χ 2 = 242.86, P = 0.001). The incidence was the lowest in 2018 (6.03/100 000), and the highest in 2020 (11.39/100 000). The reported cases were concentrated in 45 - 55 years old, accounting for 34.52% (3 461/10 025); the male to female ratio was 2.91 ∶ 1.00 (7 458/2 567); farmers were the main occupation, accounting for 82.11% (8 232/10 025). Among the 86 counties (cities, districts) in Gansu Province, Yongchang County had the highest number of reported cases in 2020 (339 cases), and Sunan Yugur Autonomous County had the highest incidence in 2020 (190.89/100 000). Spatial autocorrelation analysis showed that there was significant spatial positive correlation between the incidence rate of human brucellosis in Gansu Province from 2016 to 2020 (global Moran's I > 0, Z > 1.96, P < 0.05), showing a spatial clustering distribution. The high-high clustering areas were concentrated in Yongchang County and Sunan Yugur Autonomous County. Conclusion:In Gansu Province, the main population of human brucellosis is middle-aged male farmers, and the incidence of brucellosis is spatially clustered.

Abstract: Objective To conduct a molecular epidemiological tracing and analysis of Yersinia pestis strains isolated from two human plague outbreaks with unknown sources in Gansu Province, China. The results of this analysis would provide a basis for isolating and controlling the sources of Yersinia pestis. Methods The strains of Yersinia pestis isolated from two human plague outbreaks occurring on December 12, 2017, and September 27, 2019 were genotyped by the different region (DFR) and the clustered regularly interspaced short palindromic repeats (CRISPR). The repeat numbers of the variable number tandem repeat (VNTR) loci in the tested strains of Yersinia pestis were calculated by the multiple variable number tandem repeats analysis (MLVA), and the location of the phylogenetic tree of the tested strains was determined with the method of minimum spanning tree (MST) by the software BioNumerics 6.6. Results The strain of 20171212 lacked DFR01, DFR02, DFR03, DFR04, DFR13, DFR23, and the DFR type was identified as type 8. The space sequence of YPa was a1'-a2-a3-a4-a5-a6-a7-a35, the space sequence of YPb was b1-b2-b3-b4, the space sequence of YPc was c1-c2-c3, the gene cluster of CRISPR was Ca35', the genotype of CRISPR was 26'. MLVA clustering analysis showed that the strain clustered within in the cluster of Yuerhong pasture in Subei County and formed an independent branch. On the other hand, the strain of 20190927 lacked DFR01, DFR13 and DFR23, with the DFR type identified as type 1b. The space sequence of YPa was a1-a2-a3-a4-a5-a6-a7, the space sequence of YPb was b1-b2-b3-b4, the space sequence of YPc was c1-c2-c3, the gene cluster of CRSIPR was Ca7, the genotype of CRSIPR was 22 MLVA clustering analysis showed that the strain was located close to the cluster of Dangjinshan in Akesai County, and relatively distant from the cluster of Yuerhong pasture in Subei County. Conclusions The genotypes of strain 20171212 by DFR and CRISPR were consistent with the main genotypes of Y. pestis from Himalayana Marmota foci in Subei County, which confirmed that the human plague cases were naturally occurring locally. However, the strain gathered the cluster of Yuerhong pasture in Subei County, which indicated that the source of infection was not in Yanchiwan Town, but in the surrounding area of the Yuerhong pasture. The genotypes of strain 20190927 by DFR and CRISPR were in accordance with the main genotype of Y. pestis from Himalayana Marmota foci in Akesai County and were closer to the cluster of Dangjinshan in Aksai County than to

Objective:To analyze the changes of spatial, seasonal, and age distribution of brucellosis among humans and animals in Gansu Province and to provide a reference for the next step in formulating prevention and control measures.Methods:Reported data of brucellosis of humans and animals in Gansu Province from 2018 to 2020 were collected. The human epidemic data were obtained from "China Disease Control and Prevention Information System", and the positive data of animals were obtained from the monthly report provided by Gansu Animal Disease Control Center. Human brucellosis was classified and analyzed according to year, month, age and region, and livestock brucellosis was classified according to year, month, population and region. ArcGIS 10.2 software was used to analyze the spatial epidemiological characteristics of the data. Measuring Geographic tool was used to calculate the shifting distance of the center of the disease incidence in humans and animals from 2018 to 2020.Results:From 2018 to 2020, a total of 6 375 cases of human brucellosis were reported in Gansu Province. The 40 - 59 age group accounted for 54.96% (3 504/6 375), 1 584 cases were reported in 2018, 1 787 cases were reported in 2019, and 3 004 cases were reported in 2020. The high incidence time of human brucellosis was July and November. A total of 48 180 brucellosis-positive animals (heads) were detected, of which 47 342 were positive sheep, accounting for 98.26% (47 342/48 180). The high incidence time of brucellosis among animals was October. Among the 14 cities (prefectures), the top cities of livestock brucellosis reported were Qingyang City, Zhangye City and Jiuquan City. The center of disease incidence among humans was located in Gulang County, Wuwei City. The center of disease incidence among animals was located in Wuwei City in 2018 and Qingyang City in 2020.Conclusions:The cases of brucellosis in humans and animals in Gansu Province are on the increase. In some areas, there are problems of separation of human and animal epidemics. It is necessary to actively strengthen monitoring and implement measures to prevent and control brucellosis in humans and animals in high-risk areas to curb the spread of the epidemic.

Objective:To understand the plague epidemic characteristics in the natural foci of the Qilian Mountains-A-erh-chin Mountains Himalayan marmot plague in Gansu Province, and to provide scientific basis for innovative prevention and control of the plague in combination with local conditions. Methods:A retrospective study was used to collect the monitoring data of the natural foci of plague in Gansu Province from 2011 to 2018 (from the epidemic surveillance files of the Center for Disease Control and Prevention of Gansu Province and direct network reporting information). Descriptive epidemiological method was used to analyze the plague epidemic characteristics of natural foci of the Qilian Mountains-A-erh-chin Mountains Himalayan marmot plague in Gansu Province from 2011 to 2018, including the distribution of host animals, pathogenic and serological testing of the plague bacteria, and the epidemic characteristics of human plague. Results:From 2011 to 2018, the total average marmot density in the natural foci of the Qilian Mountains-A-erh-chin Mountains Himalayan marmot plague in Gansu Province was 0.21/hm 2, of which Tianzhu County had the highest average marmot density of 0.58/hm 2, and Jiayuguan City had the lowest average marmot density of 0.01/hm 2. A total of 381 strains of Yersinia pestis were isolated in the foci, of which 4 were isolated from human corpses, 298 were host animals, and 79 were infectious vectors. Among them, the top 3 counties (cities) of isolated strains were Aksai County (38.85%, 148 strains), Subei County (31.50%, 120 strains) and Yumen City (16.27%, 62 strains). A total of 6 860 marmot serum, 1 769 dog serum were tested, the F1 antibody positive rates were 2.70% (185/6 860), 8.42% (149/1 769); and the F1 antigen positive rate of 814 animal materials was 4.30% (35/814), respectively. There were 4 times of human plague, 4 cases occurred and 4 cases died; 3 times occurred in Subei County and 1 time in Yumen City. The onset months were July, September, November and December. Active contact with infected animals such as shepherd dogs was the main route of infection, and migrant herders were the key occupation population. Conclusions:The animal epidemic situation in the natural foci of the Qilian Mountains-A-erh-chin Mountains Himalayan marmot plague in Gansu Province is active, and the plague presents different epidemic states in different regions. The prevention and control measures should be taken according to local conditions and guided by classification to strictly prevent the occurrence and transmission of the plague.

Objective:To analyse the effects of meteorological factors on plague epidemic in Himalayana marmot plague natural foci in Subei and Sunan counties of Gansu Province. Methods:The surveillance data of plague from 1973 to 2016 in Himalayan marmot foci of Subei and Sunan counties (from Gansu Provincial Center for Disease Control and Prevention) and the meteorological factors (rainfall, temperature, relative humidity) of current, preceding first, second and third years (the first, second and third years before the reference year, from China Meteorological Data Sharing Service System) were collected. In order to build generalized additive model (GAM), the positive rate of plague was used as dependent variable while meteorological factors of the current, preceding first, second and third years were used as independent variables. The influence of meteorological factors on plague was quantitatively analyzed by using R2.3.2 software. Results:In 2006 - 2016, compared with 1974 - 1983, the average temperature in Subei rose by 0.99 ℃, the average relative humidity rose by 3.55%RH, and the average rainfall rose by 12.16 mm; in Sunan County, the average temperature rose by 1.00 ℃, the average relative humidity rose by 2.01%RH, and the average rainfall rose by 14.60 mm. From 1973 to 2016, 11 cases of human plague with 7 cases of dead (12 cases of attack) occurred in the investigated district. The average rainfall of the preceding third year of Subei rose every 1.00 mm within a certain range, the animal plague occurred rose by 0.40%. The average relative humidity of preceding second year of Subei rose every 1.00%RH within a certain range, animal plague occurred rose by 11.66%. The average rainfall of the preceding first year of Sunan rose every 1.00 mm within a certain range, the animal plague occurred rose by 1.32%. The average relative humidity of preceding third year of Sunan rose every 1.00%RH within a certain range, animal plague occurred rose by 11.96%. The average temperature of the preceding second year of Subei, Sunan rose every 1.00 ℃ within a certain range, animal plague rose 73.17%, 70.18%, respectively.Conclusions:The occurrence and prevalence of plague in Himalayana marmot are closely related to meteorological factors, and the temperature within a certain range (but not continuously) not only promotes the epidemic of plague, but also has a lag effect. In addition, the effects of different types of climate in the same foci on the prevalence of animal plague vary.

Objective:To analyze the dynamics of plague epidemic in Spermophilus alaschanicus plague foci of Gansu Province from 1962 to 2018, and to provide evidence for plague control and prevention. Methods:The data of Spermophilus alaschanicus plague in Gansu Province from 1962 to 2018 were collected and organized from epidemic surveillance and epidemic summary. The method of descriptive epidemiology was used to analyze plague, including population (regional distribution, time distribution) and animal (geographic distribution, infected animals and vectors) epidemiology. Results:There was only one case of human plague in the Spermophilus alaschanicus plague foci of Gansu Province from 1962 to 2018. The total incidence of the disease was 26 cases, 11 cases died, the incidence rate was 29.89% (26/87), and the mortality was 42.31% (11/26). The cases were mainly distributed in Liuzhai Township and Xinyuan Township of Huining County. The outbreak occurred from July to August. Plague bacteria were isolated from the plague foci of Gansu Province during two peak epidemics of the plague among animals from 1962 to 2018. The bacteria detection area was located in 2 rural areas that were the northern area of Liuzhai in Huining County, and the neighboring Zhongtian and Fuxing in Pingchuan District. Five places were determined to be the animal epidemic sites. The endemic species were Spermophilus alaschanicus and Vulpescorsac, and the vector species were Citellophilus tesquorus mongolicus and Neopsylla abagaitui. The epidemic time of animal plague was from April to August. Totally 115 positive serum F1 antibodies were obtained. Among them, 92 positive serum samples were detected in Huining County and 23 in Pingchuan District. The positive blood coagulation sites were distributed in 11 villages, 5 towns of 2 counties (districts). The surveillance results showed that 30 species of animals belonging to 5 orders, 11 families, 5 subfamilies, and 21 genera were found in the foci, most of them were Spermophilus alaschanicus, which accounting for 69.1% (2 464/3 567) of the total species of rodents in the past years. A total of 12 482.9 hm 2 were investigated by sampling method, and 9 709 Spermophilus alaschanicus were captured, with an average density of 0.78/hm 2. Conclusions:The plague is intermittently prevalent in Gansu's Spermophilus alaschanicus plague foci. So the prevention and control strategies should be adjusted in time according to the changes. In residential areas, we should take the initiative to strengthen the monitoring of rat situation and the publicity and education of human plague prevention knowledge.

Objective To analyze the relationship between meteorological variables and the prevalence of marmot plague in the Himalayan marmot foci of Subei County,Gansu Province.Methods The surveillance data (from Gansu Provincial Center for Disease Control and Prevention) on human plague,the meteorological factors (average rainfall,temperature,relative humidity) data (from China Meteorological Data Sharing Service Network) of the current and preceding (relative to current year as a reference) first,second and third years and meteorological factors data of the current and preceding first,second and third months in Subei of Himalayan marmot foci from 1973 to 2014 were collected.The association of positive rate of plague bacteriological detection and meteorological factors was evaluated by using SAS 9.3 software.The influence of meteorological factors on the epidemic of marmot plague was analyzed by the logistic regression analysis.Results From 1973 to 2014,6 human plague cases with 5 dead cases occurred in Subei County.The positive rate of plague bacteriological detection was positively correlated with the average relative humidity of current year and the average temperature of preceding first year (r =0.366,0.385,P ＜ 0.05),and it was negatively correlated with the average relative humidity of preceding third year (r =-0.304,P ＜ 0.05);the positive rate of plague bacteriological detection was positively correlated with the average rainfall of preceding first month (r =0.212,P ＜ 0.05),and it was negatively correlated with the average relative humidity of preceding second and third months (r =-0.196,-0.201,P ＜ 0.05).The risk factor of animal plague epidemic in marmot foci in Subei County was average temperature of current month [odds ratio (OR) =1.304,95％ confidence intervals (CI):1.195-1.422],and the protective factor was average relative humidity of preceding third month (OR =0.960,95％CI:0.932-0.988).Conclusions The prevalence of marmot plague is closely associated with meteorological factors in the natural plague foci of Subei County of Gansu Province.The temperature not only plays a role in promoting the prevalence of plague,but also has a lagging effect.Therefore,the meteorological factors can be considered as a reference of the plague prevalence in Himalayan marmot plague foci.