Purpose To explore the clinicopathologic features and differential diagnosis of nephrogenic adenomas(NAs)in urinary tract.Methods 27 cases of NA were collected.The clinicopathological features and differential di-agnosis were analyzed,and the relevant literatures were reviewed.Results A total of 27 cases of NA in urinary tract were included in this study,including 20 males and 7 females,ranging in age from 24 to 84 years.Among them,clini-cal manifestations included urinary tract irritation in 8 cases,hematuria in 7 cases,and no obvious symptoms or other comorbidities in 12 cases.Comorbidities:17 cases combined with urothelial tumors,4 cases with cystitis,2 cases with tuberculosis,2 cases with urethral diverticulum,and 2 cases with ureteral calculi or stenosis.Gross inspection:19 ca-ses occurred in the bladder,5 in the ureter,and 3 in the urethra.The average size of the lesions was about 4.3 mm.Local edema or protrusion of the mucosa with roughness were found in 18 cases,papillary or polypoid masses in 5 ca-ses,or follicular-like neoplasma in 4 cases.Histologic features:these lesions were mainly composed of papillary,tubu-lar and cystic structure,and eosinophilic colloid secretions were seen in the lumen.The lining epithelium was cuboidal or low columnar,some of which were 'hobnail' or signet ring-like cells,and stroma showed edema and chronic inflam-mation.Immunohistochemistry:epithelial cells expressed PAX8 and CK7,partially expressed P504S and GAT A3,but not p63 and PSA.p53 was wild type,and Ki67 proliferation index was low(1％-8％).Molecular testing:no ab-normalities were found in 14 urine FISH tests before surgery,and no fusion mutation was detected in 2 samples selected for second-generation sequencing.Treatment and follow-up:follow-up data were obtained for all cases,of which 24 un-derwent transurethral resection of bladder lesions,and the rest underwent nephroureterectomy or cystoprostatectomy.The mean follow-up was 26.6(1-59)months,and the lesion recurred in 2 cases.Conclusion NAs are relatively rare,and their final diagnosis depends on pathological examination.When the biopsy sample is small or the histomor-phology is atypical,it's often necessary to differentiate it from urothelial tumor,prostate adenocarcinoma and clear cell adenocarcinoma.Understanding the clinicopathologic and immunohistochemical features of NA is helpful to improve the diagnostic rate and avoid missed-diagnosis or misdiagnosis.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.

In order to promote the construction of a multi-point trigger intelligent surveillance and early warning system of the plague in China, the development process, application practice, advantages, and limitations of the plague surveillance and early warning system in China and its role in plague prevention and control are reviewed and analyzed. It is suggested to include multiple departments, carry out a multi-channel monitoring mechanism for plague from different perspectives, further improve the plague surveillance and early warning system, and enhance surveillance and early warning capability.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.

Purpose To explore the clinicopathologic features and differential diagnosis of nephrogenic adenomas(NAs)in urinary tract.Methods 27 cases of NA were collected.The clinicopathological features and differential di-agnosis were analyzed,and the relevant literatures were reviewed.Results A total of 27 cases of NA in urinary tract were included in this study,including 20 males and 7 females,ranging in age from 24 to 84 years.Among them,clini-cal manifestations included urinary tract irritation in 8 cases,hematuria in 7 cases,and no obvious symptoms or other comorbidities in 12 cases.Comorbidities:17 cases combined with urothelial tumors,4 cases with cystitis,2 cases with tuberculosis,2 cases with urethral diverticulum,and 2 cases with ureteral calculi or stenosis.Gross inspection:19 ca-ses occurred in the bladder,5 in the ureter,and 3 in the urethra.The average size of the lesions was about 4.3 mm.Local edema or protrusion of the mucosa with roughness were found in 18 cases,papillary or polypoid masses in 5 ca-ses,or follicular-like neoplasma in 4 cases.Histologic features:these lesions were mainly composed of papillary,tubu-lar and cystic structure,and eosinophilic colloid secretions were seen in the lumen.The lining epithelium was cuboidal or low columnar,some of which were 'hobnail' or signet ring-like cells,and stroma showed edema and chronic inflam-mation.Immunohistochemistry:epithelial cells expressed PAX8 and CK7,partially expressed P504S and GAT A3,but not p63 and PSA.p53 was wild type,and Ki67 proliferation index was low(1％-8％).Molecular testing:no ab-normalities were found in 14 urine FISH tests before surgery,and no fusion mutation was detected in 2 samples selected for second-generation sequencing.Treatment and follow-up:follow-up data were obtained for all cases,of which 24 un-derwent transurethral resection of bladder lesions,and the rest underwent nephroureterectomy or cystoprostatectomy.The mean follow-up was 26.6(1-59)months,and the lesion recurred in 2 cases.Conclusion NAs are relatively rare,and their final diagnosis depends on pathological examination.When the biopsy sample is small or the histomor-phology is atypical,it's often necessary to differentiate it from urothelial tumor,prostate adenocarcinoma and clear cell adenocarcinoma.Understanding the clinicopathologic and immunohistochemical features of NA is helpful to improve the diagnostic rate and avoid missed-diagnosis or misdiagnosis.

In order to promote the construction of a multi-point trigger intelligent surveillance and early warning system of the plague in China, the development process, application practice, advantages, and limitations of the plague surveillance and early warning system in China and its role in plague prevention and control are reviewed and analyzed. It is suggested to include multiple departments, carry out a multi-channel monitoring mechanism for plague from different perspectives, further improve the plague surveillance and early warning system, and enhance surveillance and early warning capability.

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.

Objective:To study the epidemic situation of Marmota himalayana plague and Yersinias infection in Yugur Autonomous County of Sunan (Sunan County) of Gansu Province, and to provide new ideas for prevention and control of plague. Methods:From 2014 to 2018, liver and spleen, cecum, throat swabs and blood samples of Marmota himalayana were collected on the spot in Sunan County, where Yersinia strains were isolated and identified, and plague F1 antigen and antibody were detected. Results:A total of 634 liver and spleen samples, 427 cecum samples and 426 throat swabs samples were collected from Marmota himalayana, and 23 strains of Yersinia pestis, 2 strains of Yersinia marcescens, and 1 strain of Yersinia flexneri were detected, with the detection rates of 3.63% (23/634), 0.47% (2/427) and 0.23% (1/426), respectively. The detection rate of Yersinia pestis in different years was statistically significantly different (χ 2 = 13.19, P = 0.010). A total of 1 822 serum samples of Marmota himalayana were detected, and 5 F1 antibody positive samples were detected, with a positive rate of 0.27%, the difference of positive rate between different years was statistically significant (χ 2 = 25.22, P < 0.001); 282 liver and spleen tissue homogenates of Marmota himalayana were detected, 22 F1 antigen positive samples were detected, the positive rate was 7.80%, and there was no statistically significant difference between different years (χ 2 = 7.85, P = 0.097). The 23 strains of Yersinia pestis detected were distributed in Mati Tibetan Township (12 strains), Dahe Township (6 strains) and Qifeng Tibetan Township (5 strains); 1 strain of Yersinia flexneri and 2 strains of Yersinia marcescens were both located in Dahe Township. Conclusion:There is an epidemic of plague among animals in Sunan County from 2014 to 2018, and the areas where Yersinia pestis and non pathogenic Yersinia are detected overlapped.

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 study the genotyping and regional distribution characteristics of Yersinia pestis by single nucleotide polymorphism (SNP) in Gansu Province. Methods:A total of 52 strains of Yersinia pestis isolated from Himalaya Marmot plague foci and Spermophilus alaschanicus plague foci in Gansu Province from 1962 to 2017 were selected for culture and extraction of DNA. The genomic DNA of Yersinia pestis was sequenced by the second generation of Illumina PE150 to identify the SNP sites. The species characteristics of Yersinia pestis in Gansu Province was determined by the Kimura-2-parameter model of neighbor joining of Mega 10.0 software based on the SNP sites. The molecular evolutionary tree of the groups was determined by Hasegawa-Kishino-Yano model of maximum likelihood method according to the SNP sites. Results:A total of 103 SNP sites were identified in 52 strains of Yersinia pestis in Gansu Province, including 28 intergenic loci, 43 non-synonymous mutations, 31 synonymous mutations and 1 nonsense mutation. The 52 strains of Yersinia pestis were divided into 2 biotypes and 3 groups, which were ancient type (1.IN2, 3.ANT) and medieval type (2.MED). Among them, 35 strains belonged to 1.IN2 group, 13 strains belonged to 3.ANT group, and 4 strains belonged to 2.MED group. The 1.IN2 group was further divided into 5 subgroups: the groups of Yuerhong Town and Dangchengwan Town in Subei County, the groups of Mati Town and Dahe Town in Sunan County, and the group of Xiahe County. The 3.ANT group was further divided into 2 subgroups: the groups of Hongliuwan Town in Aksay County and Machang in Dangchengwan Town of Subei County. Conclusion:The SNP method can be used to genotype Yersinia pestis from different plague foci in Gansu Province, which has certain regional characteristics.