Objective　To understand the situation of plague host vectors, indicator animals and residents infected with plague bacteria in Cangyuan County, Yunnan Province, China-Myanmar border region, and to explore the risk of plague epidemic, so as to provide reference basis for supplementary plague data and prevention and control in this area. Methods　A plague survey was carried out in three townships in Cangyuan County in 2023. The collected host animals organs and body surface parasitic fleas were bacterial cultured. Serum collected from border residents, indicator animals, and host animals was tested for plague F1 antibodies using indirect hemagglutination assay (IHA). The positive samples were rejudged by IHA, immune colloidal gold assay(GICA) and up-converting phosphor technology(UPT). Results　Totally 294 serum samples were collected from border residents, with an average age of (48.48±14.27) years old, with more females than males. Three were positive for F1 antibody against Yersinia pestis, with a positive rate of 1.02%. And 65 samples of indicator animal serum and 31 samples of Rattus tanezumi serum were collected, and the detection of plague F1 antibody was negative. And 198 rodents belonging to 3 orders, 5 families, 11 genus and 14 species were captured, with a total capture rate of 7.93%, with Rattus tanezumi (46.97%) and Rattus andamanensis (19.19%) as the dominant species. The capture rate in residential indoor areas was 3.72%, and Rattus tanezumi was the absolutely dominant species (100.00%). The capture rate in farming areas was 10.26%, the dominant species were Rattus tanezumi (36.36%), Rattus andamanensis (23.03%), Mus pahari (10.30%) and Hylomys suillus (10.30%). And 60 fleas belonging to 3 families, 5 genera and 6 species were seized, the average infection rate of fleas was 11.62%, and the total flea index was 0.30. The dominant species were Xenopsylla cheopis (28.34%), Palaeopsylla remota (23.33%), Ctenophthalmus quadratus (18.33%), Stivalius aporus (15.00%) and Palaeopsylla incurua (11.67%). A total of 198 murine organ samples were isolated and cultured, and 24 groups of flea samples were obtained, no Yersinia pestis was isolated. Conclusion　The investigation has not found any recent infection with Yersinia pestis in rodents, body surface parasitic fleas and indicator animals; however, it is found that there is still a certain proportion of positive population of plague F1 antibody in the serum of residents. Rattus tanezumi and Xenopsylla cheopis are the first dominant species of host and vector in the county, the indoor density of Rattus flavipectus exceeds 3%, reaching the animal pestis IV early warning, and there is a risk of recurrence in the plague foci.

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals ; Mice ; Colitis/chemically induced* ; Immunity, Innate ; Intestine, Small ; Lymphocytes ; Mice, Inbred C57BL

OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.

Abstract: Objective To understand the population composition and quantitative changes of plague hosts and vectors in Menglian County, Yunnan Province, to monitor and investigate the epidemic dynamics of plague, and to evaluate the epidemic risk of plague, providing a scientific basis for plague prevention and control in Yunnan's border areas. Methods Animal plague surveillance was carried out according to the "Yunnan Provincial Plague Surveillance Program", and the data of plague surveillance in Menglian County from 2016 to 2020 were collected and analyzed. In 2020, a plague survey was conducted in two border towns in Menglian County. The samples of host animals and their surface parasitic fleas in residential, agricultural, and forest areas were collected, and serum samples of border residents and plague indicator animals were collected. Yersinia pestis was isolated and cultured from host animal organs and flea samples, and indirect hemagglutination assay (IHA) was used to detect F1 antibody in serum samples. Results A total of 793 host animals, encompassing 11 species across 7 genera and 4 families in 3 orders, were captured in animal plague surveillance in Menglian County, from 2016 to 2020. Rattus tanezumi was identified as the dominant indoor and outdoor species, with composition ratios of 93.58% and 83.91%, respectively. Suncus murinus, Rattus nitidus, Tupaia belangeri, and Rattus andamanensis were common species. The average rodent density indoors and outdoors was 1.33% and 1.65%, respectively. In 2020, the special survey in Menglian County's border areas captured 313 host animals, including 15 species across 9 genera and 4 families in 3 orders. The dominant species were Rattus tanezumi, Rattus andamanensis, and Suncus murinus, with composition ratios of 47.60%, 20.13%, and 10.86%, respectively. The capture rates of indoor and outdoor host animals were 3.25% and 18.81%, respectively. There were statistically significant differences in the capture rates of indoor and outdoor host animals and the density of indoor and outdoor Rattus tanezumi between routine monitoring and special investigation (χ2=30.682，1641.931，32.690，320.415，P<0.001). From 2016 to 2020, the flea infection rate of Xenopsylla cheopis on Rattus tanezumi was 30.97%, with a flea index of 0.79. In the 2020 special survey in Menglian County's border areas, a total of 99 fleas were captured across 7 species, 7 genera, and 4 families, with Xenopsylla cheopis and Palaeopsylla remota as the dominant ectoparasitic flea species, having composition ratios of 69.70% and 20.20%, and an infection rate of 9.90%. The infection rate of Xenopsylla cheopis on the surface of Rattus tanezumi was 12.08% (18/149 ), with a flea index of 0.46. There was a significant difference in the infection rate of Xenopsylla cheopis on the surface of Rattus tanezumi between routine monitoring and special investigation (χ2=22.773, P<0.001). Laboratory test results from both routine monitoring and special investigation were negative. Conclusions　The primary species of the main hosts and vectors of plague in Menglian County are prominent, and the density of rodents in the outdoor environment is relatively high. The monitoring and investigation did not find the infection of residents and animals in recent years. However, given the localized low-grade plague endemics in the surrounding areas, it is necessary to continuously strengthen the professional and technical training at the grass-roots level and enhance the monitoring and investigation of plague and other rodent-borne diseases in the border areas to effectively improve the quality and sensitivity of monitoring, timely carry out preventive prevention and control measures, effectively detect the epidemic, and reduce the risk of epidemic.

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ²=15.851， P<0.01； χ²=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective To investigate the clinical effectiveness and adverse events of domestic programmed cell death -1 (PD-1) inhibitor in the treatment of advanced non-HBV non-HCV-related hepatocellular carcinoma (NBNC-HCC). Methods A totals of 31 patients with advanced NBNC-HCC who received domestic PD-1 inhibitor in the Affiliated Hospital of Xuzhou Medical University from June 2019 to February 2022 were retrospectively enrolled and their clinicopathological data were retrieved from their medical records and analyzed, i.e., the time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse events were recorded and statistically analyzed. The Kaplan-Meier method was used for survival analysis. Results Among these 31 patients, only one achieved the complete response and four achieved the partial response, and six had the stable disease, but 20 showed a disease progression, resulting in an ORR of 16.1% and a (DCR of 35.5%. The median TTP was 7.2 months [95% confidence interval: 6.4-8.0) months]. The incidence of adverse events was 61.30% and the common adverse events were skin rash (29.03%) and hypertension (22.58%). However, there was no grade 4 adverse reactions or related death in these patients. Conclusion Advanced NBNC-HCC patients had a relative weak response to the PD-1 inhibitor although the adverse events were controllable. Future multi-center prospective clinical trials are needed to validate the data.

Objective:To investigate and determine the epidemic scope of plague natural foci in Yulong County of Yunnan Province, and to assess its epidemic risk, so as to providing basis for monitoring, prevention and control of plague.Methods:In 2017, 2 - 3 natural villages were selected from 8 villages and towns in Yulong County according to geographical landscape, altitude, population and area. During October and November, small mammal hosts and their parasitic fleas were captured by the night trap (cage) method, Yersinia pestis was isolated from host animal organs, and plague F1 antigen and antibody were detected by colloidal gold test. Plague specific antigen was detected by reverse indirect hemagglutination test (RIHA) in self-dead small mammals. Animal serum from dogs, cats and mice were collected for detection of plague F1 antibody by indirect hemagglutination test (IHA). Results:A total of 1 019 host animals including self-dead small mammals were collected, belonging to 22 species, 12 genera, 6 families, 4 orders. Among them, 1 016 small mammals were captured by tools and 996 were outdoors, with the capture rate of 25.28% (996/3 940). The dominant species of small mammals outdoors were Apodemus chevrieri, Rattus (R.) rattus, Eothenomys miletus and Crocidura attenuate, which accounted for 30.32% (302/996), 22.09% (220/996), 17.37% (173/996) and 12.35% (123/996). The common species were Niviventer confucianus, R.nitidus and R.norvegicus, which accounted for 8.13% (81/996), 4.02% (40/996) and 1.81% (18/996). A total of 20 small mammals of 9 species were captured indoors in the residential area, and the capture rate was 1.11% (20/ 1 800). The dominant species were R.norvegicus, R.nitidus and Mus musculus, which accounted for 30.00% (6/20), 25.00% (5/20) and 10.00% (2/20). Eighteen small mammals of 8 species were infected with 67 parasitic fleas, belonging to 5 species, 5 genera, 3 families. The total flea infection rate was 1.77% (18/1 019) and the total flea index was 0.070. Among them, 49 parasitic fleas from 4 small mammals of 3 species were collected indoors. The flea infection rate was 19.05% (4/21) and the flea index was 2.333. Leptopsylla segnis had the highest flea infection rate of 9.52% (2/21) and flea index of 0.571. Ctenocephalides felis had the highest flea index of 1.571 and flea infection rate of 4.76% (1/21). They were the main flea species on the body surface of small mammals in residential areas. There were 14 small mammals infected with parasitic fleas outdoors, and 18 fleas in 5 species were collected with flea infection rate of 1.40% (14/998) and flea index of 0.018. Among them, Leptopsylla segnis had the highest flea infection rate was 0.50% (5/998) and the flea index was 0.005. The flea infection rate of Neopsylla specialis specialis was 0.40% (4/998), and the flea index was 0.004. Ctenophthalmus quadratus had the highest flea index of 0.007, and the flea infection rate ranked the third with 0.30% (3/998). The flea infection rate and flea index of Frontopsylla spadix spadix were the lowest, which were 0.20% (2/998) and 0.002, respectively. Ctenophthalmus quadratus, Leptopsylla segnis and Neopsylla specialis specialis were the dominant parasitic fleas on the surface of outdoor small mammals. A total of 419 indicator animal sera were collected, including 402 dog sera. One of them was positive by IHA, with a positive rate of 0.25% (1/402). Seventeen serum samples were collected from cats and mice, and IHA test results were negative. Yersinia pestis was isolated and cultured from the organs of small mammals and the detection of Yersinia pestis by colloidal gold test was negative. RIHA test of self-dead small mammals was negative. Conclusion:A plague indicator animal positive spot is newly found in the plague natural foci in Yulong County, and the plague epidemic monitoring, prevention and control in this region should be strengthened.

Objective:To conduct a bibliometric analysis of relevant research in the field of health management of chronic diseases in China, and to discuss the research status, hot spots and development trends.Methods:The literatures on chronic disease health management research of China in CNKI, Wanfang database, VIP database and China Biology Medicine Database from January 1, 2000 to December 31, 2020 were retrieved. The annual number of papers, published journals, authors' number of papers and cooperation, research hotspots and development trends were analyzed by CiteSpace 5.5.2 software. The corresponding visual atlas were drawn.Results:A total of 8 841 articles related to health management of chronic diseases in China were retrieved. From 2000 to 2020, the number of articles issued basically showed an upward trend year by year, and the number in 2019 was the highest, which is 1 130 (12.8%) . There are 98 journals with a total number of papers equal or over 20, of which Chinese General Practice has the largest number of papers, with 349 related literatures (3.9%) . The authors with the largest number of articles published 18 articles, and 15 authors published 10 or more articles. "Chronic disease" is the most frequent key word, with a frequency of 1 804 times. Since 2016, research hot spots have been mainly distributed in graded diagnosis and treatment, combination of medical care and so on. Conclusions:Increasing attention has been paid to the health management of chronic diseases in China, but the researchers are relatively scattered. This study intuitively presents the research overview of chronic disease health management in China, preliminarily reveals the cooperative authors, and forms a general understanding of the research hotspots and development trends, which provides a reference for future research.

Objective:To detect and analyze the contents of eight metal elements in water samples of plague foci in Yunnan Province.Methods:During the period from December 2015 to November 2016, the plague foci of Yulong, Jianchuan and Lianghe were selected as sampling sites, water samples were collected in areas with rodent activities in the 4 seasons of spring, summer, autumn and winter. The contents of eight metal elements calcium (Ca), iron (Fe), zinc (Zn), chromium (Cr), plumbum (Pb), manganese (Mn), cadmium (Cd) and cuprum (Cu) in water samples were measured by flame atomic absorption spectrometry (FAAS), and the data [median (interquartile distance)] were statistically analyzed.Results:Twenty-six, 58 and 54 water samples were collected from Yulong, Jianchuan and Lianghe plague foci, respectively. The contents of metal elements of Pb and Cd in water samples of the three plague foci [Yulong: 0.19 (0.78) and 0.08 (0.07) mg/L; Jianchuan: 0.23 (0.56) and 0.03 (0.06) mg/L; Lianghe: 0.13 (0.61) and 0.09 (0.08) mg/L] were higher than that of "Environmental Quality Standards for Surface Water" (Pb: 0.10 mg/L, Cd: 0.01 mg/L). There were significant differences in the contents of Ca and Cd elements among the three regions ( P < 0.05), but there was no significant difference in the contents of the other 6 metal elements among the three regions ( P > 0.05). The content of Ca element was the highest in Yulong plague foci, and the lowest in Lianghe plague foci ( P < 0.017). In the Yulong plague foci, there was no statistically significant difference in the content of Fe element in different seasons ( P > 0.05), and the differences in the contents of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Cr element in Jianchuan plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Ca element in Lianghe plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). Conclusion:The metal element contents of Pb and Cd are relatively abundant in water samples from 3 plague foci of Yunnan Province, and the seasonal variation trend of metal element content in water samples of Yulong and Jianchuan plague foci is similar.