Objective To investigate the prevalence of spotted fever group rickettsiae (SFGR) infections in free-living ticks and among high-risk populations in the southern margin of the Gurbantunggut Desert, Xinjiang Uygur Autonomous Region, so as to provide insights into tick-borne diseases prevention and control in this region. Methods Free-living ticks were collected from five counties (cities) in the southern margin of the Gurbantunggut Desert, Xinjiang Uygur Autonomous Region. Tick species were identified by morphology combined with mitochondrial cytochrome c oxidase subunit Ⅰ (COI) gene analysis. Four target gene fragments of Rickettsia were amplified using a nested PCR assay, including outer membrane protein B (ompB), 17-kDa common surface antigen protein (17kDa), surface cell antigen 1 (sca1), and surface cell antigen 4 (sca4) genes, to detect the prevalence of SFGR infections in tick samples. Positive PCR amplification products were purified, sequenced, and subjected to sequence alignment, and phylogenetic trees were created using the neighbor-joining (NJ) method. Serum samples were collected from individuals at a high risk of tick exposure from six counties (cities, districts) in the southern margin of the Gurbantunggut Desert, Xinjiang Uygur Autonomous Region, and serum levels of anti-R. sibirica IgG antibodies were detected among these individuals using indirect immunofluorescence assay (IFA) and statistically analyzed. Results A total of 287 free-living ticks were collected, and all were identified as Hyalomma asiaticum. The overall prevalence of SFGR infection was 78.40% (225/287) in tick samples, and five Rickettsia species were characterized, including R. sibirica, which shared 99.81% (515/516) sequence homology with the strain detected in Dermacentor sinicus from China; R. massiliae, which shared 99.80% (509/510) sequence homology with the strain detected in Rhipicephalus sanguineus from Ethiopia; R. raoultii, which shared 100.00% (516/516) sequence homology with the strain detected in Hyalomma asiaticum from Xinjiang Uygur Autonomous Region in China; R. africae, which shared 100.00% (524/524) sequence homology with the strain detected in Amblyomma splendidum from Ethiopia; and Candidatus Rickettsia barbariae, which shared 99.80% (499/500) sequence homology with the strain detected in steppe polecats from Xinjiang Uygur Autonomous Region in China, with R. sibirica (33.80% detection rate, 97/287) and R. raoultii (33.10%, 95/287) as dominant species. A total of 1 489 serum samples were collected from individuals at a high risk of tick exposure, and the seroprevalence of antiR. sibirica IgG antibodies was 30.83% (459/1 489). There were no significant differences in the seroprevalence in terms of genders (χ² = 2.23, P > 0.05) or age groups (χ² = 6.45, P > 0.05); however, there was a region-specific seroprevalence rate of anti-R. sibirica IgG antibodies (χ² = 16.05, P < 0.05). Pairwise comparisons showed lower seroprevalence rate of anti-R. sibirica IgG antibodies among high-risk individuals in Midong District of Urumqi City (22.27%, 53/238) than in Wujiaqu City (34.70%, 93/268) and Manas County(37.55%, 98/261) (both P values < 0.05); however, they were not significantly different from those in the other regions (all P values > 0.05). Conclusion Multiple SFGR species are detected in H. asiaticum ticks sampled from the southern margin of the Gurbantunggut Desert, Xinjiang Uygur Autonomous Region, where there is a potential risk of local transmission of spotted fever rickettsiosis.

ObjectiveTo investigate the regulatory effect of miR-21-5p in bone marrow mesenchymal stem cell-derived exosome （BMSC-Exo） on angiogenesis through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsBone marrow mesenchymal stem cells （BMSCs） were isolated from rats， cultured， and divided into negative control group （NC group） and inhibitor group， which were transfected with miR-21-5p negative control and miR-21-5p inhibitor， respectively， and then exosomes were extracted and identified. Exosomes were co-cultured with human umbilical vein endothelial cells （HUVECs）. MTT assay was used to measure cell proliferation （24， 48， and 72 hours）， tube formation assay was used to assess angiogenesis ability， and Western blot was used to measure the protein expression levels of phosphorylated Akt （p-Akt）， total Akt， and vascular endothelial growth factor （VEGF）. The change in the angiogenesis ability of HUVECs was observed after treatment with the PI3K inhibitor LY294002. The independent samples t-test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsFlow cytometry showed that the third-generation BMSCs showed high expression levels of CD29 （98.18%） and CD90 （97.85%） and a low expression level of CD45 （0.22%）. Quantitative real-time reverse transcription-polymerase chain reaction showed that compared with the NC group， there was a significant reduction in the relative expression level of miR-21-5p in BMSCs after transfection with miR-21-5p inhibitor （0.38±0.05 vs 1.00±0.08， t=11.38， P<0.01）. MTT assay showed that compared with the control group， the 25， 50， 100， and 200 μg/mL exosome treatment groups had a significant increase in the proliferative activity of HUVECs （all P<0.05）， among which 100 μg/mL exosome treatment for 72 hours showed the most significant pro-proliferative effect， while the 400 μg/mL exosome treatment group showed a significant reduction in the proliferative activity of HUVECs （P<0.01）. Tube formation assay showed that compared with the control group and the NC-Exo group， the inhibitor-Exo group showed a significant reduction in angiogenesis ability （both P<0.05）， and compared with the inhibitor-Exo group， there was a further significant reduction in angiogenesis ability after addition of the PI3K inhibitor LY294002 （P<0.01）. Western blot showed that compared with the control group and the NC-Exo group， the inhibitor-Exo group had significant reduction in the protein expression levels of p-Akt and VEGF （all P<0.05）， and compared with the inhibitor-Exo group， the protein expression levels of p-Akt and VEGF further decreased significantly after the addition of LY294002 （both P<0.01）. ConclusionBMSC-Exo targets and activates the PI3K/Akt signaling pathway through miR-21-5p， upregulates the expression of VEGF， and promotes vascular endothelial cell proliferation and angiogenesis.

AIM:To explore the changes of intesti-nal flora in patients with type 2 diabetes mellitus complicated with coronary heart disease after lira-glutide treatment and its correlation with glucose and lipid metabolism indexes.METHODS:Twenty-six patients with type 2 diabetes mellitus complicat-ed with coronary heart disease were selected to compare the changes of glucose and lipid metabo-lism indexes and intestinal flora(high-throughput sequencing technique)before and after liraglutide treatment,and to analyze the correlation between glucose and lipid metabolism indexes and intestinal flora.RESULTS:Compared with those before treat-ment,the indexes of glucose metabolism and lipid metabolism in the patients were significantly de-creased(P＜0.01).Liraglutide had no significant ef-fect on the diversity of intestinal flora(P＞0.05),but can significantly change the composition of intesti-nal flora(P＜0.05).While beneficial bacteria such as Lachnospiraceae increased significantly,it signifi-cantly reduced the abundance of pathogenic bacte-ria such as Escherichia_Shigella(P＜0.05),and pro-moted the production of short-chain fatty acids and body metabolism.CONCLUSION:Lilalutide can affect the composition of intestinal flora in type 2 diabetes patients with coronary heart disease,and then participate in the regulation of glucose and lipid metabolism.

AIM:To explore the changes of intesti-nal flora in patients with type 2 diabetes mellitus complicated with coronary heart disease after lira-glutide treatment and its correlation with glucose and lipid metabolism indexes.METHODS:Twenty-six patients with type 2 diabetes mellitus complicat-ed with coronary heart disease were selected to compare the changes of glucose and lipid metabo-lism indexes and intestinal flora(high-throughput sequencing technique)before and after liraglutide treatment,and to analyze the correlation between glucose and lipid metabolism indexes and intestinal flora.RESULTS:Compared with those before treat-ment,the indexes of glucose metabolism and lipid metabolism in the patients were significantly de-creased(P＜0.01).Liraglutide had no significant ef-fect on the diversity of intestinal flora(P＞0.05),but can significantly change the composition of intesti-nal flora(P＜0.05).While beneficial bacteria such as Lachnospiraceae increased significantly,it signifi-cantly reduced the abundance of pathogenic bacte-ria such as Escherichia_Shigella(P＜0.05),and pro-moted the production of short-chain fatty acids and body metabolism.CONCLUSION:Lilalutide can affect the composition of intestinal flora in type 2 diabetes patients with coronary heart disease,and then participate in the regulation of glucose and lipid metabolism.

BACKGROUND:Bone marrow mesenchymal stem cells(BMSCs)can release a large number of exosomes(Exos).The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified. OBJECTIVE:To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism. METHODS:Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs.The Exos were extracted by ultracentrifugation and named(BMSCs+miR-21-5p NC)-Exos and(BMSCs+miR-21-5p inhibitor)-Exos.BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes.The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection.TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats. RESULTS AND CONCLUSION:(1)The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells,the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group,indicating that miR-21-5p could target PIK3R1.(2)TUNEL test results showed that compared with(BMSCs+miR-21-5p NC)-Exos group,(BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate.Compared with the(BMSCs+miR-21-5p NC)-Exos group,after the addition of AKT inhibitor LY294002,the apoptosis rate was significantly increased.(3)The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p,in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

Objective:To analyze and explore the clinical characteristics and risk factors related to nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia.Methods:252 hospitalized patients with liver cirrhosis combined with atrial arrhythmia from January 2014 to December 2021 were enrolled, and their clinical characteristics were analyzed. The above-mentioned patients were divided into groups according to their nosocomial mortality rate. Among them, 45 nosocomial mortality cases were classified as the mortality group, and 207 survival cases were classified as the survival group. The differences in clinical data and laboratory data between the two groups were compared. The risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia were analyzed. The t-test, or rank-sum test, was used to compare measurement data. The chi-square test, or Fisher's exact probability method, was used to compare enumeration data. Multivariate analysis was performed by the logistic regression method.Results:Among the 252 cases, the male-to-female ratio was the same (male/female ratio: 126/126). The age range was 26 to 89 (66.77±10.46) years. Han ethnicity accounted for 79.5%. The main type of atrial arrhythmia was atrial fibrillation ( P ?

Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication;however,some patients may still have low-level viremia(LLV)after receiving entecavir,tenofovir disoproxil fumarate,tenofovir alafenamide,or tenofovir amibufenamide for 48 weeks or more.Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis,the risk of decompensated liver cirrhosis and hepatocellular carcinoma,and the reduction in long-term survival rate.Therefore,this article reviews the development,risk factors,and clinical harm of LLV after first-line treatment with nucleos(t)ide analogues,as well as different treatment regimens,in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future.

Hepatitis D is a global public health issue, and the infection rate and genotype of HDV infection vary greatly across different regions. The overlapping infection of hepatitis D virus (HDV) in patients with chronic hepatitis B virus (HBV) infection can accelerate disease progression, but hepatitis D has not been taken seriously to a large extent. Xinjiang in China is an area with a high incidence rate of hepatitis B, but there is a lack of research on hepatitis D. This article discusses the prevalence of HDV infection in Xinjiang and briefly reviews the prevalence rate of HDV infection in Xinjiang, the molecular epidemiology of HDV among different ethnic groups, and the current status of HDV infection in neighboring countries, so as to provide a reference for the conduct of molecular epidemiological research on HDV and disease prevention and control in Xinjiang.

Objective:To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region.Methods:A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment.Results:A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups ( χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups ( χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups ( χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups ( χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups ( χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups ( χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference ( P>0.05). Conclusion:The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.

Objective:To analyze the clinical characteristics of HBV-related liver cirrhotic patients with low viral load.Methods:A retrospective analysis on 481 inpatients with HBV-related cirrhosis with low viral load [HBV DNA≤2 000 IU/ml (10 4 copies/ml)] general condition, virological indicators, liver function-related indicators, complications, and incidence of complications were analyzed. The t-test was used to compare the average measurement data, and the χ2 test was used to compare the count data. Results:481 cases were mainly male (male/female: 324/157), aged 20-83 (53.31 ± 11.67) years old. Han nationality accounted for 71.518%. 386 cases were HBsAg positive. 391 cases were HBeAg positive, and 140 cases were HBV DNA positive. The average value of bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, platelets, and prothrombin were 50.59 ± 91.25 (μmol/L), 33.68 ± 7.5 (g/L), and 60.66 ± 106.95(U/L), 63.37 ± 86.19(U/L), 106.65 ± 83.22(×10 9/L), 68.82% ± 25.33%, respectively. CTP class A/B/C had 220/150/111 cases. The average values of CTP, MELD, APRI and FIB-4 were 7.61 ± 2.58, 10.98 ± 5.79, 2.34 ± 3.56, 6.91 ± 8.04, respectively. The overall incidence of complications in HBV-related cirrhotic patients with low viral load, HBV DNA negative, HBV DNA positive, HBsAg negative, and HBsAg positive were 80.0%, 82.7%, 73.6%, 85.3%, and 78.8%, respectively. Among them, 283 cases (58.84%), 197 cases (55.77%), 86 cases (61.43%), 52 cases (54.74%) and 231 cases (59.84%) were of hypersplenism, and 267 cases (55.51%), 197 cases (55.77%), 70 cases (50.00%), 56 cases (58.95%), and 211 cases (54.66%) were of esophagogastric varices. There were 59 cases (12.27%), 48 cases (14.08%), 11 cases (7.86%), 12 cases (12.63%), and 47 cases (12.18%) of rupture of esophageal and gastric varices, respectively. 202 cases (42.00%), 147 cases (43.11%), 55 cases (39.29%), 42 cases (44.21%), and 160 cases (41.45%) were of ascites, respectively. 17 cases (3.53%), 12 cases (3.52%), 5 cases (3.5%), 2 cases (2.11%), 15 (3.89%) cases were of hepatic encephalopathy, respectively. There were 6 cases (1.25%), 3 cases (0.88%), 3 cases (2.14%), 0 cases (0%), 6 cases (1.55%) of liver cancer. 29 cases (6.03%), 21 cases (6.16%), 8 cases (5.71%), 9 cases (9.47%) and 20 cases (5.18%) were of portal vein thrombosis. Compared with the overall incidence of complications, 341 HBV DNA-negative patients and 95 HBsAg-negative patients still had higher incidence of complications. The patients were grouped by age, and in < 40 years old, 40-50 years old, and > 50 years old, the overall complications were 80.8% in 42 cases, 76.8% in 116 cases and 81.7% in 227 cases, and the difference was not statistically significant. Conclusion:HBV infection patients with low viral load, and those whose HBsAg has disappeared, are still at risk of developing liver cirrhosis and even serious complications, and whether such population need antiviral therapy and benefit from it deserves further research.