Objective:To investigate impacts of soy isoflavones(SIF)on alveolar bone resorption and inflammatory response in periodontitis rats based on Slit homologue 2(Slit2)/P38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods:Rats were separated into Control group,Model group,SIF low-dose group(L-SIF,25 mg/kg)and SIF high-dose group(H-SIF,75 mg/kg),with 10 rats per group,and periodontitis model was established by ligating necks of maxillary first molars of rats with silk thread except for control group.Rats in L-SIF group and H-SIF group were given corresponding doses of SIF by gavage,Control group and Model group were given same amount of normal saline by gavage,once a day,for 4 consecutive weeks.After administration,serum Slit2,TNF-α,IL-6 and IL-1β levels were detected by ELISA;Micro-CT scan was performed to detect distance between cemen-tumenamel junction and alveolar ridge crest(CEJ-ABC),bone mineral density(BMD),bone volume fraction(BV/TV),and alveolar bone loss was evaluated;HE staining and tartrate-resistant acid phosphatase(TRAP)staining were performed to evaluate tissue inflam-mation,bone resorption and osteoclast activity;expressions of osteoprotegerin(OPG)and receptor activator of nuclear factor κB ligand(RANKL)in periodontal tissues were detected by immunohistochemistry(IHC);Western blot was performed to detect protein expressions of Slit2,P38 MAPK and p-P38 MAPK in periodontal tissues.Results:Compared with Control group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,protein level of Slit2 and p-P38 MAPK/P38 MAPK were greatly increased in Model group,BMD,BV/TV and positive ex-pression of periodontal tissues OPG were greatly decreased(all P<0.05);compared with Model group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,pro-tein levels of Slit2 and p-P38 MAPK/P38 MAPK were greatly decreased,BMD,BV/TV and OPG positive expression of periodontal tissues were greatly increased in L-SIF group and H-SIF group(P<0.05),the above indicators in H-SIF group changed greatly better than L-SIF group(P<0.05).Conclusion:SIF can inhibit alveolar bone resorption and inflammatory response in periodontitis rats and improve periodontitis,whose mechanism may be related to inhibition of Slit2/P38 MAPK signaling pathway.

To evaluate the association between serum anti-tissue transglutaminase antibody (anti-tTG) titers and the severity of histological damage to the duodenal mucosa and to predict a possible anti-tTG cutoff value for diagnosing celiac disease (CD) and villous atrophy in the domestic population. Clinical and pathological data from 76 adult CD patients with positive anti-tTG titers and duodenal biopsy results who were treated at the People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to January 2022 were retrospectively analyzed. The correlation between anti-tTG titers and the severity of duodenal mucosal damage was statistically assessed to predict the optimal anti-tTG titer cut-off value for diagnosing CD and villous atrophy. Of the 76 patients, 10 had underlying CD, and of the 66 patients with duodenal histopathology, four were Marsh Ⅰ, six were Marsh Ⅱ, and 56 were Marsh Ⅲa-c grade. In adults with CD, anti-tTG titers were shown to be associated with the severity of histological damage to the duodenal mucosa. When the anti-tTG level was ≥5 times the upper limit of normal (ULN), the sensitivity and specificity for diagnosing CD were 83.9% and 92.9%, respectively. When the anti-tTG titer was ≥8 times the ULN, the sensitivity and specificity for diagnosing villous atrophy were 67.9% and 90.0%, respectively. Anti-tTG levels had a strong predictive value for diagnosing CD in adults when titers exceeded 10 times the ULN. Thus, the anti-tTG cut-off value can be combined with clinical judgment to diagnose CD, limiting the use of invasive endoscopy.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Background:Celiac disease has a wide range of clinical manifestations and a higher prevalence in women.Aims:To evaluate the differences in clinical characteristics in adult celiac disease patients with different genders.Methods:Adult patients(age≥18 years)diagnosed as celiac disease from July 2017 to July 2022 at the People's Hospital of Xinjiang Uygur Autonomous Region were included consecutively in the retrospective study.Comparisons of baseline demography,and clinical and pathological features between different genders were performed.Results:A total of 73 adult celiac disease patients were enrolled,19 were males and 54 were females,with the ratio of male to female being 1:2.84.The peak age group of onset was 30-59 years old,with an average age of(50.2±13.6)years for men and(43.5±13.2)years for women at diagnosis.There was no significant difference in the distribution of different age groups between men and women(P>0.05),but the proportion of women in 18-49 years age group and≥50 years age group were both higher than that of men with statistical significance(P<0.05).The most common gastrointestinal symptoms were chronic diarrhea(56.2%)and abdominal pain(56.2%),and anemia was the most common extraintestinal manifestation(50.7%),which was existed in 36.8%of males and 55.6%of females.Abdominal pain and nausea/vomiting were more common in females(all P<0.05),whereas no statistically significant differences were found between male and female groups in other gastrointestinal and extraintestinal manifestations,such as chronic diarrhea,flatulence,decreased appetite,weight loss,chronic fatigue,anemia,hypoproteinemia,osteoporosis/bone loss,etc(all P>0.05).The pathological grading of small intestinal biopsy was Marsh Ⅱin 6 cases,and Marsh Ⅲa,Ⅲb and Ⅲc in 14,23,and 30 cases,respectively.No statistically significant difference was observed in pathological grading between patients with different genders(P>0.05).Conclusions:There is a marked female predominance in adult celiac disease in Xinjiang Uygur Autonomous Region,and women were diagnosed at a younger age.Chronic diarrhea,abdominal pain and anemia present as the most common gastrointestinal and extraintestinal manifes-tations.Abdominal pain and nausea/vomiting are more common in women than in men.

Objective:To analyze the expression of 25-hydroxyvitamin D [25(OH)D] in serum and vitamin D receptor (VDR) in descending duodenum of adult patients with celiac disease and the correlation between 25 (OH) D, VDR and the clinical characteristics and indexes of celiac disease.Methods:From September 1, 2020 to May 1, 2022, 37 patients who were diagnosed with celiac disease (celiac disease group) in the Department of Gastroenterology of People′s Hospital of Xinjiang Uygur Autonomous Region were enrolled. During the same period, according to gender, age and nationality matched at a ratio of 1 to 1, 37 patients who visited the hospital with suspected symptoms of celiac disease and finally were excluded from the diagnosis of celiac disease after screening (non-celiac disease group) were selected. General data and clinical characteristics of all the patients were collected, including diarrhea, bone mineral density (BMD), Marsh stage. Serum 25(OH)D levels were detected, and the expression of VDR(high or low expression) in the descending duodenum was evaluated by immunohistochemical staining. Independent sample t test, chi-square test and Spearman correlation analysis were used for statistical analysis. Results:The serum 25(OH)D level and the proportion of patients with high VDR expression in the celiac disease group were both lower than those of the non-celiac disease group ((12.40±8.93) μg/L vs. (16.78±7.09) μg/L; 45.9%, 17/37 vs. 75.7%, 28/37), and the proportion of patients with diarrhea was higher than that of the non-celiac disease group (45.9%, 17/37 vs. 21.6%, 8/37), and the differences were statistically significant ( t=-2.52, χ2=6.86 and 4.89, all P<0.05). The serum 25(OH)D level was positively correlated with the VDR expression level in the descending duodenum both in the celiac disease group and the non-celiac disease group ( r=0.75 and 0.64, both P<0.001), and was not correlated with the diarrhea symptoms in the 2 groups (both P>0.05). There was a positive correlation between serum 25(OH)D and BMD in the celiac disease group ( r=0.48, P=0.017), and serum 25(OH)D was also correlated with BMD in the non-celiac disease group ( r=0.93, P<0.001). The VDR expression level in the descending duodenum was negatively correlated with the Marsh stage in the celiac disease group ( r=-0.36, P=0.031), while the VDR expression level was not related to the Marsh stage in the non-celiac disease group ( P>0.05). Conclusions:Vitamin D metabolism imbalance exists in the serum and duodenal mucosa of adult patients with celiac disease, which is related to the severity of osteoporosis and histopathology. It is suggested that patients with celiac disease should receive vitamin D metabolism regulation treatment.

Objective:To investigate the segmentation methods of pancreatic ductal adenocarcinoma (PDAC) tumor regions in 18F-fluorodeoxyglucose (FDG) PET/CT images, as well as their impact on radiomic features-based pathological grade prediction. Methods:A total of 72 patients (46 males, 26 females, age range: 25-87 years) with pathologically confirmed PDAC and a preoperative 18F-FDG PET/CT scan in Peking Union Medical College Hospital between September 2010 and January 2016 were enrolled retrospectively. The cohort of patients was classified as well differentiated group and non-well differentiated group based on the pathological grade of PDAC, and patients were divided into training set and validation set in the ratio of 3∶1 randomly. Two physicians performed manual contours in the tumor region (referred as region of interest (ROI)_M1 and ROI_M2) and semi-automatic ROIs based on standardized uptake value (SUV) gradient edge search (referred as ROI_G) and 40% threshold applied to the maximum SUV (SUV max; referred as ROI_S) were drawn. The four types of segmentation results were compared in terms of volume and Dice similarity coefficient (DSC). Shape, first-order, and texture features were extracted from PET/CT original and preprocessed images, and the interclass correlation coefficient (ICC) was used to assess each feature′s consistency across all segmentations. Kruskal-Wallis rank sum test, independent-sample t test or z test were used to analyze the data. The area under the receiver operating characteristic curve was used to assess model accuracy, and cross validation was used to assess generalization ability. Results:There were 55 patients in the training set (14 well differentiated cases and 41 non-well differentiated cases) and 17 patients in the validation set (4 well differentiated cases and 13 non-well differentiated cases). A total of 44 selected features were predictive of the pathological grade of PDAC among 20 feature groups. There was significant difference among the volumes of ROI_M1, ROI_M2, ROI_G and ROI_S (10.29(4.01, 19.43), 9.34(4.26, 17.27), 11.86(5.52, 19.74) and 15.08(9.62, 27.44) cm 3; H=18.641, P<0.05). The degree of contour coincidence and feature consistency between ROI_M1 and ROI_M2 were both higher (DSC=0.86 (0.76, 0.90), ICC=0.86 (0.74, 0.94)). Compared to manual contours, the degree of contour coincidence and feature consistency of ROI_G (DSC: 0.86(0.75, 0.91), 0.91(0.85, 0.96); ICC: 0.87(0.72, 0.94), 0.94(0.88, 0.98)) were better. There was no statistically significant difference in model accuracy or generalization ability between ROI_M1 and ROI_G ( z=1.052, t=0.712, both P>0.05). The accuracy of ROI_M2 was better than ROI_G ( z=3.031, P=0.002), but the generalization ability of ROI_M2 was insufficient ( t=3.086, P=0.012). Conclusions:Although the manual contour prediction models are highly accurate, their performance are unstable. Semi-automatic contouring based on gradient can achieve comparable accuracy to manual contouring, and the model′s generalization ability is stronger.

Objective:To investigate the clinical manifestations and pathological features of adult celiac disease in Xinjiang Uygur Autonomous Region.Methods:From January 2016 to December 2019, the clinical data of 943 patients with gastrointestinal symptoms such as chronic diarrhea, abdominal pain, abdominal distension and visited the People′s Hospital of Xinjiang Uygur Autonomous Region were collected. All patients tested for serum anti-tissue transglutaminase antibody inmunoglobulin A (tTG-IgA). And patients with positive serum tTG-IgA underwent gastroscopy and colonoscopy examination. To observe whether duodenal and ileal mucosal villi atrophy and histopathological examination was performed. Body mass index (BMI), hemoglobin, serum calcium, serum albumin level were compared between patients with and without celiac disease. T test and chi-square test were used for statistical analysis. Results:Serum tTG-IgA was positive in 30 patients, and 28 cases were finally diagnosed as celiac disease. The detection rate of celiac disease of Kazakh patients was higher than that of Uygur and Han patients (17.3%, 9/52 vs. 3.2%, 12/375 and 1.4%, 6/427), the detection rate of celiac disease of Uygur was higher than that of Han, and the differences were statistically significant ( χ2=7.65, 5.42 and 5.98, all P<0.05). The main clinical manifestations of 28 patients with celiac disease were weight loss or marasmus (71.4%, 20/28), iron deficiency anemia (67.9%, 19/28), persistent fatigue (57.1%, 16/28) and chronic diarrhea (53.6%, 15/28). The serum tTG-IgA level of patients with celiac disease was higher than that of patients without celiac disease ((131.97±64.58) CU vs. (7.58±1.92) CU), while the levels of BMI, hemoglobin, serum calcium and serum albumin were all lower than those of patients without celiac disease ((15.4±2.9) kg/m 2 vs. (23.8±3.4) kg/m 2, (110±28) g/L vs. (138±12) g/L, (1.70±0.20) mmol/L vs. (2.52±0.15) mmol/L, and (31.5±11.6) g/L vs. (48.2±7.3) g/L, respectively), and the differences were statistically significant ( t=2.473, 2.521, 2.641, 2.734 and 2.512, all P<0.05). Under gastroscopy all patients with celiac disease had atrophy of duodenal mucosal villi, which mainly appeared as nodular mucosal atrophy, grooves and fissure like changes, and villous atrophy was confirmed by histopathology. Conclusions:The detection rates of celiac disease in Kazakh and Uyghur in Xinjiang Uygur Antonomous Region are significantly higher than that of Han nationality. Celiac disease screening has a certain clinical significance.

BACKGROUND: Exosomes are nano-scale vesicles that can be secreted by almost all types of cells in the body, which can participate in multiple cell signaling pathways by transporting signal molecules, such as proteins, lipids and miRNAs to perform intercellular communication, immune responses, and antigen presentation. Therefore, exosomes have a great value in the clinical diagnosis and treatment of diseases. Of the cell types known to produce exosomes, mesenchymal stem cells are currently the most prolific producer closely related to the occurrence and development of neurodegenerative diseases. OBJECTIVE: To review the origin and biological characteristics of mesenchymal stem cell-derived exosomes, the isolation and identification methods of exosomes, and the progress of mesenchymal stem cell-derived exosomes in the treatment of neurodegenerative diseases. METHODS: The literature search was performed in PubMed and CNKI databases, and the keywords were "mesenchymal stem cells; exosomes; MSC-exosomes; neurodegenerative diseases" in Chinese and English, respectively. RESULTS AND CONCLUSION: A total of 61 eligible literatures were enrolled. Mesenchymal stem cell-derived exosomes have low immunogenicity and long-circulating half-life and can carry small molecular substances across the blood-brain barrier, which can promote nerve cell growth and neuronal differentiation. Mesenchymal stem cell-derived exosomes help damaged nervous system function and enhance vascular neurogenesis, which is becoming an emerging treatment for neurodegenerative diseases.

Objective To observe the distribution of different types of Helicobacter pylori (H.pylori)infection in non-atrophic gastritis,atrophic gastritis and intestinal metaplasia.Methods From January 2015 to January 2017,457 hospitalized patients with gastritis were collected.All the inpatients received 14C-urea breath test(14C-UBT), H.pylori antibody typing detection, anesthesia gastroendoscopy and pathological analysis of biopsies.According to the results of H.pylori antibody typing,all patients were divided into typeⅠ H.pylori infection group,typeⅡ H.pylori infection group and H.pylori negative group.The relation among different types of H.pylori infection,age and pathological type were analyzed.Analysis of variance and chi-square test were performed for statistical analysis.Results The mean age of patients in typeⅠH.pylori infection group(n=135),typeⅡ H.pylori infection group(n=98)and H.pylori negative group(n=224)in patients with non-atrophic gastritis was(47.5 ± 9.0),(49.0 ± 9.0)and(52.0 ± 11.0)years,respectively, which were lower than those of patients with atrophy gastritis((56.8 ± 10.3),(57.5 ± 12.4)and(62.6 ± 10.4) years,respectively)and patients with intestinal metaplasia((59.2 ± 11.1),(57.5 ± 12.6)and(57.8 ± 10.0)years,respectively),and the differences were statistically significant(F=17.90,6.82 and 18.30,all P<0.01).The proportion of patients with non-atrophic gastritis in H.pylori negative group,typeⅡ H.pylori infection group and typeⅠ H.pylori infection group decreased in turn(56.3%,126/224;40.8%,40/98 and 34.8%,47/135, respectively),and the differences were statistically significant(χ2 =18.44,P<0.01).The proportion of patients with intestinal metaplasia in H.pylori negative group,type Ⅱ H.pylori infection group and type Ⅰ H.pylori infection group increased in turn(23.2%,52/224;26.5%,26/98 and 42.2%,57/135),and the difference was statistically significant(χ2 =11.44,P=0.003).There was no significant difference in the proportion of patients with atrophic gastritis among H.pylori negative group,type Ⅱ H.pylori infection group and type Ⅰ H.pylori infection group(20.5%,46/224;32.7%,32/98 and 23.0%,31/135;χ2 = 5.60,P=0.061).Conclusions Gastric atrophy is easily induced in patients with H.pylori infection.In patients without symptoms,H.pylori should be eradicated before gastric atrophy,which can provide the greatest benefit to the patients.Different types of H.pylori infection have different role in the progress of atrophic gastritis.TypeⅠ H.pylori infection accelerate the progress of atrophic gastritis,especially from atrophic gastritis to intestinal metaplasia,which should be actively eradicated.

Obiective To investigate the molecular characteristics of heteroresistant vancomycinintermediate Staphylococcus aureus(hVISA)in China and analyze the differences of the molecular characteristics between hVISA and VSSA(vancomycin-susceptible Staphylococcus aureus)isolates.Methods A total of 3 15 non-repetitive MBSA were collected from the national surveillance program in China in 2007.The isolates of hVISA were confirmed by modified population analysis profile-area under the curve(PAP-AUC).The genotypes of agr and SCCmec were determined by multiplex PCR,and spa typing was performed bv PCR and DNA sequencing.The pvl gene was detected bv PCR Results The prevalence of hVISA was 9.5%(30/315).Among 315 MRSA,SCCmec Ⅲ was the most popular type,which was found in 234 isolates(234/315,74.3%),followed by SCCmec Ⅱ,which was identified in 56 isolates (56/315,17.8%).The rate of SCCmec Ⅱ in hVISA(46.7%)was significantly hisher than in VSSA (14.7%,X~2=18.93,P＜0.001).The most prevalent agr type among 315 MRSA was agr 1 accounting for 73.6%(232/315).The agr 2 accounted for 18.7%(59/315),and agr 3 and agr 4 were very rare in clinical isolates.It was different in agr types between the two groups.The rate of agr 2 in hVISA(53.4%)was higher than in VSSA(15.1%).X~2 value was 26.08 and P value was less than 0.001 through X~2 test.There was a statistical significance in the result.There were 4 spa types in hVISA isolates,including t002 (13 isolates),t037(9 isolates),t030(6 isolates),and 1548(2 isolates).The pvl positive MRSA isolates were very low,accounting for 1.6%(5/315).Conclusions The prevalence of hVISA was relatively higher in China.Compared to VSSA,the majority(53.4%)of the hVISA strains were agr 2,which was obviously different from VSSA.hVISA isolates were more diverse by spa typing,