Objective To investigate the inhibitory effect of erianin on T cell proliferation and its underlying mechanism.Methods Peripheral blood mononuclear cells(PBMCs)were isolated using density gradient centrifugation,and T cells were purified by magnetic-activated cell sorting(MACS)with immunomagnetic beads,followed by being activated with anti-human CD3 antibodies and anti-human CD28 antibodies.The activated T cells were labeled with carboxyfluorescein succinimidyl ester(CFSE),and the effects of erianin(0.05～0.20 μmol/L)on the proliferation,apoptosis,expression of activation marker cluster of differentiation 25(CD25),cell cycle distribution of activated T cells,as well as the survival rate of resting T cells were assessed using flow cytometry.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the secretion levels of IL-2 and IL-17 in the culture supernatant of erianin-treated activated T cells.Western blotting was employed to examine the impact of erianin on the protein expression of cell division cycle protein 2(CDC2),phosphorylated CDC2(p-CDC2),and Cyclin B1.The differences were observed between the erianin-treated group and the positive control group(activation with CD3/CD28 antibodies).Results CFSE proliferation assay demonstrated that the proliferative rate of activated T cells was in a concentration-dependent decline after 0.05～0.20 μmol/L erianin treatment(P<0.0001),with a half-maximal inhibitory concentration(IC50)of 0.09±0.10 μmol/L.No significant differences were observed in apoptotic rates or survival rates among the erianin-treated groups(activated and resting T cells)and the positive control cells.Analysis of T cell activation markers revealed that erianin had no impact on CD25 expression or IL-2 secretion.However,ELISA results indicated erianin exerted a significant suppression on the secretion of pro-inflammatory cytokine IL-17(P<0.0001).Cell cycle analysis showed that erianin arrested activated T cells at the G2/M phase(P<0.05).Further mechanistic investigations demonstrated that while erianin did not alter CDC2 phosphorylation or total CDC2 expression,but it markedly down-regulated CyclinB1 expression(P<0.01).Conclusion Erianin exhibits potent immunomodulatory activity by suppressing activated T cell proliferation through down-regulating Cyclin B1.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective:To determine the optimal threshold for trigger-day progesterone levels in gonadotropin-releasing hormone (GnRH) antagonist protocols.Methods:A cohort study was performed. The clinical data were retrospectively analyzed from patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for assisted reproduction at the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital between January 2014 and May 2023. The study included 5 760 fresh transfer cycles where the female partner had undergone ovarian stimulation using a GnRH antagonist protocol. This was a single-arm study. The primary outcome measures were clinical pregnancy rate and live birth rate. The association between progesterone level on the trigger day and clinical pregnancy outcome and the dose-response relationship were analyzed by restricted cubic spline. Results:The progesterone level on the day of human chorionic gonadotropin trigger was (1.33±0.38) μg/L. Among the included cycles, 2 900 cycles underwent conventional IVF fertilization, while 2 860 cycles underwent ICSI. The biochemical pregnancy rate was 44.79% (2 580/5 760), the clinical pregnancy rate was 40.35% (2 324/5 760), and the live birth rate was 31.46% (1 812/5 760). Progesterone levels on the trigger day in GnRH antagonist protocols showed a nonlinear association with both clinical pregnancy rate and live birth rate (both P<0.001). When progesterone levels were below 0.61 μg/L, the clinical pregnancy rate increased with rising progesterone levels, but decreased significantly once this threshold was exceeded. Similarly, the live birth rate increased with progesterone levels below 0.63 μg/L and declined beyond that point. Conclusion:Progesterone levels on the optimal trigger day for achieving the highest clinical pregnancy rate and live birth rate in GnRH antagonist protocols are peak values of 0.61 μg/L and 0.63 μg/L, respectively. Using these thresholds, the impact of progesterone levels on the trigger day shows a positive effect on both clinical pregnancy rate and live birth rate up to these points, after which the effects become negative.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To determine the optimal threshold for trigger-day progesterone levels in gonadotropin-releasing hormone (GnRH) antagonist protocols.Methods:A cohort study was performed. The clinical data were retrospectively analyzed from patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for assisted reproduction at the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital between January 2014 and May 2023. The study included 5 760 fresh transfer cycles where the female partner had undergone ovarian stimulation using a GnRH antagonist protocol. This was a single-arm study. The primary outcome measures were clinical pregnancy rate and live birth rate. The association between progesterone level on the trigger day and clinical pregnancy outcome and the dose-response relationship were analyzed by restricted cubic spline. Results:The progesterone level on the day of human chorionic gonadotropin trigger was (1.33±0.38) μg/L. Among the included cycles, 2 900 cycles underwent conventional IVF fertilization, while 2 860 cycles underwent ICSI. The biochemical pregnancy rate was 44.79% (2 580/5 760), the clinical pregnancy rate was 40.35% (2 324/5 760), and the live birth rate was 31.46% (1 812/5 760). Progesterone levels on the trigger day in GnRH antagonist protocols showed a nonlinear association with both clinical pregnancy rate and live birth rate (both P<0.001). When progesterone levels were below 0.61 μg/L, the clinical pregnancy rate increased with rising progesterone levels, but decreased significantly once this threshold was exceeded. Similarly, the live birth rate increased with progesterone levels below 0.63 μg/L and declined beyond that point. Conclusion:Progesterone levels on the optimal trigger day for achieving the highest clinical pregnancy rate and live birth rate in GnRH antagonist protocols are peak values of 0.61 μg/L and 0.63 μg/L, respectively. Using these thresholds, the impact of progesterone levels on the trigger day shows a positive effect on both clinical pregnancy rate and live birth rate up to these points, after which the effects become negative.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To investigate the expression level and application value of anti-carbamylated protein(CarP)antibody in rheumatoid arthritis(RA).Methods:Demographic data and laboratory test results of RA patients,non-RA patients and healthy controls in the physical examination center were re-viewed from December 2018 to June 2019 in the Rheumatology and Immunology Department of the Peo-ple's Hospital of Xinjiang Uygur Autonomous Region.The serum concentrations of anti-CarP antibodies in all the subjects were measured by ELISA and statistically analyzed.Results:A total of 259 subjects were included in this study,including 158 in the RA group(45 serum-negative RA patients),59 in the non-RA group and 42 in the healthy control group.The concentration of anti-CarP antibody in RA group[8.31(5.22,15.26)U/mL]was higher than that in non-RA group[4.50(3.35,5.89)U/mL]and healthy control group[3.46(2.76,4.92)U/mL].The concentration of anti-CarP antibody in non-RA group was not significantly different from that in healthy control group(P=0.10).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of anti-CarP antibody in the diagnosis of RA was 58.2％,and the specificity was 93.1％.The sensitivity of the combined detection of anti-CarP antibody,anti-cyclic peptide containing citrulline(CCP)antibody and rheumatoid factor(RF)was 82.3％,and the specificity was 96.5％.The positive rate of anti-CarP antibody in serum-negative RA patients was 44.4％(20/45).Univariate Logisitic regression analysis showed that age,C-reactive pro-tein(CRP),erythrocyte sedimentation rate(ESR),RF,glucose-6-phosphate isomerase(GPI),anti-CCP antibody and anti-CarP antibody were risk factors for RA.Multivariate Logisitic regression analysis showed that anti-CCP antibody and anti-CarP antibody were independent risk factors for RA.Spearman correlation analysis showed that there was no significant correlation between anti-CarP antibody and swol-len joint count(SJC),tenderness joints count(TJC),ESR,disease activity score for 28 joints(DAS28),clinical disease activity index(CDAI),simplified disease activity index(SDAI).The concentration of anti-CarP antibody in RA with bone erosion(n=88)was higher than that in RA without bone erosion(n=70),and there was significant difference between the two groups(P＜0.05).Conclusion:Anti-CarP antibody is an effective serological marker for the diagnosis of RA.The combined detection of RF,anti-CCP antibody and anti-CarP antibody can improve its diagnostic value,and anti-CarP antibody may be an effective assistant diagnostic tool for serum negative RA.The high serum concentration of anti-CarP antibody in patients with RA may indicate an increased risk of bone erosion and should be treated early,but further cohort studies are needed for follow-up observation.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .

Objective:To investigate the positivity rate and high titer of antinuclear antibody (ANA) and anti-dsDNA antibody in healthy Tajik, Kirgiz, and Han Chinese populations in Xinjiang.Methods:A total of 3 687 cases of Tajik residents, 2 140 cases of Kyrgyz residents, and 2 034 cases of Han residents were selected as the study subjects, and ANA and anti-dsDNA antibodies were detected and comparatively analyzed. Data were analyzed using SPSS 22.0 software with χ2 test. Results:The positive rate of ANA in Tajik group was 15.1% [(555/3 687), 10.2%(147/1 445) male, 18.2%(408/2 242) female], of which high titers accounted for 25.8%(143/555). It was 16.7%(357/2 140) in the Kyrgyz group [10.3% male(101/980), 19.4%(256/1 160) female], with high titers accounting for 14.8%; and in the Han group, the positivity rate was 16.6% [9.8%(70/720) male, 19.1%(267/1 314) female], with high titers accounting for 18.4%(62/1 337). There was no significant difference in ANA positivity rate among the three ethnic groups( χ2=3.64, P=0.162), but there were differences in the percentage of high titer of ANA in Tajik ethnic group compared with Han and Kyrgyz ethnic groups(25.8% vs. 18.4%, χ2=6.02, P=0.014; 25.8% vs.14.8%, χ2=14.71, P=0.001), which accounted for a high percentage. The highest number of ANA high titers in all three groups was in the age group of 51~60 years. The ANA karyotype with the highest percentage of high titers in the Tajik and Kyrgyz populations was granular, while it was homogeneous and in the Han it was homogeneous.The positive rate of anti-dsDNA antibody in the Tajik group was 0.71%(26/3 687), of which high titer accounted for 23.1%(6/126); in the Kyrgyz group, it was 0.75%(16/2 034), and high titer accounted for 31.3%(4/14); and in the Han group, the positive rate was 0.69%(14/2 034), of which high titer accounted for 28.6%(4/64), and there was no statistical significance of in the difference in the positive rate of anti-dsDNA antibody and the proportion of high titer among the three groups( χ2=0.06, P=0.972; χ2=0.37, P=0.832). Conclusion:The percentage of ANA and anti-dsDNA antibodies and high titers varied vary among the three ethnic groups in this study, and long-term follow-up is needed to monitor keep an eye on the incidence of autoimmune diseases in people with high autoantibody titers.