Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objective To investigate the effect of the Piezo1 channel on tension-side angiogenesis and osteogenic remodeling during orthodontic tooth movement,so as to provide an experimental basis for accelerating orthodontic peri-odontal tissue remodeling.Methods This study was approved by the Animal Ethics Committee.Sixty healthy male Sprague-Dawley rats with bilateral maxillary incisors as the anchorage were selected,and nickel titanium tension springs were used to apply 0.5 N of force to the right maxillary first molar of the rats and construct an orthodontic tooth movement model.The rats were randomly divided into three groups(n=20 per group).On Days 0 and 8 of force appli-cation,equal volumes of saline(control group),100 μmol/L Piezo1 channel agonist(Yoda1 group),and 48 μmol/L Piezo1 channel inhibitor(GsMTx4 group)were injected into the buccal and palatal submucosa of the right maxillary first molar.Tooth movement distances were recorded on Days 1,3,7,and 14.Five rats from each group were sacrificed at each time point to obtain maxillary tissue samples.Hematoxylin and eosin(HE)staining was performed to observe the histophysiological changes in the tension-side periodontal tissues.Immunohistochemical staining was used to mark and count CD31-positive cells(microvascular quantification)and to detect the expression of osteocalcin(OCN)in the tension side.Results Measurements of tooth movement distance showed that the Yoda1 group exhibited significantly in-creased tooth movement distances on Days 3,7,and 14(0.238±0.008 mm,0.406±0.011 mm,and 0.746±0.013 mm,respectively)compared to the control group(P＜0.05).In contrast,the GsMTx4 group showed significantly reduced tooth movement distances on Day 7(0.282±0.011 mm)and Day 14(0.578±0.008 mm)compared to the control group(P＜0.05).HE staining results indicated that the periodontal ligament space on the tension side gradually widened with the duration of force application and then gradually returned to normal,with visible osteoblasts.Quantitative analysis of CD31-positive cells(microvascular quantification)showed that the Yoda1 group had significantly increased numbers of blood vessels on Day 3(8.027±0.225)and Day 7(14.320±0.471)compared to the control group(P＜0.05),peaking on Day 7 and then gradually decreasing.The GsMTx4 group showed significantly fewer blood vessels in the periodontal ligament on the tension side on Day 3(6.013±0.177),Day 7(9.187±0.678),and Day 14(12.613±0.334)compared to the control group(P＜0.05).Immunohistochemical results indicated that the Yoda1 group had significantly increased OCN expression on Days 1,3,7,and 14 compared to the control group(P＜0.05),while the GsMTx4 group showed re-duced OCN expression on Days 7 and 14(P＜0.05).Conclusion Activation of the Piezo1 channel promotes orthodon-tic tooth movement,tension-side angiogenesis,and osteogenic remodeling,while inhibition of the Piezo1 channel produces the opposite effect.

Objective Based on the Hood Policy Tool perspective on China's DIP policy text mining,word frequen-cy analysis and clustering analysis of the policy content,to explore the actual policy in each pilot region,to further analyze the reasons,to provide a scientific and reference for the subsequent policy adjustment and implementation.Methods Policies were included in this study from platforms such as local healthcare protection bureaus,local health-care commissions,local people's government portals,and NVivo,from which policy documents with a high degree of relevance to DIP were selected.NVivo 20.0 software was used for text coding,word frequency analysis,and analysis based on Hood's policy tool dimensions and regional distribution dimensions to further explore DIP policy specifics.Results A total of 27 policies were included,covering all pilot provinces,with a total of 1,707 policy codes.Authoritative,fiscal,informational,and organizational policy instruments accounted for 54.9％,20.3％,16.9％,and 7.9％,respectively.The percentage of coded reference points in the East,Central,West,and Northeast regions were 23.0％,20.2％,44.5％,and 8.7％,respectively.Conclusion The use of DIP policy tools in the pilot regions focused on authoritative tools and less on organization tools.Among the authoritative policy tools,the sub-tools of mechanism building were mostly used,while the sub-tools of standards and norms were less used.The focus of the policy tools varies among the pilot regions,and the use of policy tools should be tailored to the local context.

Objective To investigate the inhibitory effect of GsMTx4 on pain sensation in rats during tooth movement,open field ex-periments and immunohistochemical staining by conducting.Methods Fifty-eight male SD rats aged 5-6 weeks were selected and a right maxillary tooth movement model was constructed.The rats were randomly divided into two groups:group A(control group)and group B(GsMTx4 group).They were also divided into 5 subgroups according to 4 h,1 d,3 d,5 d,and 7 d.The left maxillary of the rats in group A was used as group C(blank control group).The open-field test was used to evaluate the pain level of rats.Immunohisto-chemical staining was used to observe the expression of nerve growth factor(NGF)and calcitonin gene-related peptide(CGRP)in peri-odontal tissues.Results At 4 h,1 d,and 3 d,the total distance traveled by rats in group B within 5 minutes in the open-field was higher than that of group A(P＜0.05).At 4 h and 1 d,the percentage of time in the center of rats in group B was higher than that in group A(P＜0.05).The expressions of NGF and CGRP in groups A and B were higher than those in group C on 1 d,3 d,5 d,and 7 d(P＜0.05).The expression of NGF and CGRP in group B were lower than those in group A at 4 h,1 d,and 3 d(P＜0.05).Conclu-sion GsMTx4 can inhibit the expression of NGF and CGRP during tooth movement and relieve the pain caused by tooth movement.

Objective:To investigate the mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Objective:To determine the predictive role of combined assessment of vasoactive-inotropic score(VIS) and lactate for the prognosis of patients with postcardiotomy cardiogenic shock(PCS) requiring venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods:222 adults with PCS requiring VA-ECMO were retrospectively analyzed and divided into four groups according to the cut-off values of VIS and lactate(Lac) at 24 h after ECMO initiation: group 1(59 cases): VIS≤14.5, Lac≤2.45 mmol/L; group 2(17 cases): VIS>14.5, Lac≤2.45 mmol/L; group 3(90 cases): VIS≤14.5, Lac>2.45 mmol/L; group 4(56 cases): VIS>14.5, Lac>2.45 mmol/L. The incidence of in-hospital mortality and other clinical outcomes were analyzed. The associations of VIS and lactate and in-hospital mortality were analyzed using Cox proportional hazards analysis.Results:The in-hospital mortality was 18.6%, 58.8%, 63.3% and 71.4% in the four groups( P<0.001), while the rate of successful weaning off ECMO was 88.1%, 88.2%, 58.9% and 33.9% respectively( P<0.001). The group 1 significantly differed from other three groups with regards to in-hospital mortality and ECMO weaning rate( P<0.05). The groups 1 also showed significantly improved cumulative 60-day survival compared with other three groups( log- rank test, P<0.05). Cox proportional hazards analysis showed age( HR=1.03, 95% CI: 1.01-1.05, P=0.001), female( HR=1.87, 95% CI: 1.27-2.76, P=0.002), VIS at 24 h after ECMO initiation( HR=1.02, 95% CI: 1.00-1.05, P=0.020), and lactate at 24h after ECMO initiation( HR=1.12, 95% CI: 1.08-1.16, P<0.001) were independently predictive of in-hospital mortality. Conclusion:Patients with VIS≤14.5 and Lac≤2.45 within 24 h after ECMO initiation had better in-hospital and 60-day outcomes, suggesting that combined assessment of VIS and lactate may be instructive for determining the prognosis of PCS patients requiring VA-ECMO support.

AIM: To explore which variables can predict the weight response to exenatide and to individualize specific therapies for patients with type 2 diabetes mellitus (T2DM) who need treatment with exenatide. METHODS: We performed a study among T2DM patients who were treated with exenatide twice daily for at least 12 months from January 2017 to December 2020. Data of the height, weight, body mass index (BMI) calculated, and HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINS), postprandial serum insulin (PINS), blood lipids and concurrent diabetic medications at baseline, 3 months, 6 months and 12 months after exenatide initiation were collected. Patients were categorized into two cohorts based on weight loss ≥3%: responders and non-responders. The binary logistic regression analysis was used to identify the major variables of weight response to exenatide. RESULTS: The duration of diabetes in the responder group was shorter than that in patients in the non-responder group (P<0.05). For patients in the responder and non-responder groups, there was a significant decrease in weight, BMI, HbA1c, FPG, PPG, homeostasis model assessment of insulin resistance (HOMA-IR) and increase in homeostasis model assessment for beta cell function (HOMA-B) compared with the prarameters before treatment with exenatide (P<0.001). The baseline weight and baseline HbA1c were associated with weight loss after 6 months of treatment with exenatide (P<0.05). CONCLUSION: Baseline weight and HbA1c improvement were positively correlated with weight loss after 6 months of treatment with exenatide and the major predictors of weight response to exenatide.

Objective:To analyze the status of extracorporeal membrane oxygenation (ECMO) for poisoned patients in China, and prognosis, complications and risk factors for death in poisoned patients supported with ECMO.Methods:The data of adult poisoned patients registered in Chinese Society of Extracorporeal Life Support (CSECLS) database were collected. Patients were divided into the survival group and death group according to the conditions at discharge. The type of poisoning, patient prognosis, hemodynamic parameters and complications before and after ECMO were retrospectively analyzed.Results:A total of 96 poisoned patients supported with ECMO were included in the database from 2017 to 2022, including 77 adult patients. The use of ECMO for poisoning was more common in Henan Province (28 cases, 36%), Guangdong Province (11 cases, 14%) and Zhejiang Province (9 cases, 8%). The number of adult poisoned patients registered in the database increased over time from 2017 to 2022, but the survival rate showed no significant difference ( P = 0.794). Agricultural poisoning was the most common indication (43%). Veno-arterial (V-A) ECMO was used in 60 patients (78%) and venovenous (V-V) ECMO in 27 patients (22%). Thirty-two patients (42%) survived to hospital discharge. The mean duration of ECMO support was 57 (34, 123) h, the mean duration of mechanical ventilation was 88 (33, 211) h, the mean length of hospital stay was 10 (2, 21) days, and the mean length of ICU stay was 9 (2, 18) days. Multivariate analysis showed that 24-h lactic acid level was significantly associated with mortality ( OR = 0.378, 95% CI: 0.183-0.779, P = 0.008). Conclusions:ECMO can be used as a salvage strategy to treat various types of severe poisoning. Although the application of ECMO is expanded rapidly in China, it is still necessary to optimize intervention indications and treatment timing, and adopt standardized ECMO management and monitoring strategies to improve the prognosis of patients.

Objective:To compare the spermatogenes response of human chorionic gonadotropin(HCG)combined with human menopausal gonadotropin(HMG)in patients with idiopathic hypogonadotropic hypogonadism(IHH)and congenital combined pituitary hormone deficiency(CCPHD), and to explore related factors.Methods:Clinical data of 90 IHH patients and 61 CCPHD patients from January, 2014 to November, 2018 were retrospectively analyzed. Spermatogenesis was compared between the two groups receiving combined gonadotropin therapy. The patients were then divided into two subgroups: spermatogenesis subgroup and nonspermatogenesis subgroup. Related factors of spermatogenesis after the combined gonadotropin therapy were investigated.Results:After the combined treatment of HCG/HMG for 3, 6, and 9 months, the patients with CCPHD revealed lower testicular sizes than those with IHH( P=0.004, 0.021 and 0.032, respectively). Compared with IHH patients, CCPHD patients had larger testicular volume increments( P<0.001), higher spermatogenesis rates( P=0.048), and shorter initial time for sperm appearance( P<0.001)after 24-month treatment. Multivariate logistic regression analysis showed that lower total cholesterol(TC)(IHH group: OR=5.508, 95% CI 1.110-27.326, P=0.037; CCPHD group: OR=4.068, 95% CI 1.077-15.371, P=0.039)was an independent risk factor of poorer spermatogenesis in patients with IHH and CCPHD. Conclusions:The patients with CCPHD demonstrate a better response to combined gonadotropin treatment than those with IHH. Lower TC is an independent risk factor for poor spermatogenesis of combined HCG/HMG therapy in patients with IHH or CCPHD.

Objective:To examine the long-term survival outcomes and identify mortality risk factors for coronary artery bypass grafting patients who received venoarterial extracorporeal membrane oxygenation(VA-ECMO) for postcardiotomy cardiogenic shock.Methods:Data from 121 consecutive venoarterial extracorporeal membrane oxygenation-treated coronary artery bypass grafting(CABG) patients at Beijing Anzhen Hospital between June 2012 and December 2016 were analyzed. There were 84 males and 24 females. The median age was 62(55, 67) years, and the median body mass index was 25(23, 27)kg/m 2. Thirty-seven patients(34%) had left main artery disease, and 56 patients(52%) underwent off-pump CABG. According to the 3 year survival outcome after ECMO, patients were divided into survival group(35 cases) and non-survival group(73 cases). The differences of clinical indicators between the two groups were compared and analyzed. Multivariable Cox regression modeling was used to identify factors independently associated with 36 month mortality. Results:Sixty-five patients(60%) could be weaned from VA-ECMO, 49 patients(45%) survived to hospital discharge, and 35 patients(32%) survived to 3 years. The median( IQR) time on VA-ECMO support was 4(3, 5) days. The median( IQR) length of ICU stay and hospital stay duration were 8(5, 12) and 20(13, 29) days, respectively. Older age( HR=1.06, 95% CI: 1.03-1.10, P<0.001), left main coronary artery disease( HR=1.62, 95% CI: 1.00-2.60, P=0.048), and vasoactive inotropic score( HR=1.09, 95% CI: 1.03-1.17, P=0.007)were independent risk factors associated with 3-year mortality. The area under the receiver operating characteristic curve for the model, which was constructed with age≥60years, left main coronary artery disease, and vasoactive inotropic score>60, was 0.88(95% CI: 0.80-0.95). Conclusion:Long-term survival of patients who survive to discharge appears favorable. Older age, left main coronary artery disease, and vasoactive inotropic score were associated with 3-year mortality in coronary artery bypass grafting patients who received VA-ECMO.