Objective To evaluate myocardial microvascular lesions in patients with type 2 diabetes mellitus(T2DM)by 2D-speckle tracking echocardiography(2D-STE)and myocardial contrast echocar-diography(MCE).Methods A total of 45 T2DM patients admitted to the Endocrine Department of The First Affiliated Hospital of Air Force Military Medical University from August to November 2022 were enrolled in this study.All the patients were divided into two groups:simple T2DM group(n=22)and T2DM with microvascular complication group(MIC,n=23).In addition,24 healthy subjects were included as normal control(NC)group.2D-STE obtained the global longitudinal strain(GLS)and global circumferential strain(GCS);MCE obtained the average acoustic intensity(A),perfusion slope(b)of left ventricular segment,then myocardial blood flow(Aβ)was calculated and compared between groups.Results Compared with NC group,GLS,GCS,β and Aβ were lower in T2DM and MIC group(P＜0.05).Among the parameters of 2D-STE and MCE,GLS and Aβ have high diagnostic performance(P＜0.05)and GCS and β have medium diagnostic performance(P＜0.05).ROC curve analysis showed that the early warning values of myocardial microcirculation disorders were-17.63%(GLS),-21.55%(GCS),0.845 s-1(β),7.045 dB/s(Aβ)in patients with T2DM.Conclusion The mechanical strain and perfusion of myocar-dium in T2DM patients have already decreased even no lesion was shown in the peripheral micro-vessels.2D-STE combined with MCE can assess the changes of myocardial elasticity and microcirculation in T2DM in real time,which is helpful for early clinical diagnosis of diabetes cardiomyopathy and intervention guidance.

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

Objective:To figure out the timing of zeroing and the location of the zero line in the central venous pressure (CVP) monitoring and invasive arterial blood pressure (IBP) monitoring, and to provide scientific and accurate data for patients management.Methods:The liquid vessel models were used to simulate the pressure measurement process of the continuous pressure monitoring system. Based on the theory of fluid mechanics and the knowledge of blood pressure physiology and cardiovascular anatomy, the composition and influencing factors of the pressure in the fluid-filled catheter system during the zeroing and placing the transducer in the zero line of CVP and IBP, were analyzed.Results:The pressure in the liquid-filled catheter system was composed of atmospheric pressure, the pressure of pumping bag, the gravity of the water column (the vertical distance between the liquid level of Murphy's dropper and pressure transducer, ΔH), and the resistance of tube wall. This pressure value is set as a pressure of 0 mmHg (1 mmHg ≈ 0.133 kPa). In the process of pressure measurement, when the pressure transducer was placed at a horizontal position of 10 cm below the highest liquid level of the vessel, the pressure measured at different catheter tip positions was all 10 cmH 2O (1 cmH 2O ≈ 0.098 kPa); When the pressure transducer was placed at the horizontal position of the highest liquid level of the vessel, the measured pressure is 0 mmHg. Conclusion:Zeroing should repeatedly be performed only when one or more conditions (atmospheric pressure, pressure of pumping bag, gravity of ΔH water column and resistance of tube wall) are changed. In the measurement process, the pressure transducer should be placed at the zero line position at any time to eliminate the influence of hydrostatic pressure and to ensure the objective and accurate value.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Objective:To explore the differences in imaging characteristics and risk factors for mortality between the young and middle-aged and elderly patients with aortic dissection.Methods:The data from 1 220 patients with aortic dissection from January 2007 to December 2015 were successively collected. They were divided into young and middle-aged and elderly groups according to their ages. The basic information, computer comography angiography and echocardiogram results, hospital admissions and surgical details were collected and compared between the two groups using single variable regression analysis.Results:The ratio of female patients in the middle-aged and elderly group (>45 years old) was significantly higher than that of the young group (≤45 years old) (24.9% vs 18.7%, P=0.014), the ratio of hypertension patients was also significantly higher than that in the young group (77.5% vs 68.1%, P<0.001). Echocardiographic parameters showed that the prevalences of left ventricular enlargement (39.9% vs 26.9%) and left ventricular dysfunction (22.3% vs 14.1%) in the young group were significantly higher than in the middle-aged and elderly group (all P<0.001). The prevalences of ascending aorta dilation [(43.04±9.12)mm vs (41.69±10.99)mm] and thrombosis (39.1% vs 28.5%) were higher ( P<0.05). Although there was no statistically significant difference in mortality within 60 days after admission between the two groups (12.0% vs 15.1%, P=0.164), univariate regression analysis showed that aortic branch involvement was the main independent risk factor for mortality in young patients. Left ventricular remodeling (left atrial enlargement, ascending aortic dilation, aortic regurgitation) and decreased heart function were the main independent risk factors for death in the elderly patients. Conclusions:The mortality rate of young and middle-aged and elderly patients with aortic dissection are comparable, but the influencing factors are different. Screening out the relevant risk factors that affect the survival rate of the two groups, and conducting targeted prevention and intervention on them areof great significance to improve the survival rate of patients.

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ² test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Objective To describe the status of non?steroidal anti?inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High?risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)". From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health?related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ2 test and Cochran?Armitage trend analysis method. Results Of 35 910 subjects, the mean age was (54.6 ± 7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend<0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend<0.05 for all). Conclusion The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Objective To describe the status of non?steroidal anti?inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High?risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)". From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health?related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ2 test and Cochran?Armitage trend analysis method. Results Of 35 910 subjects, the mean age was (54.6 ± 7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend<0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend<0.05 for all). Conclusion The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Objective To explore the expression of peripheral T cell subgroup (CD3+,CD4+,CD8+,CD4+CD25 high regulatory T cells) and the level and significance of serum cytokines in patients with silicosis.Methods One hundred and six cases patients with silicosis were collected in the Fifth People''s Hospital of Suzhou as study subjects and 56 healthy subjects as control group.Flow cytometry was used to detect the peripheral CD3+,CD4+,CD8+ and CD4+CD25 high regulatory T cells (Treg) of the patients and the control group,while chemiluminescence immunoassay was utilized to measure the peripheral serum soluble interleukin-2 receptor (sIL-2R),interleukin 6 (IL-6),interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α).Results (1) The percentages of peripheral CD3+,CD4+ and CD8+ in the silicosis group were all lower than those in the control group (t=3.755,3.828,2.347,P<0.05);the percentage of Treg cells was higher in the silicosis group than in the control group,the difference was statistically significant (t=-8.345,P<0.05).Compared with the control group,based on the one-way analysis of variance,the differences in CD3+,CD4+,CD8+ and CD4+CD25 high cells were all statistically significant (F=5.620,8.007,26.71,P<0.05);in the silicosis group,the percentage of CD4+ T cells was lower in stage III than in stage I (t=3.424,P<0.05);compared with the control group,the percentages of Treg cells in the silicosis group were lower in all stages (t=-7.934,-9.445,-5.096,P<0.05).(2) The levels of peripheral sIL-2R,IL-6,IL-8 and TNF-α in the silicosis group were higher than those in the control group,the difference were statistically significant(t=-6.952,-4.506,-2.551,-5.670,P<0.05);compared with the control group,based on the one-way analysis of variance,the differences in sIL-2R,IL-6 and TNF-α in all stages were statistically significant (F=11.03,11.31,13.22,P<0.0001);the sIL-2R was higher in patients with stage III silicosis than that of stage I (t=-2.882,P<0.05);IL-6 was significantly higher in stage II and III silicosis group than that of stage I group (t=-3.022,-2.632,P<0.05),and TNF-α was higher in patients with stage II silicosis than patients with stage I silicosis (t=-2.322,P<0.05).(3) The level of peripheral Treg cells was negatively correlated with the percentages of CD3+ and CD8+ cells in patients with silicosis (r=-0.357,-0.508,P<0.05);sIL-R2 was positively correlated with IL-6,IL-8 and TNF-α,respectively (r=0.483,0.199,0.392,P<0.05);TNF-α was positively correlated with IL-6 and IL-8,respectively (r=0.338,0.338,P<0.05).Conclusion Patients with silicosis have abnormal expression in peripheral T cell subgroups,significantly increased Treg cell and dysfunctional cytokines,which may be associated with the pathogenesis of silicosis,the detection of these indicators may have significance of diagnosis,staging,disease monitoring and prognosis of the diseases.