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.

Objective:To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage.Methods:The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ2 test between groups. Results:This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery ( P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence ( HR =181.92, 95% CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95% CI 1.289~20.889, P = 0.020), and a high dosage of HBIG ( HR = 1.012, 95% CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion:High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

Objective:To carry out prenatal diagnosis for a fetus with Meckel syndrome(MKS) and explore its genetic basis.Methods:A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.Results:The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c. 296delA (p.Lys99SerfsTer6) and c. 1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 296delA variant was predicted to be pathogenic (PVS1+ PM2_Supporting+ PP4), whilst the c. 1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+ PM3+ PP3_Moderate+ PP4). Conclusion:The c. 296delA and c. 1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.

Objective To evaluate the reliability and validity of the Chinese version of the hyperacusis scale and estimate its applicability in the Chinese population.Methods The patients admitted to the Department of Oto-laryngology of Xijing Hospital from June 2017 to December 2017 were surveyed.A total of 300 questionnaires were sent out and 293 valid questionnaires were collected with effective response rate of 97.67％.All participants comple-ted a basic information survey,pure tone audiometry and fill in the Chinese version of the hyperacusis scale.The re-liability and validity of this scale were evaluated.Results Among the 293 respondents,243(82.93％)were compli-cated with tinnitus.A total of 181 cases(61.77％)were subjectively diagnosed with hyperacusis through question-naire survey.According to the scale evaluation,174 cases(59.39％)were diagnosed with hyperacusis,and the Kappa value of conformity test of the two methods was 0.81(P＜0.001).Reliability analysis indicated a Cronbach'sα coefficient of 0.93 for the entire scale.Each dimension had a Cronbach's α coefficient＞0.60.The split-half relia-bility coefficient for the entire scale was 0.86,and for each dimension,it was＞0.60.Exploratory factor analysis of validity suggested that 25 items could be grouped under 4 factors,such as functional part,social part,emotional part and harmonic sensitivity part.These factors had eigenvalues greater than 1,accounting for 59.42％of the total variance.Post-rotation,the 25 items were distributed across the 4 components,with each item having a factor load-ing＞0.40.Confirmatory factor analysis of validity showed model fit parameters as:x2/df=1.98,GFI=0.91,AGFI=0.83,CFI=0.92,TLI=0.89,RMSEA=0.08.Each item had a standardized factor loading＞0.40.Con-clusion The Chinese version of the hyperacusis scale demonstrated strong reliability and validity,making it suitable for use among the Chinese population.

Objective:To investigate the expression level of small nucleolar RNA SNORD15A in bone marrow of patients with acute leukemia (AL) and its relationship with clinical characteristics and prognosis of patients.Methods:Bone marrow blood samples of 53 newly treated AL patients and 29 healthy subjects without clinical diagnosis of hematologic diseases or other malignant diseases (control group) at the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of SNORD15A in bone marrow blood mononuclear cells of the two groups. The median relative expression of SNORD15A (0.148) was used as the boundary, and AL patients were divided into low expression group (<0.148) and high expression group (≥0.148). The relationship between the expression level of SNORD15A and the clinical characteristics, clinical indicators and overall survival (OS) of AL patients was analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed; Cox proportional hazards model was used for univariate and multivariate analyses of OS of patients.Results:The relative expression of SNORD15A was 0.148 (0.012-1.376) in newly treated AL patients and 0.921 (0.513-2.288) in the control group, and the difference was statistically significant ( Z = -6.85, P < 0.01). The differences in SNORD15A relative expression between patients with different prognostic stratification, efficacy and with or without fever and bleeding were statistically significant (all P < 0.05). The differences in platelet count, plateletcrit and albumin levels between SNORD15A low expression group and high expression group were statistically significant (all P < 0.05), and the differences in molecular biology and cytogenetic characteristics were not statistically significant (all P > 0.05). The patients in SNORD15A high expression group had better OS than the low expression group ( P < 0.05). The results of univariate Cox regression analysis showed that SNORD15A was an influencing factor for patients' OS ( HR = 0.063, 95% CI 0.005-0.766, P < 0.05); the results of multivariate Cox regression analysis showed that fatigue ( HR = 4.754, 95% CI 1.014-22.290), fever ( HR = 0.147, 95% CI 0.029-0.746) and hemoglobin ( HR = 0.970, 95% CI 0.944 -0.998) were independent influencing factors for OS (all P < 0.05). Conclusions:SNORD15A is lowly expressed in AL and may be an indicator for disease monitoring and prognostic assessment in AL patients.

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.

Objective:To investigate the expression level of flap endonuclease 1 (FEN1) in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and its relationship with clinicopathologic features and therapeutic effect, so as to provide a new direction for disease monitoring and targeted therapy in AML patients.Methods:The data of 57 newly treated AML patients and 26 healthy individuals (the healthy control) from the First Clinical College of Guangdong Medical University and Fujian Medical University Union Hospital from November 2018 to December 2020 were retrospectively analyzed. Bone marrow samples of all subjects were collected. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect FEN1 mRNA expression in bone marrow mononuclear cells of all subjects. Bone marrow samples from 9 newly-diagnosed AML patients and 4 healthy controls were collected, and FEN1 protein expression level was detected by using Western blotting. Differences in FEN1 mRNA expression in AML patients achieving different therapeutic effects were compared among AML patients whose data with evaluable efficacy. AML patients were divided into high FEN1 expression group (≥ critical value) and low FEN1 expression group (< critical value), taking the median relative expression level of FEN1 mRNA as the critical value. The correlation of FEN1 expression level with clinicopathologic features, laboratory indicators, cellular and molecular genetic changes in AML patients at initial diagnosis was analyzed.Results:The median relative expression of FEN1 mRNA in newly treated AML patients was higher than that in healthy controls [0.696 (0.025-3.661) vs. 0.246 (0.013-1.237), Z = 1.75, P = 0.041]. Western blotting showed that the expression level of FEN1 protein in AML patients was higher than that in healthy controls. The relative expression of FEN1 mRNA in 15 recurrent AML patients was higher than that in 19 patients patients achieving complete remission (CR) [1.153 (0.047-4.172) vs. 0.259 (0.023-1.148), Z = 2.71, P = 0.009]. The proportion of patients with French-American-British(FAB) type M 5, fever at initial diagnosis and lymph node enlargement in FEN1 high expression group (32 cases) was higher than that in FEN1 low expression group (25 cases) (all P < 0.05). There were no significant differences in the proportion of gender, age, fatigue, pale skin mucosa and large liver and spleen of patients between the two groups (all P > 0.05). At initial diagnosis, the white blood cell count, lactate dehydrogenase, C-reactive protein and bone marrow primitive cell proportion in FEN1 high expression group were higher than those in FEN1 low expression group (all P < 0.05), and the hemoglobin and platelet count in FEN1 high expression group were lower than those in FEN1 low expression group (all P < 0.05). There were no significant differences in procalcitonin level, the proportion of chromosome karyotype, cytogenetic prognosis grade and patients with or without gene mutation between the two groups (all P > 0.05). Conclusions:FEN1 expression is up-regulated in AML patients and further increased in relapsed patients. FEN1 expression in AML patients is associated with adverse clinicopathological features and poor detection results of laboratory indicators, which may become indicators for disease monitoring in AML patients.

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*

Objective:To develope and analyze and optimize the performance of some kinds of environmentally friendly flexible X-ray protective materials in attempt to tackle the various environmental and high energy consumption problems in the development of traditional medical X-ray protective clothing.Methods:The Monte Carlo program was used to establish a simplified model of medical X-ray tube. The aim was to carry out numerical simulation and prediction of the shielding materials′ performance against X-ray, prepare the flexible X-ray shielding materials through experiments and test and verify the their shielding performances The development and optimization path was also obtained by comparing the result between simulation and experiment.Results:Bi was the preferred alternative to toxic Pb elements, while W was able to compensate for weak X-ray absorption zone of Bi. The shielding efficiency of the composite material doped with 25% Bi+ 25% W was able to reach 77.8% and 66.3% at 80 and 120 kV p tube voltages, respectively. Conclusions:With both the selection of elements and the optimization of functional particles, the combination of W and Bi is an economical, environmentally friendly, and efficient shielding way within the energy range of medical diagnostic X-rays. The numerical simulation helps reduce experimental costs, shorten the research period, and improve the design efficiency of X-ray shielding materials.

Objective:To explore the safety of inactivating coronavirus disease 2019(covid-19)vaccine in liver transplantation(LT)recipients.Methods:Retrospective analysis was performed for clinical data of 151 LT recipients from March 2003 to October 2019.They had stable conditions and completed the course of covid-19 vaccine.Frequencies of pain at injection site, fatigue, headache and pruritus after vaccination were recorded.The safety profiles were compared between recipients with and without local and general adverse reactions after vaccination.At the same time, recipients completing two doses of covid-19 vaccines were grouped.According to vaccine companies, they were classified into Sinovac Biotech Ltd and Beijing Biological.Based upon more than or less than 60 years, they were grouped into <60 years and ≥60 years.The safety profiles of inactivating COVID-19 vaccine were compared in subgroups.Results:Among 151 eligible LT recipients, 98 of them were in group of age <60 years and 53 in group of age >60 years.The median period between vaccination and LT was 8.44(4.37, 12.39)years and the median concentration of tacrolimus 2.5(1.8, 3.9)ng/L.Eighty-three cases completed two doses of Sinovac Biotech Ltd(Sinovac Biotech Ltd group)and 40 cases Beijing Biological(Beijing Biological group); 14 cases had combined course of Sinovac Biotech Ltd and Beijing Biological, four recipients were vaccinated with inactivated vaccine from other companies and ten recipients did not know their inactivated vaccine' companies.After immunization, 24/151(15.9%)recipients had a local and general adverse reaction.The prevalence of pain at injection site, fatigue, headache and pruritus was 9.9%( n=15), 5.2%( n=8), 1.3%( n=2)and 0.7%( n=1)respectively.No significant differences existed in age( P=0.602), gender( P=0.752), period after LT( P=0.890), trough concentration of tacrolimus( P=0.377)or versions of covid-19 vaccine( P=0.582)between 24 cases with general adverse reaction and 127 without.Local and general reactions occurred in 16/83(19.3%)in Sinovac group and 5/40(12.5%)in Beijing Biological.There was no significant inter-group difference( P=0.769). There were 98 cases(64.9%)in <60 years group, 17 cases(17.3%)had local and general reaction, 53 cases(35.1%)in ≥60 years group and 7 cases(13.2%)had a local and systemic reaction.There was no significant inter-group difference( P=0.507). Conclusions:Covid-19 vaccine is safe for long-term survival LT recipients with normal liver function.Few participants present with mild fatigue and pain at injection site.