1.Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses
Wenqiang ZHANG ; Li ZHANG ; Chenghan XIAO ; Xueyao WU ; Huijie CUI ; Chao YANG ; Peijing YAN ; Mingshuang TANG ; Yutong WANG ; Lin CHEN ; Yunjie LIU ; Yanqiu ZOU ; Ling ZHANG ; Chunxia YANG ; Yuqin YAO ; Jiayuan LI ; Zhenmi LIU ; Xia JIANG ; Ben ZHANG
Chinese Medical Journal 2024;137(5):577-587
Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
2.Three-dimensional finite element analysis of lumbar disc herniation under different body positions
Ben-Jing YIN ; Yu LU ; Fu-Tao JI ; Rong-Neng QIU ; Yuan-Yang XIE ; Ge CHEN ; Tian-Li XU ; Chao-Yu BAO ; Ju-Bao LI
China Journal of Orthopaedics and Traumatology 2024;37(6):599-604
Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.
3.Diagnostic concordance and influencing factors of quantitative flow fraction and fractional flow reserve
Rui-Tao ZHANG ; Peng-Xin XIE ; Zhen-Yu TIAN ; Lin MI ; Ji-Sheng ZHOU ; Ben-Zhen WU ; Li-Yun HE ; Li-Jun GUO
Chinese Journal of Interventional Cardiology 2024;32(9):481-488
Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and>0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8%were male.All patients had 30%-70%coronary stenosis.The consistency rate of QFR and FFR was 78.0%(n=184),and the Person correlation coefficient was 0.557(P<0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P<0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P<0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95%CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95%CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P<0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.
4.Progress in understanding of the effects of Listeria monocytogenes infection on maternal pregnancy in humans and ruminants
Kang-Li LI ; Ben LIU ; Wei-Hua ZHOU
Chinese Journal of Zoonoses 2024;40(7):656-661
Listeria monocytogenes(LM)is a parthenogenetic intracellular parasitic Gram-positive short bacillus that causes listeriosis in humans and animals.LM is considered one of the four major food pathogens in the world.Infection susceptibility during pregnancy is due to pregnancy-associated immunodeficiency and LM's tropism toward reproductive organs.LM infection in pregnancy is strongly associated with miscarriage,preterm labor,and neonatal complications.This article describes events related to LM infection in pregnancy in China and other countries;discusses recent advances in the diagnosis and treatment of listeriosis in detail;and focuses on the obstetric outcomes of LM infection in pregnancy.The aim of this article is to provide a reference for the future prevention and control of LM infection in pregnancy in humans and ruminants,as well as to support food safety.
5.Efficacy of Decitabine Combined with Preexcitation Regimen in Treatment of Newly Diagnosed AML Patients Who Did not Respond to Initial Standard Induction Chemotherapy
Li-Min HOU ; Ying GAO ; Qiu-Ying GAO ; Ben NIU
Journal of Experimental Hematology 2024;32(3):679-684
Objective:To investigate the efficacy of decitabine combined with preexcitation regimen in the treatment of newly diagnosed acute myeloid leukemia(AML)patients who have not been relieved by the first standard induction chemotherapy and its influence on the relative content of regulatory T lymphocytes(Tregs).Methods:The clinical data of 102 newly diagnosed AML patients(except acute promyelocytic leukemia)who did not relieve after initial standard induction chemotherapy in Shaanxi Provincial People's Hospital from March 2013 to March 2019 were retrospectively analyzed.Fifty-one patients who accepted pre-excitation regimen were divided into regular group,while another 51 patients treated with decitabine combined with pre-excitation regimen were divided into combination group.The efficacy,incidence of toxic and side effects,Core Scale of Quality of Life(QLQ-C30)score before and after treatment,T lymphocyte subsets(CD3+,CD4+,CD4+/CD8+,Tregs)and 3-year overall survival(OS)rate were compared between the two groups.Results:The total effective rate of combination group was 80.39%,which was significantly higher than 62.75%of regular group(P<0.05).After treatment,the QLQ-C30 score of combination group was 60.27 ±6.96,which was significantly lower than 65.73±7.96 of regular group(P<0.001).There was no statistical difference in the incidence of toxic and side effects between the two groups(P>0.05).After treatment,the levels of CD3+,CD4+,CD4+/CD8+in the combination group were higher than those in the regular group(all P<0.001),while Treg was lower(P<0.001).The 3-year OS rate in the combination group was 72.55%,which was significantly higher than 52.94%in the regular group(P<0.001).Conclusion:Decitabine combined with preexcitation regimen has a significant effect on AML patients who have not been alleviated by standard induction chemotherapy in the first course of treatment.It can reduce anti-tumor immune suppression and improve immune function by regulating the relative content of Tregs,thus prolongs survival time and improves life quality of patients without increasing adverse reactions.
6.Causal association between depression and stress urinary incontinence:A two-sample bidirectional Mendelian randomization study
Cheng-Xiao JIANG ; Wei-Qi YIN ; Jing-Jing XU ; Ying-Jiao SHI ; Li WANG ; Zhi-Bo ZHENG ; Rui SU ; Qin-Bo HU ; Jun-Hai QIAN ; Shu-Ben SUN
National Journal of Andrology 2024;30(3):217-223
Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.
7.Design of pressure reading system for splinting distal radius fractures
Jun LI ; Ben-Qi LU ; Hong-Bin JIN ; Jun LU ; Yun ZHAO ; Ai-Guo WANG
Chinese Medical Equipment Journal 2024;45(8):44-50
Objective To design a pressure reading system for splinting distal radius fractures to enable real-time monitoring of splint fixation pressure.Methods A pressure reading system for splinting distal radius fractures was developed with the components of a main contrl unit,a pressure and temperature acquisition unit and a power management unit.The main control unit had a STC15 series SCM as the main control chip,and the pressure and temperature acquisition unit was realized with a FSR400 thin film pressure sensor and a DS18B20 digital temperature measurement chip.The software of the system was developed with C language.The system developed was used to test the magnitude and distribution of the pressure on the splints by applying loads on the fixation straps at 90°,60° and 30° directions to the willow splint and 3D printing splint,respectively,with the total mass of the loads increased from 600 g to 1 200 g and each test repeated by 6 times.Results The system developed was capable of collecting the pressure values at real time and showed them on the display screen.The maximum pressure always occurred at the the connection between the fixation straps and the edge of the splints and the middle parts of the splints were subject to relatively low pressure in case of different loads,when the fixation straps were 90°,60° and 30° to the willow splint and 3D printing splint respectively.The maximum pressure on the willow splint was(239.17±4.49)g when the fixation strap was 90° to the splint and loaded with 1 200 g;the minimum pressure on the willow splint was(89.83±17.38)g when the fixation strap was 60° to the splint and loaded with 600 g.The maximum pressure on the 3D printing splint was(177.67±21.77)g when the fixation strap was 90° to the splint and loaded with 1 100 g;the minimum pressure was(66.50±3.02)g for the 3D printing splint when the fixation strap was 30° to the splint and loaded with 600 g.Conclusion The ssystem developed can read pressure values of the splint under different loads and angles,and the 3D printing splint behaves better than the willow splint in the evenness of pressure distribution.Theoretical references are provided for quantitative clinical treatment with splint fixation.[Chinese Medical Equipment Journal,2024,45(8):44-50]
8.Analysis of factors influencing the treatment outcome of pulmonary tuberculosis patients in Xinjiang Production and Construction Corps
YANG Liugen ; MA Xiaoling ; FAN Ben ; ZHAO Yongnian ; DONG Gaimei ; DUAN Lili ; Delina Sairike ; LI Fanka
China Tropical Medicine 2024;24(4):456-
Abstract: Objective To investigate the treatment outcomes of patients with pulmonary tuberculosis (PTB) in Xinjiang Production and Construction Corps and to explore the risk factors affecting these outcomes, so as to provide a scientific basis for the prevention and treatment of pulmonary tuberculosis in the corps region. Methods TB patients registered in the Corps from 2016 to 2022 were selected, and the basic demographic and clinical data of the research objects were collected by retrospective method. Log-rank test was used for univariate analysis and the Cox multivariate regression model was used to analyze the influencing factors of treatment outcomes of patients with pulmonary tuberculosis. Results From 2016 to 2022, a total of 8 838 TB patients were registered in the TB Management Information System of Xinjiang Production and Construction Corps, of which 495 cases were untreated, 43 cases had changed diagnoses, 301 cases had no treatment outcomes, 6 cases were diagnosed as extrapulmonary tuberculosis, 11 cases were diagnosed as tracheobronchial tuberculosis, and finally 7 982 TB patients were included in the study. Of the 7 982 patients, 7 578 (94.94%) were treated successfully, while 404 (5.06%) had adverse outcomes (including 32 cases of failure, 13 cases of TB death, 173 cases of non-TB death, 12 cases lost to follow-up, 94 cases of adverse reactions, 10 cases transferred to multi-drug resistance treatment, and 70 other cases). Multivariate Cox regression analysis showed that the >30 to 60-year-old and >60-year-old age groups (OR=1.565, P=0.009; OR=2.960, P<0.001), belonging to ethnic minorities (OR=1.526, P<0.001), being a patients with diabetes mellitus (OR=1.696, P=0.002), current address being in other areas of the province or patients from other provinces (OR=1.419, P=0.004; OR=1.624, P=0.001), receiving retreatment (OR=1.910, P<0.001), and absence of primary care management (OR=1.351, P=0.003) were the risk factors for unsuccessful treatment outcomes in the corps' pulmonary tuberculosis patients. Conclusions The treatment success rate of pulmonary tuberculosis patients in the Corps region is relatively high, but there is still a need to strengthen the treatment and management of the elderly, ethnic minorities, diabetes patients, non-local floating population, retreatment patients and patients who did not receive primary management.
9.Modified Danggui Beimu Kushen Pills Inhibit Tumor Growth and Regulates T Cell Subsets in H22 Hepatocellular Carcinoma-bearing Mice
Xiaojie MA ; Ben LIU ; Lei WANG ; Hailong LI ; Yaling LI ; Changtian LI ; Yali SHE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):87-96
ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model, cisplatin, low- (4 g·kg-1·d-1), medium- (8 g·kg-1·d-1), and high-dose (16 g·kg-1·d-1) modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days, the mice were sacrificed on day 15. The tumor volume was measured on days 0, 4, 8, 12, 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells, and the tumor cell-killing rate was detected by the cell counting kit-8 (CCK-8). Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) in spleen and tumor tissues. The number of CD4+ and CD8+ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry (IHC). ResultOn day 8 of drug administration, tumor volumes in all treatment groups decreased compared with that in the model group. On day 15, both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group (P<0.01), with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups, medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index (P<0.01). Compared with the model group, all treatment groups showed increased spleen index (P<0.05, P<0.01), with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups, all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4+ and CD8+ T cells and tumor cell-killing rate in the spleen and tumor tissues (P<0.01) and down-regulated mRNA and protein levels of LAG-3 (P<0.05, P<0.01). The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups (P<0.01). ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4+ and CD8+ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression, thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.
10.Effect of high fat diet intake on pharmacokinetics of metronidazole tablets in healthy Chinese volunteers
Na ZHAO ; Cai-Hui GUO ; Ya-Li LIU ; Hao-Jing SONG ; Ben SHI ; Yi-Ting HU ; Cai-Yun JIA ; Zhan-Jun DONG
The Chinese Journal of Clinical Pharmacology 2024;40(1):102-106
Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P<0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P>0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

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