1.Effect of Dahuang Xiezhuo Prescription on Inflammation and SOCS3/TLR4 Pathway in Rats with Chronic Renal Failure
Xin XIN ; Zhenhua WU ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Qian ZHANG ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):95-104
ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription (DHXZ) on inflammation and suppressor of cytokine signaling 3 (SOCS3)/Toll-like receptor 4 (TLR4) pathway in rats with chronic renal failure (CRF), and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats, 15 were randomly selected as sham group, and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling, the rats were randomly divided into model group, DHXZ low-, medium-, high-dose groups (6.825, 13.65, 27.3 g·kg-1) and Niaoduqing Granules group (2.6 g·kg-1). The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration, hematoxylin-eosin (HE) staining and Masson staining were used to observe the morphological changes of rat renal tissue, and blood creatinine (SCr), blood urea nitrogen (BUN) and blood uric acid (UA) were tested. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expressions of SOCS3, TLR4, nuclear transcription factor (NF-κB) and myeloid differentiation factor (MyD88) were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB, MyD88, NOD-like receptor protein 3 (NLRP3) and melanoma deficiency factor 2 (AIM2). ResultCompared with the sham group, the model group had a significant inflammatory response in renal tissue, and an increase in blood SCr, BUN, UTP, IL-6, TNF-α and CRP (P<0.05). The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4, NF-κB, MyD88, NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group (P<0.05). Compared with the model group, DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr, BUN, UTP, IL-6, TNF-α and CRP (P<0.05). Additionally, DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4, NF-κB, MyD88, NLRP3 and AIM2 and the mRNA expression of TLR4 (P<0.05). ConclusionDHXZ can reduce the release and expression of inflammatory factors, inhibit the inflammatory response and improve renal function, and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.
2.Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway
Yao ZHANG ; Fei GAO ; Miao TAN ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Guodong YUAN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):203-213
ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK), silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), autophagy and apoptosis in kidney tissue of rats with membranous nephropathy (MN), and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group, model group, benazepril hydrochloride group (10 mg·kg-1), and salvianolate low-, medium-, and high-dose groups (16.7, 33.3 and 66.7 mg·kg-1). The rats were modeled by injection of cationized bovine serum albumin (C-BSA) into the tail vein. After successful modeling, rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks, and then 24-hour urine, serum and kidney tissue were collected for the detection of 24-hour urinary protein (UTP), blood urea nitrogen (BUN), serum creatinine (SCr), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The pathological changes of kidneys were observed by light microscope, electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK (p-AMPK), AMPK, phospho-SIRT1 (p-SIRT1), SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, ubiquitin-binding protein (p62), B cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), and cysteine aspartic protease-7 (Caspase-7) in rat kidney tissue were determined by immunohistochemistry (IHC). ResultCompared with the conditions in the normal group, the levels of UTP, IL-6, TNF-α, CRP and MDA in the model group were increased (P<0.05) while the levels of SOD and GSH-Px were decreased (P<0.05), and there was no difference in BUN and SCr. Compared with the model group, the administration groups had lowered UTP, IL-6, TNF-α, CRP and MDA (P<0.05) while elevated SOD and GSH-Px (P<0.05). It could be seen from hematoxylin and eosin (HE) staining, Masson staining, immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant, but after treatment with benazepril hydrochloride and salvianolate, the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group (P<0.05) while the expressions of Bax, Caspase-7 and p62 were higher (P<0.05). Compared with the model group, benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in the kidney (P<0.05) while a down-regulation in the expressions of Bax, Caspase-7 and p62 (P<0.05). ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway, the up-regulation of autophagy and the reduction of apoptosis.
3.Effect and reflection of WeChat official account teaching cases on the standardized residency training of nuclear medicine residents
Yunyun ZHAO ; Hebei LI ; Qian WANG ; Ping GAO ; Jinchuan CHEN ; Keji HAO ; Yuan LI ; Liheng QIU ; Minggang YUE
Chinese Journal of Medical Education Research 2023;22(5):741-744
In order to help the standardized residency training of nuclear medicine residents, the standardized residency training base of nuclear medicine residents in Peking University People's Hospital, combined with forty-five nuclear medicine departments of teaching hospital, established the WeChat official account of "Standardized Residency Training of Nuclear Medicine" and submitted one teaching case per week. The appearance of the WeChat official account of "Standardized Residency Training of Nuclear Medicine" has made up for the shortcomings of insufficient teaching cases in a single training base, strengthened the training of residents' imaging diagnostic thinking, and promoted mutual learning among the bases. By writing teaching cases, instructors and residents have opened up ideas, increased knowledge, improved self-learning ability, and cultivated imaging diagnostic thinking. With the flexible and practical features of the WeChat official account, the consciousness and sustainability of residents' learning have been enhanced.
4.Effect of Dahuang Xiezhuo Prescription on Renal Interstitial Fibrosis of Rats with 5/6 Nephrectomy by Regulating ROS/TXNIP/NLRP3 Pathway
Wenxuan CAO ; Xin XIN ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):81-89
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the changes in renal pathology and reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway expression in the kidney tissues of rats with 5/6 nephrectomy, and to explore the mechanism of Dahuang Xiezhuo prescription in protecting renal function and delaying renal interstitial fibrosis and the possibility. MethodNinety healthy male SD rats were randomly divided into a sham operation group, a model group, low, medium, and high-dose (6.825, 13.65, 27.30 g·kg-1) Dahuang Xiezhuo prescription groups, and a Niaoduqing granule group (2.60 g·kg-1). Except the sham operation group, 5/6 nephrectomy was used to replicate the rat model of chronic renal failure (CRF). After modeling, each administration group was given the corresponding dose of drug suspension by intragastric administration, once a day for consecutive 8 weeks. After administration, serum creatinine (SCr) and urea nitrogen (BUN) levels and 24 h urinary protein quantification (UTP) levels were detected. Western blot assay was used to detect the protein expressions of thioredoxin (TRX), TXNIP, and NLRP3. The protein expressions of TRX, TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), transformation growth factor-β (TGF-β), Collagen Ⅳ, α-smooth muscle actin (α-SMA), and fibronectin (FN) were detected by immunohistochemistry. ResultAs compared with the sham operation group, serum levels of SCr, BUN, and UTP in the model group were increased (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN proteins were increased (P<0.01), and renal interstitial fibrosis significantly occurred. As compared with the model group, the levels of SCr, 24 h BUN, and UTP in the low, medium, and high-dose Dahuang Xiezhuo prescription groups and the Niaoduqing granule group were decreased to varying degrees (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN were decreased (P<0.01), and renal interstitial fibrosis was improved to varying degrees. ConclusionDahuang Xiezhuo prescription can protect renal function and delay renal interstitial fibrosis in rats with CRF.
5.Single Cell Traction Force Measured by Foldable Microplates
Lijun ZHAO ; Chenyan WANG ; Quanyou ZHANG ; Di HUANG ; Jinchuan HOU ; Weiy CHEN
Journal of Medical Biomechanics 2022;37(2):E287-E291
Objective To fabricate a foldable microplate for single cell culture and establish finite element model of the folding microplate, so as to calculate traction force of single cells during contraction in three-dimensional (3D) state.Methods The folding angle of the microplate casued by cell traction force was calculated. Then the relation between bending moment and folding angle as well as the relation between traction force and bending moment were derived by using finite element simulation, so as to realize the characterization of traction force for singel cell in 3D state.Results The folding angles of the microplate with HSF and MC3T3-E1 cells in 3D state were 73°-173° and 49°-138°, respectively. The single cell traction forces of HSF and MC3T3-E1 cells were 55-210 nN and 52-161 nN, respectively.Conclusions The proposed method for measuring traction force of single cells in 3D state by fabricating the foldable microplate for single cell culture will provide some references for further development of calculating traction forces in 3D cell adhesion, spreading and migration.
6.18F-FDG PET/CT imaging in fever of unknown origin: data from a large single-center cohort
Yuan LI ; Qian WANG ; Ziwei CHEN ; Jinchuan CHEN ; Yunyun ZHAO ; Ping GAO ; Liheng QIU ; Keji HAO ; Hebei LI ; Minggang YUE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(8):452-458
Objective:To further understand the etiological distribution of fever of unknown origin (FUO) in patients underwent 18F-fluorodeoxyglucose (FDG) PET/CT imaging, and to explore the significance of 18F-FDG PET/CT in the diagnosis of different types of diseases in FUO patients. Methods:From January 2013 to August 2019, the clinical and PET/CT image data of 466 FUO patients (194 males, 272 females, age: 3-91(52.7±20.9) years) in Peking University People′s Hospital were retrospectively analyzed. The etiological distribution of FUO patients was analyzed according to the final clinical diagnosis. PET/CT imaging manifestations were analyzed for different types of diseases in FUO patients. The role of 18F-FDG PET/CT in differential diagnosis for FUO was evaluated through clinical questionnaire. Data were analyzed by using χ2 test. Results:The common disease types in FUO patients were rheumatic and immune disease (48.7%, 227/466), infection (28.5%, 133/466) and malignant tumor (11.2%, 52/466). For PET/CT imaging, 95.5% (445/466) of the patients were positive, of which 313 (70.3%, 313/445) were found to have focal lesions, and the other 132 (29.7%, 132/445) showed only nonspecific abnormal uptake. Lesions in different types of diseases were varied in the location, morphological changes as well as FDG uptake. The results of the questionnaire showed that PET/CT imaging could benefit 95.9% (447/466) of the patients in the FUO diagnosis and treatment. PET/CT reached direct etiological diagnosis of malignant tumors more frequently than other types of diseases ( χ2 values: 14.408-25.466, all P<0.001). PET/CT helped or directly reached the etiological diagnosis of rheumatologic diseases more frequently than infection and unknown cause group( χ2 values: 7.922, 9.647, both P<0.05). Conclusion:18F-FDG PET/CT imaging has high clinical value in the diagnosis of FUO etiology and can provide multilevel diagnostic information.
7.Sex-specific and Dose-response Relationship between the Incidence of Gallstones and Components of the Metabolic Syndrome in Jinchang Cohort: A Prospective Study.
Jing Li YANG ; Jun Jun HUANG ; Ning CHENG ; De Sheng ZHANG ; Si Min LIU ; Wen Ya HUANG ; Na LI ; Pei Yao HUANG ; Jiao DING ; Nian LIU ; Kai Fang BAO ; Jie DING ; Xiao Liang CHEN ; Tong Zhang ZHENG ; Ya Na BAI
Biomedical and Environmental Sciences 2020;33(8):633-638
8.Echocardiographic evaluation of left ventricular diastolic function in patients with diastolic heart failure and comparative study of real‐time cardiac catheterization
Fen ZHANG ; Yi LIANG ; Liangjie XU ; Cuicui ZHOU ; Tingpan FAN ; Inxin X CHEN ; Weidong LI ; Wei YUAN ; Yang ZHAO ; Jingping SUN ; Jinchuan YAN
Chinese Journal of Ultrasonography 2019;28(3):218-223
Objective To evaluate the left ventricular diastolic function of patients with normal left ventricular ejection fraction ( LVEF) by echocardiography and real‐time cardiac catheter measurement ,and improve the accuracy and reliability of echocardiographic diagnosis . Methods One hundred and twenty patients with know n or suspected coronary artery disease w ho underwent coronary angiography and left ventricular catheterization were prospectively selected from July 2017 to January 2018 in the Affiliated Hospital of Jiangsu University . According to the left ventricular end diastolic pressure ( LVEDP) real‐time measurement ,the patients were divided into groups of LVEDP ≤15 mm Hg ( 43 cases ) and LVEDP > 15 mm Hg ( 77 cases) . General data were compared and the difference of echocardiographic parameters between the two groups were analyzed ,and the ROC curve of each echocardiographic parameter for diagnosing LVEDP was draw n . Results T he parameters including flow propagation velocity ( VP) ,the ratio of filling fraction of E and A ( E/A) ,early diastolic filling deceleration time ( DT ) ,the duration of mitral A ( A‐dur ,) mitral annulus velocity at the septal side ( e′sep) ,systolic pulmonary venous flow velocity ( PVs) ,diastolic pulmonary venous flow velocity ( PVd ) and PVs/PVd were used to the diagnosis of the increasing of LVEDP ,however their accuracies were low ( AUC between 0 .5~0 .7) . T he parameters including left atrial volume index ( LAVI ) , tricuspid regurgitation ( T Rmax ) ,mitral annulus velocity in lateral wall of left ventricle ( e′lat ) ,average e′,E/e′sep ,E/e′lat ,average E/e′,velocity of pulmonary vein atrial reversal ( PVa) ,pulmonary vein atrial reversal duration ( Pva‐dur) ,the difference between the duration of pulmonary venous A wave and mitral A wave( PvaD‐AD) were also used to the diagnosis of the increasing of LVEDP , but their accuracies were still poor ( AUC between 0 .7~0 .9 ) . According to the real‐time left ventricular pressure measurement and different parameters of echocardiography ,the multivariate regression equation :LVEDP= 0 .292 LAVI + 0 .35 PVa + 0 .04 T Rmax + 0 .075 ( PvaD‐AD ) -0 .109 PVs -6 .773 was put forward as a correction standard ,the accuracy of the diagnosis of LVEDP was significantly improved ( AUC =0 .922) . Conclusions T he assessment of left ventricular diastolic function needs to be performed comprehensively with multiple parameters . T he multiple regression equation can accurately evaluate left ventricular diastolic function in patients with normal LVEF .
9.Molecular docking in Nεcarboxymethyl lysine targeting scavenger receptor CD36
Zhongqun WANG ; Zhengyang BAO ; Zhen SUN ; Jinchuan YAN ; Chen SHAO ; Lihua LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2019;21(5):519-521
Objective To study whether Nεcarboxymethyl lysine(CML)can form a good molecular docking with the scavenger receptor CD36and induce a stable interaction.Methods The interaction between CML and CD36was studied by co-immunoprecipitation.The binding mode and affinity of CD36to CML were tested using AutoDock 4.2,iBabel and XQuartz-2.7.7software respectively. Results Co-immunoprecipitation showed that anti-CD36antibody magnetic bead could precipitate CD36from the total protein in RAW264.7cells and anti-CML could detect CD36 binding CML.CD36had a good molecular docking with CML,CD36and CML interacted stably with each other.The affinity of CML to 4Q4Bprotein structure of CD4extracellular domain was -29.62kJ/mol.ARG82,ASN71and THR70were the products of amino acid receptor interaction. Further docking analysis showed that CML could form 3interacting hydrogen bonds with 4Q4B,and the docking prediction inhibition constant was 6.92with a root mean square deviation of 2.54.Conclusion A good molecular docking between CML and 4Q4Bprotein structure of CD36extracellular domain can induce a stable interaction between CML and CD36.Hydrogen bonding is the main interaction mode.
10. Incidence of chronic obstructive pulmonary disease and pneumoconiosis in different occupational positions among populations from jinchang cohort
Jianing CAO ; Desheng ZHANG ; Junjun HUANG ; Nan JIANG ; Haiyan LI ; Kaifang BAO ; Jie DING ; Xiaoliang CHEN ; Li MA ; Xiaobin HU ; Juansheng LI ; Xiaowei REN ; Ning CHENG ; Yana BAI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(9):650-655
Objective:
To investigate the incidence and rank of chronic obstructive pulmonary disease and pneumoconiosis to the workers in different occupational positions in Jinchang Cohort.
Methods:
In January 2014, a cohort of follow-up population in jinchang city was taken as the research object, 17843 individuals among follow-up populations in Jinchang Cohort Study, removed the individuals with chronic obstructive pulmonary disease and pneumoconiosis before 2013, and counted the new incidence individuals diagnosed by the A-Class hospital in Grade III in Jinchang City, Gansu Province, as the investigation objects to investigate the incidence rate & rank of chronic obstructive pulmonary disease and pneumoconiosis. The statistical significance was tested by chi-square test.
Results:
The 2-year incidence rate of Chronic Obstructive Pulmonary Disease and Pneumoconiosis in the population of Jinchang Cohort Study were 11.60‰, 13.51‰ for male and 8.46‰ for female. the ranks of 2-year incidence rates of chronic bronchitis, emphysema, pneumoconiosis and other phenotypes of chronic obstructive pulmonary disease were 7.06‰、3.42‰、0.84‰、0.34‰, respectively. Incidence rate of chronic bronchitis among administrators and executive staffs were 10.45‰; incidence rate of chronic bronchitis among service staffs were 10.45‰; incidence rate of pneumoconiosis among mining staffs were 3.44‰.
Conclusion
The first incidence rank of chronic obstructive pulmonary disease and pneumoconiosis in Jinchang cohort is chronic bronchitis, and the risk factors are smoking and occupational exposure.

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