1.Effect of Osteoking on Inflammatory Injury and NF-κB/NFATc1 Signaling Pathway in Model Mice with Postmenopausal Osteoporosis
Tiantian YU ; Ruibing FENG ; Qing WANG ; Chaowen LI ; Jiahao CHEN ; Ruixuan JIANG ; Yinshuai DING ; Yong HUANG ; Hao HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):62-69
ObjectiveTo explore the possible mechanism of Osteoking (OK) on postmenopausal osteoporosis (PMOP). MethodForty adult female mice were randomly divided into a sham operation (Sham) group, osteoporosis model (OVX) group, estradiol intervention (E2) group, and OK group, with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy, and the corresponding drugs were given one week later. After 12 weeks, the body mass and uterine index of mice were measured, and the pathological changes of bone tissue and the number of osteoclasts (OCs) were determined by hematoxylin-eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Bone mineral density (BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone volume fraction (BV/TV) were measured by microcomputed tomography (Micro-CT). The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α (TNF-α) and bone resorption marker C-terminal telopeptide of type Ⅰ collagen (CTX-1) were measured by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor-kappa B p65 (NF-κB p65), phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor kappa B inhibitor alpha (IκBα), phosphorylated nuclear factor kappa B alpha (p-IκBα), nuclear factor of activated T cells 1 (NFATc1), and proto-oncogene (c-Fos) were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 (MMP-9), NFATc1, TRAP, cathepsin K (CTSK), and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the Sham group, the uterine index decreased significantly in the OVX group, and the body mass (BMI) increased significantly. The structure of bone trabeculae was completely damaged, and the number of OCs increased. BMD, Tb.N, BV/TV, and maximum load decreased, while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were up-regulated (P<0.05, P<0.01). Compared with the OVX group, the body mass of the OK and E2 groups decreased, and the uterine index increased. The bone trabeculae increased, and the number of OCs decreased. BMD, Tb.N, BV/TV, and maximum load increased, while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were decreased, and the mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were decreased (P<0.05, P<0.01). ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice, which is one of the mechanisms for treating PMOP.
2.Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency
Juan ZHANG ; Chaowen YU ; Ming WANG ; Kexing WAN ; Jing YANG ; Zhaojian YUAN ; Zhihong LIAO ; Dongjuan WANG
Chinese Journal of Pediatrics 2024;62(1):66-70
Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.
3.Radioactivity level and risk assessment of thorium in surface water in Sichuan Province, China, 2016-2021
Hui TANG ; Yuandong LI ; Chaowen BI ; Wanchong MAO ; Qian WANG ; Qiang YU ; Xin LIU ; Cheng CHEN
Chinese Journal of Radiological Health 2023;32(4):438-443
Objective To investigate the content of thorium (Th) in surface water in Sichuan Province, China, and to evaluate Th-associated health risk via water intake for residents. Methods Twenty-three monitoring sections were set in main surface water bodies in Sichuan Province. From 2016 to 2021, the Th radioactivity level in the water bodies was measured during dry and normal-water seasons. The health risk of residents was evaluated by calculating radioactive Th intake from the surface water bodies combined with the use of a health risk assessment model. Results The Th radioactivity level of the surface water bodies in Sichuan Province was 0.02-0.67 μ./L. There was no significant difference in the Th radioactivity level of different years or different surface water bodies (P > 0.05). A significant difference was observed in the Th radioactivity level of different water seasons (P < 0.05). The total mean annual committed effective doses of Th in all age groups caused by drinking water and water immersion ranged from 3.14 × 10−8 to 8.75 × 10−7 Sv, all lower than the World Health Organization (WHO)-recommended reference level of 0.1 mSv. The overall carcinogenic risks for residents in all age groups ranged from 3.93 × 10−10 to 1.09 × 10−8, all below the most rigorous control limits issued by WHO and International Commission on Radiological Protection. Conclusion The Th-associated health risk via direct water intake and water immersion in main surface water bodies of Sichuan Province is at an acceptable level. Th in main surface water bodies of Sichuan Province is safe for all age groups.
4.Drug-coated balloon vs standard angioplasty balloon in the treatment of postoperative in-stent restenosis in patients with arteriosclerosis obliterans of the lower extremity
Tao SONG ; Yong SUN ; Zhonglin NIE ; Wenbo TANG ; Chao XU ; Chaowen YU
Chinese Journal of General Surgery 2021;36(5):350-354
Objective:To compare drug-coated balloon (DCB) and standard angioplasty balloon (SAB) in the treatment of postoperative in-stent restenosis (ISR) in patients with arteriosclerosis obliterans (ASO) of the lower extremity.Methods:From Jan 2017 to Dec 2018, 43 ISR patients after percutaneous transluminal angioplasty for ASO of the lower extremity at our hospital were enrolled.Patients were divided into 2 groups with 18 patients treated by DCB and 25 by SAB. The patients were followed up for 6~12 months.Results:There was no significant difference in the incidence of complications between DCB group and SAB group ( P>0.05).Compared with that in SAB group, the plasma level of ET-1 in DCB group was lower while NO was higher at 6, 24 h and 2 weeks after surgery ( P<0.05), there was no significant difference in P-selectin ( P>0.05). The ABI values in both groups increased, and that in DCB group were higher than SAB group at 6 and 12 months after surgery ( P<0.05). The lumen loss in DCB group at 6 and 12 months after surgery was significantly lower ( P<0.05). At 6 and 12 months, the primary patency of target lesions in the DCB group was 100.00% and 88.89%, which was higher than the 72.00% and 52.00% in the SAB group ( P<0.05); the CD-TLR rate in the DCB group was 11.11%, which was lower than 48.00% in the SAB group ( P<0.05). Conclusion:DCB comes with lower postoperative ISR in ASO patients of the lower extremity.
5.Evaluation on efficacy and safety of blood-letting tape used in lower extremity varicose vein operation
Zeyu GUAN ; Tao SONG ; Chao XU ; Chaowen YU ; Yong SUN ; Yong GAO
Chongqing Medicine 2018;47(6):773-775,778
Objective To investigate the efficacy and safety of exsanguination band used in the lower extremity varicose vein operation.Methods A total of 158 cases of lower extremities varicose veins in this hospital served as the research subjects.All cases underwent the high ligation of great saphenous vein combined with punctate stripping operation.Among them,117 cases intraoperatively used the exsanguination band for blocking the lower limb blood flow (observation group),41 cases did not use the exsanguination band (control group).Then the intraoperative bleeding volume,operation time,pain degree and postoperative complications were observed in the two groups.Results Compared with the control group,the operation time,intraoperative blood loss,hematoma score,prothrombin time (PT) and fibrinogen (FIB) in the observation group were significantly decreased (P<0.05),while activated partial thrombin time (APTT) and thrombin time (TT) were significantly increased(P<0.05).The lower limb blood flow occlusion time in the observation group was 45-62 min with an average of (46.68-5.53) min.The sensory score and pain score at postoperative 2 weeks had no statistical difference between the two groups (P>0.05).No arterial abnormalities and no obvious ischemic injury were found in the injured limbs of 2 groups.Conclusion Applying the exsanguination band for transiently blocking the blood flow can effectively shorten the operation time,reduces the intraoperative bleeding amount and decreases the subcutaneous hematoma formation risk with high safety.
6.1,25(OH)2D3 protects against BLM-induced pulmonary fibrosis by inhibiting activation of STAT3
Lishan LUO ; Hangming DONG ; Chaowen HUANG ; Yahui HU ; Changhui YU ; Xuan WAN ; Haijin ZHAO ; Shaoxi CAI
The Journal of Practical Medicine 2017;33(1):59-63
Objective To investigate the impact of 1,25(OH)2D3 on histological changes and activation of STAT3 in BLM?induced pulmonary fibrosis mice. Methods 30 male C57BL/6 mice were randomly divided into control group ,BLM group and BLM+VD group. Mice in BLM group and BLM+VD group received intratracheal injection of BLM(3 U/kg). Control group were intratracheally injected equal volume of sterile saline. From the first day after the surgery,mice in BLM+VD group received intraperitoneal injection of VD (5μg/kg·d). After 21 days, H&E and Masson′s trichrome staining were carried out. Aschroft score were used to evaluate histological changes in lungs. IL?6,IL?4 and INF?γin BALF were assessed by Elisa. p?STAT3,α?SMA and Collagen I were detected by western blot (WB) and immunohistochemistry. Results Fibrosis score and level of α?SMA,Collagen I in BLM group were significantly higher than that in control group (P < 0.05). However ,treatment with VD effectively at?tenuated fibrosis (P<0.05). IL?6 and IL?4 increased while INF?γwas decreased in BALF of BLM group (P<0.05). VD could ameliorate these changes. Upregulation and neuclear translocation of p?STAT3 were observed in BLM group,while VD intervention could inhibit phosphorylation of STAT3. Conclusions VD attenuate BLM?induced pulmonary fibrosis and regulate inflammatory cytokines probably by blocking STAT3 activation.
7.Application of CT venography in diagnosis and treatment of Budd-Chiari syndrome
Xiaogao WANG ; Shiyuan CHEN ; Biao SHI ; Xiaochun QIAO ; Yong GAO ; Chaowen YU ; Zhonglin NIE
Chongqing Medicine 2016;45(8):1043-1045
Objective To investigate the application value of CT venography(CTV) in the diagnosis and treatment of Budd‐Chiari syndrome(BCS) .Methods 58 patients with BBCS in our hospital from January 2012 to January 2014 were performed the CTV examination .The inferior vena cava ,hepatic vein ,portal vein and collateral vessels were performed the reconstruction analysis . Results All the patients were definitely diagnosed as BCS after completing CTV examination ,including :19 cases of inferior vena cava(IVC) diaphragm type ,15 cases of short IVC segment occlusion ,8 cases of long IVC segment occlusion ,9 cases of hepatic vein stenosis or occlusion ,7 cases complicated by fresh thrombosis .In addition ,the different degrees of compensatory expansion of col‐lateral vesse ,intuition and comprehensiveness ,can display the position ,character and length of lesion vessel ,also observes the de‐grees of collateral vessels expansion and liver cirrhosis .
8.Different optical properties between human hepatocellular carcinoma tissues and non-tumorous hepatic tissues In Vitro.
Yuan, YU ; Chaowen, XIAO ; Kun, CHEN ; Jianwei, ZHENG ; Jun, ZHANG ; Xinyang, ZHAO ; Xinbo, XUE
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(4):515-9
There has been an ongoing search for clinically acceptable methods for the accurate, efficient and simple diagnosis and prognosis of hepatocellular carcinoma (HCC). Optical spectroscopy is a technique with potential clinical applications to diagnose cancer diseases. The purpose of this study was to obtain the optical properties of HCC tissues and non-tumorous hepatic tissues and identify the difference between them. A total of 55 tissue samples (HCC tissue, n=38; non-tumorous hepatic tissue, n=17) were surgically resected from patients with HCC. The optical parameters were measured in 10-nm steps using single-integrating-sphere system in the wavelength range of 400 to 1800 nm. It was found that the optical properties and their differences varied with the wavelength for the HCC tissue and the non-tumorous hepatic tissue in the entire wavelength range of research. The absorption coefficient of the HCC tissue (1.48±0.99, 1.46±0.88, 0.86±0.61, 2.15±0.53, 0.54±0.10, 0.79±0.15 mm(-1)) was significantly lower than that of the non-tumorous hepatic tissue (2.79±1.73, 3.13±1.47, 3.06±2.79, 2.57±0.55, 0.62±0.10, 0.93±0.16 mm(-1)) at wavelengths of 400, 410, 450, 1450, 1660 and 1800 nm, respectively (P<0.05). The reduced scattering coefficient of HCC tissue (5.28±1.70, 4.91±1.54, 1.26±0.35 mm(-1)) and non-tumorous hepatic tissue (8.14±3.70, 9.27±3.08, 2.55±0.57 mm(-1)) was significantly different at 460, 500 and 1800 nm respectively (P<0.05). These results show different pathologic liver tissues have different optical properties. It provides a better understanding of the relationship between optical parameters and physiological characteristics in human liver tissues. And it would be very useful for developing a non-invasive, real-time, simple and efficient way for medical management of HCC in the future.
9.The effect of oncolyic adenovirus SG600-IL24 expressing human MDA-7/IL-24 on apoptosis of hepatocellular carcinoma cell lines
Chaowen XIAO ; Zhihai PENG ; Congjun WANG ; Yuan YU ; Kun CHEN ; Jianwei ZHENG ; Jun ZHANG ; Xinbo XUE
Chinese Journal of General Surgery 2011;26(6):470-473
Objective To investigate the effect of oncolytic adenovirus vector SG600-IL24expressing human melanoma differentiation associated gene-7 (mda-7/IL-24) on hepatocellular carcinoma cell lines with different metastatic potential of HepG2, SMMC7721, MHCC97L and normal liver cell line LO2. Methods The oncolytic adenovirus SG600-IL24 which carrying mda-7/IL-24 gene was transfected into hepatocellular carcinoma cell lines and normal liver cell line. The mRNA and protein expression of mda7/IL-24 in HepG2, SMMC7721, MHCC97L and LO2 cell lines was confirmed by RT-PCR,ELISA assay and Western blot respectively. MTT assay and flow cytometry were used to study tumor cell proliferation and cell cycle in vitro. Hoechst33258 and flow cytometry were studied to indicate the apoptosis effects. Results It was confirmed by RT-PCR, ELISA assay and Western-blot that the exogenous mda-7/IL-24 gene was highly expressed in HepG2, SMMC7721, MHCC97L and LO2 cell lines. MTT and apoptosis detection indicated that MDA-7/IL-24 can induce the growth suppression (the inhibition rate was 75% ±2. 5% ,86% ±3. 5% ,and promotes apoptosis ( the apoptosis rate was 56. 5% ± 4. 0% , 34. 4% ± 2. 0% , 43. 3% ± 2. 5%cell lines at G2/M phase ( the blocking rate was 35. 4% ± 4. 2% , 40. 5% ± 5. 0% , 42. 0% ± 5. 0%metastatic potential hepatocellular carcinoma cell lines but not in normal liver cell line.Conclusions Oncolytic adenovirus vector SG600-IL24 can selectively induce growth suppression, promote apoptosis in hepatocellular carcinoma lines in vitro but not in normal liver cell LO2.
10.Different Optical Properties between Human Hepatocellular Carcinoma Tissues and Non-tumorous Hepatic Tissues In Vitro
YU YUAN ; XIAO CHAOWEN ; CHEN KUN ; ZHENG JIANWEI ; ZHANG JUN ; ZHAO XINYANG ; XUE XINBO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(4):515-519
There has been an ongoing search for clinically acceptable methods for the accurate,efficient and simple diagnosis and prognosis of hepatocellular carcinoma (HCC).Optical spectroscopy is a technique with potential clinical applications to diagnose cancer diseases.The purpose of this study was to obtain the optical properties of HCC tissues and non-tumorous hepatic tissues and identify the difference between them.A total of 55 tissue samples (HCC tissue,n=38; non-tumorous hepatic tissue,n=17)were surgically resected from patients with HCC.The optical parameters were measured in 10-nm steps using single-integrating-sphere system in the wavelength range of 400 to 1800 nm.It was found that the optical properties and their differences varied with the wavelength for the HCC tissue and the non-tumorous hepatic tissue in the entire wavelength range of research.The absorption coefficient of the HCC tissue (1.48±0.99,1.46±0.88,0.86±0.61,2.15±0.53,0.54±0.10,0.79±0.15 mm-1) was significantly lower than that of the non-tumorous hepatic tissue (2.79±1.73,3.13±1.47,3.06±2.79,2.57±0.55,0.62±0.10,0.93±0.16 mm-1) at wavelengths of 400,410,450,1450,1660 and 1800 nm,respectively (P<0.05).The reduced scattering coefficient of HCC tissue (5.28±1.70,4.91±1.54,1.26±0.35 mm-1) and non-tumorous hepatic tissue (8.14±3.70,9.27±3.08,2.55±0.57 mm-1) was significantly different at 460,500 and 1800 nm respectively (P<0.05).These results show different pathologic liver tissues have different optical properties.It provides a better understanding of the relationship between optical parameters and physiological characteristics in human liver tissues.And it would be very useful for developing a non-invasive,real-time,simple and efficient way for medical management of HCC in the future.


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