1.Synergistic Effect of Hydrogen and 5-Aza on Myogenic Differentiation through the p38 MAPK Signaling Pathway in Adipose-Derived Mesenchymal Stem Cells
Wenyong FEI ; Erkai PANG ; Lei HOU ; Jihang DAI ; Mingsheng LIU ; Xuanqi WANG ; Bin XIE ; Jingcheng WANG
International Journal of Stem Cells 2023;16(1):78-92
Background and Objectives:
This study aims to clarify the systems underlying regulation and regulatory roles of hydrogen combined with 5-Aza in the myogenic differentiation of adipose mesenchymal stem cells (ADSCs).
Methods:
and Results: In this study, ADSCs acted as an in vitro myogenic differentiating mode. First, the Alamar blue Staining and mitochondrial tracer technique were used to verify whether hydrogen combined with 5-Aza could promote cell proliferation. In addition, this study assessed myogenic differentiating markers (e.g., Myogenin, Mhc and Myod protein expressions) based on the Western blotting assay, analysis on cellular morphological characteristics (e.g., Myotube number, length, diameter and maturation index), RT-PCR (Myod, Myogenin and Mhc mRNA expression) and Immunofluorescence analysis (Desmin, Myosin and β-actin protein expression). Finally, to verify the mechanism of myogenic differentiation of hydrogen-bound 5-Aza, we performed bioinformatics analysis and Western blot to detect the expression of p-P38 protein. Hydrogen combined with 5-Aza significantly enhanced the proliferation and myogenic differentiation of ADSCs in vitro by increasing the number of single-cell mitochondria and upregulating the expression of myogenic biomarkers such as Myod, Mhc and myotube formation. The expressions of p-P38 was up-regulated by hydrogen combined with 5-Aza. The differentiating ability was suppressed when the cells were cultivated in combination with SB203580 (p38 MAPK signal pathway inhibitor).
Conclusions
Hydrogen alleviates the cytotoxicity of 5-Aza and synergistically promotes the myogenic differentiation capacity of adipose stem cells via the p38 MAPK pathway. Thus, the mentioned results present insights into myogenic differentiation and are likely to generate one potential alternative strategy for skeletal muscle related diseases.
2.Efficency and safety of various combined therapies in treating postoperative refractory recurrent liver cancer
Chao CUI ; Huayong CAI ; Junning CAO ; Jihang SHI ; Bingyang HU ; Wenwen ZHANG ; Hongguang WANG ; Jushan WU ; Guangming LI ; Feng DUAN ; Shichun LU
Chinese Journal of Hepatobiliary Surgery 2021;27(4):252-256
Objective:The study aimed to study the efficacy and safety of combined dual therapy using anti-programmed death (PD)-1 and tyrosine kinase inhibitor (TKI) with combined triple therapy using anti-PD-1, TKI and locoregional intervention triple therapy in patients with postoperative refractory recurrent liver cancer.Methods:Patients with postoperative refractory recurrent liver cancer who had undergone either anti-PD-1 and TKI dual therapy or anti-PD-1, TKI and locoregional intervention triple therapy between July 2016 and March 2019 at the First Medical Center, Chinese PLA General Hospital were retrospectively studied. Tumor responses were assessed by the modified response evaluation criteria in solid tumors and overall survival and progression free survival were compared. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events.Results:Of 63 patients who were included in this study, there were 25 patients in the dual therapy group (16 males and 9 females, aged 54.3±8.8 years) and 38 patients in the triple therapy group (31 males and 7 females, aged 55.5±8.4 years). The 1-year survival rate of the triple therapy group was significantly higher than the dual therapy group (94.5%vs 54.9%) ( P<0.01). The disease control rate was 64.0% (16/25) in the dual therapy group and 84.2% (32/38) in the triple therapy group, and the difference was not significant ( P>0.05). The incidence of treatment-related adverse events in the triple therapy group and the dual therapy group were 78.9% (30/38) and 80% (20/25), respectively. There was no treatment-related death in the 2 groups. Conclusions:Anti-PD-1 and TKI dual therapy and anti-PD-1, TKI and locoregional intervention triple therapy were effective and tolerable treatments for postoperative refractory recurrent liver cancer. The latter treatment had a significantly better clinical benefit on survival outcomes.
3.Evaluation of the prognostic ability of serum uric acid for elderly acute coronary syndrome patients with diabetes mellitus: a prospective cohort study.
Yang JIAO ; Jihang WANG ; Xia YANG ; Mingzhi SHEN ; Hao XUE ; Jun GUO ; Wei DONG ; Yundai CHEN ; Qing XI ; Zhenhong FU
Journal of Zhejiang University. Science. B 2021;22(10):856-865
OBJECTIVES:
This study evaluated the prognostic power of serum uric acid (UA) in predicting adverse events in elderly acute coronary syndrome (ACS) patients with diabetes mellitus (DM).
METHODS:
The analysis involved 718 ACS patients >80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012. These patients were classified into two groups based on DM status, and then followed up after discharge. The Kaplan-Meier method was used for major adverse cardiac event (MACE) rates and all-cause mortality. Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis. Receiver operating characteristic (ROC) curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM. There were 242 and 476 patients in the DM and non-DM (NDM) groups, respectively, and the follow-up time after discharge was 40‒120 months (median, 63 months; interquartile range, 51‒74 months).
RESULTS:
The all-cause mortality, cardiac mortality, and MACE rates in both DM and NDM patients were higher than those in the control group (
CONCLUSIONS
Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.
4.Reoperation for biliary-enteric strictures after hepaticojejunostomy in children with congenital biliary dilatation
Dongyang WU ; Yajun CHEN ; Tingchong ZHANG ; Dayong WANG ; Zengmeng WANG ; Jihang SUN ; Chunhui PENG ; Wenbo PANG ; Kai WANG ; Xinjie HUANG
Chinese Journal of General Surgery 2021;36(9):658-662
Objective:To evaluate clinical characteristics and treatment of postoperative anastomotic stricture in pediatric congenital biliary dilatation patients.Methods:The clinical data of 24 children with postoperative anastomotic stricture from Apr 2012 to Oct 2019 in Beijing Children's Hospital was retrospectively analyzed.Results:There were 6 males and 18 females. Patients were divided into bile- leak group (BL, n=6) and non bile-leak group (NBL, n=18) based on whether there was anastomotic leakage after primary surgery. The main symptoms in BL group was persistent obstructive jaundice, and recurrent cholangitis in NBL group. Postoperative symptoms were first shown in an average of 7.0 months in BL group, compared to 59.0 months in NBL group, P<0.05. In BL group, 4 underwent redoing hepaticojejunostomy, 2 underwent anastomosis plasty. In NBL group, 3 underwent redoing hepaticojejunostomy, 15 did anastomosis plasty with multiple biliary stones found necessitating extraction. After reoperation, one patient had bile leakage, 2 patients had recurrent cholangitis within one-month, 21 patients had uneventful recovery. Five were found to have biliary stones in long-term follow-up. Conclusions:Biliary-enteric anastomotic leakage can cause stricture in postoperative patients of congenital biliary dilatation ,reoperation is necessary in symptomatic patients.
5.Excision for congenital nasal dermoid and sinus cyst in children
Xiaojian YANG ; Jie ZHANG ; Lixing TANG ; Pengpeng WANG ; Jihang SUN ; Yining WANG ; Wentong GE
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(3):230-235
Objective:To explore the surgical effect and experience of endoscope-assisted excision for congenital nasal dermoid and sinus cyst (NDSC) in children.Methods:Fifty-three patients with congenital NDSC treated in Beijing Children′s Hospital from January 2007 to December 2018 were retrospectively reviewed, including 30 boys and 23 girls, with the age ranging from 9 to 145 months (mean age 35.6 months). The ultra-low-dose CT scan and MRI of the paranasal sinuses were performed for all patients. Excisions of NDSC under general anesthesia were performed for all patients, and surgical approaches were dependent on location and extent of the lesions according to radiographic workups. All intra-osseous patients and complicated superficial cases underwent surgical excision of NDSC and nasal reconstruction with the assistance of endoscope. Initial presentation, medical history, imaging workups, surgical approaches, complications, rates of recurrence and cosmetic outcomes were evaluated. Descriptive statistics was used for the results analysis.Results:Among 53 cases, the most common presentation included a nasal-glabella mass ( n=21, 39.6%), a dorsal punctum ( n=13, 24.5%) and a dorsal mass ( n=9, 17.0%). The sites of NDSC included nasal glabella ( n=22, 41.5%), nasal bridge ( n=27, 50.9%) and nasal tip ( n=4, 7.5%). Of all patients, 24 cases (45.3%) had superficial lesions, 19 cases (35.8%) had intraosseous extension into the frontonasal bones, 10 cases (18.9%) extended intracranially but remained extradural. Surgical approaches included transverse incision ( n=22, 41.5%), minimal midline vertical incision ( n=27, 50.9%) and external rhinoplasty ( n=4, 7.5%). All NDSC were successfully excised and no nasal reconstruction needed. All cases were followed up from 9 to 151 months with a mean of 67.3 months. Five patients (9.4%) with recurrence were observed and were managed successfully with reoperation. During the follow-up, no nasal deformity was noted, and cosmetic outcome was favorable for all patients. Conclusion:Endoscope-assisted excision has the advantage of clear vision, small trama and low recurrence rate for children with NDSC.
6.Low concentration contrast medium and low radiation dose for infants and young children abdominal CT scanning
Haoyan LI ; Jihang SUN ; Xiaomin DUAN ; Yong LIU ; Dongqian WANG ; Ling JIANG ; Qifeng ZHANG ; Tong YU ; Yun PENG
Chinese Journal of Interventional Imaging and Therapy 2018;15(4):243-246
Objective To assess the feasibility of low concentration contrast medium (270 mgI/ml) and low radiation dose (100 kV) for enhanced CT scanning in infants and young children abdominal CT examination.Methods Ninety children with abdomen tumors or abdominal injuries who underwent contrast-enhanced CT examination were selected.The patients were divided into 3 groups (each n= 30):Group A with tube voltage of 120 kV for non-contrast enhanced and parenchymal phase scanning and iodixanol contrast-medium (320 mgI/ml);group B with tube voltage of 100 kV for non-contrast enhanced and parenchyrnal phase scanning and iodixanol contrast-medium (270 mgI/rnl);group C with tube voltage of 100 kV for non-contrast enhanced and parenchymal phase scanning and iodixanol contrast-medium (270 mgI/ml).The 4-point scale was used to evaluate the quality of parenchymal phase imaging.The standard difference (SD) of CT value in subcutaneous fat,SNR and CNR of liver parenchyma,splenic parenchyma,renal cortical,renal vein,and abdominal aorta were measured at parenchymal phase,and CT dose index of volume (CTDI,ol),dose length product (DLP) and effective dose (ED) were recorded.The data were statistically analyzed among 3 groups.Results There was no significant difference of SNR,CNR nor objective scores of liver parenchyma,splenic parenchyma,renal cortical,renal vein and abdominal aorta among 3 groups (all P>0.05).The differences of CTDIvol,DLP and ED among 3 groups were statistically significant (all P<0.01).The CTDIvol had no statistical difference between group B and group C (P = 0.001,0.002),DLP (P = 0.013,0.004) and ED (P = 0.03,<0.001) of group A had statistical difference with those of group B and C.Conclusion CNR of the abdominal image can be guaranteed using low concentration contrast medium (270 mgI/ml) combined with 100 kV tube voltage for CT scanning of infants and young children,therefore satisfying clinical diagnostic requirements.
7.Relationship between miR-655 with the clinical features of glioma and its role in diagnosis and prognosis
Haicheng YAN ; Jihang XUE ; Mengyan GAO ; Yulian LI ; Wei WANG
International Journal of Laboratory Medicine 2018;39(10):1184-1187
Objective To study the relationship between miR-655 with the clinical features of glioma and its role in diagnosis and prognosis.Methods The tissues and para cancerous tissues of 97 patients with glioma were collected from January 2013 to May 2017 at the Affiliated Hospital of Inner Mongolia Medical Universi-ty.The expression of miR 655 was detected by real-time fluorescence quantitative PCR,and the diagnosis and prognosis of miR-655 in glioma were analyzed.Results The expression of miR-655 in the cancerous tissues was significantly lower than that of the paracancerous tissues of the glioma (P<0.001),which was signifi-cantly related to the size of the tumor (P=0.024) and the WHO grading (P=0.002).COX regression analy-sis showed that the expression of miR-655 (P=0.004)and the degree of tumor resection(P=0.008) were in-dependent risk factors for glioma;ROC analysis showed that the area under the curve of the glioma (AUC) under the miR-655 expression was 0.959 (95% CI:0.936 -0.982);when the expression of miR-655 was 0.755,the sensitivity and specificity of the diagnosis were 89.7% and 88.7% respectively.The Kaplan Meier analysis of the expression of glioma was statistically significant (P=0.004).The lower expression of miR-655 indicated the worse the prognosis of glioma patients,the COX analysis miR-655 was an independent risk factor for the survival of glioma patients.Conclusion miR-655 can be used as a marker of poor prognosis in diagnosis and prognosis.
8.Promotion of miR-200b promoter methylation by MMC induces fibroblast apoptosis
Shuguang WANG ; Jingcheng WANG ; Yu SUN ; Lianqi YAN ; Xiaolei LI ; Jihang DAI
The Journal of Practical Medicine 2017;33(6):876-879
Objective To explore the mechanism of the role of mitomycin C(MMC)in regulating miR-200b expression and inducing fibroblasts apoptosis. Methods Fibroblasts cultured in vitro were treated with different concentrations of MMC for 5 min and continue culture for 24 h. The expression of miR-200b were analyzed by Real-time PCR. Cell apoptosis were observed using TUNEL staining. The expression of cleaved-PARP,Bax and Bcl-2 were detected by Western blot. The methylation level of miR-200b promoter were measured by BSP. Results After treated with MMC,The expression of miR-200b significantly downregulated.TUNEL Staining analysis demonstrated MMC could significantly induce human fibroblasts apoptosis. Western blot results showed cleaved-PARP,Bax increased and Bcl-2 decreased.The methylation ratio of miR-200b promotor increased and has a significant dose dependent. Conclusion MMC induced human fibroblasts apoptosis by promoting miR-200b promoter methylation.
9.In vitro study on the improvements of Latexin on the chemosensitivity in gemcitabine-resistant pancreatic cancer cells and potential mechanism
Jihang ZHENG ; Cheng WANG ; Xiang ZHOU ; Zhanxiong XUE ; Zhenzhai CAI
Chinese Journal of Pancreatology 2017;17(2):109-113
Objective To observe the effect of Latexin treatment on the chemoresistance in gemcitabine-resistant pancreatic cancer cell line SW1990, and explore the potential mechanism.Methods Gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was induced and established by increasing gemcitabine dosage intermittently.IC50 of gemcitabine in SW1990 cells and SWl990/GZ cells pre and post Latexin treatment at the dosage of 10, 20 and 40 ng/μl for 48 h was evaluated using CCK-8 assay.The mRNA and protein expression of Latexin gene in SW1990 and SW1990/GZ cells were evaluated using qRT-PCR and Western blot, and the expression of Shh and Gli1 in 40 ng/μl Latexin treated SW1990 and SW1990/GZ cells for 48 h.Results A gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was obtained successfully, which can grow stably and passage in the media containing 150 μmol/L gemcitabine.The IC50 values of gemcitabine in SW1990 cells and SWl990/GZ cells were (3.8±0.4)μmol/L and(226.52±13.61)μmol/L, respectively, and the later was greatly higher than the former, which was statistically different (P=0.000).The drug resistance indexes (RI) was 59.6.After treated with different concentrations of Latexin(10,20,40 ng/μl), the IC50 of SW1990 cells was (3.0±0.4)μmol/L, (2.5±0.3)μmol/L and (1.8±0.3)μmol/L, respectively,and the IC50 of SW1990/GZ cells was(113.08±5.01)μmol/L,(70.26±2.31)μmol/L and (42.12±1.31)μmol/L, respectively.Compared with the untreated cells,the IC50 of gemcitabine in 20,40 ng/μl Latexin treated cells was obviously decreased, and the differences were statistically significant (P<0.05).Compared with the SW1990 cells,the expression of Latexin in SW1990/GZ cells was obviously decreased.RI were 37.7, 28.1 and 23.1,respectively.mRNA relative expression of Latexin in SW1990 and SW1990/GZ cells were 0.85±0.08 and 0.31±0.07, and protein relative expression were 0.49±0.09 and 0.13±0.05, and Latexin expression in SW1990/GZ was obviously lower than that in SW1990 cells and the difference was statistically significant (P<0.05).After being treated by 40 ng/μl Latexin, SHH mRNA in SW1990/GZ cells decreased from 0.89±0.09 (control cells) to 0.53±0.06, Gli1 mRNA decreased from 0.58±0.06 to 0.35±0.05, Shh protein decreased from 0.72±0.09 to 0.35±0.06,Gli1 protein level decreased from 0.78±0.08 to 0.28±0.03, and all the differences were statistically significant (P<0.05 or 0.01).Conclusions Latexin can significantly improve the chemosensitivity in gemcitabine-resistant pancreatic cancer cells, and the potential mechanism may be related to the inhibition of sonic hedgehog pathway activation.
10.Improve image resolution in low-dose pediatric chest CT scans with combination of adaptive statistical iterative reconstruction and sharp recon kernel
Jihang SUN ; Fanning WANG ; Xiaomin DUAN ; Yong LIU ; Zhimin LIU ; Lei SONG ; Yun PENG
Chinese Journal of Medical Imaging Technology 2017;33(5):773-777
Objective To explore the value of adaptive statistical iterative reconstruction (ASIR) and a sharp recon kernel to obtain high resolution pulmonary images in low-dose pediatric chest CT scans.Methods Totally 42 children underwent low-dose chest CT scans with ASIR were included.Age dependent noise index (NI) was used for dose optimization:NI=12 for 0-12 months old,NI=15 for >1 2 years old,NI=17 for 3-6 years old and NI=20 for ≥7 years old.Images were reconstructed to 0.625 mm using different recon kernels:Soft,Standard,Lung,and Chest kernel.ASIR blending was varied from 0 100% to provide balanced image noise and spatial resolution.Two radiologists independently evaluated images for normal lung structures,abnormal CT findings and image noise on a 5 point scale with 3 being clinically acceptable.The best kernel,as well as the match with the best ASIR weight were analyzed statistically.Results CT images with lung kernel and ASIR 60% were rated substantially better than those kernel.Conclusion ASIR 60% with a sharp lung kernel can significantly improve image quality in low dose pediatric chest CT scans.

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