1.SOX7 inhibits colorectal cancer proliferation,invasion and migration through the SHP-2/Wnt/β-catenin/ROS pathway
Xueliang WU ; Likun WANG ; Hongqing MA ; Shaodong LI ; Yan LIANG ; Zhilong HUI ; Lei HAN ; Jun XUE
Acta Universitatis Medicinalis Anhui 2024;59(7):1237-1243
Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P<0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.01),and promoted the expression of p-SHP-2 protein(P<0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P<0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P<0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P<0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P<0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.
2.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
3.Transoral stepped atlantoaxial release theory for irreducible atlantoaxial dislocation
Shaodong MO ; Hong XIA ; Zenghui WU ; Xiangyang MA ; Jianhua WANG ; Kai ZHANG ; Suochao FU ; Yu ZHANG ; Qingshui YIN ; Fuzhi AI
Chinese Journal of Orthopaedics 2022;42(23):1542-1553
Objective:To investigate the clinical efficacy of different grade transoral atlantoaxial release for the treatment of irreducible atlantoaxial dislocation.Methods:From January 2010 to December 2019, 297 patients with irreducible atlantoaxial dislocation treated by different grade releases were retrospectively analyzed, including 132 males and 165 females, aged 42.3±12.14 years (range, 10-63 years). All cases were treated by different grade releases, Grade I (196, 66.0%), Grade II (54, 18.2%), Grade III (28, 9.4%) and Grade IV (19, 6.4%). The American Spinal Injury Association (ASIA) grade and Japanese Orthopedic Association (JOA) score were recorded as the clinical evaluation index. The clivus-canal angle (CCA) and cervico-medullary angle (CMA) were measured to evaluate the reduction. The surgery time, blood loss, duration of bony fusion and complications were also analyzed.Results:The follow-up time was 14.8±10.2 months (range, 9-36 months). The surgery time of Grade I-IV were 2.02±0.35 min, 3.00±0.36 min, 4.07±0.96 min and 5.24±0.83 min, respectively ( F=385.43, P<0.001), blood loss was 84.08±27.21 ml, 153.61±31.36 ml, 268.93±48.94 ml and 444.21±109.51 ml, respectively ( F=582.39, P<0.001). The preoperative ASIA motor score of Grade I-IV were 83.85±6.68, 84.06±5.47, 84.07±5.99 and 85.00±4.11, respectively. The last follow-up were 98.34±2.38, 98.67±1.79, 98.86±1.58 and 98.32±2.11, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative JOA score of Grade I-IV were 11.44±1.73, 11.59±1.72, 11.61±1.47 and 11.32±1.80, respectively. The last follow-up were 16.22±1.00, 16.28±1.02, 16.14±1.04 and 16.16±1.07, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CCA of Grade I-IV were 110.19°±8.76°, 112.48°±7.66°, 106.61°±6.54° and 109.05°±7.79°, respectively. The last follow-up were 140.22°±8.04°, 141.86°±7.04°, 142.35°±8.62° and 140.15°±6.49°, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CMA of Grade I-IV were 113.48°±9.54°, 116.03°±8.38°, 109.55°±7.13°, and 112.46°±8.33°, respectively. The last follow-up were 144.28°±7.75°, 146.40°±6.98°, 145.81°±8.27° and 143.24°±6.36°, respectively, with statistically significant differences from preoperative ( P<0.05). Solid bony fusion was obtained except for 3 cases, the fusion time was 9.71±2.55 months (range 3-14 months). Altogether 33 complications occurred in all cases (11.1%), including 3 fusion failure, 3 cerebrospinal leak, 3 wound infection, 2 death (1 case caused by cerebrospinal leak), 11 pharyngeal discomfort, 4 postoperative pain surrounding iliac crest, and 8 malunion of iliac crest. Conclusion:Transoral stepped atlantoaxial release theory could provide guidelines for atlantoaxial dislocation treatment, and make the transoral release technique more effective and safer.
4.Role of immune response and inflammatory injury in the pathogenesis of liver failure
Tingshuai WANG ; Na WANG ; Rongzhen ZHANG ; Minggang WANG ; Shaodong HUANG ; Yuzhen MA ; Cong WU ; Dewen MAO
Journal of Clinical Hepatology 2020;36(6):1415-1419
Liver failure is a syndrome of severe liver diseases commonly seen in clinical practice, and it has a high mortality rate and thus becomes one of the critical diseases in internal medicine. Massive hepatocyte death and the extent of hepatocyte death exceeding the liver’s regenerative capacity are considered the core events in the development and progression of liver failure, and direct injury and immune-mediated inflammatory injury are the two main factors in this process. An increasing number of evidence has shown that host immune response and inflammatory cascade play an important role in the pathogenesis of liver failure. This article reviews the mechanism of action of immunoregulation (congenital and adaptive) and inflammatory injury (inflammation inducers, receptor cells, and inflammatory mediators) in the process of hepatic failure, as well as the interactions between immune response and immune cells and between inflammatory response and inflammatory factors, in order to help understand the pathogenesis of liver failure and provide new ideas for the diagnosis and treatment of liver failure and drug research and development.
5.Prevalence of human papillomavirus infection and risk of cervical cancer or precancerous lesions in 15 years follow up:a prospective cohort study
Qian ZHANG ; Shangying HU ; Ruimei FENG ; Li DONG ; Feng CHEN ; Xun ZHANG ; Qinjing PAN ; Junfei MA ; Shaodong SHI ; Fanghui ZHAO ; Youlin QIAO
Chinese Journal of Oncology 2016;38(10):792-797
Objective To evaluate the 15 years changing trends of prevalence of high risk HPV (HR?HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+) among a Chinese rural population. Methods The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province ( SPOCCS?I) and followed up by cytology and HR?HPV testing in the years of 2005, 2010, and 2014. The changes of HR?HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results The detection rates of HPV infection and CIN2+ were 15.7%?22.3% and 1.1%?4.3% for the baseline visit and the other 3 follow?ups, respectively. The cumulative risk of CIN2+ in HR?HPV positive women at baseline was significantly higher than HR?HPV negative women ( P<0.01) during the 15?year follow?up. The risk of CIN2+ in the four?times HPV positive group was 40. 0%, while the group with four?times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions The prevalence of HR?HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR?HPV positivity elevated the risk of CIN2+ compared to women whose HR?HPV test was negative. The risks of CIN2+incidence in 6 years were low among women with negative HR?HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5?6 years.
6.A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China
Yang YUNPENG ; Ma YUXIANG ; Sheng JIN ; Huang YAN ; Zhao YUANYUAN ; Fang WENFENG ; Hong SHAODONG ; Tian YING ; Xue CONG ; Zhang LI
Chinese Journal of Cancer 2016;35(5):19-24
Background: Bone metastases are common in patients with advanced cancer. Bisphosphonates (BPs) could prevent or delay the development of skeleton-related events (SREs). The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases. Methods: Consecutive cancer patients who had bone metastases and received BP treatment were enrolled. A ques-tionnaire was developed to collect the patients’clinical data, as well as information on the diagnosis and manage-ment of bone metastases. Physicians’awareness of the guidelines and knowledge of the application of BP were also assessed. Results: A total of 3223 patients with lung cancer (36.5%), breast cancer (30.9%), prostate cancer (8.5%), and gas-trointestinal cancer (5.7%) were included in this study. The sites of bone metastases were the thoracic spine (56.0 %), lumbar spine (47.1%), ribs (32.6%), and pelvis (23.2%). The SRE frequency was the highest in patients with multiple myeloma (36.6%), followed by those with lung cancer (25.9%), breast cancer (20.2%), prostate cancer (18.2%), and gas-trointestinal cancer (17.3%). Irradiation to the bone was the most frequent SRE (58% in lung cancer patients, 45% in breast cancer patients, and 48% in prostate cancer patients). Our survey also showed that 45.5% of patients received BP within 3 months after their diagnosis of bone metastases, whereas the remaining 54.5% of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases. The SRE frequency in the former group was significantly lower than that in the latter group (4.0% vs. 42.3%, P < 0.05). In patients with more than 6 months of continuous BP treatment, the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment (7.2 vs. 3.4 months, P < 0.05). In addition, 12.2% of the physicians were not aware of the efcacy of BP in preventing and delaying SRE. Only half (52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable. Conclusions: Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs. However, our survey also revealed that the proper application of BP was not as common as expected in China.
7.Prevalence of human papillomavirus infection and risk of cervical cancer or precancerous lesions in 15 years follow up:a prospective cohort study
Qian ZHANG ; Shangying HU ; Ruimei FENG ; Li DONG ; Feng CHEN ; Xun ZHANG ; Qinjing PAN ; Junfei MA ; Shaodong SHI ; Fanghui ZHAO ; Youlin QIAO
Chinese Journal of Oncology 2016;38(10):792-797
Objective To evaluate the 15 years changing trends of prevalence of high risk HPV (HR?HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+) among a Chinese rural population. Methods The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province ( SPOCCS?I) and followed up by cytology and HR?HPV testing in the years of 2005, 2010, and 2014. The changes of HR?HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results The detection rates of HPV infection and CIN2+ were 15.7%?22.3% and 1.1%?4.3% for the baseline visit and the other 3 follow?ups, respectively. The cumulative risk of CIN2+ in HR?HPV positive women at baseline was significantly higher than HR?HPV negative women ( P<0.01) during the 15?year follow?up. The risk of CIN2+ in the four?times HPV positive group was 40. 0%, while the group with four?times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions The prevalence of HR?HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR?HPV positivity elevated the risk of CIN2+ compared to women whose HR?HPV test was negative. The risks of CIN2+incidence in 6 years were low among women with negative HR?HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5?6 years.
8.Analysis on Premium Adjustment Mechanism of Critical Illness Insurance in China
Shaodong MA ; Chenggang LI ; Yang CHEN
Chinese Health Economics 2014;(5):20-23
Objective: By constructing the cash flow model, it proposed the premium adjustment mechanism of critical illness insurance(CII). Methods: Based on the practical data of critical illness insurance in China, it established some actuarial assumptions and cash flow model to simulate and analyze premium adjustment mechanism of CII. Results: ( 1) Because of the deterioration of critical illness incidence rate and the change of market interest rates , CII guaranteed premium usually resents pricing risk, which showed that the cash flow is negative, sometimes accumulated cash is negative; (2) based on the criteria of insurance cost adjustment, it is suggested that when the loss rate reached more than 70%, which could permit the insurance company adjust the premium, if the loss rate reached more than 80%, it needs to compulsory the insurance companies to adjust premium. Conclusion: The study proposes the mechanism of CII premium adjustment, provides guidance for practice.
9.Step sequential therapy in rescuing infantile postrenal acute renal renal failure induced by melamine
Geng MA ; Wenliang YU ; Yongji DENG ; Xuhua GE ; Zheng GE ; Yong LIU ; Rugang LU ; Shaodong ZHAO ; Dongmei CHEN
Chinese Journal of Emergency Medicine 2008;17(12):1241-1244
Objective To investigate clinical characteristics and emergency managements of postrenal acute renal failure(ARV)induced by melamine in infant.Method Fluid therapy for urine alkalization and hydration,cistoscope drainage and peritoneal dialysis step by step were exerted in those who had both a history of certain milk intake and ARF according to the definition of pediatric ARF which developed by Pediatric Nephrology Assembly of Chinese Pediatric Association in 1994.Results Thirty-four postrenal ARF cases with anuria due to melamine in Nanjing Children's Hospital of Nanjing Medical University were involved in the study.Seventy cases(50%)re-ceived fluid therapy only.Nine cases(26.5%)received fluid thempy and eistoscope drainagemand 4 cases (11.8%)received fluid therapy and cistoscope drainage and peritoneal dialysis.Four cases(11.8%)received ur-gent peritoneal dialysis due to severe hyperkalemia.All cases(100%)survived.The urine pH at the first day.the second day,and after the second day in those who just pass away urine were 6.1±1.0、6.5±0.7.5.3±0.4,respectively(F=4.563,P=0.026).Conclusions Fluid therapy for urine alkalization and hydration and stop sequential thempy are effective in infant with postrenal ARF induced by melamine.
10.Effects of SDF-1 on the chemotaxis of cord blood AC133+ cells
Yanping MA ; Lan MA ; Shaodong ZHAO ; Hua REN ; Junlan WANG ; Linhua YANG
Journal of Leukemia & Lymphoma 2008;17(5):331-333
Objective To explore the effects of the stromal cell-derived factor on chemotaxis of cord blood ACl33+ cells.Methods The optimal SDF-1 concentration is detected in Transwell system.Migration was calculated from the number of cells found to have passed through an 8-um pore size polycarbonate membrane.Results The chemotactic rate of fresh cord blood AC133+ cells increases along with the concentration of SDF-1,however,it tends to be stable when the concentration of SDF-1 reaches 150 ng/ml.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group with CXCR4-blocking antibody and the group without SDF-1.Conclusion Transwell Plate can simulate the phenomenon of cell crossing endothelium.The chemotactic rate of cord blood AC133+ cells increases progressively along with the concentration of SDF-1,however,the chemotactic rate tends to equability when SDF-1 reaches a certain concentration.The chemotactic rate does not have a marked change while continuing to increase the concentration of SDF-1.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group using CXCR4-blocking antibody and the group without SDF-1.


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