1.The experimental study of wild-type p53 and double suicide gene for interventional therapy in liver carcinoma
Tong DU ; Hongxin NIU ; Xikun ZHANG ; Ruogu WANG
Chinese Journal of Hepatobiliary Surgery 2013;19(8):606-610
Objective To investigate interventional procedures and polygene feasibility for the treatment of liver carcinoma.Methods pCMV-p53 plasmid-liposome complex and concentrated TKCD retrovirus of supernatant liquid were prepared along with rabbit VX2 liver tumor models of 50 adult New Zealand rabbits.VX2 liver tumors about 2 cm in diameter from 45 adult rabbits were randomly divided into 5 groups of 9.Group 1 was the control group that used 0.9% sodium chloride as a placebo.Group 2 had transcatheter arterial embolization with lipiodol as treatment.Group 3 was the lipiodol and p53 group.Group 4 was the lipiodol and TK/CD group.Group 5 was the lipiodol,p53,and TK/CD group.The microtubule(1.2f)was inserted from the femoral to hepatic artery,tumor supply arteries were demonstrated by angiograms,and the drug was slowly injected under x-ray.The VX2 liver tumors were examined with B-ultrasound and computed tomography for maximum diameter (a) and minimum diameter (b) before and 10 days after interventional therapy.Gross tumor volume (V=ab2/2) and tumor growth rate were calculated.All the adult rabbits were euthanized 8 weeks after interventional therapy (including natural deaths).Histopathological examination was taken and survival time was observed.Results The tumor volume among the 5 groups had no significant difference before interventional therapy (P>0.05).Ten days after interventional therapy,analysis of the tumor volume for variance and the T-test were carried out.The results showed that each group compared to the control showed a significant difference in inhibiting cancer growth (P<0.05).The lipiodol,p53,and TK/CD group showed the best effect.According to factorial statistic analysis (2x2),p53 or TK/CD combined with lipiodol therapy can control the tumor obviously,but no mutual synergism effect was found (P=0.793).Each treatment group showed a significant difference of prolonged survival time compared to the control group (P<0.01).The multi-treatment or multi-gene group showed the best curative effects.Conclusions Interventional therapy can be the ideal path for administering medications for gene therapy.Transcatheter arterial embolization with lipiodol,wild-type p53 gene,TK/GCV,and CD/5-Fc applied in combination can control tumor growth and prolong survival time.
2.Diagnostic value of dobutamine-stressed cardiac morphing myocardial perfusion imaging for coronary artery disease in middle-aged patients
Cheng CHANG ; Wenhui XIE ; Bei LEI ; Lihua WANG ; Ruogu LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;(1):54-58
Objective To evaluate the diagnostic value of dobutamine?stressed cardiac morphing ( CM) MPI ( CMMPI) for coronary artery disease ( CAD) in middle?aged patients. Methods A total of 97 middle?aged patients (52 males, 45 females, age 40-65 (52.98±7.74) years) from March 2011 to Febru?ary 2015 with chest distress, cardiopalmus and chest pain symptoms ( suspected CAD) were retrospectively studied. Informed consents were signed by patients before examination. All patients underwent one?day dobu?tamine?stressed/rest CMMPI and CAG within one month. The diagnostic value of CMMPI was assessed and compared with CAG. Results CMMPI revealed 42 abnormal cases and 9 normal cases in 51 cases with cor?onary artery stenosis by CAG. CMMPI found 11 abnormal cases and 35 normal cases in 46 cases with normal coronary artery by CAG. In comparison with CAG, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CMMPI were 82.35%(42/51), 76.09%(35/46), 79.38%(77/97), 79.25%(42/53)and 79.55%(35/44) respectively. The side effect was slight and transient with an inci?dence of 82.47%(80/97). Conclusion The dobutamine?stressed CMMPI has an important value for the diagnosis of CAD and the assessment of myocardial damage in middle?aged patients.
3.Integrated database-based Screening Cohort for Asian Nomadic descendants in China (Scan-China): Insights on prospective ethnicity-focused cancer screening
Yuelin YU ; Liying QIAO ; Jing HAN ; Weiwei WANG ; Weiwei KANG ; Yunjing ZHANG ; Shu SHANG ; Ruogu MENG ; Lin ZHUO ; Siyan ZHAN ; Yunfeng XI ; Shengfeng WANG
Epidemiology and Health 2023;45(1):e2023048-
Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered—namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants’ onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.
4.Epidemiology of CRKP Infection Outbreak in a Neonatal Intensive Care Unit
Weijie LI ; Liqin CHEN ; Yaling LI ; Yonghui HAN ; Xiaojuan LI ; Ruogu WANG
Journal of Kunming Medical University 2023;44(12):144-149
Objective To analyze the epidemiological characteristics of an outbreak of carbapenem resistant Klebsiella pneumoniae(CRKP)hospital infection in the neonatal intensive care unit(NICU),and to explore possible causes of the outbreak.Methods Case analysis,epidemiological studies and environmental detection methods were used to investigate the detection of CRKP in the NICU of a hospital from March 11,2022 to May 3,2022,and the causes and corresponding prevention and control measures were analyzed.Results This CRKP outbreak in the NICU occurred in two phases.The first phase was from March 11,2022,to March 30,2022,during which 3 people contracted CRKP hospital infections.The second phase was from April 13,2022,to May 3,2022,during which 4 people contracted CRKP hospital infections.The source of the hospital infection outbreak was patient No.1.All 13 CRKP cases showed sensitivity only to amikacin and tigecycline,with intermediate sensitivity to levofloxacin,and high resistance to other antibiotics.All 13 CRKP cases carried resistant genes for metalloenzymes.After the outbreak,the ward environment was sampled three times,with 35 samples taken in total,and 14 of them tested positive for CRKP.After strict environmental cleaning,disinfection,and multiple control measures,no new hospital infection cases similar to this outbreak were detected after May 13,2022.Conclusion The outbreak of NICU hospital infections may be due to the contamination of the ward environment,medical equipment,and inadequate hand hygiene of medical staff,leading to its spread.Therefore,strict cleaning and disinfection of the environmental surfaces,strengthening hand hygiene of medical staff,and implementing multiple measures can effectively control hospital infections of CRKP.
5.Expressions of HSP90α and HSP90β in colorectal cancer tissues and their clinical significances
Cunbao CHEN ; Shoutang LU ; Ruogu WANG ; Jianshu YANG ; Jianqi LI ; Yanan ZHEN ; Zhongfa XU
Journal of International Oncology 2022;49(5):282-285
Objective:To study the expressions of heat shock protein (HSP) 90α and HSP90β in colorectal cancer and paracancer tissues, and to investigate the relationships between HSP90α, HSP90β and clinicopathological features of colorectal cancer patients, and to analyze their correlation.Methods:The tumor tissues and paracancer tissues of 117 patients with colorectal cancer were selected from the Department of Gastrointestinal Surgery, Third Affiliated Hospital of Shandong First Medical University from January 2016 to December 2020. The expression levels of HSP90α and HSP90β were detected by immunohistochemistry, and the relationships between the two proteins and clinicopathological features and the correlation of their expressions were analyzed.Results:The positive expression rates of HSP90α in colorectal cancer tissues and paracancer tissues were 74.4% (87/117) and 12.0% (14/117) , and there was a statistically significant difference ( χ2=92.83, P<0.001) . The positive expression rate of HSP90β in colorectal cancer tissues and paracancer tissues was 61.5% (72/117) and 10.3% (12/117) , and there was a statistically significant difference ( χ2=66.86, P<0.001) . The expression of HSP90α was correlated with tumor location ( χ2=8.67, P=0.003) , vascular invasion ( χ2=8.68, P=0.003) , lymph node metastasis ( χ2=8.52, P=0.004) , T stage ( χ2=21.07, P<0.001) , N stage ( χ2=11.94, P=0.003) , M stage ( χ2=5.37, P=0.020) , pathological stage ( χ2=25.64, P<0.001) . The expression of HSP90β was correlated with lymph node metastasis ( χ2=4.03, P=0.045) , T stage ( χ2=11.09, P=0.007) , N stage ( χ2=6.56, P=0.038) , M stage ( χ2=12.43, P<0.001) , pathological stage ( χ2=17.34, P=0.001) . There was a positive correlation between the expressions of the two proteins in colorectal cancer tissues ( r=0.42, P<0.001) . Conclusion:The expressions of HSP90α and HSP90β in colorectal cancer tissues are significantly higher than those in paracancer tissues, and they are related to lymph node metastasis and pathological stage. There is a positive correlation between the two proteins, which may be involved in the occurrence and development of colorectal cancer and are expected to become new tumor markers.
6.Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM.
Lu ZHANG ; Yao ZHAO ; Ruogu GAO ; Jun LI ; Xiuna YANG ; Yan GAO ; Wei ZHAO ; Sudagar S GURCHA ; Natacha VEERAPEN ; Sarah M BATT ; Kajelle Kaur BESRA ; Wenqing XU ; Lijun BI ; Xian'en ZHANG ; Luke W GUDDAT ; Haitao YANG ; Quan WANG ; Gurdyal S BESRA ; Zihe RAO
Protein & Cell 2020;11(7):505-517
Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.