1.Mechanism of axonal transport dysfuction of mitochondria in Alzheimer's disease
Yihan SHEN ; Hanxiao XU ; Linhao JIANG ; Minhui XU ; Tianjiao XIA
Chinese Journal of Neuromedicine 2023;22(5):476-479
Alzheimer's disease (AD) is a central neurodegenerative disease with still unclear pathogenesis. Recent studies have shown that axonal transport dysfuction of mitochondria may contribute to AD progression. Normal mitochondrial axonal transport mainly involves microtubules, molecular motors and connexins, while AD early pathological changes can damage mitochondrial axonal transport by interfering with these proteins: accumulated β-amyloid (Aβ) impairs the function of molecular motors; abnormally modified Tau protein reduces microtubule stability; mutant presenilin-1 (PS1) can induce phosphorylation of some related proteins by activating glycogen synthase kinase-3β (GSK-3β); all these processes can damage mitochondrial axonal transport, leading to synaptic dysfunction. This review aims to clarify the possible mechanisms of axonal transport dysfuction of mitochondria in AD and provides new ideas for AD treatment.
2.Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1
Yanbin WANG ; Wei SHEN ; Yihan GAN ; Jin ZOU ; Yu ZHANG ; Lijin ZHU ; Li JU ; Zhaoqiang JIANG ; Shibo YING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(9):641-647
Objective:To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells.Methods:In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 μmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 μmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 μmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 μmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry.Results:The cell viability rate of MM cells was decreased after treated with PGZ ( P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group ( P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 μmol/L) as compared to the control group in MSTO-211H ( P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences ( P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H ( P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences ( P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion:Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.
3.Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1
Yanbin WANG ; Wei SHEN ; Yihan GAN ; Jin ZOU ; Yu ZHANG ; Lijin ZHU ; Li JU ; Zhaoqiang JIANG ; Shibo YING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(9):641-647
Objective:To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells.Methods:In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 μmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 μmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 μmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 μmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry.Results:The cell viability rate of MM cells was decreased after treated with PGZ ( P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group ( P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 μmol/L) as compared to the control group in MSTO-211H ( P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences ( P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H ( P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences ( P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion:Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.
4.Epidemiological study design of asymptomatic infection of the 2019 novel coronavirus
Na HE ; Yihan LU ; Liming LI ; Hongbing SHEN ; Weizhong YANG ; Zijian FENG
Chinese Journal of Epidemiology 2020;41(10):1577-1581
COVID-19 is caused by the 2019 novel coronavirus (2019-nCoV). COVID-19 clinical cases are considered as the principal source of infection, however, asymptomatic cases may also play a role in the transmission. Significant gap exists in terms of the proportion or prevalence and transmissibility of asymptomatic cases. This study design plans to use data from areas with different epidemiological profiles to investigate the COVID-19 epidemic in China. In each selected region, both general community residents and key populations at high risk of COVID-19 infection, including recovered COVID-19 cases, close contacts of confirmed COVID-19 cases, medical professionals, investigators at CDCs, and visitors to fever clinics, will be recruited and examined for viral RNA of 2019-nCoV and serum antibodies. Prevalence and characterization of asymptomatic cases will be determined, stratified by varied demographics and exposure risk. During the follow-up, the change in the serum antibodies will be studied prospectively in the symptomatic and asymptomatic cases to address the scientific and public health concerns of infectivity and transmissibility of 2019-nCoV.
5.Expression and clinical significance of 17β-HSD1 in malignant epithelial ovarian tumors
Yihan ZHAO ; Ying SHEN ; Shuyan DAI
Journal of China Medical University 2024;53(11):1012-1016,1024
Objective To detect 17β-hydroxysteroid dehydrogenase type 1(17β-HSD1)expression in malignant epithelial ovarian tumors and analyze its relationship with pathological features and prognosis.Methods The clinical data of 70 patients with malignant epithelial ovarian tumors,70 with borderline epithelial ovarian tumors,and 70 with benign epithelial ovarian tumors were retrospectively analyzed.Immunohistochemistry was used to detect 17β-HSD1 expression.The difference in 17β-HSD1 expression levels among three groups were compared,and the relationship between 17β-HSD1 expression and various clinicopathological features and prognosis was ana-lyzed.Results Malignant epithelial ovarian tumor tissues had high 17β-HSD1 expression that was closely related to FIGO stage,lymph node metastasis,and carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)levels(P<0.05),with no significant cor-relation with menopausal status,tumor differentiation degree,pathological type,and ascites(P>0.05).The 17β-HSD1 expression levels,preoperative CA125 and HE4 levels,tumor differentiation degree,and FIGO stage affected the prognosis of malignant epithelial ovarian tumors.Multivariate Cox regression analysis suggested that the 17β-HSD1 expression levels and FIGO stage were independent risk factors for malignant epithelial ovarian tumor.Conclusion Malignant epithelial ovarian tumors had high 17β-HSD1 expression,which is closely related to the occurrence and development of tumors and among the independent risk factors affecting the overall survival.
6.Resistance and transmission mechanisms of carbapenem-resistant Enterobacterales
Fang SHEN ; Jingjing QUAN ; Luxiang LIU ; Yihan MAO ; Dongdong ZHAO ; Yunsong YU
Chinese Journal of Microbiology and Immunology 2021;41(9):679-686
Objective:To investigate the resistance and transmission mechanism of carbapenem-resistant Enterobacterales (CRE), so as to provide the scientific evidence for the treatment and prevention of CRE infection.Methods:Seventy-six isolates of CRE isolated from Shaoxing Second Hospital between May 2016 and August 2018 were included. The isolates were re-identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The minimum inhibitory concentrations (MICs) of colistin, tigecycline, ceftazidime-avibactam, fosfomycin and other antibacterial drugs were determined using broth microdilution or agar dilution methods. PCR and sequencing analysis were performed to detect carbapenemase encoding genes ( blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48). Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to analyze homology of strains. S1-PFGE combined with Southern blot hybridization were used to locate the carbapenamase genes. Filter mating test were performed to determine the horizontal transfer ability of plasmids harboring carbapenamase genes. Results:Among the 76 isolates of CRE, 51 isolates were Klebsiella pneumoniae; 10 isolates were Escherichia coli; 15 isolates were other Enterobacterales. The 76 CREs were mainly isolated from urine, sputum and blood samples. The distribution rate of ICU was the highest (55.26%). The 76 CREs showed low resistance rates (0%, 1.33%, 18.42%) to colistin, tigecycline and ceftazidime-avibactam. The resistance rates to amikacin and fosfomycin were <45%, and the resistance rates to other drugs were >97%. The detection rate of KPC-2 carbapenemase was the highest (85.33%). The ST11 CRKP producing KPC-2 carbapenemase accounted for the highest proportion (62.75%), mainly distributed in the ICU (62.50%). Southern blot hybridization showed that blaKPC-2 was mainly located on a plasmid about 90 kb (39/63). Filter mating test showed that blaKPC, blaNDM and blaIMP could be transferred horizontally to recipient bacteria through plasmids. Conclusions:The 76 CRE isolates were only susceptible to a few antibacterial drugs, such as colistin, tigecycline and ceftazidime-avibactam. The production of KPC-2 carbapenemase was the main reason for the resistance of Enterobacterales to carbapenems. KPC-2 carbapenemase-producing ST11 Klebsiella pneumoniae was the main epidemic clone of carbapenem-resistant Klebsiella pneumoniae (CRKP). The 90 kb size plasmid was the main plasmid encoding blaKPC-2 gene. Carbapenemase genes can be transferred horizontally through plasmids. The hospital should strengthen prevention of nosocomial infections to control the clonal prevalence of CRE.
7.Atrial fibrillation detection using millimeter-wave radar
Hengji ZHOU ; Yihan YANG ; Yuanhui HU ; Yuguang CHU ; Xintian SHOU ; Yaping YOU ; Wenjing XUE ; Shaowei FAN ; Yong WANG ; Huiliang SHEN
Chinese Journal of Medical Physics 2024;41(1):81-87
A novel technology is proposed for non-contact and real-time detection of atrial fibrillation using millimeter-wave radar.A 60 GHz PCR millimeter wave radar is used to continuously detect the chest echo signal of the subject.After signal acquisition,I-Q signal is generated through I-Q demodulation,and the signal phase information is extracted using effective points phase trend evaluation for obtaining the signals from oscillations in the chest wall,from which the respiratory signals and cardiac signals are extracted through digital filtering for the analysis of cardiac movement.Whether the atrial fibrillation occurs or not is determined by the characteristics of atrial fibrillation wave in the time domain.The effective points phase trend evaluation for extracting more accurate signal phase information and the time-domain method for real-time atrial fibrillation detection are the innovations of the study.The experimental results show that the proposed method achieves a detection accuracy of 99.2%in clinic.
8. Involvement of autophagy in iron ion regulation promotes ferroptosis in cells undergoing intestinal ischemia-reperfusion injury
Jingyu ZHANG ; Yihan WANG ; Jun LI ; Ping JIN ; Yingbin WANG ; Jieting LIU ; Xiping SHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(1):36-41
AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n = 6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion + autophagy inhibitor group (I/R + 3-MA group). The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe
9.Efficacy and safety of transarterial chemoembolization combined with camrelizumab and apatinib in treatment of advanced hepatocellular carcinoma
Yihan YANG ; Wanci LI ; Binyan ZHONG ; Jian SHEN ; Xiaoli ZHU
Journal of Clinical Hepatology 2022;38(12):2755-2760
Objective To investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab and apatinib in the treatment of advanced hepatocellular carcinoma (HCC). Methods From July 2019 to June 2021, 19 patients with advanced HCC who met the inclusion and exclusion criteria in the First Affiliated Hospital of Soochow University were enrolled in this study. All patients received TACE combined with camrelizumab and apatinib. Tumor response was assessed according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST), and adverse events were assessed according to Common Terminology Criteria for Adverse Events (v5.0). The Kaplan-Meier method was used to analyze progression-free survival and overall survival and calculate 95% confidence interval (CI). Results The median follow-up time was 14.0 months for the 19 patients. As of the last follow-up based on mRECIST, 7 patients (7/19, 36.8%) achieved complete response, 9 (9/19, 47.4%) achieved partial response, and 2 (2/19, 10.5%) achieved stable disease. During follow-up, overall objective response rate and overall disease control rate reached 84.2% and 94.7%, respectively; the median duration of response reached 8.0 (3.4-13.0) months, and median progression-free survival reached 9.5 (95% CI : 4.7-14.3) months; the 6-month survival rate reached 100%, and the 12-month survival rate reached 78.9%. Among the 19 patients, 7 (36.8%) experienced serious adverse events. The most common adverse events of all grades included post-embolization syndrome after TACE (17/19, 89.5%), liver injury (14/19, 73.7%), hematologic toxicity (8/19, 42.1%), and proteinuria (8/19, 42.1%). Conclusion TACE combined with camrelizumab and apatinib has marked efficacy and controllable adverse events in the treatment of advanced HCC, which provides a potential new option for the first-line treatment of advanced HCC.
10.Accuracy and clinical outcome of a real-time surgical navigation system for the placement of quad zygomatic implants
Baoxin TAO ; Feng WANG ; Yihan SHEN ; Shengqi FAN ; Wei HUANG ; Yueping WANG ; Yiqun WU
Chinese Journal of Stomatology 2020;55(11):845-850
Objective:To evalute the accuracy and clinical outcome of a real-time navigation system for the placement of quad zygomatic implants.Methods:Twenty-four patients [9 males and 15 females, mean age was (50.8±14.7) years old], from January 2015 to December 2019, with 96 zygomatic implants placed under a real-time navigation system in Department of Second Dental Center and Department of Oral Implantology of Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine were included in the study. The preoperative and the postoperative multislice CT or cone-beam CT were fused to measure and record the entry, exit and angle deviation between the planned and placed implants. The implants were divided into groups according to implant insertion approach (real-time navigation and free-hand), implant length (<47.5 mm and ≥47.5 mm) and implant position (proximal and distal implant). And the differences of implant accuracy were analyzed. The intraoperative and postoperative complications were also recorded. The implant survival rate was evaluated after 6 months follow-up. A P value<0.05 indicates statistical significance. Results:The mean entry, exit and angle deviation of zygomatic implants were (1.49±0.64) mm, [2.03(1.58, 2.40)] mm and (2.49°±1.12°), respectively. The average entry, exit and angle deviation of the navigation guided implant insertion group were (1.45±0.60) mm, (1.96±0.44) mm and (2.66±1.13°) respectively, while those of the free-hand group were (1.50±0.64) mm, (2.04±0.79) mm and (2.50°±1.13°) respectively. There was no significant difference between the two groups ( P>0.05). The average entry, exit and angle deviation of the group with length<47.5 mm were (1.42±0.60) mm, (2.13±0.60) mm and (2.61°±1.08°) respectively and those of the group with length ≥ 47.5 mm were (1.52±0.65) mm, (1.98±0.82) mm and (2.43°±1.14°) respectively. No significant difference was found between the two groups ( P>0.05). In proximal implant group, the average entry, exit and angle deviation were (1.55±0.69) mm, (2.05±0.92) mm and (2.48°±1.16 °) respectively while those of distal implant group were (1.43±0.57) mm, (2.01±0.57) mm and (2.49°±1.10°), respectively. No significant difference was detected between the two groups ( P>0.05). All zygomatic implants were placed uneventfully. There were no intra-operative complications, and post-operative reversible complications developed in 3 patients. Two zygomatic implants were lost and the overall zygomatic implant survival rate was 97.9% (94/96) within a follow-up of 6 months. Conclusions:Quad zygomatic implant placement can be achieved with high accuracy and predictable clinical outcome under guidance of a real-time navigation system.