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.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.
3.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.
4. 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
5.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.