1.Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
ZOU HAI ; ZHANG MENGYU ; YANG XUE ; SHOU HUAFENG ; CHEN ZHENGLIN ; ZHU QUANFENG ; LUO TING ; MOU XIAOZHOU ; CHEN XIAOYI
Journal of Zhejiang University. Science. B 2024;25(9):756-772
Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
2.Research progress in the treatment of maxillary transverse deficiency with combined orthodontic-orthognathic approach
Yang WANG ; Xiaozhou MA ; Lina ZHANG ; Shujun DONG
Chinese Journal of Stomatology 2024;59(7):726-731
In combined orthodontic-orthognathic treatment, the maxillary palatine suture is closed in most patients with insufficient maxillary width, and bony expansion of the maxilla cannot be achieved by dental expansion or rapid palatal expansion (RPE) which causes buccal inclination of the maxillary posterior teeth leading to unstable results. Therefore, segmental LeFort Ⅰ osteotomy and surgically assisted RPE are often used in clinical practice. In recent years, with the application of implant anchorage technology, implant anchorage assisted RPE has been gradually applied in orthognathic treatment. This article reviewed the indications, contraindications, complications, efficacy and long-term stability in different treatment approaches including segmental LeFort Ⅰ osteotomy, surgically assisted RPE and implant-supported maxillary skeletal expansion.
3.Traditional Chinese Medicine Syndrome Element, Evolutionary Patterns of Patients with Hepatitis B Virus-Related Acute on Chronic Liver Failure at Different Stages: A Multi-Center Clinical Study
Simiao YU ; Kewei SUN ; Zhengang ZHANG ; Hanmin LI ; Xiuhui LI ; Hongzhi YANG ; Qin LI ; Lin WANG ; Xiaozhou ZHOU ; Dewen MAO ; Jianchun GUO ; Yunhui ZHUO ; Xianbo WANG ; Xin DENG ; Jiefei WANG ; Wukui CAO ; Shuqin ZHANG ; Mingxiang ZHANG ; Jun LI ; Man GONG ; Chao ZHOU
Journal of Traditional Chinese Medicine 2024;65(12):1262-1268
ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients, including 618 in the early stage, 355 in the middle stage, and 85 in the late stage, were collected from 18 clinical centers across 12 regions nationwide from January 1, 2012 to February 28, 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients, like the four diagnostic information (including symptoms, tongue, pulse) of traditional Chinese medicine (TCM), and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients, and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries, including 36 symptom information, 12 tongue information, and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF, which were liver-gallbladder damp-heat pattern, qi deficiency and blood stasis pattern, liver-kidney yin deficiency pattern, and spleen-kidney yang-deficiency pattern. In the early stage, heat (39.4%, 359/912) and dampness (27.5%, 251/912) were most common, and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern (74.6%, 461/618); in the middle stage, dampness (30.2%, 187/619) and blood stasis (20.7%, 128/619) were most common, and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern (53.2%, 189/355), and qi deficiency and blood stasis pattern (27.6%, 98/355); and in the late stage, the pattern of the disease was dominated by qi deficiency (26.3%, 40/152) and yin deficiency (20.4%, 31/152), and the patterns were dominated by qi deficiency and blood stasis pattern (36.5%, 31/85), and liver-gallbladder damp-heat pattern (25.9%, 22/85). ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF, presenting an overall trend of evolving patterns as "from excess to deficiency, transforming from excess to deficiency", which is damp-heat → blood stasis → qi-blood yin-yang deficiency.
4.Assessment of dynamic cerebral autoregulation in pilots after acute positive acceleration exposure
Yanchun YOU ; Minghao YANG ; Xiao ZHANG ; Jinjin LIU ; Xiaozhou FAN ; Siguo SUN ; Xi LIU
Chinese Journal of Ultrasonography 2024;33(3):242-246
Objective:To explore the changes of dynamic cerebral autoregulation ability in pilots exposed to acute positive acceleration(+ Gz) by transcranial Doppler combined with beat-to-beat blood pressure.Methods:A total of 26 pilots enrolled in the + 8Gz manned centrifuge trial at the Air Force Medical Center, Air Force Medical University from June to October 2022 were prospectively included. Blood pressure and heart rate were monitored in the resting state before the trial and within 5 min after centrifugation. Transcranial Doppler combined with noninvasive continuous beat-to-beat blood pressure monitor were used to detect bilateral middle cerebral artery blood flow velocity and beat-to-beat pulse pressure respectively. The transfer function analysis was applied to derive the parameters of cerebral blood flow autoregulation in each frequency band from 0.02 to 0.50 Hz, and the phase, gain and coherence were calculated. The above parameters were compared between resting state and after acute + 8Gz positive acceleration exposure.Results:Compared with the resting state, in all of the 26 pilots after acute + 8Gz positive acceleration exposure, the systolic and diastolic blood pressure and heart rate increased significantly ( P<0.001), the phase significantly increased and the gain significantly decreased in the ultra-low frequency band (0.02-0.07 Hz) ( P<0.05); whereas there were no statistical differences of gain and phase in the low frequency band (0.07-0.20 Hz) and the high frequency band (0.20-0.50 Hz) (all P>0.05). Conclusions:Transcranial Doppler combined with beat-to-beat pulse pressure can be used for the assessment of changes in immediate dynamic cerebral autoregulation after acute + Gz exposure, and transfer function analysis of ultra-low frequency band parameters is suitable for this type of evaluation.
5.Clinical characteristics of acute renal infarction: an analysis of 15 cases
Yinyin XIE ; Zhanwu LI ; Xiaozhou WANG ; Lei JIANG ; Qiang LIU ; Hao QIN ; Fangjun YANG
Chinese Journal of General Practitioners 2023;22(7):728-731
Clinical data of 15 patients diagnosed with acute renal infarction (ARI) in Affiliated Zhongshan Hospital of Dalian University from Jan 2011 to Dec 2021 were retrospectively analyzed. Of the included 15 patients, there were 14 cases of cardiac origin and 1 case of antiphospholipid syndrome. We found that there were 12 cases of atrial fibrillation, 2 cases of atrial premature beats, 12 cases of elevated level of D-dimer, 15 cases of elevated level of LDH, 11 cases of positive urine occult blood and positive urine protein. Among the 15 patients, catheter-directed thrombolysis was performed in 4 cases, of which 3 cases were revascularized successfully, intravenous thrombolysis in 2 cases and alone anticoagulation therapy in 9 cases. It is suggested that CECT or CTA can assist the early diagnosis of ARI especially in patients with acute onset and persistent abdominal pain with high risk factors of thromboembolism, high levels of LDH, microscopic hematuria and/or proteinuria. Despite prolonged embolic ischemia, try to reconstruct blood flow to save the kidney as much as possible. Late standardized anticoagulant therapy is of critical importance to prevent recurrent embolic episodes.
6.Genetic analysis of a fetus with mosaicism Y chromosome aberration.
Fanrong MENG ; Duan JU ; Xiuyan WANG ; Yunfang SHI ; Meng YANG ; Xiaozhou LI
Chinese Journal of Medical Genetics 2023;40(11):1414-1419
OBJECTIVE:
To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion.
METHODS:
A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination.
RESULTS:
Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17]. FISH showed that 69% of the cells had contained Y chromosome signals. The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g.13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance.
CONCLUSION
The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.
Female
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Pregnancy
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Male
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Humans
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Mosaicism
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DNA Copy Number Variations
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In Situ Hybridization, Fluorescence
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Y Chromosome
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Fetus
7.A study on the impact of long working hours on the psychological health of medical personnel in third class hospitals
Ningbin QUAN ; Jin WANG ; Yuhao WANG ; Ru JIN ; Daoyu YANG ; Jinbi PENG ; Yicen GU ; Yuhao HAN ; Jingyi LU ; Zhao ZHANG ; Luyao XU ; Shuling HUANG ; Xiaozhou SU ; Xudong LI
The Journal of Practical Medicine 2023;39(24):3267-3274
Objective To understand the characteristics of long-working hours exposure of medical staff,and analyze the impact of long-working hours exposure on mental health problems such as occupational stress,depression,fatigue accumulation,and insomnia.Methods The cluster random sampling method was used to select the medical staff of 12 tertiary general hospitals in Guangdong Province as the research subjects,and the"Core Scale of Occupational Stress Measurement"and other scales were used to evaluate their occupational mental health.Results The average working hours of medical staff per day were(8.99±2.18)h;2,094 people were exposed during long working hours,accounting for 78.96%.The results of binary logistics regression analysis showed that after excluding the influence of sociodemographic factors such as age,long working hours(weekly working hours greater than 40 h)were the risk factors for occupational stress,depressive symptoms and fatigue accumulation of medical staff(P<0.01),and the longer the working week,the higher the risk of occupational stress,depressive symptoms and fatigue accumulation.Weekly working hours greater than 48 hours are risk factors for insomnia(P<0.01).Conclusion Long working hours are common among delivery workers on food delivery platforms,and long working hours are a risk factor for occupational tension and fatigue.
8.An outbreak of norovirus diarrhea in a welfare home for the elderly in Shanghai
Wenjia XIAO ; Xiaozhou KUANG ; Jing ZHANG ; Jixing YANG ; Yuan NAN ; Hong YAO ; Zheng TENG ; Sheng LIN ; Xiaohuan GONG ; Xiao YU ; Hao PAN ; Xi ZHANG
Shanghai Journal of Preventive Medicine 2022;34(8):765-769
ObjectiveTo investigate an outbreak of norovirus diarrhea in a welfare home for the elderly in Shanghai, and to analyze the epidemiology and virus genotype characteristics of the epidemic, thus providing a scientific basis for the prevention and control of norovirus epidemic. MethodsCase definition was clarified. After case definition, a standardized questionnaire was used to carry out case investigation to make comprehensive analysis in combination with field epidemiological investigation and laboratory tests results. ResultsThe epidemic lasted for 14 days, and 23 cases were reported with an incidence rate of 12.37% (23/186), including 3 males and 20 females. There were more cases on the 1st, 4th and 6th floor of the main building in the welfare home, accounting for 52.17% (12/23) of total cases. 19 cases were reported in the main building, with an incidence rate of 11.59% (19/164); 4 cases were reported in the auxiliary building, with an incidence rate of 18.18% (4/22). There was no significant difference in the morbidity between the main building and the auxiliary building (χ2=0.779,P>0.05). The main clinical manifestations were vomiting and diarrhea. There was a significant difference in the incidence of vomiting symptoms among the elderly, nursing staff and other staff in the welfare home (χ2=10.216, P<0.05). But there was no significant difference in the incidence of diarrhea among the elderly, nursing staff and other staff (χ2=1.218, P>0.05). Fecal samples were collected from 23 cases, 1 case family member, 68 risk personnel and 14 environmental surface swab samples. Norovirus GⅡ was detected in stool samples of 19 cases, 1 family member and 36 risk personnel. ConclusionOutbreak of norovirus infection is reported in a welfare home in Shanghai. The close contact between the elderly and health workers might lead to the outbreak.
9.Effect of Calycosin-mediated GP130/JAK/STAT Signaling Pathway on Oxidative Injury of Astrocytes in Spinal Cord
Dehua GUO ; Xiaozhou LIU ; Chenglin WU ; Yang XU ; Guofu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):54-61
ObjectiveTo investigate the effect of calycosin-mediated glucoprotein130/Janus kinase/signal transducer and activator of transcription factor (GP130/JAK/STAT) signaling pathway on oxidative injury of astrocytes in spinal cord. MethodAstrocytes in rat spinal cord were isolated and identified by immunofluorescence detection of glial fibrillary acidic protein (GFAP). The cells were respectively pre-treated with 5, 10, 20 μmol·L-1 calycosin for 12 h, and then 100 μmol·L-1 H2O2 (24 h) was added to induce oxidative injury. Cell counting kit-8 (CCK-8) assay was employed to detect cell proliferation and select the optimal concentration of calycosin. The following experimental groups were designed: control group, model group (100 μmol·L-1 H2O2), calycosin group (20 μmol·L-1 calycosin), calycosin + LY294002 group (20 μmol·L-1 calycosin + 10 μmol·L-1 LY294002), and calycosin + Stattic group (20 μmol·L-1 calycosin + 3 μmol·L-1 Stattic). CCK-8 assay and immunofluorescence method were used to detect the proliferation of cells and flow cytometry was applied to detect cell apoptosis and cycle. The protein expression of phosphorylated (p)-JAK2, p-STAT3, p-protein kinase B (Akt), GP130, and interleukin-6 (IL-6) was detected by Western blotting. ResultCompared with the control group, the model group showed low proliferation activity and high apoptosis rate of cells (P<0.05). Compared with the model group, calycosin (20 μmol·L-1) group displayed high proliferation activity and low apoptosis rate of cells (P<0.05). Compared with calycosin (20 μmol·L-1) group, both phosphatidylinosirtol-3-kinases (PI3K) inhibitor LY294002 and STAT3 inhibitor Stattic significantly reduced the proliferation activity and increased the apoptosis rate of cells (P<0.05). The protein expression of p-JAK2, p-STAT3, p-Akt, GP130, and IL-6 in the model group was higher than that in the control group (P<0.05), and the expression of the above indicators was lower in each treatment group than in the model group (P<0.05). ConclusionCalycosin can promote the proliferation and inhibit the apoptosis of astrocytes with oxidative injury by inhibiting the phosphorylation of PI3K/Akt pathway and JAK2/STAT3 pathway.
10.Study on rAd5F35-SIVenvT vaccine in combination with rMVA-SIVenvT vaccine in mice
Xiaozhou HE ; Jing YANG ; Hongxia LI ; Yanzhe HAO ; Xia FENG
Chinese Journal of Microbiology and Immunology 2021;41(6):455-459
Objective:To analyze the immune response in mice after immunization with vaccine of rAd5F35-SIVenvT in combination with rMVA-SIVenvT to evaluate the efficacy of different immunization strategies.Methods:Two recombinant viruses were identified in vitro by PCR and Western blot. The BALB/c mice were immunized with homologous and heterologous immune strategies. The numbers of splenic lymphocytes secreting IFN-γ were measured by ELISPOT assay, meanwhile SIV gp120 antibody titer were measured by ELISA assay. Results:SIVenvT protein was expressed effectively by rAd5F35-SIVenvT and rMVA-SIVenvT in HEK293 cells. The specific immune response reached its peak at 4-week post first immunization, then decreased. SIV Env specific cellular immune response and SIV gp120 specific antibody could be detected at 4-16 weeks post first immunization. The specific cellular response was significant stronger in heterologous immunization group than homologous group at 4 week and 16 week. Furthermore, heterologous immunization induced significant higher titer of SIV gp120 antibody at 4 week than homologous group.Conclusions:Specific immune response induced by rAd5F35-SIVenvT in combination with rMVA-SIVenvT was stronger than homologous vector immunization. The results provided references for further study in nonhuman primates.

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