1.Neuroprotective effects and mechanisms of osteocalcin in an Alzheimer's disease cell model
Lilin FANG ; Qifeng ZHU ; Mingda ZHANG ; Man CUI ; Shijin LU ; Yu YAN
Journal of Army Medical University 2025;47(16):1883-1893
Objective To explore the neuroprotective effects of osteocalcin(OCN)on an Alzheimer's disease(AD)cell model and its potential mechanisms,providing a scientific basis for new therapeutic targets for AD.Methods Human neuroblastoma cell line SH-SY5Y was treated with 40 nmol/L okadaic acid(OA)for 24 h to establish an AD cell model.The cells were divided into a normal group(untreated SH-SY5Y cells),a model group(40 nmol/L OA intervention),and an OCN intervention group(intervention with various concentrations of OCN in the AD cell model),and AKT knockout/overexpression groups(AKT-KO group and AKT-OE group),and AKT-KO OCN group and AKT-OE OCN group.CCK-8 assay was used to detect the changes in cell viability.Wright's staining was employed to observe the morphological changes of AD cells.Western blotting was utilized to detect the protein levels of Tau,p-Tau,Bax,Bcl-2,Caspase-3 and their lytic types,as well as the expression of Tau,p-Tau,mTOR,AKT and p-AKT in each group after AKT knockout/overexpression.TUNEL staining and flow cytometry were applied to detect the changes in early and late apoptotic cells and the apoptotic rate in the OCN-treated AD cell model.Results ①Compared to the normal group,the model group exhibited a significant decrease in cell viability,noticeable morphological and structural damage,upregulation of p-Tau and Caspase-3,increased early and late apoptosis,and a significantly higher apoptotic rate(P<0.05).②After treatment of different concentrations of OCN for 24 h,cell viability was increased to varying degrees compared to the AD model group,with the 100 pg/mL OCN group showing a significant increase in cell viability(P<0.01)and marked improvement in cell number and morphology(P<0.01).③ Compared to the AD cell model group,the p-Tau/Tau ratio was decreased in all OCN treatment groups,particularly in the 100 pg/mL OCN intervention group,where the p-Tau/Tau ratio was significantly lower than that of the model group(P<0.01).④ Compared to the model group,a significant concentration-dependent decrease in the Cleaved Caspase-3/Caspase-3 ratio was observed when OCN concentrations ranged from 1 to 100 pg/mL,with a significant reduction in the Bax/Bcl-2 ratio in the 100 pg/mL group(P<0.000 1).⑤ The results of TUNEL staining and flow cytometry showed that,compared to the model group,all concentrations of OCN effectively inhibited the apoptosis in the AD model cells,with a significant reduction in early and late apoptotic cells and apoptotic rate in the 100 pg/mL OCN group.⑥ Compared with the control group and the model group,the P-AKT was significantly increased in the AKT-OE group after AKT overexpression(P<0.05).The expression level of AKT protein was decreased in the AKT-KO group after AKT knockout(P<0.05).When the AKT pathway was inhibited,the expression level of p-Tau was higher in the AKT-KO group than the control group(P<0.05),and when the AKT was overexpressed,the expression level was significantly inhibited(P<0.05).Conclusion OCN may inhibit cell apoptosis and reduce p-tau protein level by regulating the ratio of Caspase-3/Caspase-3 and Bax/Bcl-2,and thereby improve the morphology of AD model cells and effectively protect nerve cells,which may be related to the regulation of the AKT/mTOR pathway.
2.Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy
Youzhao MA ; Mingda ZHU ; Jingyang ZHANG ; Minhao LV ; Xiuchun CHEN ; Zhenzhen LIU
Cancer Research and Treatment 2023;55(4):1210-1221
Purpose:
Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT).
Materials and Methods:
The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined.
Results:
Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016).
Conclusion
Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.
3.A case of reversible splenial lesion syndrome characterized by increased antithyroid antibodies
Shan ZHU ; Qingqing ZHAO ; Mingda AI
Chinese Journal of Neurology 2022;55(2):159-163
Reversible splenial lesion syndrome (RESLES) is a rare clinical imaging syndrome caused by various etiologies and has no specific clinical manifestations, of which magnetic resonance imaging is characterized by reversible splenial lesion. Its etiology is complex, with infection more common, rare due to thyroid disease.The clinical data of a patient of RESLES with significantly increased anti-thyroid antibody are reported to enrich the etiology and further improve the understanding of the disease.
4.Delayed central nervous system damage caused by chlorfenapyr-indoxacarb poisoning: a case report
Shan ZHU ; Mingda AI ; Hong XU ; Chunhua WU ; Qi ZHAO
Chinese Journal of Neurology 2021;54(10):1055-1058
Chlorfenapyr and indenocarb are two new insecticides widely used in the world. In recent years, there have been a few cases of human being being poisoned by chlorfenapyr or indenocarb respectively at home and abroad, but no cases of poisoning caused by chlorfenapyr or indenocarb have been reported. A case of delayed central nervous system damage after chlorfenapyr and indoxacarb poisoning was reported for clinical reference.
5.Social cognitive impairment in patients with stroke
Shan ZHU ; Xinjie CHENG ; Mingda AI ; Xiaolei LIU
International Journal of Cerebrovascular Diseases 2020;28(9):701-708
In recent 10 years, social neuroscience has developed rapidly, which integrates social psychology, cognitive neuropsychology, and neuroscience, and puts forward the concept of social cognition. Clinical studies have shown that social cognitive impairment is easy to occur after stroke, which seriously affects the neurological rehabilitation and quality of life of patients. This article reviews the concept, mechanism, clinical manifestations, neuropsychological evaluation and intervention measures of social cognitive impairment in stroke patients, hoping to improve neurologists' awareness of the social cognitive impairment in stroke patients, actively prevent the occurrence of social cognitive impairment after stroke, and give corresponding intervention, so as to help patients better adapt to social life.
6.Application of nasal continuous positive airway pressure preferential ventilation strategy in the treatment of infant severe pneumonia
Jiuwei DONG ; Bin ZHU ; Xiaohua JIANG ; Mingda TIAN ; Yujing SUN ; Weiqiang ZHANG
Chinese Journal of Postgraduates of Medicine 2016;39(11):989-992
Objective To investigate the value of nasal continuous positive airway pressure (NCPAP) in the treatment of severe pneumonia. Methods The clinical data of 59 severe pneumonia infants who received NCPAP preferential ventilation strategy were retrospectively analyzed. Results After treatment, 50 infants were effective and 9 infants were ineffective. Before treatment, the age, RR, HR between effective group and ineffective group had no significant differences (P>0.05). But the levels of PaCO2, PaO2/FiO2 in ineffective group were significantly higher than those in effective group and the level of PaO2 in ineffective group was significantly lower than that in effective group (P<0.05). In effective group, the levels of PaO2 and PaO2/FiO2 were significantly increased after treatment for 1, 12 and 24 h, and the levels of PaCO2, RR and HR were significantly decreased (P<0.01). Conclusions NCPAP preferential ventilation strategy can reduce the use of invasive mechanical ventilation, improve oxygenation, ease dyspnea and make vital signs stable.
7.Simultaneous Determination of Active Components and Anti-diabetic Drugs in Propolis Health Foods by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry
Mingda ZHU ; Wei MA ; Dongdong CHEN ; Tao PENG ; Shujuan LI ; Guanghua ZHAO ; Yingzhang TANG
Chinese Journal of Analytical Chemistry 2010;38(2):169-174
A comprehensive analytical method based on ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of active components and anti-diabetic) drugs in propolis health foods. The samples were extracted by ultrasound extraction with methanol). The insoluble residue of extract was removed by freeze-centrifuging. The analysis was performed on an ACQUITY UPLC C_(18)) column(50 mm ×1 mm, i.d., 1.7 μm) utilizing a gradient elution profile and a mobile phase of 0.3% formic acid in water and acetonitrile. The analytes were detected using an electro spray ionization tandem mass spectrometry with multiple reaction monitoring. Qualitative and quantitative analysis was based on the peak area of the parent ion and two fragment ions. The LOD and LOQ level for 14 active components ranged from 0.7 mg/kg to 42.0 mg/kg and 2.2 mg/kg to 140 mg/kg respectively, and recoveries were 77.8%-113.6%, with the intra- and inter-day precision less than 15%. The LOD and LOQ level for 9 anti-diabetics) ranged from 0.1 mg/kg to 0.9 mg/kg and 0.3 mg/kg to 2.5 mg/kg respectively, and recoveries) were 79.3%-108.5%, with the intra- and inter-day precision less than 15%. The method is simple) and sensitive, and can be used for quality control of propolis.
8.Simultaneous Determination of 11 Appetite Suppressants in Weight-loss Functional Foods by Accelerated Solvent Extraction- High Performance Liquid Chromatography Tandem Mass Spectrometry
Wei MA ; Tao PENG ; Mingda ZHU ; Xiaojuan LI ; Qiang MA ; Dongdong CHEN ; Li LI ; Wei GUO ; Yingzhang TANG
Chinese Journal of Analytical Chemistry 2009;37(11):1583-1589
An analytical method based on high performance liquid chromatography tandem mass spectrometry has been developed for the determination of 11 appetite suppressants (fenfluramine,phenylpropanolamine,sibutramine,sertraline,rimonabant,bupropion,citalopram,fluoxetine,benfluorex,topiramate,zoni-samide). Various weight-loss functional foods were extracted under accelerated solvent extraction and separated on Waters Atlantis T3( 150 mm×2.1 mm,3μm) column. The analysis was carried out on HPLC-MS/MS by electrospray ionization using multiple reaction monitoring. Identification was achieved by ihe retention time and the ion ratio,quantification was done by the external standard curves. The limits of detection for the appetite suppressants were 0.05-4.0 mg/kg. The mean recoveries at the three spiked levels(low,middle,high) were 78.3% - 103. 6% ,with the intra-day precision less than 12% and the inter-day precision less than 15%. The method is reliable,sensitive,reproducible,and adapts to the determination of the appetite suppressants in different weight-loss functional foods.
9.Clinical Study on the Method of Reinforcing Qi,Strengthing Spleen and Clearing Heat Antitoxicant in Treating Ulcerative Colitis
Sifang ZHANG ; Weiguang ZHU ; Mingda HE
Chinese Journal of Information on Traditional Chinese Medicine 2006;0(07):-
Objective To investigate the therapeutic effect on ulcerative colitis by methods of reinforcing qi,strengthing spleen and clearing heat antitoxicant. Methods 99 patients were divided into two groups randomly:the treatment group for oral and enteroclyste use with TCM following in the principle mentioned above,the control group for oral and enteroclyste use with western medicine following in the common practice. Comparative studies on the total therapeutic effect and the improvement of TCM syndromes between the two groups were made. Meanwhile,the Pearson correlation analysis were made to explore the relationship between the clinical effectiveness and impact factors in two groups. Results There were significant differences in the total curative effect and the improvement of TCM syndromes between two groups (P
10.The manufacturing and clinical application of heterogenous acellular dermal matrix.
Duyin JIANG ; Bi CHEN ; Mingda XU ; Dahai HU ; Chaowu TANG ; Xiongxiang ZHU
Chinese Journal of Burns 2002;18(1):15-18
OBJECTIVETo lower down the antigenicity of heterogenous swine acellular dermal tissue, and to explore the feasibility of clinical using it as a composite graft for human patients.
METHODSSplit-thickness skin was harvested from healthy swines and then processed by two methods. The swine acellular dermal matrix (sADM) was prepared by removing cells from the skin with trypsin and Triton X-100. Then the cross-linked sADM (sADM(1)) and non-cross-linked sADM (sADM(0)) were embedded subcutaneously in rabbits and also transplanted onto the burn wounds of patients. The histological changes and also transplantation results were observed.
RESULTS(1) In animals with sADM(0) embedded subcutaneously, the grafted tissue was invaded immediately by host cells with obvious inflammatory reaction and tissue degradation. But there was less inflammatory reaction, and with no obvious skin degradation and contraction with sADM(1). (2) In ten burn patients with III degree burn wounds and one patient with wound in chest after scar removal, sADM and ultra-thin skin (UTS) composite graft were grafted on the wounds with autologous thin skin (ATS) and autologous razor-thin or UTS as the control. Nineteen pieces of composite skin of sADM with UTS were grafted on the wounds with survival rate of 78.9%, exhibiting no evident difference with that of ATS. When sADM(0) and UTS were grafed, there exhibited remarkable early inflammatory reaction and wound contraction with similar external appearance with that of UTS. Whereas when sADM(1) and UTS were grafted, there appeared less early inflammatory reaction and wound contraction, resulting in an even appearance and soft to touch similar to that with ATS. But ulceration occurred, with exposure of sADM(1), exposure and severe macrophage reaction to foreign body in 6 wounds of 3 cases 12.8 +/- 6.9 weeks after sADM(1) and UTS grafting.
CONCLUSIONGrafting of sADM as a dermal substitute of composite skin could alleviate early post-grafting immune reaction and improve UTS grafting results. But the delayed graft rejection couldn't be avoided.
Animals ; Burns ; surgery ; Dermatologic Surgical Procedures ; Dermis ; immunology ; transplantation ; Humans ; Rabbits ; Skin ; immunology ; injuries ; Skin Transplantation ; methods ; Skin, Artificial ; Swine ; Time Factors ; Transplantation, Heterologous ; Wound Healing

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