1.SIRT6 overexpression inhibits AngⅡ-induced cardiomyocyte apoptosis by activating AMPK/Nrf2/HO-1 pathway
Zhenhua LU ; Jing SHEN ; Wenjun HUANG ; Wei SUN ; Yongxiang MA
Chinese Journal of Arteriosclerosis 2024;32(8):663-668,676
Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ(Ang Ⅱ)-induced cardio-myocyte apoptosis by activating adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1(AMPK/Nrf2/HO-1)signaling pathway.Methods The experiment was divided into 4 groups:control group,AngⅡ group,Ang Ⅱ+SIRT6 group,Ang Ⅱ+empty vector(EV)group.The mRNA level of SIRT6 was detected by RT-PCR.The cell activity was measured by MTT assay.The cell apoptosis was analyzed by flow cy-tometry.SIRT6,cardiomyocyte apoptosis related proteins(Bax,cleaved Caspase-3,Bcl-2),DNA damage related pro-teins(γ-H2AX,p-ATM),AMPK/Nrf2/HO-1 signaling pathway related proteins(p-AMPK,Nrf2,HO-1)were measured by Western blot.The reactive oxygen species(ROS)content was determined by DCFH-DA staining.The changes of the above indexes among the groups were observed.Results Compared with control group,the mRNA and protein ex-pression levels of SIRT6 and cell activity were significantly decreased in Ang Ⅱ group.Apoptosis rate,the expressions of Bax,cleaved Caspase-3 were increased,and the expression of Bcl-2 was decreased.The expressions of γ-H2AX and p-ATM were increased,and the expressions of p-AMPK,Nrf2,HO-1 were decreased.The activity of ROS was increased(P<0.01).Compared with Ang Ⅱ+EV group,the expression of SIRT6 and cell activity were significantly increased in Ang Ⅱ+SIRT6 group.Apoptosis rate,the expressions of Bax and cleaved Caspase-3 were decreased,and the expression of Bcl-2 was increased.The expressions of γ-H2AX and p-ATM were decreased,the expressions of p-AMPK,Nrf2,HO-1 were increased.The activity of ROS was decreased(P<0.01).Conclusion SIRT6 overexpression inhibits Ang Ⅱ-induced cardiomyocyte apoptosis through activation of AMPK/Nrf2/HO-1 signaling pathway.
2.The Epidemic and etiological characteristics of hand-foot-mouth disease in Nanshan District of Shenzhen City from 2019 to 2022
Yanping MA ; Hui CHEN ; Jiazhi MA ; Chunming HU ; Jiawen RUAN ; Ying WANG ; Yongxiang DUAN ; Muhua YU ; Changyan JU
Chinese Journal of Laboratory Medicine 2024;47(9):1073-1078
Objective:To understand the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in the Nanshan District of Shenzhen City from 2019 to 2022 and to provide a scientific basis for HFMD prevention in the area.Methods:Epidemiological data on HFMD in Shenzhen Nanshan District from 2019 to 2022 in the China Information System for Disease Control and Prevention were analyzed using descriptive research methods.Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the etiology characteristics of clinical specimens from HFMD patients. The VP1 gene of the dominant pathogen coxsackievirus A6 (CV-A6) was amplified and sequenced. SepMan Pro of DNASTAR software was used for sequence assembly and MegAlign was used for nucleotide homology analysis.Results:A total of 13 195 HFMD cases were reported in Shenzhen Nanshan District from 2019 to 2022, with an average annual incidence rate of 186.18/100, 000. Summer and autumn are the main onset seasons and children under 7 years old were the main population, accounting for 93.1%. The male-to-female ratio is 1.44∶1. A total of 451 clinical HFMD specimens were detected in the laboratory, including 403 positive (87.36%) and 48 negative (10.64%). The main pathogens were CV-A6 (63.03%), coxsackievirus A16 (CV-A16) (27.79%), coxsackievirus A4 (CV-A4) (4.71%), coxsackievirus A10 (CV-A10) (1.99%), Echovirus 11 (Echo-11) (0.25%), and uncertain type accounted for 2.23%, with no detection for enterovirus71 (EV71) type. The nucleotide homology of the 13 CV-A6 strains ranged from 94.0%?99.6%, and the nucleotide homology with the prototype strain Gdula ranged 84.1%?85.8%. The results of phylogenetic tree showed that all 13 CV-A6 strains in Nanshan District were of the D3a genotype.Conclusions:FHFMD in Nanshan District of Shenzhen City in 2019-2022 shows obvious differences in population and time distribution. Therefore, it is necessary to strengthen publicity and education on HFMD prevention and control in the summer and fall seasons and among key populations. CV-A6 and CV-A16 are the dominant strains of HFMD in Nanshan District, Shenzhen in recent years, so the monitoring of the dominant strains should be improved.
3.Machine learning model based on CT radiomics for predicting severity of acute phase traumatic brain injury
Yuqi YANG ; Jianing LUO ; Yongxiang YANG ; Dongbo ZOU ; Kun WEI ; Yongli XIA ; Min CHEN ; Yuan MA
Chinese Journal of Medical Imaging Technology 2024;40(7):992-996
Objective To explore the value of machine learning(ML)models based on non-contrast CT(NCCT)radiomics features for predicting the severity of acute phase traumatic brain injury(TBI).Methods Totally 600 TBI patients were retrospectively collected as observation group,other 65 TBI patients were taken as external validation set,while 50 TBI patients were prospectively enrolled as prospective validation set.Patients in observation group were divided into high-risk subgroup(n=240)and low-risk subgroup(n=360)according to Glasgow outcome scale(GOS)at discharge.The severity of acute phase TBI in observation group was assessed by doctor A and B with the same criteria,then an artificial model was established based on clinical and NCCT data at the time of first diagnosis using logistic regression(LR)method for predicting the severity of acute phase TBI.Patients in observation group were divided into training set(n=420,including 168 in high-risk subgroup and 252 in low-risk subgroup)and test set(n=180,including 72 in high-risk subgroup and 108 in low-risk subgroup)at the ratio of 7∶3.Based on NCCT of training set,radiomics features were extracted and selected,and LR,support vector machine(SVM),random forest(RF)and K-nearest neighbor(KNN)were used to establish 4 ML models.The efficacies of the above models were validated in test set,external validation set(including 34 cases of high-risk and 31 cases of low-risk TBI)and prospective validation set(including 21 cases of high-risk and 29 cases of low-risk TBI),respectively.Results The area under the curve(AUC)of doctor A and B for evaluating the severity of acute phase TBI in observation group was 0.606 and 0.771,respectively,of artificial model was 0.824.Based on NCCT in training set,6 optimal radiomics features were selected to construct LR,SVM,RF and KNN ML models,with AUC of 0.983,0.971,0.970 and 0.984 in test set,respectively,while the AUC of artificial model was 0.708.The AUC of LR,SVM,RF,KNN ML models and artificial model in external validation set was 0.879,0.881,0.984,0.863 and 0.733,while in prospective validation set was 0.984,0.873,0.982,0.897 and 0.704,respectively.Conclusion ML models based on CT radiomics could effectively predict the severity of acute phase TBI.
4.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
5.Exosome-mediated lnc-ABCA12-3 promotes proliferation and glycolysis but inhibits apoptosis by regulating the tolllike receptor 4uclear factor kappa-B signaling pathway in esophageal squamous cell carcinoma
Junliang MA ; Yijun LUO ; Yingjie LIU ; Cheng CHEN ; Anping CHEN ; Lubiao LIANG ; Wenxiang WANG ; Yongxiang SONG
The Korean Journal of Physiology and Pharmacology 2023;27(1):61-73
Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)uclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators.Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.
6.Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing.
Lijuan MA ; Jing ZHANG ; Ling LIN ; Tuanjie WANG ; Chaofu MA ; Xiaomeng WANG ; Mingshuang LI ; Yanjiang QIAO ; Yongxiang WANG ; Guimin ZHANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2023;13(5):2188-2201
Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
7.Correlation of serum albumin level at admission with clinical prognoses in patients with acute traumatic brain injury
Dongbo ZOU ; Yuting YANG ; Yuping PENG ; Yongxiang YANG ; Jianing LUO ; Tao YANG ; Jingmin CHENG ; Yuan MA
Chinese Journal of Neuromedicine 2023;22(9):904-909
Objective:To explore the correlation of serum albumin level at admission with clinical prognoses in patients with acute traumatic brain injury (TBI).Methods:One hundred and fifty-four patients with acute moderate-extreme severe TBI (Glasgow Coma Scale [GCS] scores of 3-12 at admission) in Department of Neurosurgery, General Hospital of Western Theater Command from January 1, 2019 to December 31, 2020 were chosen. The comprehensive clinical data of these patients were collected, including age, gender, GCS scores, serum albumin level (hypoalbuminemia defined as<35 g/L), hemoglobin level, comorbidities, treatment measures, and prognoses 6 months after discharge (poor prognosis defined as Glasgow outcome Scale [GOS] scores of 1-2, and good prognosis defined as GOS scores of 3-5). Univariate and multivariate Logistic regressions were used to identify the independent factors for clinical prognoses of these patients, and differences in poor prognosis rate, length of ICU stay, and total hospital cost were compared between different groups.Results:Among the 154 patients, 43 had poor prognosis and 111 had good prognosis. Serum albumin level at admission ( OR=0.916, 95% CI: 0.843-0.996, P=0.001) and GCS scores at admission ( OR=0.701, 95% CI: 0.594-0.828, P<0.001) were independent factors for prognosis. Patients with hypoalbuminemia ( n=70) displayed significantly higher poor prognosis rate, longer ICU stays, and increased total hospitalization cost compared with those without hypoalbuminemia ( n=84, P<0.05); specifically, in patients with GCS scores of 9-12 at admission ( n=58), those with hypoalbuminemia ( n=27) exhibited significantly higher poor prognosis rate, longer ICU stays, and higher total hospitalization cost than their non-hypoalbuminemia counterparts ( n=31, P<0.05); similarly, in patients with GCS scores of 3-8 at admission ( n=96), those with hypoalbuminemia ( n=74) had significantly higher poor prognosis rate than their non-hypoalbuminemia counterparts ( n=22, P<0.05). In patients with good prognosis, those with hypoalbuminemia ( n=56) showed significantly longer total hospital stays, prolonged ICU stays, and increased total hospitalization cost compared with those without hypoalbuminemia ( n=55, P<0.05). Conclusion:Low serum albumin level at admission is likely to lead to poor prognosis, prolonged ICU stays and increased total hospitalization cost in patients with acute TBI.
8.The application value of atropine before tracheal intubation under general anesthesia in elderly patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration biopsy
Hui MA ; Min REN ; Guoxin ZHANG ; Shuyu YU ; Yongxiang ZHANG ; Yuechuan LI ; Qi WU
Chinese Journal of Geriatrics 2021;40(2):216-220
Objective:To investigate the value of atropine administration before tracheal intubation under general anesthesia in the elderly patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)biopsy.Methods:This was a case-control study.A total of 87 elderly hospitalized patients receiving chest enhanced CT test suggesting the risk of lung cancer with enlargement of mediastinal lymph nodes in 7 regions were scheduled to undergo endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)biopsy under general anesthesia.The patients were randomly divided into two groups by flipping a coin: the atropine group(n=40)and the control group(n=47). The indicators for evaluating the application values of atropine included preoperative, intra-operative and postoperative systolic blood pressure(SBP), diastolic blood pressure(DBP), heart rate, oropharyngeal and airway secretion volume, oxygen saturation, operation time, positive diagnosis rate and postoperative adverse reactions.Results:SBP and DBP were lower in the atropine group than in the control group before endotracheal intubation(131.7±15.3 mmHg vs.140.7±13.7 mmHg, 79.1±7.6 mmHg vs.85.6±7.4 mmHg, t=2.885 and 4.061, P<0.05). There was no significant difference in SBP and DBP 10 min after endoscopic operation and 10 min after tracheal extubation between the atropine group versus the control group(SBP: 109.1±11.2 mmHg vs.105.0±12.2 mmHg, 136.9±23.0 mmHg vs.129.9±11.2 mmHg, DBP: 66.9±7.5 mmHg vs.68.0±8.3 mmHg, 77.6±10.9 mmHg vs.78.5±6.4 mmHg, t=-1.617, 0.687, -1.751 and 0.448, P>0.05). There was no significant difference in HR between the two groups before endotracheal intubation( t=1.416, P>0.05), while HR was higher in the atropine group than in the control group 10 min after endoscopic operation and 10 min after tracheal extubation( t=-3.323 and -2.181, P<0.01 and P<0.05). The change rates of SBP and DBP were lower in the atropine group than in the control group 10 min after endoscopic operation and 10 min after tracheal extubation( t=7.947, -6.962, -3.187 and -3.232, P<0.01). The change rate of HR was lower in the atropine group 10 min after endoscopic operation and was higher 10 min after tracheal extubation than in the control group( t=-6.467 and -4.131, P<0.01). There were significant differences in the volume of oropharyngeal and airway secretions and fingertip oxygen saturation between the two groups before endotracheal intubation and 10 min after tracheal extubation( t=-2.334, 2.759, -3.314 and -2.767, P<0.01). The endoscopic operation time was less in the atropine group than in the control group with no statistically significant difference[(25.9±5.7)min vs.(26.4±4.7)min, t=0.391, P>0.05]. There was no significant difference in postoperative adverse reactions between the atropine group versus the control group(34 patients or 85.0% vs.43 patients or 91.5%, χ2=1.247, P>0.05). Conclusions:The application of atropine before tracheal intubation under general anesthesia is beneficial to stabilizing the intraoperative blood pressure and heart rate, and can reduce the production of postoperative oropharyngeal and airway secretions in elderly patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration biopsy.
9.Characteristics of human papillomavirus infection and abnormal cervical cytology in health check-up females in Shenzhen
Xuhuai HU ; Lu MENG ; Yongxiang GAO ; Sailimai MAN ; Yuan MA ; Cheng JIN ; Bo WANG ; Yi NING ; Liming LI
Chinese Journal of Epidemiology 2021;42(7):1205-1212
Objective:To describe the characteristics of human papillomavirus infection and thinprep cytologic test (TCT) outcome in health check-up females in Shenzhen.Methods:Use cross-sectional design, collect information from data from health check-up females in Shenzhen and describe characteristics of HPV infections screening and TCT outcomes.Results:We collected the data of 75 754 females, 103 508 females and 69 964 females received HPV detection, TCT and combined detection respectively. HPV standardized infection rate was 19.89% (95% CI: 19.45%-20.33%) and showed a "U-shaped" pattern in age distribution. The most prevalent HPV genotypes were 52, 51, 16, 58 and 53. Infection rate was higher for high-risk HPV than low-risk HPV genotype. Single infection was more common than its multiple infection. In addition, 7.48% (95% CI: 7.22%-7.75%) women were TCT positive, of whom 4.58% (95% CI: 4.40%-4.76%), 2.54% (2.40%-2.69%), 0.27% (95% CI: 0.23%-0.31%) had atypical squamous cells, low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, respectively. Overall and subtype HPV infection rates increased with severity of abnormal cervical cytology. The most prevalent HPV genotypes were 52, 58 and 16 in women with abnormal cervical cytology. Conclusions:HPV prevalence remains at a high level in Shenzhen. This study suggests that attention should be paid to HPV screening, especially in young, perimenopausal women and in high risk HPV genotype infection. Timely follow-up and cervical cytology screening are required for women with high-risk HPV infection or persistent infection. Future vaccination strategies should take account of prevalent HPV genotype.
10.Promoting Osseointegration of Dental Implants in Dog Maxillary Sinus Floor Augmentation Using Dentin Matrix Protein 1-Transduced Bone Marrow Stem Cells
Dong MA ; Yuanyin WANG ; Yongxiang CHEN ; Gang YANG ; Xin LIU
Tissue Engineering and Regenerative Medicine 2020;17(5):705-715
BACKGROUND:
Beta-tricalcium phosphate ( β-TCP) has been employed successfully as a synthetic graft material in maxillary sinus floor augmentation (MSFA) for placing dental implants. However, the lack of osteogenic and osteoinductive properties of this substitute invariably results in bone regeneration of low quality and quantity. The purpose of this study was to determine whether loading dentin matrix protein-1 (DMP1) gene-modified bone marrow mesenchymal stem cells (BMSCs) onto β-TCP promoted bone regeneration and osteointegration of dental implants in MSFA of dogs.
METHODS:
BMSCs were transduced with a lentiviral vector overexpressing the DMP1 gene (Lenti-DMP1) and with a lentiviral vector overexpressing enhanced green fluorescent protein (Lenti-EGFP) in vitro and were loaded into β-TCP scaffolds for autologous sinus grafting. Beagles received bilateral MSFA with four biomaterials (① Lenti-DMP1-transduced BMSCs/β-TCP, ② Lenti-EGFP-transduced BMSCs/β-TCP, ③ BMSCs/β-TCP, ④ β-TCP) and simultaneous implant placement at each sinus. Twelve weeks post operation, the maxillae were explanted, and every sinus was evaluated by radiographic observation, micro-CT and histological analysis. The osteogenic outcomes of bone regeneration and osseointegration were compared between the four groups.
RESULTS:
The sinuses grafted with Lenti-DMP1-transduced BMSCs/β-TCP constructs presented a significantly higher increase in compact radiopaque area, higher local bone mineral densities, greater bone-implant contact and greater bone density when compared to other three groups.
CONCLUSION
These results demonstrated that combinations of β-TCP and DMP1 gene-modified BMSCs could be used to construct tissue-engineered bone to enhance mineralization of the regenerated bone and osseointegration of dental implants in MSFA.

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