1.Antiviral Efficacy and Mechanism of BD-77 Against Novel Coronavirus SARS-CoV-2
Lei BAO ; Qinhai MA ; Shanshan GUO ; Ronghua ZHAO ; Wen XIA ; Zihan GENG ; Jing SUN ; Yanyan BAO ; Zhou XU ; Shenglong YAN ; Jinxin XIAO ; Huarong CHEN ; Chenggang HUANG ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):45-51
ObjectiveThe human angiotensin converting enzyme2 (hACE2) transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus (Delta/Omicron) to angiotensin converting enzyme2 (ACE2). Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group, SARS-CoV-2 infection group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1, with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice, detect the virus titer of the lung tissue of the mice, and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro, with median inhibitory concentration (IC50) of 526.3 mg·L-1 and 653.0 mg·L-1, respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT, Omicron, and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died, while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice, significantly lower the virus titer in the lung tissue of mice (P<0.05), and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However, its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.
2.The application of comprehensive geriatric assessment in elderly patients with head and neck cancer
Chenxi LI ; Zhongcheng GONG ; Huarong ZHAO ; Ying LIU
STOMATOLOGY 2024;44(8):630-634
The treatment of head and neck cancer is dominated by surgery and radiochemotherapy.For elderly patients,however,the rationality of invasive treatment is questioned in clinical practice.Although the proportion of geriatric patients with head and neck canc-er is increasing,there are few consistent standards in the literature and guidelines.From the perspective of evidence-based medicine,this paper presents current evidence for treatment so as to provide specific recommendations for treating head and neck cancer in the elderly.Furthermore,based on a systematic literature review,a clinical algorithm is proposed to evaluate the treatment risk of elderly patients with head and neck cancer.
3.SERPINE1 as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma
Xiaopeng GUO ; Zhen SUN ; Huarong CHEN ; Junjun LING ; Houyu ZHAO ; Aoshuang CHANG ; Xianlu ZHUO
Clinical and Experimental Otorhinolaryngology 2023;16(1):75-86
Objectives:
. Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification.
Methods:
. This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.
Results:
. SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel.
Conclusion
. This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.
4.Application of new evaluation system based on virtual simulation system in experimental teaching of functional science
Tingting ZHAO ; Lijuan YU ; Yan WANG ; Yanqing GENG ; Huarong YU ; Liling LIU ; Yingbo LI
Chinese Journal of Medical Education Research 2022;21(6):669-672
Objective:To explore the application effect of a new evaluation system based on virtual simulation system in the evaluation of functional science experiment teaching.Methods:The data of students' learning in the 2019-2020 academic year were collected, and the impact of using virtual simulation teaching system on the achievement of teaching goals under the new teaching evaluation standard was comparatively analyzed. Questionnaire survey was conducted to study students' evaluation on the virtual simulation teaching system. SPSS 22.0 was used for chi-square test.Results:The students who used the new formative evaluation standard had a virtual academic excellence rate of 75.49% (308/408), while the unused students had an excellence rate of only 32.22% (135/419), with significant differences ( P<0.01). The number of virtual simulation items required for different teaching objectives were 4, 11 and 14, respectively, and the corresponding students' virtual simulation system outstanding rate was 99.19% (246/248), 93.14% (380/408), 84.72% (488/576), with significant differences ( P<0.01). And 93.8% (348/371) students thought the learning of the virtual simulation system could help improve the success rate of the experiment, and 93.26% (346/371) of the students believed that it had improved the ability to analyze and deal with unexpected problems in the experimental class. Conclusion:The new evaluation system based on the virtual simulation system can promote the improvement of the experimental teaching quality of functional science.
5.Expressions of LSD1 and PDPN in tongue squamous cell carcinoma and their effects on prognosis
Kunlong WANG ; Yang ZHANG ; Weipeng SU ; Pan LIU ; Huarong ZHAO
Journal of International Oncology 2020;47(5):264-271
Objective:To investigate the expressions of lysine specific demethylase 1 (LSD1) and podoplanin (PDPN) in tongue squamous cell carcinoma and the correlation between LSD1 or PDPN and clinicopathological characteristics or prognosis.Methods:A total of 67 cases of tongue squamous cell carcinoma and corresponding paracancerous normal tissues in the First Affiliated Hospital of Xinjiang Medical University from January 2011 to January 2016 were selected. The expressions of LSD1 and PDPN in cancer and paracancerous tissues were detected by immunohistochemical method, and the patients were followed up for a long time to analyze the correlation between the expression of LSD1 or PDPN and clinicopathological characteristics or prognosis.Results:The expressions of LSD1 and PDPN in tongue squamous cell carcinoma tissues were higher than those in paracancerous tissues, and the differences were statistically significant ( Z=6.089, P<0.001; Z=5.781, P<0.001). The expression intensities of LSD1 and PDPN were significantly different in patients with different clinical stage ( χ2=11.487, P=0.001; χ2=8.111, P=0.004), lymph node metastasis ( χ2=4.772, P=0.029; χ2=6.206, P=0.013) and tumor size ( χ2=5.985, P=0.014; χ2=4.247, P=0.039). The expression intensity of LSD1 was also significantly different in patients with different degrees of differentiation ( χ2=6.660, P=0.010). In univariate analysis, LSD1 expression intensity was negatively correlated with progression-free survival (PFS) and overall survival (OS) ( χ2=18.930, P<0.001; χ2=16.257, P<0.001), PDPN expression intensity was negatively correlated with PFS and OS ( χ2=31.720, P<0.001; χ2=18.390, P<0.001), and tumor size was negatively correlated with PFS and OS ( χ2=5.326, P=0.021; χ2=8.843, P=0.003). Postoperative radiotherapy and clinical stage were positively and negatively correlated with OS respectively ( χ2=4.197, P=0.040; χ2=6.355, P=0.012). In multivariate analysis, LSD1 was an independent risk factor for PFS and OS ( HR=5.743, 95% CI: 1.012-32.579, P=0.048; HR=17.759, 95% CI: 2.303-136.916, P=0.006), PDPN was an independent risk factor for PFS ( HR=4.380, 95% CI: 1.258-15.254, P=0.020), postoperative radiotherapy was a protective factor for PFS and OS ( HR=0.374, 95% CI: 0.157-0.895, P=0.027; HR=0.218, 95% CI: 0.091-0.521, P=0.001), and clinical stage was an independent risk factor for OS ( HR=2.637, 95% CI: 1.107-6.280, P=0.029). In tongue squamous cell carcinoma tissues, the expression of LSD1 was positively correlated with that of PDPN ( rs=0.655, P<0.001). Conclusion:The expressions of LSD1 and PDPN in tongue squamous cell carcinoma are higher than those in adjacent tissues. LSD1 is an independent risk factor for PFS and OS, PDPN is an independent risk factor for PFS, clinical stage is an independent risk factor for OS, and postoperative radiotherapy is a protective factor for PFS and OS. There is a positive correlation between the expressions of LSD1 and PDPN in tongue squamous cell carcinoma, and they can both be used as independent predictors of prognosis in patients with tongue squamous cell carcinoma.
6. Expressions of LSD1, MGMT and Ki-67 in high-grade glioma and their influences on prognosis
Qianhui ZHANG ; Yang ZHANG ; Weipeng SU ; Song′an ZHANG ; Pan LIU ; Huarong ZHAO
Journal of International Oncology 2019;46(9):519-525
Objective:
To investigate the expressions of histone lysine-specific demethylase 1 (LSD1), O6-methylguanine DNA methyltransferase (MGMT) and cell proliferation-associated antigen Ki-67 in high-grade glioma and their influences on prognosis.
Methods:
Sixty-five cases of grade Ⅲ and Ⅳ glioma confirmed by pathology from January 2011 to June 2017 in the First Affiliated Hospital of Xinjiang Medical University were selected. Immunohistochemistry (SP method) was used to detect the expressions of LSD1, MGMT and Ki-67 in pathological specimens. The therapeutic effect was evaluated by long-term follow-up. The relationships between the three markers and pathological grade, progression-free survival (PFS) and overall survival (OS) were analyzed.
Results:
The overall positive rates of LSD1, MGMT and Ki-67 in the 65 high-grade glioma specimens were 70.8% (46/65), 60.0% (39/65) and 100.0% (65/65), respectively. There were no significant differences in the expressions of LSD1 and MGMT in grade Ⅲ and Ⅳ glioma (
7.The predictive significance of LVEF and NT-proBNP in early prognosis assess of Untypical NSTE-ACS
Yanjun ZHAO ; Huarong WANG ; Fuli LI ; Jian YU
The Journal of Practical Medicine 2017;33(14):2311-2315
Objective To investigate whether echocardiography left ventricular ejection fraction (LVEF) and NT-proBNP could be an early detective marker for patients with untypical NSTE-ACS. Methods A total of 248 ACS cases admitted to the emergency department of our hospital from January 1,2015 to June 31,2016 were retrospectively reviewed. The data included age,gender,past medical history,D-dimer,MB isoenzyme of creatine kinase(CK-MB),cardiac troponin I(cTnI),the precursor of the N-terminal pro-brain natriuretic peptide(NT-proBNP),electrocardiogram(ECG)before treatment,and the CK-MB,cTnI and LVEF,the treatment of percuta-neous coronary intervention(PCI)or thrombolytic by drugs. Survival condition and time from onset to death were recorded. According to the results of multivariate logistic regression analysis ,receiver operating characteristic curve(ROC curve)and fitting curve were drawn. The association between the LVEF and NT-proBNP before the treatment and prognosis of ACS was analyzed. Results NSTE-ACS patients with chief complaint of chest pain were less than those of STE-ACS(33.6% vs. 70.1%,P=0.003). Pre-hospital time was longer than that of STE-ACS group(67.92 ± 116.89 vs. 30.65 ± 55.59,P = 0.006). CTNI(4.37 ± 12.53 vs. 9.62 ± 18.00,P=0.011)and LVEF(53.51 ± 14.51 vs. 56.26 ± 12.30,P=0.019)were less than that of the STE-ACS group. NT-proBNP was higher than that of the STE-ACS group(2288.37 ± 4612.10 vs. 1506.84 ± 1722.51,P=0.038). mortality rates was higher than the STE-ACS group((15.3%vs. 6.8%,P=0.036). Multivariate logistic regression analysis showed that LVEF values was correlated to 28-day death(B =-0.097 ,P=0.022). The ROC curves showed that LVEF values was negative correlated with the 28-day death. However,combination of LVEF and NT-proBNP was better than single LVEF values. LVEF values was negative correlated with the NT-proBNP(r =-0.263,P=0.001), LVEF values had greater and longer survival time(B=0.401,P=0.045)but NT-proBNP was not related to surviv-al time.(B=0.00,P=0.931). Conclusion LVEF and NT-proBNP are correlated with the early risk assessment of patients with ACS,but was not correlated with the time from onset to death. The decrease in LVEF values at the early stage of NSTE-ACS may be helpful to indicate the critical condition of the ACS patients.
8.Prognostic analysis of 313 aged pancreatic cancer patients in hospital treatment between Uygur and Han nationality in Xinjiang area
Lei PEI ; Ceng CAI ; Rui MAO ; Huarong ZHAO ; Hua ZHANG ; Yongxing BAO
Practical Oncology Journal 2016;30(1):1-6
Objective To investigate the prognostic factors of survival time of the Uygur and Han nation-ality elderly patients( over 60 years) with pancreatic cancer in Xinjiang.Methods We carried on a retrospective study of 313 aged patients diagnosed with pancreatic cancer in The First Affiliated Hospital of Xinjiang Medical University from January 1st,2003 to May 30th,2015.We used Kpalan-Meier method for calculation of survival, used Log-rank method for those factors which could affect the prognosis of patients,at last we used Cox propor-tional risk model for those multiple factors which match the role.Results Three hundred and thirteen cases with pancreatic cancer had a median survival of 157 days,and survival rates of half a year,1 and 2 year were 34.8%, 18.5%,7.0%.There was a statistic difference between Uygur patients′and Han patients′survival time(P<0.05).Single factor analysis showed the nationality,tumor size,surgery,ZPS(ECOG),Clinical stage(TNM), chemotherapy and radiotherapy,carcino-embryonic antigen(CEA)level and cancer antigen 199(CA199)level before treatment with outcome(P<0.05).Multiple factor analysis showed that the clinical stage,surgery(P<0.05)can be regarded as independent prognostic decision factors.Conclusion The clinical staging,surgical treatment could be regarded as independent prognostic factors for the elderly prognosis of pancreatic cancer.Both of the Han and Uygur patients,earlier discovered and more appropriate surgery treatment are the key for the elder-ly patients with pancreatic cancer.
9.Prognostic factors of relapse and metastasis after radical resection of lung adenocarcinoma
Yafei ZHANG ; Pan LIU ; Huarong ZHAO ; Shanshan WANG ; Ruirui SUN
Journal of International Oncology 2016;43(4):254-257
Objective To explore the risk factors of local relapse and distant metastasis after radical resection of lung adenocarcinoma.Methods A total of 102 patients with lung adenocarcinoma operated in First Affiliated Hospital of Xinjiang Medical University from January 2005 to January 2010 were collected.The correlation between clinicopathological characteristics and prognosis was evaluated by single-factor and multi-factor analyses.The survival curves were plotted using Kaplan-Meier.Single-factor analysis of statistical difference was tested using Log-rank test.Multi-factor analysis of prognostic factors were produced by COX regression proportional hazards model.Results In the whole group,1,2,3 and 5 year disease-free survival rates were 74.30%,58.00%,51.50% and 44.90% respectively,and the median disease-free survival was 30 months.Single-factor analysis showed that tumor size (x2 =9.951,P =0.002),clinical type (x2 =8.460,P =0.004),differentiated degree (x2 =4.807,P =0.028),lymph node metastasis (x2 =40.516,P =0.000),pathological stage (x2 =38.769,P =0.000) were prognostic factors for local relapse and distant metastasis in postoperative patients with lung adenocarcinoma.Muti-factor analysis showed that tumor size (OR =1.943,95 % CI:1.091-3.463,x2 =5.082,P =0.024),differentiated degree (OR =2.570,95 % CI:1.451-4.552,x2 =10.467,P =0.001),lymph node metastasis (OR =3.196,95% CI:1.037-9.849,x2 =4.096,P =0.043) were independent prognostic factors for local relapse and distant metastasis in postoperative patients with lung adenocarcinoma.Conclusion Tumor size,differentiated degree and lymph node metastasis are independent prognostic factors for local relapse and distant metastasis in postoperative patients with lung adenocarcinoma.
10.Significance of diagnosis of tympanosclerosis by HRCT combined with pure tone audiometry
Zhengpeng GONG ; Huarong CHEN ; Houyu ZHAO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2016;23(9):525-528
OBJECTIVE To investigate the significance of diagnosis of tempanosclerosis by HRCT combined with pure tone audiometry. METHODS 176 patients(181 ears) with chronic suppurative otitis media in stationary phase were recruited in Guizhou Medical University Affiliated Hospital between January 2014 to December 2015. Temporal bone HRCT combined with pure tone audiometry were applied to all patients before operation to diagnose tempanosclerosis. Intraoperative exploration results was the gold standard to observe sensitivity, specificity, positive likelihood ratio and the difference of accuracy of two diagnostic methods. RESULTS 1. The sensitivity, specificity, positive likelihood, negative likelihood ratio and accuracy of tympanosclerosis diagnosed only by temporal bone HRCT were 58.55%, 93.10%, 8.49, 0.46 and 64.09% respectively. 2. The sensitivity, specificity, positive likelihood, negative likelihood ratio and accuracy of tympanosclerosis diagnosed by HRCT combined with pure tone audiometry were caculated as 94.08%, 89.66%, 9.09, 0.01 and 93.37% respectively. Type I diagnostic accordance rate was 89.66%, type II was 87.50%, type III was 84.62%and type IV was 82.14%. The total diagnosis coincidence rate was 86.18%. The diagnostic efficacy increased significantly by the combined method than by the temporal bone HRCT alone. CONCLUSION Temporal bone HRCT combined with pure tone audiometry is valuable in diagnosis of tympanosclerosis. It can provide theoretical basis for making optimal operation scheme in suspect tympanosclerosis patients.

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