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.Application of multifunctional and traditional internal stents in patients with total ureteral resection cutaneous stomy
Huarong LUO ; Yan GU ; Shengsong HUANG ; Qiongfeng XU ; Chengdang XU ; Tianru WANG
Journal of Clinical Surgery 2024;32(11):1211-1214
Objective To compare the application of multifunctional ureterostomy stent and traditional ureterostomy internal stent in patients with total ureterostomy.Methods Prospectively,102 patients with bladder cancer and undergoing elective radical cystectomy with urinary diversion admitted to our hospital from March 2019 to March 2023 were selected for the study.According to the random number rank method,the patients were divided into the study group(51 cases)and the control group(51 cases).The control group was given a traditional single-J ureteral stomy stent drainage device,and the research group was given a multifunctional ureteral stomy stent drainage device.The differences of OAI score,renal function index(eGFR),recent complications,long-term complications and quality of life(FACT-BL score)were compared between the two groups.Results OAI scores 1 month,3 months and 6 months after surgery(study group:49.33±4.07,57.29±3.90,68.25±3.76;control group:44.25±4.61,52.31±4.58,59.06±4.37)and before surgery(study group:32.71±4.32;control group:33.18±4.74)compared with higher levels(P<0.05),but the study group was higher than the control group(P<0.05).Repeated measurement ANOVA results showed that eGFR at 3 months and 6 months after surgery(study group:86.07±4.07,88.01±3.01;control group:83.09±3.06,85.06±5.09)and before surgery(study group:82.05±6.04;control group:81.03±5.06)compared with higher levels(P<0.05),but the study group was higher than the control group(P<0.05).The total rate of recent complications in the study group was lower than that in the control group(7.84%VS 23.53%,P<0.05).The total incidence of long-term complications in the study group was lower than that in the control group(43.14%VS 78.43%,P<0.05).Emotional status score,physical status score,functional status score,social and family status score,BSS score,FACT-BL total score of the two groups 6 months after surgery(study group:20.25±2.36,24.92±1.87,25.65±1.11,26.02±1.14,32.75±1.76,129.59±5.74;Control group:18.65±3.10,20.18±3.02,23.51±1.29,21.51±2.24,30.26±3.07,114.10±10.37)and preoperative(study group:14.27±3.56,16.57±3.58,17.27±2.35,17.49±2.64,23.41±5.25,89.02±13.62;Control group:14.39±3.44,16.47±3.25,17.22±2.34,17.55±2.59,23.43±5.25,89.25±13.62)were increased(P<0.05),and the study group was higher than the control group(P<0.05).Conclusion The application of multifunctional ureteral stent in patients with ureteral cutaneous stomy with total cystotomy can effectively improve the adaptability of stomy,promote the recovery of renal function,reduce the risk of short-term and long-term complications,and improve the quality of life of patients.
3.Susceptibility factors of occurrence of allergic rhinitis
Yuanhua LIU ; Yueyuan XU ; Jieqing YU ; Jing YE ; Huarong YI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(11):1624-1629
Objective:To analyze the genetic and environmental factors that may contribute to the development of allergic rhinitis (AR) in patients, and provide a scientific basis for formulating intervention measures.Methods:This is a case-control study. A cross-sectional survey was conducted on AR patients who received treatment at The First Affiliated Hospital of Nanchang University from June 2017 to March 2019 using a self-designed questionnaire on AR susceptibility factors. Logistic regression analysis of AR susceptibility factors was performed.Results:There were 242 patients in the AR group and 258 patients in the non-AR group (control group). The average age of all patients was (13.16 ± 5.63) years. 56.8% of included patients were male. Multivariate logistic regression analysis showed that AR onset was associated with neonatal jaundice ( OR = 6.043), respiratory infections within 6 months after birth ( OR = 8.123), diarrhea ( OR = 3.868), eczema ( OR = 4.540), living in urban areas ( OR = 2.477), home decoration after birth ( OR = 3.042), moldy ceilings or walls ( OR = 38.255), home gardening ( OR = 3.752), and exposure to smoking environments ( OR = 2.574). Conclusion:The etiology of AR is complex, and its onset is influenced by various factors such as genetic factors, environmental factors, and related disease factors. It is necessary to strengthen the promotion and education of AR prevention knowledge, pay attention to environmental hygiene, and take personal protection measures.
4.Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy
Huarong XU ; Jiameng QU ; Jian WANG ; Kefei HAN ; Qing LI ; Wenchuan BI ; Ran LIU
Journal of Pharmaceutical Analysis 2022;12(6):860-868
Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-Ⅰ(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,meta-bolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an ICso of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.
5.Mutation analysis of thyroid peroxidase gene in a Chinese family with congenital hypothyroidism and literature review
Huarong ZENG ; Shuhang XU ; Huifeng ZHANG ; Zhifu KE ; Xiangrong YE ; Chao LIU
Chinese Journal of Endocrinology and Metabolism 2020;36(11):956-960
In this paper, thyroid peroxidase (TPO) gene mutation was studied in a congenital hypothyroidism (CH) family with 2 patients, to explore the mechanism of c. 2268dupT homozygous mutation leading to thyroid nodules, as well as the relationship between TPO gene mutation and thyroid cancer. The result suggested that TPO gene mutation is one of the reasons for congenital hypothyroidism, TPO gene c. 2268 dupT mutations can lead to thyroid nodules, which may be related to long-term high TSH stimulation and truncated protein accumulation. TPO gene mutations have a certain correlation with thyroid cancer, the risk may increase with the increase of age, but the mechanism is not clear at present. In the future, further research on the correlation and mechanism between the two factors is needed, as well as to determine whether it is necessary to remove the thyroid gland to prevent the accarance of cancer in CH patients with TPO gene mutation with thyroid nodules.
6.A systematic strategy for screening therapeutic constituents of (Turcz) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines.
Yiwen ZHANG ; Xinyan LV ; Jiameng QU ; Xin ZHANG ; Mingyang ZHANG ; Hao GAO ; Qian ZHANG ; Ran LIU ; Huarong XU ; Qing LI ; Kaishun BI
Acta Pharmaceutica Sinica B 2020;10(3):557-568
, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.
7.Quality control of Semen Ziziphi Spinosae standard decoction based on determination of multi-components using TOF-MS/MS and UPLC-PDA technology
Di WANG ; Qing LI ; Ran LIU ; Huarong XU ; Yidi YIN ; Yifan WANG ; Huijia WANG ; Kaishun BI
Journal of Pharmaceutical Analysis 2019;9(6):406-413
A sensitive, fast and comprehensive method for the quality assessment of Semen Ziziphi Spinosae (SZS) standard decoction with characterization of its chemical components was developed and validated. UPLC-Q/TOF-MS/MS system was used to identify thirty-six chemical components of SZS standard de-coction which included nucleosides, phenolic acids, alkaloids, and flavonoids. Furthermore, a UPLC-PDA method was validated to simultaneously determine adenosine, protocatechuic acid, magnoflorine, ca-techin, protocatechin, vicenin II, spinosin, kaempferol-3-rutinoside, and 6'''-feruloylspinosin which re-present four species of characteristic compounds. The qualitative method had been validated according to Chinese Pharmacopoeia (2015 edition) in terms of lineary, repeatability, recovery and stability for all analytes, with the results showing good precision, accuracy and stability. In conclusion, the method using UPLC combined with MS and PDA provided a novel way for the standardization and identification of SZS standard decoction, and also offered a basis for qualitative analysis and quality assessment of the pre-parations for SZS standard decoction.
8. A case report of Type Ⅰ Madelung disease and literature revive
Xuanping ZHA ; Mei LIN ; Fuming LEI ; Meiling YANG ; Yanqun XIAO ; Yun XU ; Xiuming CHEN ; Huarong HUANG
Chinese Journal of Plastic Surgery 2019;35(3):296-299
A male patient, with diagnose of Madelung disease, was admitted in September 2009. He has been a heavy drinker for decades before onset of the disease. This patient was characterized by the large amount of symmetrical deposits of adipose tissue in the subcutaneous layer around neck, and without obesity on other sites. The excessive adipose tissue was surgically removed by three steps. Appearance almost returned to normal. No recurrence happened after 8 years of follow-up.
9.BRAF/ KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner
Huarong TANG ; Shifeng YANG ; Xiao HU ; Yujin XU ; Baiqiang DONG ; Jin WANG ; Yue KONG ; Honglian MA ; Xiaoqian ZHANG ; Qiang XU ; Jianjun ZHANG ; Ming CHEN
Chinese Journal of Radiation Oncology 2018;27(9):805-809
Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95%CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95%CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.
10.Final report of a prospective randomized study on thoracic radiotherapy target volumes for limited-stage small cell lung cancer
Xiao HU ; Yong BAO ; Yujin XU ; Li ZHANG ; Jin WANG ; Honglian MA ; Ying JIN ; Xiaoling XU ; Zhengbo SONG ; Fang PENG ; Huarong TANG ; Min FANG ; Yue KONG ; Mengyuan CHEN ; Baiqiang DONG ; Xinmin YU ; Hongyang LU ; Yiping ZHANG ; Yun FAN ; Ming CHEN
Chinese Journal of Radiation Oncology 2018;27(12):1046-1050
Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.

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