1.The investigation of STK15 gene amplification and overexpression in laryngeal squamous cell carcinoma.
Yan YE ; Fu-cai LI ; Shu-yun WANG ; Chan-yuan LI ; Hai-ming YUAN ; Xu ZHAO ; Wei-neng FU ; Zhen-ming XU ; Kai-lai SUN
Chinese Journal of Medical Genetics 2006;23(3):326-329
OBJECTIVETo investigate the role of STK15 gene amplification and overexpression to genesis and development of laryngeal squamous cell carcinoma (LSCC).
METHODSSTK15 gene amplification in 40 cases carcinoma tissues and normal tissues as control was detected by differential PCR approach. STK15 mRNA and protein levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry method.
RESULTSIn 40 LSCC cases, STK15 gene amplification was found in 14 tumor tissues(35%), mRNA overexpression in 27 tumor tissues(67.5%), and protein upregulated in 29 tumor tissues(72.5%). Statistics analysis showed that STK15 gene amplification and mRNA overexpression were obviously associated to differentiation degree of LSCC, and protein overexpression was closely associated with both differentiation degree and pathological grades of LSCC.
CONCLUSIONThis research results suggest that STK15 gene amplification contributes to its mRNA and protein overexpression through affecting the exact replication of centrosome and separation of chromosomes. STK15 gene thus plays a role in LSCC oncogenesis and malignant progression.
Aurora Kinase A ; Aurora Kinases ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction
2.The role of extracellular ATP in the male reproductive tract.
Wen-Liang ZHOU ; Wu-Lin ZUO ; Ye-Chun RUAN ; Zhe WANG ; Jian-Yang DU ; Yuan XIONG ; Hsiao-Chang CHAN
Acta Physiologica Sinica 2007;59(4):487-494
In addition to its well established role as a neurotransmitter, extracellular ATP has been considered as a paracrine/autocrine factor, either released from sperm or epithelial cells, in the male reproductive tract and shown to play a versatile role in modulating various reproductive functions. This review summarizes the signal pathways through which ATP induces anion secretion by the epithelia of the epididymis, as well as its epithelium-dependent modulation of smooth muscle contraction of the vas deferens. Finally, the overall role of ATP in coordinating various reproductive events in the male genital tract is discussed.
Adenosine Triphosphate
;
physiology
;
Animals
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Epididymis
;
physiology
;
Epithelium
;
physiology
;
Humans
;
Male
;
Muscle Contraction
;
Muscle, Smooth
;
physiology
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Signal Transduction
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Urogenital System
;
physiology
;
Vas Deferens
;
physiology
3.Clinical efficacy of combined therapy in children with stage 4 neuroblastoma.
Wei-Ling LIANG ; Xiao-Fan YE ; Gong ZHONG ; Jian-Jun CHEN ; Kang-Lin DAI ; Ka Leung Daniel CHEUK ; Shu MO ; Bo-Shen WANG ; Chun-Yu LI ; Xuan-Zhu JIANG ; Zhi-Yuan XU ; Li ZHOU ; Irene CHAN ; Jian-Liang CHEN ; Patrick CHU ; Pui Wah Pamela LEE ; Chi Fung Godfrey CHAN
Chinese Journal of Contemporary Pediatrics 2022;24(7):759-764
OBJECTIVES:
To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.
METHODS:
A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.
RESULTS:
The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.
CONCLUSIONS
Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Child
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Child, Preschool
;
Combined Modality Therapy
;
Humans
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Infant
;
Neuroblastoma/drug therapy*
;
Positron-Emission Tomography
;
Radionuclide Imaging
;
Retrospective Studies
;
Treatment Outcome
4.Role of acetylcholine in gelsenicine-induced death in mice.
Zhou-Yi LAI ; Hai-Bo WANG ; Rui-Ling LV ; Qiu-Chan TAN ; Zhi-Qin DENG ; Yuan WANG ; Xiao-Xue SUN ; Jia-Bao WU ; Lin-Yan ZHU ; Lei WANG ; Li-Xin CHEN ; Wen-Cai YE ; Li-Wei WANG
Acta Physiologica Sinica 2016;68(3):249-254
The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 μg/mL (from 31.1 μg/mL in the control), which was lower than that (53.9 μg/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 μg/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.
Acetylcholine
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Animals
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Death
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Indole Alkaloids
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Mice
5.Simultaneous determination of seven different components in Cynomorium songaricum Rupr. by QAMS
Jun-hua MENG ; Chan DING ; Si-yuan PENG ; Yuan LIU ; Jian-ye YAN ; Pei-wu CUI
Acta Pharmaceutica Sinica 2023;57(9):2763-2770
A quantitative analysis of multi-components by single marker method (QAMS) was established for simultaneous determination of gallic acid, protocatechuic acid, catechin, epicatechin,
6.Targeting papain-like protease for broad-spectrum coronavirus inhibition.
Shuofeng YUAN ; Xiaopan GAO ; Kaiming TANG ; Jian-Piao CAI ; Menglong HU ; Peng LUO ; Lei WEN ; Zi-Wei YE ; Cuiting LUO ; Jessica Oi-Ling TSANG ; Chris Chun-Yiu CHAN ; Yaoqiang HUANG ; Jianli CAO ; Ronghui LIANG ; Zhenzhi QIN ; Bo QIN ; Feifei YIN ; Hin CHU ; Dong-Yan JIN ; Ren SUN ; Jasper Fuk-Woo CHAN ; Sheng CUI ; Kwok-Yung YUEN
Protein & Cell 2022;13(12):940-953
The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals
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Coronavirus Papain-Like Proteases/antagonists & inhibitors*
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Cricetinae
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Humans
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Mice
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Pandemics
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SARS-CoV-2/enzymology*
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COVID-19 Drug Treatment
7.Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study.
Shao-Rui HAO ; Ren YAN ; Shan-Yan ZHANG ; Jiang-Shan LIAN ; Huan CAI ; Xiao-Li ZHANG ; Lin ZHENG ; Hong-Yu JIA ; Jian-Hua HU ; Guo-Dong YU ; Jue-Qing GU ; Chan-Yuan YE ; Ci-Liang JIN ; Ying-Feng LU ; Jiao-Jiao XIN ; Ji-Fang SHENG ; Yi-Da YANG
Journal of Zhejiang University. Science. B 2020;21(8):628-636
BACKGROUND:
Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development.
METHODS:
Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors.
RESULTS:
A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206).
CONCLUSIONS
IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis*
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Antiviral Agents/administration & dosage*
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Betacoronavirus
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C-Reactive Protein/analysis*
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COVID-19
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Case-Control Studies
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China
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Coronavirus Infections/drug therapy*
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Glucocorticoids/pharmacology*
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Hospitalization
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Humans
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Interferon alpha-2/administration & dosage*
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Nasal Sprays
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Pandemics
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Pneumonia, Viral/drug therapy*
;
Propensity Score
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Retrospective Studies
;
SARS-CoV-2
;
Sodium/blood*
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Virus Shedding/drug effects*
;
COVID-19 Drug Treatment
8.Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China.
Jiang-Shan LIAN ; Huan CAI ; Shao-Rui HAO ; Xi JIN ; Xiao-Li ZHANG ; Lin ZHENG ; Hong-Yu JIA ; Jian-Hua HU ; Shan-Yan ZHANG ; Guo-Dong YU ; Jue-Qing GU ; Chan-Yuan YE ; Ci-Liang JIN ; Ying-Feng LU ; Ji-Fang SHENG ; Yi-da YANG
Journal of Zhejiang University. Science. B 2020;21(5):369-377
BACKGROUND:
A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure.
METHODS:
We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan.
RESULTS:
Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups.
CONCLUSIONS
From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent
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Adult
;
Aged
;
Aspartate Aminotransferases
;
blood
;
Betacoronavirus
;
Case-Control Studies
;
Child
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Child, Preschool
;
China
;
epidemiology
;
Coronavirus Infections
;
epidemiology
;
physiopathology
;
therapy
;
Female
;
Humans
;
Infant
;
Infant, Newborn
;
L-Lactate Dehydrogenase
;
blood
;
Male
;
Middle Aged
;
Pandemics
;
Pneumonia, Viral
;
epidemiology
;
physiopathology
;
therapy
;
Retrospective Studies
;
Young Adult