1.Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.
Ya-Jun SHU ; Jian-Feng HE ; Rong-Juan PEI ; Peng HE ; Zhu-Hang HUANG ; Shao-Min CHEN ; Zhi-Qiang OU ; Jing-Long DENG ; Pei-Yu ZENG ; Jian ZHOU ; Yuan-Qin MIN ; Fei DENG ; Hua PENG ; Zheng ZHANG ; Bo WANG ; Zhong-Hui XU ; Wu-Xiang GUAN ; Zhong-Yu HU ; Ji-Kai ZHANG
Chinese Medical Journal 2021;134(16):1967-1976
BACKGROUND:
Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.
METHODS:
A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.
RESULTS:
V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.
CONCLUSIONS:
The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.
TRIAL REGISTRATION
http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged
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Antibodies, Viral
;
COVID-19/therapy*
;
COVID-19 Vaccines
;
Double-Blind Method
;
Humans
;
Immunization, Passive
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Recombinant Fusion Proteins
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SARS-CoV-2
2.Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis.
Bing-Rong LI ; Shi-Yun SHAO ; Long YUAN ; Ru JIA ; Jian SUN ; Qing JI ; Hua SUI ; Li-Hong ZHOU ; Yi ZHANG ; Hui LIU ; Qi LI ; Yan WANG ; Bi-Meng ZHANG
Journal of Integrative Medicine 2021;19(2):144-157
OBJECTIVE:
The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu).
METHODS:
Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing.
RESULTS:
Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.
CONCLUSION
Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.
3.Rapid Identification and Analysis of Chemical Components in Heartwood of Dalbergia cochinchinensis by UPLC-Q-TOF-MS/MS
Xiao-wei MENG ; Ding-ji CAI ; Qing ZHU ; Huan-gang ZHANG ; Meng-fei WANG ; Yang LIU ; Fang-rui TANG ; Feng SHAO ; Lan-ying CHEN ; Rong-hua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(9):143-156
Objective::To rapidly identify and analysis the chemical constituents in the methanol extract of heartwood of
4.Breast conserving surgery: a cross-sectional survey of 110 breast-conserving surgery centers in China
Shuyue ZHENG ; Yonghui SU ; Rong GUO ; Bingqiu XIU ; Jia WANG ; Qi ZHANG ; Weiru JI ; Lun LI ; Benlong YANG ; Yingying ZHANG ; Zhimin SHAO ; Jiong WU
Chinese Journal of General Surgery 2020;35(4):314-318
Objective:To determine national trends for breast conserving surgery and to explore the factors affecting the scale of breast conserving surgery in China.Methods:A questionnaire survey was mailed to 110 hospitals with an year′s volume of more than 200 breast cancer surgeries in each center in China concerning hospital variations and percentage of breast conserving surgery.Results:The overall proportion of breast conserving surgery is 21.9% for operable breast cancer in China. There is a significant positive correlation between local Gross Domestic Product (GDP) and the rate of breast conserving surgery ( P=0.001). Hospitals with higher annual operation volume have higher breast-conserving ratios( P=0.042). Compared with non-teaching hospitals, more patients with stage I breast cancer underwent breast conserving surgery in teaching hospitals ( P=0.021). After breast-conserving surgery, the proportion of positive margins needing reoperation had a lower percentage and in cancer hospitals it was the lowest ( P=0.023). The method of pathological evaluation and the remedy strategy for positive margin was not related to per capita GDP and hospital category ( P>0.05). Conclusions:This survey demonstrates the current practices of breast conserving surgery in China. Local GDP, hospital category and tumor stage were factors influencing breast conserving surgery. Breast conserving surgery in China is still at a low level compared with developed countries.
5.Current trend of breast cancer neoadjuvant treatment in China: a cross-sectional study
Jia WANG ; Bingqiu XIU ; Rong GUO ; Benlong YANG ; Qi ZHANG ; Yonghui SU ; Lun LI ; Weiru JI ; Yingying ZHANG ; Ayong CAO ; Zhimin SHAO ; Jiong WU
Chinese Journal of Oncology 2020;42(11):931-936
Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.
6.Current trend of breast cancer neoadjuvant treatment in China: a cross-sectional study
Jia WANG ; Bingqiu XIU ; Rong GUO ; Benlong YANG ; Qi ZHANG ; Yonghui SU ; Lun LI ; Weiru JI ; Yingying ZHANG ; Ayong CAO ; Zhimin SHAO ; Jiong WU
Chinese Journal of Oncology 2020;42(11):931-936
Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.
7. Current trends of breast reconstruction after mastectomy in China: a cross-sectional study
Bingqiu XIU ; Rong GUO ; Benlong YANG ; Qi ZHANG ; Jia WANG ; Yonghui SU ; Lun LI ; Weiru JI ; Yingying ZHANG ; Ayong CAO ; Zhimin SHAO ; Jiong WU
Chinese Journal of Oncology 2019;41(7):546-551
Objective:
To investigate the current trends of breast reconstruction(BR) after mastectomy in China.
Methods:
A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3% (169/183) of the questions were single-choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti-Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018.
Results:
A total of 110 units participated in the survey. In total, 87.3% (96/110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7% (6 534/61 099), among this, implant BR accounted for 65.7%(4 296/6 534), autologous BR accounted for 20.1% (1 312/6 534), and autologous combined implant BR accounted for 14.2% (927/6 534). Immediate reconstruction accounted for 67.6% (4 417/6 534) of BR, while delayed BR accounted for 32.4% (2 097/6 534). In 2017, 77.8% (35/45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6% (92/110). The proportion of reconstruction was positively correlated with the gross domestic product (GDP) per capita (
8.Current trends of breast reconstruction after mastectomy in China: a cross?sectional study
Bingqiu XIU ; Rong GUO ; Benlong YANG ; Qi ZHANG ; Jia WANG ; Yonghui SU ; Lun LI ; Weiru JI ; Yingying ZHANG ; Ayong CAO ; Zhimin SHAO ; Jiong WU
Chinese Journal of Oncology 2019;41(7):546-551
To investigate the current trends of breast reconstruction ( BR ) after mastectomy in China. Methods A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3%(169/183) of the questions were single?choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti?Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018.Results A total of 110 units participated in the survey.In total, 87.3%(96/110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7%( 6 534/61 099), among this, implant BR accounted for 65.7%(4 296/6 534), autologous BR accounted for 20.1%(1 312/6 534), and autologous combined implant BR accounted for 14.2%( 927/6 534 ). Immediate reconstruction accounted for 67.6%(4 417/6 534) of BR, while delayed BR accounted for 32.4%(2 097/6 534). In 2017, 77.8%( 35/45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6%( 92/110 ). The proportion of reconstruction was positively correlated with the gross domestic product ( GDP) per capita ( r=0.311, P=0.002). The one?step implant?based BR(IBBR) was the most preferred type in immediate BR. Two?step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6%( 62/96), while only 16.7%( 16/96) of hospitals used patient?reported outcome measure (PROM). The most commonly used PROM tool was BREAST?Q. Conclusions The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.
9.Current trends of breast reconstruction after mastectomy in China: a cross?sectional study
Bingqiu XIU ; Rong GUO ; Benlong YANG ; Qi ZHANG ; Jia WANG ; Yonghui SU ; Lun LI ; Weiru JI ; Yingying ZHANG ; Ayong CAO ; Zhimin SHAO ; Jiong WU
Chinese Journal of Oncology 2019;41(7):546-551
To investigate the current trends of breast reconstruction ( BR ) after mastectomy in China. Methods A list of hospitals with more than 200 cases of breast cancer surgery per year nationwide was obtained, and 110 institutions were selected according to the geographical distribution. The research was conducted in the form of a questionnaire survey, and 92.3%(169/183) of the questions were single?choice questions. Information such as demographics of surgeons and hospitals, number of mastectomy and BR, type and timing of BR was included in the survey. Survey formal notification letter was issued by the China Anti?Cancer Association Breast Cancer Committee and Chinese College of Surgeons, Committee of Mammary Surgeons. Questionnaires were sent to the respondents of each center by email. The survey time range was from January 1, 2017 to December 31, 2017. All data were completely collected before September 7, 2018.Results A total of 110 units participated in the survey.In total, 87.3%(96/110) of the hospitals have conducted BR surgery. The BR after mastectomy was 10.7%( 6 534/61 099), among this, implant BR accounted for 65.7%(4 296/6 534), autologous BR accounted for 20.1%(1 312/6 534), and autologous combined implant BR accounted for 14.2%( 927/6 534 ). Immediate reconstruction accounted for 67.6%(4 417/6 534) of BR, while delayed BR accounted for 32.4%(2 097/6 534). In 2017, 77.8%( 35/45) of the plastic surgery departments cooperated with general surgery departments. General BR could be conducted after mastectomy accounted for 83.6%( 92/110 ). The proportion of reconstruction was positively correlated with the gross domestic product ( GDP) per capita ( r=0.311, P=0.002). The one?step implant?based BR(IBBR) was the most preferred type in immediate BR. Two?step IBBR was the most preferred method in delayed BR. Hospitals that routinely evaluated aesthetics after BR accounted for 64.6%( 62/96), while only 16.7%( 16/96) of hospitals used patient?reported outcome measure (PROM). The most commonly used PROM tool was BREAST?Q. Conclusions The overall BR in China is on upward trend, but gap between China and the developed countries still exists. Breast surgery departments should strengthen further cooperation with plastic surgery departments. Simultaneously, the aesthetics evaluation and PROM after BR should be put a high premium.
10.Two new compounds from Smilax glaucochina.
Ji-Cheng SHU ; Min LIU ; Gen-Hua ZHU ; Rong-Hua LIU ; Feng SHAO ; Hui-Lian HUANG
China Journal of Chinese Materia Medica 2018;43(5):959-963
A new sesquiterpenes named glaucochinarol A (1) and a new phenylpropane glycoside named glcacochinaside A (2), together with six known ones, including trichothecolone (3), β-D-(6-O-trans-feruloyl)fructofuranosyl-α-D-O-glucopyranoisde (4), 3,4,5-trimethoxyphenyl-β-D-glucopyranoside (5), (4R)-p-menth-1-ene-7,8-diol-7-O-β-D-glucopyranoside (6), naringenin (7), and emodin-8-O-β-glucoside (8) were isolated from smilax glaucochina warb. Their structures were elucidated on the basis of NMR, MS and published data. Compounds 3-8 were isolated from the species for this first time.

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