1.Value of contrast-enhanced percutaneous ultrasound in the diagnosis of rotator cuff tear subtype.
Bi-Li LIU ; Yue SHAN ; Qi ZHONG ; Dan GE ; Yan-Ping LI ; Juan LYU ; Shu-Zhi GAN
China Journal of Orthopaedics and Traumatology 2023;36(10):974-981
OBJECTIVE:
To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes.
METHODS:
From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated.
RESULTS:
The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears).
CONCLUSION
Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.
Male
;
Female
;
Humans
;
Infant, Newborn
;
Infant
;
Child, Preschool
;
Child
;
Rotator Cuff Injuries/diagnostic imaging*
;
Rotator Cuff/diagnostic imaging*
;
Sensitivity and Specificity
;
Ultrasonography
;
Magnetic Resonance Imaging/methods*
;
Rupture
;
Arthroscopy
2.The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis.
Si Jin ZHONG ; Jun Jun GAO ; Ping TANG ; Yue Ping LIU ; Shu Lian WANG ; Hui FANG ; Jing Ping QIU ; Yong Wen SONG ; Bo CHEN ; Shu Nan QI ; Yuan TANG ; Ning Ning LU ; Hao JING ; Yi Rui ZHAI ; Ai Ping ZHOU ; Xin Gang BI ; Jian Hui MA ; Chang Ling LI ; Yong ZHANG ; Jian Zhong SHOU ; Nian Zeng XING ; Ye Xiong LI
Chinese Journal of Oncology 2023;45(2):175-181
Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans
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Aged
;
Treatment Outcome
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Retrospective Studies
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Combined Modality Therapy
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Chemoradiotherapy/methods*
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Urinary Bladder Neoplasms/radiotherapy*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Neoplasm Staging
3.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
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Female
;
Gestational Age
;
Humans
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Infant
;
Infant, Extremely Premature
;
Infant, Newborn
;
Pregnancy
;
Respiratory Distress Syndrome, Newborn/epidemiology*
;
Retrospective Studies
;
Treatment Outcome
4.Exploration of mechanism of "simultaneous treatment of brain and heart" of Naoxintong Capsules based on Toll-like receptor signaling pathway.
Qian-Nan LI ; Jin-Feng SHANG ; Ting-Yue JIANG ; Lei BI ; Jia-Kang JIAO ; Ying-Hui LU ; Qi SONG ; Shabuer-Jiang LIZHA ; Xin LIU
China Journal of Chinese Materia Medica 2022;47(15):4110-4118
This study aims to explore the mechanism of "simultaneous treatment of the brain and the heart" of Naoxintong Capsules(NXT) under cerebral ischemia based on Toll-like receptor(TLR) signaling pathway.Male SD rats were randomized into sham operation group, model group, NXT group, and positive drug group.Middle cerebral artery occlusion(MCAO) model rats were used in model group, NXT group, and positive drug group, respectively.Neurological function was scored with the Bederson scale, and brain infarct rate was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining.Brain edema was detected with wet-dry weight method.Hematoxylin-eosin(HE) staining and TdT-mediated dUTP nick-end labeling(TUNEL) staining were used to observe and count apoptotic cardiocytes.In addition, serum myocardial enzymes were measured.The expression of 8 TLR signaling pathway-related proteins interferon-α(IFN-α), interferon regulatory factor-3(IRF3), interferon regulatory factor-7(IRF7), TLR2, TLR4, TLR7, TLR9, and tumor necrosis factor-α(TNF-α) in the cerebral cortex and heart of rats was detected by Western blot. Brain infarct rate, neurological function score, and brain water content in NXT group decreased significantly compared with those in the model group. At the same time, the reduction in apoptosis rate of cardiocytes and the content of serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), creatine kinase(CK), and lactate dehydrogenase(LDH) were decreased in the NXT group.Systems pharmacological results and previous research showed that TLR signaling pathway played an important role in immune inflammatory response.The study of TLR signaling pathway and related proteins is helpful to elucidate the mechanism of "simultaneous treatment of the brain and the heart". Western blot results showed that NXT significantly inhibited the expression of IRF3, IRF7, TLR2, TLR7, and TNF-α in cerebral cortex and heart under cerebral ischemia.Cerebral ischemia influences cardiac functions, and TLR signaling pathway is one of the pathways for "simultaneous treatment of the brain and the heart" of NXT.
Animals
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Brain/metabolism*
;
Brain Ischemia/metabolism*
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Capsules
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Drugs, Chinese Herbal
;
Infarction, Middle Cerebral Artery/drug therapy*
;
Male
;
Myocytes, Cardiac
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Toll-Like Receptor 2/metabolism*
;
Toll-Like Receptor 7/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
5.Association of Early-Life Famine Exposure with Metabolic Dysfunction-Associated Fatty Liver Disease and Fibrosis in Adulthood.
Ran WEI ; Hong Yan QI ; Lin LIN ; Yuan Yue ZHU ; Yi ZHANG ; Jie ZHANG ; Xue Yan WU ; Chun Yan HU ; Shuang Yuan WANG ; Hong LIN ; Yu XU ; Min XU ; Yu Fang BI ; Wei Qing WANG ; Jie Li LU ; Guang NING ; Yu Hong CHEN
Biomedical and Environmental Sciences 2022;35(6):558-562
Adult
;
Age Factors
;
China
;
Famine
;
Female
;
Fibrosis
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Humans
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Liver Diseases
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Prenatal Exposure Delayed Effects
;
Sex Factors
6.Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial.
Jun Qin LEI ; Wen Yang LIU ; Yuan TANG ; Yu TANG ; Ning LI ; Hua REN ; Chi YIHEBALI ; Yong Kun SUN ; Wen ZHANG ; Xin Yu BI ; Jian Jun ZHAO ; Hui FANG ; Ning Ning LU ; Ai Ping ZHOU ; Shu Lian WANG ; Yong Wen SONG ; Yue Ping LIU ; Bo CHEN ; Shu Nan QI ; Jian Qiang CAI ; Ye Xiong LI ; Jing JIN
Chinese Journal of Oncology 2022;44(3):282-290
Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
Colorectal Neoplasms
;
Humans
;
Liver/pathology*
;
Lung/pathology*
;
Prospective Studies
;
Radiosurgery/methods*
7.Identification of potential Q-markers of Semen Armeniacae Amarum based on UPLC-MS/MS and metabonomics
Yao CHENG ; Yue-lin BI ; Xin FENG ; Jia-qi WANG ; Hao-ran XU ; Tong-hua ZHANG ; Geng-yuan YU ; Chen-ning ZHANG ; Jing-hong WANG ; Yi-kun SUN
Acta Pharmaceutica Sinica 2022;57(10):3195-3202
Bitter almonds (Semen Armeniacae Amarum) are prone to oil deterioration during storage, so they often require mashing prior to clinical use. To confirm the medical value of bitter almonds "being mashed when used" and to determine the optimal storage conditions for bitter almonds, UPLC-MS/MS was used to perform a comparative study of the chemical composition of bitter almonds in different storage states (mashed and unmashed), storage times (0, 2 and 4 weeks), and storage temperatures (25 ℃ and 4 ℃). A total of 58 substances were identified in bitter almond extracts through literature review, this group's previous work, and a Compound Discoverer software search. Statistically significant differences were found in the chemical composition and content of bitter almonds in different storage states, storage times, and storage temperatures. The results show that the chemical composition of bitter almonds stored unmashed was more stable than that of bitter almonds stored mashed; the chemical composition of bitter almonds stored at 4 ℃ was more stable than that of bitter almonds stored at 25 ℃; and the shorter the storage time, the less the chemical composition changed. Amygdalin, the main medicinal component of bitter almonds, showed statistically significant differences in content under the above three storage conditions, which can be used as a potential quality marker for bitter almonds.
8.Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant.
Xiao-Yu FAN ; Yi ZHANG ; Jia-Yi HUANG ; Ting-Ting HONG ; Jia-Yao BI ; Qi-Lin YANG ; Shou-Ying DU ; Peng-Yue LI
China Journal of Chinese Materia Medica 2021;46(17):4410-4416
This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.
Emulsions
;
Isoflavones
;
Particle Size
;
Solubility
9.Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19.
Ling Hua LI ; Hong Wei TU ; Dan LIANG ; Chun Yan WEN ; An An LI ; Wei Yin LIN ; Ke Qi HU ; Wen Shan HONG ; Yue Ping LI ; Juan SU ; San Tao ZHAO ; Wei LI ; Run Yu YUAN ; Ping Ping ZHOU ; Feng Yu HU ; Xiao Ping TANG ; Chang Wen KE ; Bi Xia KE ; Wei Ping CAI
Biomedical and Environmental Sciences 2021;34(12):976-983
Objective:
The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.
Results:
NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.
Conclusion
We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Adult
;
Aged
;
Aged, 80 and over
;
Antibodies, Neutralizing/immunology*
;
Antibodies, Viral/immunology*
;
COVID-19/immunology*
;
Female
;
Humans
;
Kinetics
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Male
;
Middle Aged
;
Neutralization Tests
;
SARS-CoV-2
10.Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali.
Chun-Hong ZHANG ; Xiao YANG ; Jing-Ran WEI ; Na-Mu-Han CHEN ; Jian-Ping XU ; Ya-Qiong BI ; Min YANG ; Xue GONG ; Zi-Yan LI ; Kai REN ; Qi-Heng HAN ; Lei ZHANG ; Xue LI ; Ming-Yue JI ; Cong-Cong WANG ; Min-Hui LI
Chinese journal of integrative medicine 2021;27(3):229-240
Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

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