1.Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9.
Ya ZHONG ; Bo-Wen ZHANG ; Jin-Tao LI ; Xin ZENG ; Jun-Xia PEI ; Ya-Mei ZHANG ; Yi-Xi YANG ; Fu-Lun LI ; Yu DENG ; Qi ZHAO
Journal of Integrative Medicine 2023;21(6):584-592
OBJECTIVE:
To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.
METHODS:
Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.
RESULTS:
EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.
CONCLUSION
Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.
Animals
;
Mice
;
Interleukin-17/metabolism*
;
Intercellular Adhesion Molecule-1
;
Imiquimod/adverse effects*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Ligands
;
Psoriasis/chemically induced*
;
Keratinocytes
;
Inflammation/drug therapy*
;
Chemokines/metabolism*
;
Interferon-gamma/metabolism*
;
Disease Models, Animal
;
Mice, Inbred BALB C
2.Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure.
Xiao-Ya LI ; Chun-Hua WU ; Ying-Jie YAN ; Deng-Hui WANG ; Meng-Jie WANG ; Zhong-Wei HOU
Chinese Acupuncture & Moxibustion 2022;42(11):1278-1284
OBJECTIVE:
To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude.
METHODS:
Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR.
RESULTS:
Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05).
CONCLUSION
Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.
Animals
;
Rats
;
Male
;
Prolyl Hydroxylases/metabolism*
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Vascular Endothelial Growth Factor A/metabolism*
;
Rats, Sprague-Dawley
;
Procollagen-Proline Dioxygenase/metabolism*
;
Brain Injuries
;
Brain/metabolism*
;
RNA, Messenger
;
Water
3.Toxicity and Mechanism of Alkaloids in Sophorae Tonkinensis Radix et Rhizoma: A Review
Deng-xiang YU ; Shu-na WANG ; Yue-meng FU ; Li-ya YANG ; Zhong-ping DENG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(6):262-271
Sophorae Tonkinensis Radix et Rhizoma (STRER) is a commonly used Chinese medicine in clinical practice, which has the effects of clearing heat, removing the toxin, alleviating edema, and relieving sore throat. In recent years, the clinical reports of STRER-induced poisoning have gradually increased, with neurotoxicity and hepatotoxicity as the main characteristics of the acute attack. Timely treatment will lead to the good prognosis, but long-term or high-dose administration will cause irreversible damage. Therefore, the safety of clinical use of STRER should be highlighted. The chemical components in STRER mainly include alkaloids, flavonoids, triterpenoids, triterpenoid saponins, and polysaccharides, as well as small amounts of proteins, organic acids, and trace elements, where alkaloids both serve as the important material basis for the pharmacodynamic action and the main substances causing toxicity. The adverse events induced by STRER and its alkaloids include nerve injury, Hepatic injury, cardiovascular injury, kidney injury and reproductive injury, and gastrointestinal reaction. Quinolizidine alkaloids are the main toxic components, mainly including matrine, oxymatrine, cytisine, sophocarpine, oxysophocarpine, sophoridine, sophoramine, and lehmannine. Many studies have been carried out on the toxicity of different extracts and alkaloids of STRER in China and abroad, but there are no comprehensive and detailed reports on the toxicity mechanism of alkaloids in STRER. As a Chinese medicine, STRER is widely used. It's an urgent problem to clarify the material basis and mechanism of toxicity caused by STRER and reduce the toxicity for good clinical application. The present study reviewed the components of alkaloids, toxicity, and toxic mechanism of extracts and alkaloids in STRER to provide the basis for further development and clinical safe and effective application of STRER.
4.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
;
Brain Abscess
;
Child
;
Child, Preschool
;
Escherichia coli
;
Female
;
Humans
;
Hydrocephalus
;
Infant
;
Infant, Newborn
;
Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
;
Streptococcus agalactiae
;
Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
5.A high relapse risk of chronic drug-induced liver injury is correlated with a greater severity of liver fibrosis.
Ya DENG ; Chun Yan WANG ; Yi Ming FU ; Zhong Bin LI ; Dong JI
Journal of Southern Medical University 2022;42(11):1655-1661
OBJECTIVE:
To construct a risk prediction model for relapse of chronic drug-induced liver injury (DILI) and explore the correlation between DILI relapse risk and liver fibrosis.
METHODS:
We retrospectively collected the clinical data of 1138 patients with chronic DILI hospitalized from January, 2017 to January, 2022, including 154 patients with and 984 without DILI relapse. Based on the results of univariable and multivariable logistic regression analyses, a risk prediction model for DILI relapse was constructed, evaluated for its discrimination and calibration using AUC value and Hosmer-Lemeshow test, and verified with a 200 times 5, 10 and 20 folds cross validation method. Spearman correlation analysis was used to evaluate the correlation between the new model and liver fibrosis, and its diagnostic efficiency for liver fibrosis was assessed by comparison with APRI and FIB-4 using ROC curve.
RESULTS:
The proportions of patients with S0, S1, S2, S3 and S4 liver fibrosis were 1.9%, 13.1%, 42.2%, 27.9% and 14.9% in the relapse group, respectively, as compared with 8.9%, 43.5%, 26.1%, 17.1% and 4.4% in the non-relapse group, respectively, showing severer liver fibrosis in patients with than those without DILI relapse. Multivariable logistic regression analysis identified LSM≥13.7 kPa (OR=4.35, 95%CI: 2.61-7.25, P < 0.001), CHE < 2500 U/L (OR=5.17, 95%CI: 2.13-12.53, P < 0.001), CHE of 2500-5000 U/L (OR=4.07, 95%CI: 2.75-6.01, P < 0.001), and AST > 2×ULN (OR=2.29, 95%CI: 1.38-3.80, P=0.001) as risk factors for relapse of chronic DILI. The ACLS model constructed based on these non-invasive indicators had an AUC value of 0.803 (95%CI: 0.78-0.83). The results of Hosmer-Lemeshow goodness of fit test (χ2=7.73, P=0.46) and the cross validation tests (average AUC of 0.803) all showed a good stability of the model. Spearman correlation analysis showed that ACLS score was positively correlated with the severity of liver fibrosis (rho=0.530, P < 0.001). At the optimal cut-off value of 3 points for diagnosing moderate liver fibrosis, the ACLS model had an AUC value of 0.78 (with specificity of 72.7% and sensitivity of 73.3%), demonstrating a better efficacy than that of APRI and FIB-4 (P < 0.001). At the cut-off value of 6 for severe liver fibrosis, the diagnostic efficacy of the model (AUC=0.83; specificity 75.7%, sensitivity 72.7%) was still better than that of APRI (P < 0.001) but comparable with that of FIB-4 (P=0.38).
CONCLUSION
The patients at high risks of chronic DILI relapse have severer liver fibrosis and should be followed up regularly for timely aggressive treatment.
Humans
;
Chemical and Drug Induced Liver Injury, Chronic
;
Retrospective Studies
;
Chronic Disease
;
Liver Cirrhosis
6.Study on mechanism of combination of Platycodonis Radix and Lilii Bulbus with homology of medicine and food in treating pneumonia.
Ya-Ling DENG ; Xian-Wen YE ; Min-Min LIU ; Ying LIU ; Quan WAN ; Min HUANG ; Ya-Ting XIE ; Tao ZHANG ; Hai-Ping LIU ; Zhong-Wei ZHANG ; Jin-Lian ZHANG
China Journal of Chinese Materia Medica 2021;46(10):2403-2412
To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.
Drugs, Chinese Herbal
;
Humans
;
Medicine, Chinese Traditional
;
Molecular Docking Simulation
;
Pneumonia/drug therapy*
;
Reproducibility of Results
7.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
;
Antibodies, Viral
;
COVID-19/therapy*
;
COVID-19 Vaccines
;
Double-Blind Method
;
Humans
;
Immunization, Passive
;
Recombinant Fusion Proteins
;
SARS-CoV-2
8.Determination of Azide Ions in Blood by Pentafluorobenzyl Derivation Followed by GC-MS.
Mao Sheng LI ; Shui Qing ZHENG ; Zhen Hai SHENG ; Si Yang HE ; Qian Ya DENG ; Chen LIANG ; Zhong Ping WU ; Fang Qi CAO ; Meng DU
Journal of Forensic Medicine 2021;37(3):378-381
Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry (GC-MS) following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 μg/mL. The lowest detection limit was 0.25 μg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 μg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.
Azides
;
Gas Chromatography-Mass Spectrometry
;
Humans
;
Ions
9.A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.
Lin CAI ; Gen-Hui CHEN ; Qian-Jin LU ; Min ZHENG ; Yu-Zhen LI ; Jin CHEN ; Jie ZHENG ; Fu-Ren ZHANG ; Jian-Bin YU ; Sen YANG ; Fu-Qiu LI ; Sheng-Xiang XIAO ; Qiu-Ning SUN ; Jin-Hua XU ; Xing-Hua GAO ; Hong FANG ; Tian-Wen GAO ; Fei HAO ; Quan-Zhong LIU ; Ya-Ting TU ; Ruo-Yu LI ; Bao-Xi WANG ; Dan-Qi DENG ; Qing-Shan ZHENG ; Hong-Xia LIU ; Jian-Zhong ZHANG
Chinese Medical Journal 2020;133(24):2905-2909
BACKGROUND:
Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.
METHODS:
We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12.
RESULTS:
The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.
CONCLUSION:
During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method
;
Follow-Up Studies
;
Humans
;
Ointments
;
Psoriasis/drug therapy*
;
Resorcinols
;
Severity of Illness Index
;
Stilbenes
;
Treatment Outcome
10.Clinical outcome of tibiotalocalcaneal fusion using cannulated screw and humeral proximal locking plate inverted fixation through a lateral transfibular approach.
De-Xiang ZHANG ; Xiao ZHONG ; Xiao-Dong DENG ; Ming XIONG ; Wen LI ; Shao-Bing ZHANG ; Ya-Xing LI ; Hui ZHANG
China Journal of Orthopaedics and Traumatology 2020;33(12):1166-1170
OBJECTIVE:
To evaluate the clinical outcome of tibiotalocalcaneal fusion using cannulated screw and humeral proximal locking plate inverted fixation through a lateral transfibular approach.
METHODS:
From June 2015 to December 2018, 15 patients underwent a tibiotalocalcaneal fusion operation using cannulated screw and inverted proximal humerus locking plate through a transfibular approach. There were 10 males and 5 females with the age ranging from 45 to 72 (58.9±6.1) years, and the course of disease ranged from 2 to 35 (11.9±7.9)years. Preoperative diagnosis included 8 cases of post traumatic arthritis, 2 cases of Charcot arthritis, 2 cases of Charcot-Marie -Tooth (CMT), 1 case of ankle tuberculosis, 1 case of talar necrosis, and 1 case of pigmented villonnodular synovitis. Among them, 8 patients were combined with simple varus deformity, 4 patients with simple valgus deformity, 2 patients with equinovarus deformity, 1 patient with equinovarus deformity, 2 patients with adduction and internal rotation of middle and forefoot. American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and the visual analogue scale (VAS) score were used to evaluate the clinical outcome at the last follow up.
RESULTS:
One lost follow up and remaining fourteen patients were followed up. The follow up time ranged from 10 to 25(16.6±4.3) months. All the 15 patients had primary healing. Fusion time ranged from 15 to 24 (16.8 ± 2.4) weeks after operation. One patient with diabetes experienced delayed union and was successfully treated with secondary bone grafting combined with Platelet-Rich Plasma (PRP) injection. The AOFAS score increased from 38.7±3.3 to 84.5±2.6 (
CONCLUSION
Tibiotalocalcaneal fusion used cannulated screw and humeral proximal locking plate inverted fixation through a lateral transfibular approach has the advantages of relatively simple technique, high fusion rate, especially for patients with posterior foot deformity, which has satisfactory short term effects.
Ankle Joint
;
Arthrodesis
;
Bone Plates
;
Bone Screws
;
Female
;
Humans
;
Humerus
;
Male
;
Retrospective Studies
;
Treatment Outcome

Result Analysis
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