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ObjectiveTo explore the mechanism of herbal pair Astragali Radix-Puerariae Lobatae Radix （AR-PLR） against type 2 diabetes mellitus （T2DM） based on network pharmacology and experimental verification. MethodThe active ingredients and targets of AR and PLR were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The related targets of T2DM were retrieved from disease databases and the common targets of drugs and diseases were extracted. The protein-protein interaction （PPI） network was analyzed and constructed by STRING and the network topology of key targets was analyzed by Cytoscape 3.7.1. Then gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analyses of core targets were carried out by DAVID to explore its possible molecular mechanism. The T2DM model was induced in rats by the high-fat diet combined with tail intravenous injection of streptozocin. The rats were divided into a normal group，a model group，a metformin group，and high-，medium- and low-dose AR-PLR groups. After four weeks of intragastric administration，the serum levels of fasting blood sugar （FBS），fasting insulin（FINS），aspartate aminotransferase（AST），alanine aminotransferase（ALT），triglyceride（TG），total cholesterol（TC），low-density lipoprotein cholesterin（LDL-C），high-density lipoprotein cholesterin （HDL-C），interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） of rats in each group were measured. The protein expression of insulin receptor substrate-2（IRS-2），phosphatidylinositol 3-kinase（PI3K），protein kinase B（Akt）， and forkhead box transcription factor O1（FoxO1） in rat liver was detected by Western blot. ResultA total of 131 core targets of AR-PLR in the treatment of T2DM were screened out by network pharmacology， where Akt1，mitogen-activated protein kinase 1 （MAPK1），TNF-α，and IL-6 were critical. As revealed by KEGG enrichment analysis， AR-PLR exerted the hypoglycemic effect mainly through the PI3K/Akt，TNF， and FoxO signaling pathways. Compared with the model group，the high- and medium-dose AR-PLR groups showed reduced FBS and FINS levels and increased glycogen level （P<0.05，P<0.01），all the AR-PLR groups showed decreased levels of AST，ALT，TG， and LDL-C （P<0.05，P<0.01）， the high- and low-dose AR-PLR groups showed decreased TC levels （P<0.05）. Compared with the model group， the high- and medium-dose AR-PLR groups showed reduced levels of IL-6 and TNF-α（P<0.05，P<0.01）， and the high-dose AR-PLR group showed increased expression of IRS-2， Akt， p-Akt， PI3K， and p-PI3K， and decreased expression of FoxO1 protein（P<0.05）. ConclusionAR-PLR has the characteristics of multi-component，Multi-target and multi-pathway in the treatment of T2DM. This herbal pair may regulate the PI3K/Akt/FoxO1 signaling pathway through IL-6， TNF-α， and other targets to affect insulin resistance， glycogen synthesis， gluconeogenesis， glucose transport， inflammation， immune response， and other processes， thereby treating T2DM.
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Shotgun based proteomics and peptidomics analysis were used to investigate the proteins and peptides in marine traditional Chinese medicine(TCM) Sepiae Endoconcha(cuttlebone). Peptides were extracted from cuttlebone by acidified methanol, and then strong cation exchange(SCX) resin was used to enrich those peptides. Also, proteins from cuttlebone were extracted and digested by trypsin. nano-LC Q Exactive Orbitrap mass spectrometry was used to analyze proteins and peptides from cuttlebone. As a result, a total of 16 proteins and 168 peptides were identified by protein database search, and 328 peptides were identified by De novo sequencing. The identified proteins were hemocyanin, enolase, myosin, actin, calmodulin, etc., and the identified peptides were derived from actin, histone, and tubulin. All these proteins and peptides were important components in cuttlebone, which would provide important theoretical and research basis for marine TCM cuttlebone investigations.
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Cations , Databases, Protein , Mass Spectrometry , Peptides , ProteomicsABSTRACT
Background@#Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.@*Methods@#Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to three tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using chi-squared test or Fisher’s exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.@*Results@#Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] years vs. 37 [32, 41] years, U =4.932, P =0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ2=9.291, P =0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6]℃ vs. 37.5 [37.0, 38.4]℃, U=2.057, P =0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ2=5.611, P=0.028) and respiratory rate (34 [18, 48] breaths/min vs. 24 [16, 60] breaths/min, U=4.030, P=0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] mg/L vs. 10.6 [1.9, 33.1] mg/L, U=1.315, P=0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62±6.60 g/L vs. 41.27±4.55 g/L, U =2.843, P =0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ2=16.01, P=0.001). Multivariate logistic analysis indicated that age (OR, 8.546; 95% CI: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003) and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.@*Conclusions@#Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature on admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.
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BACKGROUND@#Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.@*METHODS@#Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.@*RESULTS@#Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.@*CONCLUSIONS@#Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Betacoronavirus , Coronavirus Infections , Hospitals , Logistic Models , Pandemics , Pneumonia, Viral , Risk FactorsABSTRACT
BACKGROUND@#The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).@*METHODS@#Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate.@*RESULTS@#Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ = 23.257, P < 0.001), shock (11.9% vs. 0%, χ = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ = 7.655, P = 0.006).@*CONCLUSIONS@#Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Betacoronavirus , C-Reactive Protein , Coronavirus Infections , Mortality , Oxygen , Blood , Pandemics , Pneumonia, Viral , Mortality , Retrospective StudiesABSTRACT
Objective:To observe the clinical efficacy of fire-needle therapy in treating deglutition disorders due to pseudobulbar palsy in the remission stage of stroke.Methods:Sixty-two eligible subjects were divided into a fire-needle group and a rehabilitation group by a simple randomization method at a ratio of 1:1.The two groups received same basic intervention;in addition,the fire-needle group received fire-needle treatment,while the rehabilitation group received rehabilitation training.The two groups of subjects all received a 3-week treatment and were evaluated by the dysphagia severity rating scale (DSRS),modified Mann assessment of swallow ability (MMASA) and Kubota Toshio swallow test (KTST) before and after the intervention.The complications and adverse events occurred during the trial were recorded.The data were statistically analyzed.Results:At the third week,the DSRS,MMASA and KTST scores changed significantly compared with the baseline in both groups (P＜0.05),and the changes in the fire-needle group were more significant than those in the rehabilitation group (P＜0.05).The between-group comparison at the third week showed that the therapeutic efficacy in the fire-needle group was superior to that in the rehabilitation group (P＜0.05).Conclusion:Fire-needle therapy can obviously change the DSRS,MMASA and KTST scores in pseudobulbar palsy in the remission stage of stroke,and significantly enhance the therapeutic efficacy of the treatment of deglutition disorders in this stage.
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Many specific therapeutic antibody drugs have been developed for different indications. In drug development, it has been found that the antibody isotype framework can not only affect the physical and chemical properties of therapeutic antibodies, but also influence the activity and therapeutic effect. As a result, IgG isotype selection should be considered carefully in antibody drug development strategies. Because of the unique biological characteristics, IgG4 isotype has been used in some therapeutic antibodies for which effector functions are not desired. In order to provide new ideas for the development of antibody drugs, the research and application progress of IgG4 isotype in therapeutic antibody drug development has been reviewed.
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Humans , Drug Design , Immunoglobulin G , Chemistry , PharmacologyABSTRACT
Objective To investigate the relationship of the expression of vascular endothelial growth factor (VEGF)and the mi-crovessel density (MVD)with multi-slice spiral CT perfusion imaging.Methods 80 patients with solitary pulmonary nodules under-went perfusion scan by 16-slice spiral CT.Among them,45 diagnosed as lung cancer by pathology were enrolled in the study.After surgery,the slice of the pecimen was selected similar to the corresponding slice of CT images,and the immunohistochemical staining was performed to determine the expression of VEGF and the MVD.Spearman correlation analysis was used to determine the rela-tionship of expression of VEGF and the MVD with CT perfusion parameters.Results There was more expression of VEGF and the MVD in NSCLC.There were positive correlations between VEGF,MVD and BF (both P<0.05).The peak enhancement image (PEI)and TTP have significant correlations with MVD (P<0.05).Conclusion Some parameters of lung CT perfusion imaging are correlated with MVD and VEGF.
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With the development of bio-technological drugs, drug immunogenicity evaluation has become key factor of clarifying safety and efficacy of these drugs. It has become the focus to establish a stable and reliable evaluation system. Due to the advantages such as continuous real-time monitoring, surface plasmon resonance (SPR) technology has been widely used in bio-technological drugs immunogenicity assessments. Our study applied this technology to detect anti-drug antibody (ADA) of a recombinant human anti-rabies monoclonal antibody NM57 in the sera of 48 volunteers admitted in phase I clinical trials. This method could satisfy the basic requirements of detection of ADA.
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Humans , Antibodies, Anti-Idiotypic , Blood , Allergy and Immunology , Antibodies, Monoclonal , Blood , Allergy and Immunology , Antibodies, Viral , Blood , Allergy and Immunology , Rabies virus , Allergy and Immunology , Recombinant Proteins , Blood , Allergy and Immunology , Surface Plasmon ResonanceABSTRACT
During radiation for head and neck cancers,part of parotids are contained in planning target volume(PTV),which lead to parotids receiving radiation as the same as PTV.Radiation for head and neck cancers will influence the parotids.In the period of radiation,many factors will influence parotids,such as age,primary parotid volume,V10-40,weight and mean radiation dose et al.These factors will result in that the parotid volume reduces nearly 50％ and moves toward the middle line of the body.As a result,the real dose of the parotid receiving is higher than prescription dose.The excretion function of the parotid will be severely damaged after radiation,which will lead to xerostomia and influence the quality of patients life.
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Liver resection is the most effective treatment for hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly accepted as a guideline for HCC treatment, but it only recommends liver resection for the patients with HCC at stage 0 to A1. The surgical indications of the BCLC staging system need to be re-evaluated. 120 HCC patients undergoing curative liver resection were retrospectively stratified to the BCLC staging system, and the survival of the patients at stages A, B and C was analyzed. The justification of the BCLC staging system was re-evaluated. Fifty-two patients were classified at stage A, 51 at stage B and 17 at stage C respectively. The hospital mortality of this cohort was zero and the morbidity was 24.1%. The 1-, 2-, 3-year overall survival rate of this cohort was 81.6%, 68.3%, and 57.5% respectively. There was no significant difference in the survival rate between the patients at stage A and B (P>0.05). If the treatment guidelines of BCLC staging system were followed, the majority of the patients at stages A and B (77.7%, 80/103) would not have been treated surgically. Our data suggest that the surgical indications of the BCLC staging system are not justified for HCC treatment. More studies may be needed as for how to further broaden the surgical indications of the BCLC staging system in the future.
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Objective To investigate the relationship between type-2 diabetes mellitus and artery atherosclerosis(AS) in the elderly. MethodsThe clinical data of 277 elders,who were admitted in hospital between April 2005 and September 2007, were retrospectively analyzed. These elders were divided into four groups: type 2 diabetes with carotid atherosclerosis (CAS) group (group A, n=119), type 2 diabetes without CAS group (group B, n= 30), non-diabetic with CAS group (group C, n=32), non-diabetic without CAS group (group D, n=96). The correlation between carotid artery plaque and related factors were studied. Results① Compared with group C,fasting blood glucose[(7.14±2.49) mmol/L vs. (5.21±0.87) mmol/L], triglycefide [(1.41±0.78) mmol/L vs. (0.95±0.39) mmol/L],left and right common carotid artery IMT [(0.85±0.11) nun vs. (0.79±0.08) mm, (0.85±0.11)mm vs. (0.78±0.09)mm] and PI [(1.37±1.16) vs. (0.50±0.80)] of group A were significantly increased, while high density lipoprotein [(1.29±0.32) mmol/L vs. (1.58±0.45) mmol/L] is significantly decreased(P=0.01). ②Compared with group B, left and right common carotid artery IMT [(0.85±0.11) mm vs. (0.80±0.11)mm,(0.85±0.11)mm vs. (0.80±0.12)mm,PI[(1.37±1.16) vs. (0.00±0.00)]and incidence of stroke 34.5% (41/119) vs. 13.3% (4/30) of group A are significantly increased (P<0.05 or P<0.01). ③Carotid artery plaque was positively correlated with history of diabetes(r=0.051, P<0.01),hypertension(r= 0.169,P<0.01),coronary heart disease (r=0.109,P<0.05),stroke(r=0.136,P<0.05),fatty liver(r= 0.340,P<0.01),FBG(r=0.339,P<0.01),TG(r=0.195,P<0.01),APOB (r=0.152,P<0.05),but negatively correlated with HDL-C (r=-0.143, P<0.05). Conclusion The risk of AS is higher in elderly patients with type 2 diabetes than that of non-diabetes. The incidence of stroke is higher in type 2 diabetes with AS than those of type 2 diabetes without AS. Carotid artery plaque is positively correlated with diabetes, hypertension, history of coronary heart disease, history of stroke, fatty liver, FBG, TG, ApoB, but negatively correlated with HDL-C.
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In order to obviate the drawbacks of plasma immunoglobulins, the whole molecular recombinant human anti-HAV (hepatitis A virus) monoclonal antibody (anti-HAV IgG) produced and secreted by rCHO cells was purified and its physicochemical properties were extensively characterized. The rCHO cells were cultured in serum-free medium and the supernatants were collected. The recombinant human IgG molecules were sequentially purified by ultrafiltration, rProtein A Sepharose Fast Flow affinity chromatography, ion exchange chromatography and diafiltration. In affinity chromatography, prior to the target protein elution, an intermediate high salt wash step was inserted, different pH and salt concentrations were evaluated for the capacity of removing host cell DNA. The yield of the downstream purification process was approximately 40%. The purity of anti-HAV IgG thus generated was assayed with SEC-HPLC method, integration result showed that the monomeric IgG content was more than 99%. Western-blot was carried out with AP-antiHuman IgG (Fab specific) and AP-antiHuman IgG (Fc specific) respectively, the blot result demonstrated that the anti-HAV IgG is human antibody with Fab and Fc structure. The specific anti-HAV activity determined by ELISA was 100 IU/mg, with anti-HAV immunoglobulin as the working standard reference. Ligand leakage in the eluate of the affinity column was approximately 32 ng/mg IgG, while after further purification steps, it was decreased to less than 2 ng/mg IgG. Residual host cell DNA was monitored with solid dot blot assay, DNA can be removed effectively with intermediate high salt wash step in the affinity chromatography. Free sulfhydryl content of anti-HAV IgG was assayed with fluorescent spectrophotometer, the low molecular weight bands appeared in non-reducing SDS-PAGE may be caused by the presence of free sulfhydryl. The endotoxin content was less than 1EU/ mg examined by standard LAL test procedures. Anti-HAV IgG prepared with this process is able to fulfill the regulatory requirements of State Food and Drug Administration for recombinant products.