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OBJECTIVE@#To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.@*METHODS@#Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.@*RESULTS@#A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.@*CONCLUSIONS@#CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.
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Humans , Fatty Acids , Hepatitis B virus/genetics , Hepatitis B, Chronic , Metabolomics , T-Lymphocytes , TongueABSTRACT
Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from
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To systematically evaluate the clinical efficacy and safety of Danhong Injection combined with conventional therapy in improving diabetes mellitus complicated with coronary heart disease. Based on the online literature database(CNKI, Wanfang, VIP, PubMed, Web of Science, Cochran Library), the Chinese and English papers about the randomized controlled trial(RCT) of Danhong Injection in the treatment of diabetes mellitus complicated with coronary heart disease were searched comprehensively from the establishment of the databases to January 1, 2020. The papers were screened strictly according to the inclusion and exclusion criteria. Based on Jadad scale, the risk assessment of literature was carried out, and Meta-analysis was performed by STATA 12.0 software. Seventeen RCTs were included, involving 1 453 patients. The results of Meta-analysis showed that the combination of Danhong Injection and conventio-nal treatment could improve the clinical comprehensive effective rate(RR=1.47, 95%CI[1.38, 1.58], P<0.000 1), electrocardiogram(ECG) efficiency(RR=1.30, 95%CI[1.16, 1.46], P<0.000 1), efficiency of the angina pectoris(RR=1.41, 95%CI[1.25, 1.58], P<0.000 1), cholesterol level(SMD=-1.05, 95%CI[-1.95,-0.16], P=0.02), low-density lipoprotein(LDL) level(SMD=-0.50, 95%CI[-0.79,-0.21], P<0.000 1), coronary angina attack frequency(SMD=-3.71, 95%CI[-4.05,-3.36], P<0.000 1) and duration of angina pectoris(SMD=-2.96, 95%CI[-3.25,-2.66], P<0.000 1), with statistically significant differences. But the differences in fasting plasma glucose(FPG)(SMD=-0.19, 95%CI[-0.45, 0.08], P=0.16), plasma glucose of two hours after meal(2 hPG)(SMD=0.19, 95%CI[-0.11, 0.49], P=0.22), and high-density lipoprotein(HDL) level(SMD=0.10, 95%CI[-0.30, 0.49], P=0.62) after treatment were not statistically significant. Compared with the control group, there was no significant difference in adverse reactions(SMD=-2.96, 95%CI[-3.25,-2.66], P=0.75). The existing evidence shows that the combination of Western medicine and Danhong Injection can improve the clinical effect for diabetes mellitus complicated with coronary heart disease and has no obvious adverse reactions. However, due to the low level of overall literature evidence, high risk and some kind of publication bias, it still needs more high-quality randomized controlled trials and low-bias studies for further verification.
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Humans , Angina Pectoris , Coronary Disease/drug therapy , Diabetes Mellitus , Drugs, Chinese HerbalABSTRACT
Cerebrovascular diseases such as intracranial atherosclerosis, intracranial aneurysm and ischemic stroke have become the important causes of death and disability. The structural and functional changes of cerebrovascular, which are caused by various pathogenic factors, are the common pathophysiological basis of cerebrovascular diseases. At present, the etiology of cerebrovascular diseases has not been clarified. Growing evidence suggests that matrix metalloproteinases play an important role in the occurrence and development of cerebrovascular diseases. Blocking or inhibiting the expression of matrix metalloproteinases provides a new theoretical basis for non-invasive treatment of cerebrovascular diseases. This review discusses the relationship between matrix metalloproteinases and cerebrovascular diseases.
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Objective To explore the influencing risk factors of perioperative technical complications and clinical prognosis of stent-assisted coiling (SAC) for acute (≤28 d) ruptured intracranial aneurysm (RIA). Methods Acute RIA patients, who received SAC treatment in Changhai Hospital of Naval Medical University (Second Military Medical University) between Jan. 2012 and Jun. 2018, were retrospectively enrolled. The clinical and imaging data were analyzed using univariable analysis and multivariate logistic regression analysis to identify the potential risk factors of perioperative technical complications and clinical prognosis. Results A total of 509 acute RIA patients (170 males and 339 females), who underwent SAC treatment and received 30-d follow-up, were included in this study. Perioperative ischemic complications occurred in 28 cases (5.5%), and multivariate regression analysis showed that the location of aneurysms at the bifurcation of blood vessels was an independent risk factor of ischemic complications (odds ratio [OR]＝4.108, P＝0.001). Perioperative hemorrhagic complications occurred in 25 cases (4.9%), and multivariate regression analysis showed that age60 years was an independent risk factor of hemorrhagic complications (OR＝3.574, P＝0.014). The modified Rankin scale (mRS) scores of 81 patients (15.9%) ranged from 3 to 5 at discharge, 27 patients (5.3%) died with mRS score of 6, and the poor prognosis (mRS score2) rate was 21.2% (108/509). Multivariate regression analysis showed that age≥80 years, Hunt-Hess 3-5 class, perioperative ischemic complications, perioperative hemorrhagic complications and poor Glasgow coma scale (GCS) score were independent risk factors of poor prognosis (all P0.01). Conclusion For the acute RIA patients treated with SAC, the location of aneurysms at the vascular bifurcation is an independent risk factor of perioperative ischemic complications; age60 years is an independent risk factor for hemorrhagic complications; and the patients with poor GCS score at admission have a poor prognosis at discharge, and perioperative ischemic and hemorrhagic complications are independent risk factors of poor prognosis.
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<p><b>OBJECTIVE</b>The NOD/SCID/IL2Rγ (NSG) mouse strain is the most widely used immunodeficient strain for xenograft transplantation. However, the existing SCID mutation is a spontaneous mutation of the Prkdc gene, which leads to leaky T cell developmental block and difficulty in genotyping. It is therefore important to develop a new strain of NSG mice with targeted disruption of Prkdc and IL2Rγ genes.</p><p><b>METHODS</b>Targeted disruption of Prkdc and IL2Rγ genes was achieved using the CRISPR/Cas9 system. By intercrossing the knockout and NOD mice, we obtained a novel strain of NOD/SCID/IL2Rγ(NSG) mice, denoted as cNSG (Chinese NSG) mice.</p><p><b>RESULTS</b>In addition to the NOD mutation, cNSG mice exhibited a complete absence of T cells, B cells and NK cells. cNSG mice allowed more efficient engraftment of human cancer cells than the commonly used immunodeficient nude mice.</p><p><b>CONCLUSION</b>cNSG mice will provide an important xenotransplantation model for biomedical research.</p>
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Objective To analyze the index of relative apparent diffusion coefficient (rADC)of magnetic resonance diffusion weighted imaging (DWI)for nasopharyngeal carcinoma with cervical metastatic lymph node before and after treatment,assess the application value of rADC in the recent curative effect after radiotherapy and chemotherapy.Methods 45 cases of nasopharyngeal carcinoma with cervical metastatic lymph nodes proved pathologically were selected as the research objects,which was including 107 pieces of metastatic lymph nodes and underwent DWI.The rADC index of cervical metastatic lymph nodes before and after radiotherapy and chemotherapy was measured and calculated.The cervical metastatic lymph nodes were divided into effective group (CR+PR,n=84)and ineffective group(SD+PD,n=23),and the difference of the rADC index between the two groups was compared.Results For the target volume disappeared or reduced more than 30% in the effective group after treatment,the rADC index was significantly higher than that before treatment(t=4.981, P<0.05).The rADC difference between effective group and ineffective group was statistically significance (t=3.471,P<0.05).Conclusion rADC can be used as the auxiliary marker for the evaluation of short-term curative effect of nasopharyngeal carcinoma with cervical metastatic lymph nodes.
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Objective:To evaluate preliminarily immunocompetence and immunoprotection of a NMB0315 nucleic acid vaccine,a recombinant protein vaccine and a nucleic acid vaccine plus a recombinant protein vaccine against Neisseria meningitidis serogroup B in mice, and to provide reliable experimental basis for further exploration of the effective immunization methods and pathways of NMB0315 vaccine. Methods:The NMB0315 nucleic acid vaccine [ pcDNA3. 1 (+)/NMB0315 ] and recombinant protein vaccine(pET-30a/NMB0315)were prepared. Female BALB/c mice were inoculated with a NMB0315 DNA vaccine followed by boosting with recombinant protein NMB0315 through intramuscular and intraperitoneal immunization respectively. Next, humoral immunologic response and cellullar immunologic response were detected in female BALB/c mice by ELISA. The survival rate of BALB/c mice was used to evaluate immunoprotection of the vaccines in mice. Results:Specific IgG,IgG1,IgG2a,and sIgA,induced by the NMB0315 DNA vaccine(pNMB0315-CpG),protein NMB0315 vaccine(rNMB0315-FA),NMB0315 DNA vaccine prime-protein boost at week 8, were detected by indirect ELISA,the A450 values were up to(0. 505±0. 042,0. 513±0. 022,0. 342±0. 017,0. 250±0. 015),(0. 823± 0. 061,0. 807±0. 045,0. 596±0. 027,0. 450±0. 028)and(0. 694±0. 053,0. 711±0. 032,0. 455±0. 021,0. 386±0. 024)respectively, which was significantly higher than the PBS control(P<0. 05). The antibody level of protein vaccine was significantly higher than the nucleic acid vaccine group and combined immunization group ( P<0. 05 ) . The stimulation index and IFN-γ level of combined immunization group were significantly higher than the protein vaccine group and nucleic acid vaccine group(P<0. 05). The bactericidal titer of nucleic acid vaccine group, protein vaccine group and combined immunization group reached 1 :64, 1 :128 and 1 :128 respectively,and the protection rates were 70%,95% and 80% respectively. The IgG2a/IgG1 ratios of the nucleic acid vaccine group, the recombinant protein vaccine group and the combined immunization vaccine group were all less than 1 at week 2, 4, 6, 8. Conclusion:The humoral immunity effects( including mucosal immune) induced by the NMB0315 vaccines form high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine;and the cellular immune effects from high to low were as follows:the combined immunization vaccine group, the nucleic acid vaccine group, the recombinant protein vaccine group;The protection effects induced by the NMB0315 vaccines in BALB/c mice within 72 hours from high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine group.
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Objective:To evaluate preliminarily immunocompetence and immunoprotection of a NMB0315 nucleic acid vaccine,a recombinant protein vaccine and a nucleic acid vaccine plus a recombinant protein vaccine against Neisseria meningitidis serogroup B in mice, and to provide reliable experimental basis for further exploration of the effective immunization methods and pathways of NMB0315 vaccine. Methods:The NMB0315 nucleic acid vaccine [ pcDNA3. 1 (+)/NMB0315 ] and recombinant protein vaccine(pET-30a/NMB0315)were prepared. Female BALB/c mice were inoculated with a NMB0315 DNA vaccine followed by boosting with recombinant protein NMB0315 through intramuscular and intraperitoneal immunization respectively. Next, humoral immunologic response and cellullar immunologic response were detected in female BALB/c mice by ELISA. The survival rate of BALB/c mice was used to evaluate immunoprotection of the vaccines in mice. Results:Specific IgG,IgG1,IgG2a,and sIgA,induced by the NMB0315 DNA vaccine(pNMB0315-CpG),protein NMB0315 vaccine(rNMB0315-FA),NMB0315 DNA vaccine prime-protein boost at week 8, were detected by indirect ELISA,the A450 values were up to(0. 505±0. 042,0. 513±0. 022,0. 342±0. 017,0. 250±0. 015),(0. 823± 0. 061,0. 807±0. 045,0. 596±0. 027,0. 450±0. 028)and(0. 694±0. 053,0. 711±0. 032,0. 455±0. 021,0. 386±0. 024)respectively, which was significantly higher than the PBS control(P<0. 05). The antibody level of protein vaccine was significantly higher than the nucleic acid vaccine group and combined immunization group ( P<0. 05 ) . The stimulation index and IFN-γ level of combined immunization group were significantly higher than the protein vaccine group and nucleic acid vaccine group(P<0. 05). The bactericidal titer of nucleic acid vaccine group, protein vaccine group and combined immunization group reached 1 :64, 1 :128 and 1 :128 respectively,and the protection rates were 70%,95% and 80% respectively. The IgG2a/IgG1 ratios of the nucleic acid vaccine group, the recombinant protein vaccine group and the combined immunization vaccine group were all less than 1 at week 2, 4, 6, 8. Conclusion:The humoral immunity effects( including mucosal immune) induced by the NMB0315 vaccines form high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine;and the cellular immune effects from high to low were as follows:the combined immunization vaccine group, the nucleic acid vaccine group, the recombinant protein vaccine group;The protection effects induced by the NMB0315 vaccines in BALB/c mice within 72 hours from high to low were as follows:the recombinant protein vaccine group, the combined immunization vaccine group, the nucleic acid vaccine group.
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Objective To compare the clinical application value between Leep knife operation and Vaginal ligation operation in submucous uterine myoma during the basic-level hospital.Methods According to digital table method,63 cases with submucous uterine myomas were randomly divided into the trial group and control group,33 cases in the trial group used the Leep knife,30 cases in the control group used vaginal ligation operation.Results The amounts of the trial group such as operation time,complications bleeding,operation stump bleeding rate and menstrual disorder improvement rate were (8 ± 3)min,(7 ± 3)mL,0.0％,91.0％,while the amounts of the control group were (10 ± 3) min,(10 ± 4) mL,13.3％,70.0％.The difference was statistically significant (t =2.642,3.387,x2 =4.698,4.455,all P ＜ 0.05).Conclusion Leep knife operation is better than Vaginal ligation operation,because it has shorter operation time,less complications bleeding,lower operation stump bleeding rate and higher menstrual disorder improvement rate.It is worthy of applying in the basic-level hospital.
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Objective To investigate the effect and underlying mechanism of apolipoprotein E (APOE) genetic polymorphism in treating blood brain barrier (BBB) breakdown after traumatic brain injury (TBI).Methods Human APOE knock-in mice (ε3,ε4),APOE knockout mice,and APOE wild-type mice with each numbering 80 were respectively divided into TBI group (n =50),sham-operation group (n =15) and normal control group (n =15) according to the random number table.TBI group was subdivided at 1 day (n=15),3 days (n=15),and7 days (n=20).TBI was induced with a pneumatically operated injury device.BBB permeability to large or small molecules was evaluated by measuring Evans blue (EB) and fluorescein sodium (NaFI) extravasation into the damage area at 1,3,and 7 days postinjury.Brain water content was determined using the dry-wet method.Western blotting and qRT-PCR for tight junction-associated proteins Occludin and Claudin-5 were performed at 7 days postinjury.Results With respect to normal control group,BBB permeability to EB and NaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice.There appeared significant increase in BBB permeability to EB and NaFI in TBI group,with insignificant differences among rats of each genotype at 1 and 3 days postinjury (P ＞ 0.05).Whereas at 7 days postinjury,BBB permeability to EB in APOE wild-type and e3 mice returned to the normal level (P ＞ 0.05),but it re mained at a high level in APOE knockout and ε4 mice (P ＜ 0.01).Meanwhile,BBB permeability toNaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice (P ＜ 0.01).Brain water content was equivalent among rats of each genotype at 1,3 and 7 days postinjury (P ＞0.05).Western blotting and qRT-PCR demonstrated Occludin and Claudin-5 in ε4 and APOE knockout mice were significantly lower than those in ε3 and APOE wide-type mice (P ＜ 0.05).Conclusion APOE plays an important role in restoration of BBB function after TBI,but ε4 may impede the recovery of BBB breakdown after TBI through its effect on tight junction.
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A total of 100 HIN1 flu real-time-PCR positive throat swabs collected from fever patients in Zhejiang,Hubei and Guangdong between June and November 2009,were provided by local CDC laboratories.After MDCK cell culture,57 Influenza A Pandemic (H1N1) viruses were isolated and submitted for whole genome sequencing.A total of 39 HA sequences,52 NA sequences,36 PB2 sequences,31 PB1 sequences,40 PA sequences,48 NP sequences,51 MP sequences and 36 NS sequences were obtained,including 20 whole genome sequences.Sequence comparison revealed they shared a high degree of homology (96％～99％) with known epidemic strains (A/Califomia/04/2009(H1N1).Phylogenetic analysis showed that although the sequences were highly conserved,they clustered into a small number of groups with only a few distinct strains.Site analysis revealed three substitutions at loop 220 (221-228) of the HA receptor binding site in the 39 HA sequences:A/Hubei/86/2009 PKVRDQEG→PKVRDQEA,A/Zhejiang/08/2009 PKVRDQEG→PKVRDQER,A/Hubei/75/2009PKVRDQEG→PKVRDQGG,the A/Hubei/75/2009 was isolated from an acute case,while the other two were from patients with mild symptoms.Other key sites such as 119,274,292 and 294 amino acids of NA protein,627 of PB2 protein were conserved.Meanwhile,all the M2 protein sequences possessed the Ser32Asn mutation,suggesting that these viruses were resistant to adamantanes.Comparison of these sequences with other H1N1 viruses collected from the NCBI database provides insight into H1N1 transmission and circulation patterns.