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The coronavirus SARS-CoV-2 has a severe impact on global public health, and the emerging variants threaten the efficacy of the circulating vaccines. Here, we report that a single vaccination with a non-replicating chimpanzee adenovirus-based vaccine against the SARS-CoV-2 Delta variant (JS1-delta) elicits potent humoral, cellular and mucosal immunity in mice. Additionally, a single intranasal administration of JS1-delta provides effective protection against the Delta (B.1.617.2) variant challenge in mice. This study indicates that chimpanzee adenovirus type 3 (ChAd3) derived vector represents a promising platform for antiviral vaccine development against respiratory infections and JS1-delta is worth further investigation in human clinical trials. HighlightsO_LIA new chimpanzee adenoviral vaccine against the SARS-CoV-2 Delta variant was developed. C_LIO_LIThe vaccine elicited potent humoral, cellular and mucosal immunity in mice. C_LIO_LIThe vaccine protected mice from the Delta variant challenge. C_LI
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Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% global population are still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a means of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system as well as stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2. Brief summaryNb22 exhibits ultrahigh potency against Delta variant in vitro and is exploited by crystal structural analysis; furthermore, animal study demonstrates high effectiveness in the treatment and short-term instantaneous prophylaxis in hACE2 mice via intranasal administration. HighlightsO_LINb22 exhibits ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). C_LIO_LIStructural analysis elucidates the ultrapotent neutralization of Nb22 against Delta variant. C_LIO_LINb22 demonstrates complete protection in the treatment of Delta variant infection in hACE2 transgenic mice. C_LIO_LIWe complete the proof of concept of STIP against SARS-CoV-2 using intranasal Nb22 with ultrahigh potency and long-lasting retention in respiratory system. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/459055v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@144516corg.highwire.dtl.DTLVardef@3dc17forg.highwire.dtl.DTLVardef@6a8962org.highwire.dtl.DTLVardef@619cd7_HPS_FORMAT_FIGEXP M_FIG C_FIG
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BackgroundWith coronavirus disease 2019 (Covid-19) ravaging the global, concern has been aroused whether discharged Covid-19 patients with reappeared positive nucleic acid test results are infected again. ObjectiveTo analyze the clinical characteristics of discharged Covid-19 patients with reappeared positive nucleic acid test results and to track clinical outcomes of them. MethodsWe extracted clinical data on 938 Covid-19 patients from Wuhan Union Hospital (West Branch), and we obtained information about residual symptoms and nucleic acid tests after discharge through follow-up study. We evaluated the relationship of clinical characteristics and reappeared positive results. Each patient had at least 44 days of follow-up. ResultsOf 938 discharged patients, a total of 58 (6.2%) had reappeared positive nucleic acid test results and 880 remain negative. Among patients over the age of 50, the factors we found to be associated with re-positive results were coronary artery disease (14.1%, vs. 5.5% among those without coronary artery disease; odds ratio, 2.81; 95% confidence interval [CI], 1.28 to 6.15), and hypertension (9.5%, vs. 4.9% among those without hypertension; odds ratio, 2.05; 95% CI, 1.10 to 3.82). As of May 11, 2020, 54 (93.1%) re-positive patients turned negative again while two patients remained positive, and two patients was lost to the second follow-up. ConclusionCoexisting diseases including coronary artery disease and hypertension were substantial risk factors for re-positive outcomes among patients over 50. And most re-positive patients tended to return negative eventually.
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Objective To investigate the clinical superiority of Chaiqin tiaogan capsule in the treatment of hepatitis B virus.Methods 126 cases of patients admitted to hospital from January 2014 to June 2015 were randomly divided into two groups, the control group (interferon and lamivudine) and the experimental group (interferon, lamivudine and Chaiqin tiaogan capsule), each group of 63 cases.The HBsAg and HBV-DNA negative rate, the changes of liver function and the incidence of adverse reactions in the experimental group were observed and compared.Results The HBsAg negative rate and the HBV-DNA negative rate after treatment three and six months in the control group were significantly higher than the experimental group ( P<0.05).The levels of ALT, AST and DBiL in the control group and the experimental group were significantly decreased, and the levels of ALT, AST and DBiL after treatment six months in the control group were significantly lower than the experimental group ( P <0.05 ) .There were no serious adverse reactions in the control group and experimental group, there was no significant difference between two groups.Conclusion Chaiqin tiaogan capsule can effectively inhibit HBV replication and improve liver function, it has good tolerability and safety applied to clinical.
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Objective To analyze the clinical features and risk factors for mortality of patients with severe fever with thrombocytopenia syndrome (SFTS) in Zhoushan, the eastern coastal of China with high incidence of severe fever with thrambocytopenia syndrome bunyavirus infection, to provide reference for reducing the mortality rate of SFTS.Methods Clinical data of 107 cases of SFTS from Zhoushan Hospital during June 2011 to June 2016 were retrospectively analyzed.According to the prognosis, patients were divided into survival group and death group.The clinical features and the laboratory results were analyzed with a case-control method to analyze the prognostic factors.Normal distribution data were compared with the independent t test.Kolmogorov-Smirnov Z test were used in data with skewness distribution.Categorical data were analyze by chi-square test.The related risk factors were analyzed with the receiver-operating characteristic (ROC) curve and multivariate unconditioned logistics regression analysis.Results Seventeen cases among 107 STFs patients died, yielding the mortality rate of 15.9%.The proportion of patients suffering from two or more underlying diseases, with disorders of consciousness, activated partial thromboplastin time (APTT), the level of creatine kinase (CK), lactate dehydrogenase (LDH) as well as sepsis-related or sequential organ failure assessment (SOFA) score in death group were all significantly higher than those in the survival group (all P73.45 s, SOFA scores >9 were the independent risk factors for mortality of SFTS (OR=6.947, 8.459 and 11.770, respectively, all P<0.05).Conclusion Ca2+, APTT and SOFA score are the independent risk factors for prognosis of SFTS, which provide reference for prognostic evaluation of SFTS.
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Objective To explore the beauty of mesalazine combined with Bifid Triple viable bacilli clinical efficacy in the treatment of ulcerative colitis.Methods 72 patients with ulcerative colitis ( UC) in zhoushan maternal and child health hospital were selected and divided into experimental group and control group,36 cases in each group.The control group was treated with oral administration of melamine and the experimental group was treated with Bifidobacterium triple live bacteria on the basis of oral control group.The levels of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive protein ( CRP) concentration in serum of patients were detected.Follow up observation and record of the experimental group and the control group to improve the symptoms, clinical efficacy and adverse reactions after treatment.Results After treatment,serum MDA, CRP concentrations of the two groups were significantly lower than those before treatment concentration, SOD concentration was significantly increased, the differences were statistically significant (P<0.05) , serum MDA, CRP levels in the experimental group were lower than the control group, the concentration of SOD was significantly higher than control group,the differences were statistically significant (P<0.05) .After treatment, abdominal pain, diarrhea, mucus and blood stool symptoms of two groups were significantly improved compared with before treatment, abdominal pain, diarrhea and bloody mucus symptoms in the experimental group were lower than the control group(P<0.05).Incidence of adverse reactions in the experimental group was significantly lower than the control group, the differences were statistically significant (P<0.05).Conclusion The efficacy of oral administration of methadiazole in combination with Bifidobacterium triple live bacteriain the treatment of ulcerative colitis is significant, Can reduce MDA, CRP concentration, increased SOD activity.
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One hundred and ten patients with primary hepatocellular carcinoma underwent hepatectomy from 2005 to 2010.Different methods of hepatic exclusion were applied in the surgery,including 54 patients with total hepatic vascular exclusion,22 with half hepatic vascular exclusion and 34 with regional hepatic vascular exclusion.The recovery of postoperative liver function was retrospectively analyzed.The results showed that the postoperative liver function of regional hepatic vascular exclusion [ALT(311 ± 80) U/L,total bilirubin (TB) (22.2 ± 8.3) μmoL/L at 1 st day and ALT (58 ± 17) U/L,TB (11.3 ± 3.1)μmol/L at 7th day] was better than that of total hepatic vascular exclusion [ALT(874 ±299)U/L,TB (42.9± 19.1) μmol/L at 1st day (P＜0.05) and ALT (108-±52)U/L,TB (14.6±9.2) μmol/L at 7th day] (P ＜ 0.05,＞ 0.05),indicating that regional hepatic vascular exclusion can effectively reduce hepatic injury during the operation and promote recovery of liver function after operation.
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ObjectiveTo investigate the protective effects and mechanism of ursodeoxycholic acid (UDCA) on α-naphthylisothi (ANIT)-induced cholestatic liver injury in rats.MethodsA total of 48 Sprague-Dawley (SD) rats were selected.Fouty-two rats were gavaged with ANIT (100 mg/kg) to induce acute liver injury,six rats were sacrificed 24 hours after the liver injury and the rats left were evenly divided into control group which were gavaged with saline and UDCA group which were gavaged with UDCA (20 mg/kg).Six rats were sacrificed at 48 hours,72 hours and 96 hours after modeling.The six untreated rats were set as blank control group.Serum and liver tissues of all rats were kept after sacrificed.Serum levels of alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil) and total bile acid (TBA) were tested,interleukin-10 (IL-10),interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA).The expression of multidrug resistance associated protein2 (Mrp2) at mRNA level in liver tissue was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and the inflammatory reaction activity of liver tissues was inspected with Haematoidin-Eosin (HE)staining under microscope.ResultsAt 48 hours after liver injury modeling,serum TBil (143.80± 12.08) μmol/L vs.(178.50±15.19) μmol/L,TBA (13.15±3.81) μmol/L vs.(21.68±7.93)mol/L,IL-10 (44.13±3.68,37.15±6.25 ng/L),IL-6(50.80±2.09,57.32±4.63 ng/L) and TNF-α (17.53±0.84) ng/L vs,(19.10±1.64) ng/L of UDCA group and control group were compared,and the differences were statistically significant (P ＜ 0.01 or P＜ 0.05).At 72 hours after liver injury modeling,serum ALT (721.67±97.54) U/L vs.(929.50±148.29) U/L and IL-10 (54.68±6.79)ng/L vs.(43.85±4.08) ng/L of UDCA group and control group were compared,and the differences were statistically significant (P＜0.01 or P＜0.05).At 96 hours after liver injury modeling,serum ALT (156.83±14.99) U/L vs.(250.67±42.29) U/L,AST (143.67±27.45) U/L vs.(206.00±63.94) U/L and TBil (23.53±5.08) μmol/L vs.(34.02±9.98) μmol/L of UDCA group and control group were compared,and the differences were statistically significant (P＜0.01 or P＜0.05).The differences of Mrp2 expression at mRNA level in liver tissues between UDCA group and control group at 48 hours (0.77 ± 0.21,0.46 ± 0.25),72 hours (2.27 ±0.84,1.10 ±0.38) and 96 hours (3.64±0.54,2.75±0.69) after liver injury modeling were statistically significant (P＜0.01 or P＜0.05).ConclusionThe mechanism of the protective effects of UDCA on ANIT-induced liver injury may be related with the regulation of serum cytokines and liver Mrp2 expression.
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OBJECTIVE@#To investigate therapeutic effects of Jinsangsanjie capsule on vocal fold polyps and vocal nodules.@*METHOD@#Seventy-five patients with vocal fold polyps and vocal nodules were treated by taking Jinsangsanjie capsule orally. After the therapeutic course, they were all followed up for 1 month.@*RESULT@#The effective rate of vocal nodule group was 93.8%, the effective rate of vocal fold polyp group was 89.7%, the effective rate of vocal nodule with acute congestion group was 100%, the effective rate of vocal fold polyp with acute congestion group was 100%, and the effective rate of hypertrophy of vocal cords with chronic congestion group was 66.7%.@*CONCLUSION@#Jinsangsanjie capsule has definite efficacy for treatment of vocal fold polyps and vocal nodules and deserved to be recommended.
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Adult , Female , Humans , Male , Middle Aged , Capsules , Drugs, Chinese Herbal , Therapeutic Uses , Laryngeal Diseases , Drug Therapy , Phytotherapy , Polyps , Drug Therapy , Pathology , Treatment Outcome , Vocal Cords , PathologyABSTRACT
Objective To investigate the correlation of serum total bile acid (TBA) levels with the inflammation grades of liver tissue in chronic liver diseases.Methods Cyclophorase assay was used to detect the serum TBA levels in 172 patients with various chronic liver diseases,and the inflammation grades of liver tissue were determined by liver biopsy.The correlation between serum TBA levels and the inflammation grades of liver tissue was evaluated using SPSS 12.0 software.Results Serum TBA level was positively correlated with the inflammation grade of liver tissue ( r =0.275,P ＜ 0.01 ).The inflammation grade reached G2 when serum TBA was 20 μmol/L.Conclusion Serum TBA level may be useful for evaluating the inflammation grade of liver tissue in chronic liver diseases.
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OBJECTIVE@#To explore the discrepancy of HGF and Hpa expressed in laryngeal squamous cell carcinoma of different pathology grades (differentiation of high, moderate or poor), which can provide the new thought and theory evidence for clinical treatment and control metastasis or palindromic.@*METHOD@#Forty paraffin-embedded samples of laryngeal squamous cell carcinoma, forty paraffin-embedded samples of laryngeal papilloma and twelve paraffin-embedded samples of normal tissue adjacent to cancerous location of our department between May 2004 and April 2005, which were analyzed with SP immunohistochemistry staining.@*RESULT@#The positive rate of HGF were 77.5% and that of Hpa were 72.5% in laryngeal squamous cell carcinoma, which have positive correlation and were higher than that in laryngeal papilloma and normal tissue adjacent to cancerous location with significant statistical difference (P0.05), that have positive correlation with clinical stages and have negative correlation with the level of cellular differentiation. The expression of HGF and Hpa in lymph node metastasis group was significantly higher than the non-metastasis group (P<0.05).@*CONCLUSION@#The expression of HGF and Hpa in laryngeal squamous cell carcinoma are higher than that in nonmalignant ones. They correlates with lymph node metastasis, clinical stages and pathological grading, but they has no relationship with the primary locations. The positive correlation relationship of expression between HGF and Hpa might be worthiness to determine the prognosis of laryngeal squamous cell carcinoma.
