Development of novel-nanobody-based lateral-flow immunochromatographic strip test for rapid detection of recombinant human interferon α2b / 药物分析学报

Recombinant human interferon α2b(rhIFNα2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNα2b is complex.In this study,an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b.RhIFNα2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNα2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other com-mercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.

Analysis of human papillomavirus infection in 1 902 patients and drug treatment efficacy in 266 patients in Tianjin / 中华微生物学和免疫学杂志

Objective:To analyze the incidence of human papillomavirus (HPV) infection in 1 902 patients and to evaluate the efficacy of drug treatment in 266 patients, aiming to provide reference for the treatment of HPV infection.Methods:The subtypes of HPV isolated from 1 902 patients aged 15-86 years visiting the venereology outpatient clinic of Tianjin Medical University General Hospital from October 2019 to May 2021 were identified by polymerase chain reaction-reverse dot blot hybridization. Drug treatment efficacy in 266 patients of them was retrospectively analyzed.Results:The overall incidence of HPV infection in the 1 902 patients was as high as 53.84% (1 024/1 902). It was 52.60% (689/1 310) in males and 56.59% (335/592) in females. There was no significant difference in the incidence between males and females ( P>0.05). The most common HPV genotype in males and females was HPV6 [15.27% (200/1 310) and 21.96% (130/592)], followed by HPV16 [10.61% (139/1 310) and 9.46% (56/592)], HPV11 [9.31% (122/1 310) and 8.61% (51/592)], HPV52 [6.79% (89/1 310) and 8.95% (53/592)] and HPV43 [5.64% (87/1 310) and 8.45% (50/592)]. The majority of HPV-positive patients were aged between 20 and 39 years. There were 476 cases (25.03%, 476/1 902) of single-type infection and 548 cases (28.81%, 548/1 902) of multiple infection. The incidence of multiple infection was higher than that of single-type infection ( P<0.05). The incidence of multiple infection in females was higher than that in males ( P<0.05). Among the 266 patients, 106 were treated with Paiteling, a traditional Chinese medicine (TCM) preparation, and 68 of them tested negative (64.15%) after treatment. Fifty-eight patients were treated with recombinant human interferon α2b and 22 of them (37.93%) tested negative after treatment. Twenty out of the 56 subjects treated with imiquimod tested negative after treatment. Eight out of the 46 patients without treatment also turned negative. Conclusions:The incidence of HPV infection in the 1 902 patients visiting the venereology outpatient clinic was very high, and most of them were young adults. Multiple infection was more common than single-type infection. Topical application of drugs such as Paiteling, recombinant human interferon α2b and imiquimod was effective in treating HPV infection.

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B / 中华医学杂志(英文版)

Background@#Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).@*Methods@#Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.@*Results@#IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively).@*Conclusions@#IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

Efficacy and prognosis of Baofukang suppository combined with recombinant human interferonα-2b in the treatment of chronic cervicitis with HPV infection / 中国基层医药

Objective To study the clinical efficacy of Baofukang suppository and recombinant human inter -feron α-2b in the treatment of HPV infection with chronic cervicitis ,and to observe the prognosis ,thus to provide reference for its clinical treatment .Methods 120 patients with chronic cervicitis with HPV infection were selected . All patients were divided into observation group and control group by random number table method ,60 cases in each group.The observation group was treated with Baofukang combined with recombinant human interferon α-2b,and the control group was treated with recombinant human interferon α-2b.The patients were evaluated before treatment ,at the end of treatment and 3 months after treatment.The cure rate,total effective rate,recurrence rate,incidence rate of adverse reactions were observed and compared .Results In the observation group ,26 cases were cured ,the cure rate was 43.33％.In the control group ,15 cases were cured ,the cure rate was 25％.The cure rate of the observation group was higher than that of the control group ,the difference was statistically significant (χ2 =4.482,P<0.05).The total effective rate of the observation group was 98.33％,which was higher than 80.00％ of the control group,the differ-ence was statistically significant (χ2 =10.438,P <0.05).The negative rate of HPV in the control group was 38.33％,which was lower than 56.67％ in the observation group,the difference was statistically significant (χ2 = 4.043,P<0.05).The incidence rate of adverse reactions in the observation group was 11.67％,which in the control group was 10.00％,the difference was not statistically significant (χ2 =0.086,P >0.05).After treatment for 3 months,the recurrence rate was 0.00％in the observation group and 1.67％in the control group,the difference was not statistically significant (χ2 =1.008,P >0.05).Conclusion The combination of Baofukang suppository and recombinant human interferon α-2b showed good curative effect and prognosis in the treatment of chronic cervicitis with HPV infection ,and it is worthy to be popularized in clinical practice .

A multicenter controlled clinical study on the efficacy and safety of recombinant human interferon α2b spray in the treatment of hand, foot and mouth disease in children / 中华传染病杂志

Objective To evaluate the curative effect of recombinant human Interferon α2b (rhIFN α2b) spray in hand,foot and mouth disease (HMFD).Methods In total,313 HMFD children were enrolled from Beijing Ditan Hospital affiliated to Capital Medical University,Tianjing Second People's Hospital,Hebei Children's Hospital,the Second Hospital affiliated to Wenzhou Medical College,Kunming Maternal and Child Health Hospital and Guiyang Public Health Treatment Center from March,2015 to February,2017.They were divided into rhIFN α2b group (148 cases) and ribavirin group (165 cases).The children in rhIFN α2b group were given with the rhIFN α2b spray,and those in ribavirin group were given with the ribavirin spray.Meanwhile,the children were given unified standard interventions for basic treatment.The curative effect and safety between two groups was compared.The t test was used for intergroup comparison and the Wilcoxon rank test was used for non-normal quantitative data.Results At the end of the follow-up period,all kids reached the recovery level,with 144 cases in the rhIFN α2b group and 164 cases in the ribavirin group.Fever,herpes and rashes all disappeared with 7-day follow-up.The total efficiency of the rhIFN α2b group measured at the 72h after treatment was 74.15％,which showed significant differences compared with the ribavirin group with 49.09 ％ efficiency (Z=4.44,P＜0.01).As the secondary outcome measures,the complete disappearance time of fever and the immediate disappearance time of fever in the rhIFN α2b group were significantly shorter than those in the ribavirin group ([27.03±21.99] vs [33.21±26.71],t=-2.13;[23.56±13.96] vs [28.51±18.84],t=-2.07,both P＜0.05).The appetite improvement and the disappearance times of oral herpes and rashes in the rhIFN α2b group were shorter than those in the ribavirin group,with significant differences (x2 =4.94,3.17 and 3.55,respectively,all P=0.000).No adverse event in both groups.Conclusions rhIFN α2b spray treatment in HMFD is proved significantly effective,particularly,it can evidently relieve fever symptoms and promote the disappearance of oral herpes symptoms,and no adverse event is observed throughout the study,which indicates a good safety of the rhIFN α2b spray.Clinical trial registration Chinese Clinical Trial Registry,ChiCTR-OIN-17013182.

Clinical curative effect of Gongyanping capsule combined with recombinant human interferon α2b vaginal effervescent tablets in the treatment of human papillomavirus infection / 中国生化药物杂志

Objective To observe the clinical curative effect of Gong Yanping capsule combined with recombinant human interferon α2b vaginal effervescent tablets in the treatment of human papillomavirus infection.Methods80 cases of patients with cervical HPV infection in Xiangshan hospital of traditional Chinese medicine from May 2014 to May 2016 were selected, these patients were divided into Gong Yanping capsule combined with interferon treatment group (combined treatment group, 40cases) and pure Gongyanping capsule treatment group (single treatment group, 40cases) two groups according to the treatment methods, the clinical curative effects, HPV-DNA levels, HPV infection status, incidences of adverse reactions of the two groups were statistically analyzed.ResultsThe clinical total efficiency of the combined treatment group 95% (38/40) was significantly higher than the single treatment group 80% (32/40) (P<0.05), the HPV-DNA level was significantly lower (P<0.05), the HPV infection negative rate 1 months after treatment 2.5% (1/40) was significantly lower than the single treatment group 10% (4/40) (P<0.05), the negative rates 2 months, 3 months after treatment 67.5% (27/40), 97.5% (39/40) were significantly higher than the single treatment group 40% (16/40), 77.5% (31/40) (P<0.05);The difference of incidences of adverse reactions between the two groups 12.5% (5/40), 7.5% (3/40) was not significant.ConclusionThe clinical curative effect of Gong Yanping capsule combined with Recombinant Human Interferon α2b Vaginal Effervescent Tablets in the treatment of human papillomavirus infection is more significant than pure Gongyanping capsule treatment, it will not increase the adverse reactions of patients in a great extent, is safe and effective.

Clinical Observation of Recombinant Human Interferon α2b Vaginal Effervescent Capsules Combined with Radiofrequency Ablation in the Treatment of Cervical Erosion Combined with HPV Subclinical Infection / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of Recombinant human interferon α2b(rhIFN α2b) vaginal effervescent capsules combined with radiofrequency ablation in the treatment of cervical erosion with human papilloma virus (HPV)subclinical infection(SPI). METHODS:A total of 207 cervical erosion patients with SPI were selected from gynecology outpatient department of our hospital during Jul. 2014-Aug. 2015 and then divided into group A,B,C according to random number table,with 69 cases in each group. Group A was given rhIFN α2b vaginal effervescent capsules 800 thousand IU,via posterior for-nix,qd,3 days after the end of menstruation,10 days as a treatment course,for 3 courses. Group B received radiofrequency abla-tion. Group C was given constant dose of rhIFN α2b vaginal effervescent capsules combined with radiofrequency ablation. The clini-cal efficacy of 3 groups,the rate of wound healing,the rate of associated symptoms disappearance 2 weeks after surgery and the in-cidence of complications in group B and C were evaluated. The occurrence of ADR was recorded. RESULTS:The response rates of group B,C were 94.20% and 98.55%,which were significantly higher than 62.32% of group A. The response rates of SPI in group C was 92.75%,which was significantly higher than 63.77% of group B,with statistical significance(P0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:rhIFN α2b vaginal effervescent capsules combined with radiofrequency ablation can effective-ly improve the efficacy of cervical erosion with SPI,shorten the wound healing time with good safety.

Clinical Observation of Recombinant Human Interferon α2b Combined with Bozhi Glycopeptides and Thymopentin in the Treatment of HBeAg-positive Chronic Hepatitis B / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of recombinant human interferon α2b (rhIFN α2b) combined with bozhi glycopeptides or thymopentin in the treatment of chronic hepatitis B (CHB).METHODS:Ninety HBeAg-positive CHB patients were selected from our hospital during Jan.2014-Jan.2015 and then randomly divided into group A,B,C,with 30 cases in each group.Group A was given rhINF α2b for injection (Pseudomonas) 5 million IU subcutaneously,qod;group B was additionally given Bozhi glycopeptides injection 4 mL added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A;group C was additionally given Thymopentin for injection 2 mg added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A.Three groups were treated for 24 weeks.The rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg/anti-HBeAg serum,negative rate of HBV-DNA and the decrease of HBsAg and HBV-DNA were compared among 2 groups after 4,8,12,24 weeks of treatment.The occurrence of ADR was recorded.RESULTS:After 4,8,12 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg and the decrease of HBsAg among 3 groups (P＞0.05).After 4 weeks,negative rate of HBV-DNA in group B,C were significantly higher than group A;the decrease of HBV-DNA in group C were more significant than group A and B,with statistical significance (P＜0.05).After 8,12 weeks of treatment,the negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);but there was no statistical signifi cance between group B and C (P＞0.05).After 24 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBsAg among 3 groups (P＞0.05).The negative rate of HBsAg,negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);there was no statistical significance between group B and C (P＞0.05).There was no statistical significance in the incidence of ADR among 3 groups(P＞0.05).CONCLUSIONS:rhIFN α2bcombined with bozhi glycopeptides or thymopentin shows good inhibitory effect on CHB,therapeutic efficacies of them are similar in the rate of ALT recovering to normal,but transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBeAg.

Expression of growth factor independence 1 in peripheral blood sézary cells of patients with sézary syndrome / 第二军医大学学报

Objective To detect the expression of growth factor independence 1 (GFI-1) in peripheral blood of patients with Sézary syndrome and normal persons, so as to provide a theoretical basis for developing GFI-1 gene target therapy. Methods CD4+ CD7- Sézary cells (SS cells) were separated and purified from peripheral blood of 7 patients with Sézary syndrome by flow cytometry, CD4+ T cells from peripheral blood of 10 normal persons, Sézary syndrome-derived cell line Hut78 and human acute T cell leukemia cell line Jurkat as controls. The mRNA and protein expressions of GF-1were detected by qPCR and Western blotting, respectively. Then after interferon-a-2b (IFN-a2b) was used to induce Hut78 cell apoptosis, the cell proliferation wasmeasured by MTS, themRNA expression of GFI-1, cell cycle-dependent protein kinase inhibitor P21, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Caspasi-3 was detected by qPCR, and the cell apoptosis was detected by flow cytometry. Results The expression of GFI-1 mRNA in the SS cells was significantly higher than that in the Jurkat and CE4+ T cells (all P<0.05). The expression of GF-1 protein in the SS cells and Hut78 cells was significantly higher than that in the Jurkat and CD4+ T cells (all P<0.05). IFN-a2b significantly mhibited the proliferation of Hut78 cells, and the effect was concentration-dependent and time-dependent The mRNA expression of GFI-1 ln Hut78 cells was significantly decreased in a time-dependent manner at 12 h and 24 h treated with IFN-a2b, while the mRNA expressions of P21, TRAIL and Caspase-3 were significantly increased (P〈0. 05). The apoptosis of Hut78 cells was significantly increased at 12 h and 24 h treated with IFN-α2b (P〈0. 05). Conclusion The expression of GFI-1 gene in peripheral blood SS cells of patients with Sézary syndrome is increased and can be inhibited by IFN-a2b, indicating that GFI-1 gene may play an important regulatory role in tumor proliferation of SS cells in patients with Sézary syndrome.

Clinical efficacy of pegylated interferon α-2a and ribavirin combined with self-extracting traditional Chinese medicine in the treatment of chronic hepatitis C / 重庆医学

Objective To study the clinical efficacy of pegylated interferon α-2a(PEG-IFN α-2a) and ribavirin combined with self-extracting traditional Chinese medicine(TCM) in the treatment of chronic hepatitis C(CHC) of gan-shen yin-deficiency and damp-heat syndrome.Methods A total of 59 cases of CHC of gan-shen yin-deficiency and damp-heat syndrome confirmed in our hospital was randomly divided into control group(n=29) and combined group(n=30).The patients in both groups were treated with PEG-IFN α-2a injection and ribavirin,and then the self-extracting TCM was added on the patients in combined group.The differences of quantitative score,improvement of liver function,RNA negative rate of HCV,the levels of IL-21,IL-6 and TNF-α,clinical treatment of total efficiency and adverse reactions were compared between the two groups before and after treatment.Results After treatment,the quantitative scores of TCM symptoms(rib-side pain,soreness and weakness of waist and knees,abdominal distension,red tongue with yellowish fur,dizziness with heavy body,insomnia and dreaminess) in combined group were significantly lower than those in control group(P＜0.05),but the difference of quantitative scores of other TCM symptoms between the two groups was not statistically significant(P＞0.05);The levels of alanine aminotransferase(ALT),aspartate aminotransferase (AST) and total bilirubin(TBIL) in combined group were better than those in control group(P＜0.05) after 48 weeks of treatment,but the difference of the levels of albumin(ALB) and glutamyl transpeptidase(GGT) were norstatistically significant in both groups(P＞0.05);The RNA negative rate of HCV in combined group was significantly higher than that in control group after 36-week or 48-week treatment(P＜0.05),but there was no statistically significant difference between the two groups after 12-week or 24-week treatment and 24-week follow-up;The levels of TNF-α,IL-17,IL-23 in combined group were significantly lower than those in control group(P＜0.05) after 48 weeks of treatment;The total efficiency of combined group is better than that of control group (93.33％ vs.72.41％,P＜0.05).There was no significant difference in adverse reactions between the two groups(P＞0.05).Conclusion The application of PEG-IFN α-2a and ribavirin combined with the self-extracting TCM in the treatment of CHC can obviously ameliorate the clinical symptoms and liver function indexes,improve the RNA negative rate of HCV,reduce the levels of inflammatory factors,and improve the clinical efficacy.

A Case of Recurrent Myxomatous Corneal Degeneration Treated by Interferon Alpha-2b

PURPOSE: To report a case of recurrent myxomatous corneal degeneration after pterygectomy. CASE SUMMARY: A 65-year-old man with a history of abdominal keloid was referred to our hospital for assessment of a well-circumscribed, gelatinous, whitish corneal mass on the nasal corneal area of the left eye that appeared one month prior. The patient had undergone pterygectomy on his left eye 2 years ago. The patient experienced mild foreign body sensation. The other anterior segment and fundus examination of the left eye were both normal. We diagnosed the case as keloid and we performed excisional biopsy of the corneal mass. Histologic findings revealed proliferation of myxoid-appearing material in the anterior corneal stroma. On immunohistochemical examination, sections were stained positive for actin and calretinin, and negative for S-100. We diagnosed the tumor as myxomatous corneal degeneration. After six months, a recurrent mass was found on the previously excised site. Re-excisional biopsy and topical interferon α-2b treatment were then performed in response. After re-excision, there was no recurrence or complications during one year follow-up. CONCLUSIONS: Myxomatous corneal degeneration should be considered during differential diagnosis of an elevated, whitish, gelatinous lesion of the cornea with previous history of trauma or operation, such as pterygectomy. An interferon α-2b topical treatment is useful for recurrent corneal myomatous degeneration.

Randomized controlled study: Sophora flavescens gel in treatment of cervical HPV infection / 中国中药杂志

This study aimed to evaluate the efficacy of Sophora flavescens gel in treatment of cervical HPV infection. 120 patients with cervical HPV infections were selected from department of gynecology, the first affiliated hospital, Heilongjiang university of Chinese medicine. They were randomly divided into three groups: test group(S. flavescens gel, 40 cases), control group(human recombinant interferon α-2b gel, 40 cases) and combined application group(combination of the above two, 40 cases). The treatment course was three months in all three groups. Before and after treatment, the changes of HPV viral load and the changes of viral load for different HPV types were observed.The results could provide guidance for clinical application of S. flavescens gel.

Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible-Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China

BACKGROUND/AIMS: Several studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a plus ribavirin in patients infected with genotype 1 hepatitis C virus in China. METHODS: Seventy-two patients with chronic hepatitis C without fibrosis/cirrhosis were enrolled in the study. The virologic parameters and baseline serum IP-10 levels were determined. IL-28B genotypes were determined by sequencing. RESULTS: In this cohort, serum baseline IP-10 levels lower than 426.7 pg/mL could predict rapid virological response/sustained virological response (SVR). Patients carrying favorable IL28B SNP genotypes had higher SVRs than did those carrying unfavorable variants (IL28B rs12979860, p=0.002; IL28B rs8099917, p=0.020). Combining both baseline IP-10 and IL28B SNPs could improve the prediction of SVR in favorable allele carriers of IL28B, rs12979860 CC and rs8099917 TT. Serum baseline IP-10 levels and IL28B genotypes were independent predictors of SVR. CONCLUSIONS: Our study shows that the combination of baseline serum IP-10 levels and the determination of IL28B SNPs increase the predictability of SVR rates in this cohort.

A preliminary study of recombinant human interferon-α-2a activity against rabies virus in murine model.

Rabies remains an important public health problem in the world due to uncontrolled enzootic rabies. Although rabies associated fatalities may be prevented with timely immunoprophylaxis, but till date a therapeutic molecule has remained elusive. We investigated the role of rhuIFN α-2a in murine model challenged with rabies virus. Titre of 104.25 LD50/0.03 ml of 10% w/v RV CVS stock suspension were obtained. Based on 1LD50 titre, challenge dose of 50 LD50 was administered along with rhuIFN α-2a with pre-exposure (primed) and post-exposure with the rabies virus. Both showed increased survival time as compared with the virus controls. These fi ndings suggest that the rhuIFN α-2a might have some anti-viral activity, which can be used for the treatment of rabies infection. Further research on the effi cacy of interferon along with anti-viral drugs for the treatment will be helpful in designing combination therapy against the disease.

Analysis on Osmolality of Domestic Recombinant Human Interferon α2 b Injection / 中国药师

Objective:To examine the osmolality of domestic recombinant human interferon α2b injection to provide evidence for the improvement of the national quality standard. Methods:Totally 66 batches of recombinant human interferonα2b injection produced by 9 manufacturers were withdrawn, and the osmolality was determined according to the appendix of Chinese Pharmacopoeia Ⅲ(2010 edition). The results were analyzed with statistical methods. Results:The pass rate of osmolality was 98. 5%. The osmolality of more than 90% of the batches was between 85% and 115% of the intermediate value set by the manufacturers. Conclusion:Comprehensive understanding of the quality control of osmolality of domestic recombinant human interferon α2b injection is obtained, which provides data support for the improvement of quality standard of osmolality.

Sampling Results and Quality Assessment of Recombinant Human Interferon α2 a Injections / 中国药师

Objective: To evaluate the quality status of recombinant human interferon α2a injections and find out some quality problems. Methods:The statutory testing methods combining with the exploratory studies were used to examine the samples, and the quality status of recombinant human interferon α2a injections was evaluated by statistical analysis of the results. Results: All 28 bat-ches of the injections were qualified using the statutory testing methods. The exploratory studies showed that if the specific activity was determined, the qualified rate was only 87. 0%. All 7 batches of drug substances were qualified using the statutory testing methods. The exploratory studies showed that if the related protein was determined, the qualified rate was 57. 1%. Conclusion:At present the quality of recombinant human interferonα2a injections is generally good. The current standards are feasible;however, improvement is still needed. Specific activity determination should be supplemented the standards for drug products and related protein determination should be supplemented the standards of drug substances.

Clinical Effect of Interferon α-2 b on Scar Formation after Glaucoma Filtering Surgery / 中国药师

Objective:To investigate the preventive efficacy of interferon α -2b on scar formation after glaucoma filtering opera-tion. Methods:Totally 62 patients with primary glaucoma(68 eyes)were randomly divided into the observation group(31 cases with 36 eyes)and the control group(31 cases with 32 eyes). The patients in the observation group were given wet compress with a piece of cotton infiltrated by interferonα-2b,while the control group was given wet compress with a piece of cotton infiltrated by mitomycin C. After 4-month postoperative follow-up,the type of filtering bleb,complications and the changes of intraocular pressure were compared between the two groups. Results:The observation group was mainly with type II bleb(58. 33%),while the control group was mainly with type I bleb(53. 13%),and there was significant difference in the filtering bleb type between the two groups(P0. 05). The percentage of visual invariableness or improvement in the observation group was significantly higher than that in the control group(P<0. 05),and the occurrence of complications after the operation in the observation group was significantly lower than that in the control group( P<0. 05). Conclusion:Interferon α-2b is an ideal drug for anti-scarring formation after glaucoma filtration surgery.

Dynamic changes of serum hepatitis B surface antigens (HBsAg)level predict HBsAg loss in hepatitis B e antigen-negative chronic hepatitis B patients treated with pegylated interferon-α-2a / 中华传染病杂志

Objective To investigate the predictive value of on-treatment hepatitis B surface antigens (HBsAg)levels for HBsAg loss/seroconversion in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB)patients treated with pegylated interferon (peg-IFN)-α-2a.Methods HBeAg-negative CHB naive patients were collected from 2008 May to 2011 August in Beijing Ditan Hospital affiliated to Capital Medical University.Eligible patients had been HBsAg-positive,HBeAg-negative and with detectable hepatitis B virus (HBV)DNA for>6 months,had elevated alanine aminotransferase for>3 months,had no other liver diseases,and had been treated with peg-IFN-α-2a>3 months or had finished the treatment.All the enrolled patients were administered with peg-IFN-α-2a 180 μg/week.Serum HBV DNA,HBsAg,and anti-HBs levels were measured at baseline and every 3 months during peg-IFN-α-2a treatment.The primary efficacy of response to the treatment was HBsAg loss.Comparison between groups was conducted by chi-square test.The absolute levels of HBsAg and the decline rate of HBsAg at week 12 and week 24 were assessed using receiver operating characteristic (ROC)curve for predicting HBsAg loss at week 96 and week 120.Results A total of 81 patients were included into the data analysis. According to on-treatment HBsAg decline,patients were divided into completed response group (12 cases, 14.8%),partial response group (20 cases,24.7%),and poor response group (49 cases,60.5 %).On week 12 of treatment,mean HBsAg decline levels in completed response and partial response groups were 0.62(0.06,0.91)lg IU/mL and 0.19 (-0.01 ,0.48)lg IU/mL,respectively,which was not statistical different (Z =1 .581 ,P =0.209 ).Adjusting for differences of baseline factors (calculation of the mean decline of HBsAg),completed response group and partial response group had much more pronounced decline than poor response group 0.00 (-0.01 ,0.14)lg IU/mL,χ2 =9.00,P <0.01 ].On week 24, difference of HBsAg decline among the 3 groups was statistically significant (χ2 =27.72,P <0.01).The predictive ability of HBsAg cut-off level at week 24 was better than week 12 for HBsAg loss at either 96 or 120 weeks,and the differences of the area under the ROC curve were both significantly different (χ2 =3.880,P =0.049 and χ2 =4.412,P =0.036,respectively).Conclusion Dynamics of HBsAg level in early treatment of peg-IFN-α-2a can predict the therapeutic effect of patients with HBeAg-negative CHB.

Inhibitory effect of recombinant human interferon α-2b on influenza virus / 中华临床感染病杂志

Objective To investigate the effect of recombinant human interferon α-2b on influenza virus in vitro.Methods Influenza A virus subtype H1N1 and influenza B/Y virus were inoculated into Vero cells and different concentrations of interferon α-2b and oseltamivir were added.Numbers of virus plaques were observed and calculated,and quantitative RT-PCR were used to assess the inhibitory effect of interferon α-2b and oseltamivir in vitro.The nuclear export of viral ribonucleoprotein (RNP) complexes were monitored under fluorescence microscope.Results Virus plaque test showed that influenza A viruses subtype H1N1 were significantly inhibited when 10 μg/μL interferon α-2b and 10 μg/μL oseltamivir were added,and the numbers of plaques were 7.5 × 108 and 15 × 108 PFU/mL,respectively;the inhibitory effect of oseltamivir was better than that of interferon α-2b.Influenza B/Y viruses were also inhibited when 10 μg/μL interferon α-2b and 10 μg/μL oseltamivir were added,and the numbers of plaques were 1.1 × 108 and 1.5 × 108 PFU/mL,respectively.Quantitative RT-PCR results showed that the cycle threshold (CT) values of influenza A virus subtype H1N1 and influenza B/Y virus were much higher when 10 μmol/L interferon α-2b and 10 μmol/L oseltamivir were added.CT values of influenza A virus subtype H1N1 were 16,26 and 35 before and after inferferon α-2b and oseltamivir were added.CT values of influenza B/Y virus were 18,27 and 31 before and after interferon α-2b and oseltamivir were added.Reduction in the nuclear export of viral RNP in influenza A virus subtype H1N1-infected Vero cells was also observed when 10 μmol/L interferon α-2b were added.Conclusion Interferon α-2b has significantly inhibitory effect on both influenza A virus subtype H1N1 and influenza B/Y virus in vitro.

Recombinant Human Interferon α-2b Vaginal Effervescent Capsules Combined with Matrine Gels in the Treatment of Cervical Human Papilloma Virus (HPV) Subclinical Infection / 中国药师

Objective:To discuss the curative effect and security of recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels in the treatment of cervical human papilloma virus ( HPV) subclinical infection. Methods:Totally 74 cases of patients with cervical HPV subclinical infection were selected and divided into the observation group (n = 37) and the control group (n = 37) at random. The patients in the observation group were given recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels, while the patients in the control group were only given recombinant human interferon α-2b vaginal effervescent capsules for 3 treatment courses. The clinical curative effect and adverse reactions in the two groups after the medical treatment were observed, and the clinical curative effect in the 6-month follow-up after the medical treatment was observed and compared. Results:After the 3-month treatment, the total clinical efficiency in the observation group was much higher than that in the control group (P 0. 05). Six-month follow-up was performed and the total clinical efficiency in the observation group was much higher than that in the control group (P < 0. 05). Conclusion:Recombinant human interferon α-2b vaginal effervescent capsules combined with matrine gels have reliable curative effect on cervical HPV subclinical infection with high security and reliable long-term follow-up efficacy, which is benefit for the reoccurrence control of the disease.