Recombinant Human Interferon Α2b Research Articles

Study on the Recombinant Human Interferon α1b, α2b, and Gamma Transient Expression and in Vitro Activities in Tobacco.

Interferons (IFNs) are universally acknowledged for their pivotal role in antiviral and anticancer responses. Thus, the primary aim of our study was to explore the expressions of IFN-α1b, α2b, and gamma in tobacco leaves via agrobacterium-mediated transient transformation and investigate their possible activities. Briefly, fusion with green fluorescent protein tags aided in detecting the expressed IFN proteins in the foliar tissues. The genetic constructs encoding these fusion proteins were inserted into the MagnICON plant transient expression vector, followed by transformation into the Agrobacterium strain GV3101. The transformed bacteria were then used to infiltrate tobacco leaves. After post-infiltration, protein expression was confirmed within 72 h via sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the fusion proteins were subsequently purified using high-performance liquid chromatography for identification. Both the antiviral and anticancer potencies of these IFN fusion proteins were evaluated using the WISH/VSV (WISH cells/Vesicular stomatitis virus) microneutralization and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, respectively. Results indicated robust expression of the targeted IFN genes in plant tissues and significant biological activities against pathogens and cancer cells. Consequently, this study substantiated the viability of producing these therapeutic proteins in plants, potentially revolutionizing the manufacture of interferons biologically.

Effects of ganciclovir combined with recombinant human interferon-α on clinical efficacy and immune function in children with infectious mononucleosis.

To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM). This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed. After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3+ and CD8+ in the study group were significantly lower than those in the control group; after treatment, the levels of CD4+ and CD4+/CD8+ in the study group were significantly higher than those in the control group. Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM.

Efficacy of Paravertebral Injection of Interferon-α2b Combined with High-Voltage, Long-Term Pulsed Radiofrequency in DRG in Mitigation of Postherpetic Neuralgia: A Retrospective Study

ObjectiveThis investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term pulsed radiofrequency (PRF) in DRG in the mitigation of postherpetic neuralgia (PHN). MethodsThis retrospective study was performed on 84 individuals suffering from acute PHN. The participants were divided into three groups. Group H: Treat with interferon-α2b combined with high-voltage long-term PRF; Group C: Treat with high-voltage long-term PRF; Group I: Treat with the interferon-α2b. All patients in the three groups were orally administered 5 mg of morphine hydrochloride quick-release tablets when there was a burst of pain during the treatment. The pain numerical rating score (NRS), IL-6, Gal-3, and the incidence of PHN were documented prior to and following therapy. ResultsThe pain intensity of all individuals decreased following therapy. In comparison with group C, the group H NRS scores significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lesser. In comparison with that prior treatment, the recommended dosage of gabapentin capsules and morphine hydrochloride tablets with an immediate release was reduced in group H. In comparison with group C, the gabapentin orally administrated capsule and morphine hydrochloride in group H reduced significantly after treatment. There were no serious adverse reactions in the three groups. ConclusionWithin the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than the PRF or injection of interferon-α2b alone.

Observation of the Curative Effect of Recombinant Human Interferon α2b Gel Combined with LEEP Knife in Cervicitis Caused by IUD and The Effect of Copper/Low-Density Polyethylene Nanocomposite IUD

In this study, we explored the curative effect of recombinant human interferon α2b gel combined with a loop electrosurgical excision procedure (LEEP) knife to treat cervicitis. We also analyzed the clinical applications of a copper/low-density polyethylene nanocomposite intrauterine device (IUD). We selected 62 patients with IUD-induced cervicitis admitted to our hospital from March 2020 to December 2022 and divided them into experimental and control groups according to the random number table method (n = 31/group). The control group was treated with recombinant human interferon α2b gel only, while the experimental group was treated using a combination of the gel and LEEP knife. We compared the total efficacy rate of both treatments by recording the serum inflammatory cytokines levels, hospitalization, and vaginal drainage times before and after three months of treatment. We selected 50 married women of childbearing age who came to our hospital voluntarily to receive IUDs during the same period and randomly divided them into two groups (n = 25/group). Each group was administered either a copper/low-density polyethylene (Cu/LDPE) nanocomposite intrauterine device (IUD) or a TCu220C IUD. We conducted follow-ups at three, six, and 12 months after the implantation and analyzed the clinical and side effects. We observed that the total efficacy rate of the cervicitis treatment in the experimental group was 93%, 72% higher than in the control group. After six months of treatment, the tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels, and the leukocyte counts of both groups were lower than that before treatment, with the test group showing lower values than the control group. Simultaneously, the hospitalization and vaginal discharge times of the experimental group were lower than those of the control group. We also followed up on the two different IUD groups after three, six, and 12 months. Compared with TCu220C IUD, the Cu/LDPE nanocomposite IUD group showed lesser side effects, such as uterine bleeding and abdominal pain. There was no significant difference between the hemoglobin levels of both groups before and after IUD insertion. In conclusion, recombinant human interferon α2b gel combined with a LEEP knife is effective in treating cervicitis patients and can control the levels of inflammatory factors in the body. This treatment was safer and quicker and shortened the vaginal discharge time. Additionally, the clinical acceptance of Cu/LDPE nanocomposite IUD for human intrauterine contraception is good due to the low occurrence of adverse reactions, such as uterine bleeding and pain. Therefore, it should be promoted in clinical gynecological practice.

A new choice for human rabies diagnosis: A case report of metagenomics next-generation sequencing in diagnosis of human rabies

PurposeWe report a case of human rabies diagnosed by the metagenomics next-generation sequencing (mNGS). A 59-year-old man developed clinical rabies 20 days after he was bitten by dogs. Treatment included induction of coma initially; rabies vaccine was not administered. The patient was treated with propofol, midazolam, recombinant human interferon α2b, ribavirin, and amantadine. Penehyclidine was administrated to relieved the rabies induced pulmonary edema and the salivation. ResultsThe patient’s situation got worse on the 26th day after admition, and died on the 29th day finally. ConclusionThe mNGS might be a new choice for human rabies diagnosis，penehyclidine was effective in decreasing the rabies induced pulmonary edema and the salivation.

Safety and Effectiveness of Inhaling Different Dosage Recombinant Human Interferon α1B for Bronchiolitis in Children: a Systematic Review and Meta-Analysis.

Purpose To systematically evaluate the safety and effectiveness of different dosages of recombinant human interferon α1b (IFNα1b) inhaled for bronchiolitis in children. Methods 7 databases, including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang Database, and VIP, were searched. The search time was from their inception dates to March 28, 2022. A randomized controlled trial (RCT) of 2 μg/kg IFNα1b (low dosage group) monotherapy or in combination with other drugs vs. 4 μg/kg IFNα1b (high dosage group) monotherapy or in combination with the other drugs was included. The risk of bias 2.0 evaluated the RCT's quality, and the grading of recommendations assessment, development and evaluation (GRADE) tool was used for evaluating the overall quality of the evidence. Then, a meta-analysis was performed by RevMan 5.4. Results A total of 13 RCTs with 1719 children were included. The meta-analysis results showed that the high dosage group was significantly shorter than the low dosage group of the duration of hospital stays (MD = −0.40, 95%CI (−0.73, −0.07), P = 0.02) (low quality), three depressions sign disappearing time (MD = −0.60, 95%CI (−1.05, −0.14), P = 0.010) (low quality), and wheeze disappearing time (MD = −0.62, 95%CI (−1.17, −0.06), = 0.03) (low quality). There was no significant difference between the two groups in coughing disappearing time, pulmonary rales disappearing time, wheezing sound disappearing time, or adverse event rates. Conclusions Compared with low dosage IFNα1b, high dosage IFNα1b reduces the duration of hospital stays, the disappearance time of the three depression signs, and the disappearance time of wheeze in the treatment of bronchiolitis in children. Limited by the low quality of the evidence, the conclusions still need to be supported by high-quality studies.

Effect of a combination of interferon-α and ambroxol on children with pneumonia, and on serum amyloid A: A randomized controlled study

Purpose: To investigate the effect of combination of interferon-a with ambroxol on children with pneumonia, and its effect on serum amyloid A (SAA).
 Methods: A total of 140 children who presented with pneumonia in Cangzhou Central Hospital from January 2019 to November 2020 were selected and randomly assigned to control group and study group. All the children were treated with conventional therapy against cough and phlegm, anti-infection, oxygen inhalation, antipyretic, water and electrolyte correction, and nutritional support. The control group received aerosol inhalation of ambroxol + physiological saline, in addition to conventional treatment. The study group was given aerosol inhalation of recombinant human interferon-α1b + ambroxol + physiological saline. The two groups were treated continuously for 7 days. The time taken for clinical symptoms to subside in each group, as well as serum levels of amyloid A (SAA), interleukin 6 (IL-6), immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG) before treatment and 7 days post-treatment were evaluated. Clinical efficacy and incidence of adverse reactions after 7 days of treatment were also obtained and compared.
 Results: The time taken for symptom disappearance was significantly shorter in the study group than in control group, and inflammation indices were lower in the study group than in control group (p < 0.05). Levels of IgA, IgM, and IgG in the two groups after treatment were significantly elevated, but they were markedly higher in the observation group than in control group (p < 0.05). Clinical treatment efficacy was superior in the study group, relative to control (p < 0.05). However, no statistical disparity in incidence of adverse reactions was witnessed between the two groups (p > 0.05).
 Conclusion: A combination of interferon-α1b and Ambroxol may be a boon in the treatment of children with pneumonia due to its efficacy and effect on inflammatory response and SAA levels.

Functions of Traditional Chinese Medicine Combined with Recombinant Human Interferon α2b in Cervical Intraepithelial Neoplasias Patients.

Cervical cancer is a common malignant neoplasm in women, and its incidence is increasing year by year. This study explored the effects of traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients. 178 cervical intraepithelial neoplasias (CIN) combined with high-risk HPV-positive patients from June 2017 to August 2020 were divided into the study group (n = 89 cases) and the control group (n = 89 cases) by the random number table method. Patients in the control group were treated with recombinant human interferon α2b, and the study group was treated with traditional Chinese medicine (TCM) on the basis of the control group. After treatment, the recurrence rate in the study group was significantly decreased while the human papillomavirus (HPV) negative conversion rate was significantly increased. 3 months after treatment, the TCM symptom scores in the study group were lower than in the control group. Moreover, serum levels of inflammatory factors decreased in both groups, and the decrease was more significant in the study group. After treatment, the ultrasound parameters were significantly decreased in the study group than in the control group. In conclusion, traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients could effectively improve the negative conversion rate of HPV infection, the level of inflammatory factors, reduce the degree of cervical erosion, and enhance the immunity of patients with high safety and significantly improve the quality of life.

A Simplified Process for Purification and Refolding of Recombinant Human Interferon-α2b

Background: Interferon α-2b is a vital biotherapeutic produced through the recombinant DNA technology in E. coli. The recombinant IFN-α2b normally appears as intercellular IBs, which requires intensive refolding and purification steps. Method:Purification of IFN-α2b from solubilized IB was performed using two-phase extraction. To optimize refolding conditions, the effects of pH and different additives, including cysteine, cystine, urea, glycerol, Triton X-100, NaCl, and arginine, were investigated. Optimal refolding buffer (0.64 mM of urea, 5.57 mM of cysteine ​​, and 1.8 mM of cystine) was obtained using RSM. The refolding process was performed by an optimized refolding buffer in the dilution and fed-batch refolding method at different protein concentrations (25-1000 µg/mL). Result: At a final protein concentration of 500 µg/mL, the fed-batch refolding method yielded in a biological activity of 2.24 × 108 IU/mg, which was nearly twice that of dilution method. Conclusion:Fed-batch refolding method resulted in the biologically active IFN-α2b with high purity, which can be used for research and industrial purposes.

The Effects of Chinese Herbal Decoction Combined with Recombinant Human Interferon α2b on MRI Imaging, Tumor Markers, and Immune Function in Patients with Renal Cell Carcinoma.

Background To explore the clinical efficacy of traditional Chinese medicine decoction combined with recombinant human interferon α2b in the treatment of renal cell carcinoma (RCC). Methods 68 RCC patients were divided into the control group and treatment group (n = 34). The control group was treated with recombinant human interferon α2b, and the treatment group was treated with traditional Chinese medicine decoction on the basis of the control group. The clinical efficacy and life quality were observed. At the same time, the changes of immune function before and after treatment were compared. Results After one course of treatment, the effective rate and clinical benefit rate of the treatment group were higher than those of the control group. The Karnofsky score in the treatment group was better than that in the control group. In improving the immune function, the treatment group was better than the control group in increasing CD3+ and CD4+ and reducing CD8+. Conclusion Traditional Chinese medicine decoction combined with recombinant human interferon α2b has a good effect on the treatment of RCC. It can not only improve the common clinical symptoms of patients but also improve the quality of life and cellular immune function of patients.

Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.

We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases. Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins. Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone. As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation. Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes. It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency. We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.

Development of novel-nanobody-based lateral-flow immunochromatographic strip test for rapid detection of recombinant human interferon α2b

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 commercial products, with a great potential for routine use in detecting counterfeit recombinant protein products.

Interferon-α1b for the treatment of metastatic melanoma: results of a retrospective study.

Recombinant human interferon-α1b (IFN-α1b) is the first genetic engineered drug of China and is approved for cancer treatment by Chinese Food and Drug Administration. Although recombinant IFN-α1b is biologically and therapeutically active, its long-term efficacy against advanced melanoma is unknown. Ninety patients who were diagnosed with stage IV melanoma and received recombinant IFN-α1b therapy in our department were included in this study. The safety and efficacy of IFN-α1b were analyzed. IFN-α1b was overall well tolerated, with only 7.8% of the patients showing grade 3 toxicity and none with grade 4 toxicity or treatment-related death. The most common adverse effect was fever (78.9%). Furthermore, increasing the drug dosage showed no increase in the incidence of adverse events. The median overall survival (mOS) of the cohort was 14.1 months (95% confidence interval, 11.3-16.9 months). There was no significant difference of the mOS between samples of various primary sites. In the 42 patients who had not received prior adjuvant interferon therapy, the objective response rate, disease control rate and clinical benefit rate were 7.1, 28.5 and 21.4%, respectively. Our findings suggest that systemic IFN-α1b treatment is a relatively safe therapy and could prolong the survival of patients with unresectable metastatic melanoma.

Efficacy of Dorsal Root Ganglion Pulsed Radiofrequency Combined with Paravertebral Injection of Recombinant Human Interferon-α2b in Herpetic Neuralgia.

ObjectiveThe purpose of this study was to investigate the clinical efficacy of dorsal root ganglion (DRG) pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α2b in the treatment of patients with acute herpes zoster neuralgia and its preventive effectiveness on postherpetic neuralgia (PHN).MethodsA retrospective analysis of 62 patients with acute herpes zoster neuralgia was implemented. All patients were divided into two groups: pulsed radiofrequency paraspinal injection of recombinant human interferon-α2b (group P); pulsed radiofrequency combined with paravertebral injection of saline (group C). The numerical rating scales (NRS) scores were used for pain assessment, and the dose of the analgesic drug was recorded. Gal-3 and IL-6 levels in blood were compared between the two groups before treatment and at 1 week, 2, and 4 weeks after treatment. The incidence of PHN was recorded in both groups.ResultsThe pain intensity, the levels of Gal-3 and IL-6 in blood and the dose of oral administration of gabapentin capsules and morphine were reduced in all patients after treatment. Compared with group C, patients in group P had lower NRS scores, blood levels of Gal-3 and IL-6, and dosages of oral gabapentin capsules and morphine hydrochloride immediate-release tablets after treatment. The incidence of PHN was significantly lower at 8 and 12 weeks.ConclusionDRG pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α2b for acute stage herpes zoster neuralgia is a more effective treatment, and can effectively prevent the incidence rate of PHN.

Study on the Treatment of Acute Upper Respiratory Tract Infection in Children with Xiaoer Baotaikang Granules combined with Recombinant Human Interferon α2b Spray

Study on the Treatment of Acute Upper Respiratory Tract Infection in Children with Xiaoer Baotaikang Granules combined with Recombinant Human Interferon α2b Spray

The effect of recombinant human interferon α1b treatment of infants hospitalized with lower respiratory tract infection on subsequent wheezing

ObjectiveTo investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. MethodsThe clinical data of infants (n=540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n=253) and control group (n=287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. ResultsOut of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p=0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p<0.05). Binary logistic regression showed a childhood history of allergy (OR=2.14, p=0.004), no rhIFNα1b use (OR=1.70, p=0.028), and living in a crowded house (OR=1.92, p=0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR=0.44, p=0.008) and hospitalization age of ≤1-year-old (OR=0.58, p=0.024) were protective factors. ConclusionsEarly use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.

Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China

Background Clinical characteristics of patients with the coronavirus disease 2019 (COVID-19) may present differently within and outside the epicenter of Wuhan, China. More clinical investigations are needed. Objective The study was aimed to describe the clinical characteristics, laboratory parameters, and therapeutic methods of COVID-19 patients in Hunan, China. Setting The First Hospital of Changsha, First People’s Hospital of Huaihua, and the Central Hospital of Loudi, Hunan province, China. Methods This was a retrospective multi-center case-series analysis. Patients with confirmed COVID-19 diagnosis hospitalized at the study centers from January 17 to February 10, 2020, were included. The following data were obtained from electronic medical records: demographics, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, computer tomography scans, and treatment measures. Main outcome measure Epidemiological, clinical, laboratory, and radiological characteristics and treatments. Results A total of 54 patients were included (51 had the common-type COVID-19, three had the severe-type), the median age was 41, and 52% of them were men. The median time from the first symptoms to hospital admission was seven days. Among patients with the common-type COVID-19, the median length of stay was nine days, and 21 days among patients with severe COVID-19. The most common symptoms at the onset of illness were fever (74.5%), cough (56.9%), and fatigue (43.1%) among patients in the common-type group. Fourteen patients (37.8%) had a reduced WBC count, 23 (62.2%) had reduced eosinophil ratio, and 21 (56.76%) had decreased eosinophil count. The most common patterns on chest-computed tomography were ground-glass opacity (52.2%) and patchy bilateral shadowing (73.9%). Pharmacotherapy included recombinant human interferon α2b, lopinavir/ritonavir, novaferon, antibiotics, systematic corticosteroids and traditional Chinese medicine prescription. The outcome of treatment indicated that in patients with the common-type COVID-19, interferon-α2b, but not novaferon, had some benefits, antibiotics treatment was not needed, and corticosteroids should be used cautiously. Conclusion As of February 10, 2020, the symptoms of COVID-19 patients in Hunan province were relatively mild comparing to patients in Wuhan, the epicenter. We observed some treatment benefits with interferon-α2b and corticosteroid therapies but not with novaferon and antibiotic treatment in our study population.Electronic supplementary materialThe online version of this article (10.1007/s11096-020-01031-2) contains supplementary material, which is available to authorized users.

Quadruple therapy for asymptomatic COVID-19 infection patients

ABSTRACT Introduction The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. Areas covered This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. Expert opinion The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.

Biocalorimetric monitoring of glycoengineered P. pastoris cultivation for the production of recombinant huIFNα2b: A quantitative study based on mixed feeding strategies.

Real-time monitoring of glycoengineered Pichia pastoris by employing process analytical technology (PAT) tools is vital for gaining deeper insights into the therapeutic protein production process. The present study focuses on influence of mixed feed carbon substrates during the induction phases of glycoengineered P. pastoris cultivation, for recombinant human interferon α2b (huIFNα2b) production by employing calorimetric (biological heat rate, q B ) and respirometric (oxygen uptake rate and carbon dioxide evolution rate) measurements. Mixed feed stream of carbon substrates (methanol + glycerol, methanol + sorbitol) at a predetermined "C-molar ratios" were added during the induction phases. Methanol- and sorbitol-based mixed feeding approach resulted in an improved huIFNα2b titer of 288 mg/L by channeling of methanol predominantly towards an optimal functioning of AOX expression system. A stand-off between biomass yield coefficient, degree of reduction of methanol and its cosubstrate (glycerol and sorbitol) determines the fraction of carbon energy channeled toward biomass and protein production, under strict aerobic conditions. Calorespirometric monitoring and assessment of thermal yields enables a reliable prediction of process variables, leading to futuristic efficient PAT-based feed rate control.

Innovative research and clinical application of recombinant human interferon alpha1b in pediatrics(Volume I)

Recombinant human interferon α1b(IFN-α1b)is the first internationally unique novel genetic engineering medicine in China.As a major interferon subtype with natural antiviral activity, IFN-α1b has high safety and broad-spectrum antiviral effect, so it has broad application prospects in the treatment of viral diseases.Chinese pediatric doctors have taken the lead globally in conducting clinical research of IFN-α1b in the treatment of respiratory syncytial virus(RSV)pneumonia、bronchiolitis、hand-foot-mouth disease, herpetic angina、viral diarrhea, etc.A series of clinical guidance and expert consensus have been published which are in line with China′s national conditions.This article summarizes the innovative research of IFN-α1b and proposes common issues and potential application in pediatric clinical applications. Key words: Interferon-α1b; Children; Virus; Innovation