Objective: To explore the application effect of multidisciplinary collaboration mode in perioperative patients with vascularized free flap repaired maxillofacial major defect.Methods: A total of 30 cases of perioperative patients with vascularized free flap repaired maxillofacial major defect during January 1,2017 to December 31,2019 were as the routine group, and the routine group was given routine nursing intervention, and another 30 cases during February 1,2020 to February 28,2022 were as the MDT group.The MDT group was given multi-disciplinary cooperation mode nursing intervention.Comparison was made between the two groups on negative emotions by the self-rating anxiety scale（SAS）and the self rating depression scale（SDS）,pain by visual analogue scale（VAS）,and the incidence of complications.Results: After surgery, the SAS and SDS scores were lower in the MDT group than those in the routine group（P＜0.01）.The VAS scores were lower in the MDT group than those in the routine group（P＜0.05）.And the incidence of complications was lower in the MDT group than that in the routine group（P＜0.05）.Conclusion: Application of multidisciplinary collaboration mode in perioperative patients with vascularized free flap repaired maxillofacial major defect can not only reduce the incidence of postoperative complications, but also reduce the degree of postoperative pain and negative emotions, improve the comfort, and improve the quality of postoperative nursing.

BACKGROUND:Wilson disease (WD) is the most common genetic metabolic liver disease. Some studies have shown that comorbidities may have important effects on WD. Data on hepatitis B virus (HBV) infection in patients with WD are limited.AIM:To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS:The clinical data of patients with WD were analyzed retrospectively, and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS:Among a total of 915 WD patients recruited, the total prevalence of current and previous HBV infection was 2.1% [95% confidence interval (CI): 1.2%-3.0%] and 9.2% (95%CI: 7.3%-11.1%), respectively. The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B (CHB) infection. The diagnosis of WD was missed in all but two patients with CHB infection. The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo, which was significantly longer than that in patients with isolated WD (10.5 mo). The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD (63.1% vs 19.3%, P = 0.000 and 36.8% vs 4.1%, P < 0.001, respectively). Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection [odds ratio (OR) = 7.748; 95%CI: 2.890-20.774; P = 0.000)] or previous HBV infection (OR = 5.525; 95%CI: 3.159-8.739; P = 0.000) than in patients with isolated WD.CONCLUSION:The total prevalence of current HBV infection in patients with WD was 2.1%. The diagnosis of WD in CHB patients is usually missed. HBV infection is an independent risk factor for severe liver disease in WD patients. The diagnosis of WD should be ruled out in some patients with CHB infection.

钙化上皮瘤(calcified epithelioma,CE)也称为毛母质瘤(pilomatricoma,PM),是起源于毛囊外根鞘细胞的外胚层良性肿瘤.一般单发于上肢、躯干及面颈部,多发性钙化上皮瘤在临床上更是罕见.本文报告 1 例多发性钙化上皮瘤并进行相关基因检测,结合相关文献进行讨论,为临床诊疗提供参考.

背景:牙周炎患者逐年增加,采用传统的牙周治疗方法并不能恢复牙周软硬组织,因此需要制备出一种药物缓释材料辅助治疗牙周炎,恢复牙周破坏的软硬组织.目的:制备装载辛伐他汀的牛血清白蛋白微球复合水凝胶材料,检测其对辛伐他汀的双重缓释作用,并进一步研究此释药复合材料对成骨细胞黏附、增殖的影响.方法:①采用去溶剂法制备载辛伐他汀的牛血清白蛋白微球,采用透射电镜、扫描电镜观察微球的形态,测量其粒径,采用酶标仪检测载药微球的包封率、载药率及体外药物释放;②将载药微球负载到明胶水凝胶中,采用酶标仪检测水凝胶的体外药物释放,扫描电镜观察复合材料的形态;利用该水凝胶浸提液培养MC3T3-E1细胞,采用CCK-8法检测细胞增殖,碱性磷酸酶试剂盒检测细胞碱性磷酸酶的表达.结果 与结论:①透射电镜显示,载药微球呈光滑的圆球形,较为分散,未见明显聚集,微球粒径也较为均匀,80％的微球粒径在0.2-0.8μm之间;扫描电镜显示,载药微球光滑,呈圆球形,分散性较好,粒径分布较为均匀,粒径在0.2-0.8μm之间;②载药微球的包封率为68.9％-87.5％,载药率为0.95％-1.21％;③载药微球中辛伐他汀的释放曲线是温和的持续释放过程,载药水凝胶中辛伐他汀的释放曲线为前期释放速度快后期缓慢的持续释放过程,其中载药水凝胶比载药微球能更快释放并达到药物的作用浓度,在后期缓慢释放维持药物的作用浓度;④扫描电镜显示,载药水凝胶呈多孔条状结构,适合成骨细胞的黏附和生长,在水凝胶表面可以看到圆球形的载药微球;⑤载药水凝胶可促进MC3T3-E1细胞的增殖与碱性磷酸酶表达;⑥结果表明,缓释辛伐他汀微球水凝胶复合材料具有良好的生物相容性,能够促进成骨细胞的增殖与成骨分化.

Background: Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in patients with severe liver injury chronic hepatitis B (CHB) and patients with HBV-associated decompensated cirrhosis (DeCi). Methods: The characterization of the EVs in the serum was carried out for three different groups, namely, patients with severe liver injury-CHB, patients with DeCi, and healthy controls. EV miRNAs were analyzed using miRNA-seq and RT-qPCR arrays. Additionally, we assessed the predictive and observational values of the miRNAs with significant differential expressions in serum EVs. Results: Patients with severe liver injury-CHB had the highest EV concentrations when compared to the normal controls (NCs) and patients with DeCi (p < 0.001). The miRNA-seq of the NC and severe liver injury-CHB groups identified 268 differentially expressed miRNAs (|FC| > 2, p < 0.05). In this case, 15 miRNAs were verified using RT-qPCR, and it was found that novel-miR-172-5p and miR-1285-5p in the severe liver injury-CHB group showed marked downregulation in comparison to the NC group (p < 0.001). Furthermore, compared with the NC group, three EV miRNAs (novel-miR-172-5p, miR-1285-5p, and miR-335-5p) in the DeCi group showed various degrees of downregulated expression. However, when comparing the DeCi group with the severe liver injury-CHB group, only the expression of miR-335-5p in the DeCi group decreased significantly (p < 0.05). For the severe liver injury-CHB and DeCi groups, the addition of miR-335-5p improved the predictive accuracy of the serological levels, while miR-335-5p was significantly correlated with ALT, AST, AST/ALT, GGT, and AFP. Conclusions: The patients with severe liver injury-CHB had the highest number of EVs. The combination of novel-miR-172-5p and miR-1285-5p in serum EVs helped in predicting the progression of the NCs to severe liver injury-CHB, while the addition of EV miR-335-5p improved the serological accuracy of predicting the progression of severe liver injury-CHB to DeCi.

背景与目的:研究表明多种microRNA(miRNA)可能在肝癌的发生发展中发挥重要作用,其作用机制仍值得进一步研究和探讨.因此,本研究从已报道的肝癌差异表达miRNA中进一步筛选关键miRNA,并验证和探讨其作用机制.方法:从已发表的研究中筛选出肝癌组织及肝癌患者血清/血浆中与正常肝组织及正常血清/血浆中共同的差异表达miRNA;用qRT-PCR在正常肝细胞与肝癌细胞中对筛选出的目标miRNA表达情况进行验证;用过表达和抑制的方法观察目标miRNA对肝癌细胞侵袭能力(Transwell实验)与增殖能力(MTT实验)的影响,以及在30例临床标本中检测目标miRNA的表达并通过KM plotter网站分析其对肝癌患者生存的影响;通过miRDB和GEPIA数据库预测和分析目标miRNA的靶基因,并用逆转实验和双荧光素酶报告实验进一步验证.结果:在肝癌组织(vs.正常肝组织)及肝癌患者血清/血浆(vs.正常人血清/血浆)中共同高表达的miRNA有4个(miR-18a-3p、miR-221-3p、miR-222-3p、miR-224-3p),共同低表达的miRNA有2个(miR-26a-3p、miR-125b-3p).qRT-PCR实验证实,与正常肝细胞比较,miR-18a在肝癌细胞中高表达,miR-26a在肝癌细胞中低表达(均P＜0.05).过表达/抑制miR-18a-3p表达能促进/降低肝癌细胞的侵袭及生长能力(均P＜0.05),而过表达/抑制miR-26a-3p对肝癌细胞的侵袭及生长能力影响无不法确定.分析结果显示,ADCY1是miR-18a-3p的靶基因,过表达ADCY1能部分逆转miR-18a-3p对肝癌细胞的上述作用,同时,表达上调的miR-18a-3p能通过结合到ADCY1 mRNA 3'UTR抑制ADCY1的表达.结论:miR-18a-3p可能在肝癌的发生发展中起了关键作用,其在肝癌中表达上调,并能通过抑制下游靶基因ADCY1的表达增强进肝癌细胞的侵袭和增殖能力.

通常人们在医院希望医生把钱都花在治疗的药物上,非常反感检查费用过高.但是必要的检查是正确治疗的前提.辅助检查是诊断的客观证据,是疾病精准治疗的重要部分.若诊断不明确,再多、再好的治疗药物也有可能是南辕北辙.就肾综合征出血热而言,其病情变化快,治疗方案需要随时更改,精准治疗尤其重要,而客观辅助检查是精准治疗的重要保障.因此,下面所说的检查项目,都是肾综合征出血热诊治过程中不可或缺的.

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTL-NT) is a special subtype of non-Hodgkin's lymphoma derived from natural killer cells or cytotoxic T cells. Oral ulcers as the first symptom makes its diagnosis challenging because of its rarity and lack of understanding. We report a case of ENKTL-NT in this paper. We analyzed the clinicopathological features, differential diagnosis, treatment, prognosis and the causes of misdiagnosis to provide a diagnostic basis for dentists to make better clinical diagnosis and treatment.

CircRNA(circular RNA) is a new class of covalently closed circular non-coding RNAs, with the function of the microRNA sponge, regulation of gene expression, and other functions. Studies have confirmed that circRNAs are involved in the occurrence and progression of a variety of tumors, and can be used as biomarkers and therapeutic targets for tumor diagnosis and prognosis evaluation. In this paper, the expression and mechanism of circRNA in head and neck squamous cell carcinoma are reviewed.

Aims Voriconazole is a broad‐spectrum antifungal agent for the treatment of invasive fungal infections. There is limited information about the pharmacokinetics and appropriate dosage of voriconazole in patients with liver dysfunction. This study aimed to explore the relationship between voriconazole trough concentration (C trough ) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised voriconazole dosing regimen for patients with liver dysfunction. Methods The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic curves were used to explore the relationship between voriconazole C trough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed‐effects method. Dosing simulations stratified by total bilirubin (TBIL, TBIL‐1: TBIL < 51 μmol/L; TBIL‐2: 51 μmol/L ≤ TBIL < 171 μmol/L; TBIL‐3: TBIL ≥ 171 μmol/L) were performed. Results Receiver operating characteristic curve analysis revealed that voriconazole C trough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A 1‐compartment pharmacokinetic model with first‐order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance, volume of distribution and oral bioavailability were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole clearance was significantly associated with TBIL and platelet count. The volume of distribution increased with body weight. Patients with TBIL‐1 could be treated with a loading dose of 400 mg every 12 hours (q12h) for first day, followed by a maintenance dose of 100 mg q12h administered orally or intravenously. TBIL‐2 and TBIL‐3 patients could be treated with a loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily and 50 mg once daily orally or intravenously, respectively. Conclusions Lower doses and longer dosing intervals should be considered for patients with liver dysfunction. TBIL‐based dosing regimens provide a practical strategy for achieving voriconazole therapeutic range and therefore maximizing treatment outcomes.

类风湿关节炎(rheumatoid arthritis,RA)是一种慢性炎症性疾病,以关节受累为主,引起关节软骨和骨的破坏,最终导致关节畸形[1].IgA肾病是临床上常见的肾小球疾病,肾脏免疫病理表明以免疫球蛋白A为主的免疫复合物在肾小球系膜区沉积,其临床表现多样,或单纯蛋白尿、血尿,或急性乃至急进性肾炎综合征[2].目前IgA肾病确切病因及发病机制尚不明确,由于没有特异性治疗方案,约40％的IgA肾病患者在发病10～20年后进入终末期肾病[3].

新型冠状病毒肺炎防控期间,中南大学湘雅二医院基于二分法,以新冠肺炎诊断标准为分类标准,建立了包含门诊预检分诊管理、发热门诊分区布局、发热患者分级分类处置、住院患者分类管理的院内防控体系.笔者通过对实践经验进行总结和分析,以期为疫情防控及医疗机构管理提供借鉴.

目的 探讨彩色多普勒超声在早期膝关节骨性关节炎(KOA)患者药物治疗效果评价中的应用价值.方法 选取2017年1月至2019年1月接受药物治疗的早期KOA患者共80例.所有患者均接受药物治疗,分别于治疗前后接受彩色多普勒超声检查,观察膝关节关节腔积液情况、滑膜厚度、滑膜内动脉PSV、滑膜内动脉RI、滑膜内血流信号等.结果 治疗6周后,患侧膝关节关节腔积液、滑膜厚度、股骨内踝及外踝软骨厚度均较治疗前明显降低(P<0.01或P<0.05);患侧滑膜内动脉PSV较治疗前明显降低(P<0.05),而滑膜内动脉RI较治疗前明显升高(P<0.05);同时患侧膝关节滑膜血流信号丰富占比较治疗前明显减少(χ2=4.540,P<0.05).结论 彩色多普勒超声能直接显示膝关节腔、周围软组织及滑膜内血流分布情况,为临床药物治疗的疗效评价提供客观的依据.

不同于其他头颈部鳞状细胞癌,人乳头状瘤病毒(HPV)相关口咽鳞状细胞癌(OPSCC)是一类具有不同分子生物学发病机制、危险因素、临床病理特征的特殊疾病.HPV阳性OPSCC患者的预后明显优于HPV阴性患者,因此HPV的检测对OPSCC的诊断和治疗尤为重要.目前,国内外针对OPSCC中HPV生物分子标志物的检测方法多种多样,但仍然缺乏一个在该领域达成共识的规范化检测标准.本文围绕OPSCC中HPV生物分子标志物的研究现状做一总结,旨在为实验室以及临床上选择适合的生物分子标志物进行OPSCC诊断提供借鉴.

We read with great interest the letter by Janapala et al., 2020Janapala R.N. Patel J. Belfaqeeh O. Alhashmi A. Pourmand A. Novaferon, treatment in COVID-19 patients.Int J Infect Dis. 2020; (Available online 25 November 2020 In Press)https://doi.org/10.1016/j.ijid.2020.11.180Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar about our study of Novaferon as a potential antiviral drug in a randomized trial conducted in February, 2020 (Zheng et al., 2020aZheng F. Zhou Y. Zhou Z. Ye F. Huang B. Huang Y. et al.SARS-CoV-2 clearance in COVID-19 patients with Novaferon treatment: a randomized, open-label, parallel-group trial.Int J Infect Dis. 2020; 99: 84-91https://doi.org/10.1016/j.ijid.2020.07.053Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). The main points raised by these authors are addressed below. Aerosolized interferon-α (IFNα) treatment of respiratory viral infections has been generally practiced and recommended for COVID-19 treatment in China. The recommended dose of IFNα is 5 × 106 IU twice daily by inhalation, which equals a daily dose of 100 μg IFNα (1 × 107 IU daily, relative activity 1 × 108 IU/mg). As a mutant of IFNα with enhanced antiviral potency, Novaferon by aerosolized administration was thus considered a potential treatment for COVID-19. In addition, up to 40 μg Novaferon by daily injection has been applied in cancer patients and was well tolerated in a phase I trial (available at the official website of Chinese National Medicinal Products Admiration). The inhaled dose of 20 μg Novaferon twice daily (40 μg daily) for treatment of COVID-19 was determined accordingly. Our trial in early February paralleled the lopinavir/ritonavir trial by Cao et al., 2020Cao B. Wang Y. Wen D. Liu W. Wang J. Fan G. et al.A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19.N Engl J Med. 2020; 382: 1787-1799https://doi.org/10.1056/NEJMoa2001282Crossref PubMed Scopus (3751) Google Scholar in late January. At that time, nobody was able to predict the effect of lopinavir/ritonavir on COVID-19. Lopinavir/ritonavir remained a recommended standard-of-care antiviral drug for COVID-19 in China from January until the results of the RECOVERY trial of lopinavir/ritonavir were released (RECOVERY Collaborative Group, 2020RECOVERY Collaborative Group Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomized, controlled, open-label, platform trial.Lancet. 2020; 396: 1345-1352https://doi.org/10.1016/S0140-6736(20)32013-4Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar). It was rational to propose lopinavir/ritonavir as the control in our trial. Because of lack of experience, early medical interventions for COVID-19 needed to be adjustable by physicians. It was inadequate to fix the Novaferon treatment course at 7 days. Although the small sample size prevented us from stratifying the participants with regard to the actual duration of Novaferon treatment, all enrolled participants were strictly randomized into the three observation arms. The rates of viral clearance on day 6 of treatment and the time to viral clearance basically excluded the systemic impact of the slightly different treatment courses on the individual participants, and minimized bias due to the 7–10 days of Novaferon treatment. We agree with Janapala et al. that as 95% of participants in our study had moderate COVID-19, caution should be taken in extending the results to patients with severe COVID-19. As the median time to viral clearance in the Novaferon group and the lopinavir/ritonavir group was 4 days compared with 7 days in the Novaferon plus lopinavir/ritonavir group, we stated that both Novaferon groups with or without the combination of lopinavir/ritonavir exhibited a similar extent of viral clearance enhancement in comparison with the lopinavir/ritonavir group. The dynamic changes of viral loads in COVID-19 were related to the time of symptom onset and the disease severity (Zheng et al., 2020bZheng S. Fan J. Yu F. Feng B. Lou B. Zou Q. et al.Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January–March 2020: retrospective cohort study.BMJ. 2020; 369: 1-8https://doi.org/10.1136/bmj.m1443Crossref Scopus (1035) Google Scholar). It would be valuable to stratify patients on the basis of the time from symptom onset to the time of treatment in larger COVID-19 studies. Currently, several toxicity grading scales are applied in clinical studies. The World Health Organization toxicity grading scale referred in our article is given in World Health Organization, 1979World Health Organization WHO Handbook for Reporting Results of Cancer Treatment. WHO offset Publication No. 48. World Health Organization, Geneva1979https://apps.who.int/iris/handle/10665/37200Google Scholar. This work was supported by the National Science and Technology Major Project (2017ZX10202201, 2017ZX10202203), the National Key Research and Development Program of China (No. 2016YFD0500301), the Natural Science Foundation of Hunan Province of China (2018JJ2452) and Specialized Science and Technology Project of Hunan Province of China (2020SK3013).

背景与目的:甲状腺癌发病率逐年升高,但其发病机制仍不清楚,阐述甲状腺癌的发病机制对改善甲状腺癌患者的预后至关重要.研究表明,m6A甲基化调控因子高度参与癌症发生发展,具有良好的潜在预后价值.因此,本研究通过生物信息学方法分析甲状腺癌中m6A甲基化调控因子的表达并构建基于m6A甲基化调控因子的甲状腺癌预后模型.方法:从TCGA数据库下载甲状腺癌m6A甲基化调控因子的表达数据和相应的临床病理资料,通过Wilcoxon检验分析20个m6A甲基化调控因子在肿瘤和正常组织的差异表达;用一致性聚类分析将甲状腺癌患者分为两个聚类,比较两个聚类患者临床病理因素和总体生存率的差异;Lasso Cox回归分析构建风险预测模型并用ROC曲线下面积(AUC)评估模型的预测能力.结果:19个m6A甲基化调控因子在甲状腺癌和正常组织表达具有统计学差异(均P＜0.05),其中HNRNPC、IGF2BP2、FMRl在甲状腺癌组织中明显高表达,而其余表达下调.聚类分析示,cluster 1生存期低于cluster 2(P＜0.05),颈淋巴结转移发生率明显高于cluster 2(P＜0.01) 基于Lasso Cox回归分析筛选的4个基因(IGF2BP2、RBM15、YTHDF1、YTHDF3)构建风险评估模型,相比低风险组患者,高风险患者生存期明显缩短(P=0.007);ROC曲线示,该模型可以预测甲状腺癌患者的预后(AUC=0.731).结论:m6A甲基化调控因子在甲状腺癌中存在差异表达,基于甲状腺癌中关键m6A甲基化调控因子所构建的预后风险模型具有较好的预测能力,可为临床决策提供一定的依据.

Objectives:During the COVID-19 pandemic, clinicians and public health decision-makers especially focus on fever patients. Other common pathogens that may cause fever are easily overlooked. We aimed to describe the pathogen infection and epidemic trend of non-SARS-CoV-2 occurring in hospitalized patients.Methods:An observational cohort study of 733 consecutive patients admitted to Hospital Clinic of the Second Xiangya Hospital for COVID-19. All samples of a pharyngeal swab from patients with fever have been tested for nucleic acid and immune antigens of SARS-CoV-2 and Influenza A/B virus. 649 fever patients have been tested for nucleic acid in ten respiratory pathogens. Macrotranscriptome sequencing was performed on 26 samples.Results:Of a total of 733 patients with fever, 2.05% patients had confirmed SARS-CoV-2 infections. Fever patients with common respiratory pathogens in fever patients was 8.78%. There is no integration phenomenon between SARS-Cov-2 and the human genome. SARS-CoV-2 positive samples will also be infected with other viruses, especially adenovirus. Macrotranscript analysis showed that there was no significant difference in the species and genus levels of pathogens between Covid-19 patients and other fever patients. The main pathways that affect human metabolism after SARS-Cov-2 infection are the Calvin-Benson-Bassham cycle, pyrimidine deoxyribonucleotides de novo biosynthesis I and D-galactose degradation V.Conclusions:Most patients have a fever caused by common respiratory pathogens. Clinicians still need to pay more attention to infections of common respiratory pathogens in addition to SARS-CoV-2. China's public health measures to stop the spread of the epidemic have proven effective.

目的观察重组细胞因子基因衍生蛋白注射液(乐复能)治疗HBeAg阳性慢性乙型肝炎(CHB)患者的有效性及安全性。方法前瞻性收集2010年6月1日至2011年9月6日中南大学湘雅医院、中南大学湘雅二医院、中南大学湘雅三医院和湖南中医药大学第一附属医院收治的HBeAg阳性CHB患者360例。按照1∶1比例随机分为实验组(n=180)和对照组(n=180), 实验组患者予乐复能, 对照组患者予人干扰素α-2b, 双盲治疗12周后进入开放标签阶段, 在患者自愿基础上, 实验组患者继续使用乐复能, 对照组患者转向使用乐复能, 治疗12周后停药随访12周和52周。治疗和随访阶段检查血常规、肝功能、HBV DNA等指标, 分析乐复能治疗HBeAg阳性CHB患者的有效性。采用SAS 9.1.3对数据进行统计分析。结果双盲治疗12周后, 实验组和对照组的HBeAg血清转阴率分别为27.11%和16.17%, 差异具有统计学意义(χ2=5.98, P<0.05), 实验组的HBeAg血清学转换率、丙氨酸转氨酶(ALT)复常率, HBV DNA转阴率均高于对照组, 但差异均无统计学意义(P>0.05)。进入开放标签阶段和随访阶段, 实验组的HBeAg血清转阴率、HBeAg血清学转换率、HBV DNA转阴率及ALT复常率均继续升高。不良反应事件监测中, 实验组患者的头痛、乏力发生率均低于对照组(P<0.05), 其余与药物相关的重度不良事件在两组的差异无统计学意义(P>0.05)。结论乐复能可更好地促进CHB患者HBeAg转阴及血清学转换。乐复能治疗HBeAg阳性的CHB患者安全、有效。

Background: The antiviral effects of Novaferon, a potent antiviral protein drug, on COVID-19 was evaluated in the laboratory, and in a randomized, open-label, parallel-group trial. Methods: In the laboratory, Novaferon's inhibition of viral replication in cells infected with SARS-CoV-2, and prevention of SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir were evaluated. The primary endpoint was the SARS-CoV-2 clearance rates on day six of treatment, and the secondary endpoint was the time to SARS-CoV-2 clearance. Results: Novaferon inhibited viral replication (EC50 = 1.02 ng/ml), and prevented viral infection (EC50 = 0.10 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher viral clearance rates on day six than Lopinavir/Ritonavir group (50.0% vs. 24.1%, p = 0.0400, and 60.0% vs. 24.1%, p = 0.0053). The median time to viral clearance was six days, six days, and nine days for three groups, respectively, a 3-day reduction in both the Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with the Lopinavir/Ritonavir group. Conclusions: Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justify further evaluation of Novaferon. Trial registration number: Number ChiCTR2000029496 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/).