Thymosin as a possible therapeutic drug for COVID-19: A case report

BACKGROUNDThere are no effective antiviral therapies for coronavirus disease 2019 (COVID-19) at present. Although most patients with COVID-19 have a mild or moderate course of disease, up to 5%-10% of patients may have a serious and potentially life-threatening condition, indicating an urgent need for effective therapeutic drugs. The therapeutic effect of thymosin on COVID-19 has not been previously studied. In this paper, for the first time we report a case of thymosin treatment of COVID-19.CASE SUMMARYA 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness, chest pain, and fatigue. The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative. The antibody test was positive, confirming the diagnosis of COVID-19. As many orally administered drugs were not well tolerated due to gastrointestinal symptoms, an emergency use of thymosin, a polypeptide consisting of 28 amino acids, was administered by injection. Finally, after the implementation of the treatment program, symptoms and lung imaging improved significantly.CONCLUSIONIn this case report, it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms.     

四逆散加味方对雌孕激素受体阴性乳腺癌3年复发转移影响

目的:观察四逆散加味方对雌、孕激素受体阴性乳腺癌3年复发转移的影响。方法:将30例门诊患者随机分为两组。对照组15例:胸腺肽10mg/次,tid口服。治疗组15例:四逆散加味方,1剂/d,水煎2次,共取汁250mL,分2次温服;“递减式”服药法。辨证加减。两组服药均治疗2年。采用门诊复诊或电话随访,定期检查肿瘤标志物、彩超、胸片等,随访至术后3年,观察两组肿瘤复发转移率。结果:1年两组复发0例,复发率0%。2年对照组复发2例,复发率13.33%;治疗组复发0例,复发率0%。3年对照组复发4例,复发率26.66%;治疗组复发1例,复发率6.66%。两组3年复发转移率比较,差异有显著性意义(P<0.05)。结论:四逆散加味方可以明显降低雌、孕激素受体阴性乳腺癌3年复发转移率,安全性好,填补了现代医学治疗的“空窗期”,值得临床深入研究。     

严重脓毒症患者外周血单个核细胞Toll样受体2、4和髓样分化因子88在胸腺肽α1治疗过程中的基因表达变化

目的 观察严重脓毒症患者外周血单个核细胞Toll样受体（TLR）2、4基因及其信号传导通路上的髓样分化因子88（MyD88）基因表达水平在胸腺肽α1治疗过程中的变化。方法 54例严重脓毒症患者被随机分为对照组（常规治疗,28例）和治疗组（胸腺肽α1治疗,26例）,采用实时荧光定量PCR监测两组患者入院时及治疗后第3、7天外周血单个核细胞TLR2、TLR4和MyD88基因表达水平变化,并观察两组的28 d病死率。结果 治疗组的28 d病死率虽低于对照组,但差异无统计学意义（23.1%vs 35.7%,P=0.310）。治疗组的患者单核细胞TLR2、TLR4和MyD88基因表达水平逐渐上升,而对照组未见该规律,与对照组相比,治疗后第3天时治疗组的TLR2（2.31±0.79 vs 1.83±0.51）、TLR4基因表达增高（7.31±0.79 vs 6.55±0.92）;第7天时治疗组TLR2（2.75±1.17 vs 1.63±0.36）、TLR4（7.75±1.03 vs 6.39±0.72）和MyD88（4.26±0.77 vs 3.77±0.68）水平明显增高,均P〈0.05。结论 胸腺肽α1在治疗严重脓毒症患者过程中可以上调患者单核细胞的TLR2、4和MyD88基因的表达水平。     

多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究

背景与目的：乳腺癌患者体内存在严重的免疫失衡,胸腺肽α1（thymosin α1,Tα1）作为免疫增强剂发挥作用,探究多西他赛（docetaxel,DCT）联合Tα1对大鼠乳腺癌免疫微环境中调节性T细胞（regulatory T cell,Treg）数量的影响,并初步分析其作用机制。方法：随机将60只雌性SD大鼠分为模型组、DCT组（剂量为10 mg/kg）、Tα1组（剂量为0.8 mg/kg）及3个DCT+Tα1组（DCT剂量为10 mg/kg,Tα1剂量分别为0.2、0.4、0.8 mg/kg）,每组10只。给雌性SD大鼠接种大鼠乳腺癌细胞系SHZ-88建立移植瘤模型,成瘤后,DCT组、Tα1组及DCT+Tα1组分别腹腔注射相应剂量的DCT、Tα1,给药周期均为20 d,1次/d。测量大鼠肿瘤体积,采用原位末端转移酶标记（TdT-mediated dUTP nick end labeling,TUNEL）染色法检测肿瘤细胞的凋亡情况。采用流式细胞术检测大鼠肿瘤组织中CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Treg数量及表达程序性死亡［蛋白］-1（programmed death-1,PD-1）的Treg数量,采用酶联免疫吸附试验（enzyme-linked immunosorbent assay,ELISA）检测肿瘤组织中白细胞介素-10（interleukin-10,IL-10）、转化生长因子-β（transforming growth factor-β,TGF-β）的表达,采用蛋白质印迹法（Western blot）检测肿瘤组织中PD-1及程序性死亡［蛋白］配体-1（programmed death ligand-1,PD-L1）的表达。结果：与模型组相比,给药组均可明显抑制肿瘤的生长,促进肿瘤细胞凋亡,显著下调CD4 ^＋CD25 ^＋ Foxp3 ^＋ Treg数量,以及IL-10、TGF-β、PD-1和PD-L1的表达（P ＜ 0.05）,其中DCT+0.8 mg/kg Tα1组作用效果最显著,明显优于其他给药组。结论：DCT联合Tα1可抑制大鼠肿瘤的生长,其中以DCT+0.8 mg/kg Tα1效果最显著,作用机制可能是通过下调PD-1/PD-L1的表达,抑制CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Treg浸润。     

Influence of thymosin on E-rosette formation of lymphoid cells in leukemic and nonleukemic children

Summary The influence of two thymosin and two spleen control preparations on the E-rosette formation of peripheral blood lymphocytes and leukemic cells from non-leukemic children with depressed T cell values and leukemic children was investigated. Both thymosin preparations but also one of the control preparations induced a significant increase in the mean percentage of E-rosette forming PBL in the non-leukemic children with depressed T cell values. Thymosin and spleen preparations, however, did not convert the non-erythrocyte binding blasts to erythrocyte binding cells in either common or pre-TALL.     

胸腺素胶囊治疗慢性乙型肝炎的疗效

目的研究胸腺素胶囊对慢性乙型肝炎的治疗作用．方法慢性乙型肝炎２５例口服胸腺素胶囊１５ｍｇ，２次／ｄ，４个月为１疗程；另外２５例对照组给予西利宾胺１００ｍｇ，３次／ｄ，４个月为１疗程．其他治疗２组相同．结果治疗组有效率为５２％，明显高于对照组（２０％，Ｐ＜００５）．结论胸腺素胶囊对慢性乙型肝炎有明显治疗作用．     

胸腺肽α1联合大剂量地塞米松治疗慢性特发性血小板减少性紫癜的疗效分析

目的探讨胸腺肽α1（Tα1）联合大剂量地塞米松（Dex）短程冲击治疗初治慢性特发性血小板减少性紫癜（ITP）的疗效及其细胞免疫机制。方法（1）66例初诊ITP患者口服Dex 40mg/d,连用4d;其中39例同时给予Tα1 1．6mg皮下注射,每周3次,连续应用4周。（2）ELISA法检测正常对照组20例及初诊ITP患者治疗前后血浆Tα1、IFNγ、IL-2、IL-4、IL-10及转化生长因子（TGF）-β1水平。结果（1）Tα1＋Dex联合治疗组与Dex单药治疗组,完全缓解（CR）率分别为76．9％（30／39）、44．4％（12／27）（P〈0．05）;长期反应率分别为61．5％（24／39）、34．6％（9／26）,复发率分别为38．5％（15／39）、65．4％（17／26）,差异均有统计学意义（P〈0．05）。（2）Tα1＋Dex治疗后Tα1水平为（1．83±1．22）μg/L较治疗前（2．43±1．47）μg／L明显降低（P〈0．05）。（3）Tα1＋Dex治疗后患者IFNγ和IL-2的血浆水平[（11．57±4．33）、（14．56±10．76）]ng／L均较治疗前[（22．71±7．98）、（28．42±11．27）]ng／L显著降低（P〈0．01）,且与正常对照组比较[（10．23±3．97）、（8．73±8．22）]ng／L,差异无统计学意义（P〉0．05）。IL-4和IL-10的血浆水平[（9．87±4．82）、（7．90±2．71）]ng／L均较治疗前[（5．93±3．85）、（3．24±1．36）]ng／L明显升高（P〈0．05）,且与正常对照组比较,差异无统计学意义（P〉0．05）。（4）Tα1＋Dex治疗后患者血浆TGF-β1水平（4．19±1．80）μg/L较治疗前（1．31±0．71）μg／L明显升高（P〈0．01）。（5）Tα1＋Dex治疗后患者Tα1水平与TGF-β1含量之间呈显著正相关（r=0．6028,P〈0．05）。结论（1）Tα1＋Dex联合治疗可以纠正ITP患者体内Th1／Th2平衡紊乱,减少血小板破坏,其CR率高、复发率较低且耐受性好,可作为ITP治疗的一种新的尝试。（2）Tα1＋Dex治疗后患者Tα1水平与作为Th3特异性标志的TGF-β1之间呈显著正相关,可能与NK细胞的生理性抑制功能上调有关。     

Thymosin alpha 1: A comprehensive review of the literature

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.     

胸腺肽α1联合舒利迭预防COPD急性发作的临床研究

目的探讨胸腺肽α1联合舒利迭对COPD急性发作的预防作用。方法将120例COPD稳定期患者随机分为对照组与观察组,给予58例对照组患者常规治疗及舒利迭吸入,观察组患者在常规治疗及舒利迭吸入基础上给予胸腺肽α1皮下注射。随访1年,比较两组临床疗效、1年内急性发作情况及治疗前后肺功能改变。结果观察组与对照组治疗总有效率为87.0%和60.3%,观察组显著优于对照组(P=0.001);随访1年中,观察组急性发作次数、再发间隔时间及急性发作时间均显著少于对照组(P<0.05);两组治疗后肺功能FEV1、FEV1/FVC及FEV1/预计值均有所改善,P>0.05。结论胸腺肽α1联合舒利迭可有效预防COPD急性加重,效果优于单用舒利迭。