Thymosin alpha 1 for the adjuvant treatment of coronavirus disease 2019: a retrospective cohort study / 中华危重病急救医学

Objective:To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model.Results:Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality ( HR = 0.15, 95% CI was 0.04-0.55, P = 0.004), old age ( HR = 1.10, 95% CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction ( HR = 42.35, 95% CI was 2.77-648.64, P = 0.007), decrease of LYM at admission ( HR = 0.15, 95% CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone ( HR = 4.59, 95% CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients ( HR = 0.45, 95% CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×10 9/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. Conclusion:Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.

Thymosin Alpha-1 Inhibits Complete Freund's Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord / 神经科学通报·英文版

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems. The immunopotentiator thymosin alpha-1 (Tα1) has recently been reported to have anti-inflammatory and neuroprotective functions in rodents. However, how Tα1 affects inflammatory pain remains unclear. In the present study, intraperitoneal injection of Tα1 attenuated complete Freund's adjuvant (CFA)-induced pain hypersensitivity, and decreased the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in inflamed skin and the spinal cord. We found that CFA-induced peripheral inflammation evoked strong microglial activation, but the effect was reversed by Tα1. Notably, Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter (VGLUT) and down-regulated the vesicular γ-aminobutyric acid transporter (VGAT) in the spinal cord. Taken together, these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microglia-induced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.

The Effect of Thymosin Alpha 1 on Severe Acute Pancreatitis in Rats / Estudios sobre el efecto de la timosina alfa 1 sobre la pancreatitis aguda grave en ratas

ABSTRACT Objective: To observe the effect of thymosin alpha l (Tα1) on severe acute pancreatitis (SAP) in rats. Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups (eight in each group): control group (Group A), SAP group (Group B) and Tα1 treatment group (Group C). Animal models of SAP were made by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Rats in Group C were treated with Tα1 (6 mg/kg) via intraperitoneal administration prior to SAP modelling. Eight rats in each group were sacrificed at 12 hours, respectively, after modelling. The serum levels of amylase, tumour necrosis factor-α (TNF-α), interleukin-lβ (IL-lβ and interleukin-6 (IL-6) were detected in each group. The pathological scores of the tissue in the pancreas head were observed by light microscopy. Results: The levels of serum amylase of Group B were 6378 ± 538 U/L, which were significantly higher than those (4587 ± 478 U/L) of Group C (p < 0.05). The levels of serum TNF-α of Group B were 360.32 ± 28.67 pg/mL, which were higher than those (269.99 ± 26.11 pg/mL) of Group C (p < 0.05). The levels of serum IL-lβ of Group B were 435.93 ± 36.00 pg/mL, which were higher than those (312.42 ± 17.89 pg/mL) of Group C (p < 0.05). The levels of serum IL-6 of Group B were 433.90 ± 28.36 pg/mL, which were higher than those (289.98 ± 23.00 pg/mL) of Group C (p < 0.05). The pancreatic pathological scores of Group B were 13.34 ± 2.19, which were higher than those (6.39 ± 1.86) of Group C (p < 0.05). Conclusion: Thymosin alpha 1 could decrease proinflammatory cytokines and reduce pancreas injury and had a protective effect in rats with SAP. This provides a new strategy for the clinical treatment of SAP.

RESUMEN Objetivo: Observar el efecto de la timosina alfa l (Tα1) sobre la pancreatitis aguda grave (PAG) en ratas. Métodos: Veinticuatro ratas Sprague-Dawley adultas machos fueron divididas aleatoriamente en tres grupos (ocho en cada grupo): grupo de control (grupo A), grupo de PAG (grupo B) y grupo de tratamiento con Tα1 (grupo C). Los modelos animales de PAG fueron creados mediante inyección retrógrada de taurocolato de sodio al 5% en el conducto biliopancreático. Las ratas del grupo C se trataron con Tα1 (6 mg/kg) via administración intraperitoneal antes del modelado de PAG. Las ocho ratas en cada grupo fueron sacrificadas a las 12 horas, respectivamente, después del modelado. Los niveles séricos de amilasa, factor-α de necrosis tumoral (TNF-α), interleucina-β (Il-β) e interleucina-6 (IL-6) fueron detectados en cada grupo. Las puntuaciones patológicas del tejido en la cabeza del páncreas fueron observadas mediante microscopía de luz. Resultados: Los niveles de amilasa sérica del grupo B fueron 6378 ± 538 U/L, y resultaron significativamente más altos (p < 0.05) que los niveles 4587 ± 478 U/L del grupo C. Los niveles séricos de TNF-α del grupo B fueron 360.32 ± 28.67 pg/mL, y resultaron ser más altos (p < 0.05) que los 269.99 ± 26.11 pg/mL del grupo C. Los niveles séricos de Il-β del grupo B fueron 435.93 ± 36.00 pg/mL, y fueron más altos (p < 0.05) que los 312.42 ± 17.89 pg/mL) del grupo C. Los niveles de suero IL-6 del grupo B fueron 433.90 ± 28.36 pg/mL, y resultaron ser más altos (p < 0.05) que los 289.98 ± 23.00 pg/mL del grupo C. Las puntuaciones patológicas pancreáticas del grupo B fueron 13.34 ± 2.19, y resultaron ser más altas (p < 0.05) que las puntuaciones 6.39 ± 1.86 del grupo C. Conclusión: La timosina alfa pudo disminuir las citoquinas proinflamatorias y reducir la lesión del páncreas, y tuvo un efecto protector en las ratas con PAG. Esto ofrece una nueva estrategia para el tratamiento clínico de PAG.

Effect of early enteral nutrition combined with thymosin alpha-1 on patients with acute exacerbation of chronic obstructive pulmonary disease and respiratory failure / 肠外与肠内营养

Objective:To explore the effect of early enteral nutrition combined with thymosin alpha-1 (T-a1)on patients with acute exacerbation of chronic obstructive pulmonary disease and respiratory failure.Methods:One hundred and thirty five patients with acute exacerbation of chronic obstructive pulmonary disease were randomly divided into experimental A group (EN)(n =45),experimental B group (EN+T-a1)(n =45)and control group (n =45).In earlier period,experimental A group received Ruineng enteral nutrition,experimental B group received Ruineng enteral nutrition combined with intramuscular T-a1,whereas control group received general clinical therapy.The mechanical ventilation time,inflammatory index,nutritional index and T cell subset index were compared among three groups.Results:Compared to control group,nutritional index and T cell subset index in experimental A group were significantly higher while inflammatory index were lower (P ＜ 0.05),and mechanical ventilation time was shorter (P ＜ 0.05) after a week.Compared to experimental group A,nutritional and T cell subset index were significantly higher,inflammatory index were lower,and mechanical ventilation time was shorter (P ＜ 0.05) in experimental B group (P ＜ 0.05) after a week.Conclusion:Early enteral nutrition can shorten mechanical ventilation time,improve nutritional status,reduce inflammatory indicators,enhance immune function,and thereby improving clinical efficacy in patients with AECOPD combined with respiratory failure.Furthermore,early enteral nutrition combined with thymosinal treatment can improve clinical efficacy of AECOPD patients with respiratory failure.

Clinical research of thymosin alpha -1 with glucocorticoid in treatment of HBV -related acute -on -chronic liver failure / 中国基层医药

Objective To evaluate the therapeutic effect of thymosin alpha -1 with glucocorticoid in treat-ment of HBV -related hepatic failure.Methods 130 cases were randomly divided into two groups,they were all giv-en antiviral therapy,protect liver,anti -inflammatory,yellow suit the back support,etc.comprehensive treatment;and patients in treatment group were given thymosin alpha -1 with methyl -prednisone intravenously at the early stage of treating process,and then observed the clinic situation and cure rate of those sufferers,The biochemiccal indicator, PTA and blood serum HBV DNA capacity ending with the period of 4 weeks were tested.Results In both groups,the TBil,TC in serum had apparently improved compared with the baseline after the medication,the difference was signifi-cant (t =3.12,P <0.05 and t =3.05,P <0.05).The time of gastrointestinal symptoms improvement and bilirubin subsided time in treatment group were significantly shorter than those of the control group(t =3.34,P <0.01 and t =4.52,P <0.01 ).During the treatment,there was no significant adverse reaction,and there were no differences between two groups in Alt,PTA,HBV DNA,infection,gastrointestinal bleeding,hepatic encephalopathy and hepatore-nal syndrome.The effective rate of treatment group was 75.2%,which was higher than 50.3% of the control group (χ2 =11.02,P <0.01).Conclusion Patients with HBV -related hepatic failure of short -term application of thy-mosin alpha -1 with glucocorticoid treatment,can quickly improve symptoms,greatly improve the efficiency of survival rate,shortem hospitalization period,reduce side effects and enhance security.

Thymosin alpha 1 for patients with hepatocellular carcinoma after radical hepatectomy / 中国肿瘤临床

Objective: The effect of thymosin alpha 1 (Tα1) on patients with hepatocellular carcinoma (HCC) after radical hepatectomy was assessed. Methods: A total of 558 HCC patients treated by radical hepatectomy were retrospectively collected. Patients in the treatment group (n=146) received postoperative Tα1 therapy, whereas patients in the control group (n=412) did not. Propensity scale matching was conducted to improve the balance between the two groups. Changes in liver function, recurrence-free survival rates, and overall survival rates were compared between the two groups. Results: Postoperative liver function (i.e., TBIL, ALB, ALT, and PT) in the treatment group was significantly better than that in the control group (P<0.05). The one-, two-, and three-year recurrence-free survival rates and overall survival rates in the treatment group were significantly higher than those in the control group (P=0.019 and P=0.011, respectively). Conclusion:Postoperative Tα1 therapy can improve postoperative liver function, thus significantly prolonging recurrence-free survival and overall survival.

Effects of thymosin alpha 1 combined with neoadjuvant chemotherapy in breast cancer / 中国基层医药

Objective To study the impact of the thymosin alpha 1 on the toxicity and celluar immune function during neoadjuvant chemotherapy of breast cancer.Methods 83 patients of Ⅱ b-Ⅲ a stage breast cancer were randomly divided into two groups:study group(40 patients,neoadjuvant chemotherapy of CEF combined with thymosin α 11.6mg HQD) and control group(43 cases,neoadjuvant chemotherapy of CEF alone).Results Rates of gastrointestinal reaction and bone marrow depression in study group were significantly lower than those in control group.The levels of CD3,CD4,CD4/CD8 and NK in study group were significantly higher than those in control group after chemotherapy.Conclusion The combination of thymosin alpha 1 and neoadjuvant chemotherapy for breast cancer can reduce the toxicity,improve the tolerance,enhance cellular immune function and improve the quality of breast cancer patient's life.

Clinical application of thymosin alpha 1 in treatment of chronic obstructive pulmonary disease / 中国基层医药

Objective To observe the therapeutic effect of thymosin alpha 1 on patients with chronic obstructive pulmonary disease.Methods 60 patients with chronic obstructive pulmonary disease were divided into two groups at random.The two groups were given conventional treatment,and the treatment group was received thymosin alpha 11.6 mg hypodermic injection,1 every other day for 4 weeks,since then 2 times/week for 5 months.All patients were followed for 6 months,clinic every 2 weeks,1 follow-up,evaluation of clinical condition.In two groups,before treatment and 6 months after treatment the blood samples were collected for the measurement of the blood CD3,CD,and CD8 levels.Results In the treatment group,the number and days of patients with acute exacerbation were significantly lower in comparison with those of the control group(all P＜0.01).After treatment with thymosin alpha 1,blood CD4 and CD4/CD8 levels were significantly increased(all P＜0.01).Conclusion Thymosin alpha 1 had a good protection effect for the acute exacerbation of chronic obstructive pulmonary disease by incresing body cellular immune activity.

Effects of thymosin alpha-1 on T cell subsets and gastricintestinal reaction of patients with gastricintestinal tumor / 中国基层医药

Objective To observe the effects of thymosin alpha-1 on T cell subsets and gastricintestinal reac-tion of patients with gastricintestinal tumor. Methods Twenty patients with gastricintestinal tumor were divided into two groups, observe group(n = 10) received thymosin alpha-1 during chemotherapy, and control group(n = 10) only received chemotherapy, T cell subsets and gastricintestinal reaction were observed. Results Before chemotherapy, CD+4,CD+8 and CD+4/CD+8 of observe group were(43.7±7.5),(27.3±2.8) and (1.5±0.1), and control group were (39.4±6.3), (30.9±2.5) and (1.2±0.6). There was significant difference between them (P < 0.05). After chemotherapy, CD+4, CD+8 and NK cell were (40.6±6.8)、( 29.7±2.6) and (19.1±2.7), control group (35.9±5.7), (33.4±2.4) and (18.6±2.3). There was significant difference between them (P < 0.05). Effec-tive ratio of nausea and vomit of observe group were 72.5% and 60.0%, control group 40.0% and 33.3%, There were significant differences between them(P <0.05). Conclusion Thymosin alpha-1 may ameliorate the function of T cell subsets and gastricintestinal reaction of patients with gastricintestinal tumor.

Effects of early application of thymosin peptide alpha 1 on T lymphocyte subsets after hepatectomy in patients with hepatocellular carcinoma / 中国病理生理杂志

AIM: To investigate the effects of early application of thymosin peptide alpha 1 on lymphocyte subsets after operation in patients with hepatocellular carcinoma. METHODS: Forty-six patients with hepatocellular carcinoma were randomly divided into control and treatment groups for this study. Thymosin α1 at dose of 1.6 mg was injected subcutaneously on day 1, 3, and 5 after operation in treatment group. The percentages of CD3+, CD4+ and CD8+ cells, and CD4+/CD8+ ratio in both groups were counted before operation and on day 1, 4, and 7 after hepatectomy. RESULTS: CD4+ cell population and CD4+/CD8+ ratio decreased, but CD8+ increased after operation in control group (P<0 05). In thymosin peptide alpha 1 treatment group, there was no statistical difference in the percentages of CD3+, CD4+, CD8+, and CD4+/CD8+ before and after operation. In addition, thymosin α1 significantly increased CD4+ cell population and CD4+/CD8+ ratio (P<0 05). CONCLUSION: Operation suppresses the immune function in patients with hepatocellular carcinoma. Thymosin α1 increases CD4+ T lymphocyte subsets in patients after operation.

Thymosin Alpha-1 in Combination with Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients Who have Failed to Prior Pegylated Interferon and Ribavirin Treatment

Combination therapy with inteferon-alpha and ribavirin is an approved therapy for patients with chronic hepatitis C. However, even with the use of pegylated interferon, response rates are still poor in many difficult-to-treat groups, especially with genotype 1 and high viral loads. Retreatment of these patients remains challenging. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups. Thymosin alpha 1 is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. Herein, we describe two cases of retreatment patients with chronic hepatitis C who have failed prior pegylated interferon and ribavirin therapy. They received triple combination therapies of thymosin alpha 1, pegylated interferon and ribavirin and achieved sustained virological responses. These cases support that thymosin-alpha 1 may increase the efficacy of pegylated interferon plus ribavirin in the treatment of non-responders to previous combination therapy.

Meta-analysis on the effect and adverse reaction of thymosin alpha-1 in the treatment of malignant tumor / 医学研究生学报

Objective:To evaluate the effect and adverse reaction of thymosin ?1(T?1) in the treatment of malignant tumor.Methods:MEDLINE,Chinese hospital knowledge database(CHKD),Chinese Biomedical Database(CBM) were searched by key word ,and the obtained references were screened for clinical controlled trials(CCT) on the introduction of T?1 in therapy of malignant tumor.The CCT results of efficacy and safety were pooled and analyzed with a fixed or random effects model after Chi-Square testing for heterogeneity.Results:Six CCTs were included for efficacy analysis.It was found that the efficacy rate in T?1 group(70.63%) was significantly higher than that in control group(52.99%),and the value of odds ratio was 1.28 with the 95% confidence interval from 1.06 to 1.55(P

A meta -analysis of thymosin-?_1 monotherapy for chronic hepatitis B virus infection / 中国实用内科杂志

Objective To investigate the efficacy of thymosin alpha-1(T?_1,Zadaxin)monotherapy for chronic HBV infection by a meta-analysis of the published data. Methods Randomized controlled trials on thymosin alpha-1 monotherapy in chronic HBV infection were searched from electronic databases such as MEDLINE、PUBMED and Blackwell. Results Meta-analysis of 7 randomized controlled studies investigating the safety and efficacy of thymosin alpha-1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with thymosin alpha-1(1.6 mg twice weekly)almost tripled the sustained response rate(38%)compared with controls(13%).Conclusion These results suggest that a 6-month course of thymosin alpha-1 therapy is effective and safe in patients with chronic hepatitis B;thymosin alpha-1 can effectively reduce HBV replication in CHB with patients. Compared with IFN-?,thymosin alpha-1 which has less side effects is better tolerated and seems to induce a gradual and more sustained normalization of ALT and loss of HBV DNA.

Analysis of the clinical effects of thymosin ?1 on gastrointestinal carcinoma in elderly patients / 解放军医学杂志

Objective To observe and evaluate the clinical effects of thymosin ?1 on gastrointestinal carcinoma in elderly patients.Methods Ninety-six aged patients with gastrointestinal carcinoma in the General Hospital of PLA,who had received chemotherapy,were randomly divided into two groups(n=48 for each group): control group and treatment group.Patients in the treatment group received thymosin ?1 by subcutaneous injection in a dose of 1.6mg,the treatment was given once every other day and the whole course lasted for 8 weeks;while patients in the control group received physiological saline solution in the same amount only instead of thymosin.For the patients in both groups,the activities of peripheral blood T cell subsets,such as CD4+,CD4+/CD8+ and natural killer(NK),were measured by flow cytometry before the treatment and in the 2nd,4th,8th week of chemotherapy.The life quality of every patient was evaluated by Karnofsky scores at the same time.Results After the treatment,the Karnofsky scores in the treatment group were much higher than that in the control group(P