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BACKGROUND: Liver injury in a multiple organ failure model causes great troubles to clinicians’ medication. Thymosin α1 is used for treating chronic hepatitis and it has obvious protective effects against liver injury. OBJECTIVE: To investigate the protective mechanism of thymosin α1 on liver injury in a rat model of multiple organ failure, based on adiponectin (ADPN)/ protein kinase B (Akt)/nuclear factor κB (NF-κB) signaling pathway. METHODS: Male SPF Sprague-Dawley rats were randomly divided into four groups: normal group, model group, experimental group, and control group. Rats in the model group, experimental group, and control group were given intraperitoneal injection of 500 mg/kg zymosan (50 g/L) to construct the rat multiple organ failure model. Normal rats were injected intraperitoneally with equal doses of normal saline. Thirty minutes after the injection, the rats in the experimental group and the control group were injected intraperitoneally with 2 mL of thymosin α1 and ganlixin with the dose of 0.5 mg/kg daily, respectively. The normal group and the model group were injected intraperitoneally with the same dose of normal saline. After 7 days of continuous administration, liver function parameters were tested; histopathological changes of rat liver tissues and cell apoptosis were detected using hematoxylin-eosin staining and TUNEL staining; immunohistochemistry and western blot were used to detect the expression of interleukin-10, tumor necrosis factor α (TNF-α), adiponectin (ADPN), adiponectin recepror 2, AdipoR2, p-AKT and NF-κB. RESULTS AND CONCLUSION: Compared with the normal group, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin in the serum, the pathological scores of liver injury, the cell apoptotic rate, and the expression levek of TNF-α and NF-κB were significantly increased in the model group, while the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly reduced in the model group (all P < 0.05). Compared with the model group, the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, the pathological scores of liver injury, and cell apoptotic rate in the experimental group and control group were significantly reduced, and the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly increased (all P < 0.05). To conclude, thymosin α1 has a protective effect on the liver of rats with multiple organ failure induced by zymosan. The mechanism is related to the ADPN/Akt/NF-κB signaling pathway. ADPN/Akt is activated and the activation of NF-κB is inhibited, then reducing the inflammatory response.
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Objective To investigate the effect of thymosin α1 on immunity,metabolism and prognosis in elderly patients with sepsis followed by persistent inflammation,immunosuppression,and catabolism syndrome (PICS).Methods In this retrospective study,68 patients diagnosed with sepsis followed by PICS in medical intensive care unit (MICU) from Jan.2014 to Dec.2016 were involved.Thirty-four patients treated with thymosin α1 for 2 weeks were allotted to the observational group;other 34 patients were to the control group.Patients' clinical information and data of laboratory test were collected in addition.We compared patients' general information,and the indexes before and after treatment,then the indexes between the two groups to analyze the effect of thymosin α 1 on immunity and metabolism;moreover,we conducted survival analysis and compared the mortality of different periods to analyze the effect of thymosin α1 on prognosis.Results The number of monocytes,the levels of CD4/CD8 and HLADR/CD14 before and after treatment in the observational group were significantly higher than those in the control group [(0.11 ± 0.31)× 109/L vs.(-0.16 ± 0.36)× 109/L,(0.20 ± 0.94) vs.(-0.22 ± 0.74) and (5.8 ±16.3)％ vs.(-3.3 ± 18.2)％ respectively],which suggested that the number of monocytes and the levels of CD4/CD8 and HLADR/CD14 were significantly increased by thymosin α1 intervention,and the difference were statistically significant(P ＜ 0.05).Kaplan-meier survival analysis showed prognosis between the two groups was not statistically significant (P ＞ 0.05).The further analysis of mortality in different periods indicated that the mortality within 28 days,90 days and 120 days and overall mortality between the two groups [8 (23.5％) vs.12 (35.3％),18(52.9％) vs.25 (73.5％),20 (58.8％) vs.27 (79.4％) and 24 (70.6％) vs.28 (82.4％) respectively],were not statistically significant(P ＞ 0.05).Conclusions Thymosin α1 can be used to regulate the immunity of elderly patients with sepsis followed by PICS,but its effect on regulating metabolism and improving prognosis needs further study.
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Objective To investigate the effects of thymosin α1 (Tα1) on plasma TNF-α and IL-10 of rats with acute liver failure.Methods The model of acute liver failure in rats was established.The rats in intervention group were injected with Tα1;their plasma ALT, AST and TBIL contents as well as plasma TNF-α and IL-10 levels were assayed at different time points for HE staining of liver sections.Results ① ALT, AST and TBIL in model group and intervention group increased over time.Plasma ALT, AST and TBIL were significantly lower in intervention group than in model group at the same time point (P<0.05).② Manifestations of acute liver failure such as structural disorder of liver tissue, obvious necrosis of liver cells and infiltration of inflammatory cells were observed in model group and intervention group, and worsened over time.At the same time point, liver cell necrosis and infiltration of inflammatory cells were less severe than those in model group.③ TNF-α and IL-10 were significantly higher in model and intervention groups than in control group (P<0.05).Plasma TNF-α and IL-10 showed a rising trend over time in the former groups (P<0.05).At the same time point, TNF-α was significantly lower but IL-10 was significantly higher in intervention group than in model group.Conclusion Thymosin α1 has a protective effect on acute hepatic failure in rats, and it can significantly alleviate liver inflammation and necrosis.The mechanism is related to inhibition of pro-inflammatory cytokine TNF-α and upregulation of anti-inflammatory cytokine IL-10.
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Objective To investigate the application values of thymosin α1 in severe sepsis.Methods Selected 94 patients with severe sepsis in our hospital from September 2014 to October 2016,were randomly divided into observation group(n=45)and control group(n=49),the control group was given routine treatment,the observation group was given thymosin α1 on the basis of conventional treatment,observed two groups before and after treatment T cell subsets and CD14+monocyte human leukocyte antigen(HLA-DR)and so on.Results The observation group the duration of ventilator use and ICU treatment were(12.51±3.82)d and(15.81±3.18)d,significantly shorter than the control group(P< 0.05).There was no significant difference in 28d mortality between the observation group and the control group; After treatment,the CD14+monocytes HLA-DR,CD3+and CD4+T cells in the observation group were significantly improved than before treatment(P<0.05);The HLA-DR,CD3+and CD4+T cells in the observation group after treatment were(36.04± 8.90)％,(58.93±8.74)％and(43.20±9.90)％,significantly higher than those in the control group(P<0.05);The observation group after treatment TNF-α,endotoxin and CRP respectively(56.40±11.78)ng/L,(27.83±9.98)ng/L and(53.20±9.73)g/mL,significantly lower than the control group(P< 0.05).Conclusion Application of thymosin α1 in the treatment of severe sepsis,which can improve the cellular immune function,adjust the state of inflammatory response,shorten the duration of mechanical ventilation and ICU stay.
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Objective To study the effect of thymosin α1 combined with Xuebijing injection on the levels of serum CRP, TNF-α, IL-6 and IL-8 in severe pneumonia complicated with sepsis.Methods 77 severe sepsis patients with sepsis from September 2014 to August 2016 were enrolled in the study.They were divided into observation group (n=39) and control group (n=38) .Patients were given early active anti-infection, nutritional support and liquid resuscitation and other comprehensive treatment, while the control group of patients with intravenous infusion of 50 mL Xuebijing injection, while the observation group with 1.6 mg thymosinα1 subcutaneous injection on the basis of control group.The levels of CRP, TNF-α, IL-6 and IL-8 were compared between the two groups, and the clinical effect was analyzed comprehensively .Results There was no significant difference in the levels of CRP, TNF-α, IL-6 and IL-8 between the two groups before treatment.After treatment, the levels of CRP, TNF-α, IL-6 and IL-8 levels in the treatment group were significantly lower than those in the control group (P<0.05).The total effective rate of the observation group (84.6%) was significantly higher than that of the control group ( 57.9%) , the difference was statistically significant ( P<0.05 ) .Conclusion Thymosin α1 combined with Xuebijing injection in treatment of severe pneumonia with sepsis is effective, can decrease the CRP, TNF-α, IL-6 and IL-8 levels of patient.
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Objective:To explore the influence of ulinastatin combined with thymosinα1 on the immune function of patients with a-cute brain injury. Methods:Sixty-eight cases of patients with acute brain injury were divided into the control group and the observation group randomly with thirty-four ones in each. The control group was given the routine treatment, and the observation group was given ulinastatin combined with thymosinα1 additionally. After the 1-day, 3-day, 7-day and 14-day treatment, transforming growth factor-β1 (TGF-β1), interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and the other serum inflammatory cyto-kine levels, and CD4 +, CD8 +, CD4 + /CD8 +, HLA-DR and cellular immune index levels were detected in the two groups. The prog-nosis effects were evaluated by the prognostic classification of brain injury, and the adverse reactions were analyzed in the two groups as well. Results:After the 1-day treatment, there were no significant differences in the serum inflammatory cytokines and immune param-eters between the groups (P>0. 05). After the 3-day, 7-day and 14-day treatment, serum TGF-β1, IL-6, IL-10 and TNF- α levels were higher than those on the first day after the treatment, and TGF-β1 showed an increasing trend with time extension, while IL-6, IL-10, TNF-α and CD4 + and CD4 + /CD8 +rose first and then decreased. After the 3-day, 7-day and 14-day treatment, serum IL-10 and CD4 +levels in the observation group were significantly higher than those in the control group, and IL-6 and TNF-αlevels were signifi-cantly lower than those in the control group (P<0. 05). After the 3-day and 14-day treatment, CD4 + and CD8 + levels in the observa-tion were significantly higher than those in the control group, and after the 7-day and 14-day treatment, HLA-DR levels were signifi-cantly higher than those in the control group (P<0. 05). The prognosis effect of the observation group was better than that of the con-trol group with statistically significant difference (P<0. 05). Conclusion:Ulinastatin combined with thymosin α1 is used to treat the patients with acute brain injury with better cellular immune function improvement and prognosis effect, which is worthy of clinical popu-larization and application.
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OBJECTIVE:To establish a method for content determination of thymosin α1 in Thymopolypeptides enteric-coated tablets.METHODS:HPLC-MS/MS method was adopted.The determination was performed on Luna C18(2) with mobile phase consisted of 0.1％ formic acid-acetonitrile (gradient elution) at the flow rate of 0.7 mL/min.The column temperature was set at 30 ℃,and sample size was 20 μL.ESI was used with ion spray voltage of 4.5 kV,sheath gas flow rate of 60 arb,aux gas flow rate of 30 arb,sweep gas flow rate of 10 arb and capillary temperature at 320 ℃.The working mode was positive ion monitoring mode.RESULTS:The linear range for thymosin α1 was 1-1 000 ng/mL (r=0.999 9).The limit of quantitation was 1 ng/mL.The limit of detection was 0.1 ng/mL.RSDs of precision,stability and reproducibility tests were all lower than 2.0％.The recoveries were 95.0％-98.0％ (RSD=1.2％,n=6),respectively.CONCLUSIONS:The method is simple,rapid,sensitive and accurate,and can be suitable for simultaneous determination of thymosin α1 in Thymopolypeptides enteric-coated tablets.
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Objective To evaluate the clinical efficacy and prognosis of cefoperazone/sulbactam combined with thymosin α1 in the treatment of severe pneumonia caused by Acinetobacter baumannii (A.baumannii).Methods 84 patients with severe pneumonia caused by A.baumannii were randomly selected,they were divided into treatment group(n =42,cefoperazone/sulbactam combined with thymosin α1 treatment) and control group(n =42,only cefoperazone/ sulbactam treatment).Procalcitonin(PCT),C-reactive protein(CRP),white blood cell(WBC) count,peripheral blood T lymphocyte subsets,interleukin-6(IL-6),interleukin-10(IL-10),immunoglobulin G (IgG),and APACHE II score of two groups before treatment and 7 days after treatment were compared,ventilator weaning success rate,length of ICU stay,and 28-day mortality were also observed.Results After 7 day treatment,compared with the control group,CD4 + T cells,CD4 +/CD8 +,IL-10,and IgG in the treatment group were all significantly higher (all P＜0.05);PCT,CRP,WBC,IL-6,and APACHE II score all significantly declined,difference were all significant(all P＜0.05).Ventilator weaning success rate in treatment group was higher than control group (64.29％ vs 38.10％),mean length of ICU stay was shorter than control group([12.41-± 2.25]d vs[18.23 ±-2.50]d),28-day mortality was lower than control group(19.05％ vs 45.24％),difference were all significant(all P＜0.05).Conclusion Cefoperazone/sulbactam combined with thymosin α1 for the treatment of severe pneumonia caused by A.baumannii can improve the immune function of patients,reduce inflammation,increase ventilator weaning success rate,shorten ICU stay,and decrease 28 day mortality.
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Objective: To compare the therapeutic effect of thymosin α1 combining anti-coagulation medication and simple anti-coagulation mediation in treating the patients with deep venous thrombosis (DVT) formation. Methods: A total of 92 patients with lower extremity vascular ultrasound conifrmed diagnosis of DVT were studied. The patients were randomly divided into 2 groups for treatment: Combination group, the patients received thymosin α1 combining anti-coagulation medication,n=45 and Simple group, the patients received only anti-coagulation medication,n=47. The changes of their deep venous thrombosis condition after treatment were compared between 2 groups. Results: By 4 weeks treatment, the proportion of completely dissolved thrombus in Combination group and in Simple group were 67 branches (49.26%) and 54 branches (37.24%); the thrombus progression and recurrence condition were 6 branches (4.41%) and 16 branches (11.03%), allP<0.05. Conclusion: Thymosin α1 combining anti-coagulation medication has the better effect than simple anti-coagulation medication for treating DVT patients.
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Objective To explore the influence of triple anti-tumor therapy which bases on sirolimus combined huaier granule and thymosin α-1 on T lymphocyte of rat model with liver cancer recurrence after transplantation.Methods Seventy-two Sprague-Dawley(SD)rats were randomly divided into triple therapy group,sirolimus group,huaier-granule group,thymosin α-1 group,positive-control group and blank group (n=1 2 in each group).Except the blank group,rats in all the other groups were established the simulation animal model of liver cancer recurrence after liver transplantation by chemical-induced method.After the model was established,rats in the positive control group were executed to appraise whether the model was successful.The proportion of regulatory T cells (Treg)of CD4 + T lymphocytes in peripheral blood (Treg%),the percentage of CD4 + T lymphocyte of total lymphocyte(CD4 +T%)and the percentage of CD8 + T lymphocyte of total lymphocyte (CD8 +T%),were detected by the flow cytometry respectively.The relationship between Treg% and CD4 + T %,CD8 + T %,the ratio of CD4 +/CD8 + T lymphocytes(CD4 +/CD8 +)was analyzed by the method of Spearman rank correlation.Results Pathological section of rat liver tissue suggested that the rat model was established successfully.Treg % of positive control group was higher than that of blank group,the difference had statistical significance(P <0.05).Treg% of triple therapy group was significantly lower than that of the positive control group,huaier-granule group,thymosin α-1 group,and significantly higher than the blank group (all in P <0.05 ).Compared with positive-control group,CD4 +T% and CD8 +T% of triple therapy group,sirolimus group and thymosin α-1 group were significantly higher (all in P <0.05).CD4 +T%and CD8 +T% of triple therapy group were significantly higher than those of thymosin α-1 group,sirolimus group and huaier-granule group(all in P <0.05).The relationship between Treg% and CD4 +T%,CD8 +T%, CD4 +/CD8 + in peripheral blood were negatively correlated for rats in each group.In addition,the triple anti-tumor therapy decreased the negative correlation between Treg% and CD4 +/CD8 +.Conclusions Sirolimus based triple anti-tumor therapy can decrease the peripheral blood Treg level of the liver cancer rat,increase the number of T lymphocyte and CD4 +/CD8 +,and play the role of anti tumor cell growth and proliferation.
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Objective To investigate the percentage of CD4 + C125 +Tregs in peripheral blood of patients with sepsis and its effect on cell immunity so as to unravel the effect of immunomodulatory therapy on it. Method Fourty patients with sepsis in ICU were randomly (random number) divided into experimental group and control group . The patients of experimental group were treated with Ulinastatin and immunoregulation agent (Thymosin αl) as well. The blood specimens were collected just before treatment, 3 days and 8 days after treatment. The percentages of CD4 + CD25 + Tregs and lymphocyte subsets were detected by using FCM (flow cytometry), and TNF-α, IL-6 and IL-10 assayed by using ELISA, and APACHE Ⅱ scores were calculated. Results Before treatment, the percentage of CD4 + CD25 + Tregs increased, and the number of lymphocytes and the percentage of T lymphocytes decreased, especially the CD4 + T lymphocytes and CD4+/CD8+ decreased more markedly, and the levels of IL-6 and TNF-α increased. After treatment,the percentage of CD4+ CD25 + Tregs was decreased, the number of lymphocytes and CD4 +/CD8 + increased, and the levels of APACHE Ⅱ score, IL-6 and TNF-α decreased especially in the experimental group decreased more significantly (P ＜ 0. 05). Conclusions The percentage of CD4 + CD25+ Tregs in peripheral blood can reflect the immune status of patients with sepsis and become a novel indicator to estimate the progress of sepsis, and the immunity and prognosis of patients. Treating the patients with Thymosin αl and Ulinastatin can raise their immunity, decrease the levels of IL-6, TNF-α and APACHE Ⅱ score and improve their prognosis.
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Objective To explore the effect of thymosin and MVP chemotherapy on the life quality of non-small cell lung cancer(NSCLC) patients. Methods 50 cases of NSCLC patients who received MVP(MMC, VDS, DDP) chemotherapy,were randomly divided into experimental group (using thymosin α1) and control group;before chemotherapy and at the end of chemotherapy (the first 2 weeks), the quality of life was evaluated and analyzed comparatively by the FACT-L questionnaire of patients with lung cancer-Chinese version (V4.0). Results The re-sults of the experimental group score increased by (3.13±2.29),and control group score increased by(-1.07± 2.19) with significant differences (P<0.01). Conclusions Thymosin α1 can improve the short-term quality of life of the non-small cell lung cancer patients who received MVP chemotherapy.