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.

The prognostic value of thymosin β4 expression and preoperative systemic immune-inflammatory index/serum albumin level in early operable non-small cell lung cancer / 中国医师杂志

Objective:To investigate the prognostic value of thymosin β4 (TMSB4X) expression and preoperative systemic immune-inflammatory index/serum albumin (SII/ALB) level in patients with early operable non-small cell lung cancer (NSCLC).Methods:A total of 128 patients with early NSCLC admitted to Zibo Central Hospital from January 2016 to January 2021 were selected. TMSB4X and SII/ALB were detected before surgery, and they were divided into TMSB4X positive group (52 cases) and TMSB4X negative group (76 cases) according to TMSB4X expression. According to the median SII/ALB value, the patients were divided into high SII/ALB group (64 cases) and low SII/ALB group (64 cases). The relationship between TMSB4X, SII/ALB and clinical characteristics in patients with early operable NSCLC was analyzed. The survival curve was drawn by Kaplan-Meier method and the difference of progression free survival (PFS) between TMSB4X positive group and negative group, high SII/ALB group and low SII/ALB group was tested by log-rank. The influencing factors of PFS was analyzed by Cox univariate and multivariate regression.Results:There were difference in lesion site, carcinoembryonic antigen (CEA) and lymphocyte count (LY) between TMSB4X positive group and TMSB4X negative group (all P<0.05). There were significant difference in age, American Joint Committee on Cancer (AJCC) stage, ALB, cytokeratin 19 fragment (CYFRA21-1), CEA, LY, platelet count (PLT) between the high SII/ALB group and the low SII/ALB group (all P<0.05). The median PFS of TMSB4X positive group (17.11 months) was lower than that of TMSB4X negative group (26.64 months) (log rank P<0.001); The median PFS (15.82 months) in the high SII/ALB group was lower than that in the low SII/ALB group (28.24 months) (log rank P<0.0001); Cox univariate analysis showed that lesion location, AJCC stage, ALB, CYFRA21-1, CEA, LY, PLT, TMSB4X, and SII/ALB were all factors influencing PFS in early operable NSCLC patients (all P<0.05); Multivariate analysis showed that AJCC stage, LY, TMSB4X, SII/ALB were independent factors influencing PFS in early operable NSCLC patients (all P<0.05). Conclusions:The expression of TMSB4X and the preoperative level of SII/ALB can be used as prognostic indicators for patients with early operable NSCLC.

Thymosin alpha1 protects against liver injury in rats with zymosan-induced multiple organ failure / 中国组织工程研究

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.

The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy / 中华创伤杂志(英文版)

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.

Effect of thymosinβ10 on tumorigenesis and development and its mechanism / 肿瘤研究与临床

As a member of the β-thymosin family, thymosin β 10 (Tβ10) is mainly involved in the isolation of intracellular actin. Studies have shown that the expression change of Tβ10 is closely correlated with breast cancer, esophageal cancer, liver cancer, cholangiocarcinoma, ovarian cancer and other malignant tumors. Tβ10 is expressed in different states according to the type of cancers, and the mechanism is unclear. The recent research of Tβ10 in chemotherapy and serum findings play a significant role in predicting the efficacy of chemotherapy in cancer patients.

Effect of thymosin α1 on sepsis in rats / 中华麻醉学杂志

Objective To evaluate the effect of thymosin α1 (Tα1) on sepsis in rats.Methods A total of 120 pathogen-free healthy male Sprague-Dawley rats,weighing 250-300 g,aged 7 weeks,were divided into 3 groups using a random number table method:sham operation group (group S,n =24),sepsis group (group CLP,n=48) and Tα1 group (group T,n=48).Sepsis was induced by modified cecal ligation and puncture in anesthetized rats,and vena cava cannula was placed through the right jugular vein to connect the micropump infusion device.In group S,the cecum was only turned without ligation and perforation,and total venous nutrient solution 60 ml was intravenously infused daily for 3 days.After successful establishment of the model,total venous nutrient solution 60 ml was intravenously infused daily for 3 days in group CLP.After successful establishment of the model in group T,Tα1 0.18 mg/kg was subcutaneously injected daily at a fixed time,and total venous nutrient solution 60 ml was intravenously infused daily for 3 days.Twenty-four rats in group CLP and group T were selected,and the survival rate were observed within 3 days after establishing the model.At 12,24,36 and 72 h after establishing the model,6 rats were selected from each group,and blood samples were collected from the jugular vein for determination of the levels of regulatory T cells (Tregs) and T helper cell 17 (Th17) (using flow cytometry) and serum interleukin-10 (IL-10),IL-17 and tumor necrosis factor-alpha (TNF-α) concentrations (by enzymelinked immunosorbent assay),and the IL-10/TNF-cα ratio was calculated.Results Compared with group S,the level of Tregs in peripheral blood was significantly decreased at 24 h after establishing the model and was increased at 36 and 72 h after establishing the model,and the level of Th17 in peripheral blood and serum IL-10,IL-17 and TNF-α concentrations were increased at each time point after establishing the model,and the IL-10/TNF-α ratio was increased at 36 and 72 h after establishing the model in group CLP,and the levels of Tregs and Th17 in peripheral blood were significantly increased at 72 h after establishing the model,the concentrations of serum IL-10 and IL-17 were increased at each time point after establishing the model,serum TNF-α concentrations were increased at 12 and 24 h after establishing the model,and the IL-10/TNF-α ratio was increased at 36 and 72 h after establishing the model in group T (P＜0.05).Compared with group CLP,the levels of Tregs and Th17 in peripheral blood were significantly decreased,the serum IL-10 and IL-17 concentrations and IL-10/TNF-α ratio were decreased at 36 and 72 h after establishing the model,serum TNF-α concentrations were decreased at 72 h after establishing the model,and the survival rate was increased within 3 days after establishing the model in group T (P＜0.05).Conclusion Tα1 can reduce sepsis through improving the cellular immune function in rats.

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.

Effect of thymosin β 10 on tumorigenesis and development and its mechanism / 肿瘤研究与临床

As a member of the β-thymosin family, thymosin β 10 (Tβ10) is mainly involved in the isolation of intracellular actin. Studies have shown that the expression change of Tβ10 is closely correlated with breast cancer, esophageal cancer, liver cancer, cholangiocarcinoma, ovarian cancer and other malignant tumors. Tβ10 is expressed in different states according to the type of cancers, and the mechanism is unclear. The recent research of Tβ10 in chemotherapy and serum findings play a significant role in predicting the efficacy of chemotherapy in cancer patients.

Protective effect of thymosin ß4 on oxygen-glucose deprivation/reoxygenation injury in rat cortical neurons / 中国脑血管病杂志

Objective To investigate the protective effect and mechanisms of thymosin beta 4 (Tß4) on oxygen-glucose deprivation/reoxygenation (O G D / R) injury in rat cortical neurons. Methods Primary cultured cortical neurons were isolated and identified; Ischemia-reperfusion injury model of rat cortical neurons was established (oxygen glucose deprivation 6 h, reoxygenation 12 h) by OGD / R. The rats were divided into the control group,the model group and the treatment group (addition of thymosinß4 2 h before modeling); The cell counting Kit-8 (CCK8) was used to determine the optimal concentration of Tß4. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to detect apoptosis. Western blotting was used to detect the expression of 78 000 glucose-regulated protein 78 (GRP 78), CCAAT/enhancer binding protein-homologous protein (CHOP), B-cell lymphoma-2 (Bel-2) and Bax. Expression levels were compared among groups. One-way analysis of variance was used to compare the normally distributed measurement data among three groups with the SPSS19. 0 software. Results Cortical neurons were separated correctly. The optimal concentration of Tß4 was 10 (ig/L. Comparing the model group with the control group, the survival rate of cortical neurons decreased significantly (P = 0. 002), the apoptotic rate increased significantly (P < 0. 01), the expression of GRP78,CHOP and Bax was up-regulated significantly (P values were 0. 034,0 and 0. 045 .respectively),and the expression of Bcl-2 was reduced significantly (P = 0. 006). Comparing the treatment group(10 p.g/L exogenous Tß4) with the model group, cell viability increased significantly (P = 0. 008), the apoptotic rate decreased significantly (P = 0. 002),the expression of GRP78,CHOP and Bax decreased significantly (P values were 0. 032,0. 027 and 0. 019, respectively),and the expression of Bcl-2 increased significantly (P = 0.028) .The differences were statistically significant. Conclusions Tß4 inhibits OGD/R-induced endoplasmic reticulum stress-dependent apoptosis. These results provide a theoretical basis for the application of Tß4 in the treatment of cerebral ischemia-reperfusion injury.

Protective effect of thymosin β4 in ocular surface diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Thymosin is a kind of protein that is widely distributed in many tissues. It has many biological activities. Thymosin is divided into three subtypes: thymosin α, thymosin β and thymosin γ. Thymosin β4(Tβ4)is the most widely distributed in normal human body. A large number of studies have confirmed that Tβ4 has the functions of anti-inflammatory, anti-apoptosis and promoting proliferation. Ocular surface diseases are mostly related to ocular surface injury and inflammation. Therefore, promoting wound repair and healing and anti-inflammatory are the key to the treatment of ocular surface diseases. The present review mainly introduces the distribution, structure, synthesis of Tβ4 and its protective effect on ocular surface.

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 thymosin α1 on immunity, metabolism and prognosis in elderly patients with sepsis followed by persistent inflammation, immunosuppression, and catabolism syndrome / 实用医学杂志

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.

Role of thymosin β4 in treatment of non-alcoholic fatty liver disease in mice and its mechanism / 中华消化杂志

Objective To explore the role and mechanism of thymosin β4 (Tβ4) in the treatment of non-alcoholic fatty liver disease (NAFLD).Methods Forty male C57BL/J6 mice were divided into normal group,NAFLD group,low dose Tβ4 group and high dose Tβ4 group with 10 mice in each group.NAFLD mice model was established by feeding with high fat and high sugar diet for 16 weeks.The mice in low-dose Tβ4 group and high dose Tβ4 group were intraperitonealy injected with Tβ4 at 0.05 mg · kg-1 · d-1 and 0.20 mg · kg-1 · d-1,respectively,for eight weeks.The liver function indexes and serum tumor necrosis factor-α (TNF-α) level were detected;the pathological changes of liver tissue were observed under optical microscope and non-alcoholic fatty liver disease activity score (NAS) was evaluated.The protein expression levels of nuclear factor-κB p65 (NF-κB p65) and nuclear factor κB inhibit protein a (IκBa) at the protein level in liver tissue were measured by Western blotting method.The expression of TNF-α in liver tissue was detected by immunohistochemistry.Mean integral absorbance (MIA) was calculated.T test was performed for groups comparison.Results The levels of alanine aminotransferase (ALT),γ-glutamine transferase (GGT) and serum TNF-α levels of high dose Tβ4 group were all lower than those of NAFLD group ((28±17) U/L vs.(76±29) U/L,(61±39) U/L vs.(102±56) U/L,(144.1± 48.2) ng/L vs.(187.3±58.8) ng/L,respectively),and the differences were statistically significant (t=4.52,2.78 and 2.30,all P＜0.05).The NAS of low dose Tβ4 group and high dose Tβ4 group were both lower than that of NAFLD group (3.7±40.4,2.3±0.3 vs.4.6±0.3),and the differences were statistically significant (t=5.69 and 17.14,both P＜0.01).The relative expression level of Tβ4 protein of NAFLD group was lower than that of normal group (0.2±0.1 vs.1.4±0.6),and the difference was statistically significant (t=6.24,P＜0.01).The relative expression levels of Tβ4 and IκBa of high dose Tβ4 group were higher than those of NAFLD group (1.0±0.3,0.5±0.3 vs.0.2±0.1),and the differences were statistically significant (t=8.00 and 3.00,both P＜0.01).The relative expression level of NF-κB p65 in liver tissue of high dose Tβ4 group was lower than that of NAFLD group (0.6±0.3 vs.1.5±0.7),and the difference was statistically significant (t=3.74,P＜0.01).The MIA of high dose Tβ4 group was lower than that of NAFLD group (0.4±0.2 vs.0.7±0.3),and the difference was statistically significant (t=2.63,P＜ 0.01).Conclusion Tβ4 can effectively treat NAFLD probably through inhibiting the NF-κB pathway.

Changes of levels of endogenous AcSDKP and its regulatory factors in liver tissue of model rats with liver fibrosis induced by bile duct ligation / 吉林大学学报(医学版)

Objective: To explore the changes of levels of endogenous N acetyl seryl aspartyl lysylproline (AcSDKP) and its regulatory factors in liver tissue of rats with liver fibrosis induced by bile duct ligation, and to elucidate the effect of endogenous AcSDKP in the pathologic process of liver fibrosis. Methods: Forty-five healthy male rats were randomly divided into model group (the liver fibrosis rat models were set up by bile duct ligation), blocking group (the liver fibrosis rat models were treated with angiotensin-converting enzyme inhibitor before) and control group (the rats received laparotomy but not bile duct ligation); each group had 15 rats. The serum and liver tissue of the rats in various groups were gained at the 1st week, 2nd week and 4th week. The differences in the indexes of liver function, the liver fibrosis degrees, and the AcSDKP levels in liver tissue of the rats in various groups were analyzed. The levels of thymosin beta 4 (Tβ4), prolyl oligopeptidase (POP) and angiotensin converting enzyme (ACE) in liver tissue of the rats in various groups were detected by Western blotting. Results: The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) of the rats in model group were higher than those in other two groups from the 1st week (P0. 05). The ALB and the AcSDKP level in liver tissue of the rats in model group were lower than those in other two groups from the 2nd week (P0. 05). The levels procollagen type IE (PCIE), collagen type IV (CKO and hyaluronic acid (HA) in three groups had no differences at the 1st week (P>0. 05). The levels of PCIII, CIV, and HA of the rats in model group were higher than those in other two groups from the 2nd week (P 0. 05). The levels of Tβ4 and ACE in liver tissue of the rats in model group were higher than those in other two groups from the 2nd week (P 0. 05). The liver tissue of the rats in model group was basically normal at the 1st week, showed the focal necrosis at the 2nd week, and showed the flake necrosis at the 4th week. The liver tissue of the rats in blocking group and control group were basically normal at all time points. Conclusion: The endogenous AcSDKP level in the liver fibrosis rats induced by bile duct ligation is down-regulated through the axis of Tβ4-POP-AcsDKP.

The expression of thymosin beta 10 in gliomas and its clinical significance / 肿瘤

Objective: To analyze the expression and clinical significance of thymosin β10 (TMSB10) in gliomas, and to explore its biological processes involved in the occurrence and development of gliomas. Methods: A total of 339 glioma samples were collected from Beijing Tian Tan Hospital and Beijing Sanbo Brain Hospital from 2004 to 2017. Among them, 309 samples were used for the construction of the Chinese Glioma Genome Altas (CGGA) mRNA sequencing database, and 30 other samples were used for real-time fluorescence quantitative PCR to verify TMSB1 0 mRNA expression. The correlation of TMSB10 mRNA expression in the CGGA database with the clinical data of 309 glioma patients was analyzed, and the TCGA mRNA sequencing data and the REMBRANDT mRNA microarray data were simultaneously used for verification. The expression of TMSB10 in different pathological grades and molecular subtypes of gliomas was analyzed by ANOVA and t test. The relationship of TMSB10 expression and the overall survival of glioma patients was analyzed by Kaplan-Meier method, log-rank test and COX regression model. The relationship between the expression of TMSB10 and the several pathological factors of glioma was analyzed by chi-square test. The biological processes involved in TMSB10 expression were analyzed by Pearson correlation test and DAVID. Results: The expression level of TMSB10 in high-grade gliomas was significantly higher than that in low-grade gliomas (P < 0.000 1). The expression level of TMSB10 was higher in mesenchymal and isocitrate dehydrogenase (IDH) wild-type gliomas (both P < 0.000 1). The overall survival rate of patients with high expression of TMSB10 was significantly lower than that of patients with low expression of TMSB10 (P < 0.000 1). Moreover, TMSB10 was an independent prognostic factor related to overall survival for the patients with glioma (P < 0.05). TMSB1 0 might be associated with the biological process of glioma such as immune response, cell adhesion, angiogenesis, infammatory reaction and apoptosis. Conclusion: TMSB10 is one of potential factors to promote the occurrence and development of glioma, and can be used as a potential indicator to predict the prognosis of glioma patients.

Influence of Ulinastatin Combined with Thymosinα1 on Immune Function of Patients with Acute Brain In-jury / 中国药师

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.

The clinical significance of thymopeptides α1 in the treatment of severe sepsis / 中国生化药物杂志

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 28d 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.

Effect of thymosin α1 combined with Xuebijing injection on serum CRP, TNF-α, IL-6 and IL-8 levels in severe pneumonia complicated with sepsis / 中国生化药物杂志

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.

Expressions and roles of three inflammatory cytokines in chronic hepatitis B patients with nonalcoholic fatty liver disease / 中华传染病杂志

Objective To investigate the roles of cytokeratin 18 (CK18) M30 and M65,thymosin beta 4 (Tβ4) and tumor necrosis factor (TNF)-α in hepatic steatosis and development of inflammatory and fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD).Methods A total of 46 CHB patients with NAFLD and 42 CHB patients were collected.Serum CK-18 M30,M65,Tβ4 and TNF-α levels were measured by enzyme linked immunosorbent assay (ELISA) in two groups.The associations between inflammatory factors levels and biochemical or pathological indicators were analyzed.The statistical analysis was conducted by t test and chi square test of two independent samples.The correlation analysis was performed by Pearson and Logistic regression analysis.Results The mean serum CK 18 M30 level in CHB with NAFLD group was (614.48±471.43) U/L,which was significantly higher than that in CHB group (374.50±231.04) U/L (t=2.988,P＜0.01).The mean levels of CK18 M65,Tβ4 and TNF-α in CHB with NAFLD group were (369.41±262.21) U/L,(0.80±0.32) mg/L and (54.87±20.36) ng/L,respectively,and those in CHB group were (296.50±231.44) U/L,(0.68±0.30) mg/L and (51.88± 20.60) ng/L,respectively.There were no difference between CHB with NAFLD group and CHB group (t=1.378,1.810 and 0.685,respectively,all P＞0.05).In CHB with NAFLD patients,the CK-18 M30 level was positively correlated with alanine aminotransferase,triglyceride,fasting blood glucose,histology inflammation score,fibrosis score and steatosis (r=0.507,0.456,0.384,0.551,0.458 and 0.457,respectively,all P＜0.01).Tβ4 level was negatively correlated with inflammation and fibrosis score (r=0.371 and-0.308,respectively,P＜0.05).TNF-α level was positively correlated with inflammation score and steatosis (r=0.570 and 0.441,respectively,P＜0.01).CK-18 M30,Tβ4 and TNF-α were independent predictors of CHB combined with NAFLD,progressive inflammatory fibrosis and severe steatosis.Conclusions Serum CK-18 M30,Tβ4 and TNF-α levels are associated with hepatic steatosis,development of inflammation and fibrosis in CHB with NAFLD patients.

Significance for Dynamic Changes of Plasma Level Thymosinβ4 in Patients With Acute Myocardial Infarction / 中国循环杂志

Objective: To observe the dynamic changes of plasma level thymosinβ4 (Tβ4) in acute myocardial infarction (AMI) patients with intervening therapy within 15 days of onset and to explore the relationship between Tβ4 and clinical prognosis in AMI patients. Methods: Our research included 2 groups:AMI group, n=69 and Control group, the patients with suspected chest pain while CAG excluded coronary artery stenosis, n=32. Plasma levels of Tβ4 were examined in all AMI patients on admission day and every day until 15 days of onset;AMI patients were followed-up for 18 months and the endpoint was defined as major adverse cardiovascular event (MACE) occurrence. Results: ①Compared with Control group, AMI group had increased plasma level of Tβ4 on admission day and on day-15 of onset, P Conclusion: AMI may induce up-regulated expression of plasma Tβ4;with intervening therapy, Tβ4 showed a trend of“elevation-reduction-elevation-reduction”at the early stage of AMI. High expression of Tβ4 was helpful for improving clinical prognosis in AMI patients which may provide a theoretical basis for exogenous use of Tβ4 in AMI treatment.