Effect of thymalfasin on myeloid-derived suppressor cells in patients with non-small cell lung cancer.

OBJECTIVE: To observe the effect of thymalfasin on myeloid-derived suppressor cells (MDSCs) subsets in peripheral blood of patients with non-small cell lung cancer (NSCLC). METHODS: 50 cases of NSCLC (NSCLC group) diagnosed in Chest Hospital of Jiangxi Province were selected as the research subjects, and 50 healthy subjects who underwent physical examination in our hospital during the same period were selected as the healthy control group. The expression of HLA-DR-CD14-CD33+ MDSCs in peripheral blood mononuclear cells and tumor tissue single cell suspension of NSCLC patients before and after thymalfasin treatment was explored by flow cytometry. RESULTS: The proportion of MDSCs in peripheral blood of NSCLC group was 1.70±0.52%, which was significantly higher than that in peripheral blood (0.51±0.15%) of healthy controls (P < 0.05). The proportion of HLA-DR-CD14-CD33+ MDSCs in the tissues of NSCLC group was 1.65±0.43% before treatment and 1.15±0.50% after treatment (P < 0.05). The proportion of MDSCs in peripheral blood of NSCLC patients before treatment was 1.70±0.52%, and that after treatment was 0.59±0.18% (P < 0.05). CONCLUSION: Thymalfasin can reduce the number of MDSCs in peripheral blood mononuclear cells. The application of thymalfasin in the treatment of NSCLC patients can help to enhance the anti-tumor effect.

Mechanism and clinical application of thymosin in the treatment of lung cancer.

Cancer is one of the leading causes of death worldwide. The burden of cancer on public health is becoming more widely acknowledged. Lung cancer has one of the highest incidence and mortality rates of all cancers. The prevalence of early screening, the emergence of targeted therapy, and the development of immunotherapy have all significantly improved the overall prognosis of lung cancer patients. The current state of affairs, however, is not encouraging, and there are issues like poor treatment outcomes for some patients and extremely poor prognoses for those with advanced lung cancer. Because of their potent immunomodulatory capabilities, thymosin drugs are frequently used in the treatment of tumors. The effectiveness of thymosin drugs in the treatment of lung cancer has been demonstrated in numerous studies, which amply demonstrates the potential and future of thymosin drugs for the treatment of lung cancer. The clinical research on thymosin peptide drugs in lung cancer and the basic research on the mechanism of thymosin drugs in anti-lung cancer are both systematically summarized and analyzed in this paper, along with future research directions.

Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms.

INTRODUCTION: Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital. METHODS: The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%). RESULTS: The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients. CONCLUSION: Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.

The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05). The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.

Reduced numbers of naïve CD4 + T cells and an altered CD4/CD8 balance in depressed common variable immune deficiency (CVID) patients. Is thymosin-α1 a possible treatment?

In the 1990's the macrophage-T-cell-theory of depression was posed stating that low grade inflammation and an abnormal T cell system destabilize the development and function of the emotional brain in such a way, that individuals become ultrasensitive to stress. Recently we gathered evidence that indeed higher frequencies of CD4+ memory T cells, lower frequencies of naive CD4 + T cells, higher frequencies of CD8 + T cells (the latter two in part elicited by Cytomegalovirus, CMV, infection) are a characteristic of Major Depressive Disorder (MDD). In MDD patients with a history of childhood trauma and severe depression monocytes are inflammatory activated. Low grade inflammation and T cell system defects have also been reported in patients with Common Variable Immune Deficiency (CVID) (next to antibody production defects). CVID patients show a higher prevalence of mild depression. The aim of this study was to determine T cell frequencies and monocyte inflammatory activation in CVID patients with and without depression. This study confirms that CVID patients have CMV independent decreases in the frequency of naïve CD4 + T cells and it de novo shows a CMV dependent increase in the expression of inflammatory genes in monocytes. CVID patients with depression are additionally characterized by a CMV independent increase in the frequency of naïve CD8 + T cells, while lacking monocyte inflammatory activation. In conclusion, depressed CVID patients have T cell abnormalities comparable to that of patients with regular MDD. These abnormalities are presently targeted by thymosin α1 in an open-label proof of concept trial.

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report.

PURPOSE: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. PROCEDURES: The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6 mg Ta1 given subcutaneously twice weekly for 8 weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4 months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. RESULTS: To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.

A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.

BACKGROUND: Thymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. METHODS: Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. RESULTS: A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25]) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to Tα1. CONCLUSIONS: Tα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. CLINICAL TRIALS REGISTRATION: NCT04487444.

Identification and determination of structurally related peptide impurities in thymalfasin by liquid chromatography-high-resolution mass spectrometry.

Thymalfasin is an important peptide drug widely used for the single or combination treatment of hepatitis, sepsis, cancer, and immunodeficiency. Accurate purity assessment of thymalfasin material is essential for thymalfasin certified reference materials (CRMs) production and analytical method validation, in which comprehensive determination of thymalfasin-related impurities is required to avoid quantitative bias. In this study, liquid chromatography-high-resolution mass spectrometry (LC-hrMS) methods have been established to comprehensively characterize and quantify thymalfasin-related impurities using a thymalfasin China Pharmacopoeia (ChP) standard and then successfully applied to three commercial thymalfasin materials. A total of twenty-three thymalfasin-related impurities (> 0.1 mg/g) were separated, identified, and quantified in the ChP standard analyzed. The major impurities existing in thymalfasin ChP standard and commercial materials include deamination, amination, succinimide, amino acid insertion/deletion, dimers, and isomers at different mass fraction levels. In particular, over half of the thymalfasin-related impurities were found directly or indirectly arising from the labile C-terminal asparagine (Asn) residue. Given the 28th Asn residue at the C-terminus is not necessary for the biological activity of thymalfasin as reported previously, thus deletion, replacement, or modification of thymalfasin C-terminal Asn residue is proposed for new drug research and development. In summary, these results provide a further complement to the thymalfasin-related impurity profile and issue a warning for protection or processing of the thymalfasin C-terminal Asn residue.

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.

Simultaneous Determination of Nine Trace D-Amino Acids in Thymalfasin by Deuterated Acid Hydrolysis-Precolumn Derivatization-Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry / 中国药学杂志

OBJECTIVE: To develop an ultra-high performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry method for simultaneous determination of nine trace D-amino acids in thymalfasin, combined with deuterated acid hydrolysis and precolumn-derivatization. METHODS: The sample was hydrolyzed by deuterated acid, followed by precolumn-derivatization with Nα-(2, 4-dinitro-5-fluorophenyl)-L-alaninamide (FDAA). The analysis was then performed on an ACCQ-TAGTM ULTRA C18 column (2.1 mm×100 mm, 1.7 μm), with mobile phase comprising water containing 0.1% formic acid-acetonitrile gradiently eluted at a flow rate of 0.3 mL•min-1. Nine D-amino acids in thymalfasin were correctly quantified using standard curves by Xevo G2-S Q-TOF coupled with electrospray ion source in positive ion mode. RESULTS: The standard curves of the nine D-amino acids derivatives had good linearity in the ranges of the tested concentrations (r>0.991 2). The limits of quantitation of all D-amino acids derivatives were as low as 0.05-0.30 pmol. The precision and recoveries met the requirements of Chinese Pharmacopoeia (2015). The contents of D-amino acids in the samples from five companies were determined to be 25.16-1 322.01 μg•g-1. Among them, D-glutamate, D-aspartate, D-lysine and D-serine had higher contents, which were 1 105.45-1 322.01, 614.15-740.50, 358.06-388.76 and 138.78-291.60 μg•g-1, respectively. CONCLUSION: The method is sensitive, efficient and reliable, working well for simultaneous determination of nine trace D-amino acids in thymalfasin, which provides a reference for the comprehensive control of racemic peptide impurities in this synthetic polypeptide drug.

Determination of D-amino acids in thymalfasin by GC-MS based on multi-step derivatization / 药学学报

We utilized a multi-step derivatization gas chromatography-mass spectrometry method for the determination of common amino acid enantiomers, combined with deuterated hydrochloric acid hydrolysis, to identify nine trace D-amino acids in thymalfasin. We optimized the conditions for multi-step derivatization, the volume of reagent for redissolving samples, and the conditions for chromatography and mass spectrometry with isopropanol and trifluoroacetic anhydride as derivatization reagents, and validated the procedure, including sensitivity, linear range, precision, accuracy and recovery. Sixteen pairs of D/L-amino acids and glycine derivatives were separated within 29 min, with the limit of quantification as low as 0.09-2.79 μmol·L-1. Nine amino acid derivatives of thymalfasin showed a good linear relationship within the concentration range examined (r2>0.992 3). The precision results showed that RSD values were less than 10.90%. Accuracy test results of a reference substance ranged from 76.69% to 128.18%. Average recoveries of spiked samples ranged from 70.41% to 125.39%. For the nine D-amino acids assayed, D-Asp and D-Glu content in six batches of thymalfasin were highest, ranging 0.41%-0.49% and 0.25%-0.33%, respectively, with others less than 0.25%. The method is sensitive, efficient and reliable, available for seventeen common amino acids and their enantiomers, and works well with simultaneous determination of nine trace D-amino acids in thymalfasin, providing a reference for the comprehensive control of racemic peptide impurities in this synthetic polypeptide drug.

CD3+, CD4+, and CD8+ Expression in Cells in Peripheral Blood of Silicosis Patients and Intervention Effect of Thymalfasin.

OBJECTIVE: This study aims to investigate the changes in CD3+, CD4+ and CD8+ expression in cells in peripheral blood of silicosis patients, and observe the immunoregulatory effect of thymalfasin. METHODS: A total of 80 silicosis patients were enrolled in the study, randomly divided into two groups: treatment group and control group (n=40, each group). In addition, 40 healthy adults, who underwent physical examinations in our hospital, were enrolled into the health examination group. Patients in the control group and treatment group were given anti-infection treatment, according to their conditions. Patients in the treatment group additionally received thymalfasin. Then, the number of peripheral blood T lymphocyte subsets in subjects in all three groups before and after treatment was measured. RESULTS: (1) Before treatment, CD3+, CD4+ and CD8+ levels in cells were significantly lower in the treatment group and control group than in the health examination group, and the differences were statistically significant (P<0.05). (2) In the treatment group, the number of CD4+ cells in peripheral blood was significantly higher after one week of treatment, when compared to that before treatment, and the difference was statistically significant (P<0.05). CONCLUSION: In silicosis patients, CD3+, CD4+ and CD8+ cells in peripheral blood are decreased, and thymalfasin can significantly increase CD4+ cells in peripheral blood of silicosis patients.

Effect of thymalfasin on the immune function and inflammatory response in patients with severe pneumonia / 中国基层医药

Objective@#To explore the clinical efficacy of thymalfasin on the immune function and inflammatory response in the treatment of patients with severe pneumonia.@*Methods@#From June 2015 to June 2018, 86 patients with severe pneumonia in the Hospital of Zhejiang Provincial General Team of Armed Police were enrolled in the study.According to different treatment methods, they were divided into control group and treatment group, with 43 cases in each group.The control group was treated with cefoperazone/sulbactam sodium on the basis of conventional treatment.The treatment group was treated with thymalfasin on the basis of the treatment of the control group.The expression of monocyte human leukocyte antigen-DR (mHLA-DR), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured before and after treatment.At the same time, CD4+, CD8+, CD4+/CD8+ before and after treatment were examined in the two groups.The efficacy and bacterial clearance rate of the two groups were evaluated.The adverse reactions were recorded.@*Results@#After treatment, the levels of IL-6 and TNF-α in the two groups were significantly lower than those before treatment [treatment group: (44.9±11.8)ng/L, (42.9±13.1)ng/L vs. (86.5±27.9)ng/L, (79.6±28.6)ng/L, control group: (71.5±14.2)ng/L, (65.9±22.6)ng/L vs. (87.1±28.6)ng/L, (78.8±29.1)ng/L, t=9.005, 7.650, 3.203, 2.295, all P<0.05]. The expression level of mHLA-DR in the treatment group after treatment [(44.8±5.7)%] was significantly higher than that before treatment [(27.1±3.4)%, t=17.487, P=0.000]. The changes of the indicators in the treatment group were significantly better than those in the control group (t=9.447, 5.773, 8.725, all P<0.05). After treatment, the CD4+ level of the two groups were higher than those before treatment, and the CD8+ levels of the two groups were significantly lower than those before treatment, the differences were statistically significant(t=3.050, 3.429, 6.965, 13.327, all P<0.05), and the CD4+/CD8+ of the two groups were significantly increased (t=0.370, 3.314, all P<0.05). The indicators of the treatment group were improved more significantly than the control group (t=4.416, 12.355, 3.089, all P<0.05). The bacterial clearance rate of the treatment group was 88.89% (32/36), which was significantly higher than that of the control group [67.65% (23/34), χ2=4.686, P=0.030]. The clinical efficacy of the treatment group was 93.02%(40/43), which was significantly higher than 76.74%(33/43) of the control group (χ2=6.095, P=0.047). The incidence of adverse reactions between the two groups had no statistically significant difference (χ2=0.212, P=0.645).@*Conclusion@#Thymalfasin in the treatment of patients with severe pneumonia can improve the immune function, reduce the inflammatory response, improve the bacterial clearance rate and clinical efficacy, and will not increase the adverse reactions, so it is worthy of promoting.

Effect of accelerated rehabilitation surgery management combined with thymalfasin on rehabilitation quality of patients undergoing laparoscopic radical nephrectomy / 中国基层医药

Objective@#To investigate the effect of enhanced recovery after surgery program with thymalfasin in patients undergoing laparoscopic radical nephrectomy in the perioperative period to enhance the quality of rehabilitation and reduce the risk of surgical complications.@*Methods@#Retrospective analysis of the clinical data of 156 patients undergoing radical laparoscopic radical nephrectomy in the People's Hospital of Renshou County from August 2013 to June 2018 was conducted.According to the perioperative management plan, 74 patients were divided into control group(74cases) and observation group(82cases). Laparoscopic surgery was performed in both two groups.The perioperative period of the observation group was accelerated surgical rehabilitation, and thymalfasin was given before and after surgery.The control group used a traditional perioperative management program.The blood loss, postoperative recovery time and complications were compared between the two groups.@*Results@#The loss of hemoglobin during operation[(11.90±5.61)g/L]in the accelerated rehabilitation group was slightly lower than that of the control group[(17.47±5.31)g/L], and the indwelling time of plasma drainage tube, anal exhaust time and hospitalization time in the accelerated rehabilitation group were (35.96±4.47)h, (12.61±4.05)h, (121.45±4.30)h, respectively, which were significantly shorter than those in the control group[(46.81±4.55)h, (15.34±4.45)h, (193.69±5.48)h], the differences were statistically significant (t=6.351, 15.011, 4.012, 92.043, all P<0.05).@*Conclusion@#Enhanced recovery after surgery program with thymalfasin in patients undergoing laparoscopic radical nephrectomy is a safe and effective treatment.The use of thymalfasin method can accelerate the recovery of patients' immune function, and the accelerated rehabilitation program with thymalfasin can effectively reduce the probability of infection during surgery, which can effectively reduce the possibility of infection during operation, accelerate the recovery of physiological function, shorten the hospital stay of patients and improve the quality of rehabilitation of patients.

Effect of accelerated rehabilitation surgery management combined with thymalfasin on rehabilitation quality of patients undergoing laparoscopic radical nephrectomy / 中国基层医药

Objective To investigate the effect of enhanced recovery after surgery program with thymalfasin in patients undergoing laparoscopic radical nephrectomy in the perioperative period to enhance the quality of rehabilitation and reduce the risk of surgical complications.Methods Retrospective analysis of the clinical data of 156 patients undergoing radical laparoscopic radical nephrectomy in the People＇s Hospital of Renshou County from August 2013 to June 2018 was conducted.According to the perioperative management plan ,74 patients were divided into control group (74cases) and observation group(82cases).Laparoscopic surgery was performed in both two groups.The perioperative period of the observation group was accelerated surgical rehabilitation ,and thymalfasin was given before and after surgery.The control group used a traditional perioperative management program.The blood loss,postoperative recovery time and complications were compared between the two groups.Results The loss of hemoglobin during operation [(11.90 ±5.61)g／L]in the accelerated rehabilitation group was slightly lower than that of the control group [(17.47 ± 5.31) g／L], and the indwelling time of plasma drainage tube , anal exhaust time and hospitalization time in the accelerated rehabilitation group were (35.96 ±4.47) h,(12.61 ±4.05) h,(121.45 ±4.30) h,respectively,which were significantly shorter than those in the control group [(46.81 ±4.55)h,(15.34 ±4.45)h,(193.69 ±5.48)h], the differences were statistically significant ( t ＝6.351, 15.011, 4.012, 92.043, all P ＜0.05 ).Conclusion Enhanced recovery after surgery program with thymalfasin in patients undergoing laparoscopic radical nephrectomy is a safe and effective treatment.The use of thymalfasin method can accelerate the recovery of patients ＇immune function, and the accelerated rehabilitation program with thymalfasin can effectively reduce the probability of infection during surgery,which can effectively reduce the possibility of infection during operation ,accelerate the recovery of physiological function,shorten the hospital stay of patients and improve the quality of rehabilitation of patients .

Effect of thymalfasin on the immune function and inflammatory response in patients with severe pneumonia / 中国基层医药

Objective To explore the clinical efficacy of thymalfasin on the immune function and inflammatory response in the treatment of patients with severe pneumonia.Methods From June 2015 to June 2018,86 patients with severe pneumonia in the Hospital of Zhejiang Provincial General Team of Armed Police were enrolled in the study.According to different treatment methods,they were divided into control group and treatment group,with 43 cases in each group.The control group was treated with cefoperazone/sulbactam sodium on the basis of conventional treatment.The treatment group was treated with thymalfasin on the basis of the treatment of the control group.The expression of monocyte human leukocyte antigen-DR (mHLA-DR),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured before and after treatment.At the same time,CD4+,CD8+,CD4+ /CD8 + before and after treatment were examined in the two groups.The efficacy and bacterial clearance rate of the two groups were evaluated.The adverse reactions were recorded.Results After treatment,the levels of IL-6 and TNF-α in the two groups were significantly lower than those before treatment [treatment group:(44.9 ± 11.8)ng/L,(42.9 ± 13.1) ng/L vs.(86.5 ± 27.9) ng/L,(79.6 ± 28.6) ng/L,control group:(71.5 ± 14.2)ng/L,(65.9 ±22.6)ng/L vs.(87.1 ±28.6)ng/L,(78.8 ±29.1)ng/L,t =9.005,7.650,3.203,2.295,all P ＜ 0.05].The expression level of mHLA-DR in the treatment group after treatment [(44.8 ± 5.7) ％] was significantly higher than that before treatment [(27.1 ± 3.4) ％,t =17.487,P =0.000].The changes of the indicators in the treatment group were significantly better than those in the control group (t =9.447,5.773,8.725,all P ＜ 0.05).After treatment,the CD4+ level of the two groups were higher than those before treatment,and the CD8+ levels of the two groups were significantly lower than those before treatment,the differences were statistically significant(t =3.050,3.429,6.965,13.327,all P ＜ 0.05),and the CD4 +/CD8 + of the two groups were significantly increased (t =0.370,3.314,all P ＜0.05).The indicators of the treatment group were improved more significantly than the control group (t =4.416,12.355,3.089,all P ＜ 0.05).The bacterial clearance rate of the treatment group was 88.89％ (32/36),which was significantly higher than that of the control group [67.65％ (23/34),x2 =4.686,P =0.030].The clinical efficacy of the treatment group was 93.02％ (40/43),which was significantly higher than 76.74％ (33/43) of the control group (x2 =6.095,P =0.047).The incidence of adverse reactions between the two groups had no statistically significant difference (x2 =0.212,P =0.645).Conclusion Thymalfasin in the treatment of patients with severe pneumonia can improve the immune function,reduce the inflammatory response,improve the bacterial clearance rate and clinical efficacy,and will not increase the adverse reactions,so it is worthy of promoting.

Radiofrequency ablation combined with non-specific sequential immunotherapy for early hepatocellular carcinoma: a prospective study / 中华消化外科杂志

Objective To investigate the clinical effect of radiofrequency ablation (RFA) combined with non-specific sequential immunotherapy (IM) for early hepatocellular carcinoma (HCC),and analyze the factors affecting prognosis of patients after RFA.Methods The prosepctive study was conducted.The clinicopathological data of 72 early HCC patients who were admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from January 2009 to October 2015 were collected.Patients were divided into 3 groups by random number table:patients in group A underwent single RFA therapy;patients in group B underwent RFA + non-specific sequential IM (1-3 times);patients in group C underwent RFA + non-specific sequential IM (≥ 4 times).RFA was performed by the same doctors team,and non-specific sequential IM planning included thymalfasin + interleukin-2 (IL-2).Observation indicators:(1) treatment situations;(2) follow-up and survival;(3) analysis of prognostic factors after RFA.Follow-up using outpatient examination was performed to detect tumor recurrence and overall survival up to December 2015.Measurement data with normal distribution were represented as (x) ± s,and comparison among groups were evaluated with the ANOVA.Comparison of count data were analyzed using the chi-square test.The curve,rate and time of tumor recurrence after treatment,overall survival curve and time were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.The univariate analysis and multivariate analysis were respectively done using the COX proportional hazard regression model.Results Seventy-two patients were screened for eligibility,including 31 in group A,22 in group B and 19 in group C.(1) Treatment situations:patients in 3 groups underwent RFA,and contrast enhanced ultrasound showed complete tumors ablation at 5 days postoperatively.Patients in group B and C didn't have significant adverse reactions after RFA during IM therapy.(2) Follow-up and survival:72 patients were followed up for 2-66 months after treatment,with a median time of 34 months.The 1-year tumor recurrence rates after treatment in group A,B and C were respectively 19.4％,13.6％ and 10.5％,with no statistically significant difference (x2=0.714,P＞0.05).The median tumor recurrence times in group A,B and C were respectively 24.0 months,30.0 months and 33.0 months,with no statistically significant difference (x2 =3.283,P＞0.05).The median overall survival times in group A,B and C were respectively 46.0 months,56.0 months and 57.0 months,with a statistically significant difference (x2=7.079,P＜0.05).There were statistically significant differences between group A and group B and C (x2 =4.566,4.243,P＜0.05),and no statistically significant difference between group B and group C (x2 =0.078,P＞0.05).(3) Analysis of prognostic factors after RFA:results of univariate analysis showed that initial tumor,tumor number,Barcelona clinic liver cancer (BCLC)staging and sequential IM after RFA were related factors affecting prognosis of early HCC patients [hazard ratio (HR)=2.636,2.530,0.145,0.582,95％ confidence interval (CI):1.218-5.703,1.110-5.767,0.041-0.517,0.321-0.867,P＜0.05].Results of multivariate analysis showed that tumor number ＞ 1,staging B of BCLC and without sequential IM after RFA were independent risk factors affecting prognosis of early HCC patients (HR=2.376,2.683,0.567,95％CI:1.080-5.229,1.530-21.112,0.335-0.962,P＜0.05).Conclusions The non-specific sequential IM of thymalfasin + IL-2 can prolong survival time of early HCC patients after RFA.Tumor number ＞ 1,staging B of BCLC and without sequential IM after RFA are independent risk factors affecting prognosis of early HCC patients.

Application of thymalfasin in non-operative treatment of cervical cancer / 中国基层医药

Objective To observe the effect of thymalfasin on non-operative treatment of cervical cancer.Methods Seventy-eight patients with advanced cervical cancer were divided into two groups according to the digital table,each group in 39 cases.The two groups were treated with concurrent chemoradiotherapy.The observation group was given 1.6 mg of thymalfasin subcutaneously each Monday to Friday.While the control group received no additional treatment.And then the two groups were compared in terms of curative effects,adverse reactions,immune states and cellular immune functions.Results The results showed that the differences of curative effects[there were 23 patients in the control group,as compared with 31 patients in the observation group,achieved a complete response(CR),x2=3.852,P<0.05],adverse reactions(grade Ⅲ or Ⅳ radiation-induced enteritis occurred in 4 patients in the observation group,and 12 patients in the control group,x2=5.032,P<0.05;Grade Ⅲ or Ⅳ leukopenia occurred in 16 patients in the observation group,and 25 patients in the control group,x2=4.165,P<0.05;Grade Ⅲ or Ⅳ nausea,vomit occurred in 6 patients in the observation group,and 14 patients in the control group,x2=4.303,P<0.05),immune states and cellular immune functions between the two groups were significant[the counts of CD+3(t=9.236,P<0.05),CD+4(t=7.445,P<0.05),CD+4/CD+8(t=7.445,P<0.05) and NK(t=9.256,P<0.05)]were significantly higher in the observation group after treatment.Conclusion In the treatment of advanced cervical cancer,concurrent chemoradiotherapy combined with thymalfasin can improve the curative effect,reduce the side effects,improve the quality of life and enhance the immunity.

A clinical study of traditional Chinese medicine of fumigation and washing combined with thymalfasin and isotretinoin treatment for verruca plantaris / 国际中医中药杂志

Objective To evaluate the clinical effect of the homemade traditional Chinese medicine bathing prescription combined with Thymalfasin and Isotretinoin treatment for Verruca Plantaris.Methods A total of 120 patients with Verruca Plantaris were randomly divided into 3 groups according to the random number table method (each group 40). The drug therapy group was given Thymalfasin and Isotretinoin to treatment; and the Chinese medicine washing group was given traditional Chinese medicine wash-out on the basis of drug therapy; and the physical therapy group was given liquid nitrogen freezing treatment on the basis of drug therapy. All the groups were treated 12 weeks and follow-up 3 months. Four weeks were a course, and a total of 3 courses. After the treatment, the symptom grading scores (number of skin lesions, the size of skin lesions, the degree of pain and the quality of life) was compared, and the clinical effect rate was evaluated and the recurrence rate was observed.Results Twelve weeks after treatment, Chinese medicine washing group total effective rate was 97.5% (39/40), drug treatment group 87.5% (35/40), and physical treatment group 90.0% (36/40). The Chinese medicine washing group total effective rate was superior to the drug therapy and physicaltherapy groups (Z values were -3.463,-3.122,P values were 0.001, 0.002). after treatment, the number of lesions scores (2.0 ± 1.1 vs. 2.8 ± 1.5, 2.7 ± 1.6,F=3.787), the size of the lesion scores (2.3 ± 1.7 vs. 3.2 ± 1.3, 3.1 ± 1.3, F=4.657), pain degree and the quality of life scores (0.4 ± 0.5 vs. 1.0 ± 1.2, 1.0 ± 1.0,F=5.353) in the Chinese medicine washing group were significantly higher than those in the drug therapy and physical therapy groups (P<0.01). After follow-up period, the recurrence rate of Chinese medicine washing group was 10.3% (4/39), the drug treatment group 25.7% (9/35), the physical therapy group 41.7% (15/36). The difference among 3 groups was statistically significant (Z=-3.188,P<0.01).Conclusions The traditional Chinese medicine combined with Thymalfasin and Isotretinoin could reduce the number of skin lesions, narrow the range of skin lesions and reduce the degree of pain, and improve the quality of life.