Effect of thymopentin combined with levofloxacin for retreatment smear positive pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the effect of adjuvant to levofloxacin in the treatment of retreatment smear positive pulmonary tuberculosis, as well as its effect on respiratory function, immune function and inflammatory factors. Methods　One hundred cases of retreatment smear positive pulmonary tuberculosis patients admitted to Rudong County People's Hospital in Nantong city in Jiangsu province from 2017 to 2021 were randomly divided into a control group (n=50) and an observation group (n=50) according to random number table method. Both groups received conventional treatment (3 months of isoniazid, rifampicin, ethambutol, pyrazinamide / 6 months of isoniazid, rifampicin, ethambutol), with levofloxacin added to the control group, and thymopentin added to the observation group for the first three months in addition to routine treatment. The treatment effect of the two groups were compared. Results　The sputum smear conversion rate of the observation group was significantly higher than that of the control group after 3 months and 5 months of treatment (χ2=7.142, P<0.05; χ2=6.250, P<0.05). The cavity absorption time and lesion absorption time in the observation group were significantly lower than those in the control group (t=4.006, P<0.05; t=5.165, P<0.05). The turning time of bacteriological culture in the observation group was significantly lower than that in the control group (t=4.220,P<0.05). After 3 months of treatment, CD4+, CD3+, CD4+/CD8+ of the observation group were higher than those of the control group, the differences were statistically significant (t=8.885, P<0.05; t=6.274, P<0.05; t=4.357, P<0.05). After 3 months of treatment, the IFN-γ (interferon-γ) of the observation group was higher than that of the control group (t=8.892, P<0.05), whereas the , IL-10 (interleukin-10) was significantly lower than that in the control group (t=5.986, P<0.05). After 3 months of treatment, forced vital capacity (FVC), forced expiratory volume in one second (forced expiratory volume in one second, FEV 1) and the one-second rate (forced expiratory volume in one second / forced vital capacity, FEV1/FVC) in the observation group were significantly higher than those in the control group (t=11.223, P<0.05; t=10.128, P<0.05; t=4.464, P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2=0.378, P>0.05). Conclusions　Thymopentin combined with levofloxacin had a significant application effect in the treatment of retreatment smear positive pulmonary tuberculosis, s, which led to improved inflammatory reaction, respiratory function and immune function. Additionally, it can increase sputum smear conversion rate and accelerate patient recovery, improving overall treatment efficacy, with a relatively high clinical application value.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Effect of interferon-α and thymopentin on the mRNA expression of APOBEC3A and APOBEC3B in HepG2.2.15 cells / 临床肝胆病杂志

ObjectiveTo investigate the effect of synergistic intervention of interferonα (IFNα) and thymopentin (TP5) on the mRNA expression of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) in HepG2.2.15 cells. MethodsHepG2.2.15 cells were divided into blank control group, IFNα treatment group, TP5 treatment group, and IFNα+TP5 treatment group, and at 12, 24, 48, and 72 hours of treatment, quantitative real-time PCR was used to measure the mRNA expression of APOBEC3A and APOBEC3B in HepG2.2.15 cells. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank control group, the IFNα treatment group and the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at 12, 24, 48, and 72 hours of treatment (all P＜0001). Compared with the IFNα treatment group, the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at these four time points (all P＜0.001). TP5 treatment had no significant influence on the mRNA expression of APOBEC3A at each time point (all P＞0.05). There was no significant difference in the mRNA expression of APOBEC3B between the blank control group and the treatment groups (all P＞0.05). ConclusionIFNα combined with TP5 can significantly upregulate the mRNA expression of APOBEC3A in HepG2.2.15 cells.

Preparation of thymopentin supramolecular hydrogel and its application in immunomodulatory / 天津医药

Objective To prepare a thymopentin-contained supramolecular hydrogel, and characterize its micromorphology and mechanical property, and further investigate its effects on the cellular uptake and the immunomodulatory performance in vitro . Methods The self-assembling peptide containing thymopentin was prepared by solid phase synthesis method and identified using LC-MS after being purified by high performance liquid chromatography (HPLC). Supramolecular hydrogel was prepared through a heating-cooling process, and its micromorphology and mechanical property were characterized using transmission electron microscopy (TEM) and rheology. The cellular uptake efficiencies of free thymopentin and thymopentin nanofibers were observed by inverted fluorescence microscope after FITC-labeling. The abilities of free thymopentin and thymopentin nanofibers to stimulate RAW 264.7 cells to secrete tumor necrosis factor (TNF-α) were studied by enzyme-linked immunosorbent assay (ELISA). Results A macroscopic visible supramolecular hydrogel was obtained by a heating-cooling process, composing with long cross-linked nanofibers and possessing good ductility of mechanics. Compared with free thymopentin, thymopentin nanofibers showed much more enhanced cellular uptake, and better immunomodulation property as stimulating the RAW 264.7 cells to produce much higher concentration of TNF-α in vitro . Conclusion After rational structural modification, the cellular uptake and immunomodulatory activity of thymopentin, which formed nanomedicine, were significantly enhanced. This study can provide new methods and guidance for improving the therapeutic effect of thymopentin in clinical application.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate--hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. release studies revealed that sandwich films had nearly no burst release. release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4/CD8 values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.

Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.

Construction and eukaryotic expression of recombinant HSA-TP5 fusion gene expression vector / 吉林大学学报(医学版)

Objective:To construct the expression vector of the fusion protein of human serum albumin (HSA) and thymopentin (TP5) and to express it in Pichia pastoris,and to elucidate the biological activity of fusion protein.Methods:The HSA-TP5 fusion gene was constructed by gene recombination and transfected into Pichia pastoris to construct the eukaryotic expression system of HSA-TP5.The recombinant eukaryotic expression plasmid of PPICZα-HSA-TP5 was obtained by agarose gel electrophoresis and purification reagent.The two step fermentation method was used to ferment gene engineering bacteria of HSA-TP5 in high density,and the fermentation supernatant protein was precipitated and concentrated;the purified fusion protein was obtained by cation exchange chromatography and hydrophobic chromatography and analyzed by SDS-polyacrylamide gel electrophoresis.The effect of the fusion protein on the proliferation of lymphocytes was detected by MTT assay.Results:The HSA target gene fragment with length of 1 845 bp was achieved by PCR method.The HSA-TP5-pPICZαC fusion plasmid was identified by restriction endonuclease digestion,and the fragment length was 707 bp.The sequence analysis showed that the HSA and TP5 sequences of the target genes were identical with the gene sequences reported in GenBank and were fused by forward fusion.PCR method confirmed that the eukaryotic recombinant plasmid PPICZ αC-HSA-TP5 was integrated into the yeast genome,and compared with control group,the target gene PCR product length was found to be 1 860 bp.SDS-PAGE analysis showed that the expression level of HSA-TP5 fusion protein was gradually increased with the induction time within 72 h.HSA-TP5 fusion protein was purified by cation exchange chromatography and AKTA multifunctional protein purification system.The MTT assay results showed that HSA-TP5 fusion protein was consistent with TP5 protein in promoting lymphocyte proliferation activity.Conclusion:HSA-TP5 fusion protein can be obtained by constructing the eukaryotic expression system of Pichia pastoris and owns the biological activity.

Construction and eukaryotic expression of recombinant HSA-TP5 fusion gene expression vector / 吉林大学学报(医学版)

Objective:To construct the expression vector of the fusion protein of human serum albumin (HSA) and thymopentin (TP5) and to express it in Pichia pastoris,and to elucidate the biological activity of fusion protein.Methods:The HSA-TP5 fusion gene was constructed by gene recombination and transfected into Pichia pastoris to construct the eukaryotic expression system of HSA-TP5.The recombinant eukaryotic expression plasmid of PPICZα-HSA-TP5 was obtained by agarose gel electrophoresis and purification reagent.The two step fermentation method was used to ferment gene engineering bacteria of HSA-TP5 in high density,and the fermentation supernatant protein was precipitated and concentrated;the purified fusion protein was obtained by cation exchange chromatography and hydrophobic chromatography and analyzed by SDS-polyacrylamide gel electrophoresis.The effect of the fusion protein on the proliferation of lymphocytes was detected by MTT assay.Results:The HSA target gene fragment with length of 1 845 bp was achieved by PCR method.The HSA-TP5-pPICZαC fusion plasmid was identified by restriction endonuclease digestion,and the fragment length was 707 bp.The sequence analysis showed that the HSA and TP5 sequences of the target genes were identical with the gene sequences reported in GenBank and were fused by forward fusion.PCR method confirmed that the eukaryotic recombinant plasmid PPICZ αC-HSA-TP5 was integrated into the yeast genome,and compared with control group,the target gene PCR product length was found to be 1 860 bp.SDS-PAGE analysis showed that the expression level of HSA-TP5 fusion protein was gradually increased with the induction time within 72 h.HSA-TP5 fusion protein was purified by cation exchange chromatography and AKTA multifunctional protein purification system.The MTT assay results showed that HSA-TP5 fusion protein was consistent with TP5 protein in promoting lymphocyte proliferation activity.Conclusion:HSA-TP5 fusion protein can be obtained by constructing the eukaryotic expression system of Pichia pastoris and owns the biological activity.

A study on mechanisms of levofloxacin, thymopentin combined with decoction of four noble drugs for treatment of patients with severe pulmonary tuberculosis / 中国中西医结合急救杂志

Objective To study the mechanisms of levofloxacin,thymopentin combined with decoction of four noble drugs for treatment of patients with severe pulmonary tuberculosis and offer a new therapeutic strategy for treatment of the disease.Methods A total of 100 patients with severe pulmonary tuberculosis admitted to Qinghai Fourth People's Hospital from November 2013 to January 2016 were enrolled,and they were divided into a research group (50 patients) and a control group (50 patients) by random number table.The patients in two groups were treated with 2HRZE/4HR standardized therapy program.The patients in the research group were additionally treated with levofloxacin (0.5 g orally taken,1 times a day),thymopentin (1 mg intravenous injection,once a day) combined with decoction of four noble drugs (ginseng 9 g,poria 9 g,atractylodes 9 g,and licorice 6 g,all the above ingredients were immersed in 400 mL water and boiled to 100 mL,one dose orally taken daily and it was equally divided into 2 parts,one part taken in the morning and the remaining part taken in the evening).Four months after treatment,the changes of indexes of immune functions [total lymphocyte count (LY),CD4+,CD8+,and CD4+/CD8+ ratio],blood coagulation indexes [prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),D-dimer,and plasma fibrinogen (Fib)],pulmonary function indexes [forced vital capacity (FVC),peak expiratory flow rate (PEF),forced expiratory maximum volume in 1 second (FEV1),and mean maximum expiratory flow (MMEF)] and blood gas analysis indexes [arterial partial pressure of carbon dioxide (PaCO2),arterial partial pressure of oxygen (PaO2),pulse oxygen saturation (SpO2),and oxygenation index (PaO2/FiO2)] and the therapeutic effects were observed in the two groups.Results After treatment,the CD8+,TT,PT,Fib,D-Dimer and PaCO2 of two groups were decreased significantly than those before treatment (all P ＜ 0.05);while the LY,CD4+,CD4+/CD8+ ratio,FEV1,FVC,PEF,MMEF,APTT,PaO2,SpO2 and PaO2/FiO2 of two groups were all increased significantly than those before treatment (all P ＜ 0.05).The changes of the study group were more obvious than those of the control group [LY (109/L):1.79 ± 0.19 vs.1.45 ± 0.16,CD4+:0.40 ± 0.03 vs.0.33 ± 0.03,CD8+:0.20 ± 0.01 vs.0.23 ± 0.02,CD4+/CD8+ ratio:2.10 ± 0.23 vs.1.67 ± 0.20,FEV1:0.269 ± 0.004 vs.0.198 ± 0.003,FVC:(3.78 ± 0.41)％ vs.(3.14 ± 0.39)％,PEF (L/s):3.68 ± 0.26 vs.3.05 ± 0.23,MMEF (L/s):0.96 ± 0.06 vs.0.74 ± 0.05,PaO2 (mmHg,1 mmHg =0.133 kPa):95.11 ± 7.68 vs.85.23 ± 7.01,PaCO2 (mmHg):31.76± 3.26 vs.46.28±4.36,SpO2:0.96±0.08 vs.0.91 ±0.07,PaO2/FiO2 (mmHg):310.58± 11.12 vs.285.01 ± 10.76,TT (s):15.64± 1.25 vs.18.82 ± 1.54,PT (s):12.69 ± 1.01 vs.14.28 ± 1.21,APTT (s):29.01 ± 2.02 vs.25.21 ± 1.80,Fib (mg/L):233.46 ± 15.61 vs.286.27 ± 18.14,D-Dimer (μg/L):210.88 ± 14.13 vs.256.39 ± 16.47,all P ＜ 0.05].After combined treatment,the sputum negative conversion rate [94％ (47/50) vs.60％ (30/50)],the total efficiency [88％ (44/50) vs.64％ (32/50)] and the focus absorption rate [86％ (43/50) vs.60％ (30/50)] of research group were significantly higher than those of the control group (all P ＜ 0.05).Conclusions The combination of levofloxacin,thymopentin and decoction of four noble drugs on the bases of 2HRZE/4HR standardized therapy for treatment of patients with severe pulmonayr tuberculosis can help to regulate acid-base balance,improve the hypoxia condition and lung function,elevate the immune function and increase the blood circulation in the body to improve clinical efficacy.

Clinical Observation of Recombinant Human Interferon α2b Combined with Bozhi Glycopeptides and Thymopentin in the Treatment of HBeAg-positive Chronic Hepatitis B / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of recombinant human interferon α2b (rhIFN α2b) combined with bozhi glycopeptides or thymopentin in the treatment of chronic hepatitis B (CHB).METHODS:Ninety HBeAg-positive CHB patients were selected from our hospital during Jan.2014-Jan.2015 and then randomly divided into group A,B,C,with 30 cases in each group.Group A was given rhINF α2b for injection (Pseudomonas) 5 million IU subcutaneously,qod;group B was additionally given Bozhi glycopeptides injection 4 mL added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A;group C was additionally given Thymopentin for injection 2 mg added into 5％ Glucose injection 250 mL,ivgtt,qd,on the basis of group A.Three groups were treated for 24 weeks.The rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg/anti-HBeAg serum,negative rate of HBV-DNA and the decrease of HBsAg and HBV-DNA were compared among 2 groups after 4,8,12,24 weeks of treatment.The occurrence of ADR was recorded.RESULTS:After 4,8,12 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,negative rate of HBeAg,transformation rate of HBeAg and the decrease of HBsAg among 3 groups (P＞0.05).After 4 weeks,negative rate of HBV-DNA in group B,C were significantly higher than group A;the decrease of HBV-DNA in group C were more significant than group A and B,with statistical significance (P＜0.05).After 8,12 weeks of treatment,the negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);but there was no statistical signifi cance between group B and C (P＞0.05).After 24 weeks of treatment,there was no statistical significance in the rate of ALT recovering to normal,transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBsAg among 3 groups (P＞0.05).The negative rate of HBsAg,negative rate of HBV-DNA and the decrease of HBV-DNA in group B,C were significantly higher than group A,with statistical significance (P＜0.05);there was no statistical significance between group B and C (P＞0.05).There was no statistical significance in the incidence of ADR among 3 groups(P＞0.05).CONCLUSIONS:rhIFN α2bcombined with bozhi glycopeptides or thymopentin shows good inhibitory effect on CHB,therapeutic efficacies of them are similar in the rate of ALT recovering to normal,but transformation rate of HBeAg,the decrease of HBsAg and negative rate of HBeAg.

Effects of lentinan and thymopentin injection combined with PTP chemotherapy on serum TSGF, IgG, IgA, IgM and quality of life in patients with oral squamous cell carcinoma / 中国生化药物杂志

Objective To investigate the clinical effect of lentinan and thymopentin injection combined with PTP chemotherapy in oral squamous cell carcinoma patients, and to observe the effect of lentinan on serum tumor specific growth factor ( TSGF) , IgG, IgA and IgM and quality of life in patients with oral squamous cell carcinoma .Methods The clinical data of 80 cases of oral squamous cell carcinoma ( postoperative lymph node metastasis) confirmed by operation and pathology were analyzed retrospectively, and the diagnosis and treatment were analyzed.The control group were treated with PTP regimen, 80 ~120 mg/m2 of cisplatin, 50 ~80 mg/m2 of teniposide on the first day, the second to fourth day, once daily +pingyangmycin 4~6 mg/m2 , once daily, 3 to 12 days, 3 weeks for a course of treatment, a total of 6 courses.In the control group based on the use of thymopentin injection 20 mg and lentinan 2 mg+5% glucose solution 250 mL intravenous infusion, chemotherapy 2 d before the start, infusion 14 d, 3 weeks for a course of treatment, a total of 6 courses, for the observation group;two groups were 40 cases.The levels of serum TSGF, IgA, IgG, IgM and CD3 +, CD4 +, CD8 +, NK cells and TSGF in the two groups before and after treatment were measured.The quality of life of the patients was investigated by hospital-made questionnaires.The clinical efficacy and side effects were analyzed.Results TSGF levels in the two groups were significantly lower than that before treatment, and the TSGF level in the observation group was (39.1 ±4.9)U/mL, which was significantly lower than that in the control group (52.3 ±5.8) U/mL(P<0.05).After treatment, the TSGF level in observation group was lower than that in control group [(39.1 ±4.9) U/mL vs. (52.3 ±5.8) U/mL](P<0.05).The CD3 +, CD4 +, NK, IgG levels in observation group were higher than those in control group and the CD8 +level in observation group was lower than that in control group (P<0.05).The scores of physical symptoms, sleep quality, mental state and social affection levels in observation group were higher than those in control group(P<0.05).The total efficacy in observation group was lower than that in control group (77.5% vs.45.0%, P<0.05).The adverse reaction rate was 20.0% in the observation group, which was significantly lower than that in the control group (P<0.05).Conclusion The use of lentinan and thymopentin injection combined with PTP chemotherapy in the treatment of oral squamous cell carcinoma has higher clinical efficacy and less adverse reactions.

Immune formulation-assisted conventional therapy on anti-infective effectiveness of multidrug-resistant Mycobacterium tuberculosis infection mice

Objective: To study the effect of immune formulation-assisted conventional therapy on anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice. Methods: BALB/c mice were used as experimental animals, multidrug-resistant M. tuberculosis infection models were built, randomly divided into model group, moxifloxacin group, thymopentin group and combined treatment group and given corresponding drug intervention, and then colony numbers in the spleen and lung, T lymphocyte subset contents and programmed death-1 (PD-1) expression levels in peripheral blood were detected. Results: Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group; contents of CD3

Immune formulation-assisted conventional therapy on anti-infective effectiveness of multidrug-resistant Mycobacterium tuberculosis infection mice

OBJECTIVE@#To study the effect of immune formulation-assisted conventional therapy on anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice.@*METHODS@#BALB/c mice were used as experimental animals, multidrug-resistant M. tuberculosis infection models were built, randomly divided into model group, moxifloxacin group, thymopentin group and combined treatment group and given corresponding drug intervention, and then colony numbers in the spleen and lung, T lymphocyte subset contents and programmed death-1 (PD-1) expression levels in peripheral blood were detected.@*RESULTS@#Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group; contents of CD3(+)CD4(+)T cells, Th1 and Th17 in peripheral blood of moxifloxacin group and thymopentin group were higher than those of model group, and contents of CD3(+)CD8(+)T cells, Th2 and Treg were lower than those of model group; contents of CD3(+)CD4(+)T cells, Th1 and Th17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group, and contents of CD3(+)CD8(+)T cells, Th2 and Treg were lower than those of moxifloxacin group and thymopentin group; PD-1 expression levels on T lymphocyte, B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group, and PD-1 expression levels on T lymphocyte, B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.@*CONCLUSIONS@#Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant M. tuberculosis infection mice, decrease bacterial load in lung and spleen, and enhance immune function.

Efficacy and clinical nursing of thymopentin combined with ceftriaxone on patients with early syphilis serum fixation / 中国基层医药

Objective To evaluate efficacy of thymopentin combined with ceftriaxone on patients with early syphilis serum fixation.Methods A total of 108 patients with early syphilis serum fixation were chosen and divided into observation group and control group by the number of tables (54 cases in each group).The control group were underwent conventional sodium penicillin with benzathine with nursing treatment,the observation group were treated with ceftriaxone thymopentin combined with nursing treatment,changes in the relevant indicators before and after treat-ment were observed.Results After treatment,IL -2,IL -10 and other indicators in the observation group were improved compared to the control group[IL -2:the control group before treatment (20.8 ±4.9)μg/L,after treatment (42.7 ±7.3)μg/L;the observation group before treatment(19.8 ±5.1)μg/L,after treatment (54.6 ±8.3)μg/L;IL -10:the control group before treatment (76.3 ±16.1)μg/L,after treatment (51.3 ±5.4)μg/L;the observation group before treatment(78.3 ±4.1)μg/L,after treatment(23.8 ±5.1)μg/L],the differences of the two groups after treatment were statistically significant (t =3.923,8.832,all P <0.05);after treatment,the RPR negative rates of the observation group at 3,6,12 months after treatment(72.2%,85.2%,96.3%)was significantly higher than those of the control group(53.7%,57.4%,63.0%),the differences were statistically significant (χ2 =4.932,11.372, 22.842,all P <0.05);the efficacy of the observation group at 3,6,12 months after treatment(75.9%,79.6%, 75.9%)were significantly better than those of the control group (72.2%,64.8%,57.4%),the differences were statistically significant (χ2 =5.232,6.183,all P <0.05 ).Conclusion Thymopentin combined with ceftriaxone treatment of early syphilis can significantly improve its fixed immunological parameters,which coordinated with nursing measures can strengthen patient care awareness,then the efficacy will be better,so it is worthy of clinical further promotion.

Effect of 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5 on IL -17,IL -23 expression of recurrent condylomata acuminata patients / 中国基层医药

Objective To explore effect of 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5 on IL -17,IL -23 expression of recurrent condylomata acuminata patients.Methods 140 patients with recurrent condylomata acuminata were randomly divided into 3 groups.53 cases in observation group were treated by 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5,42 cases in control group 1 were treated by 5 -aminolevulinic acid -photodynamic therapy,and 45 cases in control group 2 were treated by thymopen-tin -5.24 healthy subjects were served as normal controls.IL -17,IL -23 levels were determined by enzyme linked immunosorbent assay before and after the clinical therapy.Results IL -17,IL -23 levels in the patients with recur-rent condylomata acuminata were significantly lower than those in healthy subjects(t =28.10,P <0.01;t =11.10, P <0.01).There were significant differences in IL -17,IL -23 between recurrent condylomata acuminata patients and healthy persons before treatment.There was significant difference after treatment(t =61.17,P <0.01;t =28.02, P <0.01).Conclusion 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5 in the treat-ment of recurrent condylomata acuminata inhibited IL -17,IL -23 expression,so as to achieve therapeutic effect.

Analysis and Clinical Intervention of Off-label Drug Use of Thymopentin in Our Hospital / 中国药房

OBJECTIVE:To provide reference for rational drug use in the clinic. METHODS:Medical records of 300 inpa-tients receiving thymopentin were randomly sampled from our hospital during Jul. 2013-Jun. 2014. The indication,solvent dilution, route of medication,dosage,medication course and contraindications were analyzed and evaluated. Comment result fed back and ef-fective clinical invention was done. RESULTS:There was a certain degree of off-label use of thymopentin,and the off-label drug use accounted for 38.33%. Through examination and clinical intervention on clinical rational drug use, remarkable results had been achieved. Thymopentin prescription sampling were analyzed statistically in the third quarter of 2014,and the off-label drug use rate dropped to 14%. CONCLUSIONS:We should strengthen prescription comments and feedback,effective clinical invention should be done,to promote rational use of thymopentin.

Changes in help T cell 1/2 cytokines and transcription factors in cytomegalovirus infected newborn mice and effectiveness of intervention with thymopentin / 中华围产医学杂志

Objective To observe the changes in help T cell 1/2 cytokines and transcription factors in murine cytomegalovirus (MCMV) infected newborn mice and to determine the effectiveness of intervention with thymopentin.Methods One hundred and twenty newborn BALB/c mice were randomized into a blank group,model group and thymopentin group,with 40 mice in each group.Mice in the model and thymopentin group received an intraperitoneal injection of MCMV suspension within 4-6 hours after birth at the dosage of 20 μ L to and tissue culture infections dose of 10431 U/0.1 ml,establish a systemic infection model,and the same volume of normal saline was injected into mice in the control group.Mice in the thymopentin group also received thymopentin 0.3 mg/(kg · d).On Day 3,5,7,10 and 14,8 mice in each group were sacrificed and their splenic tissues were harvested.Interferon (IFN) γ and interleukin (IL)-10 expression in the supernatant of a splenic lymphocyte culture was assessed by enzyme-linked immunosorbent assay.T-bet/GATA-3 mRNA in splenic tissues were analyzed using reverse transcription-polymerase chain reaction.One way ANOVA,including LSD and Dunnett T3 methods,was used for statistical analysis.Results (1) IFN-γ expression in the model and thymopentin groups peaked on Day 3,and was higher than that in the control group [(280.73 ± 14.88),(286.03 ± 15.44) and (149.42±5.43) pg/ml,respectively,F=183.532,P=0.000].Expression in the thymopentin group decreased after Day 3,and increased by Day 7.At Day 14,the IFN-γ expression level in the thymopentin group was higher than that in the control and model groups [(252.33±8.33),(149.07±7.05) and (148.57±4.53) pg/ml,respectively,F=385.487,P=0.000].(2) IL-10 expression in the model group gradually increased.By Day 14,the expression became obviously higher than that in the control and thymopentin groups [(71.19± 1.50),(36.67 ± 2.55) and (40.01 ± 1.28) pg/ml,respectively,F=523.670,P=0.000].IL-10 expression in the thymopentin group increased after Day 3 and decreased by Day 7.On Day 14,the expression in the thymopentin group was lower than that in the model group,but higher than that in the control group.(3) T-bet mRNA expression was obviously increased in the model and thymopentin groups.On Day 3,the expression was higher than that in the control group (relative value of gray-scale:0.74±0.02,0.71 ±0.04 and 0.30±0.01,respectively,F=741.630,P=0.000).By Day 3,the expression in the thymopentin group decreased,and gradually recovered on Day 5,and on Day 14 it was higher than that in the control and model groups (relative value of gray-scale:0.45 ± 0.01,0.30±0.01 and 0.30±0.01,respectively,F=257.571,P=0.000).(4) GATA-3 mRNA expression in the model and thymopentin groups increased on Day 3,and was higher than that in the control group (relative value of gray scale:0.48±0.02,0.53±0.01 and 0.33±0.01,respectively,F=345.167,P=0.000).On Day 14,the expression in the model group was higher than that in the thymopentin group,which was higher than that in the control group (relative value of gray-scale:0.99 ± 0.02,0.55 ± 0.02 and 0.34 ± 0.01,respectively,F=1 767.505,P=0.000).Conclusions A Th1/Th2 shift may be induced in MCMV infected neonatal mice,which manifests as a state of predominant Th2 response.Thymopentin can ameliorate this situation.

Study on Bactericidal Activity of Thymopentin Peptide and Its Derived Peptides / 中国药房

OBJECTIVE:To study the bactericidal activity of thymopentin and its derived peptides. METHODS:Agar plate count was adopted to determine the bactericidal activity of thymopentin [arginine(R)-lysine(K)-aspartic acid(D)-valine(V)-tyro-sine(Y),RKDVY],its derived peptide 1 [RKN(agedoite,N)VY] and derived peptide 2(RKKVY)to Gram negative bacterial (Proteusbacillus vulgaris,Escherichia coli) and Gram positive bacterial (Staphylococcus aureus,Enterococcus faecium). There were 15.625-1 000 μg/ml for peptides,102 CFU for bacteria. RESULTS:Three pentapeptides possessed bactericidal activity against Gram negative bacteria. The activities of RKKVY and RKNVY were stronger than RKDVY(P0.05). They also possessed bactericidal activity against Gram positive bacteria,and the activity from strong to weak was RKKVY>RKNVY>RKDVY(P<0.01). CONCLUSIONS:Thymopentin and its derived peptides possess bactericidal activity against Gram negative and positive bacteria,with dose-effect relationship.

An in vitro accelerated approach based on in vivo release to assess thymopentin release from PLGA microspheres / 国际药学研究杂志

Objective To establish an accelerated method that has good correlations with in vivo release data for formulation optimization and quality control purposes of thymopentin-loaded poly (DL-lactide-co-glycolide) (PLGA) microspheres. MethodsIn vivo thymopentin release from the microspheres was studied in Sprague-Dawley rats and relevant cumulative release curves were plotted. Key factors including release medium types, ethanol concentrations, surfactant concentrations and heating temperature were investigated for the in vitro accelerated release. The conditions for accelerated release were optimized to make the accelerated release cures fit the in vivo release well. The final optimized accelerated release method was validated in other two formulations. ResultsThe final optimized accelerated release conditions were: 20% hydro-alcoholic solutions (V/V) and 0.06% Tween 80 (W/V) as the release media, gradient heating program (0-1 h at 40 °C, 1-6 h at 45 °C and 6-30 h at 50 °C) as the media heating method. After fitted with the in vivo release curves, the correlation constant r2 of (8, 13 and 28)×103 PLGA microspheres was 0.9783, 0.9886 and 0.9780, respectively. ConclusionBy introducing alcohol into the release media and applying gradient heating program, the reported accelerated method can be used in the formulation optimization and quality control of thymopentin-loaded PLGA microspheres.

An in vitro accelerated approach based on in vivo release to assess thymopentin release from PLGA microspheres / 国际药学研究杂志

Objective To establish an accelerated method that has good correlations with in vivo release data for formulation optimization and quality control purposes of thymopentin-loaded poly(DL-lactide-co-glycolide)(PLGA)microspheres. Methods In vivo thymopentin release from the microspheres was studied in Sprague-Dawley rats and relevant cumulative release curves were plotted. Key factors including release medium types,ethanol concentrations,surfactant concentrations and heating temperature were investigated for the in vitro accelerated release. The conditions for accelerated release were optimized to make the accelerated release cures fit the in vivo release well. The final optimized accelerated release method was validated in other two formulations. Results The final optimized accelerated release conditions were: 20% hydro-alcoholic solutions (V/V)and 0.06% Tween 80 (W/V)as the release media,gradient heating program (0-1 h at 40 °C,1-6 h at 45 °C and 6-30 h at 50 °C)as the media heating method. After fitted with the in vivo release curves,the correlation constant r2 of (8,13 and 28)×103 PLGA microspheres was 0.9783,0.9886 and 0.9780,respectively. Conclusion By introducing alcohol into the release media and applying gradient heating program,the reported accelerated method can be used in the formulation optimization and quality control of thymopentin-loaded PLGA microspheres.