Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Drug-release characteristic and biological toxicity of TiO2 nanotube/hydroxyapatite loaded vancomycin coating / 中国组织工程研究

BACKGROUND: In the scheme of titanium surface modification and coating modification, the drug sustained-release system constructed by surface nanotube modification and hydroxyapatite coating modification has broad clinical application prospects. OBJECTIVE: To construct composite drug loading coating of titanium dioxide nanotube/hydroxyapatite loaded with vancomycin hydrochloride, and analyze the drug release performance and cytotoxicity of the composite coating in vitro. METHODS: A two-step anodic oxidation method was used to construct titanium dioxide nanotubes on the titanium surface, and the prepared hydroxyapatite was loaded on the surface of the nanotubes by electrophoretic deposition, so as to obtain a nanotube/hydroxyapatite composite coating structure. Subsequently, the composite coating was used as a drug-loaded platform, and vancomycin hydrochloride was loaded by physical adsorption to finally obtain a composite drug-loaded coating. The in vitro drug release properties of hydroxyapatite/vancomycin hydrochloride, titanium dioxide nanotubes/vancomycin hydrochloride, titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating were measured. Human osteoblasts were cultured with titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating extracts of different concentrations. MTT assay was used to detect cytotoxicity. Human osteoblasts were inoculated on the surface of hydroxyapatite, titanium dioxide nanotubes, titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride, and the changes of cell morphology were observed. RESULTS AND CONCLUSION: (1) Compared with hydroxyapatite/vancomycin hydrochloride, titanium dioxide nanotube/vancomycin hydrochloride coating, titanium dioxide nanotube/hydroxyapatite/vancomycin hydrochloride coating had a longer drug sustained-release effect. The release time exceeded 150 hours. (2) The 10%, 50%, and 100% concentration of titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating extract had no obvious cytotoxicity. The relative activity of osteoblasts was more than 70%. (3) The osteoblasts on the three kinds of coating surface grow well; the cytoskeleton was intact; and the nucleus-cytoplasm ratio of the cells was normal, which was not significantly different from the morphology of the cells in pure culture. (4) The results show that the coating of titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride has good drug release properties in vitro without obvious cytotoxicity.

Clinical features and individualized treatment of 39 cases of adefovir dipivoxil-induced renal hypophosphatemia and osteomalacia / 中华传染病杂志

Objective To investigate the clinical features,early diagnosis and individualized treatment of renal hypophosphatemia and osteomalacia induced by adefovir dipivoxil (ADV) in patients with chronic hepatitis B (CHB).Methods Thirty-nine CHB or hepatitis B virus (HBV)-related cirrhosis patients of renal hypophosphatemia and osteomalacia induced by ADV were consecutively collected.The clinical features were analyzed and treatment outcome was followed up.Results The mean age of the 39 patients was 54 (27-71) years old.There were 26 male and 13 female patients,and 19 patients with cirrhosis.The mean ADV treatment duration was 69 (range 18-116) months,and 31 patients were treated for 36-96 months.The mean serum phosphate was 0.68 (0.42-0.79) mmol/L.Twenty-six cases developed renal hypophosphatemic osteomaolacia,of which 14 had bone pain and 19 had abnormally elevated alkaline phosphatase (ALP).Three patients had increased serum creatinine and 24 patients had decreased estimated glomerular filtration rate (eGFR).After individualized treatment,patients gained normal serum phosphate in mean of 2.0 (range 0.5-6.0) months,and had bone pain remission in the mean of 0.8 (range 0.2-1.0) month and bone pain disappeared in the mean of 1.5 (range 0.5-5.0) months.Function indices of liver and kidney were improved gradually,and the bone mineral density examination improved slowly.Conclusions CHB and HBV-related cirrhosis patients treated with longterm ADV could develop renal hypophosphatemia and hypophosphatemic osteomalacia,which is partially reversible.Monitoring serum phosphate,creatinine and cystatin C is necessary during long-term ADV therapy.After confirmed diagnosis,withdrawal or dosage reduction of ADV,and switch to telbivudine or entecavir should be considered.Meanwhile,serum phosphate and HBV DNA level should be monitored.

Establishment and characteristics of embryonic stem cells lines from Kunming mice / 中国组织工程研究

BACKGROUND:Up to date,inbred embryonic stem cells(ESCs) line mainly derived from 129 mouse strain and C57BL/6 strain,occasionally from BALB/c mouse strain,however,few reports concerning ESCs lines derived from Ch inese Kunmingmouse strain.OBJECTIVE:To isolate and culture mouse ESCs of kunming species,additionally,to identify its biological properties.DESIGN,TIME AND SETTING:The experiment with cells as observed subjects was conducted in the institute of Urology,First Affiliated Hospital of Nanchang University from May 2006 to June 2007.MATERIALS:Blastocysts of Kunmin mice with 3.5 days of embryonic age.METHODS:Inner cell mass from 3.5 days embryonic age were isolated from Kunming species mice,cultured on feeder layers of primary mice embryonic fibroblasts,and then the cells were isolated and subsequently cultured.MAIN OUTCOME MEASURES:Colony growth was observed and determined by alkaline phosphatase (AKP) staining;The expression of stage-specific embryonic antigen (SSEA)-1,and cell specific genes of c-Myc,Nanog,Oct3/4 and Sox2 were measured by immunofluorescence and RT-PCR;finally,the ability of differentiation in vitro and in vivo was identified.RESULTS:The ESCs-like colonies presented typical morphological characteristics of ESCs,which was positive to AKP and SSEA-1,and could express several cell specific genes,such as c-Myc,Nanog,Oct3/4 and Sox2,and differentiate into various cell types in vitro and in vivo.CONCLUSION:An ESCs line is successfully dedved from Kunming mice,which has typical biological characteristics of ESCs.

Determination of the Content of Lomustine in Mouse Tumor Tissue by RP-HPLC / 中国药房

OBJECTIVE: To determine the content of lomustine in mouse tumor tissue. METHODS: Lomustine was separated and determined on a reverse-phase C18 5um column with a mobile phase of acetonitrile-H2O(54 : 46), detected at 254nm and no internal standard. RESULTS: The ca[ibration curve was 1ineaI(r = 0. 9 999) within the range of 0. 98- 15. 68ug/ml for lomus tine. The recovery ratio of lomustine was 68. 64% (n = 9). The relative standard deviation(RSD) was 0. 32%. CONCLUSION: This method is simple and accurate

Effect of Catgut-embedding Therapy for Depressive Neurosis: An Observation of 47 Cases / 广州中医药大学学报

0.05).HAMD total score and the score of seven HAMD factors were lowered in the two groups after treatment(P0.05),but CET group had a higher efficacy index(P

Preliminary report of composite external fixator in the treatment of the severely proximal tibial fractures / 中华骨科杂志

Objective To explore the clinical outcome of self-designed composite external fixator in the treatment of severely comminuted or open proximal tibial fractures. Methods From July 2000 to January 2003, 22 cases of severely comminuted or open proximal tibial fractures were treated by self-designed composite external fixators, which involved 15 males and 7 females with an average age of 43 years (range, 20-80 years). This technique consisted of indirect reduction and limited open cannulated screw or K-wires fixation in case of necessity. Results All the patients had achieved fracture union at the 5th month averagely after operation. The period of follow-up was from 6-21 months(mean, 11 months). The mean duration of external fixation was 4.5 months. 4 cases received bone autograft from the iliac crest, primary union occurred in 20 cases, 2 cases with delayed union healed after bone-grafting. No infection occurred in 6 cases with open fracture. The other 16 cases also had no infection or skin necrosis. Only 4 cases with pin track infection healed by dressing change. 19 cases had knee flexion beyond 90?(containing 3 cases with second-stage knee release), 2 was 60? and 1 was 45?. 1 case took NSAIDs intermittently because of traumatic arthritis. According to Merchant grade, 14 were evaluated as excellent, 3 as good, 3 as fair and 2 as poor. The rate of excellent and good results was 77.3%. Conclusion The composite external fixator in treating the severely comminuted or open proximal tibial fracture has the following advantages, such as less-invasion, stable fixation, early-mobilization, high union rate and fewer complication.