1.Pharmacokinetic comparison of roxithromycin under normoxic and hypoxic conditions in rats by UPLC/MS/MS
Tao SHAO ; Yi QIN ; Pingxiang XU ; Weizhe XU ; Liang ZHAO ; Yi MA ; Weijia HAO ; Ming XUE
Chinese Pharmacological Bulletin 2016;32(11):1596-1600,1601
Aim To study and compare the pharmaco-kinetic parameters of roxithromycin under normoxic and hypoxic rats. Methods A highly effective and rapid ultra-performance liquid chromatography with tandem mass spectrometry ( UPLC-MS/MS) method with posi-tive electrospray ionization source was successfully de-veloped and validated for quantification of roxithromy-cin in rat plasma. Sprague-Dawley rats were randomly divided into the hypoxia and normoxic groups. Each rat obtained a single dose of roxithromycin with 10 mg · kg-1 via intragastric administration. The pharmacoki-netic parameter comparison between normoxic and hy-poxic groups was calculated by SPSS software using in-dependent sample t test method. Results The main pharmacokinetic parameters of roxithromycin between the normoxic and hypoxic rats were:the AUC(0-t) 7 576 and 3 761 μg·h·L-1 , MRT(0-t) 5. 6 and 7. 7 h, T1/2 3. 4 h and 3. 9 h, CL 1. 5 and 3. 0 L · h-1 · kg-2 , tmax3. 1 and 3. 4 h, Cmax 1 116 and 372 μg·L-1 , re-spectively. The levels of Cmax and AUC of roxithromy-cin in hypoxic rats were statistically lower than those in normoxic rats. Conclusion The exposure level of rox-ithromycin in hypoxic rats markedly decreased. Our re-sults may provide an important experimental basis to adjust the dosage for roxithromycin in hypoxic clinical practice.
2.Newborn Hypoxic-ischemic Brain Damage Modeling in Rats
Gang CHEN ; Weizhe WANG ; Mingzhao CHEN ; Wei LIU ; Feng GAO ; Hong ZHI ; Xinwei QIAN ; Lihui ZHAO
Chinese Journal of Rehabilitation Theory and Practice 2012;18(7):612-614
Objective To model the newborn hypoxic-ischemic brain damage in rats. Methods 25 7-day-old healthy Wistar rats were divided into control group (n=12) and model group (n=13). 2 h after ligating and mutilating the unilateral common carotid arteries, the rats in the model group were put into an airtighted box with the volume fraction of 8% oxygen and 92% nitrogen for 2 h. 4 weeks after operation, all the rats were assessed behaviorally and pathologically. Results The footprint repeat space of rats were larger and more instable in the model group than in the control group (P<0.05). The time the rats crossing the balance beam was longer in the model group than in the control group (P<0.05). The escape latency of the water maze test was longer in the model group than in the control group (P<0.05). The right brain became smaller than the contralateral. HE staining showed that the cells around impaired periventricle were swelling, and cell number was less than the contralateral. The neurons decreased, some degenerated and necrosis neurocytes appeared in the impaired side. Conclusion The model of hypoxic-ischemic brain damage has been established.
3.Traditional Chinese Medicine Combined with Chemotherapy in Prevention and Treatment of Recurrence and Metastasis of Locally Advanced Gastric Cancer After Radical Resection: A Meta-analysis
Yue WANG ; Weizhe ZHAO ; Xiaojie LI ; Mengdie NAN ; Meiwen XIE ; Peijin LI ; Li HOU
Cancer Research on Prevention and Treatment 2022;49(9):913-922
Objective To explore the efficacy and safety of traditional Chinese medicine(TCM) combined with chemotherapy in the prevention and treatment of postoperative recurrence and metastasis of locally advanced gastric cancer (LAGC) by meta-analysis. Moreover, we evaluated the efficacy of TCM on the quality of life, immune indexes, and toxic and side effects during adjuvant chemotherapy. Methods The CNKI, Wanfang, PubMed, and other databases were searched by computer. Randomized controlled trials (RCTs) were searched. After literature screening and data extraction, Review Manager 5.3 software provided by Cochrane was used for meta-analysis. Results A total of 18 RCTs were included. Compared with chemotherapy alone, TCM combined with chemotherapy could improve the KPS score and CD3+ and CD4+/CD8+ index levels. The incidence rates of postoperative leucopenia, hemoglobin reduction, thrombocytopenia, nausea and vomiting, diarrhea, and neurotoxicity were reduced. In terms of postoperative QLQ-C30 score, abnormal liver function, and abnormal renal function, the incidence of TCM combined chemotherapy was similar to that of chemotherapy alone, with no statistical difference. Compared with chemotherapy alone, TCM combined chemotherapy could reduce the 1-, 2-, 3-, and 5-year cumulative recurrence and metastasis rates and prolong the disease-free survival time. Conclusion Compared with chemotherapy alone in adjuvant chemotherapy, TCM combined chemotherapy could improve the immune level and KPS score of LACC patients after surgery, reduce the incidence of adverse reactions, as well as reduce the recurrence and metastasis rate of LAGC after surgery and DFS could be improved.
4.Biological Basis of Five-phase Evolution of Malignant Tumors from Perspective of "Immune Editing"
Taicheng LU ; Bowen XU ; Jinyang WU ; Jie LI ; Baoyi NI ; Jingwen YU ; Weizhe ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):172-179
Immune escape is one of the ten hallmarks of tumors, which plays an important role in the occurrence and development of tumors. Immune escape refers to a process where tumor cells remodel and edit the immune system through the model of immune clearance, immune balance, and immune escape to "transform" the immune cells into immunosuppressive cells in the tumor microenvironment, so as to support immune escape. The five-stage evolution is the summary of tumor pathogenesis by professor LI Jie. He believes that the gradual development of tumors follows the core pathogenesis of "deficiency-cold-toxin-obstruction-collapse", in which "depression" runs through the whole process, and cancer toxin is the key. Based on immune editing, this paper combined phenotypic characteristics of tumor cells with the core pathogenesis of the five-stage evolution of professor LI to reveal the biological basis of malignant tumor five-stage evolution. The results indicate that the prominent change from deficiency to cold is the reduction of immune surveillance and the prominent change from toxin to obstruction is immune escape. The final stage of collapse is the outcome of immune failure. Depression is the booster of tumor immune editing. Therefore, the method of reinforcing the healthy Qi and removing toxins was proposed to regulate the immune editing and cut off the five-stage evolution of tumors. Supplementing Qi and warming Yang can reinforce the healthy Qi and restore immune surveillance. Removing toxins and dredging can reverse toxins and immune escape. The harmonizing method can maintain the dynamic balance of immune cells/immunosuppressive cells. Resolving depression can truncate tumor immune editing. Those methods can provide a certain reference for the treatment based on microscopic syndrome differentiation in traditional Chinese medicine (TCM). In future studies, it is necessary to further explore the specific mechanism of the regulation of immune editing with the methods of supplementing Qi and warming Yang, removing toxins and dredging, their combination, and resolving depression, so as to find out specific Chinese medicines and targets and provide more sufficient evidence for the regulation of tumor immune editing by TCM.