1.ECFect of Yang Xin Kang on Plasma Endothelin and Calcitonin - Gene Related Peptide Levels in Rats with Myocardial Hypertrophy Heart Failure
Yanshou HUANG ; Shaoxiang XIAN ; Minglu ZHOU ; Hui YANG ; Zhixi CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2001;0(01):-
[Objective] To observe levels of plasma endothelin (ET) and calcitonin gene - related peptide (CGRP) in rats with myocardial hypertrophic heart failure affected by Yang Xin Kang (composed of Radix Ginseng, Radix Ophio-pogonis, Radix flicis Pubescetis, etc.) and its mechanism. [Methods] Rat models with myocardial hypertrophic heart failure was established by subcutaneous injection of isoprenaline for 13 days. Fifty rats were allocated to five groups: normal control (Group A), model (Group B), digoxin (Group C), high dosage of Yang Xin Kang (Group D) and low dosage of Yang Xin Kang (Group E). ET and CGRP levels were measured by radioimmunoassay method. [Results] ET level in Group B was higher and CGRP level lower than those in Group A (P
2.Effect of Bao Xin Kang on Cyclic Nucleoside Phosphate Level in Vascular Smooth Muscle of Rats with Myocardial Hypertrophic Heart Failure
Yanshou HUANG ; Shaoxiang XIAN ; Hui YANG ; Minglu ZHOU ; Zhixi CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2000;0(04):-
[Objective] To investigate the effect of Bao Xin Kang (BXK) on levels of cyclic adenosine monophosphate (cGMP) and cyclic guanosine monophosphate (cAMP) in vascular smooth muscle of rats with myocatdial hypertrophic heart failure and to explore its mechanism. [Methods] Fifty rats were randomly allocated to five groups: normal control group (Group A) , model group (Group B) , digoxin group (Group C), large - dose BXK group (Group D) and small - dose BXK group (Group E). Rat models with myocardial hypertrophic heart failure were established by subcutaneous injection of isoprenaline for 13 days. Radioimmunoassay was used to measure the levels of cAMP, cGMP and the ratio of cAMP/cGMP in vascular smooth muscle. The body weight and the weight of heart, liver and lung were measured and his-tomorphologic features of heart, liver and lung also examined. [Results] The levels of cAMP and cGMP and the heart index (heart weight /body weight) and the liver index (liver weight/body weight) in Group B were increased as compared with those in Group A (P
3.Effect of qiangji jianli liquid on changes of nucleic acid and protein of spleen and kidney tissue in mice with spleen deficiency syndrome
Zhixi CHEN ; Zhiwei XU ; Xiaobin LIU ; Jinyan CHEN ; Zhiqiang LI ; Minglu ZHOU ; Zanhou HE
Chinese Journal of Tissue Engineering Research 2007;11(8):1581-1584
BACKGROUND: Qiangji jianli liquid plays a key role in prevention and cure of myasthenia gravis; however, whether changes of nucleic acid and protein are related to its mechanism or not should be studied further.OBJECTIVE: To observe the effect of qiangji jianli liquid on synthesis of nucleic acid and protein in mice with experimental spleen deficiency syndrome, and investigate the effect on myasthenia gravis and the molecular biological basis.DESIGN: Randomized controlled animal study.SETTING: Testing Center and Basic Medical College of Guangzhou University of Traditional Chinese Medicine.MATERIALS: Healthy male NIH mice, aged 4 weeks, of clean grade, weighing 17-21 g, were provided by Medical Experimental Animal Center of Guangdong Province. Qiangji jianli liquid (Guangdong Dongfang Shencao Pharmaceutical Factory); serpate solution (Guangdong Bangmin Pharmaceutical Factory); [5-methyl-3H] TdR, [5-3H] uridine and L-[4,5-3H]leucine (Atom High-nuclear Technology Application Limited Company).METHODS: The experiment was carried out in the Laboratory of Nuclear Medicine of Guangzhou University of Traditional Chinese Medicine from June to November 2005. A total of 180 healthy male NIH mice were randomly divided into normal control group, model group, 26 g/kg qiangji jianli liquid group, 13 g/kg qiangjijianli liquid group and sijunzi decoction group with 36 in each group. Except normal control group, serpate was used to establish animal models of spleen deficiency syndrome. 0.2 mg/(kg ·d) serpate was intraperitoneally injected into mice. ① 0.1 mL/(mouse·d) saline was intraperitoneally injected into mice in normal control group. ② 26 g/kg and 13 g/kg were perfused into mice in 26 g/kg and 13 g/kg qiangji jianli liquid groups, respectively, once a day. Qiangji jianli liquid consisted of beiqi, dangshen, shengma,baizhu, gaicao, etc., with 1.204 g raw drugs a milliliter. ③ 26 g/kg sijunzi decoction, which consisted of dangshen,baizhu, fuling, jiugancao, etc., was perfused into mice with the dosage of 0.5 mL/mouse in si junzi decoction group once a day. After 16 successive days, contents of DNA, RNA and protein were measured in spleen and kidney tissue; meanwhile, body mass, ratio between spleen mass and body mass, and ratio between kidney mass and body mass were also measured before modeling and after administration.MAIN OUTCOME MEASURES: ① Changes of body mass before modeling and at 16 days after administration; ② changes of mass of spleen and kidney tissues; ③ Comparisons of DNA, RNA and protein in spleen and kidney tissues at 16 days after administration.RESULTS: All 180 mice were involved in the final analysis without any loss. ① There was no significant difference of body mass (17.4-21 g) among groups before experiment (P =0.993); however, after experiment, body mass in model group was lower than that in normal control group (Q =22.84, P < 0.01); 16 days after administration, body mass was higher in qiangji jianli liquid groups (26 g/kg, 13 g/kg) and sijunzi decoction group than that in model group (Q =8.66-10.24, P < 0.01). ② Values of spleen mass/body mass and kidney mass/body mass were decreased in model group as compared with those in normal control group (Q =4.02-12.93, P < 0.01); masses of spleen and kidney tissues were increased in qiangji jianli liquid groups (26 g/kg, 13 g/kg) and sijunzi decoction group as compared with those in model group (Q =3.21-9.69, P < 0.05-0.01); ratios in 13 g/kg qiangji jianli liquid group were higher than those in model group (Q =4.07, 5.92; P < 0.05, 0.01). ③ Contents of DNA, RNA and protein in spleen tissue and contents of RNA and protein in kidney tissue were lower in model group than those in normal control group (Q =7.15-19.2, P< 0.01); however, content of DNA in kidney tissue was higher in model group than that in normal control group (Q =4.19, P < 0.05). Contents of DNA, RNA and protein in spleen tissue and contents of RNA and protein in kidney tissue were higher in 26 g/kg qiangji jianli liquid group and sijunzi decoction group than those in model group (Q =2.91-14.12, P < 0.05-0.01 ).CONCLUSION: Qiangji jianli liquid can accelerate synthesis of nucleic acid and protein; additionally, onset of spleen deficiency syndrome may be related to decreasing synthesis of nucleic acid and protein.
4.Comparison of initiation of antihypertensive therapy strategies for primary preven-tion of cardiovascular diseases in Chinese population:A decision-analytic Markov modelling study
Tianjing ZHOU ; Qiuping LIU ; Minglu ZHANG ; Xiaofei LIU ; Jiali KANG ; Peng SHEN ; Hongbo LIN ; Xun TANG ; Pei GAO
Journal of Peking University(Health Sciences) 2024;56(3):441-447
Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10%based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95%UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95%UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95%UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95%UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95%UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95%UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.
5.Identification and clinical transfusion of B (A) subgroup
Jun MIAO ; Minglu GENG ; Janbin LI ; Xiaoli MA ; Hecai YANG ; Liping WANG ; Dan LIU ; Ke ZHANG ; Chuan ZHOU ; Junjie CHENG
Chinese Journal of Blood Transfusion 2023;36(11):1012-1014
【Objective】 To carry out serological and molecular biological identification of B (A) subtype, and discuss the rational blood transfusion strategy. 【Methods】 Serological and direct sequencing methods were used to detect serotype and genotype of 7 cases of B (A) subtype, and cross matching was performed by saline medium and anti human globulin card to analyze the red blood cells(RBCs) transfusion strategy. 【Results】 The serology results of blood type of 7 samples were similar, with B(A)04/O01 in 3 cases, B(A)04/O02 in 2 cases and B(A)02/O01 in 2 cases. 7 cases of B (A) subtypes were matched with randomly selected blood donors of type O and B on the major side. 【Conclusion】 B(A) subtypes should be identified by genotyping techniques. Washed RBCs of type B and O can be used for B(A) blood type transfusion.
6.Overcoming chemotherapy resistance simultaneous drug-efflux circumvention and mitochondrial targeting.
Minglu ZHOU ; Lijia LI ; Lian LI ; Xi LIN ; Fengling WANG ; Qiuyi LI ; Yuan HUANG
Acta Pharmaceutica Sinica B 2019;9(3):615-625
Multidrug resistance (MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here, based on the previous research of -(2-hydroxypropyl)methacrylamide (HPMA) polymer-drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin (Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide (MPP) and then attached to (HPMA) copolymers (P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species (ROS) as well as reduction of adenosine triphosphate (ATP) production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.
7.Immunogenic hydrogel toolkit disturbing residual tumor "seeds" and pre-metastatic "soil" for inhibition of postoperative tumor recurrence and metastasis.
Minglu ZHOU ; Qingting ZUO ; Yuan HUANG ; Lian LI
Acta Pharmaceutica Sinica B 2022;12(8):3383-3397
Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and once-for-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition, immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell "seeds" but also resulted in abscopal effect on disturbing pre-metastatic "soil". Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.