Clinical Observation on Effect of Shuanghuang Shengbai Granule (双黄升白冲剂) on Chemotherapy Induced Myelosuppression in Tumor Patients and on Ultrastructure of Bone Marrow in Mice

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叶绿酸铜钠对再生障碍性贫血小鼠间充质干细胞功能的影响

Objective: To investigate the effects of sodium copper chlorophyllin (SCC) on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells (MSCs) from mice with aplastic anemia. Methods: A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2×1000000 lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups: the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A (CsA); and an untreated model control group (model group); while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. Results: Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 (FOXP3+) T cells was increased in T cell-MSC cocultures, and the cytokine transforming growth factor β1 was up-regulated in SCC-treated groups. Conclusion : The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with aplastic anemia.     

小鼠骨髓移植修复卵巢功能损伤

目的研究骨髓移植对化疗引起的小鼠卵巢功能损伤的修复作用。方法 48只小鼠随机分为3组:正常对照组(A组)、化疗并骨髓移植组(B组)和化疗组(C组)。B、C组小鼠每天给予环磷酰胺150 mg/kg腹腔注射,连续3 d。1周后,对B组小鼠进行骨髓移植。给药起第21、50天分两批处死小鼠,称量卵巢、子宫湿重,观察卵巢组织学变化。用Hoechest33342荧光染料标记骨髓细胞,移植入预先注射环磷酰胺的小鼠体内,2 d后取小鼠卵巢做冰冻病理切片,荧光显微镜下观察。结果给药第21、50天,B组小鼠的卵巢系数、各级卵泡数目明显高于C组而低于A组,均具有统计学意义(P<0.05)。受体鼠的卵巢内发现显示荧光的供体鼠骨髓细胞。结论骨髓移植对化疗药物引起的卵巢功能损伤具有修复作用。     

Effect of esculetin on bone metabolism in ovariectomized rats

OBJECTIVE

To determine the effect of an esculetin formulation (at 97.4% purity) on osteoporosis, and to investigate the potential underlying molecular mechanism(s).

苦参素+山莨菪碱预防非小细胞肺癌化疗后骨髓毒性的研究

目的　探讨苦参素 +山莨菪碱预防非小细胞肺癌患者化疗后骨髓毒性的机理。方法　晚期非小细胞肺癌 39例 ,随机分为A组 2 5例 ,为治疗组 ;B组 1 4例 ,为对照组。 2组均用吡柔比星(THP) +异环磷酰胺 (IFO) +卡铂 (CBP)方案与卡铂 +依托泊苷方案交替化疗 ,治疗组在化疗同时加用苦参素 +山莨菪碱。 3周期后评价疗效和不良反应。结果　A组有效率为 68.0 % ,B组有效率为 57.1 % ,2组间疗效无显著性差异 (P >0 .0 5) ;A组与B组Ⅲ～Ⅳ级骨髓毒性发生率分别为 2 8.0 %和 42 .9% ,2组间有显著性差异 (P <0 .0 5)。心脏毒性发生率A组为 1例 ,为 1 3 .6 % ,B组未发生。结论　苦参素 +山莨菪碱能有效预防非小细胞肺癌化疗后的白细胞和血小板降低 ,能明显提高患者的生活质量     

Study on the effects of Guiqi Oral Liquid in promoting recovery of hematopoiesis in acute irradiation injured mice

Objective: To explore the effects and possible mechanisms of Guiqi Oral Liquid (GQOL) on the recovery of hematopoiesis in acute irradiation injured mice.Methods: The acute irradiation injured mice were randomly divided into 2 groups: the treated group and the control group, and also a normal control group was set up with 6 mice in it receiving no treatment. After the mice in the former two groups were irradiated by 6.0 Gy⁶⁰Coγ-ray, every one of them was given 0. 4 ml GQOL or saline in equal volume through a gastric tube twice a day for 14 days. On the 4th, 8th and 14th day after irradiation, the bone marrow mononuclear cells (BMMNC) and megakaryocytes in bone marrow tissues of the mice were counted, the proportion of hematopoietic tissues (by area) was measured, and the expression of adhesion molecules, CD44 and CD54, in bone marrow were estimated by immunochemistry. The colony forming unit of spleen (CFU-S) in the mice were counted on the 8th day after irradiation.Results: On the 4th, 8th, 14th day after irradiation, the count of BMMNC and megakaryocyte, and the proportion of hematopoietic tissues in the treated group were higher than those in the control group (P<0.01 orP<0.05). CD44 and CD54 expression in the treated group were higher than those in the control group on the 4th and 8th day (P<0.01), but near normal on the 14th day (P<0.01). On the 8th day, CFU-S count in the treated group was higher than that in the control group (P<0.01).Conclusion: GQOL can regulate the expression of adhesion molecules, CD44 and CD54, in the bone marrow of the acute irradiation injured mice, which may be one of the mechanisms of GQOL in accelerating the early phase hematopoiesis recovery of mice. Supported by the National Natural Science Foundation of China (No. 39870926)     

氧化型染发剂对小鼠精子畸形和骨髓细胞微核的影响

目的探讨氧化型染发剂对小鼠精子畸形和骨髓嗜多染红细胞(PCE)微核的影响。方法将40只成年健康昆明种雄性小鼠随机分为染发剂A组、染发剂B组、染发剂C组和对照组,每组10只。3个染发剂组用氧化型染发剂染毒,每隔2d经皮染毒1次,连续染毒7次,于首次染毒后35d处死小鼠,检测精子畸形率及骨髓微核率。结果各染发剂组精子畸形率均高于对照组(P<0.008);各染发剂组小鼠精子畸形率比较差别均无统计学意义(P>0.008)。染发剂A组小鼠骨髓PCE细胞微核率变化与对照组比较差别无统计学意义(P>0.008);染发剂B组和染发剂C组小鼠骨髓PCE细胞微核率均高于对照组,差别有统计学意义(P<0.008);染发剂B组和染发剂C组骨髓细胞微核率高于染发剂A组,差别有统计学意义(P<0.008);染发剂B组与染发剂C组骨髓细胞微核率比较差别无统计学意义(P>0.008)。结论氧化型染发剂可导致小鼠精子畸形和骨髓微核率的升高,对使用者的健康存在潜在危害。     

Effect of Compound Zhebei Granule(复方浙贝颗粒)Combined with Chemotherapy on Surface Markers of Leukemia Stem Cell in Patients with Acute Myeloid Leukemia

Objective: To observe the effects of Compound Zhebei Granule(复方浙贝颗粒, CZBG) combined with chemotherapy on surface markers of leukemia stem cell(LSC) in the bone marrow of patients with acute myeloid leukemia(AML). Methods: Seventy-eight patients with AML received bone marrow aspiration and the percentages of CD34~+CD123~+ and CD33~+CD123~+ cells were tested using flow cytometry method. A total of 24 refractory or relapsed AML patients were enrolled and treated with one cycle of standard chemotherapy combined with CZBG. Bone marrow samples were obtained before and after treatment, and the percentages of CD34~+CD123~+ and CD33~+CD123~+ cells were examined by flow cytometry. Results: Compared with refractory or relapsed AML patients, patients achieved remission had a significant lower percentage of CD34~+CD123~+ cells(P0.01) and CD33~+CD123~+ cells(P0.01), indicating that controlling the LSC percentage may be important for patients with AML to achieve sustainable remission. Compared with those before treatment, the expression levels of CD34~+CD123~+ were significantly decreased after CZBG combined with chemotherapy treatment(P0.01). The percentages of CD34~+CD123~+ cells and CD33~+CD123~+ in patients achieving complete remission after CZBG combined with chemotherapy treatment were both significantly lower than those in patients with nonremission(P0.01). Conclusion: CZBG combining chemotherapy could reduce the percentages of CD34~+CD123~+ and CD33~+CD123~+ LSC, which might improve the clinical efficacy of refractory or relapsed AML.     

Clinical and experimental study on prevention and treatment of acute radiation injury in nasopharyngeal carcinoma patients by Yiqi Huoxue Yangyin recipe

Objective

To observe the effect of Chinese herbal medicine in alleviating acute toxic-adverse effect of radiotherapy and on growth of stromal cells in bone marrow.

Methods

Seventy-two patients with nasopharyngeal carcinoma (NPC) were randomly divided into two groups. Radical radiotherapy was applied to both groups. In the radiotherapeutic period, to the 36 patients in the treated group, Yiqi Huoxue Yangyin Recipe (YHYR) was given additionally by oral taking and compressing on radiation area, and to the 36 patients in the control group, vitamin B12 solution was given for gargling or compressing. Experimental study was carried out in rats of two groups, irradiated with 5.0 Gy X-ray and treated with YHYR or normal saline intraperitoneally, to observe the colony forming unit-fibroblastoid (CFU-F) in cultured bone marrow stromal cells (BMSC), taken from the rats at different time.

Results

The oral mucomembranous radiation damage occurred in 47.2% of the treated group when the dose of radiation reached to 41.4 ±9.4 Gy, while in the control group, it was 91.7% when the dose reached to 30. 9±8.9 Gy. The skin radiation damage occurrence rate in the two groups was 13.9% and 33.3% respectively when the dose of radiation reached to 50.2±5.6 Gy and 43.2±6.3 Gy respectively. Comparison of the two groups showed significant difference (P<0.01), the radiation damage was significantly slighter in the treated group. Experimental study showed that the rats in the two groups were significantly different in occurrence and degree of bone marrow function inhibition,P<0.01. The numbers of CFU-F in cultured BMSC of radiation damaged rats taken at respective different culture time were also significantly different between the two groups,P<0.01.

Conclusion

YHYR could significantly reduce acute radiation damage of mucomembrane and skin, alleviate the inhibition on bone marrow function, and eliminate the injury of radiation on BMSC.     

剔除CCR5基因供者小鼠细胞加重急性移植物抗宿主疾病

目的评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为异基因造血干细胞移植的临床应用提供科学依据。方法经过致死剂量照射的BALB/C小鼠接受异基因C57BL/6小鼠骨髓移植。根据回输的细胞不同分为4组:1)B6 CCR5 KO组,受者接受C57BL/6 CCR5-/-小鼠骨髓和脾脏细胞;2)B6 WT组,受者接受野生型C57BL/6小鼠骨髓和脾脏细胞;3)B6 CCR5 KO BMC组,受者只接受C57BL/6 CCR5-/-小鼠骨髓细胞;4)B6 WT BMC组,受者只接受野生型C57BL/6小鼠骨髓细胞。结果与B6 WT组比较,B6 CCR5 KO组小鼠以更快的速度死于急性移植物抗宿主疾病(GVHD);其受者体内的CD8+T细胞大量增生;T细胞恢复后产生更多的干扰素-γ(INF-γ)和肿瘤坏死因子-α(TNF-α),T细胞有丝分裂原刀豆素水平处于较高水平,进一步促进T细胞增生。组织学检测提示移植剔除CCR5基因受者细胞的小鼠肾脏出现病理损伤,肝脏存在更为严重的病理变化。结论剔除CCR5基因的异基因骨髓移植使GVHD发病率增加,供者CD8+T细胞在受者体内增生加重肝肾损害。提示CCR5在异基因骨髓移植中起着重要作用。     

The Effects of Ligustrazine on the Expression of bFGF and bFGFR in Bone Marrow in Radiation Injured Mice

Thebonemarrowhematopoiesisinductivemi croenvironmentismadeupofstromalcells ,extracel lularmatrixandmicrangiumsystem .Micrangiumsystemisanimportant partinthebonemarrowhematopoiesisinductivemicroenvironment .Bonemarrowisoneoforganswhicharesensitivetoradia tion .Basicfibroblastgrowthfactor (bFGF)isasin glechain peptide[1] ,whichincludes 15 4aminoacids[2 ] .bFGFbindstoitsspecificreceptor(bFGFR) ,whichstimulatestheproliferationandim migrationofendothelialcells .Itplaysanimportantroleintheembryo…     

GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis

Background

The cytokine growth differentiation factor-15 (GDF-15), a member of the TGF beta superfamily, has recently been discovered to play an important role in cardiovascular diseases. It is mostly expressed in macrophages of atherosclerotic lesions, but its impact on advanced atherosclerosis is still unknown. This study was performed to evaluate the effects of GDF-15 in an established mouse model of advanced atherosclerosis.

Methods

Thirty-eight LDL receptor deficient mice received a lethal body radiation. Half of the group was transplanted with bone marrow of GDF-15 deficient mice. Nineteen mice were transplanted with bone marrow from wild-type controls. After 24 weeks on an atherogenic diet, animals were euthanized and sections of the aortic sinus were prepared. Lesion size and lesion composition, as well as macrophage content,were evaluated.

Results

While demonstrating no difference in lesion size, LDL-receptor knockout mice transplanted with bone marrow from GDF-15 deficient mice showed enhanced macrophage accumulation and features of atherosclerotic plaque destabilization, such as thinning of fibrous caps. Immunostaining against intercellular adhesion molecule-1 further revealed an increased expression in mice receiving GDF-15-deficient bone marrow.

Conclusions

This is the first study that demonstrates a protective role of GDF-15 in advanced atherosclerosis and macrophage accumulation, possibly due to the reduced expression of adhesion molecules.     

脾多肽对化疗所致血小板减少症雌鼠的疗效及促血小板生成的机制研究

目的 研究脾多肽注射液对化疗所致血小板减少症的作用及其血小板生成机制。方法 将85只健康昆明雌鼠随机分为正常组、模型组、重组人血小板生成素（rhTPO）阳性对照组、脾多肽注射液低剂量组、脾多肽注射液高剂量组。模型组、给药组第1天单次腹腔注射70 mg/ kg 卡铂复制血小板减少症模型，正常组注射生理盐水。第2天起，不同药物连续干预15 d，并于化疗前以及化疗后第2～16天隔天尾部取血计数血小板；化疗后第8天采用瑞氏-吉姆萨染色骨髓巨核细胞，显微镜观察其形态和数量，采用流式细胞术检测骨髓巨核细胞百分率，酶联免疫吸附试验检测血清干细胞因子（SCF）、促血小板生成素（TPO）水平。结果 各组雌鼠化疗前及化疗后2 d、4 d、6 d、8 d、10 d、12 d、14 d、16 d血小板计数比较，经重复测量设计的方差分析，结果 ①不同时间点血小板计数变化有差异（F =22.413，P =0.000）；②各组血小板计数有差异（F =6.822，P =0.006）；③各组血小板计数变化趋势有差异（F =6.326，P =0.008）。镜下观察巨核细胞细胞核及胞体较其他细胞大，且随着巨核细胞的成熟，核多为不规则形态，胞质愈丰富。细胞染色后，深紫色部分为核，浅紫色部分为胞质。模型组骨髓巨核细胞数量和百分率低于正常组（P <0.05），rhTPO阳性对照组高于模型组（P <0.05），脾多肽注射液高剂量组高于模型组（P <0.05）。模型组SCF、rhTPO水平高于正常组（P <0.05），脾多肽注射液高剂量组SCF水平低于模型组（P <0.05），rhTPO阳性对照组rhTPO水平低于模型组（P <0.05）。结论 60 mg/（kg·d）脾多肽注射液能有效改善卡铂化疗所致雌鼠血小板减少症，可能与调节血清SCF因子恢复至正常水平及上调骨髓巨核细胞数量有关。     

Histopathological studies of acute and chronic effects of Calliandra portoricensis leaf extract on the stomach and pancreas of adult Swiss albino mice

Objective

To evaluate the consequence of oral administration of Calliandra portoricensis (C. portoricensis) leaf extract on the stomach and pancreas in Swiss albino mice.

Methods

Three groups of mice (B, C and D) were treated with 4 mg/kg of C. portoricensis extract. Group A was the control and received an equivalent volume of distilled water. Group B received C. portoricensis leaf extract for 7 days, Group C received C. portoricensis leaf extract for 14 days, and Group D received C. portoricensis leaf extract for 28 days. At different stages in the study, the mice were sacrificed and the stomach and pancreas were excised and fixed in 10% formol saline for histological analysis.

Results

The result showed a normal microstructural outline in groups B and C as compared with the control. However, animals in group D showed disorganization of the mucosa and discontinuation of epithelial lining of the stomach while the islets of Langerans in the pancreas were at various degree of degeneration as compared with the control mice.

Conclusions

The present finding suggests that chronic administration (28 days as seen in this study) of C. portoricensis leaf extract may inhibit the proper function of the stomach and pancreas.     

中医药在治疗癌性疼痛中的研究进展*

随着社会的进步,人们生活水平的提高,饮食结构的变化,糖尿病的发病率也逐年升高,据统计中国已成为全球糖尿病第2大国,目前约有糖尿病患者3 000万,患病率为2%至4%,其中2型糖尿病患者占绝大多数。在最近20年中,中国糖尿病发病率增     

Bailong tablet and chemotherapy in the treatment of moderate and advanced cancersand chemotherapy in the treatment of moderate and advanced cancers

Objective: To determine the effectiveness of Bailong Tablet and chemotherapy on treatment of moderate and advanced cancers.Methods: The patients were divided randomly into two groups. The treated group (n= 41) was treated with chemotherapy plus Bailong Tablet; and the control group (n= 22) treated with chemotherapy alone. Treatment effectiveness was measured with Karnofsky scores.Results: Karnofsky performance status in the treated group before and after treatment was 66.0 ± 8.7 and 68.0 ± 5.9 respectively, that in the control group was 67. 0 ± 6.8 and 53. 0 ± 7.3 respectively. The completion rate of chemotherapy in the treated group (92.6%, 38/41) was higher than that in control (77.2%, 17/22,P < 0.05). The side-effects caused by chemotherapy in the treated group were lower than that in the control group (P < 0.05). CD₃ ⁺, CD₄ ⁺ and CD₄ ⁺ /CD₈ ⁺ ratio were higher in the treated group.Conclusion: Bailong Tablet can enhance the therapeutic effect and reduce the side-effects of chemotherapy. One possible mechanism is the modulation of cellular immune function.     

Evaluation of epirubicin-induced cardiotoxicity by two-dimensional strain echocardiography in breast cancer patients

The value of two-dimensional strain echocardiography for assessing left ventricular regional systolic function in breast cancer patients who were treated with epirubicin was evaluated. A total of 116 breast cancer patients were divided into 3 groups： Thirty-eight patients in group A were given epirubicin （Epi） of 120-340 mg/m^2, 42 patients in group B received epimbicin of≥ 360 mg/m^2, and 36 patients after surging without chemotherapy served as the control group C. High frame rate two-dimensional images were recorded from apical long-axis view, four-chamber view, two-chamber view of left ventricle. Peak systolic strain of left ventricular subendocardial myocardium was measured using two-dimensional strain software. The conventional echocardiographic parameters were also obtained. Conventional echocardiography showed there was no significant changes in conventional echocardiographic parameters among the three groups （P〉0.05）. Two-dimensional strain echocardiography revealed that the peak systolic strain of left ventricular subendocardial myocardium in group A was reduced in some segments as compared with the controls （P〈0.05）. The peak systolic strain of left ventricular subendocardial myocardium in group B was reduced significantly as com- pared with group C （P〈0.05）, but that was reduced in group B just in some of the segments as compared with group A （P〈0.05）. It was concluded that two-dimensional strain echocardiography could early and sensitively display the effects of epirubicin-induced cardiotoxicity on the systolic function of left ventricular subendocardial myocardium, and early monitor the epirubicin-induced cardiotoxicity.     

中药穴位贴敷联合西药化疗治疗初治肺结核的临床疗效观察

目的:通过中药穴位贴敷联合西药化疗干预,评价穴位贴敷疗法在初治肺结核治疗中的有效性及协同作用、安全性。方法:将100例初治肺结核患者随机分为对照组和观察组,对照组予异烟肼联合利福平、吡嗪酰胺及乙胺丁醇常规化疗,观察组在西药化疗基础上联用中药穴位贴敷治疗,两组患者均连续治疗8周(强化期)。观察治疗前后的临床症状改善情况,并评价临床疗效;检测外周血CD4~+T及CD8~+T细胞绝对数改变,记录外敷的不良反应情况。结果:治疗后,两组患者的中医临床症状均得到明显改善,且观察组的症候疗效优于对照组(P0.05);两组患者治疗后的CD4~+T细胞绝对数均显著增加、CD8~+T细胞绝对数显著减低(P0.05),且观察组的改变明显大于对照组(P0.05)。未发现皮肤有明显的不良反应。结论:中药穴位贴敷联合常规西药化疗可有效改善初治肺结核患者的临床症状,改善细胞免疫状态,且安全有效。     

Clinical and experimental study on Fuzheng Baozhen Decoction () in enhancing effect of radio- and chemotherapy for malignant tumors) in enhancing effect of radio- and chemotherapy for malignant tumors

Objective: To study on Fuzheng Baozhen Decoction (FZBZD) enhancing effect of radio- and chemotherapy for malignant tumors. Methods: One hundred and Seventeen cases of malignant tumors treated with chemotherapy or/and radiotherapy. Among them 55 cases were treated together with FZBZD (group A), 30 cases together with Zhenqi Fuzheng Granules (group B), and the other 32 cases treated with radio- and chemotherapy alone (group C). Mechanism of FZBZD enhancing effect of chemotherapy in treating transplanted human lung adenocarcinoma (SPC-A-1) and sarcoma (S₁₈₀) bearing mice was conducted experimentally. Results: Effective rates (CR+PR) of group A, B and C were 63.6%, 43.3% and 37.5% respectively, that of group A being the best (P < 0.05). The survival quality of life was improved the most in group A (P < 0.05). The picture of peripheral blood (WBC, Hb, PLT count) of group A after treatment was better than that of the other two groups (P < 0.05). And CD3, CD4, NK activity, interleukin-2 levels were also improved more significantly in group A (P < 0.01) than those in the other two. Animal experiment showed that FZBZD could improve the effect of chemotherapy in inhibiting tumor growth (P < 0.01), raising cAMP/cGMP ratio (P < 0. 01) by increasing the cAMP level in cancer tissue, and enhancing cells ofG0/G1 phase and reducing cells of S phase. Conclusion: FZBZD inhibited tumor growth and enhanced the effect of radio- and chemotherapy by improving immune and hematopoietic function, cAMP/cGMP ratio and halting tumor cells in G₀/G₁ phase.     

参芪扶正注射液对化疗后小鼠造血功能影响的实验研究

目的 探讨参芪扶正注射液对化疗后小鼠造血功能的影响.方法 用5-氟尿嘧啶（5-FU）225 mg/kg腹腔注射复制骨髓抑制动物模型,治疗组给予参芪扶正注射液5 ml/kg,对照组给予同剂量生理盐水.治疗1周后,做血细胞计数、各系造血祖细胞集落（CFU-GM、CFU-E、CFU-MK）培养和骨髓病理检查.结果 参芪扶正注射液能升高外周血细胞计数：治疗组小鼠外周血的红细胞、白细胞和血小板计数均高于对照组（P〈0.05）.促进造血祖细胞增殖：治疗组小鼠的CFU-GM、CFU-E、CFU-MK集落数均大于对照组（P〈0.05）.改善骨髓抑制：骨髓病理检查对照组出现大片空白区,造血细胞稀少,而治疗组造血组织结构较完整,造血细胞量丰富.结论 化疗后小鼠在骨髓抑制、造血功能低下时,参芪扶正注射液能通过促进骨髓各系造血祖细胞的增殖,改善骨髓造血组织增生,从而促进血细胞的生成.