Protective effect of Epothilone D against traumatic optic nerve injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats.@*METHODS@#Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve.@*RESULTS@#In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment.@*CONCLUSION@#Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.

Research progress on anti-tumor activity of curcumol and its derivatives / 中草药

Curcumol, as an important component of Curcuma Rhizoma, has anti-virus, anti-inflammatory, anti-tumor and other pharmacological activities, which has attracted more and more attentions in anti-tumor research area. The progress on the natural source, anti-tumor mechanism, structural modification, and anti-tumor evaluation of curcumol are reviewed in this paper, which will provide a novel strategy for its further structural optimization.

Distinct Rab7-related Endosomal-Autophagic-Lysosomal Dysregulation Observed in Cortex and Hippocampus in APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction.</p><p><b>METHODS</b>We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis. To further explore the mechanism of EAL dysregulation in AD, components of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, activators of Rab7 (Beclin1 and UVRAG), and the negative regulator of Rab7 (Rubicon) were also measured in this two brain regions.</p><p><b>RESULTS</b>In 7-month-old APP/PS1 brain that amyloid beta initiated to accumulate intracellularly, EAL pathway, and related PI3KC3 members, UVRAG and Beclin1 were upregulated both in cortex and hippocampus (all P < 0.05). By the age of 12 months old, when abundant amyloid plaques formed, EAL markers, UVRAG, and Beclin1 were also upregulated in the cortex (all P < 0.05). However, Rab7 was decreased significantly (P = 0.0447), accompanied by a reduction of its activating PI3KC complex component Beclin1 (P = 0.0215) and enhancement of its inhibiting component Rubicon (P = 0.0055) in the hippocampus.</p><p><b>CONCLUSIONS</b>Our study implies that EAL pathway, represented as Rab7 and its PI3KC3 regulators' expressions, showed temporal and spatial variation in brains at different stages of AD. It provides new insights into the role of EAL pathway in pathogenesis and indicates potential therapeutic targets in neurodegenerative diseases.</p>

Reduction of ADRs of essential traditional Chinese medicines / 中国中药杂志

The essential traditional Chinese medicines (ETCM) are the characteristics of our National Essential Medicine List (NEML) and we should give full play to its unique advantage. The essential medicines of ETCM are specific, but also have dual characters, namely efficacy and ADRs. Although ADRs cannot be avoided, we can make efforts to control some conditions to minimize the possibility of ADRs. It is significant to give suggestions to reduce ADRs of ETCM under the ETCM system by analyzing the possibility of ADRs during ETCM selection, production distribution and use. This research focuses on ETCM, and the conclusion is also applicable to common traditional Chinese medicines.

Suggestions to strengthen quality management of herbal decoction pieces--based on production chain of herbal decoction pieces / 中国中药杂志

With the development of society and the improvement of people's living standards, the effect of Chinese medicine in treatment and health care is more and more prominent. The herbal decoction pieces are the important part of Chinese medicine,it can be applied directly to clinical treatment and it's also the raw material of Chinese patent medicine. Therefore, the quality of herbal decoction pieces is quite important. The parts of the production of herbal decoction pieces are numerous, and there are possibilities of adverse effects on the quality of the herbal decoction pieces in every part. In this paper, we based on the production chain of herbal decoction pieces, analyzed the main problem that affect the quality of herbal decoction pieces in the part of selection of Chinese herbal medicines, planting, purchasing, processing, packaging, storage and transport, such as the poor quality of seed and seedlings of plant-based Chinese medicines, some plants left their place of origin and have been introduced in the place that is not suitable for this kind of plant, the insufficient growth time and the excessive harmful substances. The purchasers and the accepters lack of professional knowledge and professional ethics. The mechanism of processing is not clear, the standards can not be uniformed, and lack of qualified person in processing, etc. So we suggest: intensify the basic research of key scientific issues. Improve the quality of persons who work in herbal decoction pieces; Establish an "integration" mode of operation in herbal decoction pieces enterprise; Breeding high quality plant resources, establish the large-scale planting basement; Make the packing of herbal decoction pieces standard; Establish the modernization traditional Chinese medicine logistics enterprise.

Clinical observation of S-1 combined with γ-ray stereotactic body radiation therapy in treatment of locally advanced pancreatic cancer / 肿瘤研究与临床

Objective To evaluate the clinical toxicity and efficacy of S-1 combined with γ-ray body stereotactic radiation therapy in treatment of locally advanced pancreatic cancer.Methods Forty-five patients with locally advanced pancreatic cancer were randomly divided into two groups.The combination group received γ-ray stereotactic body radiation therapy which was given isodose curve of 50 ％-60 ％,tumor encircling dose of 3.0-4.5 Gy per fraction depended on dimension of tumors,9-12 fractions.Combined with S-1 40 mg/m2,2 times/d,for consecutive twenty-one days for four courses.The control group was given γ-ray stereotactic body radiation therapy only.Toxicities and effects were evaluated according to the criteria of WHO and RTOG.Results The CR rates in combination group and control group were 30.4 ％ (7/23) and 13.6 ％ (3/22),the response rates were 91.3 ％ (21/23) and 63.6 ％ (14/22) (x2 =4.980,P =0.026).The rates of gastrointestinal tract side reaction in combination group and control group were 82.6 ％ and 68.2 ％ (x2 =1.267,P =0.260),myelosuppression in combination group and control group were 78.3 ％ and 63.6 ％ (x2 =1.171,P =0.279).The rate of Ⅲ-Ⅳ grade myelosuppression in combination group were higher than that in control group (x2 =4.874,P =0.027).The median progression-free survival (PFS) rates of two groups were 8 months and 6 months respectively (x2 =1.357,P ＞ 0.05),the median survival period were 17 months and 14 months (x2 =1.017,P ＞ 0.05),1 year survival rates were 60.9 ％ and 54.5 ％ respectively (x2 =0.184,P ＞ 0.05).Conclusions S-1 combined with body gamma system treatment can improve local control rate and effective rate for inoperable patients with local advanced pancreatic carcinoma,and the adverse reactions are well tolerated.This method can be used as locally advanced pancreatic cancer chemoradiation safe and effective choice.

Efficacy of stereotactic body radiation therapy with γ-knife combined with hyperthermia and targeted drug sorafenib for the treatment of recurrent and metastatic hepatocellular carcinoma / 中国肿瘤临床

Objective:To investigate the efficacy of stereotactic body radiation therapy with gamma-knife (γ-SBRT) combined with targeted drug sorafenib and hyperthermia for the treatment of recurrent and metastatic hepatocellular carcinoma. Methods:A total of 71 patients with recurrent and metastatic hepatocellular carcinoma were admitted from August 2007 to December 2009. Among these patients, 39 were treated with γ-SBRT and hyperthermia (group 1); 19 were treated with γ-SBRT combined with sorafenib and hyperthermia (group 2). Results: The total efficacy rate after a three-month treatment was 83.1% (59/71). In group 1, the following results were obtained:one-and three-year local control rates of 41.0%(16/39) and 18%(7/39), respectively;one-and three-year overall survival (OS) rates of 41.2% and 17.9%, respectively; and one- and three-year progression-free survival (PFS) rates of 38.4% and 15.4%, respectively. In group 2, the following results were obtained:one-and three-year local rates of 56.3%(18/32) and 28.1%(9/32), respectively;one-and three-year OS rates of 62.5%and 28.1%, respectively;and one-and three-year PFS rates of 59.4%and 25.0%, respectively. Significant differences in OS and PFS were observed between the two groups. Conclusion:The combination ofγ-SBRT with targeted drug sorafenib and hyperthermia can be used effectively to treat recurrent and metastatic hepatocellular carcinoma. Adverse reactions are mild, and patients can tolerate this treatment.

Investigation on situation of cervical intraepithelial neoplasia and cervial cancer among rural women in Qianjiang district of Chongqing city / 重庆医学

Objective To investigate the prevalence and the distribution in population of cervical intraepithelial neoplasia (CIN) and cervical cancer among rural women in Qianjiang district of Chongqing city .Methods From April 2010 to April 2012 ,25 128 married rural women in Qianjiang district were performed screening and detection .The individuals with the positive results were performed the colposcopy and cervical biopsy .Results 112 cases were found with the positive results of the pathological examina-tion ,including 58 cases of CINⅠ ,26 cases of CINⅡ ,19 cases of CINⅢ and carcinoma in situ and 9 cases of invasive carcinoma .The incidence rate of CIN and cervical cancer in Tujia nationality women was significantly higher than that in Han nationality women and Miao nationality women .Conclusion The cervical cancer screening is an important way to find early pathological lesions of cer-vical cancer and prevent cervical cancer ,and is the necessary measure to reduce the incidence rate of cervical cancer in rural women .

Different times and procedures of postoperative radiation and chemotherapy affecting treatment efficacy of high-grade gliomas / 中华神经医学杂志

Objective To investigate effects of different times and procedures of postoperative radiation and chemotherapy on treatment efficacy of high-grade gliomas.Methods A prospective clinical trial was conducted in 71 patients with high-grade gliomas (HGG); they were separated randomly into two groups:one group including 39 patients received chemo-radiotherapy and adjuvant chemotherapy sequentially (RC+C) and the other group including 32 patients received neo-adjuvant chemotherapy and chemo-radiotherapy and adjuvant chemotherapy sequentially (C+RC+C).The clinical benefit rate (CBP),progression free survival (PFS) and overall survival (OS) were followed up after the treatment.Results No significant difference on CBP 5 months after treatment was noted between the two groups (P＞0.05),but the CBP in the C+RC+C group (87.5％) was significantly higher than that in the RC+C group (66.7％)8 months after treatment (P＜0.05).No significant difference on OS was noted between the two groups.The median PFS of patients in C+RC+C group was 11.5 months while that in the RC+C group was 8.6 months; the PFS of patients in C+RC+C group was significantly longer that in the RC+C group (P＜0.05).Conclusion Procedure of C+RC+C can prolong the PFS of patients with HGG.

Hypoxia can induce EMT and promote invasion of breast cancer cells / 肿瘤研究与临床

Objective To study the effect of hypoxia on EMT molecule E-cadherin, Vimentin and invasion of human breast cancer MCF-7 cells, reveal the mechanism of breast cancer invasion and metastasis and provide experimental and theoretical basis. Methods Western blot was used to observe the change of HIF-1α, E-cadherin and Vimeutin during hypoxia on MCF-7. MTT was used to study the effects of viability.Transwell chamber was used to detect the ability of invasion and metastasis. Results The expression of E-cadherin was significantly lower (0.09±0.02)(t=30.98,P=0.0007) and the expression of Vimentin was significantly higher (0.69±0.04) (t=915,P=0.0000) with the extension of hypoxia.The capability of adhesion (81.23±0.74) (t=82.05,P=0.000),invasion(120±6) (t=22.78,P=0.0009) and migration(190±6) (t=23.49,P=0.000)was significantly increased after 72 h hypoxia(P＜0.05).Conclusion Hypoxia can downregulate E-cadherin and upregulate Vimentin and enhance the adhesion,invasion and migration of MCF-7.

Strategy of anti-angiogenesis and antiangiogenic drugs in NSCLC / 国际肿瘤学杂志

Development and metastasis of NSCLC are closely related to angiogenesis.Several distinct groups of vascular-targeted therapies have evolved:anti-VEGF monoclonal antibody,small molecules inhibitors,vascular disrupting agents,endothelial cell growth inhibitors,et al.Antiangiogenic treatment could make longer survival than conventional treatment.The strategy of anti-angiogenic drugs combined conventional treatment is being studied.

Safety and efficacy of three-dimensional conformal radiotherapy combined with temozolomide in treatment of diffuse brainstem gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the safety and efficacy of three-dimensional conformal radiotherapy in combination with temozolomide in treatment of patients with diffuse brainstem glioma.</p><p><b>METHODS</b>Twelve patients with MRI-confirmed diffuse brainstem glioma received 54 Gy three-dimensional conformal radiotherapy for 6 weeks with 1.8 Gy per fraction, 5 times per week. All of the patients were given daily oral temozolomide 75 mg/m(2) during radiotherapy. Four weeks after radiotherapy, all of the patients received 6 cycles of temozolomide, each cycle lasted 5 days with 28 days interval between each two cycles. 150 mg/m(2) of temozolomide was given for the first cycle for five days, followed by 200 mg/m(2) of the drug for the rest of the cycles if no significant drug-related toxicities were observed. Magnetic resonance imaging and laboratory tests were performed to evaluate the efficacy and adverse reactions.</p><p><b>RESULTS</b>In the 12 patients, CR was 1 case (8.3%), PR 6 cases (50.0%), SD 2 cases (16.7%), and PD 3 cases (25.0%). The overall clinical benefit rate was 75.0%. Progression-free survival rate was 75.0% (9/12) at 6 months and 50.0% (6/12) at 1 year. The one-year overall survival rate was 75.0%. There were no severe temozolomide-related toxicities.</p><p><b>CONCLUSIONS</b>Concurrent temozolomide with three-dimensional conformal radiotherapy and followed by 6 cycles of temozolomide chemotherapy for diffuse brainstem gliomas have a better clinical efficacy, good tolerance and with no severe toxicities.</p>

Postoperative concurrent chemoradiotherapy for high-grade cerebral glioma / 中华神经医学杂志

Objective To study the efficacy and security of postoperative radiotherapy alone and post-operative radiotherapy combined with chemotherapy in patients with high-grade cerebral glioma.Methods Fifty-nine patients with high-grade cerebral glioma confirmed by pathology, including 35 with grade Ⅲ and 24 with grade Ⅳ, admitted to our hospital from June 2004 to June 2008, were chosen in our study; these patients were randomly divided into 3 groups (A, B and C). All the patients underwent three-dimensional conformal radiation therapy (3D-CRT) with a dose of 54-66Gy/27-33f/5-7w by 6/10MV-X ray; and the median total dose was 60 Gy; group A (n=21, including 13 with grade Ⅲ and 8with grade Ⅳ) received chemotherapy with termozolomide (TMZ) at a dosage of 75 mg/m2·d during radiotherapy, following by 150-200 mg/ (m2·d) for 5 d, and enjoying 28 d per cycle for a total of 3-5cycles; group B (n=26, including 14 with grade Ⅲ and 12 with grade Ⅳ) received chemotherapy with the regimen of nimustine (ACNU) with a dosage of 90 mg/m2 on the 1st d and teniposide (VM-26) at a dosage of 60 mg/m2 on the 1st, 2nd and 3rd d, enjoying 6-8 weeks per cycle for a total of 4-6 cycles; group C (n=12,including 8 with grade Ⅲ and 4 with grade Ⅳ) received radiotherapy alone. Clinical evaluations of tumor response and adverse effects were performed periodically. The primary end points were disease progression-flee survival (PFS) and overall survival (OS) Results The effective rate in the group A, B and C was 81.0％, 71.4％ and 33.3％, respectively, indicating that significant differences exited between group C and both group A and B (P＜0.05). The incidence of gastrointestinal side effects and toxic response in the group B was obviously higher than that in the group A (P＜0.05). The 1-, 3- and 5-year survival rates in group A were 66.7％, 19.0％ and 9.5％, respectively, which were the highest among the 3groups; those in group B were 53.8％, 15.4％ and 3.8％, respectively; those in group C were 25％, 8％ and 0％, respectively. The PFS in all the patients was 8 months and OS was 15 months; log-rank test indicated that significant differences of PFS and OS existed between patients received concomitant chemoradiotherapy and radiotherapy (X2=10.710, P=0.005; X2=7.185, P=0.028); the incidence of PFS and OS in group A and B was significantly higher than that in group C (P＜0.05). Conclusion To post-operative patients with high-grade cerebral glioma, concomitant chemoradiotherapy can improve the effective rate and extend the PFS and OS. TMZ is recommended as the concomitant chemotherapy regimen, having similar therapy effect with ACNU plus VM-26, but enjoying less adverse effects.

In Vivo Kinetics and Biodistribution of a Hantaan Virus DNA Vaccine after Intramuscular Injection in Mice / 中国病毒学·英文版

To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine,pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.

Radioimmunotherapy of solid tumor / 肿瘤研究与临床

Radioimmunotherapy (RIT) is one kind of targeted immunotherapy. It is a better therapy of tumour treatment for its distinct advantages. Nowadays, it has been widely used to treat lymphoma, and part of solid tumors. In this review,basic research and clinical application related to solid tumor are summarized.

Animal biodistribution and pharmacokinetics study of ~(131)I-labelled rch24 / 肿瘤研究与临床

Objective To evaluate biodistribution and pharmacokinetics pattern of ~(131)I-labeled rch24which is the region-grafted (humanized) anti-carcinoembryonic antigen (CEA) monoclonal antibody in nude mice. Methods Nude mice bearing cancer xenografts received intravenous injections of ~(131)I- rch24, then blood, plasma, heart, liver, spleen, lung, kidney, tumor and other tissues were taken at different time point for determination the concentration of radioactivity and calculate the T/NT value. Nude mice were packeted randomly to four group of high, medium, low dose and continuous administration, blood drug concentration was detected by ELISA method at the different intervals. Then, draw the concentration-time curve and calculate the pharmacokinetics paramete. Results After administration, radioactivity of the tumour was significantly enhanced whereas radioactivity of normal tissues decreased gradually. For single administration, at the dose of low to medium, pharmacokinetics pattern was linearity -kinetics whereas for high dose group,pharmacokinetics paramete shown some behavior of non-linearity-kinetics. Conclusion Our results suggest that the ~(131)I-labeled region-grafted (humanized) anti-CEA monoclonal antibody rch24 exhibit a considerable targeting activity so as to ~(131)I radioisotopes can be concentrated specifically in tumor. The pharmacokinetics pattern of this medicine was different at different dose.

Application of PET/CT Orientation Gamma Knife in the Body Position / 医疗卫生装备

Obiective To elaborate the application of PCT/CT orientation Gamma Knife in the body.Methods From May, 2007 to May, 2008, PET/CT equipment was used on 120 cases with gamma knife body positioning and image fusion, Re-sults The PET/CT scan may not have iodine in the contrast agent to enhance the effective conduct of tumor imaging and CT position provides more simple and more accurate image information to guide target(GTV) of the outline. Conclusion The PET/CT in the gamma knife treatment can improve in the positioning accuracy of GIN, and improve treatment opportunity for iodine allergy patients.

Study of the influence of Ginsenoside Rb1 on apoptosis of primary cultured neonate rat cerebral cortical neurons caused by hypoxia / 中国康复理论与实践

@#ObjectiveTo investigate the protective mechanism of Ginsenoside Rb1 on apoptosis of primary cultured cerebral cortical neurons caused by hypoxia.MethodsThe anti apoptosis effect of Ginsenoside Rb1 on primary cultured neurons was observed by methods of the primary culture of cerebral neurons of postnatal rats in free serum with neurobasal medium supplied with 2% B27 supplement, trypan blue exclusion, hypoxic culture of neurons, Hoechst 33342 staining and immunocytochemistry.ResultsAt concentrations of 10μg/ml,50μg/ml and 100μg/ml, the Ginsenoside Rb1 dropped apoptosis rate of cerebral cortical neurons induced by hypoxia (in 100 μg/ml,P<0.05),and increased Bcl-2 protein expression (except 10μg/ml,P<0.05) and decreased Bax protein expression (except 10μg/ml,P<0.05—P<0.001) in the cerebral cortical neurons induced by hypoxia, improved the ratio of Bcl-2/Bax (except 10 μg/ml,P<0.05).ConclusionGinsenoside Rb1 is able to prevent hypoxic neurons from apoptosis in primary cultured cerebral cortical neurons from 50—100 μg/ml. The effect of anti apoptosis is through up regulation of Bcl-2 protein expression and down regulation of Bax-2 protein expression.

Progresses of Proton Therapy for carcinomas / 医疗卫生装备

As a new radiotherapy for carcinomas, Proton Therapy has been making progresses. Compared with conventional radiation, proton has a better physical characteristic and a similar biological effect. Proton Therapy consists of Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, Stereotactic Radiotherapy, Proton Scanning Radiation and et al. With the utilization of Bragg peak, Proton therapy can increase the dose of carcinoma region and reduce the dose of normal tissue, and thus it has a good curative effect and can be a good cure for many indications. In spite of the above-mentioned, Proton therapy has to be improved in the future.

Secondary structure of insulin encapsulated within liposomes / 药学学报

<p><b>AIM</b>To determine the secondary structure of insulin encapsulated within liposomes.</p><p><b>METHODS</b>The secondary structure of insulin, mixture of insulin with liposomes (I) and insulin liposomes (II) were determined by Fourier transform infrared (FTIR) spectroscopy.</p><p><b>RESULTS</b>The figures of secondary structure of insulin, sample I and II were similar. The results showed that the amount of alpha-helix and beta-sheet of insulin, sample I and II had little difference, from 36.09% (insulin) to 31.68% (sample I) and 31.45% (sample II), and from 47.83% (insulin) to 53.29% (I) and 51.36% (II), respectively. The results showed that the insulin of sample I and II did not insert in liposomes membrane, only adsorbed or extendedon the surface of the liposomes.</p><p><b>CONCLUSION</b>The secondary structure of insulin encapsulated within liposomes has not been destroyed and still remain the original state.</p>