Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway / 中国中药杂志

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.

Effect of combining different calcium concentration dialysate on calcium balance in peritoneal dialysis patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality. Therefore, maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone (iPTH) level has become the focus of attention. We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis (CAPD) patients.</p><p><b>METHODS</b>Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate (DCa1.25, PD4, 22 patients) or a combination of 1.75 mmol/L calcium dialysate (DCa1.75, PD2) and PD4 (18 patients) twice a day respectively. Total serum calcium (after albumin correction), serum phosphorus, iPTH, alkaline phosphatase (ALP) and blood pressure were recorded before and 1, 3 and 6 months after treatment commenced.</p><p><b>RESULTS</b>No significant difference was found in baseline serum calcium, phosphorus between the two patient groups, but the levels of iPTH were significantly different. No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months. In the PD4 group, serum calcium level at the 1st, 3rd, 6th months were significantly lower than the baseline (P < 0.05). There was no significant difference in serum phosphorus after 6 months treatment. iPTH was significantly higher (P < 0.001) at the 1st, 3rd, and 6th months compared with the baseline. No differences were seen in ALP and blood pressure. In the PD4+PD2 group, no significant changes in serum calcium, phosphorus, iPTH, ALP and BP during the 6-month follow-up period.</p><p><b>CONCLUSIONS</b>Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium, increase iPTH, without change in serum phosphorus, ALP, and BP. The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.</p>

Burden and related factors among care-takers of patients with Parkinson's disease / 中华流行病学杂志

Objective To assess the impact on caretaker who looked after patients with Parkinson's disease(PD) and to identify the main factors related to their burden.Methods 115 consecutive pairs of PD patients and their caretakers were included.Caregiver Burden Inventory (CBI) was used to assess the burden of PD on the caretakers.Patients were evaluated by neurologists using the United Parkinson's Disease Rating Scale(UPDRS),the Hoehn and Yahr Scale(H-Y Scale),the Activity of Daily Liring Scale(ADL),the Parkinson's Disease Quesnonnaire(PDQ-39),the Hamilton Depression Rating Scale(HAMD),the Hamilton Anxiety Rating Scale(HAMA),the Montreal Cognitive Assessment(MoCA)and the Mini-mental State Examination(MMSE).Multiple linear stepwise regression models were fired to ascertain the factors linked to the CBI.Results Based on multiple linear stepwise regression analysis,ADL(β=-0.813,t=-6.265,P=0.000)and PDQ-39(β=0.285,t=4.256,P=0.000)of patients and the age ofcaretakers(β=0.327,t=3.107,P=0.002)proved to be the main predictors of CBI.Conclusion Many factors might comprehensively affct the burden of PD on caretakers of the patients.Attention needs to be given to the early identification of factors that generating stress on 1iveretakers in order to improve their quality of life.

Effects of deep brain stimulation on expression of DARPP-32 and its phosphorylated proteins in corpus striatum of rats with dyskinesia / 上海第二医科大学学报

Objective To investigate the effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on expression of dopamine and adenosine 3'5'-monophosphate-regulated phosphor-protein(DARPP-32) and its phosphorylated proteins in corpus striatum of rat models with levodopa-induced dyskinesia. Methods The rat models of levodopa-induced dyskinesia were set up and were given STN-DBS (stimulation group). The expression of DARPP-32 and its phosphorylated proteins in corpus striatum (damage side and normal side) were detected and compared with sham-stimulation group and sham-operation group. Results There was no significant difference in the expression of DARPP-32 total protein in corpus striatum of rats with dyskinesia among three groups (P>0.05). The expression of Phosphor-Thr34-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly lower than that in sham-stimulation group and sham-operation group (P<0.05), while the expression of Phosphor-Thr75-DARPP-32 protein in the damage side of corpus striatum in stimulation group was significantly higher than that in sham-stimulation group and sham-operation group (P<0.05). Conclusion DARPP-32 and its phosphorylated proteins play an important role in the pathogenesis of levodopa-induced dyskinesia.

Online Student Preparation and Management System for Microbiology Experiment and Its Application to Experiment Teaching / 微生物学通报

Student preparation for laboratory sessions is the first step of conducting laboratory experiments. It makes students maximize use of laboratory time and efficiently perform laboratory exercises in open labs. In view of teaching features and requirements of Microbiology experiment, we designed and developed ‘Online Student Preparation and Management System of Microbiology Experiment’, which integrated func- tions of student preparation for laboratory sessions and teacher management. In the system each experiment consists of six successive parts, viz., learning objectives, principle, materials and equipments, procedure video, manipulation simulation and online quiz. Teaching practices showed that the application of the system enhanced the preparing quality and makes the management of the experiment teaching more normalized and efficient. It was an effective measure in improving experimental teaching of Microbiology.

New clinical staging system for carcinoma of nasal cavity / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a new staging system based on analysis of several presently used clinical staging systems for carcinoma of nasal cavity.</p><p><b>METHODS</b>The data of 122 patients treated from 1985 to 1997 in the cancer center of Sun Yat-sen University were analyzed, and a new clinical staging system was established using computer optimizing and screening combined with the clinical results. The survival analysis was performed by Kaplan-Meier estimates, and the multivariate analysis was achieved by Cox proportional hazard model.</p><p><b>RESULTS</b>The flaws in the presently used clinical staging systems proposed by Zhuang, Qiu, Department of Head and Neck of Cancer Center of Sun Yat-sen University and University of Florida and the AJCC'2002, were as follows: insufficient consideration of the modern tomography resulting in indefinite location of the tumor in clinical practice, the uneven distribution of patients in different stages, being unable to separate survival curves of different stages, and not containing of all necessary clinical staging information in some staging systems. However, based on our new staging system, the cases distributed in T1, T2, T3 and T4 was 16, 32, 42 and 32, and the 5-year survival rate was 78.8%, 64.6%, 49.9% and 30.0%, respectively. The cases distributed in stage I, II, III and IV was 16, 26, 45 and 35, and the 5-year survival rate was 78.8%, 68.4%, 51.3% and 29.0%, respectively. The overall 5-year survival rate was 61.6%.</p><p><b>CONCLUSION</b>Compared to the presently used clinical staging systems, the new staging system may have more advantages in various parameters for the clinical staging in the carcinoma of nasal cavity, and may be worth to be widely and clinical used.</p>

Intensity modulated radiation therapy for 122 patients with untreated nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To analyse the preliminary clinical results of intensity modulated radiation therapy (IMRT) for 122 untreated nasopharyngeal carcinoma (NPC)pafients.Methods 122 NPC pa- tients received IMRT alone from Feb.2001 to Jun.2004,with 31 females and 91 males,and a median age of 45 years(range 25-66).According to the Fuzhou Stage Classification,there were StageⅠ11 patients, StageⅡ34,StageⅢ62,and StageⅣa 15.IMRT was carried out using an inverse planning system (COR- VUS 5.0,Peacock plan) developed by the NOMOS Corp.The treatment was given with the Multi-leaf Inten- sity Modulating Collimator (MIMIC) using a slice-by-slice arc rotation approach.The prescription dose was 68 Gy/30f to the nasopharynx gross tumor volume (GTV_(nx)),60-66 Gy/30f to positive neck lymph nodes (GTV_(nd)),60 Gy/30f to the first clinical target volume (CTV_1) and 54 Gy/30f to the second clinical target volume (CTV_2).Kaplan-Meier method was used to calculate the overall survival rate (OS),distant metas- tasis-free survival rates (DMFS),and local-regional control rates from the last date of therapy.Log-rank test was used to detect the difference between groups.Results The median follow-up time was 20 months ( range 6 to46 months).The 1-,2-,and 3-year OS was 95.2%,91.4%,85.1%,DMFS was 91.9%, 88.6%,85.6%,and the local-regional control rates was 96.5%,93.2%,93.2%,respectively.Statistics of the local control rate was insignificant either for advanced T(T3+T4) stage or early T(T1+T2) stage diseases(P=0.148).The 2-year regional control rate was insignificant either for patients with N(+) or N (-),but the 2-year DMFS was significant both for patients with N(+) and N(-)lesions(P=0.004).For 17 patients who failed,there were two with residual disease and one with recurrence at the primary site (17.6%),three patients in the neck (17.6%),twelve patients (70.6%) in distant metastases.Conclu- sions Intensity modulated radiation therapy does provide excellent local-regional control for untreated NPC, especially in patients with advanced T stage or N(+) lesion.Distant metastasis is the main cause of failure. N (+) is significantly correlated with distant metastasis.

Intensity modulated radiation therapy for 49 patients with recurrent nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility, toxicity and tumor control of intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma.</p><p><b>METHODS</b>Fourty-nine patients (Karnofsky performance status (KPS) >or= 80) with local-regional recurrence in the nasopharynx were treated with full course IMRT. Three patients with cervical lymph node metastasis (N1 2 and N3 1) were further supplemented with 5 to 6 courses of chemotherapy (Cisplatin + 5-Fu) after IMRT.</p><p><b>RESULTS</b>The results of treatment plan showed that the mean dose of covering gross tumor volume (GTV) (D(95)) in the nasopharynx was 68.09 Gy and the mean volume of GTV (V(95)) receiving the 95% dose was 98.46%. The mean dose of GTV, clinical target volume CTV1 and CTV2 in the targets were 71.40 Gy, 63.63 Gy and 59.81 Gy. The median follow-up time was 9 months (range 3 to 16 months). The local-regional progression-free survival was 100% with local-regional residual disease in 3 (6.1%) cases but was complicated with nasopharyngeal mucosa necrosis in 14 (28.6%) cases after IMRT.</p><p><b>CONCLUSION</b>Intensity modulated radiation therapy, as a re-treatment option for recurrent nasopharyngeal carcinoma, is able to improve the tumor target coverage and spare the adjacent critical structures. As high dose IMRT can result in radio-necrosis of nasopharyngeal mucosa, the prescription dose of GTV should be suitably decreased to 60 - 65 Gy.</p>

Prognostic analysis of intensity modulated radiotherapy for locally recurrent nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To report the clinical outcome and prognostic factors for locally recurrent nasopharyngeal carcinoma(NPC)treated with intensity modulated radiotherapy(IMRT).Methods From January 2001 to August 2004,the data of 132 such NPC patients were analyzed retrospectively;104 male and 28 female with a median of 44.5 years(range 21-73 years).Ninety-eight patients(74.2%)were confirmed by biopsy as having NPC:9 with WHO TypeⅡand 89 WHO TypeⅢ.The other 34 patients were only diagnosed by MRI scan because of the extension/invasion was in the base of skull and/or cavernous sinus.Median interval time were 24 months(range 6-184 months).According to the 1992 Chinese Fuzhou Staging System:stageⅠ3.8 %,Ⅱ10.6 %,Ⅲ22.0% andⅣa 63.6%;T1 5.3%,T2 10.6%,T3 22.7% and T4 55.3%.Twenty-two patients had recurrence in the neck lymph nodes.IMRT was given with the sequential tomotherapy system(NOMOS Peacock systems)of 6 MV X-rays.Prescription dose was 60-70 Gy in GTV,with the fractional dose of 1.94-2.8 Gy.Sixty patients were also supplemented with two to six courses of cisplatin-based chemotherapy.Results The median volume of GTV was 39.5 cm~3(range 0.8-158.9 cm~3).The D95,V95,mean dose and fractionation dose of GTV was 66.9 Gy,98.3%,69.8 Gy and 2.32 Gy,respectively.The median follow-up time was 12 months(range,2-47 months).The 1-,2-and 3-year local progression-free rate was 96.4%,88.4% and 85.3%,respectively.The overall 1-,2-and 3-year survival rate was 6.5.9%,49.6% and 41.6%,respectively.Eleven patients developed distant metastases.Forty-seven patients were observed to devdop mucosa necrosis and/or massive hemorrhage in the nasopharynx.On univariate and multivariate analysis,fractional dose and vohane of GTV were significant prognostic factors for overall survival(P=0.016,0.009).Conclusions The local control and survival rate can be improved for patients with locally recurrent nasopharygeal carcinoma after treatment of intensity modulated radiotherapy.The fractional dose and volume of GTV are independent prognostic factors for the overall survival. The main death reasons are mucosa necrosis and/or massive hemorrhage in the nasopharynx.

Probe into rational target volume of nasopharyngeal carcinoma having been treated with conventional radiotherapy / 中华放射肿瘤学杂志

Objective To analyze the local control rate and the desimetric patterns of local recurrence in nasopharyngeal carcinoma(NPC)patients having been treated with standardized conventional radiotherapy and to evaluate the delineation of rational target volume.Methods From Jan.2000 to Dec.2000,476 patients with untreated NPC were treated by standardized conventional radiotherapy alone at the Sun Yat-sen University Cancer Center.The radiation ports were designed on a X-ray simulator.The nasopharyngeal lesion demonstrated by CT scan and the subclinical spread regions adjacent to the nasopharynx were defined as the target volume.Kaplan- Meier method was used to calculate the cumulative local recurrence rate.For patients with locad recurrence,the primary and recurrent local tumor volumes(V_(nx),V_(recur))were delineated with three-dimensional treatment planning system(3DTPS),and the dataset of radiation ports and delivered prescription dose to the 3DTPS were transferred according to the first treatment.The dose of radiation received by V_(recur)was calculated and analyzed with dose- volume histogram(DVH).Local recurrence was classified as:1.“in-port”with 95% or mere of the recurrence volume((recur)_V_(95))was within the 95% isedase;2.“marginal”with 20% to95% of _(recur)V_(95)within the 95% isedese; 3.“outside”with only less than 20% of _(recur)_V_(95)within the 95% isodose curve.Results With the median follow- up of 42.5 months(range 8～54 months),52 patients developed local recurrence.The 1-,2-,3 and 4-year cumulative local failure rate was 0.6%,3.9%,8.7% and 11.5%,respectively.Among the 42 local recurrent patients who could be analyzed by 3DTPS,52% were in-port,40% were marginal and 7% were outside.For most of the marginal recurrence and all the outside recurrence patients,the main reason of recurrence were related to the unreasonable design of the radiation port and inaccuracy in the interpretation image findings.Conclusions The outcome of better local control rate and the dosimetric pattern of local recurrence show that the target volume is reasonable for NPC in Sun Yat-sen University Cancer Center.Enhancing the capability of correct interpretation of images,accurate design of the radiation pouts and making most useful molecular or functional imaging techniques to escalate the local radiation dose are promising ways to improve the local control further and better.