Volume 90  ·   Issue 14  ·  2010

Prostate cancer is second only to lung cancer, and is the second killer of male tumor death. The clinical diagnosis and treatment of prostate cancer has accumulated rich case experience in Europe and America, and there are a large number of multi-center clinical research literature and diagnosis and treatment guidelines ~ ([1]). Prostate cancer is on the rise in China, and the understanding of it is also deepening ~ ([2-4]). In 2007, the Urology Branch of Chinese Medical Association formulated the "Prostate Cancer Diagnosis and Treatment Guidelines" suitable for Chinese people, which was revised in 2009. It can be said that there are standardized reference documents for the clinical diagnosis and treatment of prostate cancer ~ ([5]). At present, there are no conclusions and new methods in the diagnosis and treatment process.

The lack of innovation ability is one of the main obstacles to the leap-forward development of clinical research in China.Improving the innovation ability of researchers from the source of clinical research is the possible way to overcome this obstacle.On the basis of combing the process and law of clinical research, we summarized the process and law of innovation at the source of clinical research, put forward the concept and implementation method of top-level design, and applied it in recent research work, which preliminarily verified the application value of top-level design in improving the innovation ability and work efficiency of researchers.

Bone metastasis of prostate cancer (PC) is a common clinical problem, but there are many related research reports in China ~ ([1]). In recent 10 years, clinical studies abroad have proved that rational use of bisphosphate-like drugs can prevent or alleviate PC bone metastasis and bone destruction caused by endocrine therapy, improve the quality of life of PC patients, and prolong the survival time of metastatic PC patients. The 5-year survival rate of patients with PC bone metastasis was 25%, and the median survival time was 3 years ~ ([2]).

Objective To investigate the anti-proliferation and pro-apoptotic effects of different sequence schemes of zoledronic acid plus paclitaxel upon the hormone-refractory prostate cancer cell lines DU145 in vitro so as to provide the potentially optimal sequence scheme of these two drugs. Methods MTT assay and Annexin V-FITC/PI double-staining flow cytometry were employed to observe the effects of zoledronic acid plus paclitaxel upon anti-proliferation and apoptosis induction respectively. Results Inhibition of cellular growth by (44. 17 ± 5. 81) % was observed under the treatment of paclitaxel and then zoledronic acid. Such a regimen was superior to the treatment of zoledronic acid and then paclitaxel or zoledronic acid (32. 81 ±5. 13)% plus paclitaxel (36.43 ±5. 75)%. In comparisons with other groups, the treatment of paclitaxel and then zoledronic acid induced the maximal apoptosis (14. 96% ) and necrosis (14. 37% ) as shown by Annexin V-FITC/PI double-staining flow cytometry. Conclusion For the maximal anti-proliferation and apoptosis, DU145 cells should be treated with paclitaxel then zoledronic acid. Such a regimen provides the optimal scheme for the sequence-dependent treatment.

Objective To analyze the relationship between radiological characteristics of bony metastasis and PSA, Cleason score (GS) for prostate cancer patients. Methods The investigators collected the clinical data of 44 patients with prostate cancer bony metastasis and divided them into 3 groups based upon the radiological characteristics of bony metastasis. The 3 groups were osteoblast group, osteoclast group and mixed group. Results The mean age of patients was 70 years old. There were 33 cases (75.00% ) , 9 cases (20.45% ) and 2 cases (4.55% ) in osteoblast group, osteoclast group and mixed group respectively. The mean total serum PSA values were 590.3 ± 177.0 μg/L, 249.0 ±66.6 μg/L and 156.5 ±42.1 μg/L in osteoblast group, osteoclast group and mixed group respectively. No statistic significance was found for the difference of total PSA in 3 groups. Mean GS in osteoblast group was 7.4 (6-10). Twenty-two cases (66. 7% ) were of a medium-high differentiation (GS≤7) while 11 cases (33.3% ) of a low differentiation (GS >7). Mean GS in osteoclast group was 8. 0 (6-10). Among which, 3 cases (33. 3% ) were of a medium-high differentiation while 6 cases (66.7% ) of a low differentiation. Statistic significance was found for the difference of GS in 2 groups. Two cases in mixed group were assigned 8 of GS. Conclusion There is no confirmed correlation between types of bony metastasis and total serum PSA for prostate cancer patients. But the tumor differentiation reflected by Gleason score may affect the type of bony metastasis.

Objective To assess the anti-tumor immune response of cryoablation for prostate cancer. Methods Mouse model of prostate cancer was established. And the tumor-bearing mice were divided into three groups: control group ( Group A) , surgery group (Group B) and cryoablation group (Group C) . Blood samples were withdrawn before and at Days 7, 14, 21 post-treatment IFN-γ and IL-4 were analyzed by enzyme-linked immunosorbent assay (ELISA). Thl/Th2 ratio was estimated from the IFN-γ/IL-4 ratio. Lymphocytes of draining lymph node ( DLN) and spleen were isolated. And the post therapeutical number of tumor-specific IFN-γ~+ CD4 + Th cells was measured by the method of enzyme link immunal spot (ELISPOT). And tumor-specific cytolytic activity of CD8 + cytotoxic T lymphocyte (CTL) was measured by LDH assay. The rate of metastasis was assessed. Results At Day 7 post-treatment in Groups A, B and C, Thl/Th2 ratio was 4. 97 ± 0. 31, 10.07 ± 0. 62 and 13.71 ± 0. 57 respectively ( P < 0. 05); the number of IFN-γ~+ cells every 10~6 CD4 +Th cells in DLN 22. 3 ± 1. 0, 24.0 ± 1. 2 and 243.4 ± 46. 2 respectively; cytolytic activity of cytotoxic T lymphocyte against prostate cancer cells (14. 6 ± 1. 1) % , (15. 2 ± 0. 8) % and (62. 6 ± 2. 3) % respectively (P < 0. 05). But for T cells derived from spleen, there were no difference in IFN-γ~+ CD4 + Th cells or cytolytic activity of CTL among the groups. At Day 28 post treatment, the rate of DLN metastasis was 100% , 80% and 40% respectively. And the rates of lung metastasis were all 100%. Conclusion Cryoablation for prostate cancer can induce the Th1 advantage of anti-tumor immunity and generate the tumor-specific immune response in DLN. But the response remains limited. Further studies are warranted.

Objective To explore the roles of chemokine CXCL16 and its receptor CXCR6 in the directional invasion of human prostate cancer ( PCa). Methods The expression of CXCL16/CXCR6 in PCa samples and osseous tissues was determined by immunohistochemistry. The expression of CXCR6 in PC3 and LNCap cells was determined by reverse transcription-polymerase chain reaction ( RT-PCR ) and immunocytochemistry. Then the effects of CXCL16 upon the migration and invasion of human PC3 and LNCap cells were examined by Matrigel invasion assay. Results The expression of CXCR6 protein was detected in all clinical PCa samples. But no CXCL16 protein was detected. Positive CXCL16 expression was observed in human osseous tissues. Both PC3 and LNCap cells expressed CXCR6 mRNA (0. 38 ± 0. 054 vs 0.41 ±0.019 respectively) and protein. In addition, CXCL16 could promote the in vitro migration and invasion of PC3 and LNCap cell lines (invading cells 211.50 ±5. 60 vs 89.25 ±3.31 respectively). Such a promoting effect of CXCL16 could not be blocked influenced by antiCXCL12 or antiCXCR4. Conclusion CXCL16/CXCR6 axis may be another independent chemokine factor playing a significant role in the metastasis of prostate cancer.

Objective To investigate the clinicopathologic factors related to local recurrence following curative surgery for rectal cancer and explore the ways to improve the efficacies. Methods A total of 257 post-operative cases of rectal cancers from January 1995 to December 2002 were recruited. And the relation of each clinicopathologic characteristic and local post-operative recurrence was retrospectively investigated. The clinicopathologic factors and follow-up data were analyzed by uni and multi-factorial regression model by logistic regression. Results The total local recurrence rate of rectal cancer after radical operation was 18.7% , 75.0% (36/48)within 2 years and 95. 8% (45/48)within 3 years, the median time was 14. 6 months (range: 2-63). Univariate analysis showed that age, Dukes' stage, lymph node metastasis and level of CEA were significantly associated with the local post-operative recurrence ( P < 0. 05 ). Mutivariate analysis showed that age and lymph node metastasis were closely related with the local post operative recurrence ( P < 0. 05 ). Conclusion Lymph node metastasis and age are very important prognostic factors for the local post-operative recurrence. It is possible to improve the prognosis of rectum cancer by making an early diagnosis and offering a scientific standard therapy.

Objective To evaluate the efficacy of accelerated hyperfractionation (CAF) radiotherapy plus concurrent capecitabine in the treatment of locoregional recurrent rectal cancer. Methods Between June 2004 and January 2008, 53 patients with locoregional recurrent rectal cancer were treated with CAF 1. 2 Gy/f, 2 f/d plus concurrent capecitabine at an oral dosage of 825 mg/m~2 bid on each day of radiotherapy period. The first daily dose was applied at 2 h pre-irradiation, d1-14 and d22-35. After a regimen of 36 Gy/ 30 f/3 w, the feasibility of surgical resection was then evaluated by CT. Patients unsuitable for surgical resection continued CAF. And the total dose was 52. 8-57.6 Gy. Results The complete response rate was 9.8%, the partial response rate 45.1%, the effective rate 54.9%, the no-change rate 29.4%, the progression rate 15.7% , the surgical resection rate 23.5% and the R0, R1 resection rates 21.6% and 1. 9% respectively. The Time to Progression was 10. 5 months, 1-year survival rate was 84. 3% , 2-year survival rate was 61. 1% . Quality of life improved in treatment group. Toxic and adverse effects were gastrointestinal and hematological toxicities. There was no treatment-related mortality. Conclusion The 3-dimensional conformal radiotherapy plus concurrent chemotherapy may be an effective and well-tolerated regimen in patients with postoperative locoregional recurrent or mestastatic rectal cancer.

Objective The efficacy of standard chemotherapy regimen on lymphoblastic lymphoma ( LBL) is unsatisfied. This study was to evaluate the efficacy and safety of modified Hyper-CVAD regimen on Chinese patients with LBL. Methods Clinical records of 20 LBL patients who received modified Hyper-CVAD regimen in Cancer Hospital of Chinese Academy of Medical Sciences, from June 2004 to June 2008, were retrospectively analyzed in terms of response and toxicity. Results By May. 2009, the median follow up time was 17 (4-36) months. The 20 patients totally received 62 cycles regimen A and 29 cycles regimen B. 17 patients were assessable in efficacy, the total response rate (RR) was 88. 2% with complete response (CR) rate of 41. 2%. 15 patients received modified Hyper-CVAD regimen as first-line therapy(75. 0% ) , and RR was 100% with CR rate of 50. 0% (7/14). The RR of salvage therapy was 33% without CR achieved. The major toxicity was myelosuppresion, the incidence of grades 3-4 neutropenia, thrombocytopenia and anemia was 95. 0% , 75. 0% and 40. 0% , respectively. No treatment-related death was observed. Conclusions Modified Hyper-CVAD regimen was a promising regimen for the patients with LBL, and toxicity was within acceptable limits.

Objective To explore the applicability of Durie Salmon ( DS) and International Staging System (ISS) for Chinese patients with multiple myeloma (MM) and to evaluate the efficacy of major therapeutic options and the influence of various prognostic factors on survival were also evaluated. Methods The patient survival was compared with wegards to DS and ISS. Fourteen clinical and laboratory parameters were analyzed by univariate and multivariate process. Response rate, overall survival (OS) and progression- free survival (PFS) of 182 patients treated with different regimens were retrospectively analyzed. Results The median survival of patients with DS stages Ⅰ ,Ⅱ and Ⅲ were 79, 82 and 43 months, respectively. There was no significance between stage Ⅰ and Ⅱ /Ⅲ. The median survival of patients with ISS stages Ⅰ , Ⅱ and Ⅲ were 79, 49 and 43 months, respectively. Multivariate analysis suggested that age, percentage of plasma cell in bone marrow, C-neactive protein (CRP) and p2-microglobulin (2-MG) were independent prognostic factors for OS. The overall response rate (ORR) of 182 patients was 69. 2% and median OS and PFS were 49. 0 ±5. 0 and 19. 0 ±2. 1 months, respectively. The 5- and 10-year OS were 34% and 19% , respectively. Compared with those not receiving thalidomide induction, the patients on a VAD-like regimen combined with thalidomide showed a superior ORR (81. 5% vs 59. 7% , P = 0. 008) , a longer OS (79. 0 ± 29.5 vs 37.0 ±4.8 months, P = 0. 001) and a longer PFS (24.0 ±6.0 vs 14.0 ±2.7 months, P = 0. 033). Conclusion ISS is more applicable than DS, especially for low risk patients. The efficacy of VAD-like regimen combined Thal as first-line treatment is proven to be reliable. Induction therapy including thalidomide can not only improve the ORR, but also delay the relapse or progression of disease. It may even prolong the patient survival.

Objective To investigate the clinical features and risk factors of renal damage in the elderly and non-elderly patients with type 2 diabetes mellitus. Methods The data were collected from a survey of 10-year retrospective study of chronic complications of hospitalized type 2 diabetics organized by Chinese Diabetes Society. A total of 1351 patients of type 2 diabetes were selected and divided into an elderly group( ≥ 60 year)and a non-elderly group( <60 year). The patients were also divided into three groups according to urinary albumin excretion rate (AER): normoalbuminuria group ( AER <30 mg/24 h), microalbuminuria group (30≤ AER <300 mg/24 h) and macroalbuminuria group (AER ≥ 300 mg/24 h). eGFR was estimated by the equation from the MDRD study. Clinical and laboratory parameters of all patients were analyzed. Results ( 1 ) The proportions of renal insufficiency in both normoalbuminuria and microalbuminuria groups of type 2 diabetes in the elderly patients were significantly higher than those in the non-elderly patients (26.7% vs 15.8%, P<0.01; 30.5% vs 21. 3% , P<0.05 respectively); (2)in type 2 diabetic patients with renal insufficiency and normoalbuminuria, the diabetes duration (7. 7 vs 3. 8 years) , systolic blood pressure [ (146 ±24) mm Hg vs (134 ± 23) mm Hg] , diastolic blood pressure [ (84 ± 13) mm Hg vs ( 80 ± 11 ) mm Hg], proportion of hypertension (37. 8% vs 21. 1% ) , diabetic retinopathy(34. 1% vs 23.9%), cardiovascular diseases (31. 6% vs 11.3%)and cerebrovascular disease (24.4% vs 9.9% ) were significantly higher in the elderly group than in the non-elderly group (P <0. 05 or 0.01) ; (3 ) multiple logistic regression analysis revealed that the duration of diabetes ( OR = 1.046, P = 0.013) and systolic blood pressure ( OR = 1.014, P =0.002) were independently associated with renal insufficiency in the elderly type 2 diabetic patients with normoalbuminuria, whereas systolic blood pressure (OR = 1.042, P= 0.000) and 2-hour postprandial blood glucose ( OR = 1.048, P = 0. 002 ) were independent risk factors for renal insufficiency of non-elderly patients. Conclusion The elderly type 2 diabetic patients are likely to suffer renal insufficiency initially from a lower glomerular filtration rate than the non-elderly patients. Systolic blood pressure is the main risk factor in both elderly and non-elderly type 2 diabetes with normoalbuminuria and a decreased renal function. Controlling blood pressure may delay the decline of renal function.

Objective Although the aldosterone-to-renin ratio (ARR) is valuable in the screening for primary aldosteronism ( PA) . However, the hormonal determinations are both time-consuming and expensive. So we tried to use new indexes of serum sodium to urinary sodium to serum potassium to urinary potassium (SUSPUP) and serum sodium to urinary sodium to (serum potassium)~2 to urinary potassium (SUSPPUP) in screening of PA. Methods The present study included 39 patients with PA, 296 patients with essential hypertension and 158 normotensitive subjects. Serum potassium and sodium, urine potassium and sodium were measured by ion-selective electrodes. In addition, serum aldosterone concentration and plasma rennin activity after staying upright for one hour were measured by radioimmunoassay. The serum potassium and sodium, urine potassium and sodium in these groups were evaluated in the screening of SUSPPUP for differentiating PA from hypertensive patients. Results (1) Compared with healthy volunteers, the essential hypertension patients had lower levels of both serum potassium and urine sodium, higher levels of serum sodium. Compared with healthy volunteers and primary hypertension patients, the PA patients had the lowest serum potassium and highest serum sodium, urine potassium resulting in the highest SUSPUP and SUSPPUP ratio. (2) The AUCs of SUSPUP and SUSPPUP were 0. 824 and 0. 840 respectively according to the ROC curve. The optimal cutoffs of SUSPUP and SUSPPUP were 14.44 and 4.08 respectively. Conclusion The SUSPUP and SUSPPUP ratios are rapid and inexpensive indices to assess the extent of mineralocorticoid excess. Therefore they may be employed to screen PA in hypertensive patients.

Objective To evaluate the performance of tumor markers (TM) measurements in clinical laboratories by external quality assessment EQA) and investigate the comparability of assays for TM. Methods Ten quality control sera specimens were distributed to 586 laboratories by global Express Mail Services ( EMS) in March 2008 and tested twice with 5 specimens each time. Analytes were total prostate specific antigen (PSA), free PSA, carcinoembryonic antigen ( CEA ), alpha fetoprotein ( AFP) , human chorionic gonadotrophin( HCG) , β-HCG, carbohydrate antigen 19-9 ( CA19-9) , cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA125) ,β-2-miroglobin and ferritin. The collected data were divided into peer groups according to analyzers or methods and the median of peer group was adopted as the target value (TV) separately after outlier removal. Two standard deviations of the median were set as the limit of difference. Results The first TM EQA results of 2008 showed that the pass percentage of all participating laboratories ranged from 87. 3% (CA125 ) to 95. 5% ( β-2-microglobin). And the second batch ranged from 83. 5% ( HCG) to 94. 0% (β-2-microglobin). The coefficient variances ( CVs) of intra-group values determined by automatic analyzers were lesser than 15% for each test of every specimen. The CVs of radioimmunoassay ( RIA ) and enzyme-linked immunosorbent assay ( ELISA) were over 20% and 50% respectively. The inter group medians of 9 tests showed CVs > 20% with HCG 13.4% and ferritin 15.7%. The CV of paired medians of some automatic analyzers was small and showed no statistical significance (all Z < 1. 890, all P > 0. 05). Conclusion The analytical performance of automatic analyzers is superior to RIA and ELISA. There is an excellent comparability within automatic analyzers for TM measurements and a lack of comparability within RIA and ELISA. Noncomparability is found in over 80% of TM assays.

Objective To study the effects of siRNA-mediated p-catenin down-regulation on Wnt/ P-catenin signal transduction pathway in lung adenocarcinoma A549 cells. Methods A549 cell was divided into three groups: PGCsil-CTNNB1-siRNA group (transfection with β-catenin interference plasmids), negative control group ( transfection with negative control plasmids) and non-transfection group ( blank control). For each group, real-time PCR was employed to detect the expression of β-catenin and cyclin D1 (a target gene of Wnt/β-catenin pathway) . A MTT cell proliferation assay was performed to study the proliferating capacity. Flow cytometry was used for cell cycle analysis. Clone formation and Millicell chamber experiment were performed to evaluate the clone formation and migration capacities of cells. Results The expression of β-catenin and cyclin D1 in PGCsil-CTNNB1-siRNA cell decreased at the mRNA level. It was lower than negative control (0. 002 ± 0. 001 vs 0. 023 ± 0. 002, P < 0.01; 0. 005 ± 0. 002 vs 0. 040 ± 0.020, P<0. 05) and blank control groups (β-catenin mRNA: 0.021 ±0.003, P < 0.01; cyclin D1 mRNA: 0.042 ± 0. 004, P < 0. 05 ) . Also the proliferating capacity at Days 5-7 was inhibited in comparison with negative control and blank control groups (P < 0. 05, P < 0.01 ). The cell-doubling time ( 58. 1 h) was markedly longer than those of negative control group ( 37. 9 h, P < 0. 05 ) and blank control group (34. 2 h, P < 0. 05). The number of cells in G0-G1 phrase increased in PGCsil-CTNNB1-siRNA group (86. 4% ± 2. 6% ) in comparison with negative control (73. 8% ± 0. 9% , P < 0. 01) and blank control groups (75.8% ±1.5% , P<0.01). In PGCsil-CTNNBl-siRNA group, the clone formation ratio (31. 6% ±7.7%) was lower than negative control (46.9% ± 7. 3% , P < 0. 05) and blank control groups (44. 2% ±2. 5% , P < 0. 05 ) . And the number of cells ( 16. 0 ± 3. 8 ) passing through the membrane of Millicell chamber was smaller than negative control (32. 7 ±3. 1, P <0.01) and blank control groups (33.0 ± 2.7, P < 0. 01). Conclusions Knocking down p-catenin not only inhibits the Wnt/β-catenin signal transduction pathway in lung adenocarcinoma A549 cells but also decreases cell proliferation, clone formation and migration capacity. Thus it may become a novel target for lung cancer therapy.

A 20-year-old female was admitted to the Third Hospital of Hebei Medical University on April 29, 2007 due to repeated skin rash, joint swelling and pain for 1 1/2 years, fever and left lower limb ulcer for 3 days. The patient developed symmetrical red macular rash on both lower limbs without inducement 1 1/2 years ago, which did not fade when pressed, skin blisters, accompanied by swelling and pain of both knees, wrist and elbow joints, and edema of fingers of both lower limbs; He was diagnosed as "Henoch-Schonlein purpura and purpura nephritis" in a foreign hospital. He was given prednisone 40 mg orally once a day, and the symptoms improved. After 1 month of treatment, the dose was gradually reduced to 7.5 mg a day.

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a severe or even fatal inflammatory state caused by non-malignant proliferation of lymphocytes and histiocytes and secretion of a large number of inflammatory factors ~ ([1]). It can be divided into two major categories: primary hemophagocytic syndrome and acquired hemophagocytic syndrome<Acquired HPS can occur at any age, more frequently at>8 years old, and no clear immunodeficiency has been found ~ ([2]).

microRNA (miRNA) is the most active cell regulator in recent years.Different from traditional protein factors,miRNA is a kind of non-coding RNA between 19 and 22 nucleotides, which can regulate gene expression at the level of transcription and translation.Its mechanism of action is as follows: in the nucleus, miRNA gene is transcribed into the original miRNA (pri-miRNA) with cap structure and polyadenylate tail (AAAAA) by RNA polymerase Ⅱ, and the pri-miRNA is cut by the nuclease Drosha to generate 70 nucleotides of miRNA precursor (pre-miRNA) with stem-loop structure.

A 69-year-old woman came to our hospital on February 12, 2009 with "palpitations, hyperhidrosis, diarrhea for 7 years, nausea and vomiting for 2 months, aggravated for 1 day". The patient was diagnosed with "hyperthyroidism" 7 years ago, and her condition was prolonged after intermittent oral administration of propylthiouracil. Three months ago, she was treated with radioactive ~ (131). Two months ago, she had palpitations, chest tightness, shortness of breath, nausea and vomiting, obvious weight loss and weight loss of about 5 kg. Blood free triiodothyronine (FT_3) 42.85 pmol/L, blood free thyroxine (FT_4) 94.82 pmol/L, thyroid stimulating hormone (TSH) 0.13 μ IU/ml, thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were negative, no anti-thyroid drugs (ATD) were taken, nausea and vomiting worsened 1 day ago, no history of nephropathy, no history of taking vitamin A, D and thiazide diuretics were denied.

The patient was a 26-year-old female. She was married for 2 years, had 1 birth and 1 child. She was admitted to the hospital for 2 days of macroscopic hematuria and 1 day of dysuria. She underwent uterine curettage in an outside hospital for 6 weeks of intrauterine pregnancy 1 month ago, and her blood was purified 2 days after operation. The admitted blood pressure was 90/50 mm Hg (1 mm Hg =0.133 kPa), and the hemoglobin was 70 g/L. She was given bladder irrigation and blood transfusion anti-shock treatment, and her condition was stable. Urinary tract CT showed intravesical mass, about 2.0 cm (Figure 1), intrauterine mass (Figure 2), excluding intrauterine residue. Blood β-human chorionic gonadotropin (HCG) 2188 U/L (normal value<25 U/L).