Volume 124 ·  Issue 19 ·  2011

Abstract：Multiple myeloma (MM) remains an incurable neoplastic disease, although high-dose chemotherapy supported by autologous stem cells, and the latest integration of several novel agents, including thalidomide, bortezomib and lenalidomide, into each step of therapeutics have substantially improved the outcome of patients with MM.1-5 Herein, we gave our own considerations on some promising directions in the near future, aiming at further improving the survival and the quality of life of MM patients, and even achieving our final goal of the cure of MM, including highlighting stratified and individualized therapies, pursuing novel targets and strategies, unraveling the biological characteristics of myeloma initiation cells and strengthening post-transplant immunotherapies。

Abstract：Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m2(0.7-1.0 mg/m2) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m2 (0.7-1.0 mg/m2)of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2％ (13/18), 73.8％ (48/65), 78.8％ (26/33) and 78.0％ (32/41) (P=0.91), including a complete response rate of 22.2％ (4/18), 20.0％ (13/65), 33.3％ (11/33) and 29.3％ (12/41) (P=0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P ＞0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P ＞0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3％) than in group 2 (13.8％, P ＜0.05) and group 4 (14.6％, P＜O.05).Conclusions The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China。

Abstract：Background Autologous stem cell transplantation (ASCT) is a part of the standard induction therapy of multiple myeloma (MM). This case-controlled clinical trial aimed to further evaluate the therapeutic effects of ASCT as a consolidation therapy for MM and discuss factors influencing the prognosis.Methods Clinical data of 70 patients diagnosed as MM who received ASCT as a consolidation therapy in our hospital between October 1998 and August 2010 were analyzed retrospectively (ASCT group). Other 70 MM patients receiving routine chemotherapy without ASCT (non-ASCT group) during the same period were used as controls. Differences in the degree and duration of remission, progression-free survival (PFS) and overall survival (OS) were compared to explore factors that may influence the prognosis.Results The median follow-up period was 38 months (range 1-128 months). The complete response (CR) rate of ASCT group increased from 27.1％ (19/70) before ASCT to 51.4％ (36/70) after ASCT. The median PFS of ASCT group was significantly higher than non-ASCT group (45 months vs. 25 months, P ＜0.001). The median OS of ASCT group was also significantly higher (55 months vs. 30 months, P=0.016). Single-factor analysis showed that International Staging System (ISS) stage, very good partial response (VGPR) or better outcome were significantly correlated with PFS and OS (P ＜0.001). Multi-factor analysis showed that whether or not VGPR or better outcome was achieved were independent factors influencing the disease prognosis.Conclusion Used as a consolidation therapy, ASCT can achieve better responses and higher OS and PFS of MM patients。

Abstract：Background Chromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.Methods Interphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.Results As a result of interphase FISH, 77.8％ (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4％ (37/72), D13S319 47.2％ (34/72), 1q21 45.8％ (33/72) and p53 22.2％ (12/72). Osteolytic lesion,BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13.Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93％ vs. 65％, P=0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P=0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P=0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P=0.002).Patients with β2-microglobulin ＞5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months,P=0.016).Conclusions The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis。

Abstract：Background At present, revascularization is still one of the most critical technologies in orthotopic liver transplantation (OLT). Hepatic artery (HA) variations occur frequently in both donors and recipients. Moreover, there are always some pathological changes in the recipient hepatic artery. If handled improperly, it may cause complications after anastomosis.Therefore, arterial conduit could be used in primary OLT, re-OLT and multiple-OLT. This study aimed to investigate the indications, methods and techniques with usage of arterial conduit for HA revascularization during adult OLT.Methods We reviewed 1200 patients of consecutive OLTs performed during 2000-2009 in the First Affiliated Hospital of Sun Yat-sen University. Of these patients, 48 recipients with artery variations received HA revascularization with usage of arterial conduit and special postoperative managements. The indications, methods, techniques, and the managements of postoperative complications in adult OLT with usage of arterial conduit for HA revascularization were analyzed.Results In 48 cases with artery bypass, the arterial conduit were anastomosed between donor hepatic artery and recipient infrarenal aorta (n=32), between donor hepatic artery and recipient suprarenal aorta (n=10), and between donor upper abdominal organ cluster artery and recipient suprarenal aorta (n=6). The technique was applied in 4％ (48/1200 cases) of the whole OLTs performed in the same period, and the patency rate of the conduits was 100％. Forty patients (83.3％) survived, and the average survival time was 3.9 years. Eight patients (16.7％) died (all due to tumor recurrence),while the average survival time was 1.2 years. All these patients have not experienced artery-related complications in their survival time.Conclusions When recipient HA has variations or pathological changes in OLT, the donor artery should be anastomosed to recipient abdominal aorta with an arterial conduit to achieve satisfactory outcomes. For arterial anastomosis can not be routinely performed, donor iliac artery as a conduit to be anastomosed with the recipient abdominal aorta is safe and effective。

Abstract：Background Rectal carcinoma patients are often accompanied by hepatic metastasis. The aim of this study was to evaluate the therapeutic efficacy of simultaneous laparoscopic excision for rectal carcinoma with synchronous hepatic metastasis.Methods A total of 41 patients with rectal carcinoma and synchronous hepatic metastasis detected by CT scan were included in this study. Among them, 23 patients underwent laparoscopic surgery and 18 patients underwent traditional open surgery to simultaneously remove the rectal tumor and hepatic metastasis lesions. All patients received postoperative adjuvant chemotherapy. All the patients were followed up from 36 to 72 months (mean 45.3 months).Results All the operations were performed successfully and no patient was turned to open surgery in laparoscopic group. The mean blood loss, the mean postoperative hospital stay, the mean blood transfusion and the mean intestinal functional recovery time showed a significant difference between the two groups (P＜0.05). The 1-, 3- and 5-year survival rates were 82.6％, 43.5％ and 8.6％ in the laparoscopic group, without significant difference compared with the open group (77.8％, 38.9％ and 0) (P＞0.05).Conclusions Simultaneous laparoscopic excision for rectal carcinoma and synchronous hepatic metastasis is safe and effective with similar survival achieved by the traditional open abdominal surgery。

Abstract：Background Acute severe biliary pancreatitis (ASBP) is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment.Methods One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group: 50 patients who underwent endoscopic retrograde choledochopancreatography (ERCP) + endoscopic sphincterotomy (EST) + endoscopic lithotripsy basket (ESR) +endoscopic retrograde biliary drainage (ERBD)and enteral nutrition (EN), and the R group: 55 patients who underwent traditional treatment without ERCP. Subsequently,subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography (CT), cost of hospitalization and length of stay were compared between the two groups.Results All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group.Conclusions Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP。

Abstract：Background Sufficient length of the proximal landing zone (PLZ) is the key for a successful thoracic endovascular aortic repair (TEVAR) of an aortic lesion. The aim of this research was to investigate the safety, feasibility, efficacy, and problems of endovascular repair for aortic dissection with insufficient PLZ.Methods The clinical data between August 2005 and February 2010 from patients with insufficient PLZ for endovascular repair of aortic dissection were retrospectively reviewed. According to the classification proposed by Ishimaru, aortic zone 0 was involved in 3 cases, zone 1 in 10 cases, and zone 2 in 11 cases. A hybrid surgical procedure of supraortic debranching and revascularization, directly coverage the orifice of left subclavian artery, or a left common carotid artery chimney graft technique were performed to obtain an adequate proximal aortic landing zone.Results There was no significant difference in risk factors and diameter of the PLZ between Zone 0, Zone 1, and Zone 2. But the length of the PLZ was significantly different in the three groups (P ＜0.01). There was no significant difference in technical and clinical success rate between the groups.Conclusions The procedure for extending an insufficient PLZ for endovascular repair for aortic arch pathology is feasible and relatively safe. The applicability of TEVAR in such aortic disorders may be expanded。

Abstract：Background Vascular anomalies are common and multidisciplinary involved diseases. The greatest impediment to their treatment in the past was their confusing terminology and clinical heterogeneities. This hospital-based retrospective study assessed some clinical characteristics, diagnosis, therapies and outcomes of patients with vascular anomalies in southeast China.Methods A total of 592 vascular anomalies patients (patients with intracranial tissues or viscera involved were excluded), admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2006 to September 2009, were enrolled in the study. Data for clinical characteristics, diagnosis, therapies and outcomes were collected and analyzed.Results Of the 592 patients, the male:female ratios in the vascular tumor group (n=187) and the vascular malformation group (n=405) were 1∶1.49 and 1∶1.06 respectively, with no significant difference between them. The mean onset age of the vascular tumor group was significantly younger than that of the vascular malformation group (P ＜0.001). The head and neck were the most commonly (31.4％) involved areas in vascular anomalies. A total of 23.8％ of the patients with vascular anomalies had definite symptoms caused by the vascular lesions. In the vascular tumor group, 94.1％ of them were infantile hemangiomas. Venous malformation was the most common (41.0％) subtype of vascular malformations.Surgical therapy was undertaken in 94.2％ of the patients with vascular anomalies. Of the 519 patients available for the 16-58 month follow-up, 322 patients (62.0％) were cured, 108 patients (20.8％) were markedly improved, 57 patients (11.0％) were partially improved, and 32 patients (6.2％) were uncured.Conclusions Vascular anomalies are clinically heterogeneous. While the outcome is generally favorable, further effort should be made to determine the appropriate terminology and management。

Abstract：Background Fingertip defect significantly affects the appearance of the hand. The aim of this research was to evaluate the clinical effect of aesthetic fingertip reconstruction with partial second toe transfer.Methods Between July 2005 and December 2008, 17 patients underwent aesthetic fingertip reconstruction with partial second toe transfer. The mean size of fingertip defects was 0.7 cm (ranging from 0.5-1.1 cm). Anastomosis was performed between one dominant plantar digital artery and one proper digital artery, between two dorsal digital veins of the toe and two dorsal digital veins of the finger, respectively, for the reconstruction of blood supply to the reconstructed finger. Two plantar digital nerves of the toe were then sutured to two proper digital nerves of the finger for the restoration of fingertip sensation.Results All reconstructed fingers survived completely. The follow-up period ranged from 6 to 24 months, and the appearance of the reconstructed fingertip was similar to that of the normal fingertip. Two-point discrimination of the reconstructed fingertip was (7.8±1.3) mm. The recovered pinch strength of the reconstructed finger was about (89.0±5.1)％ of that of the normal finger. Donor site healed well without complications.Conclusions Partial second toe transfer is an ideal aesthetic reconstruction method for fingertip defects; it can not only achieve a satisfactory appearance of the fingertip, but can also obtain excellent sensory and motor functions。

Abstract：Background Off-pump coronary artery bypass surgery (OPCAB) has been widely applied in recent years as a less invasive method of myocardial revascularization. This study evaluated the sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system during OPCAB.Methods From April 2004 to August 2010, patients with diffuse right coronary lesions were studied retrospectively and divided into two groups. Group 1 included seventeen patients who underwent this surgery while group 2 included twenty-one patients without right coronary artery surgical therapy. All patients presented with symptoms of angina. Blood flow of bridged vessels was measured. The perioperative ventricular parameters including left ventricular ejection fraction and end diastolic diameter were compared. During follow-up, myocardial nuclide imaging and coronary angiography were carried out.Results Off-pump coronary artery bypass was performed with an average of 3.6 grafts per patient. Hospital mortality was zero. At the time of follow-up, the patients in group 1 recovered better than in group 2 (P＜0.05). In both groups, the mean New York Heart Association (NYHA) class and ejection fraction increased significantly (P＜0.001) and the mean left ventricular end-diastolic diameter decreased significantly (P ＜0.05). Myocardial blood supply of inferior wall in group 1 was obviously improved by myocardial nuclide imaging. Coronary angiography for eight patients in group 1 verified that there was blood flow to myocardium in the arterialized vein.Conclusions Sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system can be performed during OPCAB. A postoperative improvement in the cardiac functions and the quality of life was documented, increasing our expectation for extensive application。

Abstract：Background A phase Ⅲ trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5-fluorouracil (5-FU) via a continuous intravenous (CIV) infusion.Methods Chemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m2 1 hour on day 1), CDDP (30 mg/m2on days 1 and 2), and 5-FU (1500 mg·m-2·24 h-1 CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate.Results Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1％ complete remission (CR), 71％ partial remission (PR), 14％ stable disease (NC/SD), and 7.1％ progressive disease (PD). The median survival time was 13 months. Nine patients (64％) had grade Ⅲ-Ⅳ neutropenia, and 4 patients (29％) had grade Ⅳ neutropenia, among whom 1 had grade Ⅳ neutropenia with grade Ⅲ nausea and vomiting.Conclusion The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer。

Abstract：Background Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.Methods Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (/Ca-L),inward rectifier potassium current (/K1), and transient outward potassium current (/to1) were studied in rat ventricular myocytes and sodium current (/Na), slow delayed rectifier current (/Ks), and HERG current (/Kr) were investigated in transfected human embryonic kidney 293 cells.Results One hundred μmol/L paeoniflorin reduced the peak /ca-L by 40.29％ at the test potential of ±10 mV (from (-9.78±0.52) pA/pF to (-5.84±0.89) pA/pF, n=5, P=0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22±0.27) mV vs. (-5.95±0.84) mV (n=5,P=0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred μmol/L paeoniflorin completely inhibited the peak /Na and the effect was reversible. Moreover,paeoniflorin inhibited the /K1 by 30.13％ at the test potential of -100 mV (from (-25.26±8.21) pA/pF to (-17.65±6.52)pA/pF, n=6, F=0.015) without effects on the reversal potential and the rectification property. By contrast, 100 μmol/L paeoniflorin had no effects on/to1, /Ks or /Kr channels.Conclusions The study demonstrated that paeoniflorin blocked /Ca-L, /Na, and /Kf without affecting /to1, /Ks, or /Kr. The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential。

Abstract：Background Periodontal disease is closely related to type 2 diabetes and is an important complication of diabetes.This study aimed to investigate the effect of periodontal treatment on levels of blood glucose (Glu) and glycosylated hemoglobin (HbA1c) among elderly patients with type 2 diabetes and periodontal disease.Methods A total of 107 elderly patients with type 2 diabetes and periodontal disease were selected and divided into two groups according to their HbA1c levels. Group A was a well-controlled diabetic group and group B was uncontrolled.Their probing depth (PD), attachment loss (AL), the value of Glu and HbA1c were analyzed before periodontal treatment and 4 months later.Results There was a significant difference in periodontal condition between groups A and B (P ＜0.01). The periodontal condition for both groups was significantly (P＜0.01) improved after periodontal therapy. The effect of treatment in group A was more pronounced than group B, and the difference was significant (P ＜0.01). After the periodontal treatment, Glu and HbA1c were reduced significantly in both groups (P ＜0.05).Conclusions Periodontal condition is related to the control of Glu level among elderly patients with type 2 diabetes and periodontal disease. Periodontal treatment can effectively reduce the level of Glu and HbA1c as well as improve the periodontal condition in elderly type-2 diabetes patients with periodontal disease。

Abstract：Background Cartilage injury has a very poor capacity for intrinsic regeneration. The cell-based treatment strategy for the cartilage repair using differentiated bone marrow mesenchymal stem cells (BMSCs) is, however, a promising approach to the chondral repair. This study was aimed to explore the chondrogenic potential of the goat BMSCs in the Transwell co-culture system and the poly-laetide-co-glycolide (PLGA) scaffolds.Methods The BMSCs were isolated from the goat iliac crest while the chondrocytes were obtained from the goat's last costal cartilage. In the Transwell co-culture system, the BMSCs co-cultured with chondrocytes were designed as group A,whereas the goat's BMSCs induced with the chondrogenic medium were group B. Both groups A and B were the experimental groups, while group C that only contained BMSCs was the control group. In the PLGA scaffolds co-culture system, BMSCs were seeded into the PLGA scaffolds, which were suspended in the 24-well plate, and the control group was established by presence or absence of chondrocytes at the bottom of the 24-well plate. Toluidine blue staining,Alcian blue staining, collagen Ⅱ immunofluoresence, collagen Ⅱ immunochemical staining, collagen Ⅰ, collagen Ⅱ, COL2a Q-PCR and osteopontin Q-PCR were used to examine the chondrogenic conditions as well as the expressions of chondrogenic and osteogenic genes.Results Cells isolated from the aspirates of the goat bone marrow proliferated rapidly and gained characteristics of stem cells in Passage 4. However, the differentiations of chondrocytes were not apparent in Passage 3. The results from Toluidine blue staining, collagen Ⅱ immunofluoresence and PCR showed the transformation of BMSCs to chondrocytes in the Transwell co-culture system and PLGA scaffolds. Although the cartilage gene expressions were upgraded in both chondrogenesis group and co-culture system, the osteopontin gene expression, which represents osteogenic level, was also up-regulated.Conclusions The Transwell co-culture system and the PLGA scaffolds co-culture system can promote the chondrogenic differentiation of the goat's BMSCs, while up-regulated osteopontin gene expression in the Transwell co-culture system implies the osteogenic potential of BMSCs。

Abstract：Background RhoA/ Rho kinase (ROCK) pathway is involved in pulmonary arterial hypertension (PAH) and pulmonary artery smooth muscle cell (PASMC) proliferation. Inhibition of ROCK has been proposed as a treatment for PAH. But the mechanism of RhoA/ROCK pathway and its downstream signaling in proliferation of human PASMCs is unclear. We investigated the effect of fasudil, a selective ROCK inhibitor, on platelet-derived growth factor (PDGF) induced human PASMC proliferation, and the possible association between RhoA/ROCK and extracellular signal-regulated kinase (ERK),p27KiP1.Methods Human PASMCs were cultured with the stimulation of 10 ng/ml PDGF, and different concentrations of fasudil were added before the addition of mitogen. Cell viability and cell cycle were determined with MTT and flow cytometry respectively. ROCK activity, ERK activity and protein expression of proliferating cell nuclear angigen (PCNA) and p27Kip1 were measured by immunoblotting.Results By MTT assay, PDGF significantly increased the OD value that represented human PASMC proliferation, and pretreatment with fasudil significantly reversed this effect in a dose-dependent manner. After PDGF stimulation, the percentage of cells in S phase increased dramatically from 15.6％ to 24.3％, while the percentage in G0/G1 phase was reduced from 80.6％ to 59％. And pretreatment with fasudil reversed the cell cycle effect of PDGF significantly in a dose-dependent manner. PDGF markedly induced ROCK activity and ERK activity with a peak at 15 minutes, which were significantly inhibited by fasudil. In addition, fasudil significantly inhibited PDGF-induced PCNA expression and fasudil also upregulated p27Kip1 expression in human PASMCs, which decreased after PDGF stimulation.Conclusion RhoA/ROCK is vital for PDFG-induced human PASMC proliferation, and fasudil effectively inhibited PDGF-induced human PASMC proliferation by up-regulation of p27Kip1, which may be associated with inhibition of ERK activity。

Abstract：Background Human epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown.Methods In this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro.Results HE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro.Conclusion HE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion。

Abstract：Background Preeclampsia is one of hypertensive disorders in pregnancy. It is associated with abnormal lipid metabolism, including fatty acid oxidation metabolism. Long chain 3-hydroxyacyI-CoA dehydrogenase (LCHAD) plays an indispensable role in the oxidation of fatty acids. It has been reported that nitric oxide (NO) is one of the regulatory factors of the fatty acid oxidation pathway. The aim of this research was to investigate whether the nitric oxide synthase (NOS)inhibitor L-NAME may cause down-regulation of LCHAD in the pathogenesis of preeclampsia.Methods Pregnant wild-type (WT) mice were treated with L-NAME or normal saline (NS) during gestation days 7-18 (early group), days 11-18 (mid group) and days 16-18 (late group), and apoE-/- mice served as a control. Systolic blood pressure (SBP), urine protein, feto-placental outcome, plasma lipid levels and NO concentrations were measured, and the expression of mRNA and protein for LCHAD in placental tissue were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively.Results In WT and apoE-/- mice, SBP and urinary protein increased following L-NAME injection. Fetal and placental weights and NO concentrations were reduced and total cholesterol, triglycerides and free fatty acid levels were increased in early and mid L-NAME groups in WT and apoE-/- mice, compared with the NS group. There was no significant difference between the late L-NAME group and NS group. RT-PCR and Western blotting analysis showed that the mRNA and protein levels of LCHAD expression were significantly down-regulated in the early and mid L-NAME groups but not in the late L-NAME group in the WT and apoE-/- mice compared with the corresponding NS groups.Conclusions Inhibition of NO in early and mid gestation in mice may cause hyperlipidemia and suppression of fatty acid oxidation, whereas preeclampsia-like conditions in late gestation may be a maternal vascular response to inhibition of NO。

Abstract：Multiple myeloma (MM) is an incurable plasma cell malignancy and is the second most common hematological cancer. It is characterized by complex, recurrent genetic and epigenetic abnormalities. Recent publications have linked miRNAs, a novel class of gene regulators to cancer including MM. miRNAs are about 20 nucleotide, single strand, non-coding RNAs that repress gene expression by mRNA degradation or translational repression. Aberrant miRNA expression profiles have been described in MM, and their functional roles in MM pathogenesis are being increasingly recognized. This review summarizes the current literature on the role of miRNAs in MM and offers perspectives on future research and utilization of miRNAs in MM management。

Abstract：Translational research has become a globally recognized model of medical research. Chinese government and doctors have begun to discuss the plan for its development. But most articles are focusing on the advantages rather than its pros and cons. In this essay, the authors discuss the disadvantages of translational research, its effects on clinical work and medical education, highlighting some potential problems and risks in theory and practice on case basis. Some important research management requirements are summarized in this essay to help bring the therapy from the research laboratory to the patient's bedside。

Abstract：Background Human cystic echinococcosis (CE) is a parasitic zoonosis of major public health importance throughout the world. CE is endemic throughout central Asia including northwestern China. In China, CE has been reported in 21 provinces, autonomous regions and municipalities, covering approximately 87％ of China's territories. It is most common in the pastoral and semi-pastoral western provinces and regions. This study aimed to reveal the natural history, curative effect and possible re-infection risk factors of human CE through long termed follow-up of treated and untreated CE cases in Hobukesar, Xingjiang, China.Methods Follow-up studies on CE were performed twice in Hobukesar from August 2005 to October 2008, after an initial mass screening performed in 1995 and 1996. Ultrasound scan was the primary diagnostic method.Results Among 24 patients with confirmed CE, 22 were treated (surgery in 19 and chemotherapy in three). Two recurrent cases and one re-infection case were subsequently found during follow-up. The CE type of one of the recurrent cases reverted from CE4 to CE3, as classified using World Health Organization (WHO) guidelines.Conclusions Ultrasound was required to differentiate primary, recurrent and re-infection cases during epidemiological investigation and follow-up of CE. Most patients did not change their habits, which may be one possible cause of reinfection. One recurrent case suggested that, despite initial suggestion from the WHO Informal Working Group on Echinococcosis, CE4-type cysts are not inactive。

Abstract：Background Massive presacral venous plexus hemorrhage during radical resection of rectal carcinoma is rare, but when it occurs, bleeding can be uncontrollable, leading to death in some cases. Medical adhesive gauze sticking and packing and thumbtack compressive fixation are often used for hemostasis, but these methods are not effective in cases of uncontrollable massive hemorrhage. Therefore, identifying a practical, accurate, and reliable method of hemostasis in these cases is essential.Methods Between January 2004 and December 2009, we treated 3 patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma by placing small, trimmed thin steel plates at the bleeding sites. The plates were fixed with a saddle-type application of thumbtacks.Results Bleeding was successfully controlled in all 3 patients, and intestinal anastomosis was carried out after hemostasis. No complications were observed.Conclusions Application of a small, thin steel plate to the bleeding site with thumbtack fixation is a simple and effective method of hemostasis in patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma。

Abstract：Fibrovascular polyp of the hypopharynx and esophagus, a rare, benign, intraluminal and submucosal tumor, is most commonly originated from the proximal esophagus. We discussed four cases with regurgitation, respiratory symptom or the feeling of a mass in the throat. All the patients were examined with laryngoscope under general anesthesia. A transverse cervical incision was performed in one patient and the polyps were excised under laryngoscope with CO2 laser in the other three patients. All the lesions were removed successfully. Diagnostic and therapeutic principles involved in these cases are presented and discussed. The recognition of fibrovascular polyp of the hypopharynx and esophagus as a potential cause of regurgitation is paramount. Surgical excision is recommended because of the satisfactory outcome。

Abstract：A 68-year-old female patient was treated for unhealed ulcer in the fourth toe of the left foot. Clinical examinations identified severe stenosis of the proximal segment and occlusion of the distal segment of the left anterior tibial artery, and occlusion of the left posterior tibial artery and the peroneal artery. The proximal stenotic segment of the left anterior tibial artery was dilated, but the distal occlusive part failed to be re-canalized. Left anterior tibial artery to dorsal pedal artery bypass was performed on the patient with an epoxide-crosslinked, special radicals antigen-sealed, porcine-derived biological graft; debridement of the left 4th digiti pedis was also performed. Postoperation course was uneventful. The pulse of the left dorsal pedal artery was strong. The ankle brachial index (ABI) increased from 0.60 to 1.09. Warfarin and two antiplatelet drugs were given after the operation. Six months after operation, computed tomographic angiogram (CTA)identified the patent graft。

Abstract：Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor Ⅶ (rFVlla) 3.6 mg (70 μg/kg). Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were quickly corrected to normal ranges.Fibrinogen level elevated from 0.5 g/L before using rFVIla to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVlla may be effective in the management of intractable hemorrhage in patients with HLH。

Abstract：Cogan's syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis.Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS。

Abstract：We report two patients with unilateral vertical retraction syndrome. Magnetic resonance imaging (MRI) of the orbits of the two cases showed similar size and location of the orbital structure, but with dramatically different strabismus type. MRI sagittal reconstruction of the orbits suggested that abnormal muscle tissue arised from the inferior rectus, which might be associated with retraction and narrowing of the palpebral fissure and atypical strabismus as well。

Abstract：High degree atrioventricular block (HDAVB) is a serious complication of transcatheter closure of a perimembranous ventricular septal defect (PMVSD). We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure。