The replicative senescence of mesenchymal stem cells(MSC) during the in vitro expansion limits their use in the research and treatment of many disease. Also, MSC senescence may promote the individual senility, hypofunction of tissue and organ, and tumorigenesis. Thus, in order to better understand the senescent mechanism and delay the senescence, even reverse MSC senescence, the roles of signaling pathway, such as Wnt/β-catenin, MAPK/ERK, PI3K/AKT and ROS-related signaling pathway during the MSC senescence all were reviewed, so as to can deepen the under-standing of MSC senescence and provide a new thinkings for delaying, even reversing the MSC senescence.

OBJECTIVETo investigate the effect of homoharringtonine (HHT) on proliferation and apoptosis of CML cell line K562 cells and to explore its possible mechanism through mTOR pathway.

METHODSK562 cells were cultured with different concentrations of HHT or in its combination with mTOR inhibitor rapamycin (RAPA) for 24 hours. The cell viability was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry, the expressions of BCL-6, Caspase-3 and mTOR signal pathway related proteins was assayed by Western blot, the expression of BCL-6 mRNA was determined by RT-PCR.

RESULTSThe HHT inhibited proliferation and induced apoptosis of K562 cells in a concentration-dependent manner(r=0.970). With the increasing of HHT concentration, the expression level mTOR signal pathway related proteins increased(r=0.908), while the mRNA and protein expression levels of BCL-6 decreased(r=-0.961, r=-0.981), as compared with the HHT alone, the combination of HHT with RAPA could down-regulate the expression of mTOR signal pathway related protein and caspase-3, and up-regulated expression of BCL-6.

CONCLUSIONHHT induces apoptosis of K562 cells by inhibiting BCL-6 expression through mTOR signal pathway.

OBJECTIVETo investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients.

METHODSClinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/mper day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated.

RESULTSAmong 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 10/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%).

CONCLUSIONDecitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.

OBJECTIVETo investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.

METHODSThe clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.

RESULTSAmong total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).

CONCLUSIONImportance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.

OBJECTIVETo investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD).

METHODSThe method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL.

RESULTSThe sensitivity of this assay reached the 10level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P<0.01). No statistical differences were found between newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases and healthy donors (P>0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry.

CONCLUSIONHB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.

OBJECTIVETo compare of clinical effects of different surgical methods in the treatment of elderly femoral neck fractures.

METHODSFrom January 2013 to June 2016, 144 elderly patients with femoral neck were treated and divided into artificial hip replacement group and cannulated screw fixation group according to the surgical methods. In the total hip arthroplasty group, there were 89 cases, 28 males and 61 females, with an average age of(84.10±3.10) years old;Hollow nail fixation group 55 cases, 20 males and 35 females, with an average age of (86.80±2.88) years. Preoperative patients data, postoperative complications, mortality and postoperative Harris hip score were compared between the two groups.

RESULTSA total of 144 cases were followed up for 12 to 36 months with an average of 18 months. There was no significant difference between two groups in gender, fracture side, preoperative complications, osteoporosis, ASA score, injury to surgery interval, the number of patients admitted to ICU and perioperative death. However, the patients in hollow screw fixation group was older than the joint replacement group(=5.311,<0.05);The degree of preoperative fracture displacement in the joint replacement group was higher than that in the hollow nail fixation group(χ²=6.894,=0.009<0.05);Hollow nail fixation group in operation time, hospital stay, intraoperative blood loss, perioperative blood transfusion was significantly better than the number of joint replacement group(<0.05);The Harris score of the joint replacement group was higher than that of the hollow screw fixation group(<0.05).

CONCLUSIONSFor elderly femoral neck patients, if there is a significant shift in the fracture (Garden III, IV), the preferred treatment is hip replacement. Postoperative complications are relatively small, satisfactory joint function recovery. If the fracture displacement is not obvious (Garden type I, II) or patients with more medical diseases, poor physical condition, poor surgical tolerance, postoperative life expectancy is not high, the first choice is closed reduction and cannulated screw fixation.

OBJECTIVETo compare the clinical effects between anterior cervical discectomy and fusion(ACDF) combined with anterior cervical corpectomy and fusion(ACCF) and cervical posterior single open-door laminoplasty with mini-titanium plate fixation in treating three-segment cervical spondylotic myelopathy.

METHODSThe clinical data of 63 patients (39 males and 24 females) with three-segment cervical spondylotic myelopathy underwent surgical treatment from March 2014 to March 2016 were retrospectively analyzed. Among them, 43 cases were treated by ACDF combined with ACCF(anterior group), and 20 cases were treated by cervical posterior single open-door laminoplasty with mini-titanium plate fixation(posterior group). Operative time, intraoperative blood loss, postoperative complications were compared between two groups. And according to JOA score to evaluate the clinical effect.

RESULTSAll the patients were follow-up from 16 to 40 months with an average of 25.8 months. Operative time of anterior group and posterior group were (123.70±6.21) min and(118.70±5.41) min, respectively, there was no significant difference between two groups(>0.05). Intraoperative blood loss of anterior group and posterior group were (85.23±7.51) ml and (107.18±9.41) ml, respectively, there was significant difference between two groups(<0.05). In anterior group, axial symptoms occurred in 6 cases, dysphagia in 1 case, and no C₅ nerve root palsy, hoarseness and choking cough were found, the incidence rate of complication was 16.3%(7/43); and in posterior group, axial symptoms occurred in 5 cases, C5 nerve root palsy in 1 case, and no dysphagia, hoarseness and choking cough were found, the incidence rate of complication was 30.0%(6/20); there was significant defference in incidence rate of complication between two group(<0.05). At 1 week after operation and final follow-up, the JOA scores of anterior group were obviously better than that of posterior group(<0.05).

CONCLUSIONSAbove-mintioned two surgical treatment for cervical spondylotic myelopathy can provide instantly stability, the method of ACDF combined with ACCF was obviously better that of the method of cervical posterior single open-door laminoplasty in intraoperative blood loss, the incidence rate of complications, clinical effect.Thus, for the treatment of three-segment cervical spondylotic myelopathy, the method of ACDF combined with ACCF would be firstly chosen.

OBJECTIVETo compare the safety of sevoflurane anesthesia with laryngeal mask and tracheal intubation in cesarean section in women with heart disease.

METHODSFifty-two pregnant women with heart diseases undergoing cesarean section were randomized into laryngeal mask (LAM) group and tracheal intubation group. In LAM group, 6% sevoflurane was given at the rate of 6 L/min for induction with a maintenance sevoflurane concentration of 3%. In the intubation group, 1.5 mg/kg propofol and 1 µg/kg remifentanil were injected intravenously, and after achieving D0 with Narcotrend monitoring, 0.9 mg/kg rocuronium was injected and intubation was performed 1 min later. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded in the two groups before anesthesia induction (T), at intubation or laryngeal mask placement (T), skin incision (T), and extubation or laryngeal mask removal (T). The surgery to fetal birth time, uterine incision to fetal childbirth time, drug discontinuation to awake time, and newborn Apgar scores were also recorded. Sevoflurane consumption and maternal comfort during hospitalization were compared between the two groups.

RESULTSIn LAM group, HR and MBP at Tand Twere significantly lower than those in the intubation group (P<0.05). The drug discontinuation to extubation time and to awaken time were significantly shorter in LAM group than in the intubation group (P<0.05), but the operation time and fetal child birth time were comparable between the two groups (P>0.05). The women in LAM group reported better physical and psychological comforts than those in the intubation group (P<0.05). The neonatal Apgar scores and the scores of health education, satisfaction with hospital environment and service were all similar between the two groups (P>0.05).

CONCLUSIONSevoflurane anesthesia with laryngeal mask can achieve satisfactory anesthetic effects in cesarean section in women with heart disease.

OBJECTIVETo analyze the clinical effect of spinal cord decompression and lavage therapy on chronic cervical spinal cord injury and explore the possible mechanism.

METHODSFifty-seven patients with chronic cervical spinal cord injury treated in our hospital from January, 2008 to January, 2015 were enrolled, including 17 with multilevel cervical disc herniation, 25 with long segmental ossification of the posterior longitudinal ligament, 13 with hypertrophy or calcification of neck ligamentum flavum, and 2 with old cervical fractures. Open-door spinal canal laminoplasty via a posterior approach and decompression in simple extramedullary decompression was performed in 31 cases (group A), and open-door spinal cord incision decompression via a posterior approach, saline irrigation, and spinal canal laminoplasty in intramedullary decompression was performed in 26 cases (group B). The pre-operative cerebrospinal fluid in group B patients was collected to examine the inflammatory factors. All the patients were followed up and evaluated for pre- and postoperative JOA scores to calculate the improvement rate with regular examinations by X-ray, CT or MRI.

RESULTSImaging examinations 2 weeks after the operation showed obvious relief of the primary lesion in both groups, and the improvement of high signals was better in group B than in group A. The mean improvement rate at 12 months after the operation was 52.33% in group A and 61.52% in group B (P<0.05), and the mean JOA score was significantly higher in group B than in group A (14.80∓1.51 vs 13.58∓0.56; P<0.05). Cerebrospinal fluid leakage occurred in 3 cases, epidural hematoma in 2 cases, internal fixation loosening in 1 case in group A; portal shaft fracture and internal fixation loosening occurred in 1 case in group B. Postoperative recovery time was shorter in group B and entered the platform phase in 3 months. The inflammatory factors IFN-γ, IL-17F, IL-6 and sCD40L were all significantly higher than the normal levels after spinal cord injury, and the increment of IL-6 was the most conspicuous (P<0.05).

CONCLUSIONIntramedullary and extramedullary decompression can achieve better outcomes than extramedullary decompression in patients with chronic cervical cord injury. This may be related not only to relieving adhesions and secondary compression by cutting the dura under the microscope, but also to removal of local inflammatory factors.

OBJECTIVETo assess the safety and advantages of robotic pancreatic surgery (RPS) based on the single-team experience with 1010 cases.

METHODSThe clinical data of 1010 cases of RPS performed by a single team from November, 2011 to September, 2017 in our hospital were collected prospectively and analyzed. In most of cases the surgeries were performed using the third-generation da Vinci robotic surgical system.

RESULTSThe 1010 cases receiving RPS included 417 cases of robotic pancreatoduodenectomy (RPD), 428 cases of robotic distal pancreatectomy, 60 cases of robotic central pancreatectomy, 53 cases of robotic pancreatic tumor enucleation, 3 cases of Appleby procedure, and 49 cases of other operations (including 4 cases of innovative robotic retroperitoneal laparoscopic surgery, 4 cases of robotic pancreatic tumor enucleation combined with main pancreatic duct bridging repair, 1 case of single incision robotic pancreatic tumor enucleation, and 2 cases of robotic central pancreatectomy combined with end-to-end anastomosis reconstruction). The median operative time was 210 min (30-720 min) with a median intraoperative blood loss of 80 mL (10-2000 mL), a conversion rate of 4.06% (41/1010), a blood transfusion rate of 6.7% (68/1010), a mean post-operative stay of 10.87∓6.70 days, a complication rate (beyond grade III according to Clavien-Dindo scoring system) of 8.0% (81/1010), and a pancreatic fistula rate (beyond) grade B of 9.21% (93/1010). The mortality rate of the patients was 0.69% (7/1010) in 30 days and 1.31% (12//934) in 90 days. The application of RPS in total pancreatectomy increased steadily from the rate of 10.44% in 2012 to 72.06% in 2017.

CONCLUSIONThis represents to our knowledge the world largest series of robotic pancreatic resections. RPS is expected to gradually replace open procedure and laparoscopic procedure to become the primary choice of approach for pancreatectomy. After the learning curve, RPS procedure including distal pancreatectomy, robotic Appleby procedure and other operations can be safely performed, and the experiences from other centers can be beneficial to reduce severe complications in the early stage of learning.