Volume 93  ·   Issue 01  ·  2013

To explore the survival of newly diagnosed maligant gliomas patients on combined modality therapy of surgery,radiotherapy and chemotherapy.

The data of 122 newly diagnosed maligant glioma patients on combined modality therapy at our center between 2000 and 2010 were retrospectively reviewed and analyzed.The median age was 40 years old(range:5-75)and median Karnofsky performance status score(KPS)80(range:60-100).Combined modality therapy consisted of surgery(maximal safety tumor resection),followed by fractionated focal irradiation for a total dose of 54-60 Gy and then 4-6 cycles of adjuvant chemotherapy including temozolomide or nitrosourea-based regimens or other ones without temozolomide and nitrosourea.The overall and progression-free survivals were analyzed by the Kaplan-Meier method and the influencing factors screened by Cox proportional hazard model.

There were gradeⅣ (n=70)and gradeⅢ (n=52).The median survival periods were 17.0 months for gradeⅣpatients and 36.0 months for gradeⅢones.The 2,3,4 and 5-year survival rates were 32.0% vs 64.8%,19.6% vs 47.8%,11.8% vs 32.0% and 5.9% vs 25.4%(P<0.01)for gradesⅣandⅢpatients respectively.The median progression-free survivals were 9.0 vs 12.0 months and 1,2 and 3-year progression-free survival rates 30.8% vs 50.0%,12.3% vs 31.4% and 9.2% vs 17.7%(P<0.01)respectively.Multivariate analysis revealed that histologic type was an independent prognostic factor.

Combined modality therapy of surgery,adjuvant radiotherapy and chemotherapy may improve the survival of patients with malignant gliomas.

To employ whole-genome messenger RNA profiling to identify the genes involved in malignant progression in glioma.

The whole genome expressed genes were profiled in 220 glioma patients from the Chinese Glioma Genome Atlas(97 LGGs and 123 HGGs).The differential expressed genes between LGG and HGG were identified by SAM analysis.Microarray data were validated by immunohistochemistry.

Among all the detected genes,the genes up-regulated mostly in high-grade glioma were IGFBP-2,CKLF,PTTG1,OSTCL and PTTG2 while those down-regulated mostly SEC31,RRP7B,HOOK3,SNRPN and CSMD3.Validation of IGFBP-2 with immunohistochemical staining showed a good correlation with the microarray data.

A panel of potential genes of malignant transformation may serve as future targets of gene therapy for glioma.

To explore the effects of all-trans retinoic acid(ATRA)on glioma stem cell phenotype.

The glioma stem cell(GSC)from surgically resected human glioma specimens were isolated and enriched by neurosphere assay and then its differentiation was induced with all-trans retinoic acid(ATRA,1μmol/L)for 1 week.Markers were determined by flow cytometry,Western blot and reverse transcription-polymerase chain reaction(RT-PCR).Side population cells were analyzed by flow cytometry.Growth characteristics were detected by neurosphere formation assay and cell cycle analysis.GSC and the differentiated cells(1×10⁵)were implanted stereotactically and intracranially into the Balb/c nude mice to compare the survival time.All data were analyzed with the SPSS software version 17.0.

ATRA potently induced the differentiation of GSC and reduced glioma stem cell phenotype.And there were an elevated expression of glial fibrillary acidic protein(GFAP)and a reduced expression of such stem cell makers as CD133 and Nestin.The side population rate decreased.ATRA inhibited the neurosphere formation of GSC and induced the arrest of cell growth.ATRA could prolong the survival time.

GSC may be differentiated efficiently by ATRA.The stemness of GSC decreases obviously after the differentiation of ATRA and the survival time is prolonged.Thus ATRA may be applied for targeted therapies of glioma stem cell.

To assess the value and feasibility of positron-emission tomography-magnetic resonance imaging(PET-MRI)fusion technology in delineating tumor boundaries and positioning biopsy targets of gliomas so as to facilitate the diagnosis and treatment of gliomas.

A total of 18 patients with a preoperative diagnosis of gliomas discharged from our hospital from January 2010 to April 2011 were recruited.All of them underwent the preoperative examinations of MRI,fluorodeoxyglucose(FDG)PET and fluoroethyl-choline(FECH)PET.The digital image data were transferred into Brain LAB planning software and three types of images automatically fused.The tumor contours were drawn on the basis of each image modality separately.The extent of tumor resection or biopsy target was determined on the integrated information including tumor contours on PET and MRI images and intraoperative observation of tumor texture.

On PET scans,the average standard uptake value(SUV)of glioblastomas was higher than that of gradeⅡ-Ⅲgliomas.With regard to the patients with both biopsy and tumor resection,the pathological diagnosis of the specimen obtained from the PET-guided biopsy was consistent with that of subsequently resected tissue.All 11 patients undergoing tumor resection were classified according to relationship between the image-based tumor contour and actual extent of resection.Six of them benefited from contour delineated by FDG PET images and 3 of them benefited from FECH PET.The combined contribution ratio of both PET methods was 9/11.

PET-MRI fusion technology may accurately delineate tumor boundary and sensitively target the region of high proliferation or metabolism.A more radical resection and more accurate histological diagnosis can be thus achieved and yield a probably better prognosis of gliomas.

To evaluate the prognosis and efficacies of comprehensive treatment for recurrent gliomas.

A total of 62 patients diagnosed as recurrent gliomas at our hospital between May 2007 and January 2012 were reviewed and analyzed.The investigators compared the prognosis of different grades of gliomas and evaluated the efficacies of combined modality therapy of surgery,radiotherapy,chemotherapy and immunotherapy.

Their median periods of time-to-progression(TTP)and overall survival(OS)were 6.0 and 13.0 months respectively.The median TTP of WHO gradeⅡ(n=21),Ⅲ(n=13)andⅣ(n=28)recurrent gliomas were 9.0,9.0 and 5.0 months respectively.And the average OS of WHO gradeⅡ,ⅢandⅣrecurrent gliomas were 26.6,21.4 and 13.8 months respectively.The efficacious rate of chemotherapy was 26.7%.

Combined modality therapy based on chemotherapy may moderately improve the prognosis of recurrent gliomas.And the pathological grades of primary tumors are correlated with the prognosis of recurrent gliomas.

To summarize the surgical approaches and efficacies of flexion deformity caused by antebrachium muscle hemangioma.

Retrospective analysis was performed in 41 cases of flexion deformity caused by antebrachium muscle cavernous hemangioma.There were 16 males and 25 females with an age range of 14-56 years old.Twenty-nine cases were surgically treated once and 12 re-operated.Hemangioma resection and Z-shaped tendon lengthening was adopted to cure antebrachium muscle hemangioma.During the follow-ups,the operative success rate and flexible extents of forearm,wrist and finger were evaluated.

Complete resection was performed in 37 cases and partial resection in 4.All patients underwent Z-shaped tendon lengthening.The operative success rate was 90% during a follow-up period of 6-12 months.After treatment,the pains disappeared and bend function recovered.Four cases had little improvement in movement range.

The procedure of hemangioma resection and Z-shaped tendon lengthening should be performed as early as possible for hemangioma caused by antebrachium muscle cavernous hemangioma.And physical training is helpful for function reconstruction.

To discuss the angiographic findings and the safety and efficacy of interventional therapy for post-pancreaticoduodenectomy hemorrhage.

The clinical data,features of angiography,interventional treatment technology and prognosis of 29 patients underwent post-pancreaticoduodenectomy bleeding between August 2009 and June 2012 were retrospectively analyzed in our hospital.

In all 29 patients,6 cases underwent gastrointestinal bleeding,21 cases of abdominal bleeding,2 cases had abdominal cavity and gastrointestinal bleeding,hemorrhage occured 8 h—72 d after surgery.Angiographic findings including:extravasation of contrast media,and pseudo aneurysm formation,local arterial intima not smooth,stenosis,distal artery branch expansion.The success rate of interventional techniques was 93.94%,hemostatic rate was 90%.3 cases died.

The embolization therapy is a safe and effective technique,should be as the first-line diagnostic and treatment choice for patients with post-pancreaticoduodenectomy bleeding.

To discuss the surgical techniques for lung cancer larger than 10 cm.

Via a modified anterolateral thoracotomy entered through the 4th or 5th intercostal space,intrapericardial access to pulmonary vessels was obtained for pneumonectomy or extended pneumonectomy in all patients,after excluding the feasibility of lobectomy.

From March 2009 to October 2011,13 consecutive patients with lung cancer larger than 10 cm,were admitted to surgical resection via this approach for intrapericardial pneumonectomy/extending pneumonectomy.The whole processes were smooth and without any major morbidity.

The main approach for lung cancer larger than 10 cm is pneumonectomy.The key to surgical success is intrapericardial controlling of the hilum vascular.The modified anterolateral thoracotomy may facilitate this procedure.

To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer(MBC)developing successive resistance to multi-line targeting therapies.

The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department.All patients were treated with trastuzumab,lapatinib and retreated with trastuzumab sequentially.Twenty-one patients progressed during the initial trastuzumab therapy.All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently.A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis.

The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy.The time-to-progression(TTP)of prior lapatinib therapy was an influencing factor of median progression-free survival(PFS)(P<0.0001)and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival(OS)(P=0.008)of trastuzumab retreatment in our univariate analysis.The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy>12 weeks(hazard ratio(HR)=0.02,P=0.003)or whose duration of double trastuzumab treatment≤1 year(HR=0.26,P=0.03)was significantly prolonged in multivariate analysis.Meanwhile,the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment≤4 weeks decreased 89% as compared with trastuzumab retreatment(HR=0.11,P=0.004).

TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment.And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment.The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

To explore the effect of dexmedetomidine in acute postoperative pain and remifentanil-induced hyperalgesia.

From January 2011 to June 2012,120 patients scheduled for elective abdominal surgery under general anesthesia were included in this study.All patients received intravenous remifentanil infusion during operation,and dexmedetomidine was given after anesthesia induction.The postoperative mechanical pain threshold,pain visual analog scale(VAS)score,morphine consumption,and score of sedation(Ramsay)was recorded.

Relatively large-dose intraoperative remifentanil resulted in lower mechanical pain threshold and higher dose of postoperative morphine consumption.Dexmedetomidine reduced postoperative morphine consumption significantly,and increased Ramsay scores,but had no effect on mechanical hyperalgesia.

Dexmedetomidine can alleviate the acute postoperative pain effectively,but the effect is not dependent on inhibiting remifentanil-induced hyperalgesia.

To evaluate the efficacy of multimodal-antiemetic therapy on postoperative nausea and vomiting(PONV)in patients undergoing gynecological laparoscopy.

129 patients scheduled for gynecological laparoscopy were randomly allocated to a multimodal-antiemetic group(group M,with 65 cases)or an ondansetron control group(group C,with 64 cases).In group M patients received a target-controlled infusion of propofol and remifentanil,prophylactic dexamethasone 10 mg and tropisetron 4 mg were given and parecoxib sodium 40 mg was used 30 minutes before the end of surgery.In group C patients received sevoflurane and 50% nitrous oxide.Prophylactic ondansetron 4 mg was given to patients 30 min before the end of surgery.The incidence of nausea and vomiting,use of rescue antiemetic drugs were recorded for 24 h.

24 h after surgery,the incidence of patients who suffered PONV was significantly lower in Group M compared with Group C(29% vs 70%,P<0.05).At 0-2 h,2-6 h,6-24 h after surgery,the incidences of PONV were 8%,6% and 25% for group M respectively,significantly lower than those for group C,which were 33%,30% and 66% respectively(P<0.05).

Multimodal-antiemetic therapy|a regimen including total intravenous anaesthesia with propofol and remifentanil,prophylactic antimetics(dexamethasone at induction and tropisetron at end of surgery),and multimodal analgesia with parecoxib sodium could significantly reduce the incidence of PONV after gynecological laparoscopy.

To evaluate the values of ocular hemodynamics and serum endothelin-1(ET-1)in the early diagnosis of diabetic retinopathy(DRP).

A total of 85 DRP patients were examined by ophthalmoscope and fluorescein angiography and divided into 3 groups:no obvious retinopathy(n=20),non-proliferative diabetic retinopathy(n=35)and proliferative diabetic retinopathy(n=30).Control group included 15 healthy volumterrs.The peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of ophthalmic artery(OA)and central retinal artery(CRA)were measured by color Doppler energy imaging.The level of endothelin-1 was measured by radioimmunoassay.Then plasma ET-1 levels and eye vascular hemodynamic parameters were compared with correlation and diagnostic specificity after data analysis.

Compared with the control group,DRP,EDV and PSV decreased progressively while RI increased gradually(P<0.05).EDV and RI were more sensitive than PSV in diagnosis.The plasma level of ET-1was significantly higher than that of control group(P<0.05).And it was correlated positively with RI and negatively with PSV and EDV of CRA.The diagnostic value of EDV was higher than that of ET-1 level.

Ocular hemodynamics become abnormal during the early stage of DRP and worsen with the progress of DRP.An elevated plasma level of ET-1 may lead to the abnormity of retinal hemodynamics.The test of plasma ET-1 and the examination of ocular hemodynamics may play an important role in the early diagnosis of DRP.

To explore the clinical manifestations,diagnosis,treatment and prognostic features of melanocytic neoplasms of central nervous system(CNS).

A total of 24 patients with melanocytic neoplasms of CNS underwent surgery and were confirmed pathologically our hospital during 2006—2012.Their clinical data were collected.There were primitive melanocytic neoplasms(n=8)and metastatic melanoma(n=16)according to the diagnostic criteria of Willis.The scans of magnetic resonance imaging(MRI)showed hyperintensity on T1 weighted image(n=15)and hypointensity on T2 weighted image(n=20).

The outcomes were total resection(n=11),subtotal resection(n=9)and partial resection(n=4).All 8 primitive melanocytic neoplasms were followed up.Among them,2 cases died postoperatively at 15 and 40 months respectively.The remaining 6 cases survived 13-56 months after craniotomy.And 14/16 patients of metastatic melanoma were followed up,8 cases died and the mean survival period was 4.5 months.The remaining 6 cases survived 1-7 months after craniotomy.Immunohistochemical staining demonstrated that the positive rate of H MB-45 was 9/10,S-100 9/11 and Vimentin 8/11.

Melanocytic neoplasms of CNS are rare lesions with characteristic MRI features.Immunohistochemical staining helps to reach a definite pathological diagnosis.Surgical excision is recommended.Differentiation of primary and metastatic neoplasm is critical for prognostic evaluations.

To analyze the X-ray,CT and MR imaging findings in skeletal disease with primary hyperparathyroidism(PHPT),so as to discuss the clinic feature and differential diagnosis.

Thirty patients with PHPT were confirmed by surgery and pathological examination.In 15 patients the lesion were found in femur.There were 15 tibia,12 fibula,and 14 iliac lesions.In three patients lesions were found in vertebrae.Three patients had lesions in humeri.In five patients lesions were found in rib.Twelve patients had lesions in phalanges.Thirty patients were studied preoperatively with radiographs,CT and MR imaging.The imaging findings were compared with the pathologic diagnosis and confirmed by double blind method.

Radiographs of the bone in 30 patients showed generalised osteopaenia.There were 20(66.7%)cases with bone resorption,which include 12(40.0%)cases with subperiosteal resorption,11(36.7%)cases with cortical bone resorption,and 10(33.3%)cases with subchondral resorption.There were 19(63.3%)cases with osteitis fibrosa cystica/brown tumor.There were 5(16.7%)paitents sustained a pathological fracture.

X-ray,CT and MR imaging foundings reflect the imaging and pathology features in skeletal disease of PHPT.The iliac lesions could been found in common,and usually eroding sacroiliac joint.Skeletal disease of PHPT should be differentiated from osteolytic metastatic tumor of bone,osteodysplasia fibrosa,giant cell tumor of bone and aneurysmal bone cysts.

To explore the incidence of depression in movement disorders and associated factors.

A total of 121 Parkinson′s disease(PD)patients from August 2010 to June 2011 and 62 ET patients from July 2009 to June 2010 were recruited.All of them were outpatients of our hospital.PD patients received the unified Parkinson′s disease rating scale(UPDRS)-motor examination and a modified Hoehn and Yahr scale to stage the severity of their disorders while 62 essential tremor(ET)patients were evaluated with tremor rating scale for tremor-motor examination(items 1-15 of rating scale).All participants completed Hamilton depression rating scale(24 items)to measure the presence and degree of symptoms of depression.

It was found that 56.2% of PD patients and 53.2% of ET patients were depressed(HAMD score of 8 or higher).Among them,the rates of mild depression were 38.9% and 35.5%,moderate depression 15.7% and 17.7% and severe depression 1.7% and 0% in PD and ET patients respectively.No significant differences existed between each group.The factor scores of cognitive impairment were 1.81±1.86 and 1.04±1.07 in PD and ET patients while those of sense of despair were 2.95±1.97 and 4.09±2.08 in each group.The differences had statistical significance in two factor scores of two groups(P<0.05).No differences in anxiety/somatization,lose weight,day-and-night changes,block and sleep disorders between two groups.For PD patients,the motor score of UPDRS-Ⅲwas positively correlated with total H AMD score(r=0.511,P<0.01).Similarly,for ET patients,tremor rating scale for tremor-motor subscale score and H AMD score were positively correlated(r=0.828,P<0.01).

As two common movement disorders,PD and ET have a high incidence of depression.The severity of depression is similar in two groups.There is no significant intra-group difference in severity and frequency of depression.The most common symptoms are anxiety somatization,anhedonia,working difficulty,slowness and sleep disturbance.The depression and motor symptoms are positively correlated.Like the non-motor symptoms in PD,we should also pay attention to the non-motor symptoms in ET.

To explore the intervention of aspirin and the changes of CX3CL1 and its receptor CX3CR1 in a rat model of acute pulmonary embolism(APE).

The autologous blood clot method was employed to establish the animal model of APE.A total of 64 rats were randomly divided into 4 groups: normal group(control),sham operation group(sham), model group(model)and aspirin group(aspirin). The profiles of pathology and tissue immunohistochemistry of CX3CL1 and CX3CR1 were compared at 4 h versus 72 h post-embolization.

At 4 h and 72 h post-embolism,hematoxylin and eosin staining of lung tissue showed a high degree of expansion of alveolar wall vessels and congestion. Furthermore, several rats had hemorrhagic infarction under light microscope.After the dosing of aspirin, hyperemia of lung tissue and the number of rats with infarction significantly decreased. Immunohistochemistry: CX3CL1 was predominantly expressed in cytoplasm and membrane while CX3CR1 in cytoplasm and nuclear membrane.Both showed strongly positive expression in the model group(++++)and slightly positive expression in the aspirin group(+). At 4 h and 72 h post-embolization,the CX3CL1 and CX3CR1-positive cell counts of the control, sham and aspirin groups were significantly less than those of the model group(P<0.05).

Aspirin may improve the pathology and inhibit the expression of CX3CL1 and CX3CR1 in APE lung.

To explore the expression pattern of amyloid beta-protein(Aβ)in bone tissue and elucidate its possible effects on bone metabolism of proximal tibia in APP/PS1 transgenic mouse.

Immunohistochemisty and immunofluorescence were used to analyze the horizontal and longitudinal sections of proximal tibia in 9-month-old APP/PS1 transgenic mouse.And the tissues of APP/PS1 transgenic and wild-type mice were harvested to analyze the serum levels of tumor necrosis factor(TNF-α)and interleukin-6(IL-6)by enzyme-linked immunosorbent assay(ELISA).Micro-computed tomography(micro-CT)was used to analyze the changes of bone microarchitecture and bone mineral density(BMD)of proximal tibia.

Aβ was expressed in bone trabecular and osteocytes of proximal tibia in APP/PS1 transgenic mouse.As compared with wild-type mice(32.1±6.8|28.9±4.5|3.17±0.26|3.17±0.26|1229±113),the serum levels of TNF-α(42.3±7.4)and IL-6(40.9±6.7)of APP/PS1 transgenic mice significantly increased.However bone microarchitecture(1.95±0.22)and BMD(187±29|1109±104)of proximal tibia were significantly lower on micro-CT(P<0.05).

Aβis expressed in bone tissue and it is associated with the changes of bone mineral density.Thus it may play an important role in the pathogenesis of osteoporosis through the changes of TNF-αand IL-6 in APP/PS1 transgenic mouse.

To explore the molecular mechanisms of antithrombin(AT)deficiency caused by novel double heterozygous mutations.

Wild-type and mutant AT cDNA expression plasmids(ATwt,AT-c.134G>A,AT-c.342T>G,AT-c.134G>A and AT-c.342T>G)were transfected into HEK293T cells.Western blot was used to detect the AT:Ag in cell lysates.Homology was used to reestablish 3-D spatial structure of AT.Laser confocal assay was utilized to analyze the distribution of AT in endoplasmic reticulum(ER).

Compared to the wild-types,the AT expression of HEK293T cells sharply increased when they were transfected by AT-c.342T>G or AT-c.134G>A and c.342T>G.Homology modeling showed that the mutation(AT-c.342T>G)caused a decreased distance between Arg and surrounding bases as Arg′s side chain was significantly longer than Ser′s.The mutation of 13th base pair decreases the distance between AT and heparin.Laser confocal assay showed that the AT protein concreted in HEK293T cells when they were transfected by mutant plasmids(AT-c.134G>A and c.342T>G)and aggregated in ER.

The main molecular mechanism of AT deficiency in this pedigree is the disturbed AT secretion as a result of the mutation of AT-c.342T>G.