GRE T2*序列中T2*值的测量在鉴别诊断颅内出血和钙化的应用

目的　研究GRE T2*WI(扰相梯度双回波T2*WI)序列诊断与鉴别诊断颅内出血和钙化的定量分析指标。方法　以ESWAN作为金标准,对已确诊脑出血的18例38个病灶和颅内钙化7例11个病灶进行磁共振GRE T2*WI (15/30 ms)检查。测量不同病灶T2*值,进行统计学分析比较。结果GRE T2*WI序列对于血肿的发现率为CT的1.9倍,对微出血及脑干、小脑等部位出血GRE T2*WI比CT检查更有优势。出血（核心区）与钙化的T2*值有明显的统计学差异（p<0.001）,但是出血（外周区）与钙化的T2*值无明显的统计学差异（P > 0.05）。结论　GRE T2*WI序列上颅内出血和钙化T2*值的定量分析,为实现脑血管病的MR一站式诊断奠定了基础。     

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects naïve to antiretroviral therapy

Background  The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs.

Methods  Tregs were defined as CD4⁺CD25⁺CD127^lo/- T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer.

Results  Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4⁺CD25⁺CD127^lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163, P=0.004) and negatively with CD4 T-cell counts (r=−0.4153, P <0.0001). In addition, significant associations between HLA-DR expression on CD4⁺CD25⁺CD127^lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4⁺ and CD8⁺ T cells were also identified.

Conclusion  HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

     

Expectant management of heterotopic cesarean scar pregnancy

Background  Heterotopic cesarean scar pregnancy (HCSP) is a very rare but life-threatening entity and there is no optimal management strategy. Here we report a successfully managed case of HCSP with expectant treatment in a tertiary referral hospital.

Methods  A woman with HCSP after in vitro fertilization-embryo transfer opted for expectant treatment after five days of mild bleeding and ultrasound demonstrated cardiac activity disappearance of the scar pregnancy at 8⁺⁴ weeks of gestation.

Results  The patient had mild to moderate bleeding during close monitoring. Three days later, speculum examination revealed the gestational mass was partly protruding at the os of the cervix and it was removed with forceps without massive hemorrhage. A healthy male baby was delivered by cesarean section at gestational age of 36⁺⁴ weeks.

Conclusions  The expectant method might be an alternative option for a HCSP with loss of cardiac activity of the scar pregnancy, when applied under supportive management and with available emergency surgery facilities.

     

Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells

Background  Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes. Previous studies found impaired mitochondrial function and impaired Ca²⁺ influx in beta cells in diabetic patients and animal models, suggesting a role for these processes in proper insulin secretion. The aim of this study was to investigate the detailed relationship of mitochondrial function, Ca²⁺ influx, and defective insulin secretion.

Methods  We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice. Two types of Ca²⁺ channel activities, L-type and store-operated Ca²⁺ (SOC), were evaluated using whole-cell patch-clamp recording. The glucose induced Ca²⁺ influx was measured by a non-invasive micro-test technique (NMT).

Results  Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae, and mitochondrial function decreased compared with C57BL/6J mice. Ca²⁺ channel activity was increased and glucose induced Ca²⁺ influx was impaired, but could be recovered by genipin.

Conclusion  Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca²⁺ influx, but not via Ca²⁺ channel activity.

     

创伤骨科患者创伤严重程度和血浆D二聚体水平的相关分析

Background  The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies. The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.

Methods  Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured. Plasma D-dimer levels in patients of these two groups were compared. The relationship between the plasma D-dimer level and the severity of the trauma was also studied.

Results  There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group. The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01). In the acute trauma group, the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).

Conclusions  Elevated plasma D-dimer is common in trauma patients. The D-dimer level and the number of fractures in the trauma patients are closely correlated. D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus, but also an indicator of the severity of trauma in acute trauma patients.

     

Immature CD4+ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats

Background  Allogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell (DC) is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4⁺ DCs on renal allografts in the rat model.

Methods  In this study, we induced CD4⁺ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4⁺ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo.

Results  Immature CD4⁺ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo.

Conclusions  Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4⁺ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.

     

Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

Background  Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model.

Methods  Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy.

Results  The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group.

Conclusion  Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

     

Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

Background  In response to the injury of the central nervous system (CNS), the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP), which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.

Methods  We generated ephrin-B2 knockout mice specifically in CNS astrocytes. Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates. In both groups, a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury. Twenty-eight days after the injury, Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups. All the data were analyzed by t-test for between-group comparison.

Results  We successfully set up the conditional ephrin-B2 knockout mice strain, which was confirmed by genotyping and ephrin-B2/GFAP double staining. These mice developed normally without apparent abnormality in general appearance. Twenty-eight days following brain injury, histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups. Compared with wild-type group, the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P=0.005) and hippocampus (P=0.027). Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P=0.008).

Conclusions  The establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes. Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury, which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

     

Ultrasound facilitates identification of combined spinal-epidural puncture in obese parturients

Background  The palpation method is widely used in clinical practice to identify the puncture site of combined spinal-epidural (CSE) blocks, but it is usually difficult to accurately locate the puncture site in obese parturients. Accurate identification of the puncture site is crucial for successful CSE block. The objective of this study was to evaluate the impact of ultrasound imaging on the success rate of CSE puncture in obese parturients.

Methods  Sixty obese parturients with a body mass index ³30 kg/m² who were scheduled for caesarean section were randomized into two equal-sized groups for location of the puncture site: an ultrasound group and a palpation group. The success rate of puncture at the first puncture site, the number of puncture attempts, duration of CSE procedure, time taken to determine the puncture site, and the depth of the epidural space were compared between groups. The frequencies of complications such as puncture site hemorrhage, neurological damage, and inadvertent dural puncture were also studied.

Results  There were no differences in age, body weight, height, body mass index, or gestational age between the two groups. The success rate of puncture at the first puncture site was significantly higher in the ultrasound group than the palpation group (100.00% vs. 70.00%, P=0.004). The number of puncture attempts was significantly lower in the ultrasound group than the palpation group (c²=6.708, P=0.035). The time taken for determining the puncture site was (0.30±0.12) minutes in the palpation group and (2.60±0.61) minutes in the ultrasound group (P <0.001). The duration of CSE procedure was (7.67±1.52) minutes in the palpation group and (9.37±1.35) minutes in the ultrasound group (P <0.001). The depth of the epidural space was similar in both groups (P=0.586). Puncture site hemorrhage was observed in 6 (20.00%) patients in the palpation group and 2 (6.67%) patients in the ultrasound group (P=0.255).

Conclusions  Ultrasound imaging improves the rate of successful puncture at the first puncture site and decreases the number of puncture attempts. It facilitates CSE puncture in obese parturients.

     

Enhanced expression of proneurotrophins in elevated introcular pressure-induced rat retinal ischemia

Background  Proneurotrophins such as the precursor of nerve growth factor (proNGF) and the precursor of brain-derived neurotrophic factor (proBDNF) interacted with sortilin and p75^NTR to form a complex capable of activating an apoptotic signaling. We found that the expression of p75^NTR and sortilin was increased in ischemic retina induced by elevated intraocular pressure (IOP), but the protein expression changes of proNGF and proBDNF in the same situation were not clear. This study aimed to ascertain the protein expression changes of proNGF and proBDNF in ischemic retina induced by elevated IOP.

Methods  Expression of proBDNF and proNGF was examined by double-labeling immunochemistry in normal rat retina, examined using Western blotting and analyzed using statistical methods in ischemic retina induced by elevated IOP.

Results  Immunocytochemistry showed that the proBDNF expressed in the ganglion cell layer (GCL) while the proNGF primarily existsed in both the nerve fiber layers (NFL) and large ganglion cell bodies of normal rat retina. Western blotting analysis demonstrated that the molecule weights of 28 kD (proBDNF) / 25 kD (proNGF) band were increased significantly (P <0.05) at days 3, 5 and 7 after retinal elevated-IOP-induced ischemia.

Conclusion  ProBDNF expressed in the GCL and proNGF primarily presented in NFL and large ganglion cell bodies of normal rat retina, the protein expression forms of 28 kD proBDNF and 25 kD proNGF increased in ischemic retina induced by elevated IOP.

     

Proteomic analysis for detecting serum biomarkers related to smoking in humans

Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.

Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.

Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.

Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.

     

Clinical features and imaging findings in pulmonary capillary hemangiomatosis: report of two cases and a pooled analysis

Background  Pulmonary capillary hemangiomatosis (PCH) is a rare disease and no Chinese case has been reported yet. The disease is often misdiagnosed and its clinical characteristics are incompletely described. The aim of this study was to describe two Chinese cases and to clarify the clinical and radiographic parameters of patients with PCH.

Methods  Two PCH cases were presented and other cases were searched from the English literature. All available clinical and radiographic data were collected from 62 literature reported PCH cases. A pooled analysis of total 64 cases was made.

Results  Dyspnea and hemoptysis were the most common clinical symptoms of PCH. Pulmonary hypertension (PH) was found in 78% of the reported cases. PCH typically showed characteristic diffuse or patchy ground-glass opacities (GGOs) and/or multiple ill-defined centrilobular nodules in the computed tomography.

Conclusions  The diagnosis of PCH requires a high clinical suspicion. However, both clinical presentations and radiographic studies often provide clues to the diagnosis, which may prompt early lung biopsy for a definite diagnosis.

     

Progression of solitary and multifocal papillary thyroid carcinoma — a retrospective study of 368 patients

Background  Papillary thyroid carcinoma (PTC) represents one of the most frequent endocrine malignancies. Several factors have been found to be involved in determining the outcome of treatment for patients with PTC. Large tumor size, diagnosis at an early age, extra-thyroidal invasion, aggressive histological variants, and distant metastases are the most important determinants of a poor outcome. BRAF^V600E mutation has been found to be a major genetic alteration in PTC. This study aimed to evaluate progression in patients with multifocal and solitary PTC.

Methods  We performed a retrospective study to analyze 368 patients with PTC who underwent surgery, including 282 patients with solitary PTC and 86 patients with multifocal PTC. The status of BRAF^V600E mutation in all tumor foci from multifocal PTC was detected.

Results  Our study suggested that multifocal PTC was more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. The number of tumor foci did not affect progression of disease in multifocal PTC patients. Lymph node metastasis in multifocal PTC patients was associated with larger tumors, diagnosis at early stage, and extra-thyroidal invasion.

Conclusion  The status of BRAF^V600E mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age.

     

Increased expression of serum gelsolin in patients with osteosarcoma.

Background  Identification of potential serum biomarkers of osteosarcoma to aid in its early diagnosis and in the discovery of possible therapeutic targets is an area of increasing interest.

Methods  Two-dimensional difference-in-gel electrophoresis was used to assess multiple serum samples in patients with osteosarcoma. In addition, differential expression of protein biomarkers was characterized in osteosarcoma serum by using matrix-assisted desorption/ionization time-of-flight mass spectrometry coupled with database interrogation. Serum samples from four individuals with osteosarcoma and four age- and sex-matched healthy control subjects were compared.

Results  Fifty-eight significant protein spot features in the osteosarcoma sera were found. These spot features were excised, digested with trypsin, and analyzed with mass spectrometry. Gelsolin was down-regulated only in osteosarcoma. Furthermore, Western blotting and enzyme linked immunosorbent assay (ELISA) confirmed decreased levels of gelsolin in the osteosarcoma serum samples.

Conclusions  These results indicated that gelsolin might have great potential as a biomarker of osteosarcoma and as a potential target for gene therapy.

     

Impact of multidisciplinary team working on the management of colorectal cancer

Background  The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline. Colorectal cancer multidisciplinary team (MDT) working model is recommended by UK and other countries, but there is little information on the impact of MDT working on management of colorectal cancer in China. The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.

Methods  A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery, the pre-MDT cohort include 297 patients, recruited from January 1999 to November 2002, and the MDT cohort had 298 patients enrolled from December 2002 to September 2006. Information recorded included: TNM stage from histological reports, degree of differentiation, the number of examined lymph nodes and CT TNM staging performed or not, and its accuracy, including local and distant recurrence.

Results  The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group. CT TNM staging was more accurate in the MDT group compared to the pre-MDT group (P=0.044). The rate of tumor recurrence in the MDT group was lower than pre-MDT group (log-rank test, P <0.001). Multivariate analysis revealed that age (P=0.001), management after inception of the MDT (P=0.002), degree of differentiation (P=0.003), number of examined lymph nodes (P=0.002), and TNM stage (P=0.000) were important factors that independently influence overall survival.

Conclusions  The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients. MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis, evidence-based decision making, and optimal treatment planning.

     

Tissue-engineered calcium phosphate cement in rabbit femoral condylar bone defects

Background  Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time.

Methods  Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed.

Results  The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae.

Conclusion  Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.

     

Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene

Background  Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.

Methods  We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.

Results  The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P <0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.

Conclusion  MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

     

High volume practice proved the safety of off-pump coronary artery bypass surgery in left main coronary artery lesions: a two-year single center experience

Background  Left main coronary artery (LMCA) stenosis has been recognized as a risk factor for early death among patients undergoing coronary artery bypass grafting (CABG). This study aimed to assess if LMCA lesions pose an additional risk of early or mid-term mortality and/or a major adverse cardiac and cerebrovascular event (MACCE) after off-pump coronary artery bypass grafting (OPCABG), compared with non-left main coronary artery stenosis (non-mainstem disease).

Methods  From January 1, 2009 to December 31, 2010, 4869 patients had a primary isolated OPCABG procedure at Beijing Anzhen Hospital. According to the pathology of LMCA lesions, they were retrospectively classified as a non-mainstem disease group (n=3933) or a LMCA group (n=936). Propensity scores were used to match the two groups, patients from the non-mainstem disease group (n=831) were also randomly selected to match patients from the LMCA group (n=831). Freedom from MACCE in the two groups was calculated using the Kaplan-Meier method.

Results  The difference in the mortality and the rate of MACCE during the first 30 days between the non-mainstem disease group and the LMCA group did not reach statistical significance (P=0.429, P=0.127 respectively). With a mean follow-up of (12.8±7.5) months and a cumulative follow-up of 1769.6 patient-years, the difference in the freedom from MACCEs between the two groups, calculated through Kaplan-Meier method, did not reach statistical significance (P=0.831).

Conclusion  Analysis of a high volume of OPCABG procedures proved that LMCA lesions do not pose additional early and mid-term risk to OPCABG. Therefore, a LMCA lesion is as safe as non-mainstem disease lesion during the OPCABG procedure.

     

Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with peripheral T cell lymphomas: a single centre report

Background  Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy. The place for high-dose chemotherapy and autologous stem cell transplantation (ASCT) in these patients is still not clear. In this study, we presented the outcomes of PTCL patients followed these treatments in our centre.

Methods  We retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010.

Results  The 3-year overall survival (OS) of 61.9% and 3-year progression free survival (PFS) of 35.7% were observed in the 39 patient. Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further analysis revealed that patients with elevated lactate dehydrogenase, at least 2 international prognostic index (IPI) points, and extranodal involvement had a poorer outcome compared with the control group.

Conclusion  These findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.