Evaluation and treatment of marginal grafts with surgical diseases in kidney transplantation

Background  Marginal renal grafts may alleviate the shortage of suitable organs to meet an increasing demand of kidney transplantation, especially when live donors are currently limited to relatives of patients in China. The aim of this study was to investigate how to increase the available donors pool, evaluation, and treatment of marginal donors.

Methods  We had performed 121 kidney transplantation cases with living relative donors. Five out of these cases applied marginal grafts with surgical diseases, including one renal stone, one duplex kidney, one renal leiomyoma and two cases of simple renal cysts. In each case, particular surgical interventions were exerted on the graft prior to standard engrafting procedures.

Results  All recipients recovered with functioning transplants given that their serum creatinine levels declined to a normal range within one week after operation. These recipients were subsequently followed up for 10 months on average and their kidney functions remained stable.

Conclusions  Marginal renal grafts with surgical diseases, which can be treated surgically before engrafting, may provide satisfying transplantation outcomes. Positive and cautious consideration of these grafts may increase renal donor pool.

     

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.

     

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.

     

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.

     

Specific regulator of eosinophil apoptosis: Siglec-8—new hope for bronchial asthma treatment

Objective  It is known that Siglec-8 is selectively expressed on human eosinophils at a high level and mediates eosinophil apoptosis when crosslinked with its antibody. The aim of our review is to elucidate the molecular and biological characteristic of Siglec-8 and then discuss the function and possible mechanisms of Siglec-8 in eosinophils. Thereby, we will expand our understanding to the regulation of eosinophil apoptosis, and provide important clues to the treatment of asthma and other hyper-eosinophilic diseases.

Data sources  Most articles were identified by searching of PubMed online resources using the key term Siglecs.

Study selection  Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.

Results  Siglec-8 is selectively expressed on human eosinophil and can specifically induce eosinophil apoptosis.

Conclusion  The restricted expression of Siglec-8 on human eosinophil and the rapid progress in understanding its role as cell signaling and activation of death receptors have made it an attractive target for treatment of asthma and other hyper-eosinophilic diseases.

     

Antiviral therapy of decompensated hepatitis B virus-related cirrhosis

Objective  To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.

Data sources  Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis. Relevant book chapters were also reviewed.

Study selection  Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.

Results  Specific antiviral agents not only control viral replication, which permits liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant.

Conclusions  Although the treatment of end-stage liver disease is still a challenge worldwide, antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.

     

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases.However,whether these drugs can inhibit epileptogenesis remains unclear.Thi...     

Role of microRNA-181a in the apoptosis of tubular epithelial cell induced by cisplatin 

Background  Cisplatin (DDP) is one of most effective and most commonly used therapeutic agent in treating tumors, it can accumulate in the kidney and lead to acute renal failure. MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family. In the present study, we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.

Methods  HK-2 cells were cultured, transfected with microRNA-181a inhibitor for 48 hours, and stimulated with 50 µmol/L cisplatin for 24 hours. MicroRNA-181a expression was analyzed by real time PCR, and cell apoptosis was detected by flow cytometry. Moreover, Bcl-2 and Bcl-2-associated X protein (Bax) expression were measured by Western blotting.

Results  MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor, compared with that in untransfectd cells (21.19±2.01 vs. 38.87±1.97, P <0.05). Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor. Compared with DDP treated cells alone, Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.

Conclusion  One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.

     

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.

     

Gene delivery in peritoneal dialysis related peritoneal fibrosis research

Objective  To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors.

Data sources  The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011.

Study selection  Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors, adenoviral vectors, retroviral vectors, and lentiviral vectors were selected. Data were mainly extracted from 60 articles, which are listed in the reference section of this review.

Results  Non-viral vector-mediated gene delivery (including naked DNA for ex vivo, oligonucleotides, ultrasound- contrast agent mediated naked gene delivery, etc.) and viral vector-mediated gene delivery (including adenovirus, helper-dependant adenovirus, and retrovirus vectors) have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis.

Conclusions  Peritoneal fibrosis is a major complication of peritoneal dialysis (PD). Recently, the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis. The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.

     

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.

     

Effects of estrogen on collagen gel contraction by human retinal glial cells

Background  There are definite gender differences in patients with macular holes. Menopausal women over 50 years are most affected. We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells. It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.

Methods  Estrogen was used to determine its effects on collagen gel contraction, and its function was measured using morphological changes in cells. Human retinal glial cells were cultured in collagen solution. The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.

Results  Estrogen at differing concentrations had no effect on the growth of human retinal glial cells. However, after exposed to collagen gel block, less contraction was noted in the estrogen-treated group than in the control group.

Conclusions  Estrogen can inhibit collagen gel contraction by glial cells. These results suggest a mechanism for macular hole formation, which is observed in menopausal females.

     

Quantification of left ventricular mechanics using vector-velocity imaging, a novel feature tracking algorithm, applied to echocardiography and cardiac magnetic resonance imaging

Background  Tagged magnetic resonance imaging (MRI) is the non-invasive golden standard to measure myocardial deformity. Tissue Doppler Imaging can be used to assess myocardial deformity, however, it has the limitation of angle-dependence. Our study aimed to compare left ventricular torsion and strains measured by velocity-vector imaging (VVI) using echocardiography (echo-VVI) and MRI (MRI-VVI), and to validate them against harmonic phase tagged MRI (HARP MRI).

Methods  A total number of 34 subjects (14 normal and 20 patients) were evaluated. Apical and basal image of left ventricular short axis view were acquired for measurements of apical and basal rotation, circumferential and radial strain using both echo-VVI and MRI-VVI. An apical four-chamber view was obtained for measuring the distance between the apical and basal levels.

Results  The correlations of segmental rotations, circumferential and radial strains were high between echo-VVI and HARP MRI, while the agreement of apical rotation was poor. Left ventricular torsion showed much better correlation and agreement between echo-VVI and HARP MRI than apical rotation: the coefficient was 0.97, P <0.001. The correlation between MRI-VVI and HARP MRI in quantifying rotational parameters and strains was similar with echo-VVI and HARP MRI. Echo-VVI could discriminate normal and dysfunctional ventricles on either hypertensive or dilated cardiomyopathy.

Conclusion  The data from this study show that (1) it is feasible to quantify left ventricular torsion and myocardial strain using echo-VVI and MRI-VVI in normal subjects, patients with left ventricular global systolic dysfunction and segment systolic dysfunction; (2) the agreement among all mechanical parameters derived from echo-VVI, MRI-VVI, and HARP MRI remained with clinically acceptable ranges.

     

Preoperative surgical planning for intracranial meningioma resection by virtual reality

Background  The Dextroscope system by Volume Interactions (Singapore) had been applied to minimally invasive neurosurgery in many units. This system enables the neurosurgeon to interact intuitively with the three-dimensional graphics in a direct manner resembling the way one communicates with the real objects. In the paper, we explored its values in pre-operation surgical planning for intracranial meningiomas resection.

Methods  Brain computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance venography (MRV) were performed on 10 patients with parasagittal and falcine meningiomas located on central groove area; brain CT, MRI and magnetic resonance angiography (MRA) were performed on 10 patients with anterior skull base meningiomas and 10 patients with sphenoid ridge meningiomas. All these data were transferred to Dextroscope virtual reality system, and reconstructed. Then meningiomas, skull base, brain tissue, drainage vein and cerebral arteries were displayed within the system, and their anatomic relationships were evaluated. Also, the simulation operations were performed.

Results  For parasagittal and falcine meningiomas, the relationships of tumor with drainage vein and superior sagittal sinus were clearly displayed in the Dextroscope system. For anterior skull base and sphenoid ridge meningiomas, the relationships of tumor with bilateral internal carotid arteries, anterior cerebral arteries, middle cerebral arteries and skull base were vividly displayed within the virtual reality system. Surgical planning and simulation operation of all cases were performed as well. The real operations of all patients were conducted according to the simulation with well outcomes.

Conclusions  According to the virtual reality planning, neurosurgeons could get more anatomic information about meningioma and its surrounding structures, especially important vessels, and choose the best approach for tumor resection, which would lead to better prognosis for patients.

     

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.

     

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.

     

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.

     

Are Partin tables suitable for Chinese patients with prostate cancer?

Background  Recently, the number of patients with prostate cancer who needed to be treated with radical prostatectomy increased rapidly in China. There is still a difference between clinical staging and the post-operative final pathologic staging; hence, an excellent tool for accurately predicting the pathologic stages of prostate cancer is needed urgently in clinical practice. The Partin tables are the most popular and widely used tool for predicting the pathologic stages of prostate cancer because of its high accuracy and ease of implementation. The aim of this study was to externally validate the accuracy of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer.

Methods  We retrospectively analyzed the data from 203 patients with prostate cancer who underwent radical prostatectomies between June 2000 and May 2012. The accuracies of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer were evaluated using the area under the receiver operating characteristic curve (AUC).

Results  Using the 1997, 2001, and 2007 Partin tables for predicting the current cases, the AUC of organ confinement (OC) was 0.877, 0.788, and 0.726; the AUC of extracapsular extension (ECE) was 0.525, 0.615, and 0.608; the AUC of seminal vesicle invasion (SVI) was 0.875, 0.649, and 0.820; and the AUC of pelvic lymph node invasion (LNI) was 0.808, 0.758, and 0.735 respectively.

Conclusions  The accuracies of the three versions of Partin tables in predicting OC, SVI, and LNI were good, especially the 2001 Partin table for SVI. In contrast, the accuracy of the three versions of the Partin tables in predicting ECE was fair. The 1997 Partin table was much better than the 2007 table in predicting OC, and the 2001 table in predicting SVI. The 2007 Partin table did not show any advantages.

     

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.