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.

     

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.

     

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.

     

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.

     

Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

Background  Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation, migration and lumen formation capacity of human umbilical vein endothelial cells.

Methods  Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells. After 24-hour incubation, the culture supernatants were harvested and used to treat human umbilical vein endothelial cells for 24 hours. Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells. The secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.

Results  Suppression of proliferation, migration, and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide. Parthenolide decreased the levels of the angiogenic factors MMP-9, VEGF, and IL-8 secreted by the MDA-MB-231 cells.

Conclusions  Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation, migration and lumen-like structure formation of endothelial cells, thereby inhibiting tumor growth. It is a promising potential anti-angiogenic drug.

     

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.

     

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.

     

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.

     

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.

     

Long-term outcomes of surgical treatment for pulmonary carcinoid tumors: 20 years’ experience with 131 patients

Background  Bronchial carcinoids are rare malignant neuroendocrine neoplasms. Some issues regarding surgical treatment of bronchial carcinoids remain controversial, including the role of bronchoplastic surgery and necessity of systematic lymphadenectomy.

Methods  This retrospective study involved 131 consecutive patients surgically treated for carcinoid tumors at Shanghai Chest Hospital between March 1990 and August 2010.

Results  Eighty-nine (67.9%) of the patients were male, and the mean age was 46 years, ranging from 17 to 81 years. Preoperative fiberoptic bronchoscopy was performed in all patients. Endoscopic biopsy was performed in 100 patients with central tumors, and 70 (70%) patients were diagnosed as bronchial carcinoid. The resections performed consisted of 31 pneumonectomie, 32 lobectomies, 26 bilobectomies, 34 sleeve lobectomies, six bronchoplastic procedures without lung resection, and two segmentectomies. During a median of 87 months follow-up, there were nine recurrences including three local recurrences and 6 distant recurrences. No bronchial recurrences were observed. The 3-, 5- and 10-year overall survival rates of pneumonectom and bronchoplastic surgery (including sleeve lobectomy and bronchoplastic procedure without lung resection) were 93.2%, 81.0% and 69.4%, 97.5%, 91.9% and 70.0%, respectively. Multivariate Cox regression indicated that histology and nodal status were significant independent prognostic factors.

Conclusions  Bronchoplastic surgery should be considered whenever possible for central carcinoids. Systematic lymphadenectomy is recommended for bronchial carcinoid patients. Histology and nodal status were significant independent prognostic factors of overall survival of patients with bronchial carcinoid.

     

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.

     

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.

     

Transitional cell carcinoma associated with aristolochic acid nephropathy: most common cancer in chronic hemodialysis patients in China

Background  The research of cancer in patients on hemodialysis (HD) in China has not been reported. The aim of this study was to investigate the clinical and histological features and outcomes of cancer in Chinese HD patients.

Methods  The study subjects were 49 cancer patients (1.4%) out of 3448 end stage renal disease (ESRD) patients maintained on HD at China-Japan Friendship Hospital from October 1997 to July 2011.

Results  Urinary tract cancer (74%) was the most common followed by gastrointestinal tract cancer (12%), breast cancer (6%), lung cancer (4%), thyroid cancer (2%), and hematologic cancer (2%). Thirty-three patients (67%) had urinary tract transitional cell carcinoma (TCC) and 29 of them had aristolochic acid nephropathy (AAN) as underlying disease. Death occurred in eight patients out of 49, and the survival rate of HD patients with cancer was similar to those without cancer (P=0.120).

Conclusion  The urinary tract TCC is the most common cancer in HD patients with AAN in one of the centers of northern China.

     

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.

     

Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation

Background  The use of transanastomotic stents for Roux-en-Y hepatojejunostomy (RYHJ) in liver transplantation (LT) remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT.

Methods  RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents (S group), while 27 patients underwent the same procedure without transanastomotic stents (non-S group). The two groups were compared in terms of post-LT biliary complications and survival.

Results  The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5% (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0, 20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group. One and three year survival rates were 48.0% (12/25) and 34.0% (8/23), respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival (P >0.05).

Conclusion  The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT

     

Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor

Background  Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors. In this study, we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.

Methods  Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343, and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively. Expression of OPN, hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis. The radiosensitivity of cells was determined by detecting cell apoptosis, cell proliferation and cell senescence.

Results  HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment. Moreover, expression of OPN protein was upregualted upon hypoxic culture. Stable OPN-silencing also decreased cell invasion, increased cell apoptosis and cell senescence, as well as reduced clonogenic survival, resulting in increase radiation tolerance.

Conclusions  Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells. OPN seems to be an attractive target for the improvement of radiotherapy.

     

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...     

Treatment of respiratory failure in metastatic pulmonary choriocarcinoma: an experience at Peking Union Medical College Hospital, China

Background  Respiratory failure caused by metastatic pulmonary choriocarcinoma usually develops rapidly and is associated with a high mortality. The clinical management strategy is important in choriocarcinoma patients with acute respiratory failure. The objective of this study was to evaluate the clinical characteristics, treatment outcome and potential risk factors in patients with acute respiratory failure from metastatic pulmonary choriocarcinoma.

Methods  Sixteen patients with acute respiratory failure from pulmonary metastases choriocarcinoma were enrolled and treated at Peking Union Medical College Hospital from 1995 to 2010. Clinical characteristics, causes of pulmonary failure, treatment profiles and outcomes were analyzed retrospectively.

Results  The presence of respiratory infection or hemorrhage was associated with acute respiratory failure in patients with metastatic choriocarcinoma. Fifteen (93.8%) patients presented with pulmonary infection, 8 (50.0%) patients with pulmonary hemorrhage. All patients were treated with face mask or mechanical ventilation. Fourteen (87.5%) patients received initial chemotherapy at a low dosage or with modified regimens, with a median of 2 cycles (range 1 to 4). Seven patients achieved a complete remission (CR), two had a partial remission. Six CR patients remained alive with a median follow-up of 59 months (range 16 to 120). Seven patients developed progressive diseases and subsequently died.

Conclusions  Respiratory infection and hemorrhage were associated with acute respiratory failure in metastatic pulmonary choriocarcinoma. The initial administration of gentle chemotherapy regimens, accompanied with mechanical ventilation, is feasible and effective in attenuating respiratory failure in patients with metastatic pulmonary choriocarcinoma.