Volume 89  ·   Issue 30  ·  2009

pulmonary hypertension is a group of chronic pulmonary circulation diseases, which is very common in clinic. The etiology of pulmonary hypertension is complex, and can be caused by many kinds of heart, lung or pulmonary vascular diseases, etc. Its common manifestations are increased pulmonary vascular resistance, increased right heart load, and finally leading to right heart failure. It is a major health care problem that seriously affects people's health [1].

In recent years, the treatment of pulmonary arterial hypertension (PAH) has attracted much attention in the field of drug research and development. Although prostacyclin drugs, endothelin receptor antagonists and phosphodiesterase 5 inhibitors can delay the disease, they still have not achieved the goal of curing PAH. With the gradual deepening of understanding of the pathogenesis of PAH, the emergence of some new drugs and treatment strategies may improve the treatment of PAH.

Until 1990s, calcium channel blockers and lung transplantation were the only therapeutic measures for arterial pulmonary hypertension (PAH). However, with the clear understanding of the pathophysiological mechanism of PAH, specific therapeutic drugs have been developed. At present, there are three types of specific therapeutic drugs for PAH: prostacyclin analogs, phosphodiesterase 5 inhibitors and endothelin receptor antagonists.

Normal pulmonary circulation is a system with low pressure and high blood flow. During each cardiac cycle, the heart pumps blood from the right ventricle into the alveolar capillary network to complete the gas exchange. Many diseases can lead to an increase in pulmonary artery pressure, so pulmonary hypertension is not a final diagnosis and should be further examined to find the cause.

The understanding of the pathophysiology of pulmonary hypertension began with the description of "pulmonary arteriosclerosis" by Erest von Romberg in 1891, which was based on the histopathological changes of necropsy specimens. With the application of cardiac catheterization technique, the increase of pulmonary artery pressure and abnormal vasodilation response were observed in patients with pulmonary hypertension in 1950s.

Objective To explore the therapeutic effect and mechanisms of bone marrow-derived mesenchymal stem cells (MMSCs) transplantation treating pulmonary arterial hypertension (PAH) in rats models.Methods MMSCs collected from SD rat were isolated and cultured in vitro,then Hoechst 33342 staining was performed.Eighty healthy male Sprague-Dawleye rats were randomly divided into 3 groups:pulmonary arterial hypertension group (group H,30 rats),MMSCs transplanted group (group M,30 rats) and normal control group (group C,20 rats).The rats in groups H and M were given subcutaneous injection of monocrotaline (50 mg/kg) respectively to induce the model of PAH.At Day 22 post-induction,the rats in group M received sublingual intravenous injection of 1 ml MMSCs at the concentration of 5×106/ml while the rats in groups H and C were administered with equal amount of cell culture medium respectively.General observation was made about all groups and survival information were collected after another 4 weeks.At Day 21,4 rats from each group were sacrificed.And the rats in all groups were sacrificed at Day 49.The survival rate,mean pulmonary artery pressure (mPAP) and right ventricle hypertrophy index (RVHI) were determined.The microstructural alteration of small pulmonary vessel and immunohistochemistry and microvessel density assay of vascular Ⅷ factor-related antigen were performed.Results At the end of the experiment,the survival rates were 50% (15/30) and 90% (27/30) in groups H and M respectively (P<0.01).At Day 21,mPAP were (39.1±2.5) and (38.5±2.1) mm Hg in group H and M respectively,and RVHI were (34.0±3.1) % and (33.8±2.6) % in groups H and M respectively.The parameters in both groups were higher than those in group C [(15.2±1.7) mm Hg and (24.7±2.1) %,both P<0.01].At Day 49,mPAP were (42.7±2.3) and (24.7±2.1) mm Hg in group H and M respectively (P<0.01),and RVHI were (45.1±3.4)% and (38.8±3.2)% in group H and group M respectively (P<0.01).As compared with group H,the morphological metrological indices of small pulmonary arteries significantly improved in group M.The Hoechst 33342 staining showed MMSCs were colonized in lungs and differentiated into large number of neovascularization,forming plentiful collateral circulations in lung.The pulmonary arterial remodeling was reversed in group M.Immunohistochemistry also confirmed the finding that a large scale of neovascularization took place in rat lungs in group M.Microvessel density in group M [(5.2±0.8)/HP] was significantly higher than that in group H [(1.4±0.5)/HP,P<0.01].Conclusion MMSC transplantation may reverse pulmonary vascular remodeling through differentiation,neovascularization and small pulmonary arterial repair.It decreases pulmonary arterial pressure,effectively slows down even reverse monocrotaline-induced PAH progression.

Objective To investigate the outcome of dual endothelin receptor antagonist bosentan in children with congenital heart disease (CHD) associated pulmonary arterial hypertension (PAH).Methods A total of 32 children were recruited into this prospective and observational study.Among them,there were 18 cases with left-to-right shunt and 14 cases with elevated pulmonary vascular resistance (PVR) in functional single ventricle (FSV).All the cases were treated with oral bosentan,initialed from 90 days before or 8 years after operation,and were followed up periodically to analyze the clinical outcome and monitor its side effects.Results In the left-to-right shunt group,pulmonary arterial pressure (PAP) was measured at (57±26),(52±31) and (46±22) mm Hg after oral bosentan therapy at 1,2 and 3 months respectively.The measurements significantly decreased as compared with the pre-dosing level of (74±15) mm Hg (P<0.05).After a 3-months therapy of bosentan,World Health Organization functional class (WHO FC) improved significantly (P<0.01).In the elder cases,the 6-minute walking distance after a 3-month bosentan therapy significantly increased as compared with the pre-dosing level,i.e.(497±56) vs (424±31) m (P<0.05).In the FSV group,as compared with the pre-dosing level,the transcutaneous oxygen saturation increased significantly in the last follow-up during bosentan exposure,i.e.(86±5) % vs (78±6)% (P<0.01).WHO FC improved significantly (P<0.01) and the incidence of facial edema and pleural effusion was significant lower (P<0.05) in the last follow-up for the treatment group.Patients tolerated bosentan well and no significant rise in hepatic transaminases was observed.Conclusions Bosentan is safe in treating CHD associated PAH in children.In left-to-right shunt cases,oral bosentan can reduce PAP and improve both WHO FC and exercise capacity.And it can also improve WHO FC and transcutaneous oxygen saturation in FSV and reduces the occurrence of elevated PVR-related complications.

Objective To evaluate the acute effects of inhaled iloprost on hemodynamics and oxygenation in chronic thromboembolic pulmonary hypertension (CTEPH).Methods A prospective study was made.Eighteen patients with CTEPH were enrolled.At right heart catheterisation,iloprost was inhaled at 20 μg for 10 -15 min.Compare the value of heart rate (HR),mean blood pressure (mBP),mean pulmonary arterial hypertension (mPAP),right atrium pressure (RAP),pulmonary arterial wedge pressure (PAWP),cardiac output (CO),pulmonary vascular resistance (PVR),systemic vascular resistance (SVR),arterial partial pressure of oxygen (PaO2),arterial oxygen saturation (SaO2),mixed venous saturation(SvO2),pulmonary shunt fraction (Qs/Qt),alveolar-arterial partial pressure of oxygen [P (A-a) O2] before to after inhaled iloprost in these patients.Results Significant changes (before to after inhalation):mPAP,(53±11) to (47±14) mm Hg (P<0.01);PVR,(821±194) to (681±199) dyn·s·cm-5(P<0.01);RAP,(10±6) to (7±6) mm Hg (P<0.01).However,HR,PAWP,mBP,CO and SVR had no significant changes.At the same time,inhaled iloprost significantly decreased PaO2 from (58±11) to (52±6) mm Hg (P<0.01) and increased Qs/Qt from (27±11) % to (33±9)%(P<0.01)and P(A-a)O2 from(86±39) to (93±38)mm Hg(P<0.01).Conclusion Inhaled iloprost might instantly improve hemodynamics in CTEPH,but at the same time it increased arteriovenous shunts which resulted in lower PaO2.

Objective To compare the acute hemodynamic effects of adenosine versus iloprest in patients of pulmonary arterial hypertension (PAH) complicated with connective tissue diseases.Methods During right heart catheterization,18 patients of PAH complicated with connective tissue diseases sequentially received intravenous infusion of adenosine and inhaled iloprost.After the baseline hemedynamic data were obtained,an adenosine infusion was started and titrated to the maximal tolerated dose.The hemodynamic parameters were allowed to return to baseline.Then inhalation of iloprost was administered.The effects of both medicines on the patient's hemodynamics were monitored.Results As compared with the baseline values,the systolic pulmonary artery pressure and pulmonary vascular resistance significantly decreased [(71±30) vs (80±29) mm Hg and (712±440) vs (824±464) dyn·s·cm-5 respectively,both P<0.05) while the heart rate increased significantly [(93±17) vs (83±16) beat/min,P<0.05] in the adenosine group.Inhaled ilopmst could also lower the systolic pulmonary artery pressure [(66±29) vs (79±28) mm Hg,P<0.05],mean pulmonary artery pressure [(43±19) vs (52±19) mm Hg,P<0.05] and pulmonary vascular resistance [(632±440) vs (816±448) dyn· s· cm-5,P<0.05] without any effect upon heart rate.Inhaled iloprest exerted more potent effect on lowering mean pulmonary artery pressure and pulmonary vascular resistance than adenosine (P<0.05).The two medicines did not affect cardiac output,pulse oxygen saturation or systemic blood pressure.The side effects were fewer in the iloprost inhalation group than the adenosine group.Conclusion During acute vasodilator testing,inhaled iloprost was more potent than infused adenosine as a pulmonary vasodilator in PAH complicated with connective tissue diseases.

Objective To improve the diagnostic level of testicular cancer by a retrospective review of 47 cases.Methods The symptoms,signs,imaging studies,tumour markers and histological diagnoses of 47 cases were reviewed.Results The mass in testes was palpated in all patients.As a useful tool in the diagnosis of testicular cancer,scrotal uhrasonography had a detecting sensitivity over 90%.Though sensitive to retroperitoneal lymph nodes,CT had a certain level of false positive rate.Tumor markers,especially AFP,were significantly useful in the diagnosis and prognosis of testicular cancer.Histological examination showed 27 cases of seminoma,7 cases of embyonal carcinoma,6 cases of teratoma,3 cases of lymphoma,1 case of spermatocytic seminoma and 1 case of sarcoma.Conclusion Patient self-examination is extremely helpful for an earlier diagnosis.Ultrasonography and CT are invaluable in the diagnosis and staging of testicular cancer.Playing key roles in the diagnosis and prognosis of testicular cancer,tumour markers should be routinely examined.

Objective To study the diagnosis and treatment of primary pigmented nodular adrenocortical disease(PPNAD).Methods The clinical data including symptom,endocrinal examination,surgical operation and prognosis of 4 cases of PPNAD hospitalized from 2000 to 2007 were analyzed respectively,relative literature were reviewed.Results 1 case received total adrenalectomy needed adrnacortical hormone postoperatively,3 cases responded favorably to subtotal adrenalectomy and did not need adrnacortical hormone,however,1 case was diagnosed of thyriod carcinoma 2 years after subtotal adrenalectomy.Conclusions PPNAD is a rare subtype of ACTH-independent Cushing,s syndrome,the diagnosis is depend on symptom,endocrinal examination and pathology.Total adrenalectomy is suitable to the patients with obvious symptom;subtotal adrenalectomy to the patients with mild symptom,the lesion of other endocriual organ must be followed up postoperatively.

Objective To investigate the preventive action of metformin for atherosclerosis (AS) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 140 cases with T2DM were assigned to 2 groups taking metformin (n = 75) or not (n = 65).All cases received intensive control of blood glucose,blood pressure and blood lipids for 100 weeks.The data before and after intensive control were recorded and statistically analyzed.Common carotid intima-media thickness (CC-IMT) was the efficacy endpoint of AS.Results Diastolic blood pressure (DBP),fasting blood glucose,post 2-hour blood glucose,glycated hemoglobin Alc,triglyceride (TG) and total cholesterol (TC) decreased in both groups after intensive metabolic control for 100 weeks (P<0.05).Body mass index (BMI),HOMA insulin resistance index (HOMA-IR) and CC-IMT decreased in metformin group (P<0.05) while high-density lipoprotein cholesterol (HDL-C) increased (P<0.05).BMI (23.1±0.98) kg/m2,HOMA-IR (1.68±0.20) and CC-IMT(0.55±0.13)nun in metformin group were lower than those in non-metformin group [(24.1±0.05) kg/m2,2.03±1.38,(0.70±0.15)mm)] at 100 week (P<0.05).CC-IMT was positively correlated with BMI (r = 0.489,P<0.05),TC (r = 0.429,P<0.05),low-density lipoprotein cholesterol (LDL-C) (r = 0.426,P<0.05) and HOMA-IR (r = 0.428,P<0.05).Conclusion Metformin attenuates CC-IMT of patients with T2DM and it has the primary preventive effect upon AS in patients with T2DM.

Objective To evaluate serum levels of retinol-binding protein-4 (RBP-4) in firstdegree relatives (FDR) of type 2 diabetes mellitus (T2DM) with different glucose tolerance status and to observe its correlation to metabolic syndrome (MS).Methods Subjects from FDR of T2DM,including 174 with NGT,55 with IGT/IFG,and 71 patients with newly diagnosed of T2DM and 114 subjects without diabetic family history as control group [(18±7) μg/ml vs (22±8)μg/ml,(NC) [(18±7) μg/ml vs (22±8)μg/ml,were recruited.Serum RBP-4 level was measured by radioimmunoassay.Insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR).MS was diagnosed according to 2005 IDF consensus.Results (1) Serum RBP-4 levels in NC,NGT,IFG/IGT and T2DM groups were (18±7),(22±8),(24±9) and (26±9) μg/ml respectively.Serum RBP-4 was significantly elevated in NGT group of diabetic FDR as compared with NC group [(26±9) μg/ml vs (24±9) μg/ml],and increased with the severity of glucose intolerance.However,no difference was found between serum RBP-4 in the IFG/IGT and T2DM groups.(2) When the distribution of RBP-4 was stratified into quartiles (Q1-Q4),subjects in the top quartile (Q4) was not only associated with greater risk for impaired glucose regulation as compared with Q1 OR =5.26),but also significantly with risk for hypertension (OR=1.96),dyslipidemia (OR=4.14),obesity (OR = 2.18) and MS (OR = 4.30).Conclusion (1) Serum RBP-4 levels in FDR of T2 DM were elevated significantly even before the development of impaired glucose regulation and were further increased with severity of glucose tolerance,suggesting a possible role of RBP-4 in the early pathogenesis of T2DM.(2)Serum RBP-4 level was closely related to MS.

Objective To investigate the expression of CD40 in gastric cancer and explore the correlation of CD40 with the outcome of patients.Methods The expression of CD40 was examined by immunohistochemistry in human gastric cancer tissues (73 cases) and adjacent normal gastric tissues (51 cases).CD40 mRNA was detected by RT-PCR in 11 gastric cancer and 11 adjacent normal gastric tissues.The patients were followed up for 60 months.The correlation of CD40 expression and the overall survival time were evaluated by Kaplan-Meier chart and Log-Rank test.Cox model was used for multivariate analysis.Results The immunoreactivity of CD40 increased in 35/73 gastric cancer tissues (47.9%) as compared to the tumor-free tissues (P =0.0063).CD40 mRNA were detected in 72.7% (8/11) gastric cancer tissues,while not in all tumor-free tissues.After a 5-year follow-up,the survival rate was 57.9% (22/38) in CD40-negative patients,and 5.7% (2/35) in CD40-positive patients (P = 0.0022).The median survival time of patients with negative,positive,and strong CD40 expression was 56,29 and 11 months respectively (P=0.0085).Cox regession analysis suggested that CD40,lymph node metastasis and TNM stage were independent factors affecting the prognosis of gastric cancer patients.Conclusion Normal and malignant gastric tissues are found to have its own unique CD40 expression patterns.CD40 may play a role in metastatic spread of gastric cancer and its expression may be used as an important survival predictor in human gastric cancer.

Objective To analyze the change of Th1/Th2/Th17 in colonic mucosa and peripheral blood in diarrhea-predominant IBS (D-IBS) to uncover the underlying mechanism for the activation of mucosal immune system.Methods Colonic biopsy specimens and peripheral blood were obtained from patients with D-IBS (n=27) and controls (n=16).Two different groups were classified on the basis of histological assessment of biopsy specimens from D-IBS patients.One group (14 of 27) had normal conventional histology (IBS),while another group (13 of 27) had nonspecific microscopic inflammation (IBS-A).Flow cytometric detection of intracellular IFN-γ/IL-4/IL-17 cytokine production was employed to investigate Th1,Th2 and Th17 cells in colonic lamina propria and peripheral blood.Western blot was used to determine the expressions of IL-12,IL-4 and IL-17 in colonic mucosa.The levels of IL-12,IL-4 and IL-17 in peripheral blood were detected by ELISA.Results In colonic mucosa,the proportion of Th17 increased in IBS-A group as compared with controls [3.60 (4.05) vs 1.25 (3.70),P=0.045],but not in IBS group.No difference could be observed in the frequencies of Th1 and Th2 in colonic mucosa and peripheral blood.The levels of IL-12,IL-4 and IL-17 in IBS and IBS-A showed no difference in either colonic mucosa or peripheral blood.Conclusion Subgroup of D-IBS showed abnormal conventional histology,implicating the activation of mucosal immune system in pathogenesis.The shift of Th1/Th2/Th17 balance in colonic mucosa showed the enhanced Th17 activity.

Objective To compare mobilization kinetics of CD34 + cells and MNC during mobilization with either recombinant human granulocyte colony-stimulating factor (rHuG-CSF) filgrastim (Huierxue) or topneuter (Teerjin) in allogeneic hematopoietic stem cells transplantation (allo-HSCT) donors.Methods Two different agents of rHuG-CSF,Huierxue (filgrastim) and Teerjin (topneuter),were used for hematopoietic stem cells (HSC) mobilization.The HSCs mobilized by each agent were compared in mobilization efficacy,quality of stem cells,side effects in donors and influence of hematopoitic reconstitution in 52 subjects following allo-HSCT.Fifty-two HLA-matched sibling donors,receiving either (rHuG-CSF) topneuter (treatment group) or filgrastim (control group),were randomized in this study.Results The peak values of both groups,occurring at both Day4,were(38.9±3.0) ×109/L and(37.8±2.9)×109/L respectively (P >0.05).Both agents had the following effects upon the HSC parameters:(4.8±0.7)×108/kg vs (5.1±0.4)×108/kg MNC,(1.6±0.3)×106/kg vs (1.9±0.7)×106/kg) CD34 + in peripheral blood of donors;(3.8±0.5)/L vs (3.9±0.7)/L MNC;(1.3±0.7)×106/kg vs (1.5±0.4)×106/kg CD34 + in bone marrow of donors (both P>0.05).With regards to the effects upon hematopoitic reconstitution in subjects following allo-HSCT,both had rapid platelet count recovery (14.6±0.9) vs (15.2±1.6) days (P>0.05) and neutrophil count recovery (18.1±0.8) vs (17.0±1.9) days (P >0.05).The adverse events were not significantly different in the HSC donors for these two mobilization agents.Conclusion Filgrastim and topneuter demonstrate no statistically significant difference in either HSC mobilization kinetics of peripheral and bone marrow blood or hematopoitic reconstitution.Topneuter can be a reliable agent for donor HSC mobilization and recipient hematopoitic reconstitution following alIo-HSCT.

Objective To investigate the effects of ShenSongYangXin on action potential and some current channels in isolated rabbit pulmonary vein cadiomyocytes and to elucidate its possible mechanism of curing atrial fibrillation.Methods Action potentials as well as L-typo calcium channel current (ICa-L),transient outward potassium current (IK1) and inward rectifier potassium current (ITo) were recorded using whole cell patch-clamp technique.Results ShenSongYangXin prolonged the action potential duration (APD) significantly,APD90 was enlarged from (187±49) ms to (286±76) ms at the concentration of 5 mg/ml and to (312±82)ms at the concentration of 10mg/dl respectively (P<0.05).It also depressed the current of ICa-L,IK1 and ITo in a concentration-dependent manner.Conclusion ShenSongYangXin can be used to treat atrial fibrillation through its actions on multiple current channels.

Current medical history: A 36-year-old male was admitted to the hospital on January 12, 2007 due to "melena for 5 days and hematemesis for 2 days". The patient started to release black paste stool 5 days ago, once a day, about 150 g, no mucus and bloody stool, no abdominal pain, diarrhea, no nausea and vomiting, no dizziness and palpitation.

Breast cancer is a hormone-dependent tumor, and the detection of estrogen receptor (ER) and progesterone receptor (PR) levels in breast cancer patients has become a routine test item in clinical laboratory. However, the role of androgen and androgen receptor (AR) in breast cancer biology has been neglected in clinical and basic research in the past [1].

The concept of early gastric cancer was first put forward by Japanese scholars and was generally recognized. It refers to the invasion of cancer into mucosa and submucosa regardless of the metastasis of lymph nodes and distant organs. After performing standardized radical resection, the long-term survival rate has basically stabilized at over 90%. Therefore, on the premise of consolidating and improving the surgical cure rate of early gastric cancer, it has become an urgent problem to improve the postoperative quality of life of patients by appropriately narrowing the scope of gastrectomy and lymph node dissection.

In recent years, it has been found that bone morphogenetic protein type Ⅱ receptor (BMPR2) gene mutation can affect the proliferation and apoptosis of pulmonary vascular cells, and it is an important pathogenic gene in familial pulmonary hypertension (FPAH) and idiopathic pulmonary hypertension (IPAH) [1-4].

Potential risk genes for shock remain uncertain in humans. A recent trial conducted by the Association for the Study of Genetic Epidemiology in Heart and Geriatrics showed that a gene locus on chromosome 12p13 is associated with the risk of shock.

bepridil is a new long-acting calcium channel blocker with sodium and potassium channel blocking activity and can act as a calmodulin antagonist in cells. bepridil has anti-angina and class I, III and IV antiarrhythmic effects.

In order to improve the level of diagnosis and treatment of critical, difficult and rare diseases of digestive system in China, the 3rd National Academic Conference on Critical, Difficult and Rare Diseases of Gastroenterology was held in Beijing from May 21 to 24, 2009, sponsored by the Gastrology Committee of China Association for the Promotion of International Exchange in Medical Care (CAMP) and undertaken by Beijing Military Region General Hospital.

The first second-generation influenza A (H1N1) case in mainland China was discovered in Guangzhou on May 28, 2009. We continuously performed virus nucleic acid testing on three patients involved in this case to understand the virus detoxification and the evolution of the disease course of influenza A (H1N1) during the transmission process, and to provide laboratory data for the prevention and control of influenza A (H1N1) epidemic in China.