Research progress of Cryptococcus gattii meningitis with different immune status / 中华神经科杂志

Cryptococcus gattii is a kind of Cryptococcus that infects the lungs and central nervous system through the inhalation of infectious particles such as spores or Cryptococcus yeast cells. The development of clinical disease of Cryptococcus gattii may be determined by the sex, immunity and genetics of the host factors, in which immune system factors play an important role in host injury. Their defects will have serious clinical consequences. Cryptococcus gattii mainly infects the population with normal immune, and the infection of immunosuppressed population is rare. The infection mechanism, molecular types, clinical characteristics, treatment and prognosis of Cryptococcus gattii meningitis were different between the two populations. This article reviews the main differences in different immune status with Cryptococcus gattii meningitis.

Postinfectious inflammatory response syndrome in patients with cryptococcal meningitis / 中华神经科杂志

Cryptococcal meningitis is a common fungal meningitis that may present with an abnormal immune response during effective antifungal therapy and is called immune reconstitution inflammatory syndrome in human immunodeficiency virus (HIV)-infected patients. Similar phenomenon can also be seen in non-HIV patients with normal immune function in the past. Paradoxical clinical and/or imaging deterioration occurs due to strong immune response during treatment, which is called post-infectious inflammatory response syndrome. At present, it has not attracted attention. This complication is an important cause of poor prognosis in non-HIV patients. Early identification and treatment of post-infectious inflammatory response syndrome is of great significance. This article will review its possible pathogenesis, clinical manifestations, imaging characteristics, risk prediction, diagnosis, treatment and prognosis.

Clinical efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism / 中华心血管病杂志

Objective@#To assess the efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism.@*Methods@#Ten consecutive patients with intermediate-risk acute pulmonary embolism who received thrombolytic treatment with reteplase at Thrombosis and Vascular Medicine Center, Fuwai Hospital from March to November in 2016 were included.Vital signs, right ventricular diameter, systolic pulmonary artery pressure, and biochemical markers were assessed before and after thrombolytic therapy with reteplase, and bleeding complications were also observed during 3 months follow up.@*Results@#(1) For the efficacy outcomes: at 48 hours after thrombolytic treatment with reteplase, echocardiography-derived diameter of right ventricular was significant reduced from (27.9±3.8) mm to (24.8±2.6) mm (P=0.03), systolic pulmonary artery pressure decreased from (63.9±21.6) mmHg(1 mmHg=0.133 kPa) to (34.4±19.8) mmHg (P=0.02). Heart rate and breathing rate were also decreased significantly (both P<0.05), blood pressure remained unchanged post therapy.Hypoxemia was quickly corrected with an significant elevation of PaO2 and SaO2 ((65.2±14.3) mmHg vs. (80.0±9.6) mmHg, P=0.006; (90.8±3.5)% vs. (95.2 ±1.6)%, P=0.002 respectively). PaCO2 was also increased significantly (P<0.05). Serum NT-proBNP and cTnI were decreased significantly (both P<0.05). There was no recurrent pulmonary embolism or deep-vein thrombosis during the 3 months follow-up. (2) For the safety outcomes: a thrombolytic relevant hemoptysis (about 70 ml) occurred in 1 patient, and was controlled by PCC therapy.No other clinically relevant events were observed during thrombolytic treatment. Eight patients were followed more than 3 months, there was no major bleeding complication or death during the follow up period.@*Conclusion@#Treatment of intermediate-risk acute pulmonary embolism with reteplase is effective and safe and there are no obvious side effects.

Efficacy of inhaled iloprost on top of other targeted therapies for patients with pulmonary hypertension and severe right heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of inhaled iloprost on top of other pulmonary hypertension (PH) specific therapies for patients with PH and severe right heart failure.</p><p><b>METHODS</b>We consecutively enrolled WHO functional class IV patients with PH and chronic thromboembolic pulmonary hypertension (CTEPH) in Shanghai Pulmonary Hospital from January 2011 to January 2013. Inhaled iloprost was administrated to all enrolled patients, oral endothelin antagonist receptors (ERAs) and/or type 5 phosphodiasterase inhibitors (PDE5-I) were also used as basis therapies. The in-hospital outcomes and the changes of right heart functional parameters were observed.</p><p><b>RESULTS</b>Twenty-four patients with PH and 5 patients with CTEPH were enrolled. After a mean treatment duration of (23 ± 13) days, 3 patients dead and significant improvement was observed in the remaining 26 patients. Compared with the baseline, heart rate decreased from (99 ± 14) to (91 ± 12) bpm (P = 0.001), plasma NT-proBNP level decreased from 5 823 (3 029-13 248) to 3 220 (1 678-6 720) ng/L (P < 0.001), tricuspid annular plane systolic excursion (TAPSE) increased from (1.3 ± 0.4) to (1.4 ± 0.3) cm (P = 0.018), right ventricular diameter decreased (left-to-right diameter from (57 ± 11) to (53 ± 10) mm, P = 0.040, and superoinferior diameter from (69 ± 11) to (64 ± 16) mm, P = 0.027), Tbil also decreased from (41 ± 34) to (26 ± 17) µmol/L (P < 0.001). No severe side effects were observed.</p><p><b>CONCLUSION</b>The strategy of inhaled iloprost on top of other PAH-specific target therapy medications is effective and safe for PH patients with severe right heart failure.</p>

Comparison of clinical characteristics and survival on patients with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension during conventional therapy era and targeted therapy era / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the clinical characteristics and survival on Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) and familiar pulmonary arterial hypertension (FPAH) during conventional therapy era and targeted therapy era.</p><p><b>METHODS</b>IPAH and FPAH patients who were referred between Jan 1999 and Oct 2004 in Fuwai Hospital were defined as conventional therapy era group (before 2005 no PAH-specific drug was available in China). All patients in this group were followed up till Jun 2005. IPAH and FPAH patients who were referred between Sep 2006 and Aug 2011 were defined as targeted therapy era group (new PAH-specific drugs were available in China since 2006) were analyzed. All patients in this group were followed up till Dec 2013. The primary endpoints were death and therapy medicine.</p><p><b>RESULTS</b>Seventy-two patients were enrolled in conventional therapy era group, 375 were enrolled in targeted therapy era group. The mean age was (35.9 ± 12.2) years and (34.5 ± 17.4) years respectively (P = 0.67), and women was predominant in both groups. There was no difference in WHO functional class and hemodynamic data between the two groups. About 90.3% patients were treated by calcium-channel blockers (CCB) in conventional therapy era group. In targeted therapy era group, almost all patients were treated by at least one PAH-specific drug, only 3.2% patients who had a positive response to acute pulmonary vasodilator testing were treated by CCB. The median survival time was 30.4 months in conventional therapy era group and 66.2 months in targeted therapy era group. The 1-, 2-, 3- and 5- year survival rates of IPAH and FPAH patients were 68.0%, 56.9%, 38.9% and 20.8% in conventional therapy era group, and 89.3%, 78.1%, 68.2% and 53.7% in targeted therapy era group respectively (P < 0.000 1).</p><p><b>CONCLUSION</b>Compared with conventional therapy era, the survival rate of Chinese IPAH and FPAH patients is significantly improved in targeted therapy era.</p>

Long-term effects with ambrisentan monotherapy in patients with pulmonary arterial hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension (PAH).</p><p><b>METHODS</b>Patients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10, 2011 and August 30, 2012 for at least 6 months were enrolled. The efficacy endpoints were change in exercise capacity, World Health Organization (WHO) functional class and N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiographic parameters. The safety endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events.</p><p><b>RESULTS</b>A total of 18 patients with PAH were enrolled. Mean age was (39 ± 17) years, 8 (55.6%) were female, and 11 (61.1%) patients were in WHO functional class III. The median duration of treatment was 17 months (range: 6-26 months). After treatment, the 6MWD was significantly increased[ (495 ± 97) m vs. (400 ± 91) m, P < 0.001], NT-proBNP was significantly reduced [308 (53-1 645) ng/L vs. 80(22-454) ng/L, P = 0.005], the systolic pulmonary artery was significantly decreased [(62 ± 30) mmHg vs. (82 ± 41) mmHg, P = 0.001] and left ventricular end diastolic diameter was significantly increased [(44 ± 6) mm vs. (40 ± 6) mm, P < 0.004] compared to pre-treatment. WHO functional class was improved compared with baseline in 11(61.1%) patients, stable in 7(38.9%) patients. No patient died during the treatment period. No patient was withdrawn from this study for safety reasons.</p><p><b>CONCLUSIONS</b>Long-term treatment of ambrisentan can effectively improve the exercise capacity, reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan is safe and well tolerated in Chinese PAH patients.</p>

Associations of aquaporin-4 promoter polymorphism to multiple sclerosis and neuromyelitis optica in southern Chinese population / 中华神经科杂志

Objective To investigate the associations of aquaporin-4 (AQP4) promoter polymorphisms with anti-AQP4 antibody and genetic susceptibility to multiple sclerosis (MS) and neuromyelitis optica (NMO) in Southern Chinese population.Methods The polymorphisms of AQP4promoter 0 and 1 were analyzed by PCR and DNA sequencing in 18 NMO,38 MS,13 recurrent myelitis (RM),6 recurrent optic neuritis (RON)patients and 39 healthy controls. Results Fourteen polymorphism loci were observed in AQP4-promoter 0,while 6 ones were observed in AQP4-promoter 1.Among them,the incidence rate of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 in anti-AQP4 antibody-positive patients was significantly higher than that in anti-AQP4 antibody-negative patients and controls (former:13/18 vs 20/45,P =0.046; latter:13/18 vs 10/39,P =0.001 ).The incidence rates of polymorphism at position between -401 bp and -400 bp ( C inserted) of AQP4-promoter 1 in anti-AQP4 antibody-positive and -negative patients were significantly higher than that in controls( former:5/16 vs 0/28,P =0.008; latter:8/38 vs 0/28,P =0.027 ). The incidence rates of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 and position between -401 bp and -400 bp ( C inserted)of AQP4-promoter 1 in patients with NMO and MS were significantly higher than that in controls( NMO:11/18 vs 10/39,P =0.010;4/15 vs 0/28,P =0.020; MS:19/38 vs 10/39,P =0.027;8/34 vs 0/28,P =0.018).Conclusions Polymorphisms loci were observed in AQP4-promoter 0 and AQP4-promoter 1,which may have an influence on the susceptibility to MS and NMO.Polymorphism at position - 1003 bp ( A-G) of AQP4-promoter 0 may be related to the emergence of anti-AQP4 antibody in patients with NMO and MS.

Comparison of clinical features between acute disseminated encephalomyelitis and classical multiple sclerosis / 中华神经科杂志

Objective To improve differential diagnosis between acute disseminated encephalomyelitis ( ADEM) and classical multiple sclerosis ( CMS).Methods All 20 cases of ADEM and 24 cases of CMS were examined.Their epidemiological and clinical findings,laboratory features and magnetic resonance imaging ( MRI) data were analyzed using x2 test for categorical variables,Wilcoxon Rank-Sum tests for continuous variables.Results ADEM and CMS showed no sex predominance.Patients with ADEM ((27 ±15) years) were younger than CMS ((37 ±13) years,Z= -2.218,P =0.027).The following findings were more commonly seen in ADEM compared with CMS:predemyelinating infectious disease (75% vs 4%,x2 =23.652,P = 0.000),fever (65% vs 4%,x2 =18.609,P = 0.000),meningeal irritation sign (40% vs 0,x2 = 9.189,P =0.002),seizure (25% vs 0,x2 =4.514,P = 0.034),and encephalopathy.ADEM patients were more likely to present with blood leucocytosis ( (11.9 ± 5.8) ×109/L vs (8.0±3.2) ×109/L,Z= -2.030,P=0.042),high C-reactive protein (2.74 mg/L vs 0.49 mg/L,Z = - 3.028,P = 0.002),increased erythrocyte sedimentation rate (11.00 mm/h vs 7.00 mm/h,Z= -2.406,P =0.016),and cerebrospinal fluid leucocytosis (9 × 106/L vs 2×106/L,Z =- 2.781,P = 0.005).There were no differences in cerebrospinal fluid protein and oligoclonal band between the two groups.The following MRI lesions were more commonly seen in ADEM patients:cortical gray matter lesions (14/20,x2=15.213,P=0.000),basal ganglia gray matter lesions (14/20,x2 =8.910,P = 0.003),and brainstem lesions ( 14/20,x2 = 5.867,P = 0.015).In contrast,lesions in subcortical white matter (21/24,x2 = 17.628,P =0.000),periventricular area (21/24,x2 =15.213,P=0.000) and corpus callosum ( 14/24,x2 = 8.640,P = 0.003 ) were more common in the MRI image of CMS patients.The lesions in spinal cord were usually centrally distributed in ADEM (83% ),while peripherally in CMS (85%,x2 = 11.542,P = 0.001).The lesions had poorly defined margins in ADEM (95%),but well defined margins in CMS (75%,x2 =21.787,P = 0.000).Conclusion There are differences in epidemiological and clinical findings,laboratory features and MRI appearances between ADEM and CMS.

Clinical features and diagnosis in two cases general paresis of insane / 中华神经科杂志

Objective To analyse the clinical features in general paresis of insane(GPI)as to offering an early diagnosis. Methods A retrospective analysis of 2 cases of GPI was focused on their clinical manifestations. Results The clinical features of GPI showed: (1) Chronic onset, progressive development in 2 cases; (2) Dementia was key symptom.Hasegawa dementia scales were 4 and 17 in 2 cases.2 cases accompanied with abnormal mentality,such as delusion of grandeur ,euphoria and so on;(3)GPI have features of pupil change,dysarthria,muscular tension,abnormal reflection; (4) Serum and cerebrospinal fluid (CSF) syphilis antibody reaction manifested positive, CSF protein content was increased significantly, and cells increased ( with lymph cell mainly ); (5) Head MRI manifested: cerebral atrophy in 2 cases, multiple abnormal signals in cerebral parenchyma in 1 case. Conclusions GPI misdiagnosis rate is high. Important basis of diagnosis remains on clinical manifestations, laboratory and imaging examinations.

Isolation and culture of tumor stem cells in human retinoblastomas / 中国病理生理杂志

AIM:To isolate and culture tumor stem cells in human retinoblastomas (RTSC). METHODS: Retinoblastoma (RB) single cells acquired from fresh tumors of RB patients by enzyme digestion were seeded in serum-free medium at a density of 1?10~8 cells/L. Clonal cultures were plated at a density of 1?10~6 cells/L. Secondary tumor spheres were triturated again and passaged in fresh medium. The sphere-forming, proliferation and differentiation assays were performed. RT-PCR and immunocytochemistry were performed to identify the RTSC and differentiated cells. RESULTS: All RB tumors studied produced proliferating neurosphere-like tumor spheres, which were also passaged multiple times. These tumor spheres had the capability to self-renew, proliferate in SFM medium, expressed retinal progenitor cell related genes, and differentiated into neurons and glia when they were transferred to differentiation conditions.CONCLUSION:Our findings demonstrated that there were subsets of tumor stem cells resembling retinal progenitor cells in human RB, which can be isolated, cultured in SFM. The RTSC may be original cells of RB tumor, and also become the new target of tumor therapy.