[Analysis of echocardiographic features and postnatal management of fetal pulmonary valve stenosis].

Objective: To investigate the echocardiographic features, consistency of diagnosis between fetal and postnatal periods and postnatal clinical outcomes of fetal pulmonary valve stenosis (PS) with different degrees. Methods: This study was a retrospective cohort study comprising 108 cases of fetal PS diagnosed during the fetal period and followed up postnatally at Xinhua Hospital, Shanghai Jiaotong University School of Medicine from November 2012 to February 2023. Echocardiographic characteristics, including morphological and hemodynamic features were collected for all fetuses who were then were followed up to at least 6 months after birth. One-way analysis of variance and Kruskal-Wallis test were used to compare the differences in the echocardiographic features among fetuses with different degrees of PS. Subsequently, McNemar test was used to assess the consistency of diagnosis between the fetal and postnatal periods. Furthermore, Logistic regression analysis was applied to explore the risk factors for neonatal intervention in fetuses with moderate PS and the receiver operating characteristic (ROC) curve was utilized to ascertain the optimal cut-off value for continuous variables. Results: The age of the mothers of the 108 fetuses at the initial assessment was (30.8±4.0) years, and the gestational age was 26.5 (24.6, 30.0) weeks. The fetuses were categorized into mild (17 cases), moderate (49 cases), and severe groups (42 cases) based on the initial echocardiographic features. Mild PS was characterized by valve thickening and hyperechogenicity combined with systolic flow acceleration or dilation of main pulmonary artery. Moderate PS exhibited both restricted valve motion and a colorful blood flow pattern at the valve orifice. The peak flow velocities of fetuses with moderate and critical PS were notably higher than those in the mild group ((2.66±0.86) and (2.77±1.30) vs. (1.43±0.59)m/s, F=14.52, P<0.001). In critical PS, all cases showed retrograde ductal flow, with a significantly higher proportion of a small right ventricle compared to the mild and moderate PS (42.9% (18/42) vs. 0 and 2.0% (1/49), χ2=31.73, P<0.001). The proportion of severe tricuspid regurgitation was also higher (35.7% (15/42) vs. 0 and 10.2% (5/49), χ2=36.94, P<0.001). Compared to mild and severe PS, the consistency of diagnosis between fetal and postnatal periods in moderate PS was lower (40.8% (20/49) vs.13/17 and 80.3% (35/42), χ2=12.45, P=0.006). The systolic flow velocity was identified as an independent risk factor for neonatal intervention in fetuses with moderate PS (OR=7.21, 95%CI2.11-24.62). A flow velocity of ≥2.18 m/s in second trimester and ≥3.15 m/s in third trimester indicated the necessity of neonatal intervention for fetal moderate PS. Among the 108 fetuses, 68 underwent surgical intervention and all survived. Additionally, 39 fetuses were regularly followed up. A sole non-surgical fatality occurred, leading to a 6-month survival rate of 99.1% (107/108). Conclusions: Various degrees of fetal PS demonstrate distinctive morphological and hemodynamic alterations in echocardiography. The disparity in severity between the postnatal and fetal stages requires ongoing monitoring for fetal PS. The prognosis for fetal PS is generally favorable.

The composition of the intestinal microbiota after allogeneic haematopoietic stem cell transplantation and its association with graft versus host disease as assessed by 16Sribosomal ribonucleic acid.

To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.

[Outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting].

Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis.

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

[Efficacy of transcatheter pulmonary valve perforation by micro-guidewire and balloon dilation in neonates with pulmonary atresia with intact ventricular septum].

Objective: To investigate the safety and efficacy of transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The retrospective study included 21 neonates (14 males and 7 females) with PA-IVS who underwent transcatheter micro-guidewire pulmonary valve perforation and balloon dilation in Xinhua Hospital from January 2012 to December 2018. All patients underwent the pulmonary valve perforation by micro-guidewire through the Simmons catheter. During the follow-up period at 1, 3, 6, 12 months postoperatively and annually thereafter, the operative efficacy and the development of the right ventricle (RV) were evaluated by echocardiography. Statistical analyses were performed using t test. Results: A total of 21 neonates with PA-IVS were enrolled, and 13 cases were diagnosed prenatally. The median age of surgery was 6 days, the weight was (3.2±0.5) kg. The balloon/valve ratio was 1.19±0.12, and the RV pressure measured by catheter was (121±33) mmHg (1 mmHg=0.133 kPa) . The immediate postoperative RV pressure was (47±13) mmHg. The median follow-up time was 30 months. All the cases enrolled achieved biventricular circulation without death and serious complications. According to the last follow-up data including 16 cases who were followed up for 1 year or longer, the pulmonary artery transvalvular pressure was (29±15) mmHg. The postoperation ratio of right to left ventricular transverse diameter was significantly higher than that before operation (0.86+0.10 vs. 0.73+0.13, t=-2.96, P=0.006). Compared with preoperative data, the postoperation pulmonary valvular diameter Z-score was significantly higher (-1.41±0.89 vs. -2.83±1.06, t=-3.65, P=0.001) and the tricuspid valvular diameter Z-score was significantly higher (-0.52±0.29 vs. -1.34±0.81, t=-3.55, P=0.001). Conclusion: Transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation is a safe and effective initial therapy for neonatal PA-IVS.

[Population genomic researches of Escherichia coli].

Population genomics, an interdiscipline of genomics and population genetics, is booming in recent years with the rapid growth number of deciphered genomes and revolutionizes the understanding of bacterial population diversity and evolution dynamics. It also largely improves the prevention and control of infectious disease through providing more accurate genotyping and source-tracing results and more comprehensive characteristics of emerging pathogens. In this review, taking one of the best characterized bacteria, Escherichia coli, as model, we reviewed the phylogenetic relationship across its five major populations (designated A, B1, B2, D and E); and summarized researches on molecular mutation rate, selection signals, and patterns of adaptive evolution. We also described the application of population genomics in responding against large-scale outbreaks of E. coli O157:H7 and E. coli O104:H4. These results indicated that, although being a novel discipline, population genomics has played an important role in deciphering bacterial population structures, exploring evolutionary patterns and combating emerging infectious diseases.

Integrated non-invasive measurements reveal swallowing and respiration coordination recovery after unilateral stroke.

BACKGROUND: Oropharyngeal dysphagia is common after a stroke. Understanding the physiology of swallowing and its coordination with respiration in stroke recovery is crucially important. METHODS: A non-invasive swallowing assessment method was used to detect oropharyngeal swallowing and respiration coordination simultaneously during the swallowing process. This system detected movement of the larynx, submental muscle activity, and nasal airflow. Six different sizes of water boluses (maximum of 20 mL) were swallowed and assessed for each subject. KEY RESULTS: We recruited 59 healthy participants and 38 first ever unilateral stroke patients completed baseline and follow-up assessments at 3, 6, and 9 months poststroke. The results showed that oropharyngeal swallowing parameters in unilateral stroke deviate from normal patterns. For respiration coordination, the unilateral stroke group had longer swallowing apnea duration but similar frequencies of pre- and postswallowing respiratory phase patterns compared with the healthy controls. The probability of piece-meal deglutition was higher in the stroke group than in the control group. Additionally, there were gradually decreasing piece-meal deglutition probabilities among the stroke patients at follow-up, and none differed statistically from those of the controls at 6 months poststroke. CONCLUSIONS & INFERENCES: The non-invasive swallowing and respiration assessment method applied in this study detected the changes manifested in swallowing and respiration during the subacute phase of recovery in 6 months after a unilateral stroke. The study results serve as a baseline for further research and help advance dysphagia research methodologies. These assessments may be combined with bedside evaluations for clinical application.

Photoelectrochemical hydrogen generation with linear gradient Al composition dodecagon faceted AlGaN/n-GaN electrode.

We demonstrated photoelectrochemical cells (PECs) with dodecagon faceted AlGaN/n-GaN heterostructure electrode for H(2) generation, where the AlGaN/n-GaN heterostructure has a linear gradient Al composition (LGAC). The separation efficiency of the photo-generated electron-hole pairs in the electrode performs a key function in the H(2) generation efficiency of PEC cells. The linear gradient Al composition, AlGaN, could create more internal field and light absorption because of the linear graded band gap. Therefore, the zero-bias photocurrent density of PEC cells with dodecagon facet LGAC AlGaN/n-GaN heterostructure electrode is around 5.9 times larger than that of dodecagon faceted n-GaN electrode.

Distinct features between longitudinally extensive transverse myelitis presenting with and without anti-aquaporin 4 antibodies.

OBJECTIVES: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. METHODS: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. RESULTS: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-ß1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. CONCLUSION: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-ß treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.

ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease.

BACKGROUND AND PURPOSE: We recently reported a novel -62 G/A polymorphism within ataxin 8 (ATXN8) gene promoter region, with -62 G displaying significantly higher luciferase activity compared with -62 A. Phenotypic variability in spinocerebellar ataxia type 8 (SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease (PD). We aimed to investigate the association of ATXN8 -62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans-acting factor modulating the ATXN8 promoter activity. METHODS: A case-control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction (PCR) and restriction enzyme analysis. The trans-acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation (ChIP)-PCR assay, cDNA co-transfection and luciferase reporter assay. RESULTS: When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found (P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55-0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43-0.96, P = 0.030). ChIP-PCR and cDNA over-expression revealed that CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK-N-SH cells. CONCLUSIONS: Our data suggest that ATXN8 -62 G/A polymorphism plays a role in Taiwanese PD susceptibility.

Are there ethnic differences in impulsive/compulsive behaviors in Parkinson's disease?

BACKGROUND AND PURPOSE: Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson's disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS). METHODS: Two hundred and seventy-eight consecutive patients with idiopathic PD regularly followed-up at an outpatient clinic were interviewed and screened for the ICB between September 2008 and December 2008 using designated diagnostic criteria. All patients who screened positive for ICB or obsessive-compulsive disorder (OCD) were further confirmed by an experienced psychiatrist. RESULTS: Of all the studied patients, 15 patients confirmed to have ICB (lifetime prevalence: 5.60%), 3 (1.12%) were diagnosed to have DDS, 1 (0.37%) punding, 4 (1.49%) PG, 8 (2.99%) HS, 1 (0.37%) BE, 0 (0%) CS. OCD was found in one patient (0.37%). CONCLUSIONS: The prevalence of ICB is lower in Taiwan as compared with the Caucasians, with similar risk factors. The possible reasons include differences in ethnicity, environmental, cultural, and social factors as well as the dosage and selection of dopaminergic medications.

Association of eNOS gene polymorphisms with essential hypertension in the Han population in southwestern China.

Endothelial nitric oxide synthase (eNOS) plays an important role in maintaining blood pressure homeostasis and vascular integrity. Polymorphisms in the eNOS gene have been found to be associated with hypertension in different human populations, including Northern and Southern Chinese Han populations. To examine the relationship of three eNOS gene polymorphisms, T-786C (rs2070744), G894T (rs1799983), and G10T (rs7830), with hypertension in the Han population in southwestern China, we carried out a study of the genotypes of three SNPs in 510 hypertensive and 510 normotensive subjects from the Yunnan Province by using PCR-RFLP and sequencing. Our SNP analyses showed that the distribution of the T-786C polymorphism did not differ between patients and controls, and that G894T and G10T are significantly associated with hypertension in females, adjusted for covariates. Compared with the other haplotypes, haplotype H1 (TGG), carrying protective 10G and 894G alleles, significantly decreased the risk of increased essential hypertension in females, with an odds ratio of 0.68 (P = 10(-5)). These results suggest that the eNOS polymorphism is one of the factors contributing to the predisposition for essential hypertension in the Han population in southwestern China.

Acute disseminated encephalomyelitis that meets modified McDonald criteria for dissemination in space is associated with a high probability of conversion to multiple sclerosis in Taiwanese patients.

BACKGROUND: Patients with acute disseminated encephalomyelitis (ADEM) may relapse and some may ultimately convert to multiple sclerosis (MS); however, no criteria that can predict MS conversion are available to date. Our aim was to describe the clinical and magnetic resonance imaging (MRI) features of patients with an initial ADEM attack and evaluate which MRI criteria can predict conversion to MS. METHODS: We retrospectively reviewed the records of 36 patients diagnosed with ADEM. We determined clinical signs/symptoms, examined the cerebrospinal fluid (CSF), and performed brain MRI scans and compared the findings between patients who did and did not convert to MS. RESULTS: Clinical signs/symptoms, and CSF analysis show no significant difference between the two groups. The rate of conversion to MS from ADEM in Taiwanese patients is low (11%) after a mean follow-up period of 28.36 months. Modified McDonald criteria were fulfilled in 19/36 patients: 21% (4/19) of those patients developed MS according to Poser criteria subsequently. Of the other patients (17/36) who did not fulfill these criteria, none converted to MS. (log rank test; P=0.027). CONCLUSIONS: It is difficult to predict from initial clinical presentations to address which patients with ADEM will convert to MS. Patients with ADEM whose brain MRI findings met the modified McDonald criteria may have clinically isolated syndrome because they have a significantly higher probability of conversion to MS. In contrast, patients whose brain MRI findings did not meeting these criteria may be considered as having classic ADEM because they have a lower probability of conversion to MS.

Analysis of the UCHL1 genetic variant in Parkinson's disease among Chinese.

The inverse association of the functional ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) among Caucasian populations has been debated. We conducted a large-scale analysis to investigate the age-of-onset effect of the UCHL1 variant in PD among ethnic Chinese. Individual data sets from 5 centers comprising a total of 4088 study subjects were analyzed. In the univariate analysis, only data from 1 center showed a trend towards a protective effect among young subjects. However, in the combined analysis, no significant association between the UCHL1 variant and PD was detected (A allele frequency 0.531 vs. 0.528, p=0.87, OR 1.01, 95% CI 0.92-1.1). Among subjects less than 60 years old, the OR is 0.99 (95% CI 0.84-1.16, p=0.88). A multivariate logistic regression analysis showed that family history, UCHL1 variant and the interaction of UCHL1 variant and age at onset (p=0.816) were not significantly associated with PD.

Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic hyperglycemic chorea-ballism patients.

BACKGROUND: Non-ketotic hyperglycemic chorea-ballism (NKHCB) had special reversible hyperintense on T1-weighted imaging (T1WI) lesion in comparsion to gray matter. However, the mechanism accounts for these lesions is still unclear. METHODS: Patients diagnosed with NKHCB were recruited from 2002 to 2004. The demographic, clinical, magnetic resonance imaging (MRI), and spectroscopy (MRS) features were recorded at acute and remission phase. RESULTS: In 18 patients with NKHCB, the blood sugar level at onset was significantly higher than that after being free from chorea-ballism (419.50 +/- 257.33 vs. 198.22 +/- 53.97 mg/dl, P = 0.001). The serum osmolality dropped from 318.33 +/- 15.21 mOsm/kg at onset to 292.50 +/- 7.85 mOsm/kg after recovery (P < 0.001). All patients displayed T1 hyperintense lesions at contralateral basal ganglia at acute phase. Eight patients receiving follow-up MRI at remission phase, all T1 hyperintense lesions at the basal ganglia regressed. The ratios between choline-containing compounds and creatine at acute and remission phases were significant higher in lesion than in normal side, respectively (acute phase: 1.12 +/- 0.23 vs. 0.72 +/- 0.28, P = 0.038; remission phase: 1.23 +/- 0.47 vs. 0.68 +/- 0.15, P = 0.013). The lactate peaks present at 1.3 ppm on the lesion side either in acute or in remission phase of most case. CONCLUSIONS: The clinical, MRI, and MRS findings suggest that the mechanisms responsible for NKHCB may be a reversible ischaemia insult potentiated by hyperglycemia.

Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease.

Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer's disease (AD) could arise from dysfunction of the ER. Through a case-control study and an expression assay, we investigated the association of HSPA5 -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked -415 G/A and -180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for -415 AA/-180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18-0.75, P = 0.007] and -415 A/-180 G allele (OR = 0.69, 95% CI = 0.51-0.91, P = 0.009). The HSPA5 transcriptional activity of the -415 A/-180 G allele was significantly lower than that of the -415 G/-180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 -415 A/-180 G allele in Taiwanese AD susceptibility.

Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan.

BACKGROUND AND PURPOSE: This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case-control study. METHODS: Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. RESULTS: Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1-6.5, P = 0.02) was associated with female SDICH. CONCLUSIONS: This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan.