Validity of the Chinese multimorbidity-weighted index in measuring disease burden using health check-ups data in primary care.

BACKGROUND: As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. METHODS: The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). RESULTS: One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. CONCLUSIONS: CMWI, calculated based on primary care's routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients' health risks in primary care.

Outcomes and risk factors of perforating and non-perforating middle cerebral artery infarctions after intravenous thrombolysis.

The clinical symptoms of perforating arteries differ, and responses to intravenous thrombolytic therapy are heterogeneous. Here, we investigated the effect of intravenous thrombolytic therapy and the related factors influencing acute perforating and non-perforating middle cerebral artery infarctions. We analyzed 320 patients with acute middle cerebral artery infarction who received alteplase thrombolysis within 4.5 h of onset at two stroke centers from January 2016 to December 2019. Outcome measures included rates of a favorable functional outcome (modified Rankin Scale scores of 0-2), distribution of modified Rankin Scale scores, intracranial hemorrhage, and symptomatic cerebral hemorrhage at 14 days, with comparisons between perforating artery and non-perforating artery cerebral infarction groups. In the perforating vessel disease group, 12 cases (17.4%) of intracranial hemorrhage occurred, with symptomatic cerebral hemorrhage in three cases (4.3%); there were no significant differences between the perforating and non-perforating vessel disease groups (all P > 0.05). In the perforating vessel disease group, the only significant prognostic factor was the National Institutes of Health Stroke Scale score before thrombolysis (Exp(B) = 1.365; 95% confidence interval [CI] 1.124-1.659; P = 0.002), and the only significant risk factor for hemorrhagic transformation was previous perforator disease (Exp(B) = 0.078; P = 0.038). Regardless of whether an acute infarction is perforating or non-perforating, intravenous thrombolytic therapy can yield a favorable outcome. Therefore, intravenous thrombolysis should be actively administered to treat perforating artery infarctions with a high risk of disability.

A Chemoenzymatic Cascade Combining a Hydration Catalyst with an Amine Dehydrogenase: Synthesis of Chiral Amines.

The combination of biocatalysis and transition-metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co-catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process.

Higher uric acid is associated with better discharge recovery and short-term outcome in stroke patients treated with thrombolysis.

BACKGROUND: Uric acid (UA) possesses antioxidant features and potential neuroprotective effects. However, conflicting results regarding the association between serum uric acid (SUA) levels and the prognosis of stroke have been obtained. We aimed to assess whether SUA is related to discharge recovery and short-term outcomes in patients who underwent thrombolysis therapy. METHODS: We recruited 393 consecutive patients who were diagnosed with acute ischaemic stroke (AIS) and treated with thrombolysis. The demographic information, including sex and age, was collected. Haematology tests, including SUA, fasting plasma glucose (FPG), and blood lipid parameters, were performed under fasting conditions the morning after admission. The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at discharge and 3 months after onset. RESULTS: A negative correlation was observed between the levels of SUA and the National Institute of Health Stroke Scale (NIHSS) score at discharge (r = - 0.171, P = 0.003). Additionally, a positive correlation was observed between the levels of SUA and the difference between the baseline NIHSS and discharge NIHSS (r = 0.118, P = 0.032). The levels of SUA in the patients with good outcomes (353.76 ± 93.05) were higher than those in the patients with poor outcomes (301.99 ± 92.24; P = 0.015) at 3 months. The multivariate logistic regression analysis demonstrated that a higher SUA level (odds ratio 0.988, 95% confidence interval 0.985-0.991, P = 0.002) was an independent predictor of a good outcome at 3 months. CONCLUSION: Higher SUA levels were associated with better discharge recovery and 3-month outcomes in patients with ischaemic stroke who received thrombolysis.

Effects of full windshield head-up display on visual attention allocation.

This study explores the impact of full windshield head-up display (FHUD) cues on the visual attention allocation of drivers under different scenarios. Forty-eight participants with driving experience were randomly divided into two groups and asked to drive on a preset route in various virtual driving scenarios created in advance. The full windshield highlights situational cues related to the driving task, such as lane lines, safe vehicle distance warnings, navigation guidance and pedestrian cues. Regarding the perception of situational cues, the number of fixations and mean fixation duration with FHUD were lower than those without FHUD. Furthermore, the dwell time percentage of the driver's forward view with FHUD was larger than that without FHUD, and the dwell time percentage on both sides was smaller than that without FHUD. In conclusion, FHUD may help drivers more effectively perceive cues and improve drivers' visual attention allocation. Practitioner summary: FHUD may affect drivers' attention while driving. We examined the effect of FHUD on number of fixations, fixation duration and dwell time percentage in the area of interest under different weather scenarios. Experimental results indicated that FHUD could improve drivers' visual attention allocation and help drivers more effectively perceive cues. Abbreviations: FHUD: full windshield head-up display; HUD: head-up display; HDD: head-down display; AOI: area of interests; AR: augmented reality.

Long-term outcome of a Chinese cohort idiopathic retinitis, vasculitis, aneurysms, and neuroretinits (IRVAN) patients.

PURPOSE: To evaluate the clinical characteristics and treatment outcomes of idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN) in a cohort of Chinese patients. MATERIALS: The clinical history, imaging evaluation, treatment and outcomes of 42 eyes in 21 patients diagnosed with IRVAN in a 15-year period were reviewed. RESULTS: Most patients were females (90%) ranged from 15 to 58 years old. The initial decimal best corrected visual acuity (BCVA) of the patients ranged from light perception (LP) to 1.5 (0.55 ± 0.38). Eighteen eyes were in stage 2; 21 eyes in stage 3; and 1 in stage 5 at the initial visits according to the present staging system. Two eyes had vitreoretinal fibrovascular proliferation (FVP) and tractional retinal detachment (RD) at the initial visit. Intra-retinal microvascular abnormality (IRMA) was found in 7 eyes. Thirty-four eyes received retinal photocoagulation, 27 of which were pan-retinal photocoagulation (PRP). Total of 8 PPV were performed for VH, vitreoretinal FVP and RD, and macular epimembrane. Aneurysms on the head of optic nerve and artery bifurcations disappeared in 8 eyes and decreased in number in 2 eyes 1 year after photocoagulation. However, the BCVA of the patients did not have significant difference from that at the initial visits (P = 0.534). Seven eyes suffered severe visual impairment (BCVA ≤ 0.1) due to vitreoretinal FVP and tractional RD (3), exudative maculopathy (2), paracentral acute middle maculopathy (PAMM)(1), and neovascular glaucoma (NVG) (1). CONCLUSIONS: We found that IRVAN have a predilection to female gender. Vitreoretinal FVP and tractional RD and exudative maculopathy are major causes of severe visual impairment in IRVAN patients. We propose to revise the present staging system to include vitreoretinal FVP and RD in the staging of IRVAN patients.

Analysis of factors affecting the prognosis of COVID-19 patients and viral shedding duration.

The clinical characteristics of patients with COVID-19 were analysed to determine the factors influencing the prognosis and virus shedding time to facilitate early detection of disease progression. Logistic regression analysis was used to explore the relationships among prognosis, clinical characteristics and laboratory indexes. The predictive value of this model was assessed with receiver operating characteristic curve analysis, calibration and internal validation. The viral shedding duration was calculated using the Kaplan-Meier method, and the prognostic factors were analysed by univariate log-rank analysis and the Cox proportional hazards model. A retrospective study was carried out with patients with COVID-19 in Tianjin, China. A total of 185 patients were included, 27 (14.59%) of whom were severely ill at the time of discharge and three (1.6%) of whom died. Our findings demonstrate that patients with an advanced age, diabetes, a low PaO2/FiO2 value and delayed treatment should be carefully monitored for disease progression to reduce the incidence of severe disease. Hypoproteinaemia and the fever duration warrant special attention. Timely interventions in symptomatic patients and a time from symptom onset to treatment <4 days can shorten the duration of viral shedding.

The role of carotid stenosis ultrasound scale in the prediction of ischemic stroke.

INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study.

BACKGROUND & AIMS: Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS: The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS: The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY: There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.

Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa.

PURPOSE: To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population. DESIGN: Cohort study. PARTICIPANTS: A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 2701) were recruited. METHODS: All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation. MAIN OUTCOME MEASURES: Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing. RESULTS: Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup (≤5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6-16 years old, 73.74%) and late-onset subgroup (≥17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP. CONCLUSIONS: This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum is completely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to family members. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in China.

Long Non-Coding RNA (LncRNA) CAIF is Downregulated in Osteoarthritis and Inhibits LPS-Induced Interleukin 6 (IL-6) Upregulation by Downregulation of MiR-1246.

BACKGROUND Osteoarthritis (OA) affects about 40% of people older than 40 years of age, and the mechanism is not well understood. Long non-coding RNA (lncRNA) CAIF is a recently identified critical player in myocardial infarction, while its role in other human diseases is unclear. The present study aimed to investigate the role of CAIF in OA. MATERIAL AND METHODS Levels of CAIF in synovial fluid of OA patients (n=60) and healthy controls (n=60) were measuring by performing quantitative real-time polymerase chain reaction (qRT-PCR). MiR-1246 and interleukin (IL)-6 levels in synovial fluid were measured by performing qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell apoptosis analysis was performed after CHON-001 cells were treated with 500 mg/mL lipopolysaccharide (LPS) for 24 hours. RESULTS We found that CAIF in synovial fluid was downregulated in OA patients and inversely correlated with miR-1246 and IL-6. Downregulated CAIF distinguished OA patients from healthy controls. In cells of chondrogenic cell line CHON-001, CAIF overexpression mediated the inhibited expression of miR-1246 and secretion of IL-6, while miR-1246 overexpression reduced the effects of CAIF overexpression on IL-6 secretion. In addition, CAIF overexpression inhibited the apoptosis of CHON-001 cells under LPS treatment, while miR-1246 overexpression attenuated the effects of CAIF overexpression. CONCLUSIONS Therefore, CAIF may downregulate miR-1246 to improve OA.

NOVEL BEST1 MUTATIONS DETECTED BY NEXT-GENERATION SEQUENCING IN A CHINESE POPULATION WITH VITELLIFORM MACULAR DYSTROPHY.

PURPOSE: To characterize novel BEST1 mutations and the phenotype-genotype correlations in vitelliform macular dystrophy in a Chinese population. METHODS: Seventeen individuals affected by vitelliform macular dystrophy underwent detailed ophthalmic examinations, including a best-corrected visual acuity test, slit-lamp biomicroscopy, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography angiography. Next-generation sequencing was used to screen 790 genes frequently involved in common inherited nonsyndromic eye diseases in all participants. Sanger sequencing was used to identify possible disease-causing variants. RESULTS: The mean ± SD age of the patients was 44.20 ± 15.09 (range: 16-69) years. Seven novel BEST1 mutations were identified: six heterozygous missense (p.Thr307Asn, p.Ile295The, p.Leu75Pro, p.Thr2Ser, p.Ser79Tyr, and p.Val81Leu) and one frameshift (p.Glu115GlufsX120) mutation. Choroidal neovascularization was detected in two probands. One individual presented with subfoveal focal choroidal excavation. Arden ratios obtained by electrooculography were less than the 1.5 cutoff value in 7 patients. No mutations were identified in 2 patients, one of whom had a fundus appearance typical of vitelliform macular dystrophy and a decreased Arden ratio (1.2/1.2). CONCLUSION: Patients with the same heterozygous BEST1 mutations exhibited varying phenotypes. Our results have expanded the BEST1 mutation spectrum in a Chinese population with vitelliform macular dystrophy.

MULTIMODAL FUNDUS IMAGING OF OUTER RETINAL TUBULATIONS IN CHOROIDAL OSTEOMA PATIENTS.

PURPOSE: To evaluate the morphological findings of outer retinal tubulations (ORTs) shown on multimodal imaging modalities in patients with choroidal osteoma. METHODS: Nineteen eyes of 17 patients with choroidal osteoma underwent full clinical and imaging assessments. Color fundus photography, spectral-domain optical coherence tomography (OCT), and en face OCT were used to identify and detect the characteristics of ORT structures, including the shape, configuration, location, and distribution in the fundus. Optical coherence tomography angiography was implemented as an assist to differentiate tumor's feeder vessels from choroidal neovascularization. The correlations between age, gender, tumor features, best-corrected visual acuity at baseline, OCT characteristics, and the presence of ORTs were analyzed. RESULTS: Outer retinal tubulations were identified in five eyes (26.3%). All were located at the decalcified region of the tumor where the choroidal vessels, retinal pigment epithelium, and overlying outer retinal structures were considerably disrupted to varying degrees. With spectral-domain OCT, the ORTs appeared as one or multiple, round or ovoid, hyporeflective lumens with hyperreflective borders confined to the outer nuclear layer, sometimes with hyperreflective luminal content (four eyes, 80%). In one eye, ORTs were found at the focal choroidal excavation. On en face OCT, these tubulations exhibited different shapes, including a dendritic pattern in two eyes, a tube-like pattern in one eye, a circular pattern in one eye, and a hairpin pattern in one eye. Simultaneous OCT angiography imaging demonstrated that the area of choroidal neovascularization was underneath ORT in one eye and very close to ORT in two eyes. The ORTs of three eyes were above or adjacent to tumor's rich feeder vessels. Statistically, age (P = 0.007), greatest tumor linear dimension (P = 0.003), total tumor area (P = 0.002), decalcification area (P = 0.000), and the presence of intraretinal fluid (P = 0.01) and retinal pigment epithelium alterations (P = 0.038) within the foveola and central 1-mm region of patients with ORT were significantly different from those of patients without ORTs. CONCLUSION: The results of this study suggest that age, the greatest tumor linear dimension, total tumor area, decalcification area, and the presence of intraretinal fluid and retinal pigment epithelium alterations within the foveola and central 1-mm region might be risk factors for ORT formation. Spectral-domain OCT combined with en face OCT provides comprehensive imaging information for ORTs in choroidal osteoma.

Predictive multi-imaging biomarkers relevant for visual acuity in idiopathic macular telangiectasis type 1.

BACKGROUND: To evaluate the structural changes associated with visual acuity (VA) in patients with idiopathic macular telangiectasia (MT) type 1 using multimodal imaging modalities. METHODS: A retrospective study of 14 patients with MT type 1 and of 10 eyes from 10 healthy individuals as age-matched controls was conducted. The medical records of patients who had undergone colour fundus photography, spectral domain optical coherence tomography (OCT), fluorescein angiography and OCT angiography were reviewed. Central macular thickness (CMT), the areas of macular oedema and ellipsoid zone (EZ) disruption, EZ length, disorganization of the retinal inner layers (DRIL) and external limiting membrane (ELM) disruption, as measured by spectral domain OCT; and vascular density and the foveal avascular zones (FAZ) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as measured by OCT angiography, were assessed in MT type 1 eyes and correlated with VA. RESULTS: The mean baseline best-corrected VA of MT type 1 eyes was 0.45 ± 0.28. The mean CMT was 385.19 ± 75.21 µm in MT type 1 eyes and 252.43 ± 15.77 µm in contralateral eyes (Z = - 4.113, p < 0.001). The mean vessel density of the DCP was lower in MT type 1 eyes (47.25 ± 4.69%) than in contralateral eyes (53.93 ± 2.94%) and normal eyes (59.37 ± 2.50%) (Z = - 3.492, - 4.099; p < 0.001, < 0.001). The baseline logMAR VA was correlated with CMT (r = 0.682, p = 0.007), SCP density (r = - 0.652, p = 0.012), DCP density (r = - 0.700, p = 0.005), total area of EZ disruption (r = 0.649, p = 0.012); and total lengths of EZ (r = 0.681, p = 0.007), ELM (r = 0.699, p = 0.005) and DRIL (r = 0.707, p = 0.005) disruption in the 1-mm-diameter foveal region in MT type 1 eyes. CONCLUSIONS: Decreased DCP density and the presence of DRIL may be predictive biomarkers of VA in MT type 1. CMT, SCP density, total area of EZ disruption, and lengths of EZ and ELM disruption within the 1-mm-diameter central region were strongly associated with VA.

Novel BEST1 Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy.

PURPOSE: To describe the clinical features and to analyze BEST1 mutations in patients with Best vitelliform macular dystrophy (BVMD). METHODS: Thirteen individuals affected by BVMD from 6 unrelated Chinese families were studied. Complete ophthalmological examinations were performed, and the BEST1 gene was screened in all participants and 100 controls. Follow-ups were arranged within 12 months. RESULTS: All 6 probands showed typical fundus appearances of BVMD. One of the 6 had a history of angle closure glaucoma, and another showed a unilateral focal choroidal excavation on optical coherence tomography. One patient experienced progression of the macular lesion during the follow-up. The asymptomatic mutation carriers had normal fundus but abnormal Arden ratios on electro-oculograms. Besides 4 previously reported mutations (p.Ser16Phe, p.Ser144Asn, p.Glu292Lys, p.Glu300Lys), 2 novel disease-causing mutations (p.Thr307Asp, p.Arg47His) were identified, of which p.Arg47His has been reported in adult-onset vitelliform macular dystrophy. CONCLUSIONS: Our findings have expanded the mutational and clinical spectrum of BVMD in a Chinese population. Clinical presentations of angle closure glaucoma and/or focal choroidal excavation may be related to BVMD, underlining the necessity of multimodal studies and risk assessment of angle closure glaucoma in BEST1 mutation carriers. BVMD and adult-onset vitelliform macular dystrophy may share a common etiology in some cases.

[Gene mutations and clinical features of adult vitelliform macular dystrophy in 5 patients].

OBJECTIVE: To describe the clinical features as well as mutations in 2 relative genes in 5 cases with macular dystrophies presenting with vitelliform lesions in adulthood. METHODS: Case control study. A total of 5 patients visited Eye and ENT Hospital of Fudan University between January and December 2012 and diagnosed with adult onset macular dystrophy were reviewed. Patient evaluation included complete ophthalmic examinations, such as optical coherence tomography, fundus photography, electrooculogram testing and fundus autofluorescence. The Best1 and peripherin/RDS genes were screened for variation by direct DNA sequencing of coding regions and intron/exon boundaries. At the same time, 50 controls were screened in the same way to get comparisons. RESULTS: The age at the time of diagnosis ranged from 28 to 59 years with the average of 45 years. 2 patients were affected bilaterally, while the other 3 were unilateral Attack. Moreover, vitelliform lesion and macular atrophy was found in 2 eyes separately in 1 patient. Direct sequencing of PCR products spanning all exons revealed a noval missense mutation in 1 patient:1009 G>A, causing a Ala 337 Thr change in Peripherin/RDS gene exon 3, as well as a slightly reduced EOG Arden index bilaterally. There was no such change in controls. CONCLUSIONS: The AVMD related with mutations in peripherin/RDS gene has its own clinical features. The mutation near the C-terminal domain of the polypeptide may play a crucial role in the development of AVMD. There is some relevance between clinical feature and genetype in AVMD.

Diagnostic value and cognitive regulatory roles of long non-coding RNA UCA1 in Alzheimer's disease.

BACKGROUND: To explore the diagnostic role and potential mechanism of serum lncRNA UCA1 in Alzheimer's disease (AD). METHODS: UCA1 concentration was determined using quantitative RT-PCR. The receiver operating characteristic curve was plotted to assess the diagnostic value. Cell viability and apoptotic capacity were assessed by cell counting kit-8 (CCK-8) and flow cytometry. Water maze experiments were used to test cognitive function in mice. The target genes of UCA1 were identified with a dual luciferase reporter assay. Functional and pathway analysis of miR-342-3p target genes was determined using enrichment analysis. RESULTS: The concentration of UCA1 was elevated in the AD group and represented a diagnostic possibility of AD. The silenced UCA1 reduced the roles of Aß on viability and apoptosis of SH⁃SY5Y cells by sponging miR-342-3p. The impaired cognitive impairment was partly recovered by the knockdown of the UCA1/miR-342-3p axis. Potential targets of miR-342-3p were enriched in function and pathways related to AD progression. CONCLUSION: The UCA1/miR-342-3p axis contributed to the occurrence of AD by regulating cognitive ability.

A switch in the pathway of TRPC3-mediated calcium influx into brain pericytes contributes to capillary spasms after subarachnoid hemorrhage.

Calcium influx and subsequent elevation of the intracellular calcium concentration ([Ca2+]i) induce contractions of brain pericytes and capillary spasms following subarachnoid hemorrhage. This calcium influx is exerted through cation channels. However, the specific calcium influx pathways in brain pericytes after subarachnoid hemorrhage remain unknown. Transient receptor potential canonical 3 (TRPC3) is the most abundant cation channel potentially involved in calcium influx into brain pericytes and is involved in calcium influx into other cell types either via store-operated calcium entry (SOCE) or receptor-operated calcium entry (ROCE). Therefore, we hypothesized that TRPC3 is associated with [Ca2+]i elevation in brain pericytes, potentially mediating brain pericyte contraction and capillary spasms after subarachnoid hemorrhage. In this study, we isolated rat brain pericytes and demonstrated increased TRPC3 expression and its currents in brain pericytes after subarachnoid hemorrhage. Calcium imaging of brain pericytes revealed that changes in TRPC3 expression mediated a switch from SOCE-dominant to ROCE-dominant calcium influx after subarachnoid hemorrhage, resulting in significantly higher [Ca2+]i levels after SAH. TRPC3 activity in brain pericytes also contributed to capillary spasms and reduction in cerebral blood flow in an in vivo rat model of subarachnoid hemorrhage. Therefore, we suggest that the switch in TRPC3-mediated calcium influx pathways plays a crucial role in the [Ca2+]i elevation in brain pericytes after subarachnoid hemorrhage, ultimately leading to capillary spasms and a reduction in cerebral blood flow.