Novel coronavirus mutations: Vaccine development and challenges.

The ongoing global pandemic of novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 has a significant impact on global health and economy system. In this context, there have been some landmark advances in vaccine development. Over 100 new coronavirus vaccine candidates have been approved for clinical trials, with ten WHO-approved vaccines including four inactivated virus vaccines, two mRNA vaccines, three recombinant viral vectored vaccines and one protein subunit vaccine on the "Emergency Use Listing". Although the SARS-CoV-2 has an internal proofreading mechanism, there have been a number of mutations emerged in the pandemic affecting its transmissibility, pathogenicity and immunogenicity. Of these, mutations in the spike (S) protein and the resultant mutant variants have posed new challenges for vaccine development and application. In this review article, we present an overview of vaccine development, the prevalence of new coronavirus variants and their impact on protective efficacy of existing vaccines and possible immunization strategies coping with the viral mutation and diversity.

Stress-Induced Hyperglycemia and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Stress-induced hyperglycemia (SIH) is the relative transient increase in glucose during a critical illness such as intracerebral hemorrhage (ICH) and is likely to play an important role in the pathogenesis of remote diffusion-weighted imaging (DWI) lesion (R-DWIL) in primary ICH. We sought to determine the association between SIH and the occurrence of R-DWILs. METHODS: We prospectively enrolled primary ICH patients within 14 days after onset from November 2016 to May 2018. In these patients, cerebral magnetic resonance imaging was performed within 14 days after ICH onset. R-DWIL was defined as a hyperintensity signal in DWI with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. SIH was measured by stress-induced hyperglycemia ratio (SHR). SHR was calculated by fasting blood glucose (FBG) divided by estimated average glucose derived from glycosylated hemoglobin. The included patients were dichotomized into two groups by the 50th percentile of SHR, and named as SHR (-P50) group and SHR (P50+) group, respectively. We evaluated the association between SHR and R-DWIL occurrence using multivariable logistic regression modeling adjusted for potential confounders. RESULTS: Among the 288 patients enrolled, forty-six (16.0%) of them had one or more R-DWILs. Compared with the patients in the lower 50% of SHR (SHR [-P50]), the odds ratio (OR) [95% confidence interval (CI)] for the higher 50% of SHR (SHR [P50+]) group for R-DWIL occurrence was 3.13 (1.39-7.07) in the total population and 6.33 (2.19-18.30) in population absent of background hyperglycemia after adjusting for potential covariates. Similar results were observed after further adjusted for FBG. CONCLUSIONS: Our study demonstrated that SIH was associated with the occurrence of R-DWILs in patients with primary ICH within 14 days of symptom onset.

Cholinergic Grb2-Associated-Binding Protein 1 Regulates Cognitive Function.

Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer's disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons. Gab1 overexpression, on the other hand, improved cognitive function and restored hippocampal CaMKII autorphosphorylation in AD mice. These results suggest that Gab1 plays an important role in the pathophysiology of AD and may represent a novel therapeutic target for diseases involving cholinergic dysfunction.

[Determination of forbidden and restricted pesticides in Angelicae Sinensis Radix].

The present study is to establish a method for simultaneous determination of 50 kinds of pesticides in Angelicae Sinensis Radix by using liquid chromatography tandem mass spectrometry. The forbidden,restricted and customary pesticides were picked out as detecting indexes according to the principals of risk management. The factors affecting the extraction,purification,and detection were optimized,and the final condition was established as follows: the samples were extracted with acetonitrile. The separation of target compounds were performed by liquid column,and quantitative analysis was carried out by LC-MS/MS with MRM model. The calibration curves were linear in the range of 1-100 µg·L~(-1) with correction coefficients of greater than 0. 990. The recoveries of more than 93. 9%pesticides were ranged from 60% to 140% at three spiked levels. The detecting indexes in the method cover most forbidden and restricted pesticides,which is meaningful for the safety supervision of the Angelicae Sinensis Radix. With the advantage of rapidness and accuracy,this method can be used for routine determination of multi-pesticides in Angelicae Sinensis Radix.

Thalamocortical dysconnectivity in paroxysmal kinesigenic dyskinesia: Combining functional magnetic resonance imaging and diffusion tensor imaging.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is associated with macrostructural and microstructural abnormalities in the thalamus. OBJECTIVES: To examine functional and structural connectivity of thalamocortical networks in paroxysmal kinesigenic dyskinesia and to further investigate the effect of mutation of the proline-rich transmembrane protein 2 on thalamocortical networks. METHODS: Patients with paroxysmal kinesigenic dyskinesia (n = 20), subdivided into proline-rich transmembrane protein 2-mutated (n = 8) and nonmutated patients (n = 12) and healthy controls (n = 20) underwent resting-state functional MRI and diffusion imaging scan. The functional properties of correlations in neural activity (functional connectivity) and the structural properties of white matter probabilistic tractography (structural connectivity) were analyzed to characterize thalamocortical networks. Furthermore, the effect of proline-rich transmembrane protein 2 mutation on functional and structural connectivity of thalamocortical networks were examined using one-way analysis of variance among three groups. RESULTS: Patients had increased functional and structural connectivity between ventral lateral/anterior thalamic nuclei and a lateral motor area, as compared to controls. This functional connectivity positively correlated with disease duration. Interestingly, proline-rich transmembrane protein 2-mutated patients showed decreased functional connectivity and preserved structural connectivity, between mediodorsal nucleus and prefrontal cortex, compared to nonmutated patients and controls. CONCLUSIONS: Thalamomotor/premotor hyperconnectivity suggests abnormal communication between thalamus and motor cortex in patients. Furthermore, thalamoprefrontal hypoconnectivity in proline-rich transmembrane protein 2-mutated patients might indicate that proline-rich transmembrane protein 2 mutations result in inefficient thalamoprefrontal integration. Our findings facilitate a deeper understanding of the crucial role of thalamocortical dysconnectivity in the pathophysiological mechanisms of paroxysmal kinesigenic dyskinesia. © 2017 International Parkinson and Movement Disorder Society.

TMPyP4-regulated cell proliferation and apoptosis through the Wnt/ß-catenin signaling pathway in SW480 cells.

BACKGROUND: The aim of this study was to investigate the potential effects of the 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of SW480 cells and the underlying mechanisms by which TMPyP4 exerted its actions. METHODS: After treated with different doses of TMPyP4, cell viability was determined by MTT method, the apoptosis was observed by flow cytometry (FCM) and the expression of Wnt, GSK-3ß, ß-catenin and cyclinD1 was measured by RT-PCR and Western blot analysis. RESULTS: The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of SW480 cells in a dose-dependent manner. In addition, the downregulation of Wnt, ß-catenin and cyclinD1 expression levels was detected in TMPyP4-treated SW480 cells. However, followed by the block of Wnt signaling pathway using siRNA methods, the effects of TMPyP4 on proliferation and apoptosis of SW480 cells were significantly reduced. CONCLUSION: It indicates that the TMPyP4-inhibited proliferation and -induced apoptosis in SW480 cells was accompanied by the suppression of Wnt/ß-catenin signaling pathway. Therefore, TMPyP4 may represent a potential therapeutic method for the treatment of colon carcinoma.

Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

BACKGROUND: Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. METHOD: A retrospective chart review of the patient was performed. RESULTS: We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. CONCLUSION: We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare.

Prevalence of hyperhomocysteinaemia and some of its major determinants in Shaanxi Province, China: a cross-sectional study.

The aim of the present study was to investigate the prevalence of hyperhomocysteinaemia (HHCY; total plasma homocysteine (tHcy) concentration >15 µmol/l) and its major determinants in healthy Chinese northerners. A descriptive and cross-sectional study was conducted in Shaanxi Province, China. The study sample included 2645 participants (1042 men and 1603 women) aged >20 years. Demographic characteristics and lifestyle factors were assessed via questionnaire interviews and physical examination. Plasma levels of homocysteine and folate and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism were determined according to standard methods. The prevalence of HHCY was 67·7 % (81·4 % in men and 58·8 % in women). The geometric mean of tHcy concentration was 19·1 µmol/l. The OR of HHCY were 0·44 (95 % CI 0·34, 0·57) for women v. men; 1·95 (95 % CI 1·41, 2·70), 1·41 (95 % CI 1·05, 1·88) and 0·76 (95 % CI 0·64, 0·89) for participants with smoking and alcohol drinking cessation and improved physical activity levels, respectively; 0·25 (95 % CI 0·17, 0·38), 0·33 (95 % CI 0·22, 0·49) and 0·56 (95 % CI 0·36, 0·88) for participants with an education level of elementary school, secondary school and university v. illiterate, respectively; 1·41 (95 % CI 1·13, 1·75) and 3·05 (95 % CI 2·35, 3·97) for participants with CT and TT v. CC genotype at MTHFR 677C â†’ T polymorphism, respectively. These results demonstrate that the prevalence of HHCY is considerably high in Chinese northerners, especially in TT subjects, suggesting that implementation of tHcy-lowering strategies, such as lifestyle changes, is necessary.

Adaptation of muscles of the lumbar spine to sudden imbalance in patients with lower back pain caused by military training.

OBJECTIVE: This study aims to investigate the effects of sudden load changes (expected and unexpected imbalance) on the activity of muscles of the lumbar spine and their central motor control strategy in military personnel with or without chronic low back pain (LBP). DESIGN: Bilateral sudden imbalance was examined (2 × 2 factorial design). SETTING: The 117th PLA Hospital, Hangzhou, China PARTICIPANTS: Twenty-one male subjects with lower back pain and 21 male healthy control subjects were active members of the Nanjing Military Region land forces. OUTCOME MEASURES: Independent variables: LBP vs. healthy controls and imbalance anticipation (expected and unexpected imbalance). DEPENDENT VARIABLES: rapid reaction time (RRT) and intensity of rapid reaction (IRR) of bilateral lumbar (L3-L4) erector spinae (ES), lumbar (L5-S1) multifidus (MF), and abdominal external oblique muscles. Results Under expected or unexpected sudden imbalance conditions, subjects with LBP demonstrated significantly greater IRR than healthy controls in ipsilateral and contralateral ES and MF, respectively (P < 0.05 for all). IRR of contralateral ES was significantly larger than that of the ipsilateral ES. A significant group effect of RRT of both ipsilateral and contralateral ES muscles and a significant time expectation effect on RRT of contralateral MF muscles were also observed. RRT of the contralateral ES muscles was significantly lower than that of the ipsilateral ES muscles (P < 0.001). CONCLUSIONS: Sudden imbalance prolonged RRT of selected trunk muscles in patients with chronic LBP. The activation amplitude increased. The results may provide a theoretical basis for a study on the pathogenesis of chronic LBP.

The awareness rate of knowledge of chronic diseases and influencing factors among 4790 adults in anhui province: An online survey using WeChat.

Objective: To investigate public awareness about core information regarding chronic diseases and identify factors influencing that awareness among Anhui Province residents, provide a scientific basis for policy-making, and formulate corresponding intervention measures. Methods: From March to April 2021, 12 provincial-level representative counties and districts of Anhui province in the China Adult Chronic Disease and Nutrition Surveillance were selected as survey sites, and 4790 residents were recruited for the survey using stratified multi-stage cluster random sampling. Basic details about the study participants were collected and their awareness of core information about major chronic diseases was measured through an online survey using WeChat. Results: In 2021, the awareness rate of core information about chronic diseases among residents of Anhui Province was 54.93%. Multivariate logistic regression analysis showed that a higher awareness rate was associated with the following factors: non-housework occupations (agriculture, forestry, animal husbandry, and fishery: OR = 1.309, commercial services and production and transportation: OR = 1.450, institutions, and professional and technical personnel: OR = 1.461), a high education level (high school/junior high school/technical school OR = 1.357, college and above OR = 2.133), and residence in the southern and northern Anhui areas (southern Anhui OR = 1.282, northern Anhui OR = 1.431); whereas in rural areas (by district and country) (OR = 0.863), the awareness rate was low (all P < 0.05). Conclusions: The awareness rate of core information about chronic diseases among residents of Anhui, China, is low. It is necessary to strengthen awareness about chronic disease prevention and management by targeting specific groups of people in this region.

Anti-Toxoplasma gondii effect of tylosin in vitro and in vivo.

BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.

Overexpression of IQGAP1 in human pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate. A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis, prevention, and treatment of this deadly disease. The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types. Currently, we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer. METHODS: IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues (adjacent tissues) by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry. The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed. RESULTS: Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues. Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer (80.0%, 48/60) compared with adjacent tissues (18.3%, 11/60) (P<0.001). Moreover, overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation (P<0.05). CONCLUSION: The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression, and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.

[Bacterial profiles in conjunctival sac of dry eyes and normal eyes in middle- and old-aged Yi populations].

OBJECTIVE: To compare the bacterial profiles in conjunctival sac of dry eyes and normal eyes in Yi people aged 40 years or old. METHODS: A cross-sectional survey was conducted with standardized training and protocol. A total of 140 dry eyes of 70 individuals from Yi people in Jiulong county underwent ophthalmological examinations. The secretions of the inferior palpebral conjunctival sac were embrocated and inoculated on blood plates for 48 hours. The bacteria were separated and identified. Another 132 normal eyes from 66 Yi individuals were examined as controls. RESULTS: Bacterial positive cultivations were found in 72.1% (101/140) of dry eyes and 67.4% (89/132) of normal eyes, respectively. The difference was not statistically significant (P = 0.397). No gender difference in the bacterial positive rates was found either. Gram-positive bacteria were the main bacteria in both dry eyes (95.2%, 98/103) and normal eyes (91.1%, 82/90), predominantly staphylococcus epidemids and corynebacterium. There were no statistical differences in the constituents of bacteria in Gram classification and numbers of bacteria between dry eyes and normal eyes (P > 0.05). CONCLUSION: The bacterial profile in conjunctival sac of dry eyes is similar to that of normal eyes in Yi people aged 40 years or over. Gram-positive bacteria are the main bacteria.

Salt reduction behavior of adults in Anhui province in 2019: a cross-sectional survey of 3,378 participants.

Objective: A high-sodium diet is an important risk factor for hypertension in the Chinese population, which can increase the risk of cardiovascular and cerebrovascular diseases. Although a large number of related studies have been carried out in Anhui province, clear, effective salt reduction interventions and policies that can be widely promoted have not yet been formed. This study sought to understand the prevalence and precise measures of salt reduction behavior, the variables affecting salt reduction behavior, and the reasons why salt reduction behavior was not practiced in Anhui Province, China. Methods: The total number of participants in the study was 3,378. Using a multi-stage stratified cluster random sampling method, residents between the ages of 18 and 69 years in 10 counties and districts were selected from March to October 2019. A survey questionnaire and physical measurements were given to each participant. The influencing factors of residents' salt reduction behavior were examined using a multi-factor unconditional logistic regression analysis. The chi-squared (χ2) test was used to analyze the implementation of salt reduction behaviors among different age groups and gender, the factors influencing the implementation of salt reduction measures, and the reasons for not implementing salt reduction measures. Results: A history of hypertension was associated with salt reduction strategies (P = 0.014). Patients with hypertension were more likely to adopt salt reduction behaviors than those without hypertension (OR = 1.218, P = 0.040). The influence of eating out on the adoption of salt-reduction measures varied by age group (χ2 = 50.463, P < 0.001) and gender (χ2 = 81.348, P < 0.001). Conclusion: In summary, residents of the Anhui Province are not very knowledgeable about salt reduction. Age, gender, education level, hypertension, and marital status are the main determinants. Our findings have significant implications for policymakers who want to devise salt reduction strategies.

Glycemic control and its influencing factors in type 2 diabetes patients in Anhui, China.

Objective: To investigate the status of glycemic control and analyze its influencing factors in patients with type 2 diabetes (T2D) in Anhui, China. Methods: 1,715 T2D patients aged 18-75 years old were selected from 4 counties or districts in Anhui Province in 2018, using a convenience sampling method. All patients have undergone a questionnaire survey, physical examination, and a glycosylated hemoglobin (HbA1c) test. According to the 2022 American Diabetes Association criteria, HbA1c was used to evaluate the glycemic control status of patients, and HbA1c < 7.0% was defined as good glycemic control. The influencing factors of glycemic control were analyzed by multivariate unconditional logistic regression. Results: The prevalence of good glycemic control among people with T2D in the Anhui Province was low (22.97%). On univariate analysis, gender, education level, occupation, region, smoking, drinking, waist circumference and disease duration (all P < 0.05) were significantly associated with glycemic control. The factors associated with pool glycemic control were female gender [OR = 0.67, 95%CI (0.52, 0.86), P = 0.001], higher level of education [OR = 0.47, 95%CI (0.27, 0.83), P = 0.001], living in rural areas [OR = 1.77, 95%CI (1.39, 2.26), P < 0.001], central obesity [OR = 1.58, 95%CI (1.19, 2.09), P = 0.001] and longer duration of disease [OR = 2.66, 95%CI (1.91, 3.69), P < 0.001]. Conclusions: The prevalence of good glycemic control in people with T2D in Anhui Province was relatively low, and gender, region, education level, central obesity and course of the disease were influencing factors. The publicity and education on the importance of glycemic control should be further strengthened in T2D patients, and targeted intervention measures should be carried out for risk groups.

The detection rate and influencing factors of high-risk groups of cardiovascular disease in Anhui, China: A cross-sectional study of 99,821 residents.

Objective: To investigate the detection rate and influencing factors of high-risk population of cardiovascular disease in Anhui province. Methods: From March 2017 to August 2019, the residents aged 35-75 years old were selected using the multi-stage stratified cluster sampling method in 8 counties and districts of Anhui Province, and questionnaire survey, anthropometric measurement, and collection of biological samples were carried out among them. Results: A total of 99,821 residents in Anhui Province were finally investigated, and among them 21,426 residents were detected to be high-risk groups of cardiovascular disease. The detection rate of high-risk groups was 21.46%. According to the high-risk types, the high-risk groups can be clustered. 74.57% of them had only one high-risk type, 22.57% of them had two high-risk types, and 2.86% had three or more high-risk types. The results of Generalized Linear Mixed Model (GLMM) showed that male, age ≥45 years old, not married, occupation as a farmer, annual family income <25,000 yuan, drinking, overweight and obesity, pre-central obesity and central obesity, snoring, feeling fatigued, sleepiness, and self-reported history of diabetes were more likely to be risk factors of cardiovascular disease (all P value < 0.05). Conclusion: The detection rate of high-risk groups of cardiovascular disease in Anhui Province is relatively high. Individualized intervention measures as well as comprehensive prevention and control strategies should be adopted focusing on the distribution characteristics of risk factors of high-risk groups.

Changes in Serum Neutralizing Antibodies Levels During Convalescence of COVID-19 Patients.

Detection of serum-specific SARS-CoV-2 antibody has become a complementary means for the identification of coronavirus disease 2019 (COVID-19). As we already know, the neutralizing antibody titers in patients with COVID-19 decrease during the course of time after convalescence, whereas the duration of antibody responses in the convalescent patients has not been defined clearly. In the current study, we collected 148 serum samples from 37 confirmed COVID-19 cases with different disease severities. The neutralizing antibodies (Nabs), IgM and IgG against COVID-19 were determined by CLIA Microparticle and microneutralization assay, respectively. The time duration of serum titers of SARS-CoV-2 antibodies were recorded. Our results indicate that IgG (94.44%) and Nabs (89.19%) can be detected at low levels within 190-266 days of disease onset. The findings can advance knowledge regarding the antibody detection results for COVID-19 patients and provide a method for evaluating the immune response after vaccination.

DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina.

Netrin-1 and DCC are well known for their roles in neurite growth, axonal guidance, and neuronal migration. Recently, a number of studies showed that DCC is involved in the induction of apoptosis, and this proapoptotic activity can be blocked in the presence of Netrin-1. However, here, we found that DCC is required for the survival of two types of neurons selectively in the developing mouse retina where DCC is abundantly expressed. Our results showed that the DCC(-/-) retina displayed a reduced ganglion cell layer with relatively normal neuroblastic layer. Immunostaining assays revealed that in DCC(-/-) mice, initial neurogenesis within retina was unchanged while the numbers of differentiated retinal ganglion cells and displaced amacrine cells in ganglion cell layer were greatly reduced due to increased apoptosis. By contrast, other neuronal types including horizontal cells, bipolar cells, amacrine cells, photoreceptors, and Müller cells appeared normal in DCC mutant retinas. Moreover, DCC(kanga) mice that lack the intracellular P3 domain of DCC receptor displayed the same defects as DCC(-/-) mice. Thus, our findings suggest that DCC is a key regulator for the survival of specific types of neurons during retinal development and that DCC-P3 domain is essential for this developing event.

[Bacterial profiles in conjunctival sac of middle-aged and elderly Qiang with dry eyes and normal eyes].

OBJECTIVE: To compare the bacteria profiles in conjunctival sac of Qiang aged 40 years and over between those with dry eyes and those with normal eyes. METHODS: This survey was undertaken with a standardized protocol in Beichuan county. Ophthalmological examinations were performed on 54 individuals with dry eyes (108 eyes) and 52 individuals with normal eyes (104 eyes). The secretion of the inferior palpebral conjunctival sac was embrocated and inoculated on blood plate for 48-72 hours. The bacteria was separated and identified. RESULTS: Positive cultural results were found in 57.4% (62/108) of dry eyes and 61.5% (64/104) of normal eyes. The difference was not statistically significant (P=0.540). No gender and occupational differences in positive cultural results were found (P>0.05). Both the dry eyes and normal eyes were dominated by Gram-positive bacteria, with corynebacterium, staphylococcus epidemids and sphingomonas paucimobilis as main bacteria. Samples taken from the dry eyes produced 73 strains bacteria, 52 (83.8%) with a single strain of bacteria and 10 (16.2%) with co-existed strains of bacteria. The samples taken from the normal eyes were more likely to have co-existed strains of bacteria (P=0.000). Of the 87 strains of bacteria, 64.0%, were single strain and 36.0% were coexisted strains. Fifteen species of bacteria were cultivated from the dry eyes, significantly less than the number of species (24) cultivated from the normal eyes (P=0.027). CONCLUSION: There is no difference in bacterial positive rate in the conjunctival sac between dry eyes and normal eyes of Qiang aged 40 years and over. Gram-positive bacteria is the dominant bacteria. Normal eyes are more likely to have multiple coexisted bacteria compared with dry eyes.

Clinical and molecular characterization of seven patients with Danon disease.

Danon disease is an X-linked glycogen storage disease characterized by skeletal myopathy, cardiomyopathy and intellectual impairment. It is caused by a loss-of-function mutation in the lysosome-associated membrane protein-2 (LAMP2) gene. In the present study, exon and boarding intron analysis of 96 cardio disease-associated genes was performed in 770 patients with hypertrophic cardiomyopathy (HCM) using second-generation sequencing. Next, the identified mutations were confirmed in family members of the patients and 300 healthy controls. Detailed clinical, electrocardiographic (ECG) and echocardiographic findings were recorded. A pathogenic mutation in LAMP2 was identified in 7 patients who phenotypically presented with HCM. A total of four patients had a fragmented QRS complex (fQRS) on surface ECG. In addition, two patients presented with ventricular preexcitation with a short PR interval. Compared with the patients with protein kinase AMP-activated non-catalytic subunit γ2 syndrome and Fabry disease, the 7 patients with Danon disease presented at an earlier age, had a smaller left atrial size, a thinner maximal left ventricular wall thickness and a lower probability of pacemaker implantation. Compared with 12 sex- and age-matched patients with sarcomere-protein mutations, the 4 patients with Danon disease had a lower left ventricular outflow tract gradient and worse diastolic function. The present study provided a comprehensive comparison of different pathologies presenting with HCM and reported on features of early-onset Danon disease, including the characteristic preexcitation and fQRS on ECG. This may provide valuable information that may be utilized for the early diagnosis and treatment of patients with Danon disease. The present study was registered as a clinical trial with ClinicalTrials.gov (Sep. 2, 2016; registry no. NCT02888132).