Urban virtual environment landscape design and system based on PSO-BP neural network.

In the last few years, with the fast growing of neural network field such as those for virtual reception and enhanced nature, the practice and theory of conventional landscape are impacted and challenged by virtual landscape based on these sorts of neural network technologies. On the one hand, the virtual landscape changes the carrier of landscape design from material real world to the networked virtual world, which breaks the traditional way of generating landscape and the way of expression of results. On the other hand, the virtualized and networked morphological characteristics of the virtual landscape itself and its capacity that can offer users a sense of immertion, interplay and enjoyment of the experience provide a way of extending and deepening the realm of scenery. It is also a new type of landscape that conforms to the trend of the times created in the background of the fast evolution of scientific and technical development. Virtual landscape brings new construction thinking and practical means for the application of digital city, the construction of urban context, and the development and utilization of relics. It provides an important research source for thinking about the relationship between current humanities and science, material and virtual, history and contemporary. After the research and experiment on the urban environment landscape design of PSO-BP neural network, the experimental data showed that before using the neural network method to improve Yanta East Garden, 57% of the crowd were satisfied with the overall impression of Yanta East Garden, and 17% were dissatisfied. After the improvement, 67% were satisfied with the landscape of Yanta East Garden, only 5% were dissatisfied, and the landscape satisfaction increased by 10%. The survey group believed that the landscape color of Yanta East Garden was full of historical flavor, especially the small sculptures convey the unique Qin Opera culture. The above data show that the method based on neural network is very suitable for the improvement and development of urban landscape design.

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.

BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Identification of Potential Hub Genes Related to Acute Pancreatitis and Chronic Pancreatitis via Integrated Bioinformatics Analysis and In Vitro Analysis.

Acute pancreatitis (AP) and chronic pancreatitis (CP) are considered to be two separate pancreatic diseases in most studies, but some clinical retrospective analyses in recent years have found some degree of correlation between the two in actual treatment, however, the exact association is not clear. In this study, bioinformatics analysis was utilized to examine microarray sequencing data in mice, with the aim of elucidating the critical signaling pathways and genes involved in the progression from AP to CP. Differential gene expression analyses on murine transcriptomes were conducted using the R programming language and the R/Bioconductor package. Additionally, gene network analysis was performed using the STRING database to predict correlations among genes in the context of pancreatic diseases. Functional enrichment and gene ontology pathways common to both diseases were identified using Metascape. The hub genes were screened in the cytoscape algorithm, and the mRNA levels of the hub genes were verified in mice pancreatic tissues of AP and CP. Then the drugs corresponding to the hub genes were obtained in the drug-gene relationship. A set of hub genes, including Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9, were identified through analysis, demonstrating their pivotal roles in the progression from AP to CP. Notably, these genes were found to be enriched in the Helper T-cell factor (Th17) signaling pathway. Up-regulation of these genes in both AP and CP mouse models was validated through quantitative real-time polymerase chain reaction (qRT-PCR) results. The significance of the Th17 signaling pathway in the transition from AP to CP was underscored by our findings. Specifically, the essential genes driving this progression were identified as Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9. Crucial insights into the molecular mechanisms underlying pancreatitis progression were provided by this research, offering promising avenues for the development of targeted therapeutic interventions.

Neuroinflammation-associated miR-106a-5p serves as a biomarker for the diagnosis and prognosis of acute cerebral infarction.

BACKGROUND: Acute cerebral infarction (ACI) is a common cerebrovascular disease. Previous studies have shown that some abnormally expressed microRNAs (miRNAs) play important roles in ACI. This study aimed to investigate the role of miR-106a-5p in the diagnosis and prognosis of ACI patients, and analyze the regulatory potential of miR-106a-5p on the inflammation of BV-2 microglial cells. METHOD: Serum and cerebrospinal fluid (CSF) samples were collected from 98 ACI patients, and the expression of serum miR-106a-5p was analyzed using qRT-PCR. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-106a-5p. The association of miR-106a-5p with ACI prognosis was evaluated using the logistic analysis. In vitro experiments were performed in BV-2 cells by oxygen glucose deprivation (OGD) treatment, and the effects of miR-106a-5p on BV-2 inflammation were assessed using an enzyme linked immunosorbent assay (ELISA). RESULT: It was observed that miR-106a-5p was significantly upregulated in the serum and CSF of ACI patients (all P < 0.001), and had considerable diagnostic accuracy. The highest serum miR-106a-5p was observed in severe ACI cases, and miR-106a-5p expression was significantly increased in unfavorable prognosis patients. Serum and CSF expression of miR-106a-5p was positively correlated with proinflammatory cytokines in ACI patients, and the inflammation of OGD-induced BV-2 cells was suppressed by miR-106a-5p reduction. CONCLUSION: MiR-106a-5p is overexpressed in ACI patients and may serve as a diagnostic and prognostic biomarker for ACI. Furthermore, miR-106a-5p may be involved in ACI progression by regulating neuroinflammation.

A Novel Heterozygous Missense Variant in Parathyroid Hormone 1 is Related to the Occurrence of Developmental Dysplasia of the Hip.

Introduction: Developmental dysplasia of the hip (DDH) is one of the most common diseases in the pediatric orthopedics, with an incidence of 1-5%. Genetic factors are the bases of the pathogenesis of DDH, but the pathogenic variants and pathogenesis of DDH are still unknown. There are no key accurate diagnostic or prognostic molecular markers for DDH. The purpose of our study was to screen for genetic variant associated with DDH and explore its pathogenesis. Materials and Methods: The genetic variation of DDH was tested by variant NGS-based exome analyses, verified by the Sanger sequencing. Results: A four-generation family in which DDH was present in three generations was recruited. A novel heterozygous missense variant c.629C>T (p.(Ala210Val)) in exon 7/8 of the parathyroid hormone 1 receptor (PTH1R) gene was identified through screening of two affected and one unaffected family members. The candidate variant was validated in all available family members with all three affected members being positive for the PTH1R variant. Conclusion: Our results are highly supportive of PTH1R as a novel candidate gene for DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic variants associated with DDH.

Establishment of pediatric developmental dysplasia of the hip biobank: Shanghai children's hospital experience.

Developmental dysplasia of the hip (DDH) is a debilitating condition that affects 1-7% of newborns. Children with DDH, not treated early and effectively, will easily lead to disability. A better understanding of the biology of DDH is critical to the development of prognostic biomarkers and novel therapies. The purpose of this study was to establish a biobank of DDH genetic resources, to facilitate clinical and basic scientific research. The biological specimen and clinical data of DDH were collected in Shanghai Children's Hospital from 2014 to 2021. The collection of blood samples was performed at definitive diagnosis and review, tissue specimens were performed at definitive surgery. The clinical data was collected at the whole stage of DDH patients at diagnosis, treatment and follow-up. A total of 528 patients with DDH were enrolled in this study, 90 were men and 438 were women, with the mean age of 4.67 years. The numbers of tissue and blood specimens reached 2172 and 1490, respectively. The quality test results showed that the DNA concentration decreased slightly with the extension of storage time, but the DNA purity did not change. Meanwhile, the extension of storage time slightly affected the stability of protein of tissue samples but did not affect the expression of the housekeeping gene. The DDH biobank built has the potential of monitoring disease pathogenesis and progress, which could provide specimens to the researchers improving the biological understanding and provide guidance of clinical treatment of this disease to clinicians.

Preoperative Fasting Times for Patients Undergoing Elective Surgery at a Pediatric Hospital in Shanghai: The Big Evidence-Practice Gap.

PURPOSE: Preoperative fasting is a necessary experience for pediatric patients undergoing elective surgery. The American Society of Anesthesiologist guideline shows that preoperative fasting times were reduced and safe (no solid food up to 8 hours, no fluid or formula up to 6 hours, no breast milk up to 4 hours, and no clear fluids up to 2 hours before surgery). However, preoperative fasting is usually more prolonged than the suggested time. This study aimed to investigate the duration of preoperative fasting for elective surgery at a pediatric hospital in Shanghai, China, and compare it with the evidence from guidelines. DESIGN: The study used a descriptive cross-sectional design. METHODS: A total of 211 children under anesthesia in a Shanghai's pediatric hospital were included in the study. The preoperative fasting status was assessed using a self-administered record card of preoperative fasting developed by Chinese researchers. FINDINGS: The results indicated that the length of time fasted preoperatively was longer for all participants than that recommended by the American Society of Anesthesiologists. With the long length of fasting time, it is evident that the majority of children experienced hunger (17.5%), thirst (19.4%), and anxiety (16.1%) as indicated with 8 points of the Likert 10-point scale. The degrees of these experiences were relevant to the length of preoperative fasting time. CONCLUSIONS: A big gap was revealed between the recommendation and actual practice, and children underwent an uncomfortable experience before the surgery. These results suggest that evidence-based clinical improvement is required, and the recommended preoperative fasting instruction transform into clinical practice should be promoted.

The low contagiousness and new A958D mutation of SARS-CoV-2 in children: An observational cohort study.

AIMS: To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19. METHODS: This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case: Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R0 were compared among the groups. RESULTS: The infection rate among 211 individuals was 64% (135/211). The SAR in Groups 2 and 3 was 71% (73/103) and 3% (1/30), respectively; the median R0 in Groups 2 and 3 was 2 (range: 1-8) and 0 (range: 0-1), respectively. Compared with adult cases, the SAR and R0 of pediatric cases were significantly lower (p<0.05). We obtained SARS-CoV-2 sequences from the same infant's throat and fecal samples at a two-month interval and found that the new spike protein A958D mutation detected in the stool improved thermostability theoretically. CONCLUSIONS: Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.

Low serum level of apolipoprotein A1 may predict the severity of COVID-19: A retrospective study.

BACKGROUND: Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate blood lipid profiles in patients with COVID-19 and to explore their predictive values for COVID-19 severity. METHODS: A total of 142 consecutive patients with COVID-19 were included in this single-center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID-19 in comparison with 77 age- and gender-matched healthy subjects, their predictive values for COVID-19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves. RESULTS: There were 125 and 17 cases in the non-severe and severe groups, respectively. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non-severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID-19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800-0.935, p < 0.001), along with interleukin-6 (IL-6) (adjusted OR: 1.097, 95% CI: 1.034-1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834-0.941); moreover, the risk model established using ApoA1 and IL-6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932-0.995). CONCLUSION: Blood lipid profiles in patients with COVID-19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID-19.

Do post-COVID-19 symptoms exist? A longitudinal study of COVID-19 sequelae in Wenzhou, China.

OBJECTIVE: We conducted a cohort of tracing discharge patients of COVID-19. MATERIALS AND METHODS: We used the Mann-Whitney U test, χ2 test, or Fisher's exact test to compare differences between age groups and gender groups where appropriate. RESULTS: Our study provides insights into the nature and severity of medical conditions specific to survivors of COVID-19. CONCLUSIONS: It also highlights the potential mental health issues resulting from infectious disease outbreaks within communities.

OBJECTIFS: Nous avons suivi une cohorte de patients à la sortie du COVID-19. MATÉRIAUX ET MÉTHODES: Nous avons utilisé les test de Mann­Whitney U, de Fisher ou du Chi2 pour comparer les différences entre les groupes d'âge et de genre, le cas échéant. RÉSULTATS: Notre étude fournit un aperçu de la nature et de la gravité des troubles médicaux propres aux survivants du COVID-19. CONCLUSIONS: Elle met également en lumière les problèmes de santé mentale potentiels découlant des éclosions de maladies infectieuses dans les collectivités.

Absent immune response to SARS-CoV-2 in a 3-month recurrence of coronavirus disease 2019 (COVID-19) case.

BACKGROUND: The viral persistence in patients with Coronavirus Disease 2019 (COVID-19) remains to be investigated. METHODS: We investigated the viral loads, therapies, clinical features, and immune responses in a 70-year patient tested positive for SARS-CoV-2 for 3 months. FINDINGS: The patient exhibited the highest prevalence of abnormal indices of clinical features and immune responses at the first admission, including fever (38.3 â„ƒ), decreased lymphocytes (0.83 × 109/L) and serum potassium (3.1 mmol/L), as well as elevated serum creatinine (115 µmol/L), urea (8.6 mmol/L), and C-reactive protein (80 mg/L). By contrast, at the second and the third admission, these indices were all normal. Through three admissions, IL-2 increased from 0.14 pg/mL, 0.69 pg/mL, to 0.91 pg/mL, while IL-6 decreased from 11.78 pg/mL, 1.52 pg/mL, to 0.69 pg/mL, so did IL-10 from 5.13 pg/mL, 1.85 pg/mL, to 1.75 pg/mL. The steady declining trend was also found in TNF-α (1.49, 1.15, and 0.85 pg/mL) and IFN-γ (0.64, 0.42, and 0.27 pg/mL). The threshold cycle values of RT-PCR were 26.1, 30.5, and 23.5 for ORFlab gene, and 26.2, 30.6, and 22.7 for N gene, showing the patient had higher viral loads at the first and the third admission than during the middle term of the disease. The patient also showed substantially improved acute exudative lesions on the chest CT scanning images. CONCLUSIONS: The patient displayed declining immune responses in spite of the viral shedding for 3 months. We inferred the declining immune responses might result from the segregation of the virus from the immune system.

The potential role of serum angiotensin-converting enzyme in coronavirus disease 2019.

BACKGROUND: To explore the clinical significance of serum angiotensin-converting enzyme (ACE) activity in coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, a total of 136 consecutive patients with confirmed COVID-19 were recruited. Demographic and clinical data were recorded. The serum ACE activity was measured at baseline and during the recovery phase, and its relationship with clinical condition was analyzed. RESULTS: Of the 136 patients with confirmed COVID-19, the 16 severe patients were older and had a higher body mass index (BMI) and proportion of hypertension than the 120 nonsevere patients. In comparison to those of normal controls, the baseline serum ACE activities of subjects in the severe group and nonsevere group were decreased, with the lowest level in the severe group. However, the serum ACE activity increased in the recovery phase, and there were no significant differences among the severe group, nonsevere group and normal control group. CONCLUSION: Serum ACE activity could be used as a marker to reflect the clinical condition of COVID-19 since low activity was associated with the severity of COVID-19 at baseline, and the activity increased with the remission of the disease.

Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow-up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID-19 in a single medical center. The clinical features of patients during their hospitalization and 2-week postdischarge quarantine were collected. RESULTS: Among the 98 COVID-19 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid during 2-week postdischarge quarantine. The median time from discharge to SARS-CoV-2 nucleic acid re-positive was 4 days (IQR, 3-8.5).The median time from symptoms onset to final respiratory SARS-CoV-2 detection of negative result was significantly longer in re-positive group (34 days [IQR, 29.5-42.5]) than in non-re-positive group (19 days [IQR, 16-26]). On the other hand, the levels of CD3-CD56 + NK cells during hospitalization and 2-week postdischarge were higher in re-positive group than in non-re-positive group (repeated measures ANOVA, P = .018). However, only one case in re-positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS-CoV-2 nucleic acid detection, but most of the re-positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow-up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.

Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019.

OBJECTIVE: To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. RESULTS: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. CONCLUSION: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.

Screening for Developmental Dysplasia of the Hip in Infants in Tibet Identifies Increased Prevalence Associated with Altitude.

BACKGROUND Developmental dysplasia of the hip (DDH), also known as congenital hip dislocation or congenital hip dysplasia is usually diagnosed at birth. Studies on DDH at high-altitude are rare. Tibetans live mainly at altitudes above 3,500 m, and the prevalence of DDH in this population is not currently known. This cross-sectional epidemiological study aimed to identify the prevalence and associated risk factors for DDH in Tibet. MATERIAL AND METHODS Between 1st June 2015 and 30 June 2016, infants in Tibet aged between 0-6 months and from ten districts at different altitudes in Shigatse, Tibet were referred to our hospital for the assessment of DDH. All the infants underwent clinical evaluation for DDH and ultrasound testing using the Graf method. RESULTS There were 606 infants who met the study inclusion criteria, including 253 female infants and 353 male infants, of which 106 infants had DDH. The prevalence of DDH in Shigatse, Tibet was approximately 174.9/1000 infants (106/606). Altitude was strongly associated with increased risk of DDH in Tibet (r=0.82, P=0.004). CONCLUSIONS This is the first epidemiological study of DDH in the Tibetan population. The results showed that DDH is prevalent among native Tibetan people in Shigatse, and there was a significant correlation between altitude and the prevalence of DDH. Further studies are needed to investigate the mechanism of the association between altitude and the increased incidence of DDH in infants.

Evaluation of the Effectiveness of Clinical Pharmacists' Consultation in the Treatment of Infectious Diseases: A Single-Arm, Prospective Cohort Study.

Background: With the implementation of Antimicrobial Stewardship Program, clinical pharmacists' consultation (CPC) for infectious diseases (ID) is gradually adopted by many hospitals in China. We conducted a cohort study to evaluate the effectiveness of CPC in ID treatment on patient outcomes and potential determinants. Methods: Based on a registry database, a prospective cohort study was conducted in Guizhou Provincial People's Hospital. The main exposure factor was whether clinician adopted the suggestion from clinical pharmacist. The outcome was effective response rate (ERR) of ID patients. The variables associated with the outcome (e.g., age, gender, severity of infection, liver function, and kidney function) were also prospectively recorded. A multilevel model was performed to analyze the factors related to ERR. Results: A total of 733 ID inpatients were included in the final analysis according to the predesigned inclusion and exclusion criteria. The proportion of clinical pharmacists' suggestions adopted by clinicians and ERR were 88.13 and 69.03%, respectively. Significant data aggregation (P < 0.05) for individuals at the level of department was observed. According to the two-level variance component model, liver dysfunction (Adjusted Odds Ratio (AOR) = 0.649, 95%Credible Interval (CI): 0.432-0.976), severity of infection (AOR = 0.602, 95%CI: 0.464-0.781), and adopting the suggestion from pharmacist (AOR = 1.738, 95%CI: 1.028-2.940) had significant association with ERR. Conclusion: Our study suggests that the effect of CPC on ID treatment is significant. The policy/decision makers or hospital managers should be cognizant of the critical value of clinical pharmacists in ID treatment.

A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a complex disorder of the hip joint affecting 1-5‰ of newborns. While genetic influence on DDH has been long known, DDH has not been ascribed to any specific genetic event. The present study reported on variants contributing to DDH susceptibility in a family with four individuals affected across three generations. Whole-exome sequencing was performed in three affected and two unaffected individuals of a pedigree with DDH. Candidate variants were confirmed by Sanger sequencing and then validated in available family members and 37 sporadic DDH patients. Two novel heterozygous, inframe mutations causing multi-nucleotide substitution polymorphisms (c.1432_1440delCAGCAGCAG corresponding with p.Gln478_480del and c.1440_1441insCAG corresponding with p.Gln480ins) in exon 11 of chromosome 4 in bone morphogenetic proteins-2-inducible kinase (BMP2K) were identified; these were found in members of the pedigree affected by DDH and in the unaffected grandmother of the proband, who was deemed to be the carrier of potential mutations, but not in the unaffected normal control saunt of the proband. These two variants shared the same genomic coordinate but with different types of mutation in BMP2K. BMP2K is known to be associated with bone and cartridge development and heterozygous mutations were found to be present in 4/4 (100%) of the affected family members, 4/15 (26.7%) of the unaffected family members and 0/7 (0%) of the unaffected unrelated family members. Genotyping of 37 unrelated, sporadic DDH patients showed that three cases were positive for the BMP2K c.1432_1440delCAGCAGCAG variants (8.12%). These findings provided strong evidence for the role of BMP2K variants in causing DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic sites associated with DDH.

Color demosaicking via fully directional estimation.

Given a natural image from the single sensor, the key task is to properly reconstruct the full color image. This paper presents an effectively demosaicking algorithm based on fully directional estimation using Bayer color filter array pattern. The proposed method smoothly keeps access to current reconstruction implementations, and outperforms the horizontal and vertical estimating approaches in terms of the perceptual quality. To analyze the target of existing methods, the proposed algorithm use the multiscale gradients in single green channels as the diagonal information for the auxiliary interpolation. Furthermore, two group of weights (one is from the horizontal and vertical directions, another is from the diagonal and anti-diagonal directions) are built. Combinational weight is better suited for representing neighbor information. Another contribution is to better use the prior result. While calculating the same type of color difference, we divide all the color difference values into two interleaved parts. Estimated value in the first part will guide the subsequent color difference in the second part. It less brings the artifact of the interpolation procedure. Experimental results show that this adaptive algorithm is efficient both in the objective and subjective output measures.

The application of multiple miRNA response elements enables oncolytic adenoviruses to possess specificity to glioma cells.

Adenovirus-mediated virotherapy is one of the promising therapeutic approaches for glioma treatment. However, its replication efficiency and specificity still failed to meet the requirements for clinical treatment. To improve the anti-tumor activity and specificity of oncolytic adenoviruses (OA), we applied multiple miRNA response elements (MREs) of miR-124, miR-128, miR-146b and miR-218, whose expressions were downregulated in glioma cells, to enable OA to be specific to glioma. Adenoviral E1A protein regulated by these 4 MREs (OA-4MREs) was shown to be highly expressed in glioma cells, but not in normal cells. The selective E1A expression led to glioma-specific replication and cytotoxicity of OA-4MREs. Animal experiments also showed that OA-4MREs exhibited improved anti-tumor activities for both subcutaneous and intracranial glioma xenografts, without significant toxicity to normal brain and liver tissues. Collectively, we demonstrated that oncolytic adenovirus, whose replication was regulated by MREs, may be promising biological agents for glioma treatment.

[Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke].

OBJECTIVE: To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population. METHODS: A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene. RESULTS: An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01). CONCLUSION: Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.