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Objective To report 5 cases of amyloid arthropathy with joint flexion contracture as the first manifestation,and perform a literature review to improve the understanding of the disease.Methods Retrospective analysis of the clinical manifestations,laboratory and imaging results clinical data of patients with immunoglobulin light chain(AL)amyloidosis related amyloid arthropathy with joints flexion contracture as the first manifestation at the Department of Rheumatology and Immunology,the First Medical Center of People's Liberation Army General Hospital from January 2012 to February 2022.Meanwhile searching the database(CNKI,Wanfang Data,PubMed),excluding myeloma-associated amyloid arthropathy,and analyzing the literature results comprehensively.Results There were a total of 5 patients with amyloid arthropathy with joint flexion contracture as the initial manifestation in this center,including 4 males and 1 female.By February 2022(searching CNKI,Wanfang Data and PubMed),two eligible patients were selected,all males.A total of 7 patients were included with male-to-female ratio of 6:1.The median age was 30-year-old(range from 19 to 73).Spine and limb joints were involved,especially finger joints(7 cases,100%).Soft tissue was involved in 5 patients(71.4%),carpal tunnel syndrome in 4 patients(57.1%),giant tongue in 3 patients(42.9%),shoulder pad sign in 2 patients(28.6%),muscle swelling in 2 patients(28.6%).Five patients were misdiagnosed as rheumatoid arthritis(RA)and 1 patient was misdiagnosed as spondyloarthritis(SpA).The median time of delayed diagnosis was 24 months(2-204 months).The laboratory results showed that 3 patients(42.9%)were positive for immunoelectrophoresis,all of which were λ light chain.Only 1 patient was positive for HLA-B27,while the other patients were negative for autoantibodies and rheumatoid factors.Only 1 patient had elevated C reactive protein(CRP)and erythrocyte sedimentation rate(ESR).Ultrasound examination of the lesion site of 5 patients(71.4%)showed hypoechoic area around the joint,thickening of ligaments or periarticular tenosynovitis.Five patients(71.4%)underwent X-ray examination,of which 4 patients had no bone destruction,1 patient had soft tissue swelling with bone erosion and subchondral cyst.MRI was performed in 5 patients(71.4%),in which low signal on T1 weighted image,medium signal on T2 weighted image and edema signal on peripheral tendon sheath were seen in 1 patient.One patient(14.3%)underwent emission computed tomography(ECT)without abnormal uptake.Conclusion Joint flexion contracture may be the first sign of amyloid arthropathy.Vigilance for amyloid arthropathy is warranted when there is associated soft tissue involvement,negative autoantibodies,and imaging showing no joint destruction but surrounding soft tissue abnormalities.
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OBJECTIVE@#To evaluate the clinical features, laboratory and imaging results, treatment and outcomes of eosinophilic fasciitis (EF) and assess the value of ultrasound in the diagnosis of EF.@*METHODS@#We retrospectively analyzed the clinical data of 45 patients with EF treated in our center from January 1, 2006 to February 28, 2022. The consistency between the diagnoses of EF based on ultrasound and MRI findings was assessed.@*RESULTS@#In the 45 EF patients (male/female ratio 3.5:1), the age of onset ranged from 16 to 64 years with a mean disease course of 22.6 months. The average time from symptom onset to diagnosis was 16 months. The most common possible trigger of the disease was vigorous exercise (10/45), causing symmetrical lesions in the limbs, most commonly in the forearms (86.7%) and lower legs (80%). Clinical features of EF included subcutaneous swelling and induration (95.6%), arthralgia and arthritis (55.6%), groove sign (42.2%), hand joint contractures (42.2%), skin pigmentation (37.8%), and peau d'orange appearance (13.3%). Eosinophilia was found in 31 patients (68.9%). Hypergammaglobulinemia was seen in 23/44 (52.3%) and positive antinuclear antibodies in 9 (20%) of the patients. Twentyone of the patients were treated with high-dose methylprednisolone (≥200 mg daily for 3 to 5 consecutive days), and compared with the patients who did not receive this treatment, these patients more frequently experienced relapse before admission, had more extensive involvement, and had a higher rate of hypergammaglobulinemia without fever, but these differences were not statistically significant. Of the 31 patients (68.9%) with follow-up data (for a median of 3.2 years [range 0.2-15.9]), complete remission was achieved in 12 (38.7%) patients, and the accumulative complete remission rate was 44.1% at 5.5 years. No specific baseline characteristics or immunosuppressants were found to correlate with the treatment response. A total of 26 patients underwent both ultrasound and MRI examination, and the Kappa value of the diagnostic results between ultrasound and MRI was 0.91.@*CONCLUSION@#EF is characterized by symmetrical subcutaneous swelling and induration in the limbs, accompanied by eosinophilia and hypergammaglobulinemia. Glucocorticoid is effective for treating EF. Ultrasound examination can identify thickening of subcutaneous fascia for an early diagnosis of EF.
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Humains , Femelle , Mâle , Nourrisson , Enfant d'âge préscolaire , Études rétrospectives , Hypergammaglobulinémie , Éosinophilie , Échographie , Main , Contracture , Résultat thérapeutiqueRésumé
AIM: To compare the accuracy of different intraocular lens(IOL)calculation formulas in cataract patients with axial length longer than 28mm and a history of radial keratotomy(RK).METHODS: Retrospective study. The medical records of 19 cataract patients(29 eyes)after RK and with axial length longer than 28mm who underwent cataract surgery from January 2011 to July 2020 in Beijing Tongren Hospital were analyzed. The absolute error(AE)of the difference among three different formulas was calculated. AE refers to the absolute value between the actual spherical equivalent after cataract surgery and the spherical equivalent predicted by the IOL formula. The AE values of the three formulas and the percentages of eyes with AE≤0.5, 0.75, 1.0, and 2.0D were calculated and compared.RESULTS: The AE values of the three formulas were significantly different(χ2=8.759, P=0.013). The Barrett True-K formula had the smallest median AE, which was only 0.62(0.20, 1.15)D, followed by the Haigis formula 0.76(0.34, 1.26)D, and the Holladay 1(D-K)formula had the largest 1.01(0.49, 1.62)D. The percentages of affected eyes with AE ≤0.5, 0.75, 1.0, and 2.0D for the Barrett True-K formula were 48%, 59%, 69%, and 93%, which were equal to or higher than the other two formulas.CONCLUSION: The Barrett True-K formula is more recommended among the three formulas for cataract patients after RK and with axial length longer than 28 mm.
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BACKGROUND@#Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples.@*METHODS@#From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR.@*RESULTS@#We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ).@*CONCLUSION@#MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.
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Humains , Instabilité des microsatellites , Tumeurs colorectales/diagnostic , Répétitions microsatellites/génétique , Réparation de mésappariement de l'ADNRésumé
OBJECTIVES@#To study the etiology and clinical features of children with ascites, so as to provide a basis for the diagnosis and treatment of ascites in children.@*METHODS@#The medical data of the children with ascites, who were hospitalized from January 1, 2010 to December 31, 2019, were retrospectively reviewed.@*RESULTS@#Among the 165 children with ascites, the male/female ratio was 1.53:1, and the mean age of onset was (6±4) years. The causes of ascites included surgical acute abdomen (39 children, 23.6%), infectious diseases (39 children, 23.6%), neoplastic diseases (27 children, 16.4%), hepatogenic diseases (18 children, 10.9%), pancreatitis (10 children, 6.1%), cardiogenic diseases (8 children, 4.8%), rheumatic immune diseases (6 children, 3.6%), and nephrogenic diseases (5 children, 3.0%). According to the age of onset, there were 33 infants, 24 young children, 30 preschool children, 41 school-aged children, and 37 adolescents. Surgical acute abdomen and hepatogenic diseases were the main causes of ascites in infants (P<0.05). Neoplastic disease was the leading cause in young children (P<0.05). Infectious diseases were the most common cause in adolescents (P<0.05).@*CONCLUSIONS@#Surgical acute abdomen, infectious diseases, neoplastic diseases, and hepatogenic diseases are the common causes of ascites in children, and there are some differences in the leading cause of ascites between different age groups.
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Adolescent , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Nourrisson , Mâle , Abdomen aigu/complications , Ascites/étiologie , Maladies transmissibles , Tumeurs/complications , Pancréatite/complications , Études rétrospectivesRésumé
C2H2 transcription factors play an important role in plant growth, development and the regulation of secondary metabolism. This article identifies members of the C2H2 gene family in Cannabis sativa L. at the genome level. Chromosomal location and linkage, evolutionary relationships, and identification of conserved motifs was determined from the C. sativa genome and transcriptome data using bioinformatics tools and on-line websites such as TBtools, MEGA software, NCBI, PlantTFDB, ExPASy, HMMSCAN, MEME, WoLFPSORT and PlantCARE. The results show that C. sativa contains 30 members of the C2H2 gene family (named CsC2H2-1-CsC2H2-30) distributed on 9 chromosomes. The encoded proteins range in length from 138 to 635 amino acids, and the theoretical isoelectric points range from 5.85 to 9.52. Molecular weights range from 15 909.48 to 68 445.53 Da. Transcriptome analysis showed that CsC2H2 was differentially expressed in the female flowers, bracts, leaves, and stems of the Diku variety and female flowers of nine different varieties of C. sativa. Quantitative real-time PCR verified that CsC2H2-1, CsC2H2-5, and CsC2H2-19 were significantly expressed in the female flowers and bracts of the Diku variety. This provides a theoretical basis for in-depth study of the function of the C2H2 gene family and the breeding of high-quality C. sativa varieties.
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Phytohormones play an important role at all stages of plant growth, influencing plant growth and development and regulating plant secondary metabolism, such as the synthesis of flavone, flavonol, anthocyanin, and other flavonoids. Flavonoids, a group of important secondary metabolites ubiquitous in plants, have antioxidative, anti-microbial, and anti-inflammatory activities and thus have a wide range of potential applications in Chinese medicine and food nutrition. With the development of biotechnology, phytohormones' regulation on flavonoids has become a research focus in recent years. This study reviewed the research progress on the mechanism of common phytohormones, such as abscisic acid, gibberellin, methyl jasmonate, and salicylic acid, in regulating flavonoid metabolism, and discussed the molecular mechanism of the synthesis and accumulation of flavonoids, aiming at clarifying the key role of phytohormones in modulating flavonoid metabolism. The result is of guiding significance for improving the content of flavonoids in plants through rational use of phytohormones and of reference value for exploring the mechanism of hormones in regulating flavonoid metabolism.
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Acide abscissique , Flavonoïdes , Régulation de l'expression des gènes végétaux , Gibbérellines , Développement des plantes , Facteur de croissance végétalRésumé
Objective To construct a polymerase chain reaction-capillary electrophoresis (PCR-CE) detection method using ChlB gene and NIES gene, investigate the method's specificity and sensitivity, and to evaluate its application value in drowning diagnosis. Methods The specific primers ChlB and NIES were designed for the conserved sequence of chlorophyte ChlB gene and cyanophyte NIES gene in GenBank to construct PCR-CE detection method; 50 species of standard DNA samples were amplified; the sensitivity was determined by gradient concentration detection of positive standard samples; 25 actual cadaver lung tissue samples (drowned: 20, natural death: 5) were detected, and the simultaneous detection results of microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM) were simultaneously compared. Results The minimum DNA detection concentration of primers ChlB and NIES was 0.161 ng and 0.109 ng, respectively, which could specifically amplify chlorophyte (Chlorella pyrenoidosa) and cyanophyte [Microcystis aeruginosa (producing and not producing toxin)] widespread in water. The product fragments were 156 bp and 182 bp, respectively. The results of non-drowning tissues were negative. Conclusion This method has high sensitivity and specificity. It can be applied to the detection of plankton related to drowning and combined with MD-VF-Auto SEM method, can increase the detection range of plankton related to drowning and improve the evidence power of drowning diagnosis.
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Humains , Chlorella , Diatomées/génétique , Noyade/diagnostic , Rein , Foie , Poumon , Plancton/génétiqueRésumé
Objective:To analyze the sequence characteristics,chromosomal location,gene structure,conserved motifs,phylogenetic evolution and differential gene expressions of the <italic>Cannabis sativa</italic> YABBY transcription factor family,in order to provide a molecular basis for in-depth study of <italic>YABBY</italic> gene function and theoretical support for the selection and breeding of superior hemp varieties. Method:The bio-informatics method was used to identify and analyze the <italic>CsYABBY </italic>gene family of the original hemp seed plant. PlantTFDB,ExPASy,MEME,CELLO,PLANTCARE and other online websites and TBtools,MEGA,DNAMAN and other software were used for prediction,visualization and analysis. Result:<italic>C. sativa</italic> contains 6 <italic>YABBY</italic> gene members distributed on 5 chromosomes,in which 5 members are localized in the nucleus and 1 in extracellular, they consist of 185-235 amino acids, and the isoelectric point is between 5.05 and 9.34, the molecular weight is between 20 582.45-26 282.7 Da. All of CsYABBY proteins contain two conserved domains, namely Zinc finger domain and YABBY domain. <italic>CsYABBY</italic> genes have multiple cis-acting elements,and their expressions differ in different tissues and cultivars. Conclusion:The expressions of CsYABBY may be affected by hormones and externally environmental factors. <italic>CsYABBY</italic> gene expressions are tissue-specific. In addition,YABBY transcription factor family may play an important role in regulating the development of <italic>C. sativa</italic> female flowers,and subfamilies YAB1 and YAB5 may be involved in the synthesis of cannabinoids.
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Bacterial non-coding RNAs (ncRNAs) are pivotal transcriptional regulators during bacterial proliferation and infection processes.Bacterial ncRNAs play important roles in responding to environmental changes and regulating bacterial gene expression to resist environmental stress.Transcriptome profiling of neonatal meningitis-causing Escherichia coli K1 RS218 (NMEC) reveals abundant ncRNAs.Bioinformatic analyses identified 45 potential ncRNAs.Comparative genome analyses of non-pathogenic E.coli K12 and NMEC identified 300 NMEC-specific sequences (above 100 bp), which contain 9 NMEC-specific ncRNAs (Nsr).Moreover, deletion of one ncRNA, Nsr21, enhanced NMEC survival and proliferation in mouse blood (P< 0.01) , compared to the wild-type RS218 control, in a mouse tail vein injection model.qRT-PCR analysis further revealed expression of Nsr21 decreased in NMEC collected from mouse blood compared to that in NMEC collected from in vitro medium (P<0.001) , indicating that NMEC downregulates Nsr21 expression to benefit its survival and proliferation in blood.This study suggests that the NMEC genome contains a number of ncRNAs, which may be involved in regulating NMEC pathogenicity.During infection process in the blood, NMEC enhances its proliferation ability in blood by downregulating the expression of Nsr21.
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LBD(lateral organ boundaries)transcription factors play an important role in the regulation of plant growth, development and secondary metabolism. In order to explore the function of LBD genes in cannabis, the Cannabis sativa genome and transcriptome were used to identify the C. sativa LBD gene family, and analyzed their expression patterns. Our results showed that the cannabis LBD contains 32 members, which were divided into two major categories, seven sub-families. Class Ⅰ was divided into 5 sub-families, named Class Ⅰ_a to Class Ⅰ_e, while Class Ⅱ was divided into 2 sub-families, including Class Ⅱ_a and Class Ⅱ_b. Analysis showed that the number of amino acids encoded LBDs was between 172 and 356, and the isoelectric point was between 4.92 and 9.43. The mole-cular weight of LBD was between 18 862.92 Da and 40 081.33 Da, and most members are located in the nucleus. Chromosome positioning of LBD showed that 32 members were unevenly distributed on 10 chromosomes of C. sativa LBD transcription factor domain, gene structure and motifs are relatively conservative, and the characteristics of different class members are similar. The upstream promoter region of the gene contains a variety of cis-acting elements related to plant hormones and environmental factors, C. sativa LBD genes have different expression patterns in the stems, leaves, and flowers of ZYS varieties(low tetrahydrocannabinol, high cannabidiol). The members of the LBD gene family are mainly expressed in the flowers and stems of ZYS varieties, while members expressed in the leaves very few; Class Ⅱ members CsLBD21 and CsLBD23 are expressed in flowers and stems, and CsLBD8 and CsLBD18 are expressed in flowers, stems and leaves. These genes may participate in the growth and development of cannabis and affect the biosynthesis of cannabinoids. This study laid the foundation for the subsequently functional research of the cannabis LBD gene family.
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Humains , Cannabis/métabolisme , Régulation de l'expression des gènes végétaux , Médecine traditionnelle chinoise , Phylogenèse , Protéines végétales/métabolisme , Graines/métabolismeRésumé
Unraveling the genetic basis of medicinal plant metabolism and developmental traits is a long-standing goal for pharmacologists and plant biologists. This paper discusses the definition of molecular genetics of medicinal plants, which is an integrative discipline with medicinal plants as the research object. This discipline focuses on the heredity and variation of medicinal plants, and elucidates the relationship between the key traits of medicinal plants(active compounds, yield, resistance, etc.) and genotype, studies the structure and function, heredity and variation of medicinal plant genes mainly at molecular level, so as to reveal the molecular mechanisms of transmission, expression and regulation of genetic information of medicinal plants. Specifically, we emphasize on three major aspects of this discipline.(1)Individual and population genetics of medicinal plants, this part mainly highlights the genetic mechanism of the domestication, the individual genomics at the species level, and the formation of genetic diversity of medicinal plants.(2)Elucidation of biosynthetic pathways of active compounds and their evolutionary significance. This part summarizes the biosynthesis, diversity and molecular evolution of active compounds in medicinal plants.(3) Molecular mechanisms that shaping the key agronomic traits by internal and external factors. This part focuses on the accumulation and distribution of active compounds within plants and the regulation of metabolic network by environmental factors. Finally, we prospect the future direction of molecular genetics of medicinal plants based on the rapid development of multi-omics technology, as well as the application of molecular genetics in the future strategies to achieve conservation and breeding of medicinal plants and efficient biosynthesis of active compounds.
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Voies de biosynthèse , Génomique , Biologie moléculaire , Amélioration des plantes , Plantes médicinalesRésumé
Natural indigo, as one of the oldest dyes, is also a pivotal dye utilized in cotton fabrics today. A diversity of plants rich in indigo compounds belong to traditional Chinese herbal medicines. Indigo compounds have a variety of biological and pharmacological activities, including anticonvulsant, antibacterial, antifungal, antiviral and anticancer activities. A substantial progress in indigo biosynthesis has been made lately. This paper summarizes the value of indigo from the aspects of cultural history, biosynthetic pathways and the medicinal activities of its related derivatives involved in the pathways. In addition, the latest research advancements in indigo biosynthetic pathways is demonstrated in this paper, which would lay the theoretical foundation for the exploration and utilization of natural indigo.
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Voies de biosynthèse , Agents colorants , Carmin d'indigo/métabolisme , Indigofera/métabolismeRésumé
Objective:To investigate the effect of Ru′ai Shuhou prescription (RSR) drug-containing serum on the proliferation and invasion ability of breast cancer cells MDA-MB-453 based on the biological axis of stromal cell-derived factor-1(SDF-1)/chemokine receptor 4 (CXCR4). Method:A model of MDA-MB-453 cells with SDF-1-induced high expression of CXCR4 was established, and the rat drug-serum containing RSR and blank rat serum were prepared respectively. The cells were divided into fetal bovine serum control group (Blank), blank rat serum group, SDF-1+blank rat serum group, SDF-1+RSR group, AMD3100+ SDF-1+blank rat serum group, and AMD3100+ SDF-1+RSR group. After intervention for 48 h, cell proliferation was detected by cell counting kit-8 (CCK-8) assay, cell invasion ability was detected by transwell assay, and mRNA and protein expressions of CXCR4, matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. Result:As compared with the blank serum group, the proliferation of MDA-MB-453 cells was promoted and expression of CXCR4 mRNA was increased significantly when SDF-1 was 100 μg·L-1 (P<0.05). As compared with SDF-1+blank rat serum group, RSR inhibited the proliferation and invasion of MDA-MB-453 cells induced by SDF-1, and at the same time, down-regulated the mRNA and protein expressions of CXCR4, MMP-2 and MMP-9 (P<0.05). After pre-treatment with AMD3100 for 24 h, the inhibitory effect of RSR to cell proliferation was significantly increased (P<0.05), and meanwhile, the decreases in mRNA and protein expression of CXCR4, MMP-2 and MMP-9 were more obvious, with statistically significant differences (P<0.05). Conclusion:Through SDF-1/CXCR4 biological axis, RSR could down-regulate the expression of MMP-2 and MMP-9, reduce the degradation of extracellular matrix (ECM), and then inhibit the metastasis of MDA-MB-453 cells. In addition, it has a synergistic effect with CXCR4 inhibitor AMD3100.
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To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.
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Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.
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Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.
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Chorea-acanthocytosis (ChAc) is the most common subtype of neuroacanthocytosis syndrome, characterized by the presence of acanthocytes and neurological disorders. It is thought to be caused by VPS13A mutations. Characteristic movement disorders in ChAc is choreiform movements affecting both trunk and extremities and prominent orolingual dyskinesia is pathognomonic. Acanthocytosis in peripheral blood smear, elevated serum creatine kinase and atrophy of heads of caudate nuclei and dilation of the anterior horn of the lateral ventricles in magnetic resonance imaging could assist the diagnosis of ChAc. Botulinum toxin injection is a possible treatment for the typical orofacial dystonia. Deep brain stimulation is a novel surgical treatment modality. Most cases chose globus pallidus internus as target. Patients with dystonia as a major manifestation will benefit more from high-frequency stimulation and those with major findings of chorea and dysarthria are suitable for low-frequency stimulation. More evidence of long-term outcomes is warranted.
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Objective To investigate the correlation of wavefront aberration and myopic development in school-age children.Methods Together 150 school-age children (300 eyes) in Beijing city were collected and underwent cycloplegic refractometry for detect the refraction status and Allegretto wavefront aberrometry for the measurement of wavefront aberration for 1-year follow up.Results Totally 132 children were successfully followed up and only 120 children were included in this study.The average increased diopter was (0.74 ± 0.55) D.It was found that the development of myopia was correlated with age,myopic duration and the baseline diopter (all P < 0.01),and the wavefront aberration was correlated with age (P < 0.05).There were significant difference in the third order RMS value and C7 (coma) between the myopic children with rapid progress and slow progress.C12 (spherical aberration) was significantly correlated with the change of diopter (P < 0.05).Conclusion Both third order RMS and C7 (coma) may be the major contributors for myopia progress in school-age children,and the increased diopter may polarize the spherical aberration toward minus values.
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Objective To assess the outcomes of OASIS iris expander in phacoemulsification surgery of cataract with small pupil.Methods A prospective case-control study was conducted in 22 microcoria cataract patients (22 eyes).And they were randomly divided into group A and B,in which the pupils of group A were dilated by tearing instruments in 13 eyes,and the pupils of group B were dilated using OASIS iris expander in 9 eyes.All patient underwent phacoemulsification with 3.2 mm clear corneal incision and were followed up at postoperative 1 week,1 month,3 months and 6 months.Finally,the best corrected visual acuity (BCVA),intraocular pressure (IOP),corneal endothelial cell counts,pupil size before and after surgery were recorded and analyzed by an independent sample t test.Results All procedures were completed successfully by the same skilled doctor.Intraocular lenses were implanted in capsule completely,and no complications occurred.At 6 months after operation,patients'BCVA in group A (0.41 ± 0.30) and group B (0.77 ± 0.23) was significantly higher than that in group A (0.17 ±0.14) and group B (0.16 ±0.14) before operation,but there was no statistical difference between the two groups (all P >0.05);whereas there was no significant change in the IOP of group A and B at 6 months after operation (1 kPa =7.5 mmHg) and before operation [(14.22 ±6.00) mmHg vs.(15.70 ± 5.70) mmHg)] (all P > 0.05).Moreover,corneal endothelial cell counts in group A [(1486 ±718) cells · mm-2] and B [(1246 ±516)cells · mm-2] were significantly smaller than those before operation [(2498 ±564)cells · mm-2 vs.[(2424 ± 640) cells · mm-2],with no significant difference (P=0.091).The postoperative diameter of the pupil in group A [(4.00 ±0.88) mm] and group B [(4.70 ± 1.57) mm] after operation was larger than that in group A [(2.30 ±0.35)mm] and group B [(1.94 ±0.50)mm] before operation,and there was no statistical difference between the two groups (all P >0.05).Conclusions OASIS iris expander can help to dilate and hold pupils and does not affect the postoperative visual acuity and intraocular pressure in mlcrocoria cataract phacoemulsification.The postoperative pupils become larger,and it is necessary to pay attention to protect corneal endothelial cell during usage of OASIS iris expander.