Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.

OBJECTIVE: Mutations in BMPR2 (bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH. METHODS: SMC-specific Bmpr2-/- mice (BKOSMC) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from BKOSMC mice, human PASMC with BMPR2 reduced by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation were compared to controls, to investigate the phenotype and underlying mechanism. RESULTS: BKOSMC mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (ß-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (ß-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension. CONCLUSIONS: Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Analysis of population structure and genetic diversity of Camellia tachangensis in Guizhou based on SNP markers.

BACKGROUND: Camellia tachangensis F. C. Zhang is a five-compartment species in the ovary of tea group plants, which represents the original germline of early differentiation of some tea group plants. METHODS AND RESULTS: In this study, we analyzed single-nucleotide polymorphisms (SNPs) at the genome level, constructed a phylogenetic tree, analyzed the genetic diversity, and further investigated the population structure of 100 C. tachangensis accessions using the genotyping-by-sequencing (GBS) method. A total of 91,959 high-quality SNPs were obtained. Population structure analysis showed that the 100 C. tachangensis accessions clustered into three groups: YQ-1 (Village Group), YQ-2 (Forest Group) and YQ-3 (Transition Group), which was further consistent with the results of phylogenetic analysis and principal component analyses (PCA). In addition, a comparative analysis of the genetic diversity among the three populations (Forest, Village, and Transition Groups) detected the highest genetic diversity in the Transition Group and the highest differentiation between Forest and Village Groups. CONCLUSIONS: C. tachangensis plants growing in the forest had different genetic backgrounds from those growing in villages. This study provides a basis for the effective protection and utilization of C. tachangensis populations and lays a foundation for future C. tachangensis breeding.

The Clinical Nursing Pathway Plus Low-flow Oxygen Breathing Effects on Blood Glucose and Urine Ketones in Diabetic Ketoacidosis Patients.

Objective: To assess the effects of the clinical nursing pathway (CNP) on blood glucose and urine ketones in patients with diabetic ketoacidosis (DKA). Methods: A total of 60 patients with DKA (20 type I and 40 type II) treated in the Department of Endocrinology at Anhui Second People's Hospital from January 2018 to May 2022 were recruited and randomly assigned to receive routine nursing (control group) or CNP plus routine nursing (observation group), with 30 patients in each group. The observation group received the clinical nursing pathway (CNP) along with routine nursing care. As part of the CNP, low-flow oxygen therapy was administered to the patients. Low-flow oxygen therapy involves the delivery of oxygen at a lower flow rate compared to high-flow oxygen therapy. In this study, a flow rate of 2 L/min was used. The low-flow oxygen was administered to the patients through a nasal cannula or a similar device. Outcome measures included symptom relief and length of hospital stay. Results: The observation group showed a significantly higher decline rate of blood glucose in patients than in the control group. Patients in the observation group had a more rapid disappearance of urine ketones versus those in the control group. CNP plus routine nursing resulted in a significantly shorter length of hospital stay versus routine nursing (RR:0.79, 95% CI (1.078, 4.511), P < .05). Conclusion: CNP plus continuous low-flow oxygen breathing facilitates the decline of blood glucose, removes ketone bodies, mitigates DKA symptoms, and shortens the length of hospital stay.

Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil.

OBJECTIVE: This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. METHODS: Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. RESULTS: A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. CONCLUSION: There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.

[Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province].

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

PPARγ-p53-Mediated Vasculoregenerative Program to Reverse Pulmonary Hypertension.

RATIONALE: In pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage and impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), and p53. OBJECTIVE: We investigated the vasculoprotective and regenerative potential of a newly identified PPARγ-p53 transcription factor complex in the pulmonary endothelium. METHODS AND RESULTS: In this study, we identified a pharmacologically inducible vasculoprotective mechanism in pulmonary arterial and lung MV (microvascular) endothelial cells in response to DNA damage and oxidant stress regulated in part by a BMPR2 dependent transcription factor complex between PPARγ and p53. Chromatin immunoprecipitation sequencing and RNA-sequencing established an inducible PPARγ-p53 mediated regenerative program regulating 19 genes involved in lung endothelial cell survival, angiogenesis and DNA repair including, EPHA2 (ephrin type-A receptor 2), FHL2 (four and a half LIM domains protein 2), JAG1 (jagged 1), SULF2 (extracellular sulfatase Sulf-2), and TIGAR (TP53-inducible glycolysis and apoptosis regulator). Expression of these genes was partially impaired when the PPARγ-p53 complex was pharmacologically disrupted or when BMPR2 was reduced in pulmonary artery endothelial cells (PAECs) subjected to oxidative stress. In endothelial cell-specific Bmpr2-knockout mice unable to stabilize p53 in endothelial cells under oxidative stress, Nutlin-3 rescued endothelial p53 and PPARγ-p53 complex formation and induced target genes, such as APLN (apelin) and JAG1, to regenerate pulmonary microvessels and reverse pulmonary hypertension. In PAECs from BMPR2 mutant PAH patients, pharmacological induction of p53 and PPARγ-p53 genes repaired damaged DNA utilizing genes from the nucleotide excision repair pathway without provoking PAEC apoptosis. CONCLUSIONS: We identified a novel therapeutic strategy that activates a vasculoprotective gene regulation program in PAECs downstream of dysfunctional BMPR2 to rehabilitate PAH PAECs, regenerate pulmonary microvessels, and reverse disease. Our studies pave the way for p53-based vasculoregenerative therapies for PAH by extending the therapeutic focus to PAEC dysfunction and to DNA damage associated with PAH progression.

Exploring the Common Gene Signatures Between Myocardial Infarction-Reperfusion Injury and the Gut Microbiome Using Bioinformatics.

BACKGROUND: This bioinformatics report attempts to explore the cross-talk genes, transcription factors (TFs), and pathways related to myocardial ischemia-reperfusion injury (MIRI) as well as the gut microbiome. METHOD: The datasets GSE61592 (three MIRI and three sham samples) and GSE160516 (twelve MIRI and four sham samples) were selected in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) identification (p < 0.05 and |log FC (fold change)| ≥1) together with functional annotation (p < 0.05) was implemented. The Cytoscape platform established the protein-protein interaction (PPI) network. Genes associated with gut microbiome disorder were extracted based on the DisGeNET database, and those associated with MIRI were overlapped. The Recursive Feature Elimination (RFE) algorithm was adopted for selecting features, and cross-talk genes were predicted by the Support Vector Machine (SVM) models. A network encompassing cross-talk genes along with the TFs was thereby established. RESULT: The MIRI datasets comprised 138 shared DEGs, with 101 showing up-regulation whereas 37 showing down-regulation. Notably, the PPI interwork for MIRI contained 2517 edges along with 1818 nodes. By using RFE and SVM methods, six feature genes with the highest prediction were identified: B2m, VCAM-1, PDIA4, Ptgds, Mlxipl, and ACADS. Among these genes, B2m and PDIA4 were most highly expressed in MIRI and the gut microbiome disorder. CONCLUSION: B2m and PDIA4 were identified to be significantly correlated with candidate cross-talk genes of MIRI with gut microbiome disorder, implying a similarity between MIRI and Gut microbiome disorder (GMD). These genes can serve as an experimental research basis for future studies.

Co-Expression of Multiple PAX Genes in Renal Cell Carcinoma (RCC) and Correlation of High PAX Expression with Favorable Clinical Outcome in RCC Patients.

Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (PAX) gene family encodes transcription factors, which orchestrate multiple processes in cell lineage determination during embryonic development and organogenesis. Several PAX genes have been shown to be expressed in RCC following its onset and progression. Here, we performed real-time quantitative polymerase chain reaction (RT-qPCR) analysis on a series of human RCC cell lines, revealing significant co-expression of PAX2, PAX6, and PAX8. Knockdown of PAX2 or PAX8 mRNA expression using RNA interference (RNAi) in the A498 RCC cell line resulted in inhibition of cell proliferation, which aligns with our previous research, although no reduction in cell proliferation was observed using a PAX2 small interfering RNA (siRNA). We downloaded publicly available RNA-sequencing data and clinical histories of RCC patients from The Cancer Genome Atlas (TCGA) database. Based on the expression levels of PAX2, PAX6, and PAX8, RCC patients were categorized into two PAX expression subtypes, PAXClusterA and PAXClusterB, exhibiting significant differences in clinical characteristics. We found that the PAXClusterA expression subgroup was associated with favorable clinical outcomes and better overall survival. These findings provide novel insights into the association between PAX gene expression levels and clinical outcomes in RCC patients, potentially contributing to improved treatment strategies for RCC.

NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer.

Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma, NUSAP1 and ILF2 mRNA expression levels are positively correlated, elevated, and associated with poor clinical outcomes. Our study identifies a novel role for NUSAP1 in regulating R-loop formation and accumulation in response to DNA damage through its interactions with ILF2 and hence provides a potential therapeutic target.

Robust Self-Supported SnO2-Mn2O3@CC Electrode for Efficient Electrochemical Degradation of Cationic Blue X-GRRL Dye.

Exploration of highly efficient and robust catalyst is pivotal for electrocatalytic degradation of dye wastewater, but it still is a challenge. Here, we develop a three-dimensional self-supported SnO2-Mn2O3 hybrid nanosheets grown on carbon cloth (noted by SnO2-Mn2O3@CC) electrode via a simple hydrothermal method and annealing treatment. Benefitting from the interlaced nanosheets architecture that enlarges the surface area and the synergetic component effect that accelerates the interfacial electronic transfer, SnO2-Mn2O3@CC electrode exhibits a superior electrocatalytic degradation efficiency for cationic blue X-GRRL dye in comparison with the single metal oxide electrode containing SnO2@CC and Mn2O3@CC. The degradation efficiency of cationic blue X-GRRL on SnO2-Mn2O3@CC electrode can reach up to 97.55% within 50 min. Furthermore, self-supported architecture of nanosheets on carbon cloth framework contributes to a robust stability compared with the traditional electrode via the multiple dip/brush coating accompanied by the thermal decomposition method. SnO2-Mn2O3@CC electrode exhibits excellent recyclability, which can still retain a degradation efficiency of 94.12% after six cycles. This work may provide a new pathway for the design and exploration of highly efficient and robust electrooxidation catalysts for dye degradation.

[Diagnostic value of whole exome sequencing for patients with intellectual disability or global developmental delay].

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD). METHODS: 134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome. CONCLUSION: WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.

[The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension.

BACKGROUND: Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC. METHODS: RNA sequencing was applied to pulmonary arterial SMC (PASMC) from PAH patients with and without a BMPR2 (bone morphogenetic receptor 2) mutation versus control PASMC to uncover genes required for their heightened proliferation and glycolytic metabolism. Assessment of differentially expressed genes established metabolism as a major pathway, and the most highly upregulated metabolic gene in PAH PASMC was aldehyde dehydrogenase family 1 member 3 (ALDH1A3), an enzyme previously linked to glycolysis and proliferation in cancer cells and systemic vascular SMC. We determined if these functions are ALDH1A3-dependent in PAH PASMC, and if ALDH1A3 is required for the development of pulmonary hypertension in a transgenic mouse. Nuclear localization of ALDH1A3 in PAH PASMC led us to determine whether and how this enzyme coordinately regulates gene expression and metabolism in PAH PASMC. RESULTS: ALDH1A3 mRNA and protein were increased in PAH versus control PASMC, and ALDH1A3 was required for their highly proliferative and glycolytic properties. Mice with Aldh1a3 deleted in SMC did not develop hypoxia-induced pulmonary arterial muscularization or pulmonary hypertension. Nuclear ALDH1A3 converted acetaldehyde to acetate to produce acetyl coenzyme A to acetylate H3K27, marking active enhancers. This allowed for chromatin modification at NFYA (nuclear transcription factor Y subunit α) binding sites via the acetyltransferase KAT2B (lysine acetyltransferase 2B) and permitted NFY-mediated transcription of cell cycle and metabolic genes that is required for ALDH1A3-dependent proliferation and glycolysis. Loss of BMPR2 in PAH SMC with or without a mutation upregulated ALDH1A3, and transcription of NFYA and ALDH1A3 in PAH PASMC was ß-catenin dependent. CONCLUSIONS: Our studies have uncovered a metabolic-transcriptional axis explaining how dividing cells use ALDH1A3 to coordinate their energy needs with the epigenetic and transcriptional regulation of genes required for SMC proliferation. They suggest that selectively disrupting the pivotal role of ALDH1A3 in PAH SMC, but not endothelial cells, is an important therapeutic consideration.

IL-6 induced enhanced clearance of proANP and ANP by insulin-degrading enzyme in T1DM mice.

Cardiovascular disease (CVD) is a prevalent cause of morbidity and mortality in type I diabetes mellitus (T1DM). However, the pathophysiological mechanisms underlying the relationship between CVD, CVD risk factors, and T1DM have not yet been sufficiently explored. Here, we report that insulin-degrading enzyme (IDE) effectively degrades the precursor of atrial natriuretic peptide (proANP) in HEK293T cells. The pro-inflammatory cytokine IL-6 elicited a significant dose-dependent increase in IDE protein expression. Inhibition of the ERK/MAPK signaling pathway with selumetinib abolished the IL-6-stimulated increase in IDE protein levels and decreased ANP secretion in H9C2 cells. Importantly, the T1DM mouse model displayed lower proANP in the heart and ANP in serum, due to increased IDE expression and activity. Our results suggest a novel role of IL-6 in ANP metabolism via IDE and provide possibilities for new potential therapeutic strategies for diabetes-related cardiovascular complications.

Population structure analysis to explore genetic diversity and geographical distribution characteristics of cultivated-type tea plant in Guizhou Plateau.

BACKGROUND: Tea plants originated in southwestern China. Guizhou Plateau is an original center of tea plants, and is rich in germplasm resources. However, the genetic diversity, population structure and distribution characteristics of cultivated-type tea plants in the region are unknown. In this study, we explored the genetic diversity and geographical distribution of cultivated-type tea accessions in Guizhou Plateau. RESULTS: We used 112,072 high-quality genotyping-by-sequencing to analyze the genetic diversity, principal components, phylogeny, population structure, and linkage disequilibrium, and develop a core collection of 253 cultivated-type tea plant accessions from Guizhou Plateau. The results showed Genetic diversity of the cultivated-type tea accessions of the Pearl River Basin was significantly higher than that of the cultivated-type tea accessions of the Yangtze River Basin. Three inferred pure groups (CG-1, CG-2 and CG-3) and one inferred admixture group (CG-4), were identified by a population structure analysis, and verified by principal component and phylogenetic analyses. The highest genetic distance and differentiation coefficients were determined for CG-2 vs CG-3. The lower genetic distance and differentiation coefficients were determined for CG-4 vs CG-2 and CG-4 vs CG-3, respectively. We developed a core set and a primary set. The primary and core sets contained 77.0 and 33.6% of all individuals in the initial set, respectively. The primary set may serve as the primary population in genome-wide association studies, while the core collection may serve as the core population in multiple treatment setting studies. CONCLUSIONS: The present study demonstrated the genetic diversity and geographical distribution characteristics of cultivated-type tea plants in Guizhou Plateau. Significant differences in genetic diversity and evolutionary direction were detected between the ancient landraces of the Pearl River Basin and the those of the Yangtze River Basin. Major rivers and ancient hubs were largely responsible for the genetic exchange between the Pearl River Basin and the Yangtze River Basin ancient landraces as well as the formation of the ancient hubs evolutionary group. Genetic diversity, population structure and core collection elucidated by this study will facilitate further genetic studies, germplasm protection, and breeding of tea plants.

The misdiagnose and treatment of a concealed kind of supernumerary nostril: a case report and review.

BACKGROUND: Supernumerary Nostril, also called triple nostrils or accessory nostril, is a rare congenital nasal malformation. CASE PRESENTATION: We report one conceal case of supernumerary nostril in a 19-years-old men which is misdiagnosed to a simple small nasal skin pit. Ordinary surgical excision led to recurrent infection of the lesion postoperatively, and was eventually required secondary surgery and the lesion was finally confirmed by pathological biopsy as a trinasal nostrils. CONCLUSIONS: Through this case, we stress the essential role in differential diagnosis, confirming the diagnosis and seeking for better solutions. Level of Evidence V.

Bedside handover with structured and relayed forms in a postanesthesia care unit: A pre- and post-implementation study.

BACKGROUND: Early postoperative patients are vulnerable. Poor communication between health care professionals may seriously damage patients' wellbeing. There is a risk of information loss when bedside handover is performed. OBJECTIVES: To investigate whether the implementation of structured and relayed forms to shift-to-shift bedside handovers improve the frequency of appropriate handover elements and reduces the incidence of adverse events and postoperative length of stay for patients in a postanesthesia care unit. METHODS: This quality improvement project was conducted in a postanesthesia care unit of a tertiary stomatological hospital in China. The study population was patients under surveillance in the postanesthesia care unit for >12 h. A pre- and post-implementation approach was employed. The pre-implementation of unstructured bedside handovers and the post-implementation of bedside handovers with structured and relayed forms were compared. The indicators measured were appropriate handover elements, adverse patient events, and postoperative hospital stay. RESULTS: There were 387 and 395 morning handovers observed pre- and post-implementation of bedside handovers with structured and relayed forms, respectively. Of the 21 elements that should be delivered, 17 elements were noted to be improved. No improvement was found in the incidence of adverse events and postoperative hospital stay. CONCLUSIONS: Bedside handovers with structured and relayed forms increased the incidence of appropriate handover elements. The use of structured and relayed forms did not affect on the incidence of adverse events and postoperative hospital stay. Individualized relayed handover forms may be developed and implemented according to the characteristics in which they are administered.

[Distribution of variants of 88 recessive genetic disease-related genes among 1314 individuals from Chenzhou, China].

OBJECTIVE: To determine the carrier rate for common recessive genetic diseases in Chenzhou region in order to provide a reference for carrier screening in this region. METHODS: Targeted capture and high-throughput sequencing were carried out to detect potential variants of 79 genes associated with 88 recessive genetic diseases. Couples at risk were provided with prenatal diagnosis upon their subsequent pregnancies. RESULTS: A total of 1314 individuals were enrolled, among whom 355 (27.02%) were found to be carrier for at least one disease. The carrier rates for 8 diseases have exceeded 1%, with the most common two including thalassemia (11.72%, 154/1314) and autosomal recessive deafness (5.48%, 72/1314). Ten couples were found to be at risk for producing affected offspring. Among these, five females were carriers for X-linked recessive genetic diseases. Following genetic counseling, seven couples had accepted prenatal diagnosis, and 3 affected fetuses were diagnosed. CONCLUSION: The disease types and pathogenic variants of Chenzhou region have differed from previously reported. Further research is required to validate the above finding with a larger populations.

Oscillatory self-organization dynamics between soliton molecules induced by gain fluctuation.

In passively mode-locked fiber lasers (PMLFLs), the dissipative solitons (DSs) can self-organize to form complex structures through delicate interactions. However, it is still elusive to control these soliton structures by external influences. We here find that at a certain critical power, the location between two soliton molecules can be controlled by a slow modulated pump power. After applying the pump power with periodic fluctuation, two soliton molecules oscillate from the state of soliton molecular complex to stable distribution with maximum inter-molecular separation. During this process, the internal structure of each soliton molecule keeps steady. The slow gain depletion and recovery mechanism which plays a dominant role affects the motion of soliton molecules. These results could further expand the molecular analogy of spectroscopy and stimulate the development of optical information storage and processing.