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Coilia nasus , a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C. nasus . Genotyping of the female population based on whole-genome resequencing yielded 2 120 695 high-quality SNPs, 39 of which were suggestively associated with ovarian development. Of note, a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified, with cpne5a determined as the causal gene of the peak. Therefore, single-marker and haplotype association analyses were performed on cpne5a , revealing four genetic markers ( P <0.05) and seven haplotypes (r 2 >0.9) significantly associated with the phenotype. Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary, respectively, between individuals of different body sizes. Integrating the GWAS and transcriptome analysis results, this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion, extracellular matrix, angiogenesis, and gap junctions involved in population-asynchronous ovarian development. The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C. nasus strains exhibiting population-synchronous ovarian development in the future.

Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Bone morphogenetic protein 2 plays an important role in the regulation of osteoblast proliferation and differentiation. Phylogenetic analysis showed that the bmp2 ortholog evolved from the same ancestral gene family in vertebrates and was duplicated in teleost, which were named bmp2a and bmp2b. The results of whole-mount in situ hybridization showed that the expression locations of bmp2a and bmp2b in zebrafish were different in different periods (24 hpf, 48 hpf, 72 hpf), which revealed potential functional differentiation between bmp2a and bmp2b. Phenotypic analysis showed that bmp2a mutations caused partial rib and vertebral deformities in zebrafish, while bmp2b -/- embryos died massively after 12 hpf due to abnormal somite formation. We further explored the expression pattern changes of genes (bmp2a, bmp2b, smad1, fgf4, runx2b, alp) related to skeletal development at different developmental stages (20 dpf, 60 dpf, 90 dpf) in wild-type and bmp2a -/- zebrafish. The results showed that the expression of runx2b in bmp2a -/- was significantly downregulated at three stages and the expression of other genes were significantly downregulated at 90 dpf compared with wild-type zebrafish. The study revealed functional differentiation of bmp2a and bmp2b in zebrafish embryonic and skeletal development., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intermuscular bones (IBs) are mineralized spicules, present in the myosepta of many, but not all, teleost species. IBs are often small and sharp, and they consequently limit how the fish can be processed; the IBs may cause injury or trauma if lodged in consumers' throats or mouths, and therefore affect the appeal of the fish to many consumers. The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established. Here, the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish. The analysis defined 18 distinct cell types. Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. In particular, the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants. Among those, runx2b -/- mutants completely lost IBs, while swimming performance, growth and bone mineral density were not significantly different from runx2b +/+ zebrafish. Comparative single-cell RNA sequencing (scRNA-seq) analysis in runx2b -/- and runx2b +/+ zebrafish revealed the role of osteoblasts in IB formation. In addition, differentially expressed genes were enriched in the transforming growth factor β/bone morphogenetic protein (TGF-β/BMP) pathway after runx2b deletion. This study provides evidence for the crucial role of runx2b regulation in IB formation. Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs, which can improve the safe consumption and economic value of many farmed fish species., (© The Author(s) 2022. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor β (TGF-β) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b , which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs ( rgs9a , rgs9b , rcvrn2 , guca1d , grk1b , opn1mw4, and gc2 ) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Wan, Zhou, Nie, Chen, Diao and Gao.)

This study reports the application of an aromatic tricarboxylic acid, 2,5-di(4-carboxylphenyl)nicotinic acid (H3dcna) as a versatile and unexplored organic building block for assembling a new series of metal(ii) (M = Co, Ni, Zn, Fe, and Mn) complexes and coordination polymers, namely [M(Hdcna)(phen)2(H2O)]·H2O (M = Co (1), Ni (2)), [Zn(μ-Hdcna)(phen)]n (3), [Co(μ-Hdcna)(bipy)(H2O)2]n·nH2O (4), [Zn2(μ-Hdcna)2(bipy)2(H2O)4]·6H2O (5), [Zn(μ3-Hdcna)(H2biim)]n (6), [Ni2(Hdcna)2(μ-bpb)(bpb)2(H2O)4] (7), [Fe(μ4-Hdcna)(μ-H2O)]n·nH2O (8), and [Mn3(μ5-dcna)2(bipy)2(H2O)2]n·2nH2O (9). Such a diversity of products was hydrothermally prepared from the corresponding metal(ii) salts, H3dcna as a principal multifunctional ligand, and N-donor mediators of crystallization (1,10-phenanthroline, phen; 2,2'-bipyridine, bipy; 2,2'-biimidazole, H2biim; or 1,4-bis(pyrid-4-yl)benzene, bpb). The obtained products 1-9 were fully characterized by standard methods (elemental analysis, FTIR, TGA, PXRD) and the structures were established by single-crystal X-ray diffraction. These vary from the discrete monomers (1, 2) and dimers (5, 7) to the 1D (3, 4, 6) and 2D (8, 9) coordination polymers (CPs). Structural and topological characteristics of hydrogen-bonded or metal-organic architectures in 1-9 were highlighted, revealing that their structural multiplicity depends on the type of metal(ii) source and crystallization mediator. Thermal stability as well as luminescent, magnetic, or catalytic properties were explored for selected compounds. In particular, the zinc(ii) derivatives 3, 5, and 6 were applied as efficient heterogeneous catalysts for the cyanosilylation of aldehydes with trimethylsilyl cyanide at room temperature. The catalytic reactions were optimized by tuning the different reaction parameters (solvent composition, time, catalyst loading) and the substrate scope was also explored. Compound 5 revealed superior catalytic activity leading to up to 75% product yields, while maintaining its original performance upon recycling for at least four reaction cycles. Finally, the obtained herein products represent the unique examples of coordination compounds derived from H3dcna, thus opening up the use of this multifunctional tricarboxylic acid for generating complexes and coordination polymers with interesting structures and functional properties.

Intermuscular bones (IBs) specially exist in lower teleost fish and the molecular mechanism for its development remains to be clarified. In this study, different staining methods and comparative proteomics were conducted to investigate the histological structure and proteome of IB development in Megalobrama amblycephala , including four key IB developmental stages (S1-IBs have not emerged in the tail part; S2-several small IBs started to ossify in the tail part; S3-IBs appeared rapidly; S4-all the IBs appeared with mature morphology). Alcian blue and alizarin red S stained results indicated that IBs were gradually formed from S2 to S4, undergoing intramembranous ossification without a cartilaginous phase. A total of 3368 proteins were identified by using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. Functional annotation showed that proteins which were differentially expressed among stages were involved in calcium, MAPK, Wnt, TGF-β, and osteoclast pathways which played a critical role in bone formation and differentiation. Three proteins (collagen9α1, stat1, tnc) associated with chondrocytes did not exhibit significant changes through S2 to S4; however, proteins (entpd5, casq1a, pvalb, anxa2a, anxa5) which associated with osteoblasts and bone formation and differentiation showed significantly a higher expression level from S1 to S2, as well as to S3 and S4. These further demonstrated that development of IBs did not go through a cartilaginous phase. The inhibitors of TGF-β and Wnt pathways were tested on zebrafish (sp7/eGFP) and the results indicated that both inhibitors significantly delayed IB development. This study provides a comprehensive understanding of the IB ossification pattern, which will help further elucidate the molecular mechanisms for IB development in teleosts.

Objectives: The present study reviews the delivery of a pilot curriculum-mentorship-based peer vocational support workers training in a Hong Kong public psychiatric hospital. The present paper reports (1) on the development of a peer vocational support workers training - Job Buddies Training Program (JBTP) in Hong Kong; and (2) preliminary findings from both quantitative and qualitative perspectives., Method: The curriculum consists of 15-session coursework, 8-session storytelling workshop and 50-hour practicum to provide Supported Employment Peer Service (SEPS) under the mentorship of occupational therapists. Six trainees were assessed using three psychosocial assessments and qualitative methods., Findings: Compared to the baseline, the Job Buddies (JB) trainees showed an increase in awareness of their own recovery progress, occupational competence and problem-solving skills at the end of the training. Their perceived level of self-stigma was also lessened. In post-training evaluation, all Job Buddies trainees said they perceived positive personal growth and discovered their own strengths. They also appreciated the help from their mentors and gained mutual support from other trainees and from exposure with various mini-projects in the training., Conclusions and Implications: This pilot study provides an example of incorporating peer support and manualized training into existing work rehabilitation service for our JB trainees. Further studies on the effectiveness of service provided by peer support workers and for development on the potential use of peer support workers in other clinical and rehabilitation settings with larger subjects will be fruitful., (Copyright © 2016. Published by Elsevier B.V.)

The Xin'an female doctors in the Ming and Qing Dynasties could be divided into 4 categories: viz., those who provide general medical services for women patients; those who provide supplementary services for delivery women; those who serve as an assistant of their practicing husband; and those who continued to practice medicine after their husband's death. Although the latter two types could be respected by their families and praised by the society, these female medical practitioners were undervalued and overlooked generally in the society where males were the main body of the medical circle and, moreover, they were not well educated, as well as the influence of Confucianist thoughts of "honorable men and humble women" , hence, their deeds were rarely seen in historical records. However, the emergence of female doctors had certain social causes, and their contributions to local health care should not be ignored.

Objective: To study the efficacy of metformin intervention on insulin resistance during catch-up growth in mice with fetal growth restriction (FGR)., Methods: Mouse models of FGR were established by low protein diet feeding of the pregnant mice. Both the newborn female mice with FGR and normal control (NC) mice were randomized for feeding with a standard diet (SF) or a high-fat diet (HF) after weaning and treatment with gavage of either metformin or normal saline. The mice were examined for vaginal opening time and the estrous cycle at the age of 8 weeks. At the age of 12 weeks, 6 mice in anestrus from each group were fasted for 12 h for measurement of body weight, height, poundera index (PI), fasting blood glucose (FBG), fasting insulin (Fins), follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and the HOMA-IR was calculated. The reproductive capacity of female mice was assessed by mixing them with male mice at the ratio of 2:1. The 3 × 2 factorial analysis was conducted to determine the interactions between FGR, high-fat feeding and metformin., Results: Factorial analysis showed that FGR and high-fat feeding had significant effects on the PI index, Fins, HOMA-IR, vaginal opening time, and AMH (P<0.05). Metformin significantly affected the factors related to high-fat feeding including weight, PI, FPG, Fins, HOMA-IR and estrous cycle (P<0.05) and the factors related to FGR with the exception of height and FSH (P<0.05). FGR significantly affected the factors tested except for body weight (P<0.05); high-fat feeding affected all the factors but the FSH (P<0.05); metformin affected all the factors but the height and FSH (P<0.05). In the female mice treated with saline, the pregnancy rates differed significantly between FGR mice with high-fat feeding and control mice with standard feeding, and between FGR mice with standard feeding and high-fat feeding (P<0.05)., Conclusion: FGR mice can present with delayed puberty with rare ovulation and adulthood insulin resistance, and high-fat feeding after birth can promote the catch-up growth of FGR mice. Metformin intervention is effective for improving insulin resistance and reproductive-endocrine disorders in FGR mice during catch-up growth.

Yi du ( Medicine Reading )was a primer of traditional Chinese medicine. The original author was Wang Ji of the Ming Dynasty, and the book was block-printed and published, after the supplement made by Cheng Yingmao of the Qing Dynasty during the reign of Kangxi Emperor of the Qing Dynasty. The editions of the book preserved in Nanjing Library and China Institute for History of Medicine and Medical Literature of China Academy of Chinese Medical Sciences was the original version in the reign of Kangxi Emperor. The edition in Shanghai University of Traditional Chinese Medicine was the amended version of original version in the reign of Kangxi Emperor. The version of Edo Period in the Cabinet Library of National Archives of Japan was the reprinted edition of the amended version of original version in the reign of Kangxi Emperor. The transcript of Mr . Wang Shishan ' s Medicine Reading of the Qing Dynasty in Nanjing Library and Suzhou Library was the hand-copied version of the original one, with 75 syndromes, including external contraction, internal injuries, woman miscellaneous diseases etc. and all sorts of prescriptions. Cheng Yingmao added his preface, 14 syndromes of children diseases and prescription verse, supplemented general notices, properties of materia medica, pulse manifestations, and revised some texts of pathogenesis to form the 7 volumes. The former 5 volumes of Yi du were in 4-character verses, the 6(th)~7(th) volumes were in 7-character verses, and the pill prescriptions were in prose, which made more convenient for beginners to read, remember, and for recitation.

Aim: To investigate the genetic mutations that are associated the hereditary autosomal dominant cataract in a Chinese family., Methods: A Chinese family consisting of 20 cataract patients (including 9 male and 11 female) and 2 unaffected individuals from 5 generations were diagnosed to be a typical autosomal dominant cataract pedigree. Genomic DNA samples were extracted from the peripheral blood cells of the participants in this pedigree. Exon sequence was used for genetic mutation screening. In silico analysis was used to study the structure characteristics of connexin 46 (CX46) mutant. Immunoblotting was conduceted for testing the expression of CX46., Results: To determine the involved genetic mutations, 11 well-known cataract-associated genes (cryaa, cryab, crybb1, crybb2, crygc, crygd, Gja3, Gja8, Hsf4, Mip and Pitx3) were chosen for genetic mutation test by using exon sequencing. A novel cytosine insertion at position 1195 of CX46 cDNA (c.1194&#95;1195ins C) was found in the samples of 5 tested cataract patients but not in the unaffected 2 individuals nor in normal controls, which resulted in 30 amino acids more extension in CX46C-terminus (cx46fs400) compared with the wild-type CX46. In silico protein structure analysis indicated that the mutant showed distinctive hydrophobicity and protein secondary structure compared with the wild-type CX46. The immunoblot results revealed that CX46 protein, which expressed in the aging cataract lens tissues, was absence in the proband lens. In contrast, CX50, alpha A-crystallin and alphaB-crystallin expressed equally in both proband and aging cataract tissues. Those results revealed that the cx46fs400 mutation could impair CX46 protein expression., Conclusion: The insertion of cytosine at position 1195 of CX46 cDNA is a novel mutation site that is associated with the autosomal dominant cataracts in this Chinese family. The C-terminal frameshift mutation is involved in regulating CX46 protein expression.

High-density genetic maps based on SNPs are essential for fine mapping loci controlling specific traits for fish species. Using restriction-site associated DNA tag sequencing (RAD-Seq) technology, we identified 42,784 SNPs evenly distributed across the Megalobrama amblycephala genome. Based on 2 parents and 187 intra-specific hybridization progenies, a total of 14,648 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs) of maternal and paternal map. The total length of the integrated map was 3,258.38 cM with an average distance of 0.57 cM among 5676 effective loci, thereby representing the first high-density genetic map reported for M. amblycephala. A total of eight positive quantitative trait loci (QTLs) were detected in QTL analysis. Of that, five QTL explained ≥35% of phenotypic variation for growth traits and three QTL explained ≥16% phenotypic variation for gonad related traits. A total of 176 mapped markers had significant hits in the zebrafish genome and almost all of the 24 putative-chromosomes of M. amblycephala were in relatively conserved synteny with chromosomes of zebrafish. Almost all M. amblycephala and zebrafish chromosomes had a 1:1 correspondence except for putative-chromosome 4, which mapped to two chromosomes of zebrafish caused by the difference in chromosome numbers between two species.

The lethal-7 ( let-7 ) miRNA, known as one of the first founding miRNAs, is present in multiple copies in a genome and has diverse functions in animals. In this study, comparative genomic analysis of let-7 miRNAs members in fish species indicated that let-7 miRNA is a sequence conserved family in fish, while different species have the variable gene copy numbers. Among the ten members including let-7a/b/c/d/e/f/g/h/i/j, the let-7a precursor sequence was more similar to ancestral sequences, whereas other let-7 miRNA members were separate from the late differentiation of let-7a. The mostly predicted target genes of let-7 miRNAs are involved in biological process, especially developmental process and growth through Gene Ontology (GO) enrichment analysis. In order to identify the possible different functions of these ten miRNAs in fish growth development, their expression levels were quantified in adult males and females of Megalobrama amblycephala , as well as in 3-, 6-, and 12-months-old individuals with relatively slow- and fast-growth rates. These ten miRNAs had similar tissue expression patterns between males and females, with higher expression levels in the brain and pituitary than that in other tissues ( p < 0.05). Among these miRNAs, the relative expression level of let-7a was the highest among almost all the tested tissues, followed by let-7b , let-7d and let-7c/e/f/g/h/i/j . As to the groups with different growth rates, the expression levels of let-7 miRNAs in pituitary and brain from the slow-growth group were always significantly higher than that in the fast-growth group ( p < 0.05). These results suggest that let-7 miRNA members could play an important role in the regulation of growth development in M. amblycephala through negatively regulating expression of their target genes.

Background: Intermuscular bones (IBs) and ribs both are a part of skeletal system in teleosts, but with different developing process. The chemical composition of fish IBs and ribs as well as the underlying mechanism about their development have not been investigated. In the present study, histological structures showed that one bone cavity containing osteoclasts were existed in ribs, but not in IBs of Megalobrama amblycephala. We constructed the first proteomics map for fish bones including IBs and ribs, and identified the differentially expressed proteins between IBs and ribs through iTRAQ LC-MS/MS proteomic analysis., Results: The proteins extracted from IBs and ribs at 1- to 2-year old M. amblycephala were quantified 2,342 proteins, with 1,451 proteins annotated with GO annotation in biological processes, molecular function and cellular component. A number of bone related proteins as well as pathways were identified in the study. A total of 93 and 154 differently expressed proteins were identified in comparison groups of 1-IB-vs-1-Rib and 2-IB-vs-2-Rib, which indicated the obvious differences of chemical composition between these two bone tissues. The two proteins (vitronectin b precursor and matrix metalloproteinase-2) related to osteoclasts differentiation were significantly up-regulated in ribs compared with IBs (P < 0.05), which was in accordance with the results from histological structures. In comparison groups of 1-IB-vs-2-IB and 1-Rib-vs-2-Rib, 33 and 51 differently expressed proteins were identified and the function annotation results showed that these proteins were involved in regulating bone development and differentiation. Subsequently, 11 and 13 candidate proteins in comparison group of 1-IB-vs-1-Rib and 1-IB-vs-2-IB related to bone development were validated by MRM assays., Conclusions: Our present study suggested the different key proteins involved in the composition of fish ribs and IBs as well as their growth development. These findings could provide important clues towards further understanding of fish skeletal system and the roles of proteins playing in regulating diverse biological processes in fish.

Xin'an imperial medical officials of the Ming and Qing Dynasties was a special group of Xin'an doctors. It had exerted a positive and active impact on the development of traditional Chinese medicine. Rooted in the Xin'an region, with higher literacy and noble medical ethics and medical knowhow, through the imperial enlistment, examination, and other ways to enter the palace as imperial medical officials. During their tenure, they wrote books and communicated and merged with the folk medicine actively. After retiring, they were still involved actively in folk medicine activities, thus promoting and influencing the development of local medicine. The formation of Xin'an community of imperial medical officials in the Ming and Qing Dynasties was closely related to the prosperity of regional culture and commerce, and the development of medicine in Xin'an region.

Obstructed defecation syndrome (ODS) is a functional disorder commonly encountered by colorectal surgeons and gastroenterologists, and greatly affects the quality of life of patients from both societal and psychological aspects. The underlying anatomical and pathophysiological changes of ODS are complex. However, intra-rectal intussusception and rectocele are frequently found in patients with ODS and both are thought to play an important role in the pathogenesis of ODS. With the development of evaluation methods in anorectal physiology laboratories and radiology studies, a great variety of new operative procedures, especially transanal procedures, have been invented to treat ODS. However, no procedure has been proved to be superior to others at present. Each operation has its own merits and defects. Thus, choosing appropriate transanal surgical procedures for the treatment of ODS remains a challenge for all surgeons. This review provides an introduction of the current problems and options for treatment of ODS and a detailed summary of the essential assessments needed for patient evaluation before carrying out transanal surgery. Besides, an overview of the benefits and problems of current transanal surgical procedures for treatment of ODS is summarized in this review. A report of clinical experience of some transanal surgical techniques used in the authors' center is also presented., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests in this article.

Intermuscular bone (IB), which occurs only in the myosepta of lower teleosts, is attracting more attention because they are difficult to remove and make the fish unpleasant to eat. By gaining a better understanding of the genetic regulation of IB development, an integrated analysis of miRNAs and mRNAs expression profiling was performed on Megalobrama amblycephala. Four key development stages were selected for transcriptome and small RNA sequencing. A number of significantly differentially expressed miRNAs/genes associated with bone formation and differentiation were identified and the functional characteristics of these miRNAs/genes were revealed by GO function and KEGG pathway analysis. These were involved in TGF-β, ERK and osteoclast differentiation pathways known in the literature to affect bone formation and differentiation. MiRNA-mRNA interaction pairs were detected from comparison of expression between different stages. The function annotation results also showed that many miRNA-mRNA interaction pairs were likely to be involved in regulating bone development and differentiation. A negative regulation effect of two miRNAs was verified through dual luciferase reporter assay. As a unique public resource for gene expression and regulation during the IB development, this study is expected to provide forwards ideas and resources for further biological researches to understand the IBs' development.

Hybridization plays an important role in fish breeding. Bream fishes contribute a lot to aquaculture in China due to their economically valuable characteristics and the present study included five bream species, Megalobrama amblycephala, Megalobrama skolkovii, Megalobrama pellegrini, Megalobrama terminalis and Parabramis pekinensis. As maternal inheritance of mitochondrial genome (mitogenome) involves species specific regulation, we aimed to investigate in which way the inheritance of mitogenome is affected by hybridization in these fish species. With complete mitogenomes of 7 hybrid groups of bream species being firstly reported in the present study, a comparative analysis of 17 mitogenomes was conducted, including representatives of these 5 bream species, 6 first generation hybrids and 6 second generation hybrids. The results showed that these 17 mitogenomes shared the same gene arrangement, and had similar gene size and base composition. According to the phylogenetic analyses, all mitogenomes of the hybrids were consistent with a maternal inheritance. However, a certain number of variable sites were detected in all F1 hybrid groups compared to their female parents, especially in the group of M. terminalis (♀) × M. amblycephala (♂) (MT×MA), with a total of 86 variable sites between MT×MA and its female parent. Among the mitogenomes genes, the protein-coding gene nd5 displayed the highest variability. The number of variation sites was found to be related to phylogenetic relationship of the parents: the closer they are, the lower amount of variation sites their hybrids have. The second generation hybrids showed less mitogenome variation than that of first generation hybrids. The non-synonymous and synonymous substitution rates (dN/dS) were calculated between all the hybrids with their own female parents and the results indicated that most PCGs were under negative selection.

Background: Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients., Methods and Results: Hybrid positron emission tomography and magnetic resonance using (18)F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery., Conclusions: Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments., (© 2016 American Heart Association, Inc.)

History of Famous Family in Xin'an includes abundant information and important value of the medical cultural history, including the medical family, medical ethics and the number of the famous doctors and its distribution, the medical books and its outline the medical ethics, the diseases. As for the 115 famous doctors recorded in this book, Shexian county owns the most while Jixi county owns the least, and of the average number of famous doctors among the 10, 000 local people, Yixian county owns the most while Xiuning county owns the least. History of Famous Family in Xin'an includes 26 medical books, ranging from medical literature study, gynecological treatment, external medical treatment, diagnosis and treatment of pediatric diseases, ancient medical case records, medical education, acu-moxibustion and summary of other medical experiences. The book also demonstrates the noble morality of doctors, development of doctor' family, and records of paralytic stroke, epistaxis, tuberculous consumptive diseases, furunculosis, dystocia and some infectious diseases.

Background: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study., Methods: 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4-6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed., Results: A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R(2) of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R(2) 0.95, P < 0.0001, bias 0.7 ± 5.1 %)., Conclusions: T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR.

Intermuscular bone (IB), which occurs only in the myosepta of the lower teleosts, is attracting more attention of researchers due to its particular development and lack of genetic information. MicroRNAs (miRNAs) are emerging as important regulators for biological processes. In the present study, miRNAs from IBs and connective tissue (CT; encircled IBs) from six-month-old Megalobrama amblycephala were characterized and compared. The results revealed the sequences and expression levels of 218 known miRNA genes (belonging to 97 families). Of these miRNAs, 44 known microRNA sequences exhibited significant expression differences between the two libraries, with 24 and 20 differentially-expressed miRNAs exhibiting higher expression in the CT and IBs libraries, respectively. The expressions of 11 miRNAs were selected to validate in nine tissues. Among the high-ranked predicted gene targets, differentiation, cell cycle, metabolism, signal transduction and transcriptional regulation were implicated. The pathway analysis of differentially-expressed miRNAs indicated that they were abundantly involved in regulating the development and differentiation of IBs and CT. This study characterized the miRNA for IBs of teleosts for the first time, which provides an opportunity for further understanding of miRNA function in the regulation of IB development.

Objective: To study the effects of erythropoietin (EPO) on serum levels of neuron-specific enolase (NSE) and S-100B in neonates with hypoxic-ischemic encephalopathy (HIE) and the underlying mechanism., Methods: Forty neonates with HIE were randomly divided into conventional treatment (n=20) and EPO treatment groups (n=20). Twenty healthy full-term neonates born during the same period were randomly selected as the normal control group. The conventional treatment group received conventional treatment, while the EPO treatment group received conventional treatment as well as EPO [200 IU/(kg.d)] which was given by intravenous infusion from the second day after birth. The course of treatment was 7 days. Blood samples of the three groups were collected on the first day after birth (before treatment) and the ninth day after birth (after treatment). Serum levels of NSE and S-100B were measured by double-antibody sandwich ABC-ELISA., Results: Before treatment, the two treatment groups had significantly higher serum NSE and S-100B levels than the normal control group (P<0.01), whereas no significant differences in the levels of NSE and S-100B were observed between the conventional treatment and EPO treatment groups (P>0.05). The serum NSE and S-100B levels on the ninth day after birth were significantly lower than those on the first day after birth in the three groups (P<0.01). After treatment, the serum NSE and S-100B levels were significantly lower in the EPO treatment group than in the conventional treatment group (P<0.05)., Conclusions: Dynamic monitoring of serum NSE and S-100B levels may be helpful for the early diagnosis of HIE and the assessment of brain injury repair in newborns with HIE. EPO may be helpful for the repair of neurons and glial cells.

Ovarian cancer is the second most common gynaecological cancer worldwide, and its molecular mechanism has not been completely understood. Ets-1 is a member of the Ets transcription family and can play important roles in the regulation of extracellular matrix remodelling, invasion, angiogenesis and drug resistance in several malignancies, including ovarian cancer. In the current study, we downloaded two datasets from Gene Expression Omnibus database and sought to explore the regulation mechanism of Ets-1 in ovarian cancer by computational analysis of gene expression profiles. Microarray analysis identified a total of 548 genes that were regulated by Ets-1 in ovarian cancer. Functional annotation of these genes revealed that Ets-1 may be involved in several biological processes, both physiological and pathological, such as system development, response to stimulus, vascular endothelial growth factor (VEGF) production, morphogenesis, cell proliferation, cell adhesion and signal transduction. Further, DNA methylation analysis of the DEGs found that 26.5% (145) of them were differentially methylated genes in ovarian cancer. Our results provide insight into the mechanism of Ets-1 regulating the transcription of its target genes in the complex and multistep process of ovarian cancer progression.

MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.

Temperature dependent Raman spectra of BiB3 O6 crystal and its melt were recorded and the microstructure of BiB3 O6 melt was predicted. Multiple theoretical methods including quantum chemistry ab initio calculation and DFT (Density Function Theory) methods were applied to simulate the BiB3 O6 crystal and melt structure and Raman spectra. It was demonstrated that B-O triangles and Bi lattice in the crystal reveal little affected in structure while B-O tetrahedra shows severe distortion with increasing temperature, especially B-O tetrahedra disappears after being completely melt. The microstructure of BiB3 O6 melt consists of six-member ring, [B6 O12](6-), which varies in bond lengths and angles individually. Cation Bi behaves to balance the charge of anion cluster, and the oxygen coordination number of cation Bi is 3, different from the crystal situation in which cation Bi is coordinated with 6 oxygens.

Background: The human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear., Aims: To explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells., Methods: The gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting., Results: The hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA., Conclusions: Increased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.

Objective: To analyse incidence of the severe complications of hypertensive disorder complicating pregnancy and the influence on the outcome of pregnancy., Methods: A retrospective study of 4107 cases among 71 020 cases who delivered in hospitals from 1995 to 2004 in Guangzhou was conducted., Results: The morbidity of hypertensive disorder complicating pregnancy was 5.78%, in which the morbidity of severe pre-eclampsia was 27.78% (1141/4107), of mitis pre-eclampsia was 72.22% (2966/4107). Maternal mortality rate was 0.19% (8/4107), and the specific mortality rate was 11.26/100 000. The proportion of severe complications of hypertensive disorder complicating pregnancy from high to low was as follows: placental abruption 1.68% (69/4107), DIC 1.36% (56/4107), hypertensive disorder complicating pregnancy induced cardiopathy (induced cardiopathy) 1.05% (43/4107), renal failure 0.97% (40/4107), cerebrovascular accident 0.58% (24/4107), and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome 0.51% (21/4107). Mortality caused by severe complications of hypertensive disorder complicating pregnancy were as follows: cerebrovascular accident 17% (4/24), HELLP syndrome 10% (2/21), DIC 5% (3/56) and induced cardiopathy 2% (1/43). The proportion of perinatal mortality from severe complications were as follows: placental abruption 43% (33/77), HELLP syndrome 42% (10/24), DIC 34% (22/64), renal failure 25% (11/44), cerebro vascular accident 24% (6/25) and induced cardiopathy 16% (8/49)., Conclusions: (1) The morbidity of severe complications from high to low are: placental abruption, DIC, induced cardiopathy, renal failure, cerebro vascular accident and HELLP syndrome. (2) The main causes of mortality for gravida and puerperant are: cerebro vascular accident, HELLP syndrome, DIC and induced cardiopathy. (3) The major complications harmful to perinatal newborns are in the order of: placental abruption, HELLP syndrome, DIC, renal failure, cerebro vascular accident and induced cardiopathy.

We report a rare case of partial rhombencephalosynapsis coexistent with Chiari II malformation in a 6-year-old girl and discuss the features of these entities on magnetic resonance imaging.

Objective: To study the clinical application of GnRHa prior to uterine myomectomy and its effect on the clinical outcome of pregnancy., Methods: A retrospective review of the medical records in 20 cases of uterine myomectomy over a period of 6 years was performed. The changes of uterus and myoma volumes in response to preoperative GnRHa was observed, and the rate of relapse in the follow-up, time of impregnation, spontaneous abortion after the impregnation, time of delivery after the operation and the aura threatening uterine rupture, and uterine rupture during the delivery were assessed., Results: Application of GnRHa produced significant improvement in the clinical symptoms and resulted in obviously reduced volumes of the uterus and myoma. The myoma volume reduction was close to 50% in these cases, and relapse occurred in only 1 case. No spontaneous abortion was found after GnRHa application. The average time of pregnancy was 34+/-3.5 weeks, and aura for uterine rupture was found in 1 case at 33 weeks of pregnancy after GnRHa application., Conclusion: Application of GnRHa can correct anemia, decrease the relapse rate of myoma, reduce uterus and myoma volumes, to make possible smaller incision for uterine myomectomy that leaves smaller scar in the uterus and decrease intraoperative bleeding, also relieving endometrial injuries to promote the conditions for impregnation and minimize the risks of uterine rupture and total hysterectomy for the benefit of normal delivery.