Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

Exercise combined with lysine-inositol vitamin B12 promotes height growth in children with idiopathic short stature.

OBJECTIVE: This study was aimed to systematically determine the effect of exercise combined with lysine-inositol vitamin B12 (VB12) therapy on the height of children with idiopathic short stature (ISS). METHODS: Sixty children with ISS were randomly divided into observation and control groups (N = 30). Each group was given lysine-inositol VB12 oral solution (10 mL bid). Simultaneously, the observation group exercised following the "ISS exercise instruction sheet". The height (H), growth velocity (GV), height standard deviation score (HtSDS) and other indicators were compared after 6 and 12 months of intervention, respectively. After 12 months of intervention, the biochemical indicators of the two groups, together with the correlation between the average days of exercise per week and average minutes of exercise per day, GV and serum growth hormone were analyzed. RESULTS: After 6 and 12 months of treatment, the GV, serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels in the observation group were significantly higher than those in the control group, and HtSDS was significantly lower than that in the control group (P<0.01). After 12 months of treatment, the height of the observation group was significantly higher than that of the control group (P<0.05). There was no significant difference in the biochemical indicators between two groups (P>0.05). Average days of exercise per week and average minutes of exercise per day were positively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were negatively correlated. Average minutes of exercise per day were negatively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were positively correlated. CONCLUSION: Regular and moderate stretching exercises combined with lysine-inositol VB12 can effectively promote height growth of children with ISS, which is clinically safe. The mechanism promotes serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels.

Identification and Genome Characterization of Novel Feline Parvovirus Strains Isolated in Shanghai, China.

Feline panleukopenia virus (FPV) is the causative agent of hemorrhagic gastroenteritis in feline animals. FPV has been evolving over time, and there have been several different strains of the virus identified. Some of these strains may be more virulent or more resistant to current vaccines than others, which highlights the importance of ongoing research and monitoring of FPV evolution. For FPV genetic evolution analysis, many studies focus on the main capsid protein (VP2), but limited information is available on the nonstructural gene NS1 and structural gene VP1. In the present study, we firstly isolated two novel FPV strains circulating in Shanghai, China, and performed full-length genome sequencing for the desired strains. Subsequently, we focused on analyzing the NS1, VP1 gene, and the encoding protein, and conducted a comparative analysis among the worldwide circulating FPV and Canine parvovirus Type 2 (CPV-2) strains, which included the strains isolated in this study. We found that the 2 structural viral proteins, VP1 and VP2, are splice variants, and VP1 has a 143 amino-acid-long N-terminal compared to VP2. Furthermore, phylogenetic analysis showed that divergent evolution between FPV and CPV-2 virus strains were clustered mostly by country and year of detection. In addition, much more continuous antigenic type changes happened in the process of CPV-2 circulating and evolution compared to FPV. These results stress the importance of the continuous study of viral evolution and provide a comprehensive perspective of the association between viral epidemiology and genetic evolution.

Phylogenetic Characteristics of Canine Parvovirus Type 2c Variant Endemic in Shanghai, China.

Canine parvovirus type 2 (CPV-2) has spread and mutated globally over the past 40 years. In the present study, 206 samples from dogs suspected of CPV-2 infection were collected from five veterinary clinics in Shanghai city, China. The average positive rate for CPV-2 was detected to be 40.78% using the PCR method. Using an F81 cell (feline kidney cell) culture, the isolates of three CPV-2c strains were obtained. The near full-length genome sequences of the isolates were determined and submitted to GenBank: CPV-SH2001 (MW650830), CPV-SH2002 (MW811188), and CPV-SH2003 (MW811189). By comparing the amino acid sequences of 12 CPV strains with those of 48 related strains retrieved from GenBank, all of the CPV strains from Shanghai were typed as belonging to a relatively new CPV-2c variant spreading in Asia, with typical amino acid residues (5Gly, 267Tyr, 324Ile, and 370Arg) in the VP2 protein. The divergence time of this new CPV-2c clade was estimated by the phylogenetic tree using the maximum likelihood and RelTime with Dated Tips (RTDT) approaches. Our results indicate that the 426 and 324 VP2 amino acid residues are under strong selection pressure with a posterior probability of 0.966 and 0.943, respectively. Therefore, this study provides insight into the phylogenetic characteristics of the current CPV-2c variant in Shanghai city, China.

Genomic Characteristics and Selection Signatures in Indigenous Chongming White Goat (Capra hircus).

The Chongming white goat (CM) is an indigenous goat breed exhibits unique traits that are adapted to the local environment and artificial selection. By performing whole-genome re-sequencing, we generated 14-20× coverage sequences from 10 domestic goat breeds to explore the genomic characteristics and selection signatures of the CM breed. We identified a total of 23,508,551 single-nucleotide polymorphisms (SNPs) and 2,830,800 insertion-deletion mutations (indels) after read mapping and variant calling. We further specifically identified 1.2% SNPs (271,713) and 0.9% indels (24,843) unique to the CM breed in comparison with the other nine goat breeds. Missense (SIFT < 0.05), frameshift, splice-site, start-loss, stop-loss, and stop-gain variants were identified in 183 protein-coding genes of the CM breed. Of the 183, 36 genes, including AP4E1, FSHR, COL11A2, and DYSF, are involved in phenotype ontology terms related to the nervous system, short stature, and skeletal muscle morphology. Moreover, based on genome-wide F ST and pooled heterozygosity (Hp) calculation, we further identified selection signature genes between the CM and the other nine goat breeds. These genes are significantly associated with the nervous system (C2CD3, DNAJB13, UCP2, ZMYND11, CEP126, SCAPER, and TSHR), growth (UCP2, UCP3, TSHR, FGFR1, ERLIN2, and ZNF703), and coat color (KITLG, ASIP, AHCY, RALY, and MC1R). Our results suggest that the CM breed may be differentiated from other goat breeds in terms of nervous system owing to natural or artificial selection. The whole-genome analysis provides an improved understanding of genetic diversity and trait exploration for this indigenous goat breed.

Genetic Dissection of Hypertrophic Cardiomyopathy with Myocardial RNA-Seq.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder of the myocardium, and pathogenic mutations in the sarcomere genes myosin heavy chain 7 (MYH7) and myosin-binding protein C (MYBPC3) explain 60%-70% of observed clinical cases. The heterogeneity of phenotypes observed in HCM patients, however, suggests that novel causative genes or genetic modifiers likely exist. Here, we systemically evaluated RNA-seq data from 28 HCM patients and nine healthy controls with pathogenic variant identification, differential expression analysis, and gene co-expression and protein-protein interaction network analyses. We identified 43 potential pathogenic variants in 19 genes in 24 HCM patients. Genes with more than one variant included the following: MYBPC3, TTN, MYH7, PSEN2, and LDB3. A total of 2538 protein-coding genes, six microRNAs (miRNAs), and 1617 long noncoding RNAs (lncRNAs) were identified differentially expressed between the groups, including several well-characterized cardiomyopathy-related genes (ANKRD1, FHL2, TGFB3, miR-30d, and miR-154). Gene enrichment analysis revealed that those genes are significantly involved in heart development and physiology. Furthermore, we highlighted four subnetworks: mtDNA-subnetwork, DSP-subnetwork, MYH7-subnetwork, and MYBPC3-subnetwork, which could play significant roles in the progression of HCM. Our findings further illustrate that HCM is a complex disease, which results from mutations in multiple protein-coding genes, modulation by non-coding RNAs and perturbations in gene networks.

The complete mitochondrial genome of Microtus fortis calamorum (Arvicolinae, Rodentia) and its phylogenetic analysis.

Microtus fortis is a special resource of rodent in China. It is a promising experimental animal model for the study on the mechanism of Schistosome japonicum resistance. The first complete mitochondrial genome sequence for Microtus fortis calamorum, a subspecies of M. fortis (Arvicolinae, Rodentia), was reported in this study. The mitochondrial genome sequence of M. f. calamorum (Genbank: JF261175) showed a typical vertebrate pattern with 13 protein coding genes, 2 ribosomal RNAs, 22 transfer RNAs and one major noncoding region (CR region).The extended termination associated sequences (ETAS-1 and ETAS-2) and conserved sequence block 1 (CSB-1) were found in the CR region. The putative origin of replication for the light strand (O(L)) of M. f. calamorum was 35bp long and showed high conservation in stem and adjacent sequences, but the difference existed in the loop region among three species of genus Microtus. In order to investigate the phylogenetic position of M. f. calamorum, the phylogenetic trees (Maximum likelihood and Bayesian methods) were constructed based on 12 protein-coding genes (except for ND6 gene) on H strand from 16 rodent species. M. f. calamorum was classified into genus Microtus, Arvcicolinae for the highly phylogenetic relationship with Microtus kikuchii (Taiwan vole). Further phylogenetic analysis results based on the cytochrome b gene ranged from M. f. calamorum to one of the subspecies of M. fortis, which formed a sister group of Microtus middendorfii in the genus Microtus.