ALBINO EMBRYO AND SEEDLING is required for RNA splicing and chloroplast homeostasis in Arabidopsis.

Pentatricopeptide repeat (PPR) proteins form a large protein family and have diverse functions in plant development. Here, we identified an ALBINO EMBRYO AND SEEDLING (AES) gene that encodes a P-type PPR protein expressed in various tissues, especially the young leaves of Arabidopsis (Arabidopsis thaliana). Its null mutant aes exhibited a collapsed chloroplast membrane system, reduced pigment content and photosynthetic activity, decreased transcript levels of PEP (plastid-encoded polymerase)-dependent chloroplast genes, and defective RNA splicing. Further work revealed that AES could directly bind to psbB-psbT, psbH-petB, rps8-rpl36, clpP, ycf3, and ndhA in vivo and in vitro and that the splicing efficiencies of these genes and the expression levels of ycf3, ndhA, and cis-tron psbB-psbT-psbH-petB-petD decreased dramatically, leading to defective PSI, PSII, and Cyt b6f in aes. Moreover, AES could be transported into the chloroplast stroma via the TOC-TIC channel with the assistance of Tic110 and cpSRP54 and may recruit HCF244, SOT1, and CAF1 to participate in the target RNA process. These findings suggested that AES is an essential protein for the assembly of photosynthetic complexes, providing insights into the splicing of psbB operon (psbB-psbT-psbH-petB-petD), ycf3, and ndhA, as well as maintaining chloroplast homeostasis.

Rice DSP controls stigma, panicle and tiller primordium initiation.

Tiller and seed number are key determinants of rice (Oryza sativa) yield. These traits are mainly affected by tiller, panicle, spikelet and stigma formation, but to date, no single gene involved in the development of all these organs has been identified. Here, we found a rice mutant defective stigma and panicle (dsp) with greatly reduced numbers of tillers and panicle branches, and ovaries lacking stigmas, due to defects in primordium initiation. We cloned DSP using sequencing-based mapping and verified its function with the CRISPR/Cas9 system. DSP encodes a transcription factor containing an APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) domain that recognizes the GCC motif and a transcription-activating domain at the site of 244-314 that contains an angiosperm-related (AR) motif. Mutating the AR motif resulted in the dsp mutant phenotypes, whereas mutating the AP2/ERF domain led to seedling death. DSP directly regulated PINOID (PID) expression to determine the emergence of rice stigmas, and PID overexpression partially rescued the stigma defect in the dsp cr2-8 and dsp mutants. Moreover, DSP indirectly affected LAX PANICLE1 (LAX1) expression to determine tiller primordium formation and synergistically regulated panicle primordium development. Our results indicated that DSP was a key regulator that modulated different genetic pathways to control the initiation of stigma primordia, the axillary meristem formation of tillers and panicle branches, which revealed their molecular mechanisms and cross-networks, laying the vital foundation for rice yield and trait improvement.

Tracheal extubation under Narcotrend EEG monitoring at different depths of anesthesia after tonsillectomy in children: a prospective randomized controlled study.

Objective: This study aims to investigate whether tracheal extubation at different depths of anesthesia using Narcotrend EEG (NT value) can influence the recovery quality from anesthesia and cognitive function of children who underwent tonsillotomy. Methods: The study enrolled 152 children who underwent tonsillotomy and were anesthetized with endotracheal intubation in our hospital from September 2019 to March 2022. These patients were divided into Group A (conscious group, NT range of 95-100), Group B (light sedation group, NT range of 80-94), and Group C (conventional sedation group, NT range of 65-79). A neonatal pain assessment tool, namely, face, legs, activity, cry, and consolability (FLACC), was used to compare the pain scores of the three groups as the primary end point. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were used to evaluate the cognitive function of children in the three groups before and after surgery as the secondary end points. Results: Differences were observed in the awakening time and FLACC scores after awakening among the three groups (P < 0.05). Among them, Group A exhibited a significantly shorter awakening time and higher FLACC score after awakening than those in Groups B and C (both P < 0.05). The total incidence of adverse reactions in Group B was significantly lower than that in Groups A and C (P < 0.05). No significant difference was observed in MMSE and MoCA scores before the operation and at 7 days after the operation among the three groups (P > 0.05), but a significant difference was found in MMSE and MoCA scores at 1 day and 3 days after the operation among the three groups (P < 0.05). In addition, MMSE and MoCA scores of the three groups decreased significantly at 1 day and 3 days after the operation than those at 1 day before the operation (P < 0.05). Conclusion: When the NT value of tonsillectomy is between 80 and 94, tracheal catheter removal can effectively improve the recovery quality and postoperative cognitive dysfunction of children.

Hyperoside alleviates postmenopausal osteoporosis via regulating miR-19a-5p/IL-17A axis.

PROBLEM: Postmenopausal osteoporosis (PMO) is a common osteoporosis. Hyperoside (Hyp), a natural flavonoid compound, has anti-osteoporotic effects, but the underlying mechanisms remain poorly understood. Inflammatory cytokine IL-17A is upregulated in PMO and plays vital roles in bone loss, but the upstream regulatory factors and mechanisms are still unknown. METHOD OF STUDY: Twenty PMO patients and 20 healthy control subjects were included to analyze IL-17A expression changes and screen dys-regulated miRNAs in the peripheral blood of PMO patients. miR-19a-5p mimics and inhibitor were transfected into RAW264.7 osteoclasts, and injected into bilateral ovariectomized (OVX) mice to explore the regulatory effect of miR-19a-5p on IL-17A. OVX mice were randomly grouped and treated with different doses of Hyp to uncover the effective targets for the medicine in PMO disease. RESULTS: MiR-19a-5p was downregulated in PMO patients and the expression level was negatively correlated with that of IL-17A. miR-19a-5p could directly bind to the 3'UTR of IL-17A and regulate its expression. Both in vitro and in vivo studies demonstrated that miR-19a-5p mimics decreased the expression of IL-17A, RANK and Cathepsin K, while miR-19a-5p inhibitor significantly increased the expression of IL-17A, RANK, and Cathepsin K. Importantly, the Hyp could improve bone structure of OVX mice by enhancing miR-19a-5p-mediated IL-17A downregulation. CONCLUSION: Overall, these data demonstrated that miR-19a-5p/IL-17A axis might serve as novel therapeutic candidate for PMO. Hyp could relieve bone resorption by targeting the miR-19a-5p/IL-17A axis in OVX mice and exhibited prospective for the treatment of PMO.

Clinical Application of Ultrasound Microscopy-Guided Pediatric Brachial Plexus Nerve Block Anesthesia.

In order to investigate the anesthetic effect and safety of the ultrasound-guided brachial plexus block in pediatric upper limb surgery, this study retrospectively analyzed the anesthetic effect of the ultrasound-guided brachial plexus block in pediatric upper limb surgery. From January 2016 to December 2017, 82 children undergoing upper limb surgery in hospital A were selected and randomly divided into two groups by the coin method, with 41 children in each group. Ultrasound-guided brachial plexus block anesthesia and conventional anatomic localization brachial plexus block anesthesia were performed. The anesthetic drug dosage of sensory block at anesthesia completion time and motor block at onset time was compared between the two groups; the one-time puncture success rate and incidence of anesthesia complications were compared between the two groups (local anesthesia poisoning, nerve injury, pneumothorax, hematoma, and phrenic nerve palsy). The results showed that the anesthesia completion time in the study group was slightly longer than that in the control group. The sensory and motor block occurred earlier in the study group than in the control group. Low doses of narcotic drugs are used. The one-time puncture success rate of the study group was higher than that of the control group. The incidence of anesthesia complications was lower than that of the control group. The one-time puncture success rate was 92.8% in the study group and 75.7% in the control group. Ultrasound-guided brachial plexus block anesthesia has a significant effect in pediatric upper limb surgery, which can improve the anesthetic effect and reduce the incidence of complications, and is worthy of clinical promotion.

miR-513c-5p Suppression Aggravates Pyroptosis of Endothelial Cell in Deep Venous Thrombosis by Promoting Caspase-1.

Deep vein thrombosis (DVT) is a common peripheral vascular disease. Secondary pulmonary embolism (PE) caused by DVT leads to substantial patient death. Inflammation has been suggested as a key factor in the pathophysiology of DVT, however, involvement of pyroptosis-related inflammatory factors in DVT formation remains unclear. Here, we proposed that post-transcriptional modification of caspase-1 might be a crucial trigger for enhanced pyroptosis in vascular endothelial cells (VECs), and consequently contributed to severer symptoms in DVT patients. In order to explore the involvement of pyroptosis in DVT, peripheral blood mononuclear cells were collected from 30 DVT patients, and compared with the healthy controls, we found caspase-1 was increased both in mRNA and protein levels. miRNA microarray analysis demonstrated that down-regulated miR-513c-5p was significantly negatively correlated with the expression of caspase-1. In vitro assays suggested that miR-513c-5p overexpression could ameliorate the expression of caspase-1, and thus decreased the production of cleaved gasdermin D (GSDMD) and interleukin (IL)-1ß and IL-18 in VECs. The dual-luciferase reporter assay identified direct binding between miR-513c-5p and the 3' untranslated region of caspase-1 encoding gene. The administration of miR-513c-5p mimics through tail vein injection or caspase-1 inhibitor (vx-765) by intraperitoneal injection remarkably decreased the volume of blood clots in vivo, whereas miR-513c-5p inhibitor aggravated thrombosis formation and this effect was dramatically weakened when treated in combination with vx-765. Collectively, these results revealed that the pyroptosis of VECs induced by decreased miR-513c-5p was involved in DVT progression and indicated a potential therapeutic strategy of targeting the miR-513c-5p/caspase-1/GSDMD signal axis for DVT management.

Effectiveness comparisons of Chinese patent medicine on insomnia: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: In recent years, the incidence of insomnia is increasing. However, the existing therapy methods for cannot fundamentally treat the disease. Meanwhile, Chinese patent medicine (CPM) plays an active role in the treatment of insomnia. However, there is no comparison and ranking of the efficacy of every CPM. Therefore, our study will use network meta-analysis to compare the efficacy of different CPM on insomnia, in order to provide evidence-based medical evidence for clinical treatment. METHODS: We will search CNKI, Wanfang, VIP, CBM, Pubmed, Cochrane Library, Embase for the randomized controlled trials of CPM in the treatment of insomnia (up to December 31, 2020). We will use RevMan5.3, Stata15.1 and ADDIS software for statistical analysis. We will draw the surface under cumulative ranking area to predict the order of efficacy. RESULTS: We aim to rank the efficacy and safety of different CPM for the treatment of insomnia. CONCLUSION: CPM plays a positive role in the treatment of insomnia and can provide evidence support for clinicians and patients. INPLASY REGISTRATION NUMBER: INPLASY2020120121.

Comparison of efficacy and safety of complementary and alternative therapies for scapulohumeral periarthritis: A protocol for Bayesian network meta-analysis.

BACKGROUND: Scapulohumeral periarthritis is a disease with high incidence and great pain. The current western treatments with many side effects, poor efficacy cannot fundamentally solve the problem. Complementary and alternative therapies have played an excellent role in the treatment of scapulohumeral periarthritis. However, it is not clear which complementary and alternative therapy is more effective. Therefore, we propose a protocol to compare the efficacy and safety of various complementary and alternative therapies through network meta-analysis (NMA) to provide choice guidance for the therapy. METHODS: A comprehensive search will be conducted for randomized controlled trials of complementary and alternative therapy for scapulohumeral periarthritis as well as ongoing trials. The time limit is from the establishment of the database until January 2021. Literature and data extraction were completed independently by two researchers. Through pairwise comparison and meta-analysis of Bayesian NMA, all the evidences are evaluated comprehensively. STATA16.0 and WinBUGS1.4.3 software will be used for data processing and analysis, and recommendation evaluation will be used to develop and assess grades to classify the quality of NMA evidence. RESULTS: Through the analysis, we will obtain the ranking of the efficacy and safety of different complementary and alternative therapies in the treatment of scapulohumeral periarthritis, in order to provide reference for clinical selection of treatment methods. CONCLUSION: Complementary and alternative therapies of scapulohumeral periarthritis plays a positive role in improving the symptoms of scapulohumeral periarthritis. This study can provide evidence support for clinicians and patients.International Platform of Registered Systematic Review and Meta-Analysis Protocols registration number: INPLASY202140044.

Effectiveness comparisons of Chinese patent medicine on sciatica: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Sciatica is one of the common clinical diseases. Studies have proved the efficacy of Chinese patent medicine (CPM) in the treatment of sciatica, so far, there has not been a complete systematic review of its effectiveness and safety, and the comparative efficacy and safety of CPM have not been ranked. Therefore, it is necessary to evaluate the efficacy and safety of these CPM by means of systematic review and network meta-analysis (NMA), and to compare them in order. METHODS: We will search PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, CBM and other databases for RCTs of CPM in the treatment of sciatica, (database established until December 30, 2020). In addition, we will manually search the "Pharmaceutical Information", "National Essential Drug List", "Chinese Pharmacopoeia", etc. to inquire about drug instructions, and screen the market circulation and clinically commonly used CPM. We will use RevMan software, gemtc package, GeMTC software for statistical analysis, and draw the surface under cumulative ranking area (SUCRA) to predict the order of curative effect of treatment measures. RESULTS: Our study will compare and evaluate the effectiveness of CPM in the treatment of sciatica, and rank different CPM. The outcome indicators will include clinical efficacy, pain degree, lumbar spine function and adverse events. CONCLUSION: Our research will provide support for clinical practice. INPLASY REGISTRATION NUMBER: INPLASY2020110073.

Comparison of efficacy and safety of complementary and alternative therapies for Parkinson's disease: A Bayesian network meta-analysis protocol.

BACKGROUND: In recent years, the incidence of Parkinson's disease (PD) has been on the rise. However, the existing therapy of PD cannot fundamentally treat the disease. Meanwhile, the complementary and alternative therapies of PD have played a positive role in the treatment of PD. Traditional meta-analysis was only able to compare 2 interventions, while the efficacy and safety of many complementary and alternative therapies were not comparable. Therefore, this study compared the efficacy and safety of different complementary and alternative therapies through network meta-analysis (NMA). METHODS: A comprehensive search of randomized controlled trials of complementary and alternative therapies for PD, as well as trials currently in progress, will be conducted until August 2020. Literature and data extraction were independently completed by two researchers. Through the meta-analysis of pairwise comparison and Bayesian NMA, all evidences are comprehensively evaluated. Use STATA15.0 and WinBUGS1.4.3 software for data processing and analysis, and use grading of recommendations assessment development and evaluation to classify the quality of evidence in the NMA. RESULTS: The aim of this study is to obtain a ranking of efficacy and safety of different complementary and alternative therapies for PD. CONCLUSION: Complementary and alternative therapies for PD have positive significance in improving the symptoms of PD, and can provide evidence support for clinicians and patients. INPLASY REGISTRATION NUMBER: INPLASY202080079.

Comparison of efficacy and safety of Chinese patent medicine in the treatment of postmenopausal osteoporosis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is the focus and difficult problem in the world at present, and we found that Chinese patent medicine(CPM) shown a more miraculous effect. Many kinds of Chinese patent medicine have been proved to be effective in the treatment of this disease, but it is still unclear which kind of Chinese patent medicine has the best effect. Therefore, we propose a network meta-analysis (NMA) protocol to observe the efficacy of various CPM for this disease and provide guidance for clinical practice. METHODS: We will use the NMA method to complete this study. First, all the randomized controlled trials of CPM or CPM combined with western medicine in the treatment of PMOP were collected by searching all online Chinese and English databases. The information time limit is from the establishment of the database to August 30, 2020. Then 2 staff members will sift through all the literature and analyze the data using Stata and Winbugs. RESULTS: Through this analysis, we will observe and rank the clinical effects of different CPM for PMOP. The main evaluation indexes include: New fracture, Quality of life, Severe side effects, Death from all causes. Secondary outcome indicators include Bone Mineral density, clinical efficiency, and some laboratory indicators, such as estradiol, serum calcium, serum, etc. CONCLUSION:: This study will rank the therapeutic effects of various proprietary Chinese medicines in the treatment of PMOP, which will be helpful in improving the PMOP treatment regimen.INPLASY registration number: INPLASY202090047.

Whole-Transcriptome Selection and Evaluation of Internal Reference Genes for Expression Analysis in Protocorm Development of Dendrobium officinale Kimura et Migo.

Dendrobium officinale Kimu et Migo has increased many researchers' interest for its high medical and horticultural values and the molecular mechanism of its protocorm development remains unclear. In this study, 19 genes from 26 most stably expressed genes in whole transcriptome of protocorms and 5 housekeeping genes were used as candidate reference genes and screened with 4 application softwares (geNorm, NormFinder, BestKeeper and RefFinder). The results showed that a few reference genes could effectively normalize expression level of specific genes in protocorm development and the optimal top 2 reference genes were ASS and APH1L. Meanwhile, validation of GNOM, AP2 and temperature induced gene (TIL) for normalization demonstrates the usefulness of the validated candidate reference genes. The expression profiles of these genes varied under protocorms and temperature stress according to the stablest and unstablest reference genes, which proved the importance of the choice of appropriate reference genes. The first systematic evaluation of stably expressed genes will be very useful in the future analysis of specific genes expression in D. officinale.

An increased duplication of ZRS region that caused more than one supernumerary digits preaxial polydactyly in a large Chinese family.

Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear. In this article, we reported a family case of more than one redundant finger polydactyly on the thumb side for bilateral hands with a pedigree chart of the family. Results of quantitative PCR (qPCR) and sequence analysis suggested that the relative copy number (RCN) of ZRS but not point mutation (including insertion and deletion) was involved in all affected individuals.