N6-methyladenine DNA modification in Drosophila.

DNA N(6)-methyladenine (6mA) modification is commonly found in microbial genomes and plays important functions in regulating numerous biological processes in bacteria. However, whether 6mA occurs and what its potential roles are in higher-eukaryote cells remain unknown. Here, we show that 6mA is present in Drosophila genome and that the 6mA modification is dynamic and is regulated by the Drosophila Tet homolog, DNA 6mA demethylase (DMAD), during embryogenesis. Importantly, our biochemical assays demonstrate that DMAD directly catalyzes 6mA demethylation in vitro. Further genetic and sequencing analyses reveal that DMAD is essential for development and that DMAD removes 6mA primarily from transposon regions, which correlates with transposon suppression in Drosophila ovary. Collectively, we uncover a DNA modification in Drosophila and describe a potential role of the DMAD-6mA regulatory axis in controlling development in higher eukaryotes.

Aberrant DNA N6 -methyladenine incorporation via adenylate kinase 1 is suppressed by ADAL deaminase-dependent 2'-deoxynucleotide pool sanitation.

Intracellular decay of N6 -methyladenine (m6A)-containing RNA potentially induces aberrant N6 -methyl-2'-adenine (6mdA) misincorporation into DNA. Biophysically, misincorporated 6mdA may destabilize the DNA duplex in a manner similar to bona fide methylated 6mdA DNA, thereby affecting DNA replication and transcription. Utilizing heavy stable isotope labeling and ultrasensitive UHPLC-MS/MS assay, we demonstrate that intracellular m6A-RNA decay does not generate free 6mdA species, nor lead to any misincorporated DNA 6mdA in most mammalian cell lines tested, unveiling the existence of a sanitation mechanism that prevents 6mdA misincorporation. Depletion of deaminase ADAL increases the levels of free 6mdA species, concomitant with the presence of DNA-misincorporated 6mdA resulting from intracellular RNA m6A decay, suggesting that ADAL catabolizes 6mdAMP in vivo. Furthermore, we show that the overexpression of adenylate kinase 1 (AK1) promotes 6mdA misincorporation, while AK1 knockdown diminishes 6mdA incorporation, in ADAL-deficient cells. We conclude that ADAL together with other factors (such as MTH1) contributes to 2'-deoxynucleotide pool sanitation in most cells but compromised sanitation (e.g., in NIH3T3 cells) and increased AK1 expression may facilitate aberrant 6mdA incorporation. This sanitation mechanism may provide a framework for the maintenance of the epigenetic 6mdA landscape.

RNA 5-Methylcytosine Facilitates the Maternal-to-Zygotic Transition by Preventing Maternal mRNA Decay.

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity.

ABSTRACT: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.

Flanking strand separation activity of RecA nucleoprotein filaments in DNA strand exchange reactions.

The recombinase RecA/Rad51 ATPase family proteins catalyze paramount DNA strand exchange reactions that are critically involved in maintaining genome integrity. However, it remains unclear how DNA strand exchange proceeds when encountering RecA-free defects in recombinase nucleoprotein filaments. Herein, by designing a series of unique substrates (e.g. truncated or conjugated incoming single-stranded DNA, and extended donor double-stranded DNA) and developing a two-color alternating excitation-modified single-molecule real-time fluorescence imaging assay, we resolve the two key steps (donor strand separation and new base-pair formation) that are usually inseparable during the reaction, revealing a novel long-range flanking strand separation activity of synaptic RecA nucleoprotein filaments. We further evaluate the kinetics and free energetics of strand exchange reactions mediated by various substrates, and elucidate the mechanism of flanking strand separation. Based on these findings, we propose a potential fundamental molecular model involved in flanking strand separation, which provides new insights into strand exchange mechanism and homologous recombination.

Ultracoherent Gigahertz Diamond Spin-Mechanical Lamb Wave Resonators.

We report the development of an all-optical approach that excites the fundamental compression mode in a diamond Lamb wave resonator with an optical gradient force and detects the induced vibrations via strain coupling to a silicon vacancy center, specifically, via phonon sidebands in the optical excitation spectrum of the silicon vacancy. Sideband optical interferometry has also been used for the detection of in-plane mechanical vibrations, for which conventional optical interferometry is not effective. These experiments demonstrate a gigahertz fundamental compression mode with a Q factor of >107 at temperatures near 7 K, providing a promising platform for reaching the quantum regime of spin mechanics, especially phononic cavity quantum electrodynamics of electron spins.

RNA-Activated CRISPR/Cas12a Nanorobots Operating in Living Cells.

Active clustered regularly interspaced short palindromic repeats (CRISPR/Cas12a) systems possess both cis-cleavage (targeted) and trans-cleavage (collateral) activities, which are useful for genome engineering and diagnostic applications. Both single- and double-stranded DNA can activate crRNA-Cas12a ribonucleoprotein (RNP) to achieve cis- and trans-cleavage enzymatic activities. However, it is not clear whether RNA can activate the CRISPR/Cas12a system and what is critical to the trans-cleavage activity. We report here that RNA can activate the CRISPR/Cas12a system and trigger its trans-cleavage activity. We reveal that the activated crRNA-Cas12a RNP favors the trans-cleavage of longer sequences than commonly used. These new findings of the RNA-activated trans-cleavage capability of Cas12a provided the foundation for the design and construction of CRISPR nanorobots that operate in living cells. We assembled the crRNA-Cas12a RNP and nucleic acid substrates on gold nanoparticles to form CRISPR nanorobots, which dramatically increased the local effective concentration of the substrate in relation to the RNP and the trans-cleavage kinetics. Binding of the target microRNA to the crRNA-Cas12a RNP activated the nanorobots and their trans-cleavage function. The repeated (multiple-turnover) trans-cleavage of the fluorophore-labeled substrates generated amplified fluorescence signals. Sensitive and real-time imaging of specific microRNA in live cells demonstrated the promising potential of the CRISPR nanorobot system for future applications in monitoring and modulating biological functions within living cells.

Accurate Quantification of Ten Methylated Purine Nucleosides by Highly Sensitive and Stable Isotope-Diluted UHPLC-MS/MS.

The dynamic landscape of cellular nucleotides/nucleosides associated with RNA metabolism, particularly in diseases like cancer, has spurred intensive interest. Here, we report a robust stable isotope-diluted UHPLC-ESI-MS/MS method for accurate quantification of 12 purine ribonucleosides, including 10 methylated purine nucleosides. By the use of thermally decomposable ammonium bicarbonate (NH4HCO3) as a mobile phase additive for UHPLC-MS/MS detection, the ESI-MS/MS signal responses of these target compounds were enhanced by 1.7-24.5 folds. Noteworthily, three methylated guanosine isomers (m1G, m2G, and m7G) and two methylated adenosine isomers (m1A and m6A) that are indistinguishable directly by mass spectrometry were well resolved with optimal UHPLC separation. Combined with methanol extraction and solid-phase extraction (SPE) pretreatment, the method quantified intracellular concentrations of three modified nucleosides (Gm, m1G, and m2G), which would otherwise be undetectable because of significant suppression of their signals by the interfering cellular matrix. Nine purine nucleosides were simultaneously quantified in 293T cells, and their concentrations ranged by 4 orders of magnitude. Overall, the method presents high recovery rates over 90% for endogenous modified purine nucleosides in cultured cells, along with good precision, linearity, and LOD ranging from 0.30 fmol to 0.37 pmol per 5 × 105 cells. The developed UHPLC-MS/MS method holds potential for screening purine nucleosides as diagnostic and prognostic biomarkers and for quantifying purine epigenetic nucleosides post-cell metabolome analysis, thereby providing a valuable analytical tool for intracellular nucleoside quantification in future clinical research.

Identification and characterization of circular RNAs involved in the fertility stability of cotton CMS-D2 restorer line under heat stress.

BACKGROUND: As a vital type of noncoding RNAs, circular RNAs (circRNAs) play important roles in plant growth and development and stress response. However, little is known about the biological roles of circRNAs in regulating the stability of male fertility restoration for cytoplasmic male sterility (CMS) conditioned by Gossypium harknessii cytoplasm (CMS-D2) cotton under high-temperature (HT) stress. RESULTS: In this study, RNA-sequencing and bioinformatics analysis were performed on pollen grains of isonuclear alloplasmic near-isogenic restorer lines NH [N(Rf1rf1)] and SH [S(Rf1rf1)] with obvious differences in fertility stability under HT stress at two environments. A total of 967 circRNAs were identified, with 250 differentially expressed under HT stress. We confirmed the back-splicing sites of eight selected circRNAs using divergent primers and Sanger sequencing. Tissue-specific expression patterns of five differentially expressed circRNAs (DECs) were also verified by RT-PCR and qRT-PCR. Functional enrichment and metabolic pathway analysis revealed that the parental genes of DECs were significantly enriched in fertility-related biological processes such as pollen tube guidance and cell wall organization, as well as the Pentose and glucuronate interconversions, Steroid biosynthesis, and N-Glycan biosynthesis pathways. Moreover, we also constructed a putative circRNA-mediated competing endogenous RNA (ceRNA) network consisting of 21 DECs, eight predicted circRNA-binding miRNAs, and their corresponding 22 mRNA targets, especially the two ceRNA modules circRNA346-miR159a-MYB33 and circRNA484-miR319e-MYB33, which might play important biological roles in regulating pollen fertility stability of cotton CMS-D2 restorer line under HT stress. CONCLUSIONS: Through systematic analysis of the abundance, characteristics and expression patterns of circRNAs, as well as the potential functions of their parent genes, our findings suggested that circRNAs and their mediated ceRNA networks acted vital biological roles in cotton pollen development, and might be also essential regulators for fertility stability of CMS-D2 restorer line under heat stress. This study will open a new door for further unlocking complex regulatory mechanisms underpinning the fertility restoration stability for CMS-D2 in cotton.

Ustilaginoidea virens-secreted effector Uv1809 suppresses rice immunity by enhancing OsSRT2-mediated histone deacetylation.

Rice false smut caused by Ustilaginoidea virens is a devastating rice (Oryza sativa) disease worldwide. However, the molecular mechanisms underlying U. virens-rice interactions are largely unknown. In this study, we identified a secreted protein, Uv1809, as a key virulence factor. Heterologous expression of Uv1809 in rice enhanced susceptibility to rice false smut and bacterial blight. Host-induced gene silencing of Uv1809 in rice enhanced resistance to U. virens, suggesting that Uv1809 inhibits rice immunity and promotes infection by U. virens. Uv1809 suppresses rice immunity by targeting and enhancing rice histone deacetylase OsSRT2-mediated histone deacetylation, thereby reducing H4K5ac and H4K8ac levels and interfering with the transcriptional activation of defence genes. CRISPR-Cas9 edited ossrt2 mutants showed no adverse effects in terms of growth and yield but displayed broad-spectrum resistance to rice pathogens, revealing a potentially valuable genetic resource for breeding disease resistance. Our study provides insight into defence mechanisms against plant pathogens that inactivate plant immunity at the epigenetic level.

Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma.

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.

Chlorobenzoquinones Aggravate RSL3-Induced Ferroptosis in ROS-Dependent Manner.

Chlorobenzoquinones (CBQs) are a class of emerging water disinfection byproducts that pose significant risks to public health. In this study, we found that three CBQs (tetrachloro-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone, and 2-chloro-1,4-benzoquinone) can significantly aggravate cell death caused by Ras-selective lethal small molecule 3 (RSL3). Further study showed that the cell death caused by CBQs, either alone or in combination with RSL3, was related to iron accumulation and GPX4 inactivation, suggesting the occurrence of ferroptosis. Furthermore, reactive oxygen species are found to play a potential key role in mediating the toxicity of CBQs in CBQs and RSL3-induced ferroptosis. These findings will be helpful in understanding the toxic mechanism of CBQs to mammalian cells.

Ligand Modification-Free Methods for the Profiling of Protein-Environmental Chemical Interactions.

Adverse health outcomes caused by environmental chemicals are often initiated via their interactions with proteins. Essentially, one environmental chemical may interact with a number of proteins and/or a protein may interact with a multitude of environmental chemicals, forming an intricate interaction network. Omics-wide protein-environmental chemical interaction profiling (PECI) is of prominent importance for comprehensive understanding of these interaction networks, including the toxicity mechanisms of action (MoA), and for providing systematic chemical safety assessment. However, such information remains unknown for most environmental chemicals, partly due to their vast chemical diversity. In recent years, with the continuous efforts afforded, especially in mass spectrometry (MS) based omics technologies, several ligand modification-free methods have been developed, and new attention for systematic PECI profiling was gained. In this Review, we provide a comprehensive overview on these methodologies for the identification of ligand-protein interactions, including affinity interaction-based methods of affinity-driven purification, covalent modification profiling, and activity-based protein profiling (ABPP) in a competitive mode, physicochemical property changes assessment methods of ligand-directed nuclear magnetic resonance (ligand-directed NMR), MS integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), thermal proteome profiling (TPP), limited proteolysis-coupled mass spectrometry (LiP-MS), stability of proteins from rates of oxidation (SPROX), and several intracellular downstream response characterization methods. We expect that the applications of these ligand modification-free technologies will drive a considerable increase in the number of PECI identified, facilitate unveiling the toxicological mechanisms, and ultimately contribute to systematic health risk assessment of environmental chemicals.

Benefit of axicabtagene ciloleucel versus chemoimmunotherapy in older patients and/or patients with poor ECOG performance status with relapsed or refractory large B-cell lymphoma after 2 or more lines of prior therapy.

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow-up of 24 months for patients receiving axi-cel and 60 months for patients receiving CIT, 12-month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24-0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi-cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi-cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi-cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi-cel in older patients and patients with ECOG PS = 2 with R/R LBCL.

Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1.

Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase1,2. Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions2-4. However, how such a unique feature of the oocyte methylome is determined and its contribution to the developmental competence of the early embryo remains largely unknown. Here we demonstrate the importance of Stella, a factor essential for female fertility5-7, in shaping the oocyte methylome in mice. Oocytes that lack Stella acquire excessive DNA methylation at the genome-wide level, including in the promoters of inactive genes. Such aberrant hypermethylation is partially inherited by two-cell-stage embryos and impairs zygotic genome activation. Mechanistically, the loss of Stella leads to ectopic nuclear accumulation of the DNA methylation regulator UHRF18,9, which results in the mislocalization of maintenance DNA methyltransferase DNMT1 in the nucleus. Genetic analysis confirmed the primary role of UHRF1 and DNMT1 in generating the aberrant DNA methylome in Stella-deficient oocytes. Stella therefore safeguards the unique oocyte epigenome by preventing aberrant de novo DNA methylation mediated by DNMT1 and UHRF1.

Cooperative Action between SALL4A and TET Proteins in Stepwise Oxidation of 5-Methylcytosine.

TET family enzymes successively oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, leading to eventual demethylation. 5hmC and TET enzymes occupy distinct chromatin regions, suggesting unknown mechanisms controlling the fate of 5hmC within diverse chromatin environments. Here, we report that SALL4A preferentially associates with 5hmC in vitro and occupies enhancers in mouse embryonic stem cells in a largely TET1-dependent manner. Although most 5hmC at SALL4A peaks undergoes further oxidation, this process is abrogated upon deletion of Sall4 gene, with a concomitant reduction of TET2 at these regions. Thus, SALL4A facilitates further oxidation of 5hmC at its binding sites, which requires its 5hmC-binding activity and TET2, supporting a collaborative action between SALL4A and TET proteins in regulating stepwise oxidation of 5mC at enhancers. Our study identifies SALL4A as a 5hmC binder, which facilitates 5hmC oxidation by stabilizing TET2 association, thereby fine-tuning expression profiles of developmental genes in mouse embryonic stem cells.

Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.

The regulatory role of N(6)-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in pre-mRNA splicing remains an enigma. Here we show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 (SRp20) while blocking SRSF10 (SRp38) mRNA binding. Transcriptome assay with PAR-CLIP-seq analysis revealed that YTHDC1-regulated exon-inclusion patterns were similar to those of SRSF3 but opposite of SRSF10. In vitro pull-down assay illustrated a competitive binding of SRSF3 and SRSF10 to YTHDC1. Moreover, YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 depletion, can be restored by reconstitution with wild-type, but not m(6)A-binding-defective, YTHDC1. Our findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs.

A Case of Mycobacterium Fortuitum Infection in the Left Thigh.

BACKGROUND: In March 2024, our hospital confirmed a case of Mycobacterium fortuitum infection in the left thigh. In January 2024, the patient underwent buttock augmentation surgery at a private plastic surgery hospital. One month after the surgery, the patient sought medical attention at the plastic surgery hospital, due to pain in both legs while sitting. Upon examination, two subcutaneous masses were found in the left thigh, the tumors were painful to pressure, with obvious redness and swelling and elevated skin temperature; therefore, the patient was treated with intravenous infusion (cephalosporin drugs), but after one month of treatment, no significant improvement was observed. In order to seek additional diagnosis and treatment, the patient came to our hospital for treatment. METHODS: Clinical treatment of the left lower limb included wound debridement, abscess incision and drainage, and photodynamic therapy with 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). During surgery, subcutaneous tough tissue was taken for pathogen examination, including acid fast staining, bacterial culture, and identification. Additional auxiliary examinations: urine routine, blood routine, coagulation function, liver function, kidney function, blood lipids, and blood sugar. RESULTS: Bacterial acid-fast staining: positive. Bacterial Culture and Identification (MALDI-TOF MS): Mycobacterium fortuitum. Clinical treatment plan: clarithromycin 500 mg po bid, moxifloxacin 400 mg po qd, abscess incision and drainage, ALA-PDT. After 24 days of treatment, the patient's condition was good, the surgical incision healed well, there was no bleeding, exudation, or bruising, no redness, swelling, or tenderness, and the skin temperature was normal. The patient improved and was discharged. CONCLUSIONS: This article reports a case of Mycobacterium fortuitum infection in the left thigh. The Mycobacterium fortuitum was quickly and accurately identified by MALDI-TOF MS, and reasonable treatment measures were adopted clinically. The patient improved and was discharged. I hope that in the future, this study can provide assistance for the clinical diagnosis and treatment of Mycobacterium fortuitum infections.

Characterization and Classification of Frontal Hairline Contours and Growth Directions in Chinese Women.

BACKGROUND: Hair transplantation has become a major method for improving upper facial contour. Hairline contour (HC) and hair growth direction (HGD) are the main factors affecting postoperative aesthetic outcomes. However, studies on natural HC and HGD in Chinese women are scarce. OBJECTIVE: To summarize the HC and HGD of hairlines in Chinese female participants. MATERIALS AND METHODS: Standard photographs of the forehead were obtained from healthy Chinese volunteers older than 18 years. Hairline contour features were classified into 5 groups: round, bell-shaped, M-shaped, rectangular, and triangular. Hair growth direction was classified into 5 groups: Type ⅠA, Type ⅠB, Type ⅡA, Type ⅡB1, and Type ⅡB2. The authors performed hairline corrections in female participants. RESULTS: A total of 568 women participated in this study. The proportions of participants with different HC features were as follows: round (8.10%), bell-shaped (15.84%), M-shaped (23.24%), rectangular (44.19%), and triangular (8.63%). The proportions of participants with different HGDs were as follows: Type ⅠA (7.75%), Type ⅠB (27.64%), Type ⅡA (30.81%), Type ⅡB1 (28.34%), and Type ⅡB2 (5.46%). CONCLUSION: Both HC and HGD were categorized into 5 types in Chinese women. Shaping the hairline into a round type along with the preexisting direction was suggested in most instances.

The impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes: a meta-analysis.

INTRODUCTION: Newer neuraxial local anesthetic agents which have been used as epidural analgesia have shown to provide reliable pain relief during labor. Ropivacaine and levobupivacaine are newer agents now used for labor analgesia. However, even though few studies have made their comparison with bupivacaine, ropivacaine and levobupivacaine have seldom systematically been compared. Therefore, in this analysis, we aimed to systematically show the impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes. METHODS: http://www. CLINICALTRIALS: gov , Web of Science, MEDLINE, EMBASE, Cochrane database and Google Scholar were searched for studies comparing ropivacaine versus levobupivacaine for labor analgesia. Maternal and fetal outcomes were considered as the endpoints in this analysis. The RevMan software 5.4 was used to analyze data in this study. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the data post analysis. RESULTS: A total number of 2062 participants were included in this analysis whereby 1054 participants were assigned to ropivacaine and 1008 participants were assigned to levobupivacaine. The main results of this analysis showed that epidural ropivacaine was not associated with significantly higher risk of hypotension (RR: 0.71, 95% CI: 0.43 - 1.17; P = 0.18) and pruritus (RR: 1.12, 95% CI: 0.89 - 1.42; P = 0.34) when compared to levobupivacaine for labor analgesia. However, the risk of nausea and vomiting was significantly higher with ropivacaine (RR: 1.60, 95% CI: 1.05 - 2.44; P = 0.03). Spontaneous vaginal delivery (RR: 0.99, 95% CI: 0.89 - 1.42; P = 0.83), instrumental vaginal delivery (RR: 1.13, 95% CI: 0.89 - 1.45; P = 0.32) and the risk for cesarean section (RR: 0.76, 95% CI: 0.42 - 1.37; P = 0.35) were not significantly different. When fetal outcomes were assessed, Apgar score < 7 at 1 min (RR: 1.01: 95% CI: 0.57 - 1.80; P = 0.97), abnormality of fetal heart rate (RR: 1.45, 95% CI: 0.55 - 3.79; P = 0.45) and neonatal asphyxia (RR: 0.35, 95% CI: 0.10 - 1.18; P = 0.09) were also similarly manifested. CONCLUSIONS: To conclude, our analysis showed both epidural ropivacaine and levobupivacaine to be equally effective for labor analgesia in terms of maternal and fetal outcomes. No major adverse maternal and fetal outcome was observed in this analysis. However, considering the several limitations of this analysis, further larger studies should be able to solve and clarify this issue.