FKBP3 aggravates the malignant phenotype of diffuse large B-cell lymphoma by PARK7-mediated activation of Wnt/ß-catenin signalling.

Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/ß-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/ß-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.

Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

The impact of empathy on medical students: an integrative review.

INTRODUCTION: Empathy is considered the ability to understand or feel others emotions or experiences. As an important part of medical education, empathy can affect medical students in many ways. It is still lacking a comprehensive evaluation of the existing articles on empathy's impact on medical students, despite the existence of many articles on the topic. OBJECTIVES: To summarize the impact of empathy on medical students during medical education from four perspectives: mental health, academic performance, clinical competence, and specialty preference. METHODS: The search terms used for retrieval were "empathy", "medical student", "mental health", "depression", "anxiety", "burnout", "examinations", "academic performance", "clinical competence", "specialty preference" on PubMed, EBSCO, and Web of Science before January 2024. The search was carried out by two reviewers. Titles and abstracts were screened independently and reviewed based on inclusion/exclusion criteria. A consensus was drawn on which articles were included. RESULTS: Our results indicated that high empathy was a positive factor for mental health, However, students with high affective empathy were more likely to suffer from depression, anxiety, and burnout. Empathy was found to be unrelated to academic performance, but positively correlated with clinical competence, particularly in terms of communication skills. Medical students with high levels of empathy tended to prefer people-oriented majors. CONCLUSIONS: Medical students who score higher on the self-reported empathy scales often have better mental health, better communication skills, and tend to choose people-oriented specialties. But empathy is not related to academic performance. Additionally, the different dimensions of empathy have different impacts on medical students. It is necessary to design targeted courses and training for medical students to enhance their empathy.

GRAVEN: a database of teaching method that applies gestures to represent the neurosurgical approach's blood vessels and nerves.

BACKGROUND: In this era of rapid technological development, medical schools have had to use modern technology to enhance traditional teaching. Online teaching was preferred by many medical schools. However due to the complexity of intracranial anatomy, it was challenging for the students to study this part online, and the students were likely to be tired of neurosurgery, which is disadvantageous to the development of neurosurgery. Therefore, we developed this database to help students learn better neuroanatomy. MAIN BODY: The data were sourced from Rhoton's Cranial Anatomy and Surgical Approaches and Neurosurgery Tricks of the Trade in this database. Then we designed many hand gesture figures connected with the atlas of anatomy. Our database was divided into three parts: intracranial arteries, intracranial veins, and neurosurgery approaches. Each section below contains an atlas of anatomy, and gestures represent vessels and nerves. Pictures of hand gestures and atlas of anatomy are available to view on GRAVEN ( www.graven.cn ) without restrictions for all teachers and students. We recruited 50 undergraduate students and randomly divided them into two groups: using traditional teaching methods or GRAVEN database combined with above traditional teaching methods. Results revealed a significant improvement in academic performance in using GRAVEN database combined with traditional teaching methods compared to the traditional teaching methods. CONCLUSION: This database was vital to help students learn about intracranial anatomy and neurosurgical approaches. Gesture teaching can effectively simulate the relationship between human organs and tissues through the flexibility of hands and fingers, improving anatomy interest and education.

Nanomechanical Signatures of Extracellular Vesicles from Hematologic Cancer Patients Unraveled by Atomic Force Microscopy for Liquid Biopsy.

Cells release extracellular vesicles (EVs) as the carriers for intercellular communications to regulate life activities. Particularly, it is increasingly apparent that mechanical forces play an essential role in biological systems. The nanomechanical properties of EVs and their dynamics in cancer development are still not fully understood. Herein, with the use of atomic force microscopy (AFM), the nanomechanical signatures of EVs from the liquid biopsies of hematologic cancer patients were unraveled. Single native EVs were probed by AFM under aqueous conditions. The elastic and viscous properties of EVs were measured and visualized to correlate EV mechanics with EV geometry. Experimental results remarkably reveal the significant differences in EV mechanics among multiple myeloma patients, lymphoma patients, and healthy volunteers. The study unveils the unique nanomechanical signatures of EVs in hematologic cancers, which will benefit the studies of liquid biopsies for cancer diagnosis and prognosis with translational significance.

Genome-Wide Association Study and Prediction of Tassel Weight of Tropical Maize Germplasm in Multi-Parent Population.

Tassel weight (TW) is a crucial agronomic trait that significantly affects pollen supply and grain yield development in maize breeding. To improve maize yield and develop new varieties, a comprehensive understanding of the genetic mechanisms underlying tassel weight is essential. In this study, tropical maize inbred lines, namely CML312, CML373, CML444, and YML46, were selected as female parents and crossed with the elite maize inbred line Ye107, which served as the common male parent, to develop a multi-parent population comprising four F8 recombinant inbred line (RIL) subpopulations. Using 6616 high-quality single nucleotide polymorphism (SNP) markers, we conducted genome-wide association analysis (GWAS) and genomic selection (GS) on 642 F8 RILs in four subpopulations across three different environments. Through GWAS, we identified 16 SNPs that were significantly associated with TW, encompassing two stable loci expressed across multiple environments. Furthermore, within the candidate regions of these SNPs, we discovered four novel candidate genes related to TW, namely Zm00001d044362, Zm00001d011048, Zm00001d011049, and Zm00001d031173 distributed on chromosomes 1, 3, and 8, which have not been previously reported. These genes are involved in processes such as signal transduction, growth and development, protein splicing, and pollen development, all of which play crucial roles in inflorescence meristem development, directly affecting TW. The co-localized SNP, S8_137379725, on chromosome 8 was situated within a 16.569 kb long terminal repeat retrotransposon (LTR-RT), located 22.819 kb upstream and 26.428 kb downstream of the candidate genes (Zm00001d011048 and Zm00001d011049). When comparing three distinct GS models, the BayesB model demonstrated the highest accuracy in predicting TW. This study establishes the theoretical foundation for future research into the genetic mechanisms underlying maize TW and the efficient breeding of high-yielding varieties with desired tassel weight through GS.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

The effects of thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens on TGF-ß signaling pathway and Th17 cells differentiation in Jurkat cells by transcriptomics.

Thioredoxin peroxidase (TPx) protein from the excretory-secretory antigens (ESAs) of Cysticercus cellulosae (C. cellulosae) has been shown to regulate the differentiation of host Treg and Th17 cells, resulting in an immunosuppressive response dominated by Treg cells. However, the molecular mechanism by which TPx protein from the ESAs of C. cellulosae regulates the imbalance of host Treg/Th17 cell differentiation has not been reported. TPx protein from porcine C. cellulosae ESAs was used to stimulate Jurkat cells activated with PMA and ionomycin at 0, 24, 48, and 72 h. Transcriptomic analysis was performed to investigate the signaling pathways associated with Jurkat cells differentiation regulated by TPx protein from C. cellulosae ESAs. Gene Set Enrichment Analysis (GSEA) revealed that TPx protein from porcine C. cellulosae ESAs could induce upregulation of the TGF-ß signaling pathway and downregulation of Th17 cell differentiation in Jurkat cells. TPx protein from porcine C. cellulosae ESAs can activate the TGF-ß signaling pathway in Jurkat cells, thereby regulating the differentiation of Treg/Th17 cells and leading to an immunosuppressive response dominated by Treg cells, enabling evasion of the host immune attack. This study provides a foundation for further validation of these pathways and further elucidates the molecular mechanisms underlying immune evasion caused by porcine C. cellulosae.

Repurposing of the antihistamine mebhydrolin napadisylate for treatment of Zika virus infection.

Zika virus (ZIKV) infection can lead to severe neurological disorders and fetal defects, which has become a public health problem worldwide. However, effective clinical treatment for ZIKV infection was still arduous. Antihistamines are attractive candidates for drug repurposing due to their low price and widespread availability. Here we screened FDA-approved antihistamine drugs to obtain anti-ZIKV candidate compounds and identified mebhydrolin napadisylate (MHL) that exhibits the potent inhibition of ZIKV infection in various cell lines in a histamine H1 receptor-independent manner. Mechanistic studies suggest that MHL acts as a ZIKV NS5 RNA-dependent RNA polymerase (RdRp) inhibitor, supported by a structure-activity relationship (SAR) analysis showing the correlation between the inhibitory effect upon viral RNA synthesis and ZIKV infectivity. Furthermore, MHL was shown to bind ZIKV NS5 RdRp in vitro and predicted to interact with key residues at the active site of ZIKV NS5 RdRp by molecular docking analysis. Our data together suggest that MHL suppresses ZIKV infection through the inhibition of ZIKV NS5 RdRp activity. This study highlights that MHL might be a promising clinical anti-ZIKV therapeutic.

Preliminary Exploration of a New Clitoral Hood Classification System and Treatment Strategy.

BACKGROUND: Increasing attention has been given to clitoral hoods in recent years, but few studies have been conducted on the classification and treatment strategies of clitoral hood hypertrophy. The purpose of this article is to introduce a new system of clitoral hood classification based on relevant anatomy and make recommendations for clitoral hood reduction. METHODS: The clitoral hood region is divided into the central zone (zone C) and the lateral zone (zone L). According to the anatomical characteristics of each zone, patients can be divided into 5 types: standard form, central hypertrophy, lateral hypertrophy, composite hypertrophy and special type. Central hypertrophy is further divided into wide and long clitoral hoods, and horizontal and vertical redundancy are addressed using bilateral clitoral hood triangular skin resection and inverted horizontal V-shaped skin resection, respectively. Lateral hypertrophy can be treated with vertically oriented excision. Composite hypertrophy is corrected by combining these methods to remove redundant tissue depending on the situation. RESULTS: 1135 patients were classified according to the new classification system and 789 participants were given corresponding treatment measures. Thirty-four patients (4.3%) experienced complications, and 15 (1.9%) underwent revision surgery. Six months after the procedure, clitoral hood images improved significantly without paresthesia, and the overall satisfaction rate of the patients regarding clitoral hood reduction was 95.7%. CONCLUSIONS: The clitoral prepuce is an important part of the aesthetic unit of female vulva. The new clitoral hood classification strategy systematically summarizes the anatomical characteristics of the clitoral hood and clearly makes recommendations for surgical options. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Trilobal Methods for Composite Reduction Labiaplasty.

BACKGROUND: It is difficult to plan a simple and effective surgical strategy for patients with horizontal and vertical redundant tissue of the labia minora and clitoral hood redundancy. A single edge resection or wedge resection labiaplasty with clitoral hood reduction that simultaneously resolves these three issues has yet to be reported. This study investigated the clinical effects and safety of trilobal labiaplasty via a composite incision. METHODS: The single-center, retrospective, observational study included data from patients with hypertrophy of the labia minora and clitoral hood who underwent trilobal labiaplasty. RESULTS: Altogether, 136 patients (average age: 31.6 ± 8.82 years; range: 21-53 years; 224 sides) sought surgery for aesthetic (39/136, 28.7%), functional (17/136, 12.5%), or both reasons (80/136, 58.8%). Overall, 134 patients (134/136, 98.5%) were followed up for 3 months. No serious complications or malformations occurred. Three patients (2.2%) underwent secondary repair surgery due to incomplete bilateral symmetry, 122 (91.0%) scored ≥ 21 points on the Female Genital Self-Image Scale, 107 (91.5%) were satisfied with the cosmetic outcomes, and 93 (95.9%) were satisfied with the functional improvement. CONCLUSIONS: Trilobal labiaplasty performed via a composite incision using edge and wedge labiaplasty to adjust horizontal and vertical hypertrophy of the labia minora and remove lateral folds of the clitoris is a safe and effective method to improve the appearance and rearrange the position of the clitoral hood and clitoral frenulum while preserving the fine structure of the surrounding tissue. This method results in few complications and high functional and aesthetic satisfaction rates. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Synthesis of Silica-Based Quaternized Adsorption Material and Study on Its Adsorption Behavior for Pu(IV).

In this research, we explored the synthesis optimization of the silica-based quaternized adsorption material (SG-VTS-VPQ) and its adsorption behavior for Pu(IV). By optimizing the synthesis process, the grafting amount of 4-vinylpyridine reached 1.25 mmol·g-1. According to the analysis of NMR and XPS, the quaternization rate of pyridine groups reached 91.13%. In the adsorption experiments, the thermodynamic experiment results show that the adsorption of Pu(IV) by SG-VTS-VPQ is more in line with the Langmuir adsorption model and the adsorption type is a typical chemical adsorption; the kinetic results show that adsorption process is more in line with the pseudo first-order kinetic model, and the larger specific surface area of SG-VTS-VPQ plays an important role in the adsorption. The results of the adsorption mechanism show that the adsorption of Pu(IV) by SG-VTS-VPQ is mainly complex anion Pu(NO3)62- and Pu(NO3)5-. This research provides in-depth and detailed ideas for the surface modification and application of porous silica gel, and at the same time provides a new way to develop the direction of the analysis of pretreatment materials in the spent fuel reprocessing field.

Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression.

Cervical cancer is a common gynecological malignancy afflicting women all over the world. Ginsenoside Rh2 (GRh2), especially 20(S)-GRh2, is a biologically active component in the natural plant ginseng, which can exhibit anticancer effects. Here, we aimed to investigate the effect of 20(S)-GRh2 on cervical cancer and elucidate the underlying mechanism through RNA-seq. In this study, the CCK-8 assay showed that 20(S)-GRh2 inhibited HeLa cell viability in a time- and dose-dependent manner. Caspase 3 activity and Annexin V staining results showed that 20(S)-GRh2 induced apoptosis of HeLa cells. Gene function enrichment analysis revealed that the biological process gene ontology (GO) terms were associated with the apoptotic signaling pathway. Biological process GO terms' similarity network indicated that apoptosis might be from endoplasmic reticulum stress (ERs). Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that 20(S)-GRh2 primarily modulates apoptosis pathway genes. Combined protein-protein interaction network, hub gene screening, and qPCR validation data showed that ERs-related genes (ATF4 and DDIT3) and the downstream apoptotic genes (JUN, FOS, BBC3, and PMAIP1) were potential novel targets of 20(S)-GRh2-inducing cervical cancer cell apoptosis. Differential transcript usage analysis indicated that DDIT3 is also a differential transcript and its usage of the isoform (ENST00000552740.5) was reduced by 20(S)-GRh2. Molecular docking suggested that 20(S)-GRh2 binds to the targets (ATF4, DDIT3, JUN, FOS, BBC3, and PMAIP1) with high affinity. In conclusion, our findings indicated that 20(S)-GRh2 might promote ERs-related apoptosis of cervical cancer cells by regulating the DDIT3-based targets' signal pathway. The role of 20(S)-GRh2 at the transcriptome level provides novel targets and evidence for the treatment of cervical cancer.

Collaborative Optimal Formation Control for Heterogeneous Multi-Agent Systems.

In this paper, the distributed optimal control method is used to study the cooperative formation of heterogeneous multi-agents in the air-ground environment. The considered system consists of an unmanned aerial vehicle (UAV) and an unmanned ground vehicle (UGV). The optimal control theory is introduced into the formation control protocol, the distributed optimal formation control protocol is designed, and the stability is verified by graph theory. Furthermore, the cooperative optimal formation control protocol is designed, and the stability is analyzed using a block Kronecker product and matrix transformation theory. Through the comparison of simulation results, the introduction of optimal control theory shortens the formation time of the system and accelerates the convergence speed of the system.

[Pharmacokinetic interaction of Jiaotai Pills and Fluoxetine in rats with CUMS-induced depression].

A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.

20(S)-Ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway.

20(S)-Ginsenoside Rh2 (GRh2) has various biological activities including anticancer effects. However, no reports have investigated the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRh2. In this study, we found that 20(S)-GRh2 suppressed proliferation and induced apoptosis in HeLa cells by activating the intrinsic apoptotic pathway and causing mitochondrial dysfunction. 20(S)-GRh2 enhanced cell autophagy through promoting the phosphorylation of AMPK, depressed the phosphorylation of AKT, and suppressed mTOR activity. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3-MA) enhanced 20(S)-GRh2-induced apoptosis, while the autophagy inducer rapamycin promoted cell survival. Moreover, the apoptosis inhibitor Z-VAD-FMK significantly restrained the apoptosis and autophagy induced by 20(S)-GRh2 in HeLa cells. We found that 20(S)-ginsenoside Rh2-induced protective autophagy promotes apoptosis of cervical cancer cells by inhibiting AMPK/mTOR pathway.

Knockdown of p62/sequestosome enhances ginsenoside Rh2-induced apoptosis in cervical cancer HeLa cells with no effect on autophagy.

p62/sequestosome is a multifunctional adaptor protein that participates in a wide variety of cellular processes. 20(S)-Ginsenoside Rh2 (G-Rh2) has various biological effects, including anticancer activity. We found that G-Rh2 can induce apoptosis and autophagy in HeLa cells. G-Rh2 significantly enhanced the transcriptional level of p62. A siRNA was constructed to knock down p62 and assess its effect on apoptosis induced by G-Rh2. p62 protein levels were successfully downregulated in cells transfected with the p62-specific siRNA. Silencing of p62 further decreased cell viability while also enhancing cell apoptosis, reactive oxygen species generation, the ratio of Bax to Bcl-2, and the cleavage of PARP. p62 knockdown decreased expression levels of Nrf2. Moreover, silencing of p62 had no significant effect on autophagy induced by G-Rh2. These results suggest that combining G-Rh2 treatment with inhibition of p62 may be a potential treatment strategy for cervical cancer.

A New Concept for Central Wedge Resection in Labiaplasty.

OBJECTIVE: The aim of the study was to develop a new concept for central wedge resection to improve surgical results. Currently, the most common postoperative complications of the regular central wedge (RV) resection technique are wound dehiscence and scar contracture. METHODS: A case-control study was applied to randomly divide 119 patients with labia minora hypertrophy deformities into 2 groups: new central wedge (NV) (n = 57) and RV (n = 62). All patients underwent the corresponding corrective surgery to repair the deformity. During the NV procedure, we changed the direction of the scalpel to form 2 inclined sections and sutured these sections together to achieve nonparallel closure lines. The patients in the 2 groups were followed up at 1 and 6 months postoperatively. We described the details of this method and evaluated the treatment outcomes of the 2 groups. RESULTS: Patient age, labia minora width, and procedure time were not significantly different between the 2 groups (p > 0.05). However, the visual analog scale (VAS) scores in the 2 groups were significantly different (p < 0.05). Two patients in the NV group were somewhat dissatisfied because of lymphoedema and asymmetry; 6 patients in the RV group expressed dissatisfaction with scarring, healing complications, and asymmetry. A minor corrective operation was performed for asymmetry, and the dehiscence healed spontaneously. The patient with edema is still being followed up. CONCLUSION: The surgical method we introduced was indicated to be a simple and effective procedure that avoided wound dehiscence and scar contracture, which are common with the regular approach.

MiRNA-429 alleviates ketamine-induced neurotoxicity through targeting BAG5.

Ketamine is a kind of anesthetic broadly applied in clinic. However, growing evidence has indicated that ketamine may induce neurotoxicity. Previous studies showed that mircoRNAs (miRNAs) participate in various aspects of biological regulations. In our work, we aimed to reveal the role of miR-429 in ketamine-induced neurotoxicity. The qRT-PCR was used to measure the miR-429 levels in ketamine-treated PC12 cells. TUNEL staining and caspase 3 activity detection assays were performed to assess cell apoptosis. A Cellular Reactive Oxygen Species Detection Assay Kit was utilized to detect ROS activity. A luciferase reporter assay was conducted in HEK-293T cells to test the binding between miR-429 and BAG5. Herein, we found that ketamine could induce the apoptosis and ROS activity in PC12 cells. The qRT-PCR results showed that miR-429 expression was downregulated by treatment of ketamine in a dose-dependent manner. Overexpression of miR-429 alleviated ketamine-induced neurotoxicity in PC12 cells. Mechanically, BAG5 was identified to be a target of miR-429 and negatively regulated by miR-429. Moreover, BAG5 expression was upregulated after ketamine treatment. Rescue assays revealed that overexpression of BAG5 reversed the suppressive effects of miR-429 upregulation on ketamine-induced neurotoxicity in PC12 cells. In summary, miR-429 attenuates ketamine-induced neurotoxicity in PC12 cells by the downregulation of BAG5.

[Effects of Jiaotai Pills on CUMS-induced depression model in mice based on changes of SIRT1 expression in hippocampus].

The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1ß, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1ß, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.