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Cong-Cong He, Dong-Mei Lin, Hui-Zhen Liu, Fei-Fei Wang, Xiu-Fang Guo, Xiao-Bo Zhang, Yi-Qin Ai, Li-Min Meng School of Nursing, Gannan Medical University, Ganzhou City, Jiangxi Province, People’s Republic of ChinaCorrespondence: Li-Min Meng, School of Nursing, Gannan Medical University, No. 1 Medical Road, Ganzhou, People’s Republic of China, Tel +86 15970987999, Email 278646437@qq.comBackground: The pain-fatigue-sleep disturbance symptom cluster is commonly experienced by breast cancer patients, and a variety of nonpharmacological interventions are used to treat this symptom cluster.Objective: To compare the efficacy of nonpharmacological interventions in improving the symptoms of the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients.Methods: A comprehensive literature search was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, CNKI, and Wanfang databases to identify randomized controlled studies from database inception to May 2022. Two reviewers independently performed data retrieval and risk of bias assessments. The consistency model was used to conduct network meta-analyses (NMA) based on the frequentist framework to assess the interventions, which were ranked by the surface under the cumulative ranking curve (SUCRA). Finally, the CINeMA application was used to evaluate the results of the NMA and the evidence of quality. The results Twenty-three eligible studies assessing 14 interventions were included. According to SUCRA values, among the management effects of the three symptoms, the effect of progressive muscle relaxation (PMR) ranked first, followed by mindfulness-based stress reduction (MBSR). The overall evidence quality of our study ranges from very low to moderate.Conclusion: PMR and MBSR were effective interventions for the pain-fatigue-sleep disturbance symptom cluster in breast cancer patients. Clinical recommendations prioritize PMR for symptom management, followed by MBSR. However, this should be interpreted cautiously, as the confidence in the evidence was not high.Keywords: breast cancer, pain-fatigue-sleep disturbance symptom cluster, nonpharmacological intervention, systematic review, network meta-analysis

Meng-Qi Chen,1 Wen-Rui Shi,1 Hao-Yu Wang,2 Zhao Li,1 Xiao-Fan Guo,1 Ying-Xian Sun1 1Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Cardiology, Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaCorrespondence: Ying-Xian SunDepartment of Cardiology, The First Hospital of China Medical University, 155 Nanjing, North Street, Heping District, Shenyang, 110001, People’s Republic of ChinaEmail yxsun_cmu@outlook.comPurpose: Some studies have established an association between hypertension or obesity and the risk of diabetes. This study aimed to examine the interaction of hypertension and obesity on diabetes.Participants and Methods: The data of 11,731 Chinese men and women were analyzed from the 2012– 2013 Northeast China Rural Cardiovascular Health Study. The interaction was examined by both additive and multiplicative scales. General obesity was measured by body mass index (BMI); central obesity was defined by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR).Results: After controlling for potential confounders, the odds ratios for diabetes were 3.864 (3.205– 4.660), 4.500 (3.673– 5.514), 4.932 (3.888– 6.255) and 4.701 (3.817– 5.788) for the combinations of hypertension and BMI, WC, WHtR or WHpR, respectively, which had the highest risk of diabetes among the four combinations. Notwithstanding the multiplicative interactions showed statistically significant in all analyses, the results of additive interactions were not consistent, suggesting the diabetes risk from female BMI (relative excess risk due to interaction (RERI): 1.136, 95% CI: 0.127– 2.146, attributable proportion due to interaction (AP): 0.267, 95% CI: 0.057– 0.477, synergy index (S):1.536, 95% CI: 1.017– 2.321) or female WHpR (RERI: 1.076, 95% CI: 0.150– 2.002, AP:0.205, 95% CI: 0.037– 0.374, S:1.340, 95% CI: 1.012– 1.775) was additive to the risk from hypertension.Conclusion: The findings suggest that high BMI and high WHpR have synergistic interactions with hypertension on the risk of diabetes for females. The results of this study also suggest that BMI and WHpR, rather than WC, should be used for the diagnosis of metabolic syndrome in Chinese population.Keywords: interaction, diabetes, hypertension, general obesity, central obesity

Background: The colon cancer prognosis is influenced by multiple factors, including clinical, pathological, and non-biological factors. However, only a few studies have focused on computed tomography (CT) imaging features. Therefore, this study aims to predict the prognosis of patients with colon cancer by combining CT imaging features with clinical and pathological characteristics, and establishes a nomogram to provide critical guidance for the individualized treatment., Aim: To establish and validate a nomogram to predict the overall survival (OS) of patients with colon cancer., Methods: A retrospective analysis was conducted on the survival data of 249 patients with colon cancer confirmed by surgical pathology between January 2017 and December 2021. The patients were randomly divided into training and testing groups at a 1:1 ratio. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with OS, and a nomogram model was constructed for the training group. Survival curves were calculated using the Kaplan-Meier method. The concordance index (C-index) and calibration curve were used to evaluate the nomogram model in the training and testing groups., Results: Multivariate logistic regression analysis revealed that lymph node metastasis on CT, perineural invasion, and tumor classification were independent prognostic factors. A nomogram incorporating these variables was constructed, and the C-index of the training and testing groups was 0.804 and 0.692, respectively. The calibration curves demonstrated good consistency between the actual values and predicted probabilities of OS., Conclusion: A nomogram combining CT imaging characteristics and clinicopathological factors exhibited good discrimination and reliability. It can aid clinicians in risk stratification and postoperative monitoring and provide important guidance for the individualized treatment of patients with colon cancer., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mutations in the well-known Myostatin ( MSTN ) produce a 'double-muscle' phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTN Del73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN , resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTN Del73C mutation with FGF5 knockout sheep highlights a dominant 'double-muscle' phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTN Del73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca 2+ -dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes., Competing Interests: MC, YZ, KY, XX, XZ, JZ, SW, ZL, YY, XG, SQ, GY, SW, HL, AW, GL, SD, HH, FL, DL, ZL No competing interests declared, (© 2023, Chen, Zhao, Yu et al.)

The flavonoid contents of different bamboo-leaf extracts and their relationships to antioxidant activity were investigated in this study by preparing nine samples using two commercially available bamboo-leaf extract products and seven bamboo-leaf extracts such as Phyllostachys edulis . A high performance liquid chromatography (HPLC) method was established to determine seven flavonoid components (orientin, isoorientin, vitexin, isovitexin, tricin, luteolin and luteoloside) in these samples, which were separated using a SymmetryShield TM RP8 column (250 mm×4.6 mm, 5 μm) under gradient-elution conditions using acetonitrile as mobile phase A and 0.5% (v/v) acetic acid aqueous solution as mobile phase B. The antioxidant activities of the samples were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assays, with half inhibitory concentration (IC 50 ) as an indicator and the butylated hydroxytoluene (BHT) and tert -butylhydroquinone (TBHQ) antioxidants as positive controls. Pearson correlation was then used to analyze the relationship between flavonoid content and antioxidant activity. The HPLC method was found to be accurate and reliable for determining the flavonoid contents of the bamboo-leaf extracts. The seven flavonoids were well separated, and good linear relationships were exhibited (correlation coefficients ( R 2 )≥0.9990). Furthermore, the contents of the seven flavonoids in the bamboo-leaf extracts ranged from 14.97 to 183.94 mg/g, with the highest content of 183.94 mg/g recorded for Phyllostachys edulis . The bamboo species exhibited significantly different flavonoid contents, with Phyllostachys edulis showing the highest orientin, isoorientin, and vitexin levels of 38.45, 101.30, and 9.42 mg/g, respectively. Moreover, the bamboo-leaf extracts exhibited IC 50 values of 78.23-179.41 mg/L for DPPH-radical-scavenging, while values of 203.48-1250.81 mg/L were recorded for hydroxyl radicals. The Phyllostachys edulis leaf extract exhibited the strongest antioxidant activity, with the lowest IC 50 values of 78.23 and 203.48 mg/L for DPPH and hydroxyl, respectively; it showed greatly significant for the further development and application of Phyllostachys edulis . Finally, the relationships between flavonoid content and the DPPH- and hydroxyl-radical-scavenging activities (based on the IC 50 values) were correlated, which revealed that the orientin and isoorientin contents are closely related to the antioxidant activities of the bamboo-leaf extracts. Consequently, the orientin and isoorientin contents can be used as indicators for evaluating the antioxidant activities of bamboo-leaf extracts.

In this study, we analyzed the clinical efficacy of Zishen Yutai pills (ZSYTP) combined with metformin hydrochloride on infertile women diagnosed with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). Patients were assigned into 3 groups: the ZSYTP group (n = 50), the metformin group (n = 50), and the combination group (ZSYTP combined with metformin hydrochloride, n = 50), based on their respective and the indicated treatments before undergoing IVF-ET. Then, their glucose metabolism indices, sex hormone indices, traditional Chinese medicine (TCM) syndrome scores, and outcomes of IVF-ET were compared. Baseline characteristics were not significantly different between the 2 groups. After treatment, various parameters such as body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FIN), homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T) levels, and TCM syndrome scores were found to be reduced compared to pretreatment levels in both groups. Moreover, the improvement observed in the treatment group exceeded that of the control group. Specifically, the observation group displayed significantly lower gonadotropin (Gn) dosage and duration, as well as a reduced abortion rate compared to the control group. Furthermore, the observation group had higher numbers of obtained eggs, high-quality embryos, eggs obtained through IVF-ET, average transferred embryos, clinical pregnancy rate, and embryo implantation rate compared to the control group. Pretreatment with ZSYTP combined with metformin before IVF-ET in PCOS patients improves the outcome of IVF-ET., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome., Methods: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry., Results: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78., Conclusion: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome., (© 2024. The Author(s).)

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear., Aim: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC., Methods: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells., Results: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells., Conclusion: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1β and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xue, Yuan, Hou, Meng, Liu, Cheng, Zhao, Li, Guo, Di, Li and Zhang.)

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts., (© 2023. People´s Military Medical Press.)

Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were scattered. Here, we explore the evolution and distribution of this deadly virus from a novel panorama view. Multiple bioinformatic software tools were employed to analyze the phylogenetic diversity, evolution, spatiotemporal, and distribution of RABVs. The analyses were based on 1,202 qualified full-length genomes of RABVs and numerous literatures. Of the 10 distinct phylogenetic clades of RABV that we identified, more frequent intra- and inter-clade recombination occurs in the sequences of Asian-SEA, Arctic, and Cosmopolitan clades isolated from China, while according to existing sequence information, RABV might originate from bats (posterior probability, PP = 0.75, PP = 0.60 inferred from N and L genes, separately) in North America (PP = 0.57, PP = 0.62 inferred from N and L genes, separately). Due to the difference in evolutionary rate of N (2.22 × 10 -4 subs/site/year, 95% HPD 1.99-2.47 × 10 -4 subs/site/year) and L genes (1.67 × 10 -4 subs/site/year, 95% HPD 1.59-1.74 × 10 -4 subs/site/year), the root age was 1,406.6 (95% HPD 1,291.2-1,518.2) and 1,122.7 (95% HPD 1,052.4-1,193.9) inferred from N and L genes, separately. Among other findings, Mephitidae plays an important role in the interspecific transmission and communication of RABV, which we found tends to spread to populations genetically proximate to the host. We also identified amino acids under positive selection in different genes of different clades as well as single nucleotide variation sites important for different lineages. IMPORTANCE Rabies virus is widely distributed all over the world, and wild animals are its largest potential reservoir. Our study offers a panorama view about evolution and distribution of rabies viruses and emphasizes the need to monitor the transmission dynamics of animal rabies.

Yellow fluorescent silicon quantum dots (y-SiQDs) with 22.2% fluorescence quantum yield were synthesized by a simple hydrothermal method using 3-glycidoxypropyl triethoxysilane (GOTS) and m-aminophenol. The excitation wavelength is 550 nm with an emission wavelength of 574 nm, which effectively avoids the interference of biological autofluorescence. Notably, the synthesis approach does not require any post-modification and the y-SiQDs can be directly used for hydrogen sulfide (H 2 S) quantification due to static quenching. It exhibits high sensitivity and excellent selectivity for H 2 S with a 0.2-10 μM (R 2  = 0.9953) linear range and detection limit of 54 nM. y-SiQDs have excellent stability and biocompatibility and can be used for H 2 S imaging in living cells and onion tissues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Red-tail catfish (Hemibagrus wyckioides) is an important commercially farmed catfish in southern China. Males of red-tail catfish grow faster than females, suggesting that all-male catfish will produce more significant economic benefits in aquaculture practice. However, little research has been reported on sex determination and gonadal development in red-tail catfish., Results: In this study, we performed the first transcriptomic analysis of male and female gonads at four developmental stages at 10, 18, 30, and 48 days post hatching (dph) using RNA-seq technology. A total of 23,588 genes were screened in 24 sequenced samples, of which 28, 213, 636, and 1381 differentially expressed genes (DEGs) were detected at four developmental stages, respectively. Seven candidate genes of sex determination and differentiation were further identified. Real-time quantitative PCR (RT-qPCR) further confirmed that anti-Mullerian hormone (amh), growth differentiation factor 6a (gdf6a), testis-specific gene antigen 10 (tsga10), and cytochrome P450 family 17 subfamily A (cyp17a) were highly expressed mainly in the male, while cytochrome P450 family 19 subfamily A polypeptide 1b (cyp19a1b), forkhead box L2 (foxl2), and hydroxysteroid 17-beta dehydrogenase 1 (hsd17b1) were highly expressed in the female. The KEGG pathway enrichment data showed that these identified DEGs were mainly involved in steroid hormone biosynthesis and TGF-β signaling pathways., Conclusions: Based on RNA-seq data of gonads at the early developmental stages, seven DEGs shared by the four developmental stages were identified, among which amh and gdf6a may be the male-biased expression genes, while foxl2, cyp19a1b and hsd17b1 may be the female-biased expression genes in red-tail catfish. Our study will provide crucial genetic information for the research on sex control in red-tail catfish, as well as for exploring the evolutionary processes of sex determination mechanisms in fish., (© 2023. The Author(s).)

Background: Poria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM)., Objective: The purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials., Methods: English (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration's procedures. Stata software (13.0) was used for data analysis., Results: Seventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87)., Conclusion: Evidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated., Trail Registration: This review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Di et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3., Competing Interests: None

Micro-nano bubbles (MNBs) play important roles in the reduction of membrane fouling during membrane separation; however, such improvements are always attributed to the reduced concentration polarization on the surface of membranes and little attention has been paid on the variations of physicochemical properties of the feed caused by MNBs. In this study, the separation efficiencies of the feed containing humic acid (HA), bovine serum albumin (BSA), sodium alginate (SA) or dyes can be improved by MNBs during ultrafiltration, and the normalized fluxes can be maximally increased to 139% and 127% in the dead-end and cross-flow modes, respectively in the treatment of HA solution. We further reveal that the decreased apparent viscosity of the feed in the presence of MNBs is the key factor that enhances the normalized flux during ultrafiltration. This study gives new insight on the importance of MNBs in membrane separation and provides valuable clues for other chemical processes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A simple, fast and reliable method based on capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) detection was developed for the simultaneous analysis of NO released both inside and outside cells at the single-cell level closer to physiological conditions. After pre-capillary dual-labeling derivatization with a group of cells, single cells were injected into the separation capillary and lysed. The subsequent separation and detection of NO derivatives were achieved within 4.0 min producing mass limits of detection of 3.0 and 10.7 amol for intra- and extracellular NO, respectively. The developed method was successfully applied for simultaneous measurement of NO released both inside and outside single RAW 264.7 macrophage cells., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background and Objectives: The present study aimed to investigate the hypothesis that dietary amino acid intakes are associated with the risk of sarcopenia through a community-based observational study., Methods and Study Design: A total of 1,140 participants (72.7±6.3 y) were recruited from an annual health check-up program in Qingdao, China. Skeletal muscle mass, muscle mass functions and biochemical parameters were measured by standard methods. Dietary intake was assessed by 3-day, 24-hour food records. The odds ratios (ORs) and 95% confidence intervals (CIs) of sarcopenic risk across quartiles of amino acid intakes were calculated using a multivariable- adjusted logistic regression model. Generalized linear models were used to assess the associations between dietary amino acid intakes and muscle mass functions., Results: The prevalence of sarcopenia was 4.1%. Compared with the lowest category intake, the highest category of branched chain amino acids (BCAAs) (OR=0.11; 95% CI: 0.01, 0.90; p for trend=0.119), isoleucine (OR=0.11; 95% CI: 0.01, 0.89; p for trend=0.122) and tryptophan (OR=0.10; 95% CI: 0.01, 0.87; p for trend=0.176) was negatively correlated with sarcopenic risk with adjustment for potential confounding factors. Generalized linear model analysis showed that gait speed was positively correlated with dietary intakes of lysine, threonine, leucine, valine, tryptophan, BCAAs and aromatic amino acids (p<0.05)., Conclusions: Higher intakes of BCAAs were associated with a lower risk of sarcopenia, which might beneficially protect against sarcopenia and improve physical function of the elderly.

Red swamp crayfish ( Procambarus clarkii ) is a commercially important species in global aquaculture and most successfully invasive freshwater shrimp in China. In order to determine the genetic basis of growth- and sex-related traits, a high-density genetic linkage map was constructed using 2b-RAD sequencing technology in a full-sib family. The consensus map contains 4,878 SNP markers assigned to 94 linkage groups (LGs) and spanned 6,157.737 cM with an average marker interval of 1.26 cM and 96.93% genome coverage. The quantitative trait locus (QTL) mapping for growth and sex traits was performed for the first time. QTL mapping uncovers 28 QTLs for growth-related traits in nine LGs, explaining 7.9-14.4% of the phenotypic variation, and identifies some potential candidate growth-related genes such as mih , lamr , golgb1 , nurf301 , and tbcd1 within the QTL intervals. A single major locus for sex determination was revealed in LG20 that explains 59.3-63.7% of the phenotypic variations. Some candidate sex-related genes, such as vps4bl , ssrf , and acot1 , were identified in the QTL intervals and found to be differentially expressed in the muscle tissues between the females and the males. Furthermore, the identified SNPs were revealed to be female heterozygotes, suggesting that red swamp crayfish might have the female heterogametic ZZ/ZW sex determination system. The present study provides a valuable resource for marker-assisted selection and genetic improvement and for further genetic and genomic research in red swamp crayfish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Zhou, Liu, Li, Zhou, Wang and Gui.)

The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.

Background: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms., Methods: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined., Results: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation ( P <0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P <0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P <0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK , DJ1 , LRRK2 , Mfn-1 , Mfn-2 , and OPA1 . The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons., Conclusions: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury., Competing Interests: Conflicts of interests: The authors have no conflict of interest to declare., (Copyright: © World Journal of Emergency Medicine.)

Objective: The relationship between dietary nut intake and hyperuricemia risk remains unclear. The aim of this study was to investigate the relationship between different nut intake and hyperuricemia risk with a cross-sectional study., Design: A semi-quantitative FFQ was adopted to collect dietary information. Biochemical and anthropometric parameters were measured by standard methods. Multivariate-adjusted logistic regression models were implemented to analyse the relationship between individual nut intake and hyperuricemia risk., Setting: Qingdao University in Shandong Province, China., Participants: During 2018-2019, a total of 14 056 undergraduates (6862 males and 7194 females) aged 15-25 years participated in the study., Results: After adjusting for multiple confounding factors, compared with the lowest quartile, the highest quartile intakes of pine nut (95 % CI (0·51, 0·98)) was significantly associated with 29 % reduction in hyperuricemia risk, the highest quartile intake of walnut (OR = 0·78; 95 % CI (0·58, 1·05)) was marginally negatively associated with hyperuricemia risk., Conclusions: The present study showed that the relationships between intakes of different nuts and hyperuricemia risk were different. Increased dietary intakes of walnut and pine nut are negatively associated with the hyperuricemia.

Background: The resection of small colorectal polyps (≤10 mm) is routine for endoscopists. However, the management of one of its main complications, namely delayed (within 14 days) postpolypectomy bleeding (DPPB), has not been clearly demonstrated. We aimed to assess the role of coloscopy in the management of DPPB from small colorectal polyps and identify the associated factors for initial hemostatic success., Methods: We conducted a retrospective study of 69 patients who developed DPPB after the removal of colorectal polyps of ≤10 mm and underwent hemostatic colonoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2013 and June 2021. Demographics, clinical variables, and colonoscopic features were collected independently. We applied univariate and multivariate analyses to assess factors associated with initial hemostatic success., Results: General colonoscopy without oral bowel preparation was successfully performed in all the patients, with a median duration of 23.9 (12.5-37.9) minutes. Among 69 patients, 62 (89.9%) achieved hemostasis after initial hemostatic colonoscopy and 7 (10.1%) rebled 2.7 ± 1.1 days after initial colonoscopic hemostasis and had rebleeding successfully controlled by one additional colonoscopy. No colonoscopy-related adverse events occurred. Multivariate analysis showed that management with at least two clips was the only independent prognostic factor for initial hemostatic success (odds ratio, 0.17; 95% confidence interval, 0.03-0.91; P = 0.04). All the patients who had at least two clips placed at the initial hemostatic colonoscopy required no further hemostatic intervention., Conclusions: Colonoscopy is a safe, effective, and not too time-consuming approach for the management of patients with DPPB of small colorectal polyps and management with the placement of at least two hemoclips may be beneficial., (© The Author(s) 2021. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Objective: Long noncoding RNA DNAJC3-AS1 (DNAJC3-AS1) was a newly identified tumor-related lncRNA. The aim of the present study was to explore the prognostic value and diagnostic of DNAJC3-AS1 (DNAJC3-AS1) expression in breast cancer (BC) patients. Patients and Methods . The expression of DNAJC3-AS1 was detected in 170 BC tissues and matched normal breast samples by qRT-PCR. The diagnostic value of DNAJC3-AS1 was examined by receiver-operating characteristic (ROC) assays. The correlation of DNAJC3-AS1 with clinicopathological features and prognosis was also statistically analyzed. CCK-8 assays, colony formation assays, and Transwell assays were applied to examine the potential function of DNAJC3-AS1 on tumor progression. Western blot was used to examine the expression of EMT-related proteins., Results: The expression of DNAJC3-AS1 in BC specimens was higher than that in the adjacent nontumor tissues ( p < 0.01). Diagnostic assays revealed that DNAJC3-AS1 has considerable diagnostic accuracy, with an area under the ROC curve (AUC) of 0.7457 ( p < 0.001). High DNAJC3-AS1 expression was positively associated with lymph node metastasis ( p = 0.010) and clinical stage ( p = 0.023). A survival study revealed that patients with high DNAJC3-AS1 expression had shorter overall survival ( p = 0.0067) and disease-free survival ( p < 0.0001) than those with low DNAJC3-AS1 expression. More importantly, multivariate assays indicated that DNAJC3-AS1 was an independent prognostic factor in BC patients. Functional assays confirmed that silence of DNAJC3-AS1 distinctly suppressed the proliferation, metastasis, and EMT progress of BC cells., Conclusions: DNAJC3-AS1 may be a prognostic and diagnostic biomarker for BC patients., Competing Interests: The authors declare that no conflict of interest exists in the paper., (Copyright © 2021 Yi Zhang et al.)

Background and Objectives: As an endocrine organ, the mass of skeletal muscle is closely related to human health. The present study aimed to investigate the relationship between regional skeletal muscle and nonalcoholic fatty liver disease (NAFLD) in Chinese elders., Methods and Study Design: A total of 1,328 participants (579 males and 749 females), aged 65 to 96 years were recruited between March to November 2020 in Qingdao, China. Of these, 400 cases and 400 healthy controls, matched by gender and age (±3 years), were included in the study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and body weight was adopted to standardize skeletal muscle mass to obtain skeletal muscle mass indexes., Results: Inverse associations were observed for trunk muscle mass index (TMI) (OR=0.42; 95% CI: 0.19, 0.93; p for trend=0.083) and leg skeletal muscle mass index (LMI) (OR=0.41; 95% CI: 0.18, 0.97; p for trend=0.012) with NAFLD risk after adjustment for age, body mass index, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, dietary intakes of energy, carbohydrate, protein and fat, smoking, alcohol drinking, education and physical activity. Dose-response analysis indicated that per standard deviation increment of LMI was associated with 23% (95%CI: 0.63, 0.95) reduction of NAFLD risk., Conclusions: The present study demonstrates that higher TMI and LMI are associated with a lower NAFLD risk.

Combining sweet sorghum (SS) with alfalfa for ensiling has the potential to make a high-quality silage with relatively a better nutrient balance. However, the existing data are insufficient about how changes in ratios of SS to alfalfa in different silage mixtures affect animal performance and meat quality. Therefore, the objective of this study was to determine the effect of feeding total mixed rations containing mixed silages of SS and alfalfa on growth performance, nutrient digestibility, carcass traits and meat quality of Karakul sheep. Five total mixed rations were formulated with different SS proportions at 100%, 80%, 60%, 40%, and 20% on a fresh weight basis. Thirty 4-month old male Karakul sheep with 25.5 ± 1.4 kg BW were randomly allocated into five treatment groups, each with six lambs for this experiment. The results indicated that the Karakul sheep consuming total mixed rations containing SS-Alfalfa (SS-AF) silage mixtures with a lower proportion of SS tended to increase nutrient digestibility, growth performance, carcass traits, and meat quality. Feeding diets with SS at 40% and 20% inclusion rate showed a significant linear increase in the apparent digestibility of DM, CP and NDF, as well as subcutaneous fat thickness and water holding capacity (P < 0.5). Moreover, reduction in SS inclusion rate in these diets caused significant (P < 0.05) linear and quadratic increases in DM intake, final BW, average daily gain, carcass weight, and the amino acid contents of meat (P < 0.05). Conversely, feeding diet with lower SS inclusion rate led to decrease in feed conversion ratio and shear force significantly (P < 0.05) for these sheep. It appears that 40% inclusion of SS was the optimal rate in making the SS-AF silage mixture for lambs to achieve a superior production performance and high-quality meat products in Karakul sheep. However, further research is needed to investigate the effect of feeding SS-AF silage mixtures alongside contrasting ingredients on rumen function, ruminal microorganisms and digestive enzyme activity of sheep and other ruminant animals., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Previous studies have shown that BMPR1B promotes follicular development and ovarian granulosa cell proliferation, thereby affecting ovulation in mammals. In this study, the expression and polymorphism of the BMPR1B gene associated with litter size in small-tail Han (STH) sheep were determined. The expression of BMPR1B was detected in 14 tissues of STH sheep during the follicular phase as well as in the hypothalamic-pituitary-gonadal (HPG) axis of monotocous and polytocous STH sheep during the follicular and luteal phases using quantitative polymerase chain reaction (qPCR). Sequenom MassARRAY ® single nucleotide polymorphism (SNP) technology was also used to detect the polymorphism of SNPs in seven sheep breeds. Here, BMPR1B was highly expressed in hypothalamus, ovary, uterus, and oviduct tissue during the follicular phase, and BMPR1B was expressed significantly more in the hypothalamus of polytocous ewes than in monotocous ewes during both the follicular and luteal phases ( P < 0.05 ). For genotyping, we found that genotype and allele frequencies of three loci of the BMPR1B gene were extremely significantly different ( P < 0.01 ) between the monotocous and polytocous groups. Association analysis results showed that the g.29380965A > G locus had significant negative effects on the litter size of STH sheep, and the combination of g.29380965A > G and FecB (Fec - fecundity and B - Booroola; A746G) at the BMPR1B gene showed that the litter size of AG-GG, AA-GG, and GG-GG genotypes was significantly higher compared with other genotypes ( P < 0.05 ). This is the first study to find a new molecular marker affecting litter size and to systematically analyze the expression of BMPR1B in different fecundity and physiological periods of STH sheep., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2021 Yu-Liang Wen et al.)

Introduction: Herbal medicine is commonly used by patients with chronic cough, but the role of herbal medicine for cough variant asthma (CVA) has not yet been clearly defined. For the first time, we performed a meta-analysis to integrate the current evidence of randomized controlled trials (RCTs) on this topic and assess the efficacy of herbal medicine in adults with CVA., Methods: A comprehensive search was conducted in electronic databases to identify RCTs of herbal medicine for adult CVA. Cochrane systematic review methods were followed, and the Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence., Results: Twenty-eight RCTs were included. Compared with placebo, moderate-quality evidence from two studies showed that herbal medicine was associated with reduced cough symptom score (CSS) (MD -1.15 points; 95% CI, -1.67 to -0.63) and visual analogue scale (VAS) (MD -1.76 points; 95% CI, -2.66 to -0.86). Compared with montelukast, low- to moderate-quality evidence from 11 studies indicated that herbal medicine was associated with improved Leicester Cough Questionnaire (LCQ) (MD 2.38 points; 95% CI, 1.32 to 3.44), reduced CSS (SMD -0.81 points; 95% CI, -1.09 to -0.53), and VAS (MD -1.34 points; 95% CI, -1.82 to -0.86). There were no significant differences between herbal medicine and ICS plus bronchodilator., Conclusions: In adults with CVA, herbal medicine may result in improved quality of life and reduced cough frequency and severity scores compared with placebo or montelukast. Herbal medicine was not better than ICS plus a bronchodilator but the evidence is very uncertain., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yuan-Bin Chen et al.)

Doxorubicin (DOX) could trigger congestive heart failure, which largely limited the clinical use of DOX. microRNAs (miRNAs) were closely involved in the pathogenesis of DOX-induced cardiomyopathy. Here, we aimed to investigate the effect of miR-152 on DOX-induced cardiotoxicity in mice. To study this, we used an adeno-associated viral vector to overexpress miR-152 in mice 6 weeks before DOX treatment, using a dose mimicking the concentrations used in the clinics. In response to DOX injection, miR-152 was significantly decreased in murine hearts and cardiomyocytes. After DOX treatment, mice with miR-152 overexpression in the hearts developed less cardiac dysfunction, oxidative stress, inflammation, and myocardial apoptosis. Furthermore, we found that miR-152 overexpression attenuated DOX-related oxidative stress, inflammation, and cell loss in cardiomyocytes, whereas miR-152 knockdown resulted in oxidative stress, inflammation, and cell loss in cardiomyocytes. Mechanistically, this effect of miR-152 was dependent on the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in response to DOX. Notably, Nrf2 deficiency blocked the protective effects of miR-152 against DOX-related cardiac injury in mice. In conclusion, miR-152 protected against DOX-induced cardiotoxicity via the activation of the Nrf2 signaling pathway. These results suggest that miR-152 may be a promising therapeutic target for the treatment of DOX-induced cardiotoxicity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wen-Bin Zhang et al.)

Ynamides, though relatively more stable than ynamines, are still moisture-sensitive and prone to hydration especially under acidic and heating conditions. Here we report an environmentally benign, robust protocol to synthesize sulfonamide-based ynamides and arylynamines via Sonogashira coupling reactions in water, using a readily available quaternary ammonium salt as the surfactant.

Background: Small extracellular vesicles (sEVs) from bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential for cerebral ischemic diseases. However, the mechanisms by which BMSC-derived sEVs (BMSC-sEVs) protect neurons against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we explored the neuroprotective effects of BMSC-sEVs in the primary culture of rat cortical neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) injury., Methods: The primary cortical neuron OGD/R model was established to simulate the process of cerebral I/R in vitro . Based on this model, we examined whether the mechanism through which BMSC-sEVs could rescue OGD/R-induced neuronal injury., Results: BMSC-sEVs (20 μg/mL, 40 μg/mL) significantly decreased the reactive oxygen species (ROS) productions, and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Additionally, BMSC-sEVs prevented OGD/R-induced neuronal apoptosis in vivo , as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) leakage, decreased terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining-positive cells, down-regulated cleaved caspase-3, and up-regulated Bcl-2/Bax ratio. Furthermore, Western blot and flow cytometry analysis indicated that BMSC-sEV treatment decreased the expression of phosphorylated calcium/calmodulin-dependent kinase II (p-CaMK II)/CaMK II, suppressed the increase of intracellular calcium concentration ([Ca 2+ ] i ) caused by OGD/R in neurons., Conclusions: These results demonstrate that BMSC-sEVs have significant neuroprotective effects against OGD/R-induced cell injury by suppressing oxidative stress and apoptosis, and Ca 2+ /CaMK II signaling pathways may be involved in this process., Competing Interests: Conflicts of interest: The authors indicated no potential conflicts of interest., (Copyright: © World Journal of Emergency Medicine.)

Background: In recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma., Methods: A bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro , along with a mouse xenograft model in vivo , to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data., Results: Bioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression., Conclusions: Our data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-1970). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The performance of the cathode significantly affects the ability of the electro-Fenton (EF) process to degrade chemicals. In this study, a simple method to modify the graphite felt (GF) cathode was proposed, i.e. oxidizing GF by hydrothermal treatment in nitric acid. The surface physical and electrochemical properties of modified graphite felt were characterized by several techniques: scanning electron microscope (SEM), water contact angle, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and linear scanning voltammetry (LSV). Compared with an unmodified GF (GF-0), the oxygen reduction reaction (ORR) activity of a modified GF was significantly improved due to the introduction of more oxygen-containing functional groups (OGs). Furthermore, the results showed that GF was optimally modified after 9 h (GF-9) of treatment. As an example, the H 2 O 2 generation by GF-9 was 2.26 times higher than that of GF-0. After optimizing the process parameters, which include the initial Fe 2+ concentration and current density, the apparent degradation rate constant of levofloxacin (LEV) could reach as high as 0.40 min -1 . Moreover, the total organic carbon (TOC) removal rate and mineralization current efficiency (MCE) of the modified cathode were much higher than that of the GF-0. Conclusively, GF-9 is a promising cathode for the future development in organic pollutant removal via EF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Plant architecture and disease resistance are the key factors that control the production of yield. However, the mechanism behind these factors is largely unknown. In this study, we identified that indeterminate domain 3 ( IDD3 ) was obviously induced by inoculation of Rhizoctonia solani AG1-IA. Plants that overexpressed IDD3 (IDD3 OX) were more susceptible, while idd3 mutants showed a similar response to sheath blight disease compared with wild-type plants. Interestingly, IDD3 OX plants developed a wider tiller angle and exhibited altered shoot gravitropism, while idd3 knock-out mutants showed no visible morphological differences compared with the wild-type plants. IDD3 is ubiquitously expressed in different tissues and stages, and the IDD3 transcript was induced by exogenously applied auxin. Expression of the PIN-FORMED (PIN) and Aux/IAA genes was altered in IDD3 OX compared with wild-type plants. Furthermore, IDD3 OX plants are sensitive to auxin and the polar auxin transporter inhibitor N-1-naphthylphalamic acid (NPA). Further yeast-one hybrid, chromatin immunoprecipitation (ChIP) and transient assays revealed that IDD3 directly represses PIN1b via promoter binding. Inoculation with R. solani indicated that PIN1b RNAi plants are more susceptible to sheath blight disease (ShB) compared with the wild-type. Taken together, our analyses suggest that IDD3 controls plant architecture and the resistance of rice to ShB via the regulation of PIN auxin transporter genes.

Objective: To evaluate the performance of 3.0T magnetic resonance imaging examination (MRI) for the local detecting of muscle invasive bladder cancer following transurethral resection of bladder tumor (TURBT)., Methods: Retrospective study identified 55 patients with pathology-proven bladder cancer who underwent transurethral resection of bladder tumor followed by 3.0T magnetic resonance imaging between September 2012 and April 2019 in our hospital. Two radiologists reviewed pelvic magnetic resonance imaging together and judged muscle invasive bladder cancer. Sensitivity, specificity and accuracy were calculated for the presence of muscle invasion by T2 weighted imaging (T2WI) only, diffusion-weighted imaging (DWI) only and T2WI+DWI compared with the findings at radical cystectomy as the reference standard., Results: Of the 55 patients with pathological results from radical cystectomy, 3.64% (2/55) had no residual disease; 29.09% (16/55) were non-muscle invasive bladder cancer on pathology, including 13 cases in T1 and 3 cases in Ta; 34.55% (19/55) were in stage T2 depending on pathology, 25.45% (14/55) in T3, and 7.27% (4/55) in T4. The average age was 60.76 years, ranging from 42 to 82 years. There were 48 males and 7 females in our study. Before pelvic MRI examination, all the patients received transurethral resection of bladder tumor, including 16 cases taking the operation in our hospital and 39 cases in other hospitals. The interval between the pelvic MRI examination and transurethral resection of bladder tumor was more than 2 weeks in all the patients. They all underwent radical cystectomy within 1 month after the pelvic MRI examination, and no patient underwent radiotherapy or chemotherapy in our study during the interval between the MRI examination and radical cystectomy. T2WI only, DWI only, and T2WI+DWI of 3.0T magnetic resonance imaging for readers were with sensitivity: 94.59%, 83.78%, 91.89%; with specificity: 66.67%, 77.78%, 72.22% and with accuracy: 85.45%, 81.82%, 85.45%, respectively., Conclusion: 3.0T MRI may have a role in diagnosing muscle invasive bladder cancer following TURBT. T2WI has the advantage of detecting the location of bladder tumor, and DWI has the advantage of differentiating between the benign and malignant lesion. 3.0T MRI T2WI+DWI has a good utility in the detection of muscle invasive bladder cancer following TURBT with satisfied accuracy.

Background and Objectives: The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies., Methods and Study Design: A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis., Results: Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration., Conclusions: The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.

Fos-like antigens (Fosl) including Fosl1 and Fosl2 exclusively heterodimerize with Jun members to form AP-1 complex, thereby participating in various cellular progresses including cell cycle regulation. However, expression patterns of these two genes during embryonic development remains largely unknown. In the present study, both temporal and spatial expression patterns of fosl1 and fosl2 were examined during embryonic development of Xenopus tropicalis. Real-time quantitative PCR results showed that the expression of the two genes was increased from stage 2 to stage 42. However, expression level of fosl1 is much higher than that of fosl2 at stage 42. Whole-mount in situ hybridization showed that fosl1 was expressed in eyes, branchial arch, notochord, otic vesicle, and liver. However, fosl2 was expressed in lung primordium from stage 34 to stage 38, in addition to the moderate expression in eyes and branchial arch at stage 42. Thus, the developmental expression patterns of these two fosl genes is different in Xenopus embryos. These results provide a basis for further functional study of these two genes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Animal studies have shown the beneficial effect of betaine supplementation on reducing body fat, while the data from human studies are controversial and inconsistent. The objective of the present systematic review was to investigate the effects of betaine intervention on treating obesity in humans and quantitatively evaluate the pooled effects based on randomized controlled trials with a meta-analysis. The PubMed and Scopus databases, and the Cochrane Library, were searched up to September 2019. Weighted mean differences were calculated for net changes in obesity-related indices by using a random-effects model. Publication bias was estimated using Begg's test. Six studies with 195 participants were identified. Betaine supplementation significantly reduced the total body fat mass (-2.53 kg; 95% CI: -3.93, -0.54 kg; I 2 = 6.6%, P = 0.36) and body fat percentage (-2.44%; 95% CI: -4.20, -0.68%; I 2 = 0.0%, P = 0.44). No changes were observed regarding body weight (-0.29 kg; 95% CI: -1.48, 0.89 kg; I 2 = 0.00%, P = 0.99) and body mass index (-0.10 kg/m 2 ; 95% CI: -5.13, 0.31 kg/m 2 ; I 2 = 0.00%, P = 0.84). The results suggested that dietary betaine supplementation might be an effective approach for reducing body fat.

The results of epidemiological studies on the relationship between fruit and vegetable intake and lung cancer risk were inconsistent among participants with different smoking status. The purpose of this study was to investigate these relationships in participants with different smoking status with prospective cohort studies. A systematic literature retrieval was conducted using PubMed and Scopus databases up to June 2019. The summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated by random-effects model. The nonlinear dose-response analysis was carried out with restricted cubic spline regression model. Publication bias was estimated using Begg's test. Nine independent prospective studies were included for data synthesis. Dietary consumption of fruit was negatively correlated with lung cancer risk among current smokers and former smokers, and the summery RRs were 0.86 (95% CI: 0.78, 0.94) and 0.91 (95% CI: 0.84, 0.99), respectively. Consumption of vegetable was significantly associated with reduced risk of lung cancer for current smokers (summary RR = 87%; 95% CI: 0.78, 0.94), but not for former smokers and never for smokers. Dose-response analysis suggested that risk of lung cancer was reduced by 5% (95% CI: 0.93, 0.97) in current smokers, and reduced by 4% (95% CI: 0.93, 0.98) in former smokers with an increase of 100 grams of fruit intake per day, respectively. Besides, dose-response analysis indicated a 3% reduction in lung cancer risk in current smokers for 100 gram per day increase of vegetable intake (95% CI: 0.96, 1.00). The findings of this study provide strong evidence that higher fruit consumption is negatively associated with the risk of lung cancer among current smokers and former smokers, while vegetable intake is significantly correlated with reducing the risk of lung cancer in current smokers. These findings might have considerable public health significance for the prevention of lung cancer through dietary interventions.

Background and Aims: Mucosal healing is regarded as a clinical endpoint of Crohn's disease (CD), and transmural healing is correlated to the concept of deep remission. Current therapies to induce mucosal and transmural healing in CD are not satisfactory. Exclusive enteral nutrition (EEN) is underestimated therapy and its value has not been fully evaluated. Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients., Methods: This was a prospective, single-center, open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University. All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein, erythrocyte sedimentation rate, platelets, hemoglobin, body mass index, CD activity index, simple endoscopic score for CD and bowel sonography. Azathioprine was combined to prevent relapse., Results: In this prospective observational study, 29 CD patients with an average age of 28.9 years were identified. After oral EEN treatment, 23 patients (79%) achieved complete mucosal healing, and the mean time to reach mucosal healing was 123 days (ranged from 50 to 212 days). Although only five patients (17%) achieved transmural healing, a significant reduction was observed in bowel-wall thickness (9.41 ± 3.06 vs 4.97 ± 1.76 mm, P  < 0.001) and a significant improvement was observed in complications (including fistulas, abscess, ascites, stricture) assessed by bowel sonography (all P  < 0.05)., Conclusions: Oral EEN therapy is highly effective for inducing mucosal healing in CD patients. Both CD patients at active stage and those at clinical remission show excellent clinical response to oral EEN.

Aim: To investigate whether monocyte to HDL cholesterol ratio (MHR) can improve the risk stratification of reduced renal function by estimating atherosclerosis. Patients & methods: The cross-sectional study included 8159 subjects (males: 45.73%, mean age: 54.12 years) from Northeast China in 2013. Results: Each standard deviation increase of MHR brought 42.9% additional risk of reduced renal function in males. In females, MHR strongly correlated with reduced renal function before it reached a breakpoint (MHR = 0.25). Additionally, net reclassification improvement identified the value of MHR (0.199; 95% CI: 0.030-0.369; p = 0.021) to improve the risk classification of renal function reduction. Conclusion: This study implicates that MHR is independently associated with reduced renal function and can refine the risk stratification of renal function reduction.

The patient was a female infant aged 1 month and 29 days. She was admitted to the hospital due to convulsions for 6 days and increased blood glucose level for 5 days. She had unstable blood glucose levels. The level of glycosylated hemoglobin was too high to measure. Urine glucose was positive (+ - ++++). The levels of fasting C-peptide and insulin were 0.19 ng/mL and 11.68 μIU/mL respectively. High-throughput sequencing of the genetic endocrine disease gene Panel (412 detected genes, including 49 known diabetes-related genes) showed that the EIF2AK3 gene in the infant had two novel compound heterozygous mutations, c.2731&#95;2732delAG and c.2980G>A, both of which were located in the kinase domain. The infant was diagnosed with Wolcott-Rallison syndrome (WRS). As a rare autosomal recessive disease, WRS is characterized by neonatal diabetes, multiple epiphyseal dysphasia and liver disease. Neonatal diabetes is a prerequisite for the diagnosis of WRS. The EIF2AK3 gene is the pathogenic gene of WRS.

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Objectives: Tanshinone IIA (T. IIA), one of the most pharmacologically active components extracted from Salviae miltiorrhiza , has anti-inflammatory and antioxidant features. The aim of the present study is to investigate the benefit of T. IIA on asthma using a murine model of asthma induced by ovalbumin (OVA)., Materials and Methods: Male BALB/c mice were used in the present study. The mice were sensitized by OVA intraperitoneal injection on days 0 and 14, and received aerosolized OVA challenge for 30 min daily on days 21-23. T. IIA (10 mg/kg twice daily) intraperitoneal injection was performed on days 18-23., Results: Treatment of T. IIA reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF) ( P <0.05 for all cases). The OVA-induced elevation of total white blood cells as well as differential white blood cells in BALF and blood were inhibited by T. IIA ( P <0.05 for all cases). Moreover, airway hyperresponsiveness was dampened in T. IIA-treated group ( P <0.05). T. IIA inhibited the activation of nuclear factor-κB in asthmatic mice ( P <0.05). The activity of nuclear factor erythroid-2-related factor 2 was enhanced in T. IIA-treated group ( P <0.05). T. IIA elevated the activities of heme oxygenase-1, glutathione peroxidase, and superoxide dismutase ( P <0.05 for all cases)., Conclusion: T. IIA inhibits OVA-induced airway inflammation and hyperresponsiveness. T. IIA is a potential therapeutic agent for asthma., Competing Interests: No conflict of interest was involved in this research.