Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

Protective Effect of Dihydromyricetin Against Exercise-Induced Muscle Damage and Its Mechanism.

Objective To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.Methods Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight ·d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.Conclusion DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Medical image segmentation of gastric adenocarcinoma based on dense connection of residuals.

BACKGROUND AND OBJECTIVE: Accurate segmentation of gastric cancer based on CT images of gastric adenocarcinoma is crucial for physicians to screen gastric diseases, clinical diagnosis, preoperative prediction, and postoperative evaluation plans. To address the issue of the inability of the segmentation algorithm to depict the correct boundaries due to unclear gastric contours in the lesion area and the visible irregular band-like dense shadow extending to the perigastric region, a 3D medical image segmentation model 3D UNet based on residual dense jumping method is proposed. METHODS: In the method we proposed, Residual Dense Block, which is applied to the image super-resolution module to remove CT artifacts, and Residual Block in ResNet are further fused. The quality of CT images is improved by Residual Dense Skip Block, which removes banded dense shadows, preserves image details and edge information, captures features, and improves the segmentation performance of gastric adenocarcinoma. The Instance Normalization layer position is modified to select the best result. Different loss functions are also combined in order to obtain the best gastric adenocarcinoma segmentation performance. RESULTS: We tested the model on a hospital-provided gastric adenocarcinoma dataset. The experimental results show that our model outperforms the existing methods in CT gastric adenocarcinoma segmentation, in which the method combining the hybrid loss function of Dice and CE obtains an average dice score of 82.3%, which is improved by 5.3% and 3.8% compared to TransUNet and Hiformer, respectively, and improves the cross-merge rate to 70.8%, compared to nnFormer, nnUNet by 1% and 0.9%, respectively. CONCLUSIONS: The residual jump connection structure indeed improves segmentation performance. The proposed method has the potential to be used as a screen for gastric diseases and to assist physicians in diagnosis.

Genetically Predicted Causal Effects of Gut Microbiota and Gut Metabolites on Digestive Tract Cancer: A Two-Sample Mendelian Randomization Analysis.

Background: Evidence from numerous observational studies and clinical trials has linked gut microbiota and metabolites to digestive tract cancer. However, the causal effect between these factors remains uncertain. Methods: Data for this study were obtained from the MiBioGen, TwinsUK Registry, and FinnGen (version R8). Two-sample Mendelian randomization analysis with inverse variance weighting method was primarily used, and the results were validated by heterogeneity analysis, pleiotropy test, and sensitivity analysis. Results: At P < 5 × 10-8, our analysis identified four gut microbiotas as risk factors for digestive tract cancer and six as risk factors for colorectal cancer. Conversely, one gut microbiota exhibited protection against bile duct cancer, and two showed protective effects against stomach cancer. At P < 1 × 10-5, our investigation revealed five, six, three, eight, eight, and eight gut microbiotas as risk factors for esophageal, stomach, bile duct, liver, pancreatic, and colorectal cancers, respectively. In contrast, four, two, eight, two, two, and five gut microbiotas exhibited protective effects against these cancers. Additionally, GABA, a metabolite of gut microbiota, displayed a significant protective effect against colorectal cancer. Conclusion: In conclusion, specific gut microbiota and metabolites play roles as risk factors or protective factors for digestive tract cancer, and a causal relationship between them has been established, offering novel insights into gut microbiota-mediated cancer development.

A Golgi-Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy.

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy.

Seasonal malaria chemoprevention in Africa and China's upgraded role as a contributor: a scoping review.

BACKGROUND: Children under five are the vulnerable population most at risk of being infected with Plasmodium parasites, especially in the Sahel region. Seasonal malaria chemoprevention (SMC) recommended by World Health Organization (WHO), has proven to be a highly effective intervention to prevent malaria. Given more deaths reported during the COVID-19 pandemic than in previous years due to the disruptions to essential medical services, it is, therefore, necessary to seek a more coordinated and integrated approach to increasing the pace, coverage and resilience of SMC. Towards this end, fully leverage the resources of major players in the global fight against malaria, such as China could accelerate the SMC process in Africa. METHODS: We searched PubMed, MEDLINE, Web of Science, and Embase for research articles and the Institutional Repository for Information Sharing of WHO for reports on SMC. We used gap analysis to investigate the challenges and gaps of SMC since COVID-19. Through the above methods to explore China's prospective contribution to SMC. RESULTS: A total of 68 research articles and reports were found. Through gap analysis, we found that despite the delays in the SMC campaign, 11.8 million children received SMC in 2020. However, there remained some challenges: (1) a shortage of fully covered monthly courses; (2) lack of adherence to the second and third doses of amodiaquine; (3) four courses of SMC are not sufficient to cover the entire malaria transmission season in areas where the peak transmission lasts longer; (4) additional interventions are needed to consolidate SMC efforts. China was certified malaria-free by WHO in 2021, and its experience and expertise in malaria elimination can be shared with high-burden countries. With the potential to join the multilateral cooperation in SMC, including the supply of quality-assured health commodities, know-how transfer and experience sharing, China is expected to contribute to the ongoing scale-up of SMC. CONCLUSIONS: A combination of necessary preventive and curative activities may prove beneficial both for targeted populations and for health system strengthening in the long run. More actions are entailed to promote the partnership and China can be one of the main contributors with various roles.

Drug resistance related genes in lung adenocarcinoma predict patient prognosis and influence the tumor microenvironment.

Lung adenocarcinoma (LUAD) is the predominant type of non-small lung cancer (NSCLC) with strong invasive ability and poor prognosis. The drug resistance related genes are potentially associated with prognosis of LUAD. Our research aimed to identify the drug resistance related genes and explore their potential prognostic value in LUAD patients. The data used in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Firstly, we screened drug resistance related genes in LUAD by differential gene analysis, univariate Cox regression and drug sensitivity analyses. Subsequently, we constructed a risk score model using LASSO Cox regression analysis, and verified whether the risk score can predict the survival of LUAD patients independent of other factors. Moreover, we explored the immune infiltration of 22 immune cells between high-risk and low-risk patients. Totally 10 drug-resistance positively related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) were identified in LUAD. The risk score model of LUAD constructed with these 10 genes could reliably predict the prognosis of LUAD patients. 18 pathways were significantly activated in high-risk group compared with low-risk group. In addition, the infiltration proportion of multiple immune cells was significantly different between high-risk and low-risk groups, and the proportion of M1 phagocytes was significantly higher in the high-risk group compared with the low-risk group. The drug resistance related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) could predict the prognosis of LUAD patients. Clarifying the roles and mechanisms of these 10 genes in regulating drug resistance in LUAD will help to improve individualized clinical treatment protocols and predict patient sensitivity to treatment.

Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Probiotic fermentation is a mild and safe biological method to boost the performance of herbs. Portulaca oleracea L. (PO), with folklore records of purgative, anti-dermatological and anti-epidemic effects, has been demonstrated to possess anti-inflammatory, immunomodulatory, and antioxidant properties. However, the potential of PO for the treatment of atopic dermatitis (AD) has not been sufficiently explored. AIM OF STUDY: This study aimed to evaluate the therapeutic benefits of PO and fermented Portulaca oleracea L. (FPO) and explore their intrinsic mechanisms. METHODS: By utilizing 2,4-dinitrofluorobenzene-induced AD mice as a model, the histopathology of the lesions was observed using H&E and toluidine blue staining methods; the levels of immunoglobulin E (Ig E), histamine (HIS), and thymic stromal lymphopoietin (TSLP) in serum were measured using ELISA, whereas, the expression of inflammatory cytokines in skin lesion was measured using ELISA and immunohistochemistry experiments. The expression of tumor necrosis factor-α (TNF-α), IKKα, NF-κB mRNA was measured using qPCR; and the expression of TNF-α、p-IKKα, p-IκBα, p-NF-κB was measured using western blotting. RESULTS: Both 20 mg/mL PO and FPO alleviated mast cell infiltration and lesion pathology, reduced serum levels of Ig E, HIS and TSLP, down-regulated the expression of AD-related inflammatory cytokines, such as, TNF-α, interferon-γ, and interleukin-4, and increased filaggrin expression. Furthermore, they inhibited the expression of TNF-α, IKKα, and NF-κB genes and TNF-α, p-IKKα, p-NF-κB and p-IκBα proteins associated with the NF-κB signaling pathway. CONCLUSIONS: PO and FPO has a positive therapeutic potential on AD, indicating that it may be employed as alternative therapies for AD.

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS.

The present study aimed to explore the potential roles of the methyltransferase­like 3 (METTL3)­mediated methylation of RAS related (RRAS) mRNA in the tumorigenesis and development of bladder cancer (BCa). For this purpose, the relative expression levels of METTL3 in BCa specimens and cell lines were measured using reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. The association between the METTL3 expression level and the clinical characteristics of patients with BCa was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis databases. Cellular experiments were performed to confirm the effects of METTL3 on the proliferative, migratory and invasive capacities of BCa cells. RT­qPCR, western blot analysis, methylated RNA immunoprecipitation (MeRIP)­qPCR and dual­luciferase report assays were utilized to verify the METTL3/RRAS/YTH N6­methyladenosine (m6A) RNA binding protein 2 (YTHDF2) regulatory axis in BCa. The results revealed that METTL3 expression was markedly increased in BCa specimens and cell lines, and was associated with poor clinical characteristics of patients with BCa. In vitro and in vivo assays demonstrated that the silencing of METTL3 markedly suppressed the proliferative, migratory and invasive capacities of BCa cells. MeRIP­PCR and dual­luciferase report assays indicated that METTL3 could bind to the m6A sites of RRAS mRNA and suppress the transcriptional activity of RRAS. YTHDF2 could recognize the m6A sites of RRAS and mediate RRAS degradation. On the whole, the findings of the present study reveal the pivotal role of METTL3­catalyzed m6A modification in BCa tumorigenesis and development. The change could facilitate BCa tumor growth and metastasis by suppressing RRAS expression in an m6A YTHDF2­dependent manner. Targeting the METTL3/RRAS/YTHDF2 regulatory axis may thus prove to be a promising strategy for the diagnosis and therapy of BCa.

L-kynurenine induces NK cell loss in gastric cancer microenvironment via promoting ferroptosis.

BACKGROUND: Natural killer (NK) cells play a major role in body's fighting against various types of cancers. Their infiltration in the tumor microenvironment (TME) of gastric cancer (GC) are significantly decreased, which has been reported as a robust prognostic marker. However, the causes leading to NK cells loss in GC TME remains poorly understood. METHODS: We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. Then through using the specific inhibitors for different types of cell death and examining the surrogate markers, we confirmed ferroptosis in NK cells. Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. RESULTS: We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. Further analysis revealed L-KYN induced ferroptosis in NK cells via an AHR-independent way. Moreover, we found NK cells with higher GPX4 expression showed resistance to L-KYN induced ferroptosis. Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC. CONCLUSIONS: Our study revealed a novel mechanism to explain the decline of NK cell number in GC TME. Notably, we also developed a potential immunotherapy strategy, which might be beneficial in clinical treatment in the future.

Fabrication of glycated yeast cell protein via Maillard reaction for delivery of curcumin: improved environmental stability, antioxidant activity, and bioaccessibility.

BACKGROUND: The application of curcumin (CUR) in the food industry is limited by its instability, hydrophobicity and low bioavailability. Yeast cell protein (YCP) is a by-product of spent brewer's yeast, which has the potential to deliver bioactive substances. However, the environmental stresses such as pH, salt and heat treatment has restricted its application in the food industry. Maillard reaction as a non-enzymatic browning reaction can improve protein stability under environmental stress. RESULTS: The CUR was successfully encapsulated into the hydrophobic core of YCP/glycated YCP (GYCP) and enhanced by hydrogen bonding, resulting in static fluorescence quenching of YCP/GYCP. The average diameter and dispersibility of GYPC-CUR nanocomplex were significantly improved after glucose glycation (121.40 nm versus 139.70 nm). Moreover, the encapsulation capacity of CUR was not influenced by glucose glycation. The oxidative stability and bioaccessibility of CUR in nanocomplexes were increased compared with free CUR, especially complexed with GYCP conjugates. CONCLUSION: Steric hindrance provided by glucose conjugation improved the enviriomental stability, oxidative activity and bioaccessibility of CUR in nanocomplexes. Thus, glucose-glycated YCP has potential application as a delivery carrier for hydrophobic compounds in functional foods. © 2022 Society of Chemical Industry.

Multilevel Heterogeneity of Colorectal Cancer Liver Metastasis.

Colorectal cancer liver metastasis (CRLM) is a highly heterogeneous disease. Therapies that target both primary foci and liver metastasis are severely lacking. Therefore, understanding the features of metastatic tumor cells in the liver is valuable for the overall control of CRLM patients. In this review, we summarize the heterogeneity exhibited in CRLM from five aspects (gene, transcriptome, protein, metabolism, and immunity). In addition to genetic heterogeneity, the other four aspects exhibit significant heterogeneity. Compared to primary CRC, the dysregulation of epithelial-mesenchymal transition (EMT)-related proteins, the enhanced metabolic activity, and the increased infiltration of immunosuppressive cells are detected in CRLM. Preclinical evidence shows that targeting the EMT process or enhancing cellular metabolism may represent a novel approach to increasing the therapeutic efficacy of CRLM.

The prognostic value of retinol binding protein in geriatric hip fractures after surgeries: A propensity score matching and 1-year follow-up study.

BACKGROUND: We aimed to explore the predictive value of retinol binding protein (RBP) for outcomes of hip fractures. METHODS: Patients with hip fractures who underwent hip surgeries between December 2017 and February 2021 and met the inclusion criteria were analyzed. Propensity score matching was used to reduce the bias of co-factors and ROC curves based on matched populations were created to determine the optimal cutoff point of RBP. The outcomes between patients with low levels of RBP and high levels of RBP were compared. RESULTS: Four hundred eighty patients were enrolled in this study and 69 patients died within one year. After a 1:1 PSM, patients with more than 1-year survival had significantly higher RBP (p = 0.013) than those who died within one year, as well as patients divided by 6-months survival (p = 0.012). Logistics analysis showed that low RBP may be an independent risk factor for 3-month survival, 6-month survival, 1-year survival, and 3-month free walking ability. CONCLUSION: RBP may be associated with the survival and 3-month walking abilities of patients with hip fractures.

A platinum-ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors.

Regulation of tumor hypoxia and redox homeostasis is a promising strategy for cancer therapy. Nanocatalytic medicine has played more and more important roles in this field because it can cleverly convert the efficiency and selectivity of catalysis into high therapeutic efficiency. Herein, we developed a platinum(iv)-ruthenium hybrid prodrug, named as Pt-Ru, for efficient chemo-catalytic synergistic therapy of hypoxic tumors. The ruthenium hybridization endowed the Pt(iv) prodrug with multi-enzyme catalytic activity, that is, mimicking catalase (CAT) to generate O2 in situ, mimicking peroxidase (POD) to produce reactive oxygen species, and mimicking glutathione peroxidase (GPx) to deplete GSH, thus effectively overcoming tumor hypoxia and cisplatin resistance. As a result, Pt-Ru treatment led to a superior anticancer efficacy to cisplatin both in vitro and in vivo. This work suggested redox homeostasis regulation as a tantalizing angle for developing the next generation of platinum drugs.

Crack Detection of Threaded Steel Rods Based on Ultrasonic Guided Waves.

Fatigue cracks are typical damage of threaded steel rods under dynamic loads. This paper presents a study on ultrasonic guided waves-based, fatigue-crack detection of threaded rods. A threaded rod with given sizes is theoretically simplified as a cylindrical rod. The propagation characteristics of ultrasonic guided waves in the cylindrical rod are investigated by semi-analytical finite element method and the longitudinal L(0, 1) modal ultrasonic guided waves in low frequency band is proposed for damage detection of the rod. Numerical simulation on the propagation of the proposed ultrasonic guided waves in the threaded rod without damage shows that the thread causes echoes of the ultrasonic guided waves. A numerical study on the propagation of the proposed ultrasonic guided waves in the threaded rod with a crack on the intersection of the smooth segment and the threaded segment shows that both linear indexes (Rf and ARS) and nonlinear indexes (ßre' and ß') are able to detect the crack. A constant-amplitude tensile fatigue experiment was conducted on a specimen of the threaded rod to generate fatigue cracks in the specimen. After every 20,000 loading cycles, the specimen was tested by the proposed ultrasonic guided waves and evaluated by the linear indexes and nonlinear indexes. Experimental results show that both the linear and nonlinear indexes of the ultrasonic guided waves are able to identify the crack before it enters the rapid growth stage and the nonlinear indexes detect the crack easier than the linear indexes.

Prealbumin as a nutrition status indicator may be associated with outcomes of geriatric hip fractures: a propensity score matching and 1-year follow-up study.

AIM: Nutrition status may affect bone metabolism and regeneration in the elderly. However, few studies reported a sensitive nutrition indicator or evaluation tool for geriatric hip fractures. This study aimed to explore if prealbumin (PAB), a critical nutrition-related protein, is related to the prognosis of hip fractures. METHODS: Patients with hip fractures who met the inclusion criteria were included in our study. Geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) were calculated. Propensity score matching (PSM) was used to reduce the influence of confounding factors and ROC curves were conducted to explore the optimal cutoff points of PAB and to compare the prognostic value between GNRI, PNI, and PAB. Then Cox and Logistics analyses were performed to identify the relation between PAB and outcomes of hip fractures. RESULTS: Out of the 546 patients enrolled in this study, 91 patients died within one year. After a 1:1 PSM, the patients with less than 1-year survival had significantly lower PAB (p < 0.001) than those who were still alive at one year. ROC curves showed that the PAB may sensitively predict 6-month survival (AUROC: 0.695), 1-year survival (AUROC: 0.696), and 1-year-free walking ability (AUROC: 0.642). Logistics analysis showed that low PAB may be an independent risk factor for survival and 1-year-free walking ability. CONCLUSION: Low levels of PAB may be associated with poor survival and walking abilities of older patients after surgery for hip fracture.

Identification of metastasis-related long non-coding RNAs in lung cancer through a novel tumor mesenchymal score.

Long non-coding RNAs (lncRNAs) have been proven to play critical roles in epithelial-mesenchymal transition (EMT) and metastasis of lung cancer. However, the biological functions and related mechanisms of lncRNAs are unclear. In addition, the EMT-based prognosis prediction in lung cancer still lacks investigation. Here, we established the methodology of identifying critical metastasis-related lncRNAs using comprehensive datasets of cancer transcriptome, genome and epigenome, and also provided tools for prognosis prediction in lung cancer. Initially, important mesenchymal marker genes were identified to compose the tumor mesenchymal score, which predicted patient prognosis in lung cancer, especially lung adenocarcinoma (LUAD). The score was also correlated with several crucial biological and physiological processes, such as tumor immune and hypoxia. Based on the score, lung cancer patients was classified into epithelial and mesenchymal subtypes, and lncRNAs which exhibited expressional dysregulation, promotor methylation alteration and copy number variation between the two subtypes in LUAD were identified and underwent further prognostic analyses. Finally, we identified 14 lncRNAs as EMT-related and significant biomarkers in prognosis prediction of LUAD. As validation, lncRNA RBPMS-AS1 was proven to be co-expressed with epithelial biomarkers, suppressive for A549 cell migration, invasion and EMT, and also significantly associated with better outcomes of LUAD patients, suggesting the potential of RBPMS-AS1 to serve as a lncRNA epithelial biomarker in metastasis of LUAD. Based on the identified lncRNAs, an EMT-linked lncRNA prognostic signature was further established. Taken together, our study provides robust predictive tools, potential lncRNA targets and feasible screening strategies for future study of lung cancer metastasis.

[Acupuncture combined with western medication for ocular myasthenia gravis: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism. METHODS: A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 µs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method. RESULTS: After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 µs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05). CONCLUSION: Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.

Axial Stress Measurement of Steel Tubes Using Ultrasonic Guided Waves.

Axially loaded steel tubes are widely used as primary structural members in civil engineering structures. In this paper, a stress measurement method for axially loaded steel tubes is developed based on the linear relationship between the group velocity of guided waves in the steel tube and the stress of the steel tube. The propagation modes of guided waves in a typical steel tube are analyzed using semi-analytical finite element method. A torsional mode T(0,1) is adopted to conduct the measurement. Experiments are carried out to calibrate the linear relationship between the group velocity of guided waves in a steel tube and the stress of the steel tube. The calibrated linear relationship is verified by another round of experiments on the same steel tube specimen. There is an average error of 8.2% between the stresses predicted by the calibrated linear equation and those obtained from strain gauges. Via this study, the guided wave-based stress measurement method has been successfully extended to axially loaded steel tubes.