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It is increasingly appreciated that long non-coding RNAs (lncRNAs) associated with alternative splicing (AS) could be involved in aggressive hepatocellular carcinoma. Although many recent studies show the alteration of RNA alternative splicing by deregulated lncRNAs in cancer, the extent to which and how lncRNAs impact alternative splicing at the genome scale remains largely elusive. We analyzed RNA-seq data obtained from 369 hepatocellular carcinomas (HCCs) and 160 normal liver tissues, quantified 198,619 isoform transcripts, and identified a total of 1,375 significant AS events in liver cancer. In order to predict novel AS-associated lncRNAs, we performed an integration of co-expression, protein-protein interaction (PPI) and epigenetic interaction networks that links lncRNA modulators (such as splicing factors, transcript factors, and miRNAs) along with their targeted AS genes in HCC. We developed a random walk-based multi-graphic (RWMG) model algorithm that prioritizes functional lncRNAs with their associated AS targets to computationally model the heterogeneous networks in HCC. RWMG shows a good performance evaluated by the ROC curve based on cross-validation and bootstrapping strategies. As a conclusion, our robust network-based framework has derived 31 AS-related lncRNAs that not only validates known cancer-associated cases MALAT1 and HOXA11-AS, but also reveals new players such as DNM1P35 and DLX6-AS1with potential functional implications. Survival analysis further provides insights into the clinical significance of identified lncRNAs.

Nanocrystalline metals and alloys with grain sizes smaller than 100 nm have attractedextensive interest due to their improved mechanical, physical and chemical properties.Although electrodeposition has been one of the methods for synthesizing nanocrystallinematerials, properties of nanocrystalline electrodeposits are less evaluated, especially fortribological applications or potential applications in nanoscale devices such asMEMS and NEMS. In this work, nanocrystalline and microcrystalline copperdeposits were produced by pulse and direct current electrodeposition processesrespectively. Effects of deposition parameters, such as the peak density, frequency,current-on time and current-off time of the pulse current (PC), on the grain size wereinvestigated for the purpose of process optimization. The grain size of nanocrystallinecoatings was determined using x-ray diffraction and atomic force microscopy (AFM).Mechanical and tribological properties of the deposits were investigated usingnanoindentation, nanoscratch and microscratch techniques. It was demonstrated that thenanocrystalline film was markedly superior to regularly grained film made by direct current(DC) plating; the nanocrystalline deposit shows higher hardness, lower frictioncoefficient and lower wear rate. The surface electron stability and chemical reactivityof the deposits were also evaluated by measuring their electron work function(EWF). Results indicate that the nanocrystalline surface is more electrochemicallystable than the DC-plated one. This increased stability result is attributed to theformation of a stronger and more adherent passive film on the nanocrystallinecopper, confirmed by potentiodynamic polarization and electrical contact resistancemeasurements. [ABSTRACT FROM AUTHOR]

A novel lactic acid bacterial strain (designated N163-3-2 T ), isolated from traditional Chinese pickle ('Suan cai'), was characterized using a polyphasic approach. Strain N163-3-2 T was most closely related to the type strains of Lacticaseibacillus baoqingensis, Lacticaseibacillus manihotivorans, and Lacticaseibacillus porcinae, having 97.9-98.4% 16S rRNA gene, 82.0-85.1% pheS, 87.5-87.8% rpoA, and 85.8-86.7% concatenated pheS and rpoA sequence similarities. Strain N163-3-2 T had 74.4-81.7% ANI, 22.6-23.9% dDDH, and 74.0-75.1% AAI values with L. baoqingensis 47-3 T , L. manihotivorans DSM 13343 T and L. porcinae JCM 19617 T , less than the threshold for species demarcation (95-96%, 70% and 95-96%, respectively), indicating that strain N163-3-2 T represented a novel species of the genus Lacticaseibacillus. Based upon the data obtained in the present study, a novel species, Lacticaseibacillus jixiensis sp. nov., is proposed, and the type strain is N163-3-2 T (= CCTCC AB 2024125 T  = JCM 36999 T )., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed., Study Design: Descriptive laboratory study., Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists., Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers., Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts., Clinical Relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion., (© 2024 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

This study proposes an innovative method for structural health monitoring of simply supported PCI girder bridges based on dynamic strain and edge computing. Field static and dynamic load tests were conducted on a bridge consisting of a span with newly replaced PCI girders and numerous spans with old PCI girders. Both the static and dynamic test results showed that the flexural rigidity of the old PCI girders decreased significantly due to deterioration. To improve the efficiency of on-site monitoring data transmission and data analysis, this study developed a smart dynamic strain gauge node with the function of edge computing. Continuous data with a sampling frequency of 100 Hz were computed at the sensor node. Among the computed results, only the maximum dynamic strain data caused by the passage of the heaviest vehicle within 1 min were transmitted. The on-site monitoring results indicated that under routine traffic conditions, the dynamic strain response of the new PCI girder was smaller than that of the deteriorated PCI girder. When the monitored dynamic strain response has a tendency to magnify, attention should be paid to the potential prestress loss or other deterioration behaviors of the bridge.

There are few studies on the changes of gut microbiota in patients with gallstones, especially in patients with asymptomatic gallstones, and there are some deficiencies in these studies, for instance, the effects of metabolic factors on gut microbiota are not considered. Here, we selected 30 asymptomatic gallstone patients from the survey population, and 30 controls according to the age and BMI index matching principle. The 16SrDNA technology was used to detect and compare the structural differences in the gut microbiota between the two groups. Compared with healthy controls, the abundance of gut microbiota in patients with gallstones increased significantly, while the microbiota diversity decreased. At the level of phylum, both groups were dominated by Firmicutes , Bacteroides , Proteobacteria , and Actinobacteria . At the genus level, there were 15 species with significant differences in abundance between the two groups. Further subgroup analysis found that only unclassified Lactobacillales showed differences in the intestines of gallstones patients with hypertension, non-alcoholic fatty liver disease, or patients with elevated BMI (≧24). The structure of gut microbiota in patients with gallstones changed significantly, and this might be related to the occurrence of gallstones, rather than metabolic factors such as hypertension, non-alcoholic fatty liver disease, and obesity., 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 Song, Cai, Zeng and Xie.)

Mast cells (MCs) are strategically located at the host-environment interface and their non-allergic roles in the immune-surveillance of pathogens have recently gained more attention. However, MC-caused detrimental regulation of immune inflammations can promote viral invasion. Currently, the role of MCs in retroviral infection remains elusive. We have recently proved that human gut MCs could capture and transfer HIV-1 to CD4 + T cells for promoting viral spread; MC-released histamine augments HIV-1-induced functional polarization of dendritic cells to cause immunosuppression via stimulating the differentiation of regulatory T cells. In this study, we used a murine model of MuLV/Friend virus infection to address MC role in acute retroviral infection in vivo . The acute infection of MuLV/Friend virus could be established in C57BL/6 wild type mice, but viral acquisition showed low efficiency in C57BL/6- Kit W - sh/W - sh (Sash) mice which lack MCs. In mechanism, we found that MuLV/Friend virus triggered MC activation for degranulation; MC degranulation subsequently activated the granulocyte-like myeloid derived suppressive cells (G-MDSCs) to inhibit CD8 + T cells- and NK cells-mediated antiviral immune responses. The reconstruction of MCs in Sash mice promoted acute retroviral infection by regulating G-MDSCs functions and antiviral immune responses. Importantly, the administration of MC stabilizers to block cell degranulation elevated antiviral immune response and consequently suppressed retrovirus infection. This study uncovers a specific role of MCs in acute retroviral infection and elucidates the underlying immune-mechanisms. Targeting MCs may provide a novel approach for controlling acute infection by retroviruses., 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 Song, Wu, Zhang, Su and Wang.)

Since the meniscus is an important stabilizing structure of the knee joint and has a significant role in load-bearing and shock absorption, so the complete structural and functional reconstructions of the teared menisci should be done not only after partial meniscectomy but also post total meniscectomy. So far, animal experiments and good clinical practice have showed that TMAT after total meniscectomy has partially solved the problem of structural and functional reconstructions after total meniscectomy. However, partial meniscectomy will also lead to accelerated knee degeneration, and its proportion is much higher than that of patients with total meniscectomy. Herein, the feasibility of PMAT after partial meniscectomy was investigated for the first time by using the 40% posterior horn meniscectomy model of the medial meniscus in Beagle dogs, and also for the first time, TMAT group and the total meniscectomy group were used as control groups. Compared with the TMAT, the transcriptomics evaluation, scanning electron microscope observation, histological regeneration and structure, biomechanical property, inflammation environment, and the knee function post PMAT were more similar to that of normal meniscus was first reported. This study provides a PMAT scheme with clinical translational value for the complete structural and functional reconstruction of the patients with partial meniscectomy and fills the gap in the field of teared meniscus therapy on the basis of quite well clinical applications of the meniscus repair and the TMAT., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The strict tolerance space of three-dimensional (3D) crystalline structures is still a significant challenge in the area of switching dielectrics in comparison with lower-dimensional structures. Generally, the function of crystalline materials can be given or adjusted by controlling the environment in which synthesis takes place or the packing rearrangement. Using this method, special functional enhancements or changes in the dielectrics can be realized by improving the synthetic strategies. Here, a 3D switchable dielectric compound [MeHdabco]K(BF4)3 was achieved by employing the temperature selective effect. In particular, its structure is completely different from the usual 3D perovskite structure, which is constructed using two different cation-template frameworks. Moreover, the 3D [MeHdabco]K(BF4)3 shows a structural phase transition at 358 K. The thermal analysis (differential scanning calorimetry (DSC)) and X-ray diffractometry results provided evidence of these phase changes. This work provides a feasible strategy that can be used to achieve the different structures of an 'isomer', and enrich the method used for designing diverse functional materials.

Inflammation plays a major role in the development of myocardial ischemia-reperfusion (IR) injury. Recombinant human brain natriuretic peptide (rhBNP), a man-made version of a peptide that is elevated in heart failure, exhibits anti-inflammatory effects in various tissues. However, its role in myocardial IR injury remains unclear. In this study, we demonstrate that treatment with rhBNP provided protection for mice against myocardial IR injury as manifested by reduced infarct size and well-preserved myocardial, attenuated inflammatory infiltration and CD4 + T cell proliferation function, and inhibited expression of proinflammatory related genes. Furthermore, mechanistic studies revealed that rhBNP inhibited Jurkat T proliferation by promoting PI3K/AKT/mTOR phosphorylation. Collectively, our data suggest that the administration of rhBNP during IR injury could expand our understanding of the cardioprotective effects of rhBNP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020 Kun-Peng Li et al.)

Background: Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear., Methods: PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis., Results: A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events., Conclusion: Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans., (Copyright © 2020 Chen, Yan, Yuan, Ye, Xu, Zhou, Mao, Guan, Song, Sun, Wang, Chen, Wang, Fan, Yang, Song, Jiang and Yu.)

Objective: To explore the prevalence of and risk factors for gallstone disease in Shanghai, China., Methods: A population-based cross-sectional study was conducted in Shanghai between 2016 and 2017. Using a three-stage stratified sampling strategy, 4009 participants (1753 men and 2256 women) from 10 districts were enrolled., Results: The overall prevalence of gallstones was 6.83% (6.22% for men vs 7.31% for women, P = 0.173). According to the multivariate analysis, individuals aged ≥40 years (odds ratio [OR] 3.058, 95% confidence interval [CI] 2.110-4.433, P < 0.001), hypertension (OR 1.479, 95% CI 1.076-2.034, P = 0.016), thyroid disease (OR 1.409, 95% CI 1.029-1.928, P = 0.032), a family history of gallstones (OR 2.234, 95% CI 1.362-3.662, P = 0.001) and a waist-to-height ratio ≥0.5 (OR 1.656, 95% CI 1.197-2.292, P = 0.002) had an increased risk of developing gallstones. The risk of gallstone disease was 2.232 (95% CI 1.167-4.268, P = 0.015) times higher in individuals with elevated C4 levels than in those with normal C4 levels. Diabetes (OR 4.144, 95% CI 1.171-14.671, P = 0.028) was a risk factor for the formation of gallstones with diameters ≥1 cm, and men were more susceptible to develop multiple stones (OR 2.356, 95% CI 1.321-4.200, P = 0.004)., Conclusion: Individuals aged ≥40 years, with a history of hypertension and familial gallstones, a high waist-to-height ratio, thyroid disease and high C4 levels were related to an increased risk of gallstone disease., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

Objective: To observe the effects of acupuncture on resting-state functional connectivity (rs-FC) in patients with refractory peripheral facial paralysis, and to preliminarily explore the central mechanism of acupuncture for this disease., Methods: Twenty patients with refractory peripheral facial paralysis were selected as subject and treated with acupuncture at Qianzheng (EX-HN 16), Fengchi (GB 20), Cuanzhu (BL 2), Dicang (ST 4), Jiache (ST 6), Shuigou (GV 26), Chengjiang (CV 24), Yifeng (TE 17), Touwei (ST 8), Sibai (ST 2), Yingxiang (LI 20) and Hegu (LI 4), once every other day, three times a week, 15 times as a course of treatment. The 1-course treatment was given. The score of Sunnybrook (Toronto) facial grading system was used to evaluate the clinical efficacy before and after the treatment. In addition, 20 healthy volunteers were selected as control. For patients, the resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment, for healthy volunteers, the scans were performed when they were recruited. The brain magnetic resonance images were analyzed with left primary motor area (LMⅠ) and right primary motor area (RMⅠ) as regions of interest. The differences of rs-FC between patients with refractory peripheral facial paralysis before and after treatment and healthy volunteers were compared., Results: Compared before treatment, the Sunnybrook score was increased after the treatment ( P <0.05). Compared with healthy volunteers, the functional connection between bilateral primary motor areas (MⅠ) and multiple brain areas were enhanced in patients before treatment, and most of brain areas were located in the anterior motor area (middle frontal gyrus, superior frontal gyrus), posterior central gyrus, anterior cuneiform lobe, middle temporal gyrus, inferior temporal gyrus and cerebellum lobe. Compared before treatment, the left inferior frontal gyrus was the strong functional connection area between LMⅠ and whole brain after acupuncture treatment, and there was no significant difference between RMⅠ and resting-state whole brain. Compared with healthy volunteers, the functional connections between bilateral MⅠ and multiple brain regions were enhanced after acupuncture, and most of the main brain regions were consistent with those before treatment., Conclusion: (1) Acupuncture could effectively improve the clinical symptoms of refractory peripheral facial paralysis. (2) The brain function of patients with refractory peripheral facial paralysis has been changed before acupuncture, which may be caused by the reactive compensation of the brain. (3) Acupuncture could enhance the functional connection between LMⅠ and left inferior frontal gyrus to promote the compensatory response, which may be one of the central mechanisms of acupuncture for refractory peripheral facial paralysis.

The aim of this work is to convert agroforestry residue to a novel adsorbent (M-1CTA-SDS-BT) used for adsorptive benzene sequestration from aqueous solution. In this study, the anionic surfactant-coated-cationized banana trunk was synthesized and characterized for batch adsorption of benzene from aqueous solution. The surface morphology, surface chemistry, surface area, and pore properties of the synthesized adsorbents were examined. It was proven that surface cationization successfully increased the benzene adsorption capacity of sodium dodecyl sulfate-coated adsorbents. The Langmuir isotherm model satisfactorily described the equilibrium adsorption data. The maximum benzene adsorption capacity (q max ) of 468.19 μmol/g was attained. The kinetic data followed the pseudo-second-order kinetic model in which the rate-limiting step was proven to be the film diffusion. The batch-adsorbent regeneration results indicated that the M-1CTA-SDS-BT could withstand at least five adsorption/desorption cycles without drastic adsorption capacity reduction. The findings demonstrated the adsorptive potential of agroforestry-based adsorbent as a natural and cheap material for benzene removal from contaminated water.

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01-1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03-2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24-0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85-1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03-9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12-28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.

Acupuncture was proven beneficial in treating allergic inflammation. We aimed to explore the regulation underlying the effects of acupuncture on Feishu, an acupoint most commonly used in the acupuncture therapy for respiratory diseases, with respect to the system of sympathetic nerve neurotransmitter acetylcholine (Ach). Male Wistar rats were randomly grouping. No treatment was taken in the normal group. Allergic asthma was induced using ovalbumin on the model, Feishu acupuncture, and sham acupuncture groups; then control or acupuncture treatment lasting for 3 weeks was performed. Bronchoalveolar lavage fluid (BALF) from the four groups was examined. And pulmonary tissues were subjected to histological analysis with H&E staining; besides, immunofluorescent staining, quantitative PCR, and western blot were used to detect synthetase (ChAT) and Ach hydrolase (AchE), and its muscarinic receptors (mAchRs) M1-M3. There was inflammatory infiltration in the lung upon allergic asthma, which was alleviated by the Feishu acupuncture. The eosinophilic granulocytes, neutrophils, and lymphocytes in BALF from the Feishu acupuncture group were all significantly decreased compared with those of the model and sham acupuncture groups. The specific acupuncture on Feishu upon allergic asthma put down the pulmonary expression of ChAT, repaired at the level of gene expression the pulmonary expression of mAchR M1, and restored the pulmonary expression of mAchR M2 (especially in the bronchiolar epithelium) which has a role in inhibiting Ach release; while sham acupuncture had no effect. These results confirmed the therapeutic effects of Feishu acupuncture on allergic asthma, suggesting that the mechanisms may involve suppression of the Ach signal both from its synthesis and during its release.

To investigate the expression patterns of activation-induced cytidine deaminase (AID) variants in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and examine their clinical implications, we isolated PBMCs from healthy controls (HC, n = 33) and patients with AS (n = 62), and measured mRNA expression of AID variants and translesion synthesis (TLS) polymerases using quantitative real-time polymerase chain reaction. The proportion of patients with AS in whom AID splicing variant (sv) 2 was expressed was significantly higher than that of HC (p = .031). 80.7% of AS patients were treated with tumour necrosis factor inhibitor (TNFi). Significantly higher proportion of the TNFi-treated group expressed sv2 compared to the TNF-naïve group (p = .037). And we compared the level of AID variants expression between the TNFi-treated group and the TNF-naïve group. The expression levels of AID full-length (FL) and sv1 were significantly lower in the TNFi-treated group than the TNF-naïve group (FL: p = .002, sv1: p = .045). In addition, we investigated mRNA expression levels of translesion synthesis (TLS) polymerases in PBMCs from patients with AS and HC. The expression level of TLS pol ι was significantly lower in patients with AS than in HC (p = .007). In conclusion, AS patients expressed significantly higher levels of sv2 than HC. TNFi treatment restored the gene expression of the AID variants (FL, sv1, and sv2) in patients with AS. A clear understanding of the underlying cellular and molecular mechanisms will help to identify the pathogenesis of AS better and to develop novel therapeutic targets.

Objective: To investigate the changes in tumor necrosis factor alpha (TNF-α) serum levels after cardiopulmonary bypass (CPB) in children with congenital heart disease (CHD), followed by a meta-analysis to analyze the clinical value of TNF-α in CPB., Methods: Our cohort study enrolled 67 CHD children, assigned into off-pump group (n=32) and CPB group (n=35). The TNF-α serum levels in two groups were detected by ELISA before the operation (T1), at the end of the operation (0 hour, T2), and after 24 hours of the operation (T3). For meta-analysis, literature search was conducted to identify published case-control articles about the changes of TNF-α serum levels with CPB of CHD., Results: The TNF-α levels in CPB group were lower than that in the off-pump group at T3 (P=.006). TNF-α level at T3 was significantly lower than that at T1 and T2 (all P<.05). Meta-analysis results further confirmed that the TNF-α levels of CHD children were dramatically decreased at T3 as compared to that at T1 and T2 (both P<.001)., Conclusion: The TNF-α serum levels showed a transient and dramatic decline after 24 hours of CPB, and it may act as an important biological indicator for monitoring the efficacy of CPB in CHD children., (© 2016 Wiley Periodicals, Inc.)

Obiective: To explorethe correlation between Neo-Bioscore and disease-free survival (DFS) after neoadjuvant therapy in patients with breast cancer in China. Methods: The clinical and pathological data of 429 patients with early or locally advanced breast cancer who received neoadjuvant therapy at the No.307 Hospital of PLA from January 1, 2005 to December 31, 2015 were analyzed and we followed up their DFS. Results: Neo-Bioscore were closely related to DFS (χ(2)=47.662, P <0.001). When the groups were divided by Neo-Bioscore 3, they weremore relevantto DFS ( HR =5.093 vs HR =2.044), equivalent tothe role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for hormone receptor (HR) positive patients who were premenopausalafter neoadjuvant chemotherapy, andmore relevantto DFS than whetherthe pathologic complete response (pCR)grouping in the same molecular pathology subgroup of HR positive/human epidermal growth factor receptor 2 (HER-2)negative ( P <0.001 vs P =0.166), HER-2 positive ( P <0.001 vs P =0.166), HRnegative/HER-2 negative ( P <0.001 vs P =0.166). Conclusions: Neo-Bioscore could be used as an early indicator of predicting DFS for breast cancer patients after neoadjuvant therapy.When the groups were divided by Neo-Bioscore 3, they were more relevant to DFS, equivalent to the role of traditional recurrence risk grouping in guiding the choice of adjuvantendocrine regimen for premenopausal HR positive patients, andmore relevantto DFS than whetherthe pCRgrouping in the same molecular pathology subgroup.

This study was conducted to investigate the potential application of oil palm empty fruit branches (OPEFB) as adsorbents to remove organic methylmercurry, MeHg(II), and inorganic Hg(II) from aqueous solution. The OPEFB was functionalized with amine containing ligand namely 3-ureidopropyltriethoxysilane (UPTES) aiming for better adsorption performance towards both mercury ions. The adsorption was found to be dependent on initial pH, initial concentraton, temperatures, and contact time. The maximum adsorption capacities (Q m.exp ) of Hg(II) adsorption onto OPEFB and UPTES-OPEFB were 0.226 and 0.773 mmol/g, respectively. The Q m.exp of MeHg(II) onto OPEFB, however, was higher than UPTES-OPEFB. The adsorption kinetic data obeyed the Elovich model and the adsorption was controlled by the film-diffusion step. The calculated thermodynamic parameters indicate an endothermic adsorption process. Adsorption data analysis indicates that the adsorption mechanism may include ion-exchange, complexation, and physisorption interactions. The potential applications of adsorbents were demonstrated using oilfield produced water and natural gas condensate. The UPTES-OPEFB offered higher selectivity towards both mercury ions than OPEFB. The regenerability studies indicated that the adsorbent could be reused for multiple cycles.

Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

An effective organoalkoxysilanes-grafted lignocellulosic waste biomass (OS-LWB) adsorbent aiming for high removal towards inorganic and organic mercury (Hg(II) and MeHg(II)) ions was prepared. Organoalkoxysilanes (OS) namely mercaptoproyltriethoxylsilane (MPTES), aminopropyltriethoxylsilane (APTES), aminoethylaminopropyltriethoxylsilane (AEPTES), bis(triethoxysilylpropyl) tetrasulfide (BTESPT), methacrylopropyltrimethoxylsilane (MPS) and ureidopropyltriethoxylsilane (URS) were grafted onto the LWB using the same conditions. The MPTES grafted lignocellulosic waste biomass (MPTES-LWB) showed the highest adsorption capacity towards both mercury ions. The adsorption behavior of inorganic and organic mercury ions (Hg(II) and MeHg(II)) in batch adsorption studies shows that it was independent with pH of the solutions and dependent on initial concentration, temperature and contact time. The maximum adsorption capacity of Hg(II) was greater than MeHg(II) which respectively followed the Temkin and Langmuir models. The kinetic data analysis showed that the adsorptions of Hg(II) and MeHg(II) onto MPTES-LWB were respectively controlled by the physical process of film diffusion and the chemical process of physisorption interactions. The overall mechanism of Hg(II) and MeHg(II) adsorption was a combination of diffusion and chemical interaction mechanisms. Regeneration results were very encouraging especially for the Hg(II); this therefore further demonstrated the potential application of organosilane-grafted lignocellulosic waste biomass as low-cost adsorbents for mercury removal process., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating LTR activity contribute to HIV-1 latency, and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleocytoplasmic shuttling protein that regulates multiple cellular signaling pathways and HIV-1 production. We recently reported that nuclear Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to increased Gag production. Here we demonstrate new functions of Naf1 in regulating HIV-1 persistence. We found that Naf1 contributes to the maintenance of HIV-1 latency by inhibiting LTR-driven HIV-1 gene transcription in a nuclear factor kappa B-dependent manner. Interestingly, Naf1 knockdown significantly enhanced viral reactivation in both latently HIV-1-infected Jurkat T cells and primary central memory CD4 + T cells. Furthermore, Naf1 knockdown in resting CD4 + T cells from HIV-1-infected individuals treated with antiretroviral therapy significantly increased viral reactivation upon T-cell activation, suggesting an important role of Naf1 in modulating HIV-1 latency in vivo Our findings provide new insights for a better understanding of HIV-1 latency and suggest that inhibition of Naf1 activity to activate latently HIV-1-infected cells may be a potential therapeutic strategy., Importance: HIV-1 latency is characterized mainly by a reversible silencing of LTR promoter-driven transcription of an integrated provirus. Cellular and viral proteins regulating LTR activity contribute to the modulation of HIV-1 latency. In this study, we found that the host protein Naf1 inhibited HIV-1 LTR-driven transcription of HIV genes and contributed to the maintenance of HIV-1 latency. Our findings provide new insights into the effects of host modulation on HIV-1 latency, which may lead to a potential therapeutic strategy for HIV persistence by targeting the Naf1 protein., (Copyright © 2016 American Society for Microbiology.)

Objective: Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD., Methods: Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann-Whitney test) for continuous variables, Chi-square test (or Fisher's exact test) and trend test for categorical variables, and logistic regression analysis., Results: Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4&#95;92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05-4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20-432.56, p = 0.037)., Conclusion: PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA.

Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS). We analyzed the predict values of pCR rate for patient outcome, and the predict factors for DFS by univariate and multivariate Analysis. Results: A total of 416 BC patients confirmed by pathology were enrolled and received treatment and assessment in this study. The overall pCR rate was 23.1% (96/416). The pCR rate was 6.9% (14/204) in patients of HR+ /HER2- Subtype, 41.5% (27/65) in HR-/HER2+ Subtype, 30.9% (17/55) in HR+ /HER2+ Subtype, and 41.1% (37/91) in HR-/HER2- Subtype. The correlation of the pathological status and the patient outcome was analyzed in all patients. Compared with no pCR group, pCR group had significant higher DFS rates. In HER2+ Subtype and HR-/HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achieved pCR. In HR+ /HER2- Subtype, DFS rates of patients who achieved pCR was higher than that of who didn't achievced pCR, but without statistics difference. The Cox proportional hazards regression analysis revealed that ER status, T stage, pCR affected the patient outcome of BC. Conclusion: So far, pCR was an established prognostic factor: reaching a pCR could predicte improved survival in HER2-enriched BC and triple-negative breast cancer (TNBC) subgroup, while data remain controversial for the luminal subtypes. Our results do not support the use of pCR as a surrogate end point of treatment efficacy in unselected patients with BC submitted to neoadjuvant systemic therapy.

Objectives: To evaluate the efficacy of tocilizumab (TCZ), a monoclonal antibody against the interleukin (IL)-6 receptor, for refractory adult-onset Still's disease (AOSD) in the Korean population., Methods: This retrospective study included 22 Korean patients with refractory AOSD who were given TCZ at one of seven university hospital-based clinics for rheumatic disease. Patients were subdivided into groups according to disease course: monocyclic, systemic polycyclic, and chronic articular. Modified Pouchot scores, including laboratory and clinical findings, were analysed at 6 months and 12 months., Results: TCZ was given at 4-8 mg/kg every 4-5 weeks (8 mg/kg every 4-5 weeks in 18 patients, 6 mg/kg every 4 weeks in 2, and 4 mg/kg every 4 weeks in 2) for 7.5 months (median, IQR: 4.0-12.3). A good response (measured as a decrease of >2 in the modified Pouchot score) was achieved in 50.0% of patients (11 of 22) at 6 months and in 64.3% (9 of 14) at 12 months. The dose of corticosteroid dose was reduced from 11.5 mg/day (median, IQR: 10.0-21.3) immediately before TCZ therapy to 7.5 mg/day (median, IQR: 5.0-10.0, p=0.002) at 6 months and finally to 6.3 mg/day (median, IQR: 5.0-7.5, p=0.002) at 12 months. Only one patient discontinued TCZ treatment due to facial swelling accompanied by high blood pressure. In all others, adverse events subsided with delayed TCZ therapy, and TCZ therapy was continued successfully without problems., Conclusions: TCZ was effective for treating Korean AOSD patients who were refractory to conventional therapy or other anti-cytokine biologics, showing a corticosteroid-sparing effect and an acceptable tolerance profile.

In this study, chars from coconut pith (CP) were prepared aiming for superior adsorption towards elemental mercury (Hg(o)). The yield, proximate analysis, textural characteristics, surface functional groups and elemental composition analyses of the chars produced at pyrolysis temperature of 300 °C, 500 °C, 700 °C and 900 °C were compared. The surface area, pore volume, ash and carbon content of chars increased, while the yield and moisture content decreased with increasing pyrolysis temperatures. The changing of physical and chemical properties of the chars produced at variety pyrolysis temperature was much effect on the Hg(o) adsorption performance and definitely provides important information on the Hg(o) adsorption mechanism. The highest Hg(o) adsorption capacity was observed for CP900 (6067.49 μg/g), followed by CP700 (2395.98 μg/g), CP500 (289.76 μg/g), CP300 (1.68 μg/g), and CP (0.73 μg/g). The equilibrium data were well described by the Freundlich adsorption isotherm model. The pseudo-second order best described the kinetic data of the Hg(o) adsorption onto CP and CP300. For chars produced at higher pyrolysis temperature, however, the pseudo-zero order and pseudo-second order fitted well for the adsorption and breakthrough regions, respectively. The Hg(o) adsorption capacity of chars obtained from high pyrolysis temperature of CP significantly outperformed the commercial activated carbon (Darco KB-B) as well as superior to chars reported in the literature indicating the CP can be used as a precursor for preparation of chars as elemental mercury adsorbents., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to evaluate the association between specific anti-cyclic citrullinated peptide antibody (ACCPA) and pulmonary abnormalities in rheumatoid arthritis (RA) subjects., Methods: Computed tomography (CT) images of 83 subjects with RA were evaluated in a blind fashion. Enrolled subjects underwent autoantibody testing to determinate titer of ACCPA and rheumatoid factor, and pulmonary function testing. Visual CT assessment included lobar analysis for extent of semi-quantitative total interstitial lung disease score (ILDS) and each airway abnormality score (bronchiectasis, bronchial wall thickening, centrilobular nodules, and expiratory air trapping). Correlation tests, and simple and multiple regression analyses were performed to determine the relationship between the visual CT abnormalities, physiologic parameters, and autoantibody titers., Results: ACCPA-positive subjects had a greater extent and higher prevalence of small airway abnormalities including centrilobular nodules and air trapping compared to ACCPA-negative subjects (all p < 0.05). Bronchiectasis and bronchial wall thickening correlated with the ratio of forced expiratory volume in 1 s and forced vital capacity (FVC) (r = -0.236 and r = -0.329, all p < 0.05), and ILDS correlated with FVC and the diffusing capacity of the lung for carbon monoxide (r = -0.218 and r = -0.366, all p < 0.05). Bronchial wall thickening and air trapping correlated with ACCPA titers (r = 0.235 and r = 0.264, all p < 0.05). Air trapping and bronchial wall thickening were significantly associated with ACCPA titers., Conclusion: In ACCPA (+) RA, visual CT assessment of large and small airways beyond RA-ILD, which is attributable to RA-related autoimmunity, can provide valuable information regarding airway abnormalities, regardless of the patients' physiologic airflow limitations.

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Freestanding ultrathin metallic nanosheets (FUMNSs) with atomic thickness attract extensive attention because they display remarkable advantages over their bulk counterparts by virtue of their large specific area, high aspect ratio, and unsaturated surface coordination. The state of the art of research on FUMNSs is reviewed here, wherein the important progress from the aspects of material category, synthetic strategy, and practical application are introduced, and it is demonstrated that FUMNSs will play an important role in the fields of optoelectrics, catalysis, and magnetism., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

"Feishu" (BL 13) is a commonly used acupoint in experimental study,'but its definite position has not been described in current books about acupoints. In the'present paper, the authors introduced three methods for determining the anatomical location of "Feishu" (BL 13) acupoint in rats. The Wistar rats (200 ± 20) g were anesthetized with 10% chloral hydrate first, and then, fixed at the prone position. The highest point of the spinous process of the second thoracic vertebra was used as the marker for positioning the spinal vertebra. The point, 7 mm lateral to the site below the spinous process of the 3rd thoracic vertebra is just the "Feishu" (BL 13). In order to determine the 3rd thoracic vertebra, three methods are recommended to be adopted: 1) finding the 5th thoracic vertebra process parallel to the inferior angle of the scapula first, then going upwards to find the 3rd thoracic vertebra , 2) finding the 1st thoracic vertebra along the 1st rib, then going downward to find the 3rd thoracic vertebra, and 3) taking the 6th lumbar vertebra (parallel to the hip-joint) as the bone-marker and going upward to find the 3rd thoracic vertebra. When "Feishu" (BL 13) punctured, a filiform needle was straight inserted into the skin, then downward to the subcutaneous tissue, muscular layer (including the trunk cutaneous muscle, trapezius muscle, broadest muscle of back, serratus muscle of back, atalanto-longest muscle, longest muscle of neck, longest muscle of thorax, lumbar longest muscle, the medial part of the longest muscle, cervico-spinal muscle of back-, semispinal muscle of neck, biventer cervicis, and multifidus muscles) about 6 mm in depth.

As a promising material for photoelectrical application, MoS2 has attracted extensive attention on its facile synthesis and unique properties. Herein, we explored a novel strategy of laser ablation to synthesize MoS2 fullerene-like nanoparticles (FL-NPs) with stable photoresponse under high temperature. Specifically, we employed a millisecond pulsed laser to ablate the molybdenum target in dimethyl trisulfide gas, and as a result, the molybdenum nanodroplets were ejected from the target and interacted with the highly reactive ambient gas to produce MoS2 FL-NPs. In contrast, the laser ablation in liquid could only produce core-shell nanoparticles. The crucial factors for controlling final nanostructures were found to be laser intensity, cooling rate, and gas reactivity. Finally, the MoS2 FL-NPs were assembled into a simple photoresponse device which exhibited excellent thermal stability, indicating their great potentialities for high-temperature photoelectrical applications.

The preparation of chars and activated carbon as low-cost elemental mercury adsorbents was carried out through the carbonisation of coconut husk (pith and fibre) and the activation of chars with potassium hydroxide (KOH), respectively. The synthesised adsorbents were characterised by using scanning electron microscopy, Fourier transform infrared spectroscopy and nitrogen adsorption/desorption analysis. The elemental mercury removal performance was measured using a conventional flow type packed-bed adsorber. The physical and chemical properties of the adsorbents changed as a result of the carbonisation and activation process, hence affecting on the extent of elemental mercury adsorption. The highest elemental mercury (Hg°) adsorption capacity was obtained for the CP-CHAR (3142.57 µg g(-1)), which significantly outperformed the pristine and activated carbon adsorbents, as well as higher than some adsorbents reported in the literature., (© The Author(s) 2014.)

Aim: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer., Materials and Methods: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides., Results: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy., Conclusions: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected., (Copyright © 2014. Published by Elsevier Ltd.)

Prognostic factor analysis has been conducted to determine whether the parameters of clinical data and biomarkers would predict differential progression-free survival (PFS) or overall survival (OS) from lapatinib-based therapy in patients with primary or acquired resistance to trastuzumab. Treatment with lapatinib plus capecitabine for HER2-positive metastatic breast cancer (MBC) with primary or acquired resistance to trastuzumab was analyzed retrospectively. Tumor biomarkers, which came from the biopsies before the starting of lapatinib therapy, were evaluated by immunohistochemistry (IHC). Prognostic factors related to PFS or OS of the lapatinib therapy were assessed by univariate and multivariate analysis. Ki-67 index and liver metastases were the significant prognostic factors for predicting PFS of subsequent lapatinib therapy in the univariate analysis and the multivariate analysis. The risk for disease progression in patients who had a Ki-67 index<40% was 59% less than that in patients had Ki-67 ≥ 40 (HR = 0.41, 95% CI, 0.23-0.74, P = 0.003). TTP of prior trastuzumab therapy, liver metastases, and the number of metastatic sites were three independent prognostic factors of subsequent lapatinib therapy. Ki-67 index was the significant prognostic factors for predicting PFS of the subsequent second line targeted therapy in patients with trastuzumab resistance.

The tumor suppressor gene, PTEN , has previously been demonstrated to be involved in breast tumorigenesis and tumor progression. The aim of the present study was to investigate the expression and significance of PTEN in breast carcinomas, to detect the mutation frequency of PTEN in sporadic breast carcinoma tissues and to determine the association between PTEN promoter methylation and gene expression. Immunohistochemical methods were used to analyze the expression of the PTEN gene in 146 cases of breast carcinoma and 10 cases of normal breast tissue closely adjacent to the carcinoma. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was used to analyze conformation polymorphisms in 45 breast carcinoma and 10 normal breast tissues. Point mutations of abnormal single stranded conformation were detected by DNA sequencing. The methylation of the PTEN promoter was analyzed by methylation-specific PCR. Expression of PTEN was detected in 57.5% (84/146) of patients with breast carcinoma. By contrast, PTEN expression was detected in 100% of normal samples. Expression of PTEN was found to negatively correlate with the tumor size, the pathological stage and the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in breast cancer. The 2-year disease-free survival of patients with a high expression of PTEN was higher compared with those with low PTEN expression (P<0.05). Missense mutations in exon 2 of PTEN were identified in 1/45 breast cancer cases. PTEN promoter methylation was detected in 31.1% (14/45) of breast carcinomas, of which 64.3% (9/14) were associated with a loss of PTEN expression. The tumor suppressor gene, PTEN , was abnormally expressed in the breast carcinomas. The number of PTEN mutations were low (1/45) in the sporadic breast cancer cases analyzed in the present study and PTEN promoter methylation may have been the main mechanism leading to the decreased expression of PTEN . These results indicate that PTEN is important for the tumorigenesis, development and prognosis of breast cancer.

Objective: To observe the preliminary efficacies and adverse events of sunitinib in the treatment of metastatic breast cancer ulcer., Methods: From December 2008 to May 2010, patients with advanced breast cancer ulcer took a single sunitinib. The dosage was adjusted on the basis of adverse events. And clinical response was evaluated., Results: Nine patients with advanced breast cancer ulcer finished the treatment. The objective response and the clinical benefit time to progression of sunitinib were 3 and 7 patients with metastatic breast cancer ulcer, and the median time to progression (TTP) was 2.0 months. The most common adverse events included fatigue, hand-foot syndrome, neutropenia, thrombocytopenia and hypertension., Conclusion: Single-agent sunitinib treatment of refractory advanced breast cancer ulcer has marked efficacies. However, neutropenia, thrombocytopenia and hypertension are the major dose-limited toxicities.

Objective: To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients., Methods: A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed., Results: Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences., Conclusions: The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

Objective: To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies., Methods: The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis., Results: The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P < 0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy > 12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004)., Conclusion: TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

Objective: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year., Methods: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported., Results: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed., Conclusion: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Aim: There is growing evidence that two recently recognized, unique subsets of CD4(+) T-cells, T-helper 17 cells (Th17) and CD4(+) CD25(+) regulatory T-cells (Treg), may play important roles in the pathogenesis of psoriasis. This study sought to investigate the relationship between Th17 cells and psoriasis or psoriatic arthritis (PsA)., Methods: Peripheral blood CD4(+) T-cells were isolated from 47 patients with psoriasis and 47 controls, and were cultured under various stimulatory conditions. The Th17 cells and regulatory Treg cells were detected by flow cytometry. Plasma interleukin (IL)-17 was measured by enzyme-linked immunosorbent assay., Results: The proportion of Th17 and Treg cells from peripheral blood mononuclear cells showed no difference between patients with psoriasis and controls. However, psoriasis and PsA patients demonstrated a higher proportion of induced Th17 cells, which was correlated with psoriasis area severity index score. The level of plasma IL-17A in psoriasis was higher than that in controls., Conclusion: Th17 cells may play important roles in the pathogenesis of psoriasis and psoriatic arthritis., (© 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Objective: To explore the chemotherapeutic efficacies and prognostic factors of metastatic triple-negative breast cancer., Methods: The clinicopathologic data of 151 patients with metastatic triple-negative breast cancer were collected from September 1994 to November 2011 and their clinicopathologic characteristics, recurrence and survival were analyzed., Results: Platinum plus taxol or vinorelbine was significantly higher than others for these patients (42.1% vs 23.1%, P = 0.022). The median overall survivals of those on first-line chemotherapy with partial remission, stable disease and progressive disease were 29.6, 24.7 and 13.1 months respectively. The differences were statistically significant (P = 0.045). Two or three-line chemotherapy showed no obvious statistical relationship with total overall survival. Simple factor analysis showed that the number of metastasis, visceral metastases and the efficacies of first-line chemotherapy were correlated with overall survival (all P < 0.05). Multivariate Cox regression showed that disease-free survival and the efficacies of first-line chemotherapy were the independent prognostic factors of metastatic triple-negative breast cancer., Conclusion: The combined chemotherapy of platinum may achieve better efficacies in the treatment of metastatic triple-negative breast cancer. And the efficacies of first-line chemotherapy are closely correlated with survival.

Objective: To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer., Methods: We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel., Results: The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021)., Conclusion: There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.

Objective: To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer., Methods: Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles., Results: Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01)., Conclusions: The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

To investigate a quantitative reverse transcription polymerase chain reaction (QRT-PCR) assay different from 21-gene assay which can be used to prognosticate the risk of recurrence in patients with estrogen receptor (ER) positive, lymph node (LN) negative breast cancer. To accurately determine the relationship between the Recurrence Score (RS) derived from our assay and the risk of distant recurrence in Chinese patients with LN negative and positive breast cancer through the analysis of paraffin tissues. We obtained archival paraffin-embedded tissues from patients with invasive breast cancer and varying axillary lymph node involvement. QRT-PCR reaction was performed by using the method of SYBR Green I dye with primers. Expression of the 21-genes was converted to RS by a prespecified algorithm. We then assessed the probability of the test to accurately predict distant recurrence-free survival in this retrospective cohort. Ninety-three patients were eligible based on gene expression profiles. In our population, most breast cancer patients were premenopausal (82.6%), at early stage (93.6%) and ER positive (91.4%). Median follow-up was 65.9 months. The 5-year recurrence-free survival rate for the group was 58.8%. The concordance between the reverse transcription-PCR and immunohistochemical (IHC) measurement for ER, progesterone receptor (PgR), and HER-2 determinations was high and comparable. High RS was predictive of an elevated risk of relapse (p < 0.001). In subgroups of patients, RS had significantly predictive performance both in node-negative (p = 0.009) and node-positive patients (p = 0.038). Multivariable analysis showed that nodal status, adjuvant hormonal therapy and RS were significantly related to prognosis. RS category is a better predictor than the other risk assessment criteria or clinicopatholic features, with which we can determine more accurately the risks for recurrence of various patients. We have established an easy and economical QRT-PCR assay and validated in concordance with IHC measurements for ER, PgR, and HER-2. RS was associated with distant recurrence among Chinese patients with hormone receptor (HR) positive breast cancer. This study may promote the use of RS estimated from the expression of the 21-gene set for prognostication and routine clinical diagnostic application in Chinese populations., (© 2011 Wiley Periodicals, Inc.)