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Shi-Ming Zhang, Qing-Ge Zhu, Xiao-Xiao Ding, Song Lin, Jing Zhao, Lei Guan, Ting Li, Bing He, Hu-Qin Zhang The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an JiaoTong University, Xi’an, 710049, China Background: The prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial.Methods: We searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery.Results: A total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66–0.90, p=0.001) and on OS was 0.72 (95% CI 0.66–0.80, p

Background: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis., Objective: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis., Materials and Methods: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC)., Results: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC 50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-β, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group., Conclusions: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH 50 0.11 and AP 50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade., (© 2023 Wiley-VCH GmbH.)

Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient's renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma., (© 2023. Springer Nature Limited.)

A memory-efficient implementation scheme for the discontinuous Galerkin volume integral equation method (DGVIE) using Schaubert-Wilton-Glisson (SWG) basis functions is proposed to analyze electromagnetic scattering from inhomogeneous dielectric objects. For this proposed scheme, almost no half-SWG basis functions are needed for the elements separating nonconformal meshes, while these half-SWG basis functions are indispensable for the conventional DGVIE-SWG method. This is realized by applying the divergence-free condition of the electric displacement vector explicitly for nonconformal meshes separating neighboring subdomains of an inhomogeneous dielectric body. Therefore, the number of unknowns of the conventional DGVIE method can be further reduced. As a result, the memory of the proposed DGVIE method is only about half of the conventional one for inhomogeneous dielectric problems. Meanwhile, the total solution time has been reduced by the use of the proposed scheme. Particularly, the proposed DGVIE-SWG method is efficient in memory usage not only for inhomogeneous dielectric cases with high contrast ratio but also for cases with relatively low contrast ratio.

As the harvest season of most fruit is concentrated, fruit maturation manipulation is essential for the fresh fruit industry to prolong sales time. Gibberellin (GA), an important phytohormone necessary for plant growth and development, has also shown a substantial regulatory effect on fruit maturation; however, its regulatory mechanisms remain inconclusive. In this research, preharvest GA3 treatment effectively delayed fruit maturation in several persimmon (Diospyros kaki) cultivars. Among the proteins encoded by differentially expressed genes, 2 transcriptional activators (NAC TRANSCRIPTION FACTOR DkNAC24 and ETHYLENE RESPONSIVE FACTOR DkERF38) and a repressor (MYB-LIKE TRANSCRIPTION FACTOR DkMYB22) were direct regulators of GERANYLGERANYL DIPHOSPHATE SYNTHASE DkGGPS1, LYSINE HISTIDINE TRANSPORTER DkLHT1, and FRUCTOSE-BISPHOSPHATE ALDOLASE DkFBA1, respectively, resulting in the inhibition of carotenoid synthesis, outward transport of an ethylene precursor, and consumption of fructose and glucose. Thus, the present study not only provides a practical method to prolong the persimmon fruit maturation period in various cultivars but also provides insights into the regulatory mechanisms of GA on multiple aspects of fruit quality formation at the transcriptional regulation level., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

It remains unclear whether metabolic profiles differ within the subtypes of primary aldosteronism (PA). This meta-analysis aimed to compare the blood parameters related to lipid and glucose metabolism at baseline between unilateral PA and bilateral PA. A search was performed using PubMed, Web of Science, and Sciencedirect databases, supplemented by hand-searching of related references. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for each parameter. Twenty-one studies involving 4197 patients with PA were included. Compared with bilateral PA groups, unilateral PA groups demonstrated significantly lower low-density lipoprotein cholesterol (LDL-C, SMD: -.14 mmol/L, 95% CI: -.20, -.07), total cholesterol (TC, SMD: -.16 mmol/L, 95% CI: -.23, -.09), triglyceride (TG, SMD: -.22 mmol/L, 95% CI: -.29, -.16), fasting blood glucose (FBG, SMD: -.11 mmol/L, 95% CI: -.18, -.04), hemoglobin A1c (HbA1c, SMD: -.21%, 95% CI: -.30, -.13), and homeostasis model assessment-insulin resistance (HOMA-IR, SMD: -.40, 95% CI: -.58, -.23). No significant difference was found in high-density lipoprotein cholesterol (HDL-C) level between the two groups (SMD: .40 mmol/L, 95% CI: -.02, .11). To sum up, comparison of several blood metabolic parameters between the two subtypes suggested that the bilateral PA may associate with a higher prevalence of impaired glucose and lipid metabolism than unilateral PA; however, results should be treated with caution. Additional well-designed studies are needed to prove the present results and better elucidate the link between metabolic abnormalities and etiologies of each PA subtype., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: To investigate the effect of traditional Chinese manual therapy (TCMT) in alleviating pain and dysfunction in patients with lumbar disc herniation (LDH)., Methods: Sixty-six patients with LDH were recruited as the study cohort and randomly assigned to an observation group and a control group. The patients in the observation group underwent TCMT, whereas those in the control group underwent conventional lumbar traction (LT). The observed indexes comprised primary index, which referred to clinical efficacy, and secondary indexes, which include Simplified McGill Pain Questionnaire, Oswestry Disability Index (ODI), range of motion (ROM) of the lumbar spine, difference in muscle tone (MT) and pressure pain threshold (PPT) of the bilateral erector spinae, and serum inflammatory factor levels., Results: The total effective rate was significantly higher in the observation group than in the control group (96.67% vs. 66.67%, P < 0.001). Compared with the control group after treatment, patients in the observation group had significantly lower ODI, pain rating index, visual analog scale and present pain intensity scores (all P < 0.05), and had significantly smaller differences in MT and PPT of the bilateral erector spinae (both P < 0.001), but had remarkably greater ROM of the lumbar spine ( P < 0.001). In addition, interleukin (IL)-6, IL-8, and interferon-γ concentrations in the observation group were significantly lower than those in the control group after treatment (all P < 0.05)., Conclusion: TCMT has positive effects on alleviating pain and improving dysfunction of patients with LDH and helps in reducing serum inflammatory factor levels., Competing Interests: None., (AJTR Copyright © 2022.)

Crematogaster matsumurai (Forel 1901) is an important arboreal ant species commonly found on Phyllostachys heterocycla (Carr.) in Lishui, Zhejiang, China. This study analyzed the mitochondrial genome sequence of C. matsumurai and discussed its phylogenetic relationship in Hymenoptera. The circular mitochondrial genome was 16,028 bp long, including a standard set of 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and 13 protein-coding genes (PCGs), which showed the typical insect mitochondrial genome arrangement. The AT and GC contents of the mitochondrial genome sequence were 76.92% and 23.08%, respectively. The maximum-likelihood (ML) phylogenetic analysis based on whole mitochondrial genome sequences showed that C. matsumurai is closest to Crematogaster teranishii ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Starting with low metastatic capability, T4N0M0 (diameter ≥ 7 cm) non-small cell lung cancers (NSCLCs) constitute a unique tumor subset, as with a large tumor size but no regional or distant metastases. We systematically investigated intratumoral heterogeneity, clonal structure, chromosomal instability (CIN), and immune microenvironment in T4N0M0 (≥7 cm) NSCLCs., Methods: Whole-exome sequencing, RNA sequencing, and multiplex immunohistochemistry (mIHC) staining were conducted to analyze 24 spatially segregated tumor samples from eight patients who were pathologically diagnosed with T4N0M0 (diameter ≥ 7 cm) NSCLCs. The adjacent normal tissues and peripheral blood served as controls., Results: In total, 35.2% of mutations and 91.1% of somatic copy number alterations were classified as subclonal events, which exhibited widespread genetic intratumoral heterogeneity. In contrast, a low degree of CIN was observed. None of the patients had genome doubling. The burden of loss of heterozygosity, aneuploidy, and the genome instability index of these tumors were significantly lower than those in the TRACERx cohort. Expression profiles revealed significantly upregulated expression of cell division-related signals and the G2/M checkpoint pathway. In addition, a similar expression pattern of the immune microenvironment was observed in different regions of the tumor, which was confirmed by mIHC profiles., Conclusions: Our study indicates the presence of intratumoral genetic heterogeneity and immune microenvironmental heterogeneity features in T4N0M0 NSCLCs, and the low degree of CIN may be related to the low metastatic capability., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Astringency is a dry puckering mouthfeel mainly generated by the binding of tannins with proteins in the mouth. Tannins confer benefits such as resistance to biotic stresses and have antioxidant activity, and moderate concentrations of tannins can improve the flavor of fruits or their products. However, fruits with high contents of tannins have excessive astringency, which is undesirable. Thus, the balance of astringency formation and removal is extremely important for human consumption of fruit and fruit-based products. In recent years, the understanding of fruit astringency has moved beyond the biochemical aspects to focus on the genetic characterization of key structural genes and their transcriptional regulators that cause astringency. This article provides an overview of astringency formation and evaluation. We summarize the methods of astringency regulation and strategies and mechanisms for astringency removal, and discuss perspectives for future exploration and modulation of astringency for fruit quality improvement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic pain of knee osteoarthritis (KOA) greatly affects the quality of life and functional activities of patients. It is important to clarify the underlying mechanisms of KOA pain and the analgesic effect of different therapies. Neuroimaging technology has been widely used in the basic and clinical research of pain. In the recent years, neuroimaging technology has played an important role in the basic and clinical research of KOA pain. Increasing evidence demonstrates that chronic pain in KOA includes both nociceptive and neuropathic pain. The neuropathic mechanism involved in KOA pain is complex, which may be caused by peripheral or central sensitization. In this paper, we review the regional changes of brain pathophysiology caused by KOA pain based on magnetic resonance imaging (MRI), electroencephalogram (EEG), magnetoencephalogram (MEG), near-infrared spectroscopy (NIRS) and other neuroimaging techniques. We also discuss the central analgesic mechanism of different KOA therapies, with a focus on the latest achievements in the evaluation and prediction of pain. We hope to provide new thoughts for the treatment of KOA pain, especially in the early and middle stages of KOA.

Objective: To observe the analgesic effect of manipulation loading on chronic low back pain (CLBP) model rats and the expression of inflammatory factors in psoas major muscle tissue, and to explore the improvement of manipulation on local inflammatory microenvironment., Methods: Thirty two SPF male SD rats weighing 340-360g were randomly divided into blank group, sham operation group, chronic low back pain model group and treatment group, with 8 rats in each group. In the model group, L 4 -L 6 lumbar vertebrae were implanted with external link fixation system (ELFS). After implantation of ELFS, the treatment group received manualintervention with 5N force and 2Hz frequency on both sides of the spine, 15 min / time, once a day, for 14 consecutive days. Paw with drawl threshold (PWT) and paw withdrawl latency (PWL) was measured before modeling and on the 1st, 3rd, 7th, 10th and 14th day after intervention. At the end of the treatment cycle, the concentrations of calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in psoas muscle were detected by enzyme-linked immunosorbent assay (ELISA)., Results: There was no significant difference in PWT and PWL between the blank group and the sham operation group after modeling ( P >0.05);after modeling, PWT and PWL in the CLBP model group and the treatment group were significantly decreased( P <0.01);PWT in the treatment group was not significantly improved than that in the CLBP model group on the 1st and 3rd day after manual loading( P >0.05);on the 7th day after manual loading, the pain threshold value in the treatment group was higher than that in the CLBP model group, but there was no significant difference There was no significant difference between the two groups ( P =0.056>0.05). On the 10th and 14th day of treatment, the mechanical pain threshold of the treatment group began to rise, and it was statistically significant compared with CLBP model rats ( P <0.05, P < 0.01);on the 1st and 3rd day after manual treatment, the PWL of the treatment group was not significantly improved compared with CLBP model group ( P >0.05);on the 7th day, the PWL of the treatment group was significantly higher than that of CLBP model group, there was statistical significance ( P =0.016<0.05). Manual loading improved thermal hyperalgesia in CLBP rats until the end of the experiment. The contents of CGRP and NGF in psoas major muscle of CLBP model group were higher than those of blank group and sham operation group ( P <0.01). After treatment, the contents of CGRP and NGF decreased significantly( P <0.01)., Conclusion: Local massage loading has analgesic effect on CLBP rats, at the same time, it can inhibit the content of CGRP and NGF in psoas muscle tissue of CLBP rats, and improve the local inflammatory microenvironment.

Persimmon ( Diospyros kaki Thunb.) fruit is unique due to the continuous accumulation of soluble tannins during fruit development in most cultivars, which causes undesired astringency. High-CO 2 treatment was the most effective widely used method for astringency removal. However, differential effects of high-CO 2 treatment between cultivars were observed and the molecular basis remained inclusive. Previously, one cultivar ("Luoyangfangtianshengshi," LYFTSS) showed rapid deastringency, while two cultivars ("Shijiazhuanglianhuashi," SJZLHS; "Laopige," LPG) showed slow deastringency in response to high-CO 2 (95% CO 2 ) treatment. In this study, the metabolites (acetaldehyde and ethanol) related to deastringency were further analyzed and both acetaldehyde and ethanol were higher in SJZLHS and LYFTSS than that in LPG, where acetaldehyde was undetectable. Based on the RNA-seq data, the weighted gene coexpression network analysis (WGCNA) revealed that one module, comprised of 1773 unigenes, significantly correlated with the contents of acetaldehyde and ethanol ( P < 0.001). Further analysis based on the acetaldehyde metabolism pathway indicated that the differentially expressed structural genes, including previously characterized DkADH and DkPDC and also their upstream members (e.g., PFK, phosphofructokinase), showed positive correlations with acetaldehyde production. Quantitative analysis of the precursor substances indicated that sucrose, glucose, and fructose exhibited limited differences between cultivar except for malic acid. However, the content of malic acid is much less than the total soluble sugar content. To verify the correlations between these genes and acetaldehyde production, the fruit from 14 more cultivars were collected and treated with high CO 2 . After the treatment, acetaldehyde contents in different cultivars ranked in 30.4-255.5 μg/g FW. Real-time polymerase chain reaction (PCR) and correlation analysis indicated that the EVM0002315 (PFK) gene, belonging to carbohydrate metabolism, was significantly correlated with acetaldehyde content in fruit. Thus, it could be proposed that the differentially expressed carbohydrate metabolism related genes (especially PFK ) are the basis for the variance of acetaldehyde production among different persimmon cultivars.

Background: Plastic bronchitis is an uncommon but severe respiratory disease characterized by formation of casts in tracheobronchial tree. It can lead to airway obstruction and even respiratory failure., Case Presentation: Plastic bronchitis is mostly seen in both post-cardiac surgery patients, especially Fontan procedure, and infections including those caused by influenza viruses, Mycoplasma pneumoniae or tuberculosis. But it has rarely been reported to be associated with adenovirus infection. We report 2 cases of plastic bronchitis arising from adenovirus serotype 7 infection, manifested in repeated high fever, cough, and progressive dyspnea, and were diagnosed and eventually cured by bronchoscopy., Conclusions: Plastic bronchitis is a rare, variable and potentially fatal disease. In the cases we described, the cause was associated with adenovirus serotype 7 and its treatment required intervention with bronchoscopy and adequate control of the underlying disease.

Most persimmon (Diospyros kaki) cultivars are astringent and require post-harvest deastringency treatments such as 95% CO2 (high-CO2 treatment) to make them acceptable to consumers. High-CO2 treatment can, however, also induce excessive softening, which can be reduced by adding 1-methylcyclopropene (1-MCP). Previous studies have shown that genes encoding the ETHYLENE RESPONSE FACTORS (ERFs) DkERF8/16/19 can trans-activate xyloglucan endotransglycosylase/hydrolase (DkXTH9), which encodes the cell wall-degrading enzyme associated with persimmon fruit softening. In this study, RNA-seq data between three treatments were compared, namely high-CO2, high-CO2+1-MCP, and controls. A total of 227 differentially expressed genes, including 17 transcription factors, were predicted to be related to persimmon post-deastringency softening. Dual-luciferase assays indicated that DkNAC9 activated the DkEGase1 promoter 2.64-fold. Synergistic effects on transcription of DkEGase1 that involved DkNAC9 and the previously reported DkERF8/16 were identified. Electrophoretic mobility shift assay indicated that DkNAC9 could physically bind to the DkEGase1 promoter. Bimolecular fluorescence complementation and firefly luciferase complementation imaging assays indicated protein-protein interactions between DkNAC9 and DkERF8/16. Based on these findings, we conclude that DkNAC9 is a direct transcriptional activator of DkEGase1 that can co-operate with DkERF8/16 to enhance fruit post-deastringency softening., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Persimmon ( Diospyros kaki ) is an oriental perennial woody fruit tree whose popular fruit is produced and consumed worldwide. The persimmon fruit is unique because of the hyperaccumulation of proanthocyanidins during fruit development, causing the mature fruit of most cultivars to have an astringent taste. In this study, we obtained a chromosome-scale genome assembly for 'Youshi' ( Diospyros oleifera , 2n = 2x = 30), the diploid species of persimmon, by integrating Illumina sequencing, single-molecule real-time sequencing, and high-throughput chromosome conformation capture techniques. The assembled D. oleifera genome consisted of 849.53 Mb, 94.14% (799.71 Mb) of which was assigned to 15 pseudochromosomes, and is the first assembled genome for any member of the Ebenaceae. Comparative genomic analysis revealed that the D. oleifera genome underwent an ancient γ whole-genome duplication event. We studied the potential genetic basis for astringency development (proanthocyanidin biosynthesis) and removal (proanthocyanidin insolublization). Proanthocyanidin biosynthesis genes were mainly distributed on chromosome 1, and the clustering of these genes is responsible for the genetic stability of astringency heredity. Genome-based RNA-seq identified deastringency genes, and promoter analysis showed that most of their promoters contained large numbers of low oxygen-responsive motifs, which is consistent with the efficient industrial application of high CO 2 treatment to remove astringency. Using the D. oleifera genome as the reference, SLAF-seq indicated that 'Youshi' is one of the ancestors of the cultivated persimmon (2n = 6x = 90). Our study provides significant insights into the genetic basis of persimmon evolution and the development and removal astringency, and it will facilitate the improvement of the breeding of persimmon fruit., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2019.)

Hypoxic environments are generally undesirable for most plants, but for astringent persimmon, high CO 2 treatment (CO 2 > 90%), also termed artificial high-CO 2 atmosphere (AHCA), causes acetaldehyde accumulation and precipitation of soluble tannins and could remove astringency. The multiple transcriptional regulatory linkages involved in persimmon fruit deastringency have been advanced significantly by characterizing the ethylene response factors (ERFs), WRKY and MYB; however, the involvement of zinc finger proteins for deastringency has not been investigated. In this study, five genes encoding C2H2-type zinc finger proteins were isolated and designed as DkZF1-5 . Phylogenetic and sequence analyses suggested the five DkZF s could be clustered into two different subgroups. qPCR analysis indicated that transcript abundances of DkZF1/4 were significantly upregulated during AHCA treatment (1% O 2 and 95% CO 2 ) at day 1, DkZF2 / 5 at both day 1 and 2, while DkZF3 at day 2. Dual-luciferase assay indicated DkZF1 and DkZF2 as the activators of deastringency-related structural genes ( DkPDC2 and DkADH1 ) and transcription factors (DkERF9/10). Moreover, combinative effects between various transcription factors were investigated, indicating that DkZF1 and DkZF2 synergistically showed significantly stronger activations on the DkPDC2 promoter. Further, both bimolecular fluorescence complementation (BiFC) and yeast two hybrid (Y2H) assays confirmed that DkZF2 had protein-protein interactions with DkZF1. Thus, these findings illustrate the regulatory mechanisms of zinc finger proteins for persimmon fruit deastringency under AHCA.

Objective: To compare the efficacy and safety of complete transperitoneal laparoscopic nephroureterectomy (CTNU) and traditional retroperitoneoscopic nehroureterectomy (TRNU) for the management of upper urinary tract urothelial carcinoma(UTUC)., Methods: We retrospectively collected the clinical data of UTUC patients who underwent CTNU or TRNU surgery from January 2011 to December 2018 in Peking University First Hospital and Fujian Provincial Hospital, and compared the clinical characteristics, perioperative parameters, and follow-up results between the CTNU and TRNU surgeries., Results: Finally, a total of 266 cases were included, with 94 cases in the CTNU group and 172 cases in the TRNU group. The proportion of left side lesions was bigger in TRNU group when compared with CTNU group (P<0.05). No significant differences were observed in clinical characteristics, such as age, gender, body mass index (BMI), American society of anesthesiologists score (ASA score) and tumor laterality. All surgery procedures were completed. The vascular resparing was performed by reason that left arteria renalis was injured accidently during surgical operation in one case of TRNU group. No serious complications were observed in both CTNU and TRNU groups. In CTNU group, operating time was (202.9±76.7) min, estimated blood loss was (68.4±73.3) mL, drainage duration was (3.9±1.5) d, drainage volume was (181.7±251.5) mL, and postoperative hospital stay was (7.8±4.1) d. In TRNU group, operating time was (203.5±68.7) min, estimated blood loss was (130.2±252.1) mL, drainage duration was (4.3 ±1.6) d, drainage volume was (179.1±167.5) mL, and postoperative hospital stay was (8.2±3.7) d. The estimated blood loss in CTNU group was significantly less than that in TRNU group (P=0.005).The median follow-up time was 39 months (range: 1-88 months). The 5-year overall survival rate (OS), cancer specific survival rate (CSS), intra-vesical recurrence free survival rate (IvRFS), disease free survival rate (DFS) of CTNU group was 75.6%, 86.9%, 73.8%, 57.5%, respectively. The OS, CSS, IvRFS and DFS of TRNU group was 66.3%, 83.5%, 75.9%, 58.6%, respectively.No significant differences were observed in the OS, CSS, IvRFS and DFS between the CTNU and TRNU groups., Conclusion: CTNU technique is a safe and effective surgical option, and further prospective randomized controlled trial is needed for further evaluation.

Identification and functional characterization of hypoxia-responsive transcription factors is important for understanding plant responses to natural anaerobic environments and during storage and transport of fresh horticultural products. In this study, yeast one-hybrid library screening using the persimmon ( Diospyros kaki ) pyruvate decarboxylase ( DkPDC2 ) promoter identified three ethylene response factor (ERF) genes ( DkERF23 / DkERF24 / DkERF25 ) and four WRKY transcription factor genes ( DkWRKY/DdkWRKY5 / DkWRKY6 / DkWRKY7 ) that were differentially expressed in response to high CO 2 (95%, with 4% N 2 and 1% oxygen) and high N 2 (99% N 2 and 1% oxygen). Yeast one-hybrid assays and electrophoretic mobility shift assays indicated that DkERF23, DkERF24, DkERF25, DkWRKY6, and DkWRKY7 could directly bind to the DkPDC2 promoter. Dual-luciferase assays confirmed that these transcription factors were capable of transactivating the DkPDC2 promoter. DkERF24 and DkWRKY1 in combination synergistically transactivated the DkPDC2 promoter, and yeast two-hybrid and bimolecular fluorescence complementation assays confirmed protein-protein interaction between DkERF24 and DkWRKY1. Transient overexpression of DkERF24 and DkWRKY1 separately and in combination in persimmon fruit discs was effective in maintaining insolubilization of tannins, concomitantly with the accumulation of DkPDC2 transcripts. Studies with Arabidopsis ( Arabidopsis thaliana ) homologs AtERF1 and AtWRKY53 indicated that similar protein-protein interactions and synergistic regulatory effects also occur with the DkPDC2 promoter. We propose that an ERF and WRKY transcription factor complex contributes to responses to hypoxia in both persimmon fruit and Arabidopsis, and the possibility that this is a general plant response requires further investigation., (© 2019 American Society of Plant Biologists. All Rights Reserved.)

Background: Hydrocelectomy is the gold standard for the treatment of hydrocele, but it often causes complications after surgery, including hematoma, infection, persistent swelling, hydrocele recurrence, and chronic pain. In recent years, several methods for minimally invasive treatment of hydrocele have been introduced, but they all have limitations. Herein, we introduce a new method of individualized minimally invasive treatment for hydrocele., Aim: To present a new method for the treatment of adult testicular hydrocele., Methods: Fifty-two adult patients with idiopathic testicular hydrocele were included. The key point of this procedure was that the scope of the resection of the sheath of the tunica vaginalis was determined according to the maximum diameter (d) of the effusion measured by ultrasound and the maximum diameter of the portion of the sheath pulled out of the scrotum was approximately πd/2. The surgical procedure consisted of a 2-cm incision in the anterior wall of the scrotum, drainage of the effusion, and dissection of part of the sheath of the tunica vaginalis. After the sheath was peeled away to the predetermined target extent, the pulled-out sheath was removed. The intraoperative findings and postoperative complications were analyzed., Results: All patients were successfully treated with a median operation time of 18 min. The median maximum diameter of the effusion on ultrasound was 3.5 cm, and the median maximum diameter of the resected sheath was 5.5 cm. Complications occurred in four (7.7%) patients: two (3.8%) cases of mild scrotal edema, one (1.9%) case of scrotal hematoma, and one (1.9%) case of wound infection. All of the complications were grade I-II. Recurrent hydrocele, chronic scrotal pain, and testicular atrophy were not observed during a median follow-up of 12 mo., Conclusion: We report a new technique for individualized treatment of testicular hydrocele, which is quantitative and minimally invasive and yields good outcomes. Further study is warranted to verify its potential value in clinical practice., Competing Interests: Conflict-of-interest statement: The authors have stated that they have no conflicts of interest.

Purpose: Esophageal carcinoma (EC) is one of the most aggressive type cancers and dysregulation of retinoid X receptor α (RXRα) involves various tumors. However, the relationship of RXRα with the clinicopathological factors of EC, particularly prognostic characteristics, remains unclear. This present study was to evaluate the effect of RXRα expression in the development of EC., Methods: The mRNA and protein expression level of RXRα in EC and normal esophageal tissues using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The subcellular localization was detected by immunohistochemistry (IHC) analysis. The clinicopathological parameters were included age, sex, tumor size, differentiation, TNM stages and lymph node metastasis. Kaplan-Meier method and Cox's regression analyses were performed to evaluate the prognosis of 60 patients with EC., Results: RXRα was elevated in EC tissues comparing with normal esophageal tissues at both mRNA and protein levels. The overexpression level of RXRα was closely associated to the tumor differentiation, TNM stage and lymph node metastasis of patients with EC. In addition, EC patients with RXRα high expression had significantly lower disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed RXRα expression as an independent predictor for the DFS and OS rate of patients with EC., Conclusions: Our results showed that overexpression of RXRα was correlated with unfavorable prognosis, suggesting that RXRα may serve as a potential targeted therapeutic marker in the treatment of EC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Plant responses to anaerobic environments are regulated by ethylene-response factors (ERFs) in both vegetative and productive organs, but the roles of other transcription factors (TFs) in hypoxia responses are poorly understood. In this study, eight TFs (DkbHLH1, DkMYB9/10/11, DkRH2-1, DkGT3-1, DkAN1-1, DkHSF1) were shown to be strongly up-regulated by an artificial high-CO2 atmosphere (1% O2 and 95% CO2). Dual-luciferase assays indicated that some TFs were activators of previously characterized DkERFs, including DkMYB10 for the DkERF9 promoter, DkERF18/19 and DkMYB6 for the DkERF19 promoter, and DkERF21/22 for the DkERF10 promoter. Yeast one-hybrid and cis-element mutagenesis confirmed these physical interactions with one exception. The potential roles of these TFs in persimmon fruit deastringency were analysed by investigating their transient over-expression (TOX) in persimmon fruit discs, which indicated that DkMYB6TOX, DkMYB10TOX, DkERF18TOX, and DkERF19TOX were all effective in causing insolubilization of tannins, concomitantly with the up-regulation of the corresponding genes. These results indicated that multiple TFs of different classes are responsive to high-CO2/hypoxia in fruit tissues, and that a TF-TF regulatory cascade is involved in the hypoxia responses involving the Group VII DkERF10, and DkERFs and DkMYBs.

Artificial high-CO2 atmosphere (AHCA, 95% CO2 and 1% O2) has been widely applied as a postharvest de-astringency treatment for persimmon fruit. AHCA increases expression of transcription factors, including ethylene response factors (DkERF), that target de-astringency genes. Here, the promoter of DkERF9, a previously characterized AHCA-inducible and de-astringency regulator, was utilized to screen a cDNA library by yeast one hybrid assay. A novel NAC transcription factor, named DkNAC7, was identified. Dual-luciferase assay indicated that DkNAC7 could not only trans-activate the promoter of DkERF9, but also activated the previously identified deastringency-related gene DkPDC2. Real-time PCR analysis showed that DkNAC7 was up-regulated by AHCA treatment, in concert with the removal of astringency from persimmon fruit and subcellular localization showed DkNAC7 was located in the nucleus. Thus, these results indicate that DkNAC7 is a putative transcriptional activator involved in regulating persimmon fruit deastringency by trans-activition on both DkERF9 and DkPDC2, which encodes pyruvate decarboxylase.

Removal of astringency by endogenously formed acetaldehyde, achieved by postharvest anaerobic treatment, is of critical importance for many types of persimmon fruit. Although an anaerobic environment accelerates de-astringency, it also has the deleterious effect of promoting excessive softening, reducing shelf life and marketability. Some hypoxia-responsive ethylene response factors (ERFs) participate in anaerobic de-astringency, but their role in accelerated softening was unclear. Undesirable rapid softening induced by high CO 2 (95%) was ameliorated by adding the ethylene inhibitor 1-MCP (1 μL/L), resulting in reduced astringency while maintaining firmness, suggesting that CO 2 -induced softening involves ethylene signalling. Among the hypoxia-responsive genes, expression of eight involved in fruit cell wall metabolism (Dkβ-gal1/4, DkEGase1, DkPE1/2, DkPG1, DkXTH9/10) and three ethylene response factor genes (DkERF8/16/19) showed significant correlations with postdeastringency fruit softening. Dual-luciferase assay indicated that DkERF8/16/19 could trans-activate the DkXTH9 promoter and this interaction was abolished by a mutation introduced into the C-repeat/dehydration-responsive element of the DkXTH9 promoter, supporting the conclusion that these DkERFs bind directly to the DkXTH9 promoter and regulate this gene, which encodes an important cell wall metabolism enzyme. Some hypoxia-responsive ERF genes are involved in deastringency and softening, and this linkage was uncoupled by 1-MCP. Fruit of the Japanese cultivar 'Tonewase' provide a model for altered anaerobic response, as they lost astringency yet maintained firmness after CO 2 treatment without 1-MCP and changes in cell wall enzymes and ERFs did not occur., (© 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

The miRNAs play important regulating roles in the pathogenesis of hepatocellular carcinoma (HCC). To uncover key regulating miRNAs in HCC that were neglected by traditional analyzing methods of transcriptomics data, we proposed a novel molecular-network-based omics' (MNBO) method. With this method, we predicted HCC-regulating miRNAs, and confirmed the role of a novel miR-590-3P/ EED axis by a clinical study and in vitro , in vivo wet-experiments. The miR-590-3P is significantly down-regulated in HCC patients. And low level of miR-590-3P in HCC is associated with poor prognosis of patients. In HCC cell lines, the miR-590-3P suppressed cell proliferation by inhibiting the transformation G1 phase to S phases of the cell cycle. Moreover, the miR-590-3P inhibited migration and invasion of HCC cells. Further investigations indicated that miR-590-3P play its roles by inhibiting polycomb protein EED. The experiments in animal model implied miR-590-3P could be a potential therapeutic agent for HCC in the future. In conclusion, the discovery of miR-590-3P revealed the MNBO would be a useful strategy to uncover key regulating miRNAs in HCC., Competing Interests: CONFLICTS OF INTEREST Authors have declared that no competing interest exists.

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients. Now, we will review the landscape of driver genes in NSCLC including the characteristics, detection methods, the application of target therapy and challenges., Competing Interests: CONFLICTS OF INTEREST There are no potential conflicts of interest.

The purpose of this study was to screen for changes in chemokine and chemokine-related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated. Finally, total serum samples were collected from HCC patients with HBV/cirrhosis (n = 16) or liver cirrhosis (n = 16) and from healthy controls (n = 16). The serum mRNA and protein expression levels of CXCL1 in primary liver cancer patients were detected by qRT-PCR and western blot analysis, respectively. Several genes were up-regulated in tumor tissues during the progression period, including CXCL1, CXCL2, CXCL3, and IL-1β, while CXCR1 expression was down-regulated. CBRH-7919 cells carrying CXCL1 siRNA resulted in decreased tumor growth in nude mice. The differences in serum CXCL1 mRNA and protein levels among the HCC, hepatic sclerosis (HS), and control groups were significant (P < 0.001). The mRNA and protein levels of CXCL1 in the HCC group were up-regulated compared with the HS group or the control group (P < 0.001). Several chemokine genes were identified that might play important roles in the tumor microenvironment of HCC. These results provide new insights into human HCC and may ultimately facilitate early HCC diagnosis and lead to the discovery of innovative therapeutic approaches for HCC., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Persimmon fruit are unique in accumulating proanthocyanidins (tannins) during development, which cause astringency in mature fruit. In 'Mopanshi' persimmon, astringency can be removed by treatment with 95% CO2, which increases the concentrations of ethanol and acetaldehyde by glycolysis, and precipitates the soluble tannin. A TGA transcription factor, DkTGA1, belonging to the bZIP super family, was isolated from an RNA-seq database and real-time quantitative PCR indicated that DkTGA1 was up-regulated by CO2 treatment, in concert with the removal of astringency from persimmon fruit. Dual-luciferase assay revealed that DkTGA1 had a small (less than 2-fold), but significant effect on the promoters of de-astringency-related genes DkADH1, DkPDC2 and DkPDC3, which encode enzymes catalyzing formation of acetaldehyde and ethanol. A combination of DkTGA1 and a second transcription factor, DkERF9, shown previously to be related to de-astringency, showed additive effects on the activation of the DkPDC2 promoter. Yeast one-hybrid assay showed that DkERF9, but not DkTGA1, could bind to the DkPDC2 promoter. Thus, although DkTGA1 expression is positively associated with persimmon fruit de-astringency, trans-activation analyses with DkPDC2 indicates it is likely to act by binding indirectly DkPDC2 promoter, might with helps of DkERF9.

Background: We investigated whether there had been an improvement in the quality of reporting for randomised controlled trials of acupuncture and moxibustion published in Chinese journals. We compared the compliance rate for the quality of reporting following the publication of both the STRICTA and CONSORT recommendations in China., Methods: Four Chinese databases were searched for RCTs of acupuncture from January 1978 through to December 2012. The CONSORT and STRICTA checklists were used to assess the quality of reporting. Data were collected using a standardised form. All included RCTs were divided into three distinct time periods based on the time that CONSORT and STRICTA were introduced in China, respectively. Pearson's χ2 test and/or Fisher's exact test were used to assess differences in reporting among three groups., Principal Findings: A total of 1978 RCTs were identified. Although the percentage of all the items has increased over time with the introduction of CONSORT and STRICTA in China, the actual compliance in several important methodological components, including sample size calculation (0% vs. 0% vs. 1.2%, for pre-CONSORT and pre-STRICTA, post-CONSORT but pre-STRICTA, and post-CONSORT and post-STRICTA, respectively), randomisation sequence generation (1.4% vs. 15% vs. 26.3%) and implementation (0% vs. 0% vs. 1.3%), allocation concealment (0% vs. 1.4% vs. 4.9%), and blinding (0% vs. 5.7% vs. 9.1%), remains low. Moreover, no RCTs have reported the setting and context of treatment and no descriptions of the participating acupuncturists have been provided thus far., Conclusions: Overall, the quality of the reporting of RCTs of acupuncture and moxibustion published in Chinese journals has improved since CONSORT and STRICTA were introduced in China, though the actual compliance rate of some important items were still low as of 2012. In the future, Chinese journals should enhance the adoption of the CONSORT and STRICTA statement to improve the reporting quality of the RCTs of acupuncture and moxibustion and to ensure the truth and reliability of the conclusions.

We investigated the effect of high phosphorus content on the sodium-phosphate cotransporter (NaPi-IIa and NaPi-IIl). Forty-eight Sprague-Dawley rats were divided into 3 groups: high-phosphorus group (HP) with fructose diphosphate sodium injection; self-manufactured low-phosphorus diet group (LP); and normal diet group (NP). At the 1st, 2nd, 4th, and 6th weeks, 4 rats from each group were sacrificed for detecting serum levels of calcium, phosphorus, and intact parathyroid hormone. Semi-quantitative retrovirus-polymerase chain reaction was used to detect the expression of NaPi-IIa and NaPi-III mRNA in kidney. At the 1st, 2nd, 4th, and 6th weeks, serum phosphorus and parathyroid hormone levels in HP group were significantly higher than those in LP and NP groups (P < 0.05). Serum calcium levels in the 3 groups showed no difference (P > 0.05). Comparing the expression of NaPi-IIa mRNA in HP group with LP and NP groups, NaPi-IIa mRNA expression was significantly reduced in HP group (P < 0.05), while NaPi-IIa mRNA expression in LP group began increasing at the 4th week (P < 0.05). At the 1st, 2nd, and 4th weeks, the expression of NaPi-III mRNA in HP, LP, and NP groups showed no clear differences (P > 0.05), while at the 6th week in HP group, NaPi-III mRNA expression was slightly increased compared to in LP and NP groups (P < 0.05). Hyperphosphatemia significantly affected NaPi-IIa and NaPi-III mRNA expression, and a factor promote an increase in intact parathyroid hormone independently of calcium.

Hepatocellular carcinoma (HCC) is an aggressive malignancy and a major cause of cancer-related mortality worldwide. Our previous study shows that chemokine (C-X-C motif) ligand 1 (CXCL1) was upregulated and CXCR1 was downregulated in tumor tissues as compared to peritumor tissues by chemotaxis assay. As the status of CXCL subgroups and their receptors affect progression of HCC, we evaluated potential mechanisms of CXCL1 associated with anticancer effects in HCC based on our previous study. The effects of targeting CXCL1 by RNA interference (RNAi) on the proliferation and apoptosis of CBRH-7919 cells were observed in vitro and in vivo. Additionally, whether CXCL1 knockdown significantly reduce the activity of STAT3, NF-κB and HIF-1 or not were also estimated. RNAi of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice by inhibited cells proliferation and induced apoptosis. In conclusion, these findings suggest that CXCL1 plays critical roles in the growth and apoptosis of HCC. RNAi of CXCL1 inhibits the growth and apoptosis of tumor cells, which indicates that CXCL1 may be a potential molecular target for use in HCC therapy.

We established a rat model of hyperphosphatemia and investigated the systemic effects of high phosphorus (P). Sprague Dawley rats were randomly divided into high (HP), low (LP), and normal (NP) P groups (N = 12 each), which received injections of fructose diphosphate sodium, or were fed self-manufactured low phosphorus or normal diets, respectively. In each group, 4 rats were sacrificed at the first, third, and sixth week to detect the serum (Scr) and urinary creatinine and P, and calcium (Ca) levels. The HP group's serum P and intact parathyroid hormone (iPTH) were significantly higher than those in the other groups at the first, third, and sixth weeks, (P < 0.05); the LP group's serum P was lower than the NP group's at the third week (P < 0.05), while at the sixth week, the serum P and iPTH were lower (P < 0.05). No significant differences were detected for blood Ca+ (P > 0.05). The HP group's Scr increased (P < 0.01), whereas the fractional excretion decreased (P < 0.05) significantly. Thighbone and lumbar spine bone densities differed significantly between groups in the third week (P < 0.05); LP group densities were lower than NP group measures (P < 0.05). Crystallized stones were not observed microscopically following hematoxylin and eosin staining of the kidney. We successfully established a hyperphosphatemia rat model, and high blood P was found to significantly influence renal function and bone density. These results might provide a foundation to study the effects of hyperphosphatemia in rats.

We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

Aim: To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice., Methods: CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed., Results: Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1β protein., Conclusion: These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.

The combined effect of side-coupled gain cavity and lossy cavity on the plasmonic response of metal-dielectric-metal (MDM) surface plasmon polariton (SPP) waveguide is investigated theoretically using Green's function method. Our result suggests that the gain and loss parameters influence the amplitude and phase of the fields localized in the two cavities. For the case of balanced gain and loss, the fields of the two cavities are always of equi-amplitude but out of phase. A plasmon induced transparency (PIT)-like transmission peak can be achieved by the destructive interference of two fields with anti-phase. For the case of unbalanced gain and loss, some unexpected responses of structure are generated. When the gain is more than the loss, the system response is dissipative at around the resonant frequency of the two cavities, where the sum of reflectance and transmittance becomes less than one. This is because the lossy cavity, with a stronger localized field, makes the main contribution to the system response. When the gain is less than the loss, the reverse is true. It is found that the metal loss dissipates the system energy but facilitates the gain cavity to make a dominant effect on the system response. This mechanism may have a potential application for optical amplification and for a plasmonic waveguide switch.

A pot experiment was conducted to study the effects of adding different amounts of wheat straw (0 g x kg(-1), N0; 2.08 g x kg(-1), N1) and phosphorus (0 mg x kg(-1), P0; 100 mg x kg(-1), P1; 200 mg x kg(-1), P2; 400 mg x kg(-1), P3) on microorganism community in a soil of low-phosphorus. Adding straw and phosphorus had significant effects on the soil microbial total biomass (MTB), bacterial biomass (MB), fungal biomass (FB), and fungi to bacteria ratio (F/B), which all decreased in order of N1P1>N1P0>N1P2>N1P3>N0P1>N0P2>N0P3. MTB, MB, FB and F/B ratio of the wheat straw addition treatments were all significantly higher than in the non-straw addition treatments under the same level of phosphorus addition. As for the same wheat straw addition, MTB, MB, FB and F/B ratio increased firstly and then decreased with increasing the level of phosphorus addition, and the combinations of P1 level were optimal.

Objective: Major histocompatibility complex class I chain-related A (MICA) is a stress-inducible glycoprotein that can be shed as a soluble protein. This study was conducted to determine the expression of MICA in renal cell carcinoma (RCC) and examine the clinical relevance of soluble MICA (sMICA) in this disease., Methods: Immunohistochemistry and real-time PCR analyses were performed to assess the expression of MICA in 48 pairs of RCC and adjacent normal renal tissues. Serum levels of sMICA were measured in 48 RCC patients, 12 patients with benign renal tumors, and 20 healthy individuals. The correlations between sMICA levels and clinicopathological parameters were analyzed and the diagnostic performance of sMICA in RCC was evaluated., Results: RCCs exhibited elevated expression of MICA compared to adjacent normal tissues. Serum concentrations of sMICA were significantly greater in RCC patients (348.5 ± 32.5 pg/ml) than those with benign disease (289.3 ± 30.4 pg/ml) and healthy controls (168.4 ± 43.2 pg/ml) and significantly correlated with advanced tumor stage, lymph node metastasis, distant metastasis, vascular invasion, and higher histological grade. Using a cut-off point of 250 pg/ml, sMICA demonstrated a specificity and sensitivity of 63.2% and 75.6%, respectively, in distinguishing between RCC and benign renal tumors., Conclusion: MICA expression is upregulated in RCC and increased serum sMICA levels predict aggressive tumor behavior. However, the applicability of sMICA alone is limited in distinguishing RCC from benign renal tumors.

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used for the treatment of cardiovascular diseases. Several factors may affect TMP exposure after topical administration, resulting in large variability and demanding further elucidation of drug distribution. This paper describes a new efficient reliable LC-MS/MS assay for the determination of TMP in dermal microdialysate, where TMP was separated on an Agilent C(18) column (3.5 µm, 100 mm × 2.1 mm i.d.) using a mixture of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow-rate of 0.3 mL/min. The retention time was 1.89 min for TMP and 1.17 min for the internal standard (caffeine). Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for TMP was not altered through the implant lifetime. The validation and sample analysis results showed that the method is precise, accurate and well suited to support dermal microdialysis experiments., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: To study the mechanisms of tuina manipulation for treating the dislocation of bone in cervical spondylosis (CS) patients by observing the effects of tuina manipulation on the three-dimensional (3D) angles., Methods: From August to December 2009 20 CS patients were assigned to Group 1 (10 cases, treated with relaxing manipulation) and Group 2 (10 cases, treated with relaxing manipulation and joint regulation). Besides, 10 healthy subjects were recruited as the normal group (treated with relaxing manipulation). Before and after manipulation intervention, all of them were scanned from the base of the skull to the first thoracic vertebra using Philips 64 spiral CT under equal conditions, thus obtaining the volume data. The 0.625 mm thickness was reconstructed using ITK reconstruction software provided by the digital medical laboratory, Software College of Shanghai Jiaotong University. The reconstruction of each cervical skeleton was finished referring to CT data. Changes of the 3D angles were compared among the three groups., Results: The regulation of the 3D C2 vertebra: Results of Group 2 were significantly larger than those of the normal group at X-, Y-, and Z-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X- and Z-axis (P < 0.05). But results of Group 1 were significantly larger than those of the normal group at Z-axis (P < 0.05). The regulation of the 3D C3 vertebra: Results of Group 2 were significantly larger than those of the normal group at X- and Y-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X-axis (P < 0.05). But results of Group 1 were significantly larger than those of the normal group at X-axis (P < 0.05). The regulation of the 3D C4 vertebra: Results of Group 2 were significantly larger than those of the normal group at X- and Y-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X- and Z-axis (P < 0.05). There were no significant difference among the three groups in the 3D spaces of C1, C5, C6, and C7. The larger 3D space was shown in Group 2 than in Group 1 and the normal group., Conclusions: The relaxing manipulation combined with joint regulation significantly improved the 3D angles of C2, C3, and C4 in CS patients. The mechanism of tuina manipulation for treating the dislocation of bone in CS patients might lie in adjusting the 3D space of the cervical spine, and improving its functions.

The purpose of this study was to evaluate percutaneous penetration and arrhythmogenic effects of aconitine after transdermal administration, compared with the oral route. Skin penetration of aconitine was tested by a microdialysis technique in rats and in vivo recovery was determined by retrodialysis. After oral and transdermal administration of aconitine, dialysate was sampled at 20 min intervals until the end of the experiment for the determination of concentration of aconitine in skin. Blood samples were collected and analyzed using a validated HPLC-MS/MS method. In addition, we concurrently recorded the electrocardiogram (ECG). The in vivo recovery of aconitine in the skin was calculated to be 39.59%. The C(max) values for aconitine absorbed into the skin after oral and transdermal administration were 1.51 ± 0.53 and 2723.8 ± 848.8 ng/mL, respectively, and within the plasma, 215.86 ± 79.29 and 20.92 ± 3.15 ng/mL. The C(max) value for the plasma concentration of aconitine after oral administration was approximately 10 times higher than with the transdermal route. For oral administration, the ECG revealed various types of arrhythmias at a period of T(max) , which is normal in transdermal gel administration. These results indicate that transdermal aconitine gel is a safe formulation that can deliver the drug in sufficient amounts and safe concentrations to produce therapeutic action in rats., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objectives: Ginsenoside Rg1 (GRg1), one of the major active constituents of Panax notoginseng, has shown anti-inflammatory and antinocioceptic activity, but its role in keratinocytes needs further study. We have examined the inhibitory effect of GRg1 on transient receptor potential vanilloid-1 (TRPV1) activation in keratinocyte HaCaT cells and explored its involved mechanism., Methods: HEK 293T cells over-expressing exogenous TRPV1 were constructed and named HEK 293T-TRPV1 cells. The effects of GRg1 on production of interleukin-8 (IL-8) and prostaglandin E(2) (PGE(2) ), calcium influx, the expression of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) transcriptional activity in HEK 293T-TRPV1 and HaCaT cells were examined by ELISA, Fluo 3-AM fluorescence probe, Western blot and Dual-Luciferase Reporter Assay, respectively., Key Findings: The results showed that GRg1 blocked intracellular calcium by both capsaicin and proton activation in a TRPV1-dependent manner. Furthermore, GRg1 inhibited the expression of COX-2 and NF-κB transcriptional activity induced by capsaicin in keratinocytes. The inhibitory effect of GRg1 was similar to capsazepine, an antagonist of TRPV1. More importantly, GRg1 dose-dependently inhibited capsaicin-induced PGE(2) and IL-8 secretion in HaCaT cells and HEK 293T-TRPV1 cells., Conclusions: These data showed that GRg1 could inhibit TRPV1 mediated responses in HaCaT cells, indicating that GRg1 acted as a TRPV1 antagonist., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Objective: To explore the mechanism of manipulation in treating cervical spondylosis., Methods: From August 2008 to December 2009, 65 patients with cervical spondylosis were randomly divided into manipulation group and traction group. There were 32 patients in manipulation group, of which 30 cases obtained followed-up, including 10 males and 20 females, ranging in age from 30 to 65 years,with an average of (42.31 +/- 13.23) years; the mean course of diseases was (12.40 +/- 6.23) months, and the average weight was (61.21 +/- 10.23) kg. In traction group, there were 33 patients, 30 cases obtained follow-up, including 11 males and 19 males, ranging in age from 30 to 65 years, with an average of (45.54 +/- 14.35) years; the mean course of diseases was (13.25 +/- 6.06) months and average weight was (62.31 +/- 10.45) kg. Biodex III Isokinetic Testing System and TeleMyo 2400 T Surface EMG was applied to test the mechanical properties and fatigue of neck muscles before and after treatment., Results: The mechanical properties of neck muscles: measuring in the 60 degrees/s and 120 degrees/s angular velocity, there were no significant difference (P > 0.05) in peak torque (PT), average power (AP), peak torque of flexor/extensor peak torque ratio (F/E) before treatment, while manipulation group was improved more than traction group in PT, AP, F/E after treatment (P < 0.05), and there was significant difference (P < 0.05). For the degree of fatigue: there was no significant difference (P > 0.05) in IEMG, MPF compared by two groups before treatment, but the manipulation group was improved more than the traction group in IEMG, MPF after treatment (P < 0.05), and there was significant difference (P < 0.05) on the right side., Conclusion: Manipulation can improve contraction forces and work efficiency of neck muscle, coordination ability of flexors and extensors muscles, efficiency of neck muscle, and recover mechanical properties and can alleviate fatigue of neck muscles in patients with cervical spondylosis.

Spinal "Gucuofeng" mainly is considered as abnormalities of joint function. Manipulative maneuver have obviously effect in adjustment of spinal "Gucuofeng", and the technical key point is utilization of principle of lever to achieve safe, effective and labor-saving purpose. After clinical practice, the general principle of manipulative maneuver in adjustment of spinal "Gucuofeng" can be summed up as pull stretch traction, first-induced instability, reverse adjustment,withdraw along situation.

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.