Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Juxtaposed membranes underpin cellular adhesion and display unilateral cell division of multicellular magnetotactic prokaryotes.

Multicellular magnetotactic prokaryotes (MMPs) exhibit peculiar coordination of swimming along geomagnetic field lines. Approximately 40-80 cells assemble, with a helical geometry or axisymmetry, into spherical or ellipsoidal MMPs respectively. To contribute to a comprehensive understanding of bacterial multicellularity here we took multiple microscopic approaches to study the diversity, assembly, reproduction and motility of ellipsoidal MMPs. Using correlative fluorescence in situ hybridization and scanning electron microscopy analysis, we found an unexpected diversity in populations of ellipsoidal MMPs in the Mediterranean Sea. The high-pressure freezing/freeze substitution fixation technique allowed us to show, for the first time, that cells adhere via juxtaposed membranes and are held together by a rimming lattice. Fluorescence confocal microscopy and ultrathin section images revealed not only the one-layer hollow three-dimensional architecture, but also periphery-core unilateral constriction of constituent cells and unidirectional binary fission of the ellipsoidal MMPs. This finding suggests the evolution toward MMPs multicellularity via the mechanism of incomplete separation of offspring. Remarkably, thousands of flagellar at the periphery surface of cells underpin the coordinated swimming of MMPs in response to mechanical, chemical, magnetic and optical stimuli, including a magnetotactic photokinesis behaviour. Together these results unveil the unique structure and function property of ellipsoidal MMPs.

Ultrastructure of ellipsoidal magnetotactic multicellular prokaryotes depicts their complex assemblage and cellular polarity in the context of magnetotaxis.

Magnetotactic multicellular prokaryotes (MMPs) consist of unique microorganisms formed by genetically identical Gram-negative bacterial that live as a single individual capable of producing magnetic nano-particles called magnetosomes. Two distinct morphotypes of MMPs are known: spherical MMPs (sMMPs) and ellipsoidal MMPs (eMMPs). sMMPs have been extensively characterized, but less information exists for eMMPs. Here, we report the ultrastructure and organization as well as gene clusters responsible for magnetosome and flagella biosynthesis in the magnetite magnetosome producer eMMP Candidatus Magnetananas rongchenensis. Transmission electron microscopy and focused ion beam scanning electron microscopy (FIB-SEM) 3D reconstruction reveal that cells with a conspicuous core-periphery polarity were organized around a central space. Magnetosomes were organized in multiple chains aligned along the periphery of each cell. In the partially sequenced genome, magnetite-related mamAB gene and mad gene clusters were identified. Two cell morphologies were detected: irregular elliptical conical 'frustum-like' (IECF) cells and H-shaped cells. IECF cells merge to form H-shaped cells indicating a more complex structure and possibly a distinct evolutionary position of eMMPs when compared with sMMPs considering multicellularity.

A novel species of ellipsoidal multicellular magnetotactic prokaryotes from Lake Yuehu in China.

Two morphotypes of multicellular magnetotactic prokaryotes (MMPs) have been identified: spherical (several species) and ellipsoidal (previously one species). Here, we report novel ellipsoidal MMPs that are ∼ 10 × 8 µm in size, and composed of about 86 cells arranged in six to eight interlaced circles. Each MMP was composed of cells that synthesized either bullet-shaped magnetite magnetosomes alone, or both bullet-shaped magnetite and rectangular greigite magnetosomes. They showed north-seeking magnetotaxis, ping-pong motility and negative phototaxis at a velocity up to 300 µm s(-1) . During reproduction, they divided along either their long- or short-body axes. For genetic analysis, we sorted the ellipsoidal MMPs with micromanipulation and amplified their genomes using multiple displacement amplification. We sequenced the 16S rRNA gene and found 6.9% sequence divergence from that of ellipsoidal MMPs, Candidatus Magnetananas tsingtaoensis and > 8.3% divergence from those of spherical MMPs. Therefore, the novel MMPs belong to different species and genus compared with the currently known ellipsoidal and spherical MMPs respectively. The novel MMPs display a morphological cell differentiation, implying a potential division of labour. These findings provide new insights into the diversity of MMPs in general, and contribute to our understanding of the evolution of multicellularity among prokaryotes.

Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils.

High levels of acetyl-CoA are considered a key metabolic feature of metastatic cancers. However, the impacts of acetyl-CoA metabolic accumulation on cancer microenvironment remodeling are poorly understood. In this study, using human hepatocellular carcinoma (HCC) tissues and orthotopic xenograft models, we found a close association between high acetyl-CoA levels in HCCs, increased infiltration of tumor-associated neutrophils (TANs) in the cancer microenvironment and HCC metastasis. Cytokine microarray and enzyme-linked immunosorbent assays (ELISA) revealed the crucial role of the chemokine (C-X-C motif) ligand 1(CXCL1). Mechanistically, acetyl-CoA accumulation induces H3 acetylation-dependent upregulation of CXCL1 gene expression. CXCL1 recruits TANs, leads to neutrophil extracellular traps (NETs) formation and promotes HCC metastasis. Collectively, our work linked the accumulation of acetyl-CoA in HCC cells and TANs infiltration, and revealed that the CXCL1-CXC receptor 2 (CXCR2)-TANs-NETs axis is a potential target for HCCs with high acetyl-CoA levels.

Novel rod-shaped magnetotactic bacteria belonging to the class Alphaproteobacteria.

Novel large, rod-shaped magnetotactic bacteria (MTB) were discovered in intertidal sediments of the Yellow Sea, China. They biomineralized more than 300 rectangular magnetite magnetosomes per cell. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that they are affiliated with the Alphaproteobacteria and may represent a new genus of MTB.

[Electroacupuncture preconditioning relieves cutaneous passive anaphylaxis by down-regulating IP3 mediated ROS/TRPM2 signaling pathway and inhibiting mast cell degranulation in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning of "Quchi" (LI11) and "Xuehai" (SP10) on mast cell (MC) degranulation, and expressions of inositol triphosphate(IP3), reactive oxygen species (ROS), transient receptor potential (TRP) M2, calmodulin (CaM) in rats with urticaria, so as to reveal its molecular mechanism under-lying improving urticaria. METHODS: Thirty-two male SD rats were randomly divided into blank control, model, preconditioning of EA (Pre-EA) and medication groups (n=8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days, and those of the medication group received gavage of loratadine tablets diluted solution (1 mg/kg) once a day for 10 days. The times of rat's scratching the sensitized skin were recorded, the diameter of the sensitized blue spots was measured and the degranulation rate of skin MCs was counted under microscope after toluidine blue staining. The expression levels of IP3, ROS, TRPM2 and CaM in the skin tissue were measured by immunohistochemistry and western blot, respectively. RESULTS: Compared with the blank control group, the scratching times, diameter of the sensitized blue spots, degranulation rate of MCs, and the expression levels of ion channel related proteins (IP3, ROS, TRPM2 and CaM) were significantly increased (P<0.01) in the model group. In comparison with the model group, the scratching times, diameter of sensitized blue spot, degranulation rate of MCs, and the expression levels of IP3, ROS, TRPM2 and CaM in both pre-EA and medication groups were significantly down-regulated (P<0.01, P<0.05). No significant differences were found between Pre-EA and medication groups in down-regulating the levels of the above-mentioned 7 indexes. CONCLUSION: EA-LI11 and SP10 preconditioning can reduce the cutaneous anaphylaxis in urticaria rats, which may be related to its effects in inhibiting the degranulation of MCs, and the expression of TRP channel related proteins.

Classification and biomarker gene selection of pyroptosis-related gene expression in psoriasis using a random forest algorithm.

Background: Psoriasis is a chronic and immune-mediated skin disorder that currently has no cure. Pyroptosis has been proved to be involved in the pathogenesis and progression of psoriasis. However, the role pyroptosis plays in psoriasis remains elusive. Methods: RNA-sequencing data of psoriasis patients were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed pyroptosis-related genes (PRGs) between psoriasis patients and normal individuals were obtained. A principal component analysis (PCA) was conducted to determine whether PRGs could be used to distinguish the samples. PRG and immune cell correlation was also investigated. Subsequently, a novel diagnostic model comprising PRGs for psoriasis was constructed using a random forest algorithm (ntree = 400). A receiver operating characteristic (ROC) analysis was used to evaluate the classification performance through both internal and external validation. Consensus clustering analysis was used to investigate whether there was a difference in biological functions within PRG-based subtypes. Finally, the expression of the kernel PRGs were validated in vivo by qRT-PCR. Results: We identified a total of 39 PRGs, which could distinguish psoriasis samples from normal samples. The process of T cell CD4 memory activated and mast cells resting were correlated with PRGs. Ten PRGs, IL-1ß, AIM2, CASP5, DHX9, CASP4, CYCS, CASP1, GZMB, CHMP2B, and CASP8, were subsequently screened using a random forest diagnostic model. ROC analysis revealed that our model has good diagnostic performance in both internal validation (area under the curve [AUC] = 0.930 [95% CI 0.877-0.984]) and external validation (mean AUC = 0.852). PRG subtypes indicated differences in metabolic processes and the MAPK signaling pathway. Finally, the qRT-PCR results demonstrated the apparent dysregulation of PRGs in psoriasis, especially AIM2 and GZMB. Conclusion: Pyroptosis may play a crucial role in psoriasis and could provide new insights into the diagnosis and underlying mechanisms of psoriasis.

The Arabidopsis eukaryotic translation initiation factor 3, subunit F (AteIF3f), is required for pollen germination and embryogenesis.

Previous studies have shown that subunits E (eIF3e), F (eIF3f) and H (elF3h) of eukaryotic translation initiation factor 3 play important roles in cell development in humans and yeast. eIF3e and eIF3h have also been reported to be important for normal cell growth in Arabidopsis. However, the functions of subunit eIF3f remain largely unknown in plant species. Here we report characterization of mutants for the Arabidopsis eIF3f (AteIF3f) gene. AteIF3f encodes a protein that is highly expressed in pollen grains, developing embryos and root tips, and interacts with Arabidopsis eIF3e and eIF3h proteins. A Ds insertional mutation in AteIF3f disrupted pollen germination and embryo development. Expression of some of the genes that are essential for pollen tube growth and embryogenesis is down-regulated in ateif3f-1 homozygous seedlings obtained by pollen rescue. These results suggested that AteIF3f might play important roles in Arabidopsis cell growth and differentiation in combination with eIF3e and eIF3h.

Desulfovibrio is not always associated with adverse health effects in the Guangdong Gut Microbiome Project.

Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira, Coprococcus,Ruminococcus,Akkermansia, Roseburia,Faecalibacterium, andBacteroides, and was negatively associated with harmful genera, such as Clostridium,Escherichia,Klebsiella, and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.

Tanshinone IIA Combined With Cyclosporine A Alleviates Lung Apoptosis Induced by Renal Ischemia-Reperfusion in Obese Rats.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project.

Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.

[Effect of electroacupuncture on expressions of Lyn and Syk in mast cells of subcutaneous loose connective tissue in rats with urticarial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria. METHODS: A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg-1•d-1) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells. RESULTS: In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (P<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (P<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (P<0.01). CONCLUSION: Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.

Complete Genome Insights into Lactococcus petauri CF11 Isolated from a Healthy Human Gut Using Second- and Third-Generation Sequencing.

Lactococcus petauri CF11 was originally isolated from the gut of healthy humans. To determine the underlying molecular and genetic mechanisms of the probiotic potential of CF11, we performed complete genome sequencing, annotation, and comparative genome analysis. The complete genome of L. petauri CF11 comprised of 1,997,720 bp, with a DNA G+C content of 38.21 mol% containing 1982 protein coding genes and 16 rRNA operons. We found that 1206 genes (56.05%) were assigned a putative function using the gene ontology (GO) resource. The gene products of CF11 were primarily concentrated in molecular function and biological processes, such as catalysis, binding, metabolism, and cellular processes. Furthermore, 1,365 (68.87%) genes were assigned an illative function using COGs. CF11 proteins were associated with carbohydrate transport and metabolism, and amino acid transport and metabolism. This indicates that CF11 bacteria can perform active energy exchange. We classified 1,111 (56.05%) genes into six KEGG functional categories; fructose-bisphosphate aldolase and the phosphoenol pyruvate:phosphotransferase system (PTS), which are necessary in producing short-chain fatty acids (SCFAs), were excited in the carbohydrate metabolic pathway. This suggests that L. petauri CF11 produces SCFAs via glycolysis. The genomic island revealed that some regions contain fragments of antibiotic resistance and bacteriostatic genes. In addition, ANI analysis showed that L. petauri CF11 had the closest relationship with L. petauri 159469T, with an average nucleotide consistency of 98.03%. Taken together, the present study offers further insights into the functional and potential role of L. petauri CF11 in health care.

[Lower frequency electroacupuncture is better in promoting recovery of limb locomotion in rats with sciatic nerve injury by reducing local inflammatory reaction].

OBJECTIVE: To observe the effect of different frequencies (2 Hz, 100 Hz) of electroacupuncture (EA) on limb locomotion and the expression of inflammatory factors IL-1ß, IL-6, TNF-α in sciatic nerve, and nuclear factor kappa B (NF-κB) in lumber(L)4-L5of spinal cord in rats with sciatic nerve injury (SNI), so as to reveal its mechanisms underlying improvement of SNI. METHODS: A total of 48 SD rats (half male and half female) were equally divided into blank control, model, low frequency (2 Hz) EA and high frequency (100 Hz) EA groups. The SNI model was established by clamping the spinal nerve. EA intervention (2 Hz, 100 Hz, 1 mA), starting on the 8th day after modeling, was applied to "Huantiao" (GB30) on the injured side for 15 min, once daily for 14 consecutive days. The sciatic function index (SFI) was calculated to assess the injured hindlimb recovery with reference to BAIN's and colleagues' methods. Histopathological changes of the sciatic nerve were displayed by H.E. staining. The expressions of IL-1ß, IL-6 and TNF-α in the sciatic nerve tissue were detected by immunohistochemistry, and the expression of NF-κB in the spinal cord was detected by using Western blot. RESULTS: After modeling, the SFI level on day 8 was significantly decreased in the model group (P<0.01), and no significant differences were found among the model, low frequency EA and high frequency EA groups before the EA intervention (P>0.05). Following the treatment (at the 22nd day), the SFI values of both low frequency EA and high frequency EA groups were significantly increased (P<0.01), suggesting an improvement of the limb motor function, and the SFI of the low frequency EA group was notably higher than that of the high frequency EA group (P<0.01). In comparison with the blank control group, the expression levels of IL-1ß, IL-6, TNF-α in the sciatic nerve and NF-κB protein in the spinal cord were significantly up-regulated (P<0.05). Following EA intervention, the increased expression levels of IL-1ß, IL-6, TNF-α and NF-κB proteins were significantly down-regulated in both low frequency EA and high frequency EA groups (P<0.05), and the therapeutic effect of low frequency EA was markedly superior to that of high frequency EA in down-regulating the expression levels of IL-1ß, IL-6, TNF-α and NF-κB protein (P<0.05). H.E. staining showed increase of Schwann cells in number, cellular swelling, and disintegration of the axons and myelin sheath, and appearance of vacuolar degeneration in the model group, which was relatively milder in both low frequency EA and high frequency EA groups, particularly in the low frequency EA group. CONCLUSION: EA of GB30 at 2 Hz and 100 Hz can promote the recovery of hindlimb motor function in SNI rats, which is probably related to its function in inhibiting the inflammatory response, and facilitating the repair of the damaged sciatic nerve. 2 Hz EA is better than 100 Hz EA in the therapeutic effect.

Type I collagen or gelatin stimulates mouse peritoneal macrophages to aggregate and produce pro-inflammatory molecules through upregulated ROS levels.

BACKGROUND: Extracellular matrix (ECM) comprising the environments of multicellular society has a dynamic network structure. Collagen is one of the ubiquitous components of ECM. Collagen affects the inflammatory response by regulating the release of pro-inflammatory cytokines from cells. Gelatin, denatured collagen found temporally in tissues, is supposed to be pathophysiologically involved in tissue remodeling, inflammation caused by tissue damage. Previous reports indicate that, phorbol myristate (PMA)-stimulated human U937 (lymphoma cell line) cells that are often used as macrophage-like cells, show cell aggregations when cultured on type I collagen (col I) or gelatin-coated dishes, accompanying the changes of production and release of proinflammatory factors. However, it still remains to be examined whether collagen and gelatin affects normal macrophages as well. AIM: This study aims to investigate the effect of col. I, the main component of collagenous protein and its denatured product, gelatin, on mouse peritoneal macrophages (MPMs). METHODS: MTT assay, flow cytometric analysis of ROS, biochemical detection of antioxidant levels, ELISA assay, and western blot were used. RESULTS: MPMs formed multicellular aggregates on col. I - and gelatin-coated dishes with a concentration- and time-dependent manner. Further studies showed that the culture on col. I and gelatin up-regulated the protein expression and secretion of pro-inflammatory molecules such as IL-1ß, TNFα and prostaglandin E2 (PGE2) in MPMs. The levels were higher in the cells on gelatin than those on col. I. ROS levels are significantly increased in the cells cultured on both col. I- and gelatin-coated dishes, accompanying decreased levels of antioxidant enzyme catalase (CAT) and anti-oxidant glutathione (GSH), and enhanced nuclear translocation of NF-κB. CONCLUSION: Col I - or gelatin-coated culture induced the formation of multicellular aggregates and increased production of NF-κB-associated pro-inflammatory molecules in MPMs through up-regulation of ROS levels.

[Characteristics of soil phosphorus fractions of different vegetation types in subtropical forests and their driving factors.] / äºšçƒ­å¸¦ä¸åŒæ¤è¢«ç±»åž‹åœŸå£¤ç£·ç»„åˆ†ç‰¹å¾åŠå ¶å½±å“å› ç´ .

Soil P fraction, microbial biomass P (MBP), and activities of acid phosphomonoesterase (ACP) and phosphodiesterase (PD) were analyzed under evergreen broad-leaved forest, mixed forest and coniferous forest in Daiyun Mountains. The results showed that labile-P comprised only 1.0%-4.5% of soil total phosphorus (TP). The ratio of soil carbon to organic phosphorus (C:Po) was >200, indicating phosphorus limitation across the three vegetation types. Organic phosphorus (Po) was a significant fraction of soil P, which accounted for 44.8%-47.1% and 28.6%-30.6% of TP in A and B horizons, respectively. Results from the redundancy analysis showed that the changes in P fractions were mainly driven by PD in the A horizon and by ACP in the B horizon. Moreover, the activities of PD and ACP had a significant negative correlation with Po. The results suggested that phosphorus deficiency occurred in the three vegetation types, and that PD and ACP could play major roles in the depletion of soil Po in response to phosphorus limitation in subtropical forests.

Stratified Platelet-to-lymphocyte Ratio: A Novel Target for Prognostic Prediction of Hepatocellular Carcinoma after Curative Liver Resection.

Background and Aims: Platelet-to-lymphocyte ratio (PLR) has been shown to predict prognosis of cancers. We aimed to evaluate the prognostic value of stratification of PLR in patients after curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1804 patients who underwent CLR for suspected HCC between January 2007 and January 2014 were screened for the study. All of the patients were categorized into equal tertiles according to the number of patients and the distribution of PLR. Prognostic significance was determined for overall survival (OS) and was assessed using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. Results: The optimal cut-off points of preoperative PLR were: (T1) 11.98-75.00, (T2) 75.00-113.33 and (T3) 113.33-567.50. There were obvious differences in each PLR tertile with mortality within 36 months of CLR (plog-rank < 0.001). Multivariable analysis suggested that the level of PLR (HR = 1.004, 95%CI: 1.001-1.008, p = 0.006), portal vein thrombosis (HR = 3.406, 95%CI: 1.185-9.794, p = 0.023), number of nodules (HR = 1.810, 95%CI: 1.345-2.437, p < 0.001), Child-Turcotte-Pugh score (HR = 1.741, 95%CI: 1.129-2.684, p = 0.012) and microvascular invasion (HR = 2.730, 95%CI: 1.777-4.196, p < 0.001) were significant predictors of mortality. Kaplan-Meier analysis of overall survival (OS) demonstrated that each PLR tertile showed a progressively worse OS and apparent separation (plog-rank = 0.016). The highest 5-year OS rate following CLR (58%) was revealed in tertile 1. In contrast, the lowest 5-year OS rate (30%) was revealed in tertile 3. Conclusion: Stratified preoperative PLR could strengthen the predictive power for OS in HCC patients with CLR.

Association of low-density lipoprotein cholesterol within the normal range and NAFLD in the non-obese Chinese population: a cross-sectional and longitudinal study.

OBJECTIVES: The relationship between normal low-density lipoprotein cholesterol (LDL-c) levels and non-alcoholic fatty liver disease (NAFLD) in non-obese individuals remains unclear. We aimed to investigate the precise prevalence and incidence of NAFLD within the normal LDL-c range in non-obese individuals. DESIGN: Cross-sectional and longitudinal study. SETTING: Wenzhou Medical Center of Wenzhou People's Hospital from 2010 to 2014. PARTICIPANTS: 183 903 non-obese individuals were enrolled from a cross-sectional population, and a total of 16 173 initially NAFLD-free non-obese individuals were included who completed a 5-year follow-up examination in the longitudinal population. RESULTS: In our study, NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. The cross-sectional study showed that at baseline, the prevalence of NAFLD was 13.9% in non-obese individuals with normal LDL-c levels. The prospective study demonstrated that NAFLD-free participants developed NAFLD during the 5-year follow-up period, with a cumulative incidence of 14.4%. In addition, the ORs for NAFLD in the cross-sectional population were 1.11 (95% CI 1.04 to 1.18), 1.37 (95% CI 1.27 to 1.47) and 1.56 (95% CI 1.43 to 1.69), respectively, after adjusting for known confounding variables. The HRs for NAFLD in the longitudinal population were 1.15 (95% CI 0.98 to 1.36), 1.32 (95% CI 1.10 to 1.58) and 1.82 (95% CI 1.47 to 2.52), compared with Q1. Individuals with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD in non-obese individuals. CONCLUSIONS: NAFLD is prevalent in the non-obese Chinese population. Furthermore, this is the first study to demonstrate that increased normal LDL-c levels are independently associated with an elevated risk of NAFLD in non-obese individuals.

Novel species and expanded distribution of ellipsoidal multicellular magnetotactic prokaryotes.

Multicellular magnetotactic prokaryotes (MMPs) are a peculiar group of magnetotactic bacteria, each comprising approximately 10-100 cells of the same phylotype. Two morphotypes of MMP have been identified, including several species of globally distributed spherical mulberry-like MMPs (s-MMPs), and two species of ellipsoidal pineapple-like MMPs (e-MMPs) from China (Qingdao and Rongcheng cities). We recently collected e-MMPs from Mediterranean Sea sediments (Six-Fours-les-Plages) and Drummond Island, in the South China Sea. Phylogenetic analysis revealed that the MMPs from Six-Fours-les-Plages and the previously reported e-MMP Candidatus Magnetananas rongchenensis have 98.5% sequence identity and are the same species, while the MMPs from Drummond Island appear to be a novel species, having > 7.1% sequence divergence from the most closely related e-MMP, Candidatus Magnetananas tsingtaoensis. Identification of the novel species expands the distribution of e-MMPs to Tropical Zone. Comparison of nine physical and chemical parameters revealed that sand grain size and the content of inorganic nitrogen (nitrate, ammonium and nitrite) in the sediments from Rongcheng City and Six-Fours-les-Plages were similar, and lower than found for sediments from the other two sampling sites. The results of the study reveal broad diversity and wide distribution of e-MMPs.