Artesunate-loaded thermosensitive chitosan hydrogel promotes osteogenesis of maxillary tooth extraction through regulating T lymphocytes in type 2 diabetic rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats. METHODS: T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored. RESULTS: Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4+ T, CD8+ T, and CD4+:CD8+ T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla. CONCLUSIONS: Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.

Mechanism and effects of artesunate on the liver function of rats with type 1 diabetic periodontitis.

Periodontitis is an inflammatory disease of the gums. Periodontitis in diabetic patients can aggravate insulin resistance; however, its molecular and biological mechanism remains unclear. This study aimed to explore the effects of diabetic periodontitis on liver function and determine the mechanism by which artesunate improves liver function. Rats with streptozotocin-induced diabetes were divided into five groups: normal control (NC), diabetic periodontitis (DM + PD), artesunate intervention (ART), insulin intervention (INS), and combined medication intervention (ART + INS) groups. Drug interventions were then administered to the rats in each group as follows: 50 mg/kg artesunate to the ART group, 6 U/kg insulin to the INS group, and 50 mg/kg artesunate + 6 U/kg insulin to the ART + INS group. Blood samples, liver tissues, and the maxillary alveolar bone were collected postsacrifice. ART was found to significantly ameliorate hyperglycemia, blood lipid concentrations, and liver function. The levels of inflammatory factors reduced; the effect was more pronounced in the ART + INS group. Artesunate presumably inhibits the TLR4/NF-κB signaling pathway and expression of downstream inflammatory factors, thereby exerting a protective effect on diabetes-related liver function. This offers a fresh approach to treat diabetes mellitus.

GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity induced by anthracycline-/paclitaxel-based chemotherapy in breast cancer patients.

BACKGROUND: The link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer. METHODS: This study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy. RESULTS: There were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I-III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141-16.000, P = 0.031) was an independent variable associated with neutropenia. CONCLUSIONS: The findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.

The Mechanism of Piezocatalysis: Energy Band Theory or Screening Charge Effect?

Piezocatalysis, a newly emerging catalysis technology that relies on the piezopotential and piezoelectric properties of the catalysts, is attracting unprecedented research enthusiasm for applications in energy conversion, organic synthesis, and environmental remediation. Despite the rapid development in the past three years, the mechanism of piezocatalysis is still under debate. A fundamental understanding of the working principles of this technology should enable the future design and optimization of piezocatalysts. Herein, we provide an overview of the two popular theories used to explain the observed piezocatalysis: energy band theory and screening charge effect. A comprehensive discussion and clarification of the differences, relevance, evidence, and contradiction of the two mechanisms are provided. Finally, challenges and perspectives for future mechanistic studies are highlighted. Hopefully, this Review can help readers gain a better understanding of piezocatalysis and enable its application in their own research.

Cobalt Single Atoms Embedded in Nitrogen-Doped Graphene for Selective Oxidation of Benzyl Alcohol by Activated Peroxymonosulfate.

The development of novel single atom catalyst (SAC) is highly desirable in organic synthesis to achieve the maximized atomic efficiency. Here, a Co-based SAC on nitrogen-doped graphene (SACo@NG) with high Co content of 4.1 wt% is reported. Various characterization results suggest that the monodispersed Co atoms are coordinated with N atoms to form robust and highly effective catalytic centers to activate peroxymonosulfate (PMS) for organic selective oxidation. The catalytic performance of the SACo@NG/PMS system is conducted on the selective oxidation of benzyl alcohol (BzOH) showing high efficiency with over 90% conversion and benzaldehyde selectivity within 180 min under mild conditions. Both radical and non-radical processes occurred in the selective oxidation of BzOH, but the non-radical oxidation plays the dominant role which is accomplished by the adsorption of BzOH/PMS on the surface of SACo@NG and the subsequent electron transfer through the carbon matrix. This work provides new insights to the preparation of efficient transition metal-based single atom catalysts and their potential applications in PMS mediated selective oxidation of alcohols.

Role of Artesunate on cardiovascular complications in rats with type 1 diabetes mellitus.

BACKGROUND: The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. RESULTS: The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). CONCLUSIONS: ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.

Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) acts as the key enzyme catabolizing pyrimidines, and may affect the tumor progression. DPYD gene mutations affect DPD activity. The relationship between DPYD IVS14+1G>A, c.1627A>G, c.85T>C and lymph node metastasis (LNM) and distant metastasis (DM) of colorectal cancer (CRC) was investigated. METHODS: A total of 537 CRC patients were enrolled in this study. DPYD polymorphisms were analyzed by polymerase chain reaction (PCR)-Sanger sequencing. The relationship between DPYD genotypes and clinical features of patients, metastasis of CRC was analyzed. RESULTS: About DPYD c.1627A>G, A/A (57.7%) was the most common genotype, followed by A/G (35.6%), G/G (6.7%) genotypes. In c.85T>C, T/T, T/C, and C/C genotypes are accounted for 83.6%, 16.0%, and 0.4%, respectively. Logistic regression analysis revealed that DPYD c.1627A>G A/G and G/G genotypes in the dominant model (A/G + G/G vs. A/A) were significant risk factors for the LNM (p = 0.029, OR 1.506, 95% CI = 1.048-2.165) and DM (p = 0.039, OR 1.588, 95% CI = 1.041-2.423) of CRC. In addition, DPYD c.1627A>G polymorphism was more common in patients with abnormal serum carcinoembryonic antigen (CEA) (>5 ng/ml) (p = 0.003) or carbohydrate antigen 24-2 (CA24-2) (>20 U/ml) level (p = 0.015). CONCLUSIONS: The results suggested that DPYD c.1627A>G A/G, G/G genotypes are associated with increased risk of LNM and DM of CRC.

Evaluating the role of RAD52 and its interactors as novel potential molecular targets for hepatocellular carcinoma.

BACKGROUND: Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed. METHODS: Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein-protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression. RESULTS: In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52-RAD51 had the firmest binding structure with the lowest E-total energy (- 1120.5 kcal/mol) among the RAD52-RAD51, RAD52-CFL1, and RAD52-XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening. CONCLUSIONS: Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study's findings regarding the multigene prediction and diagnosis of HCC are valuable.

Evaluation of in vitro toxicity of silica nanoparticles (NPs) to lung cells: Influence of cell types and pulmonary surfactant component DPPC.

Cultured human lung epithelial cells, particularly A549 cells, are commonly used as the in vitro model to evaluate the inhalational toxicity of nanoparticles (NPs). However, A549 cells are cancer cells that might not reflect the response of normal tissues to NP exposure. In addition, the possible influence of pulmonary surfactant also should be considered. This study used silica NPs as model NPs, and evaluated the toxicity of silica NPs to both 16HBE human bronchial epithelial cells and A549 adenocarcinomic cells, with or without the presence of pulmonary surfactant component dipalmitoyl phosphatidylcholine (DPPC). We found that silica NPs induced cytotoxicity at the concentration of 128 µg/mL in 16HBE cells but not A5490 cells, and the cytotoxicity of silica NPs to 16HBE cells was inhibited by DPPC. Intracellular reactive oxygen species (ROS) was only induced in 16HBE cells, accompanying with decreased thiol levels. Moreover, 16HBE cells internalized more silica NPs compared with A549 cells, and the internalization was reduced with the presence of DPPC in both types of cells. The retention of ABC transporter substrate Calcein was only significantly induced by silica NPs at high concentrations in 16HBE cells, and was partially reduced due to the presence of DPPC. In addition, ABC transporter inhibitor MK571 increased the toxicity of silica NPs to both types of cells, with 16HBE cells being more sensitive. Our data revealed that the cell types and pulmonary surfactant components could influence the toxicological consequences of silica NPs to human lung cells. Therefore, it is recommended that in vitro studies should carefully select suitable models to evaluate the inhalational toxicity of NPs.

Compensating Unknown Time-Varying Delay in Opto-Electronic Platform Tracking Servo System.

This paper investigates the problem of compensating miss-distance delay in opto-electronic platform tracking servo system. According to the characteristic of LOS (light-of-sight) motion, we setup the Markovian process model and compensate this unknown time-varying delay by feed-forward forecasting controller based on robust H∞ control. Finally, simulation based on double closed-loop PI (Proportion Integration) control system indicates that the proposed method is effective for compensating unknown time-varying delay. Tracking experiments on the opto-electronic platform indicate that RMS (root-mean-square) error is 1.253 mrad when tracking 10° 0.2 Hz signal.

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. METHODS: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. RESULTS: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). CONCLUSION: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

[Malaria Incidence and Control in Baoshan City during the Twelfth Five-Year Plan Period].

A retrospective analysis was made on malaria incidence in Baoshan City of Yunnan Province during the 2011-2015 Twelfth Five-Year Plan Period. The epidemiological characteristics and endemic situation of malaria were analyzed. A total of 1 301 malaria cases were reported in Baoshan City during 2011-2015, with an average incidence rate of 10.2 per 100 000 individuals, showing a relatively low prevelence of malaria. The cases were mostly imported（98.5%, 1 282/1 301）. No local malaria cases were found in Baoshan City since 2014. The cases were mostly in Tengchong City（65.6%, 853/1 301）, and mainly in the age range of 20-50 years （84.4%, 1 098/1 301）.

[Analysis of Time Distribution of Malaria Incidence in Baoshan City During 1990-2014].

The malaria epidemic data in Baoshan city from 1990 to 2014 were analyzed with concentration ratio and circular distribution. Results showed that the incidence of malaria in Baoshan city displayed a trend of decrease from 1990 to 2014. The total concentration ration M was 0.36, the circular distribution r was 0.30, and the average angle α was 148.78°. The malaria incidence peaked on May 31, with the epidemic period being from March 2 to August 29, which is inconsistent with the seasonal ebb and flow of local malaria vector.

Supporting Nano Catalysts for the Selective Hydrogenation of Biomass-derived Compounds.

The selective hydrogenation of biomass derivatives presents a promising pathway for the production of high-value chemicals and fuels, thereby reducing reliance on traditional petrochemical industries. Recent strides in catalyst nanostructure engineering, achieved through tailored support properties, have significantly enhanced the hydrogenation performance in biomass upgrading. A comprehensive understanding of biomass selective upgrading reactions and the current advancement in supported catalysts is crucial for guiding future processes in renewable biomass. This review aims to summarize the development of supported nanocatalysts for the selective hydrogenation of the US DOE's biomass platform compounds derivatives into valuable upgraded molecules. The discussion includes an exploration of the reaction mechanisms and conditions in catalytic transfer hydrogenation (CTH) and high-pressure hydrogenation. By thoroughly examining the tailoring of supports, such as metal oxide catalysts and porous materials, in nano-supported catalysts, we elucidate the promoting role of nanostructure engineering in biomass hydrogenation. This endeavor seeks to establish a robust theoretical foundation for the fabrication of highly efficient catalysts. Furthermore, the review proposes prospects in the field of biomass utilization and address application bottlenecks and industrial challenges associated with the large-scale utilization of biomass.

A novel type-II-II heterojunction for photocatalytic degradation of LEV based on the built-in electric field: carrier transfer mechanism and DFT calculation.

Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this work, a novel type-II-II Ag2CO3/Bi2WO6 (AB) heterojunction was synthesized by hydrothermal reaction and in situ-precipitation methods. The mechanisms of charge transfer and carrier separation at the interface of heterojunctions and the influence on the photocatalytic activity were investigated. The degradation of levofloxacin (LEV) under visible light irradiation was employed to evaluate the photocatalytic performance of AB. The results showed that 85.4% LEV was degraded by AB, which was 1.38 and 1.39 times higher than that of Bi2WO6 and Ag2CO3, respectively. The work functions of the different crystal planes in the AB heterojunction, which was calculated by density functional theory, are a significant difference. The Fermi energy (Ef) of Ag2CO3 (- 6.005 eV) is lower than Bi2WO6 (- 3.659 eV), but the conduction band (CB) is higher. Therefore, using AB heterojunctions as an example, the research explored the mechanism of type-II-II which CB and Ef of one semiconductor cannot simultaneously surpass those of another material, based on the built-in electric field theory. Through this analysis, a deeper understanding of type-II heterojunctions was achieved, and providing valuable insights into the behavior of this specific heterojunction system.

Single atom manganese catalyst boosting selective oxidation of alcohols with activated peroxymonosulfate.

Selective oxidations are important reactions in organic synthesis for fine chemical industry and conventional methods are expensive and produce a lot of toxic wastes. Herein, we demonstrate a facile and environmentally benign technique for liquid phase selective oxidation based on graphene-supported Mn single-atom-catalyst (SAMn-G) for efficient peroxymonosulfate (PMS) activation. The active Mn component in the developed SAMn-G catalyst reached single-atomic dispersion on graphene substrate via the coordination of individual Mn atoms with the doped N from the graphene framework. SAMn-G activated PMS via a nonradical-dominated pathway, which could convert aromatic alcohols into aldehydes or ketones at a mild temperature. The SAMn-G catalyst exhibited superior conversion and aldehyde selectivity in alcohol oxidation in comparison with their counterpart catalysts possessing either homogeneous Mn ions or oxide particles. The high activation efficiency of SAMn-G is due to the synergistic effect between Mn atoms and graphene substrate, as well as the dominated reaction pathway from nonradical oxidation, which is more selective than these free radicals to oxidize the alcohols. Concerted experimental evidence indicates that the non-radical oxidation process was highly possible to follow the electron transfer mechanism by PMS/organic adsorption on the surface of the catalyst. This study provides a fundamental understanding of PMS activation mediated by single atom catalyst for organic synthesis and the achieved insights can also help the catalyst design for other liquid phase selective oxidation processes.

Artesunate Alleviates Kidney Fibrosis in Type 1 Diabetes with Periodontitis Rats via Promoting Autophagy and Suppression of Inflammation.

To explore the effect of periodontal disease on the progression of diabetic kidney disease (DKD), to observe the effects of artesunate (ART) intervention on periodontal and kidney tissues in type 1 diabetic rats with periodontitis, and to explore the possibility of ART for the treatment of DKD. Rat models of diabetes mellitus, periodontitis, and diabetes mellitus with periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, and P. gingivalis ligation applied sequentially. Ten weeks after modeling, ART gavage treatment was given for 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to investigate the inflammatory factors, fibrogenisis, autophagy-related factors, and proteins in periodontal and kidney tissues, and 16S rDNA sequencing was used to detect the changes in dental plaque fluid and kidney tissue flora. Compared to the control group, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and COL-IV in the periodontal disease (PD) group were increased. The protein expression of TGF-ß1, Smad3, and COL-IV increased in the DM group and the DM + PD group, and the expression of TGF-ß1, Smad3, and COL-IV was upregulated in the DM + PD group. These results suggest that periodontal disease enhances renal fibrosis and that this process is related to the TGF-ß1/Smad/COL-IV signaling pathway. Among the top five dominant bacteria in the kidney of the DM + PD group, the abundance of Proteobacteria increased most significantly, followed by Actinobacteria and Firmicutes with mild increases. The relative abundance of Proteobacteria, Actinobacteria, and Firmicutes in the kidney tissues of DM and PD groups also showed an increasing trend compared with the CON group. Proteobacteria and Firmicutes in the kidney of the PD group and DM + PD group showed an increasing trend, which may mediate the increase of oxidative stress in the kidney and promote the occurrence and development of DN. Periodontal disease may lead to an imbalance of renal flora, aggravate renal damage in T1DM, cause glomerular inflammation and renal tubulointerstitial fibrosis, and reduce the level of autophagy. ART delays the process of renal fibrosis by inhibiting the TGF-ß-Smad signaling pathway.

KRAS/NRAS Mutations Associated with Distant Metastasis and BRAF/PIK3CA Mutations Associated with Poor Tumor Differentiation in Colorectal Cancer.

Background: The occurrence, progression, and prognosis of colorectal cancer (CRC) are regulated by EGFR-mediated signaling pathways. However, the relationship between the core genes (KRAS/NRAS/BRAF/PIK3CA) status in the signaling pathways and clinicopathological characteristics of CRC patients in Hakka population remains controversial. Methods: Patients were genotyped for KRAS (codons 12, 13, 61, 117, and 146), NRAS (codons 12, 61, 117, and 146), BRAF (codons 600), and PIK3CA (codons 542, 545 and 1047) mutations. Clinical records were collected, and clinicopathological characteristic associations were analyzed together with mutations of studied genes. Results: Four hundred and eight patients (256 men and 152 women) were included in the analysis. At least one mutation in the four genes was detected in 216 (52.9%) patients, while none was detected in 192 (47.1%) patients. KRAS, NRAS, BRAF, and PIK3CA mutation status were detected in 190 (46.6%), 11 (2.7%), 10 (2.5%), 34 (8.3%) samples, respectively. KRAS exon 2 had the highest proportion (62.5%). Age, tumor site, tumor size, lymphovascular invasion, and perineural invasion were not associated with gene mutations. KRAS mutations (adjusted OR 1.675, 95% CI 1.017-2.760, P=0.043) and NRAS mutations (adjusted OR 5.183, 95% CI 1.239-21.687, P=0.024) appeared more frequently in patients with distant metastasis. BRAF mutations (adjusted OR 7.224, 95% CI 1.356-38.488, P=0.021) and PIK3CA mutations (adjusted OR 3.811, 95% CI 1.268-11.455, P=0.017) associated with poorly differentiated tumor. Conclusion: KRAS/NRAS mutations are associated with distant metastasis and BRAF/PIK3CA mutations are associated with poor tumor differentiation in CRC. And the results provided a better understanding between clinicopathological characteristics and gene mutations in CRC patients.

[Expression and significance of Th17 cells and related cytokines in a murine model of systemic sclerosis].

OBJECTIVE: To study the expression and significance of Th17 cells and related cytokines in the peripheral blood, skin and lung in a murine model of systemic sclerosis (SSc). METHODS: Twenty female BALB/c mice were randomly divided into 2 groups, including a control group and a bleomycin(BLM) -injected-4-week group (SSc group). Pathological changes of the skin and lung were detected. The proportion of CD4(+)IL-17(+)Th17 cells in the peripheral blood, skin and lung of the mice was determined by flow cytometry. The mRNA expressions of RORγt, IL-17A, and IL-6 of the skin and lung were evaluated by real-time PCR. Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and IL-6 in the serum. RESULTS: Dermal inflammation and the score of PF were significantly increased in the SSc group as compared with the control group (2.60±0.84 vs. 0.40±0.52, 2.80± 1.81 vs.0.60±0.70). Hydroxyproline(HYP) contents of the skin and lung were obviously increased in the SSc group than in the control group [(3.17±1.74) mg/g vs. (1.45±0.40) mg/g,(0.53±0.14) mg/g vs. (0.38±0.16) mg/g], all P<0.05. The percentage of Th17 cells in the peripheral blood, skin and lung of the SSc group were significantly increased as compared with the control group [(2.07±0.89)% vs. (1.02±0.32)%,(5.80±2.02)% vs. (1.64±0.58)%,(5.24±2.43)% vs. (1.92±0.98)%,P <0.01]. Compared with the control group, the mRNA levels of IL-17A, RORγt, IL-6 in the skin and lung of the SSc group were higher. The levels of IL-17, IL-6 of the SSc group in the serum were significantly increased, all P<0.05. The frequency of Th17 cells, and the levels of IL-17 and IL-6 in the blood had a positive correlation with dermal and pulmonary inflammation, fibrosis and HYP contents of the skin and lung, The frequency of Th17, IL-17 and IL-6 in the skin and lung had, respectively, a positive correlation with dermal and pulmonary inflammation, HYP contents of the skin and lung, all P<0.01. CONCLUSION: Th17 cells were significantly increased in the peripheral blood, skin and lung of a murine model of SSc, and had an intimate relationship with inflammation and fibrosis of the skin and lung, and involved the pathogenesis of SSc through producing IL-17, IL-6.

Genome-Wide Population Structure Analysis and Genetic Diversity Detection of Four Chinese Indigenous Duck Breeds from Fujian Province.

The assessment of population genetic structure is the basis for understanding the genetic information of indigenous breeds and is important for the protection and management of indigenous breeds. However, the population genetic differentiation of many local breeds still remains unclear. Here, we performed a genome-wide comparative analysis of Jinding, Liancheng white, Putian black, and Shanma ducks based on the genomic sequences using RAD sequencing to understand their population structure and genetic diversity. The population parameters showed that there were obvious genetic differences among the four indigenous breeds, which were separated groups. Among them, Liancheng white and Shanma ducks may come from the same ancestor because the phylogenetic tree forms three tree trunks. In addition, during the runs of homozygosity (ROH), we found that the average inbreeding coefficient of Liancheng white and Putian black ducks was the lowest and the highest, respectively. Five genomic regions were considered to be the hotspots of autozygosity among these indigenous duck breeds, and the candidate genes involved a variety of potential variations, such as muscle growth, pigmentation, and neuroregulation. These findings provide insights into the further improvement and conservation of Fujian duck breeds.