Formononetin ameliorates muscle atrophy by regulating myostatin-mediated PI3K/Akt/FoxO3a pathway and satellite cell function in chronic kidney disease.

Muscle atrophy is a common complication in chronic kidney disease (CKD). Inflammation and myostatin play important roles in CKD muscle atrophy. Formononetin (FMN), which is a major bioactive isoflavone compound in Astragalus membranaceus, exerts anti-inflammatory effects and the promotion of myogenic differentiation. Our study is based on myostatin to explore the effects and mechanisms of FMN in relation to CKD muscle atrophy. In this study, CKD rats and tumour necrosis factor α (TNF-α)-induced C2C12 myotubes were used for in vivo and in vitro models of muscle atrophy. The results showed that FMN significantly improved the renal function, nutritional status and inflammatory markers in CKD rats. Values for bodyweight, weight of tibialis anterior and gastrocnemius muscles, and cross-sectional area (CSA) of skeletal muscles were significantly larger in the FMN treatment rats. Furthermore, FMN significantly suppressed the expressions of MuRF-1, MAFbx and myostatin in the muscles of CKD rats and the TNF-α-induced C2C12 myotubes. Importantly, FMN significantly increased the phosphorylation of PI3K, Akt, and FoxO3a and the expressions of the myogenic proliferation and differentiation markers, myogenic differentiation factor D (MyoD) and myogenin in muscles of CKD rats and the C2C12 myotubes. Similar results were observed in TNF-α-induced C2C12 myotubes transfected with myostatin-small interfering RNA (si-myostatin). Notably, myostatin overexpression plasmid (myostatin OE) abolished the effect of FMN on the phosphorylation of the PI3K/Akt/FoxO3a pathway and the expressions of MyoD and myogenin. Our findings suggest that FMN ameliorates muscle atrophy related to myostatin-mediated PI3K/Akt/FoxO3a pathway and satellite cell function.

Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway.

Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and autophagy are the primary molecular mechanisms involved in muscle atrophy. Calycosin, a major component of Radix astragali, exerts anti-inflammatory, anti-oxidative stress and anti-autophagy effects. We investigated the effects and mechanisms of calycosin on skeletal muscle atrophy in vivo and in vitro. 5/6 nephrectomy (5/6 Nx) rats were used as a model of CKD. We evaluated bodyweight and levels of serum creatinine (SCr), blood urea nitrogen (BUN) and serum albumin (Alb). H&E staining, cell apoptosis, oxidative stress biomarkers, autophagosome and LC3A/B levels were performed and evaluated in skeletal muscle of CKD rat. Calycosin treatment improved bodyweight and renal function, alleviated muscle atrophy (decreased the levels of MuRF1 and MAFbx), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels in skeletal muscle of CKD rats. Importantly, calycosin reduced autophagosome formation, down-regulated the expression of LC3A/B and ATG7 through inhibition of AMPK and FOXO3a, and increased SKP2, which resulted in decreased expression of CARM1, H3R17me2a. Similar results were observed in C2C12 cells treated with TNF-α and calycosin. Our findings showed that calycosin inhibited oxidative stress and autophagy in CKD induced skeletal muscle atrophy and in TNF-α-induced C2C12 myotube atrophy, partially by regulating the AMPK/SKP2/CARM1 signalling pathway.

Establishment and characterization of a novel 'double-hit' follicular lymphoma cell line, FL-SJC.

About 5 per cent of follicular lymphoma (FL) cases are double-hit (DH) lymphomas. Double-hit follicular lymphoma (DHFL) cell lines can improve our understanding and drug development on FL. But there are only few DHFL cell lines. Here, we established a new MYC/BCL2 DHFL cell line, FL-SJC. The cells were obtained from the hydrothorax of a patient with MYC/BCL2 DHFL and cultured for 140 passages in vitro. FL-SJC cells demonstrated CD19++ , CD20+ , CD22++ , HLA-DR+ , CD10+ , CD38+ , Lambda+ CD23- , CD5- and Kappa- . The chromosome karyotypic analysis confirmed the co-existence of t(8;22)(q24;q11) and t(14;18)(q32;q21), as well as additional abnormalities involving chromosomes 2 and 3. Fluorescence in situ hybridization analysis (FISH) showed IGH/BCL2 fusion gene and the MYC rearrangement. In addition, the FL-SJC cells displayed KMT2D/MLL2 and CREBBP gene mutations. After subcutaneous inoculation of FL-SJC cells, the SCID mice developed solid tumour masses within 6-8 weeks. FL-SJC cells were proven to be free of Epstein-Barr (EB) virus infection and be multidrug-resistant. In a conclusion, the FL-SJC cell line has been identified as a novel MYC/BCL2 double-hit follicular lymphoma that can be used as a potentially available tool for the clinical and basic research, together with the drug development for MYC/BCL2 DHFL.

POLR1D promotes colorectal cancer progression and predicts poor prognosis of patients.

RNA polymerase I subunit D (POLR1D), which is involved in synthesis of ribosomal RNA precursors and small RNAs, has been shown to be overexpressed in several human cancer types. Nevertheless, the role of POLR1D in the progression of colorectal cancer (CRC) remains unknown. The following study aimed to investigate the role and underlying mechanism of POLR1D in CRC progression. In this report, we found that POLR1D was significantly up-regulated in CRC through data mining of oncomine database. Furthermore, the immunohistochemistry (IHC) staining of a tissue microarray (TMA) of 75 human CRC patients showed that the expression level of POLR1D was positively correlated to tumor size and poor survival of CRC patients. Aberrant expression of POLR1D significantly promoted cell proliferation and migration in vitro, as well as tumor growth in vivo. Conversely, POLR1D knockdown displayed the opposite effects. The flow Cytometry assays showed that POLR1D fostered cell cycle progression at G1-S transition and inhibited cell apoptosis. Finally, at the molecular level, we demonstrated that POLR1D-induced the promotion of G1-S cell cycle transition was mediated by activation of wnt-ß-catenin signaling and inactivation of p53 signaling. Our results suggested that POLR1D may function as a risk factor for predicting the outcome of CRC patients, as well as a potential therapeutic target for CRC.

SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway.

BACKGROUND: Cervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis. METHODS: In our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo. RESULTS: SKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells. CONCLUSIONS: We suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K-Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.

CT characteristics in 24 patients with POEMS syndrome.

BACKGROUND: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) syndrome is a complicated and rare disease. Systematic research on computed tomography (CT) imaging characteristics in POEMS syndrome is scanty. The role of CT in diagnosis needs to be assessed. PURPOSE: To retrospectively analyze the CT imaging features in 24 patients with POEMS syndrome and evaluate the role of CT in diagnosis of this disease. MATERIAL AND METHODS: Twenty-four patients with confirmed POEMS syndrome were included in the study. Chest and abdominal CT images were analyzed. RESULTS: The three minor diagnostic criteria for POEMS syndrome (extravascular volume overload, organomegaly, and bone lesions) can be detected effectively by CT. Extravascular volume overload involved multiple serous cavities: hydrothorax, hydropericardium, and ascites, which were found in 79.2%, 41.7%, and 54.2% patients, respectively. The volume of effusion was small to moderate. Organomegaly involved multiorgans: hepatomegaly was found in 45.8% patients, splenomegaly in 54.2%, and lymphadenopathy in 75% patients. Hepatospleen exhibited moderate homogeneous enlargement without local enhanced signal after injection of contrast material. Bone lesions were classified into three groups: osteosclerotic, osteolytic, and mixed lesions. Osteosclerotic lesions, taking multiple, scattered, and variably sized high-density plaque-like appearance, were found in 20.8% patients. Osteolytic lesions, exhibiting punched-out low-density image, were found in 4.2% patients. Mixed ones, holding both common characteristics of them, were detected in 8.3% patients. These CT abnormalities disappeared after effective treatment. CONCLUSION: CT plays vital role in the confirmation of the three minor diagnostic criteria for POEMS syndrome: extravascular volume overload, organomegaly, and bone lesions.

Ecological study of community-level factors associated with chronic mountain sickness in the young male chinese immigrant population in Tibet.

BACKGROUND: Chronic mountain sickness (CMS) is a complex medical and public health problem that seriously affects highland immigrants. This study investigated relationships between community-level factors and CMS. METHODS: In this ecological study, data on age- and ethnicity-standardized CMS rates, community factors, and controlling variables were obtained from 2009-2010 surveys of 108 Chinese highland military units. Associations among variables were examined using correlation tests, analyses of covariance, and logistic regression. RESULTS: The rate of CMS ranged from 1.25% to 36.58% (mean: 14.65%, standard deviation: 8.15%) among military units. Partial correlation tests indicated that medicine expenditure was strongly negatively correlated with CMS (r = -0.267, P = 0.005). Analyses of covariance indicated that communities with oxygen-generating systems had lower CMS rates (F = 9.780, P = 0.002), whereas urban location (F = 5.442, P = 0.022) and construction duty (F = 4.735, P = 0.011) were associated with higher CMS rates. The multiple logistic model showed that medicine expenditure (OR = 0.897, P = 0.022), oxygen-generating system (available vs unavailable: OR = 0.827, P = 0.020), community type (urban vs rural: OR = 1.228, P = 0.019), and occupation (construction vs logistics: OR = 1.240, P = 0.029) were significantly associated with CMS. CONCLUSIONS: We identified community-level, health-related factors that were associated with CMS among young male immigrants. To alleviate the burden of CMS in these highland immigrant populations, further investment should be made in medicine and oxygen-generating systems, and preventive interventions should be implemented among construction workers. Further research should investigate the effects of urbanization on CMS development.

Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet.

BACKGROUND: In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population. METHODS: We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated. RESULTS: Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs. CONCLUSION: The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases.

Predictive value of basal exhaled nitric oxide and carbon monoxide for acute mountain sickness.

OBJECTIVE: The purpose of this study was to examine the relationship between acute mountain sickness (AMS) and the fraction of exhaled nitric oxide (Fe(NO)) and carbon monoxide (Fe(CO)) before ascent to high altitude and to evaluate their predictive value for AMS. METHODS: A total of 314 healthy young male recruits were voluntarily enrolled. Before ascent to an elevation of 4300 m, their Fe(NO) and Fe(CO) values, demographic factors, drinking and smoking history, vital capacity, and forced vital capacity were obtained. The investigators followed the subjects in the first exposure week to obtain their Lake Louise Score (LLS) each day. Subjects with LLS > 4, headache, and at least 1 other symptom were diagnosed with AMS, and the highest LLS of each individual during 7 days was considered the final LLS score. RESULTS: The AMS group had lower Fe(NO) (P = .003) and Fe(CO) (P < .001) values, and a lower smoking rate (P < .001) than the non-AMS group. Mean Fe(NO) and Fe(CO) values were 11.03 ppb (95% CI, 9.07 to 12.98) and 4.39 ppm (95% CI, 3.76 to 5.02), respectively, in the AMS group, and 14.74 ppb (95% CI, 13.25 to 16.23) and 6.10 ppm (95% CI, 5.49 to 6.72), respectively, in the non-AMS group (P < .0001). Using linear regression, both Fe(NO) and Fe(CO) were found to be significantly associated with the group's maximal LLS. Using logistic regression, Fe(NO) and Fe(CO) were also found to be significantly associated with AMS. CONCLUSIONS: Basal Fe(NO) and Fe(CO) are significantly negatively correlated with AMS development. However, the gases have only modest predictive value for the development of AMS.

Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction.

Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of muscle atrophy. The aim of this study was to explore the effects and mechanisms of paeoniflorin on CKD skeletal muscle atrophy. We demonstrated that paeoniflorin significantly improved renal function, calcium/phosphorus disorders, nutrition index and skeletal muscle atrophy in the 5/6 nephrectomized model rats. Paeoniflorin ameliorated the expression of proteins associated with muscle atrophy and muscle differentiation, including muscle atrophy F-box (MAFbx/atrogin-1), muscle RING finger 1 (MuRF1), MyoD and myogenin (MyoG). In addition, paeoniflorin modulated redox homeostasis by increasing antioxidant activity and suppressing excessive accumulation of reactive oxygen species (ROS). Paeoniflorin alleviated mitochondrial dysfunction by increasing the activities of electron transport chain complexes and mitochondrial membrane potential. Furthermore, paeoniflorin also regulates mitochondrial dynamics. Importantly, paeoniflorin upregulated the expression of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and phosphorylation of AMP-activated protein kinase (AMPK). Similar results were observed in C2C12 myoblasts treated with TNF-α and paeoniflorin. Notably, these beneficial effects of paeoniflorin on muscle atrophy were abolished by inhibiting AMPK and SIRT1 and knocking down PGC-1α. Taken together, this study showed for the first time that paeoniflorin has great therapeutic potential for CKD skeletal muscle atrophy through AMPK/SIRT1/PGC-1α-mediated oxidative stress and mitochondrial dysfunction.

KIEGLFN: A unified acne grading framework on face images.

BACKGROUND AND OBJECTIVE: Grading the severity level is an extremely important procedure for correct diagnoses and personalized treatment schemes for acne. However, the acne grading criteria are not unified in the medical field. This work aims to develop an acne diagnosis system that can be generalized to various criteria. METHODS: A unified acne grading framework that can be generalized to apply referring to different grading criteria is developed. It imitates the global estimation of the dermatologist diagnosis in two steps. First, an adaptive image preprocessing method effectively filters meaningless information and enhances key information. Next, an innovative network structure fuses global deep features with local features to simulate the dermatologists' comparison of local skin and global observation. In addition, a transfer fine-tuning strategy is proposed to transfer prior knowledge on one criterion to another criterion, which effectively improves the framework performance in case of insufficient data. RESULTS: The Preprocessing method effectively filters meaningless areas and improves the performance of downstream models.The framework reaches accuracies of 84.52% and 59.35% on two datasets separately. CONCLUSIONS: The application of the framework on acne grading exceeds the state-of-the-art method by 1.71%, reaches the diagnostic level of a professional dermatologist and the transfer fine-tuning strategy improves the accuracy of 6.5% on the small data.

Population level determinants of acute mountain sickness among young men: a retrospective study.

BACKGROUND: Many visitors, including military troops, who enter highland regions from low altitude areas may suffer from acute mountain sickness (AMS), which negatively impacts workable man-hours and increases healthcare costs. The aim of this study was to evaluate the population level risk factors and build a multivariate model, which might be applicable to reduce the effects of AMS on Chinese young men traveling to this region. METHODS: Chinese highland military medical records were used to obtain data of young men (n = 3727) who entered the Tibet plateau between the years of 2006-2009. The relationship between AMS and travel profile, demographic characteristics, and health behaviors were evaluated by logistic regression. Univariate logistic models estimated the crude odds ratio. The variables that showed significance in the univariate model were included in a multivariate model to derive adjusted odds ratios and build the final model. Data corresponding to odd and even years (2 subsets) were analyzed separately and used in a simple cross-validation. RESULTS: Univariate analysis indicated that travel profile, prophylactic use, ethnicity, and province of birth were all associated with AMS in both subsets. In multivariate analysis, young men who traveled from lower altitude (600-800 m vs. 1300-1500 m, adjusted odds ratio (AOR) = 1.32-1.44) to higher altitudes (4100-4300 m vs. 2900-3100 m, AOR = 3.94-4.12; 3600-3700 m vs. 2900-3100 m, AOR = 2.71-2.74) by air or rapid land transport for emergency mission deployment (emergency land deployment vs. normal land deployment, AOR = 2.08-2.11; normal air deployment vs. normal land deployment, AOR = 2.00-2.20; emergency air deployment vs. normal land deployment, AOR = 2.40-3.34) during the cold season (cold vs. warm, AOR = 1.25-1.28) are at great risk for developing AMS. Non-Tibetan male soldiers (Tibetan vs. Han, AOR = 0.03-0.08), born and raised in lower provinces (eastern vs. northwestern, AOR = 1.32-1.39), and deployed without prophylaxis (prophylactic drug vs. none, AOR = 0.75-0.76), also represented a population at significantly increased risk for AMS. The predicted model was built; the area under receiver operating characteristic curve was 0.703. CONCLUSION: Before a group of young men first enter a high altitude area, it is important that a health service plan should be made referring to the group's travel profile and with respect to young men's ethnicity and province of birth. Low-cost Chinese traditional prophylactic drugs might have some effect on decreasing the risk of AMS, although this needs further verification.

Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population.

BACKGROUND AND AIM: Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters. METHODS: In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction. RESULTS: The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP. CONCLUSION: In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs.

Endothelial dysfunction plays important roles in vascular dysfunction under diabetic conditions. The generation of advanced glycation end products (AGEs), which can induce inflammation and oxidative stress, is pivotal in endothelial dysfunction. Salidroside, a major active compound in Rhodiola rosea, exerts protective effects against vascular diseases. To study the effects and mechanism of salidroside in diabetes-induced vascular endothelial dysfunction, an in vitro model was established with AGEs-induced human umbilical vein endothelial cells (HUVECs). Then, cell viability, cell apoptosis, pro-inflammatory cytokines and oxidative biomarkers were tested to determine the effects of salidroside at 10, 50 and 100 µM doses on AGEs induced HUVECs. Additionally, RNA-Seq and bioinformatics analyses were used to search for the underlying mechanism of salidroside. The results showed that salidroside promoted cell viability and significantly alleviated cell apoptosis in AGEs-induced HUVECs. Furthermore, salidroside remarkably decreased the levels of the pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 and impeded the expression of VCAM-1 and ICAM-1 induced by AGEs. Additionally, salidroside promoted superoxide dismutase (SOD) activity and increased catalase (CAT) and glutathione peroxidase (GSH-Px) levels while inhibiting the intracellular generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in AGEs-induced HUVECs. Importantly, salidroside alleviated endothelial inflammation and oxidative stress by activating AMPK phosphorylation and inhibiting NF-ĸB p65 and NLRP3 inflammasome activation. Therefore, we used compound C, an accepted AMPK inhibitor, to further demonstrate the mechanism. Interestingly, the phenomenon produced by salidroside was abolished. Our findings suggest that salidroside ameliorates AGEs-induced endothelial inflammation and oxidative stress, partially via the AMPK/NF-κB/NLRP3 signaling pathway.

Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas.

Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC). Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was generally dependent on the degree of methylation at the promoter region. Furthermore, expression of SLIT2 was restored in relatively low-expressing cell lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and the decrease in expression was significantly correlated with CpG island hypermethylation. This decrease of SLIT2 expression was also associated with lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721 cells induced by recombinant adenovirus suppressed cell growth, migration, and invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may be important in the development and progression of HCC. Thus, SLIT2 may be useful as a therapeutic target in the treatment of HCC.

Atractylenolide III Attenuates Muscle Wasting in Chronic Kidney Disease via the Oxidative Stress-Mediated PI3K/AKT/mTOR Pathway.

Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.

A rare case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation.

Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes > 200 × 109/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19+, CD20+, HLA-DR+, CD22+, CD5+, Kappa+, CD25dim, CD71dim, Lambda-, CD7-, CD10-, CD23-, CD34-, CD33-, CD13-, CD14-, CD117-, CD64-, CD103-, and CD11c-. The karyotype showed complex abnormality: 46XX,+ 3,-10, t(8;14)(q24; q32)[11]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.

Factors associated with acute mountain sickness in young Chinese men on entering highland areas.

AIM: The aim of this study was to explore the prediction factors for incidence of acute mountain sickness (AMS) in young males newly entering highland areas. METHODS: A retrospective study of 4367 records of male highland soldiers from 2000 to 2005 was done. The factors were tested by logistic regression. RESULTS: After selection by univariate model, ethnicity, altitude, season, deployment type, and prophylaxis were inserted into a multivariate model. The adjusted odds ratio (AOR) was 0.078 for Tibetan compared with Han. AORs for altitudes 3600 to 3700, 4000 to 4300, and 4600 to 4700 m versus 2900 to 3100 m were 4.490, 4.532, and 4.964, respectively. AOR for cold season versus warm season was 1.332. AORs for emergency land deployment and air deployment versus normal land deployment were 2.261 and 1.614, respectively. The AOR was 0.741 for prophylaxis versus none. The area under receiver operating characteristic curve was 0.731 (optimal cutoff = 0.370). CONCLUSIONS: Adjusting for altitude, risk factors that contributed to AMS were being non-Tibetan, cold season, greater speed of transport, emergency conditions, and without prophylaxis. The model established is acceptable for assisting AMS prediction.

Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p < 0.05). Survival and recurrence analyses showed that KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both p<0.01). And in vitro studies revealed that KMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.