Burden and trend of dietary risk-related colorectal cancer in China and its provinces: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The objective of this experiment was to evaluate the spatial pattern and temporal trend of colorectal cancer (CRC) burden attributed to dietary risk factors in China from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. METHODS: Numbers and age-standardised rates of deaths, disability-adjusted life years (DALYs) and corresponding average annual percentage change (AAPC) were determined. The joinpoint regression analysis was used to assess the temporal trends of CRC deaths and DALYs from 1990 to 2019. RESULTS: In China, the number of diet-attributable CRC deaths and DALYs in 2019 were 90.41 (95% uncertainty interval: 65.69, 114.67) and 2234.06 (1609.96, 2831.24) per-1000 population, marking 2.05% and 1.68% annual increases since 1990, respectively. The region with the highest increase in age-standardised rates (ASRs) of diet-related CRC deaths and DALYs was in Taiwan with an AAPC of 2.00% (1.51, 2.48), whereas the highest decline in ASRs of CRC deaths and DALYs was observed in Hong Kong with an AAPC of -0.63% (-0.90, -0.35) (all P < 0.05). Nationally, men suffered higher CRC deaths and DALY burdens attributable to dietary risks than did women. Regarding the specific diet group, diets low in calcium, milk, and whole grains contributed to CRC deaths and DALYs the most. CONCLUSIONS: Diet is an important contributor to increasing CRC burden in China. Necessary measures should be taken to kerb the growing burden attributed to dietary factors, particularly in males and in regions with middle Socio-demographic Index or lower.

[The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain].

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

[Correlation between Helicobacter pylori enrichment and clinical and pathological characteristics of colorectal adenoma].

Objective: Aim to observe the enrichment of Helicobacter pylori (Hp) in adenoma tissue of patients with colorectal adenoma and analyze its effect on the clinical and pathological characteristics of colorectal adenoma. Methods: The data of 1 622 cases of gastroenteroscopy in the Endoscopy Center of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine from January 2019 to June 2021 were collected retrospectively. The general data, gastric HP infection, clinical and pathological features, HP methyl blue special staining, HP immunohistochemical staining and toll-like receptor5(TLR5) protein immunofluorescence of colorectal adenomas were compared between the colorectal adenoma group (743 cases) and the control group (879 cases). Results: There were 743 cases in the colorectal adenoma group, aged (54.5±12.3) years, and 56.0% were male. There were 879 cases in the control group, aged (55.6±12.1), and 58.4% were male. Gastric Hp was positive in 361 cases in the colorectal adenoma group with a positive rate of 48.6% and in 331 cases in the control group with a positive rate of 37.7%. The difference was statistically significant (P<0.001). Gastric HP infection significantly increased the risk of Hp enrichment in colorectal adenomas (OR=28.590;95%CI:18.554-44.055; P<0.001). At the same time, Hp enrichment in colorectal adenomas was the promoting factor of positive events in adenoma diameter, pathological adenoma type, and adenoma malignancy (RR=0.804,3.163,3.089,2.463, P<0.001). It was also found that the expression of TLR5 protein was increased in HP-enriched adenomas. Conclusion: There is a positive correlation between gastric HP infection and intestinal HP enrichment. The effect of intestinal HP enrichment on the clinical and pathological characteristics of colorectal adenoma is statistically significant, and its tumor-promoting effect may be related to the upregulation of mucosal TLR5 protein.

[Studying the correlation between ferritin and non-alcoholic fatty liver disease].

Objective: To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease. Methods: Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction. Results: Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ​​the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion: Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

[Study of liver fat and iron deposition quantification based on magnetic resonance imaging in rats with nonalcoholic fatty liver disease].

Objective: To investigate the accuracy of magnetic resonance imaging (MRI) for quantitative determination of liver fat and iron content through a rat model of non-alcoholic fatty liver disease (NAFLD) induced by methionine-choline deficient (MCD) diet. Methods: Sixty SD rats were randomly divided into experimental (MCD-diet group, n = 30) and normal control group (normal diet, n = 30). Rats were subjected to special MRI examinations at the ends of 2, 4, and 8 weeks. Proton density fat fraction (PDFF) and R2* value were obtained, and then the rats were sacrificed. The liver tissues were stained with HE, Prussian blue, etc. Liver tissue non-heme iron (NHI) homogenate was determined by flame atomic absorption spectrometry. According to different data, one-way analysis of variance, t-test or χ (2) test was used for statistical analysis. Results: PDFF and R2 * values in the MCD diet group at 2, 4 and 8 weeks were 23.37% ± 9.20%, 28.07% ± 6.84%, 25.40% ± 7.04% (P < 0.01) and 90.58 ± 15.92, 104.12 ± 13.47, 106.35 ± 15.76 (P < 0.05), respectively, which were significantly higher than the normal control group PDFF (2.39% ± 0.50%, 2.45% ± 0.45%, 3.26% ± 0.80%) and R2* (48.93 ± 7.90, 54.71 ± 5.91, 64.25 ± 15.76). Additionally, with the disease progression, R2 * had gradually increased, which was consistent with the NHI trend in liver tissue homogenates of each group. Conclusion: MRI, as a non-invasive quantitative method, can accurately assess liver fat and iron content in fatty liver disease, and with the degree of severity of fat changes, iron deposits tend to increase.

MiR-150 alleviates EMT and cell invasion of colorectal cancer through targeting Gli1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-150 alleviates EMT and cell invasion of colorectal cancer through targeting Gli1, by H. Fan, X. Liu, W.-W. Zheng, Z.-H. Zhuang, C.-D. Wang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21): 4853-4859-PMID: 29164577" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13726.

Atomically dispersed Ni in cadmium-zinc sulfide quantum dots for high-performance visible-light photocatalytic hydrogen production.

Catalysts with a single atom site allow highly tuning of the activity, stability, and reactivity of heterogeneous catalysts. Therefore, atomistic understanding of the pertinent mechanism is essential to simultaneously boost the intrinsic activity, site density, electron transport, and stability. Here, we report that atomically dispersed nickel (Ni) in zincblende cadmium-zinc sulfide quantum dots (ZCS QDs) delivers an efficient and durable photocatalytic performance for water splitting under sunlight. The finely tuned Ni atoms dispersed in ZCS QDs exhibit an ultrahigh photocatalytic H2 production activity of 18.87 mmol hour-1 g-1. It could be ascribed to the favorable surface engineering to achieve highly active sites of monovalent Ni(I) and the surface heterojunctions to reinforce the carrier separation owing to the suitable energy band structures, built-in electric field, and optimized surface H2 adsorption thermodynamics. This work demonstrates a synergistic regulation of the physicochemical properties of QDs for high-efficiency photocatalytic H2 production.

[Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms].

Objective: To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN). Methods: Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test. Results: In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012). Conclusions: Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.

The applied anatomy and clinical significance of the proximal, V1 segment of vertebral artery.

BACKGROUND: The aim of the study was to probe the morphological features of the proximal segment (V1) of vertebral artery (VA) in a sample of Chinese cadavers. MATERIALS AND METHODS: The origin, course and outer diameter at origin of the pre-vertebral part of the VAs were evaluated in 119 adult cadavers. RESULTS: It was found that 94.12% of the VAs originated from the subclavian arteries, bilaterally. The variant origins were present in 5.88% of the cadavers and all originated directly from the arch of the aorta. All the variations were observed on the left side of male cadavers. The average outer diameters at origin of the normal and variation groups were 4.35 ± 1.00 mm and 4.82 ± ± 1.42 mm, respectively, p = 0.035. In the normal group, but not in the variation group, the average diameter in the males was significantly larger than that in the females (4.50 ± 0.99 mm, 3.92 ± 0.92 mm, respectively, p = 0.000). In addition, only 5 cadavers in the normal group had hypoplastic VAs (4.20%, 4 males, 3 right-sided). Vertebral artery dominance (VAD) was present in 91 (69 males) out of 112 cadavers and more common on the left (n = 48). In addition, 3 cadavers satisfied conditions for coexistence of VAD and vertebral artery hypoplasia. All 7 cadavers in the variation group exhibited VAD, which was more common on the right side (n = 5). CONCLUSIONS: The morphologic variations and frequencies described above have implications for the early prevention, abnormal anatomy detection, accurate diagnosis, safe surgery and endovascular treatment of cardiovascular and neurological disease.

Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models.

Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-α secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro-computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis-induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-Β ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.

Apparent diffusion coefficient measurement in luminal breast cancer: will tumour shrinkage patterns affect its efficacy of evaluating the pathological response?

AIM: To determine which region of interest (ROI) placement method of apparent diffusion coefficient (ADC) measurement has the best performance for predicting pathological complete response (PCR) at two cycles of neoadjuvant chemotherapy (NAC) according to different tumour shrinkage patterns of luminal breast cancer and to assess the evaluative accuracy of ADC value combined with other clinicopathological indicators. MATERIALS AND METHODS: Sixty-one patients who underwent NAC for histopathologically confirmed breast cancer were enrolled in this retrospective study. The ADC values of different shrinkage patterns (concentric shrinkage, nest or dendritic shrinkage, and mixed shrinkage) for tumours shown by diffusion-weighted imaging (DWI) were measured independently using three ROI placement methods (single-round, three-round, and freehand). Intraclass correlation coefficients (ICCs) were used to assess the interobserver variability in the ADC values. Multivariate logistic regression analysis was performed to identify the independent predictors of PCR. RESULTS: The best placement method found was single-round ROI in all the patients (AUC=0.863). When analysed separately, the effectiveness results differed: the single-round method was optimal for concentrically shrinking tumours (AUC=0.970); the freehand method was optimal for nest or dendritically shrinking tumours (AUC=0.714); and the three-round method was optimal for mixed shrinking tumours (AUC=0.975). Multivariate logistic analysis showed that oestrogen receptor (ER), ΔADC% and tumour diameter reduction (ΔD%) were independent factors in evaluating the PCR. CONCLUSION: The methods for measuring ADC values vary across different shrinkage patterns of luminal tumours. ΔADC%, ER and ΔD% were independent factors for evaluating the PCR.

Utility of apparent diffusion coefficient as an imaging biomarker for assessing the proliferative potential of invasive ductal breast cancer.

AIM: To determine the clinical utility of apparent diffusion coefficient (ADC) metrics for the non-invasive assessment of tumour proliferation indicated by Ki-67 labelling index (LI) in invasive ductal breast cancer. MATERIALS AND METHODS: Eighty patients with 80 histopathologically proven invasive ductal breast cancers underwent diffusion-weighted imaging with b-values of 0 and 800 s/mm2 at a 3-T system. ADC metrics including ADCmean, ADCmedian, ADCmin, ADCmax, and ΔADC (ADCmax-ADCmin) were recorded from the entire tumour volume on ADC maps, and correlated with the Ki-67 LI. Ki-67 staining of ≥14% was considered to indicate high proliferation and <14% was considered to indicate low proliferation. RESULTS: ADCmin, ADCmax, and ΔADC showed significant correlations with the Ki-67 LI (for all tumours, r=-0.311, 0.436, and 0.551, respectively; for luminal/human epidermal growth factor receptor 2 (HER2)-negative group, r=-0.437, 0.512, and 0.639, respectively; all p<0.01), whereas ADCmean and ADCmedian showed no significant correlation (both p>0.05). Receiver operating characteristic (ROC) curve analysis for the differentiation of high- from low-proliferation groups showed that ΔADC yielded the highest area under the ROC curve for the whole tumour population (0.825; 95% confidence interval [CI]: 0.724, 0.901), as well as for the luminal/HER2-negative group (0.844; 95% CI: 0.692, 0.940). CONCLUSION: ΔADC may serve as a promising imaging biomarker for the prediction of Ki-67 proliferation status in invasive ductal breast cancer.

SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer.

SRY (sex determining region Y)-box 9 (SOX9) is required for oncogenic Kras-mediated acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasias (PanINs) and ultimately pancreatic ductal adenocarcinoma (PDAC). However, how oncogenic Kras affects SOX9 activity is not yet understood, and SOX9-associated genes in PDAC are also unknown at all. Here, we investigated the mechanistic link between SOX9 and oncogenic Kras, studied biological function of SOX9, and identified SOX9-related genes and their clinical significance in patients with PDAC. Our studies reveal that oncogenic Kras induces SOX9 mRNA and protein expression as well as phosphorylated SOX9 expression in human pancreatic ductal progenitor cells (HPNE) and pancreatic ductal cells (HPDE). Moreover, oncogenic Kras promoted nuclear translocation and transcriptional activity of SOX9 in these cells. TAK1/IκBα/NF-κB pathway contributed to induction of SOX9 by oncogenic Kras, and SOX9 in turn enhanced NF-κB activation. SOX9 promoted the proliferation of HPNE and PDAC cells, and correlated with minichromosome maintenance complex components (MCMs) and mediator of DNA damage checkpoint 1 (MDC1) expression. The overexpressive MDC1 was associated with less perineural and lymph node invasion of tumors and early TNM-stage of patients. Our results indicate that oncogenic Kras induces constitutive activation of SOX9 in HPNE and HPDE cells, and Kras/TAK1/IκBα/NF-κB pathway and a positive feedback between SOX9 and NF-κB are involved in this inducing process. SOX9 accelerates proliferation of cells and affects MCMs and MDC1 expression. MDC1 is associated negatively with invasion and metastasis of PDAC.

MiR-150 alleviates EMT and cell invasion of colorectal cancer through targeting Gli1.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) is related to colorectal cancer invasion and metastasis. Glioma-associated oncogene homolog 1 (Gli1) abnormal expression is associated with EMT, invasion, and metastasis in various cancers. MiR-150 is found downregulated in colorectal cancer pathogenesis. Bioinformatics analysis shows the complementary targeted relationship between miR-150 and the 3'-UTR of Gli1 mRNA. This study explores the role of miR-150 in regulating Gli1 expression, colorectal cancer cell EMT, and invasion. MATERIALS AND METHODS: Dual luciferase assay confirmed the targeted relationship between miR-150 and Gli1 predicted by bioinformatics analysis. MiR-150 and Gli1 expressions were compared in NCM460, SW480, and SW620 cells. Cell colony formation and invasion were tested in SW480 and SW620 cells. Anip973 and AGYZ83-a cells were treated by 10 ng/mL TGF-ß1 to detect miR-150 and Gli1 expressions. SW620 cells were cultured in vitro and divided into five groups, including miR-NC, miR-150 mimic, si-NC, si-Gli1, and miR-150 mimic + si-Gli1 groups. RESULTS: MiR-150 specifically inhibited Gli1 expression. The level of miR-150 was significantly downregulated, while Gli1 was elevated in SW480 and SW620 cells compared with that in NCM460 cells. SW620 exhibited markedly stronger invasive and colony formation abilities than SW480. The level of miR-150 was apparently reduced, whereas Gli1 was increased in SW620 than that in SW480 cells after the treatment of TGFß1. MiR-150 mimic and/or si-Gli1 transfection markedly reduced Gli1 and Snail levels, upregulated E-cadherin expression, and attenuated cell colony formation and invasion. CONCLUSIONS: Downregulation of miR-150 and elevation of Gli1 promote the development and invasion of colorectal cancer cell EMT. MiR-150 attenuated the progression of colorectal cancer cell EMT via inhibiting Gli1.

[Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting activation of Kupffer cells].

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion: Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.

Exploring the regulatory role of isocitrate dehydrogenase mutant protein on glioma stem cell proliferation.

OBJECTIVE: Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. PATIENTS AND METHODS: Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue. RESULTS: The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation. CONCLUSIONS: Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.

[Establishment and evaluation of a mouse model of nonalcoholic steatohepatitis-related hepatocellular carcinoma].

OBJECTIVE: To establish an apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) double-knockout (ApoE(-/-)/LDLR(-/-)) mouse model of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) induced by high-fat and high-cholesterol (HFHC) diet. METHODS: ApoE(-/-) knockout mice were crossed with LDLR(-/-) knockout mice to obtain ApoE(-/-)/LDLR(-/-) mice. The ApoE(-/-)/LDLR(-/-) mice mated with each other, and the offspring were injected with low-dose streptozotocin (STZ) at 2-3 days after birth. Some mice were fed with HFHC diet after weaning as the model group (n = 15), and some mice were fed with normal diet as the control group (n = 15). Mice were sacrificed at the end of weeks 10, 16, and 20 (5 mice at each time point). The body weight was measured. Liver tissue and blood were collected to measure biochemical parameters, evaluate the pathological changes in the liver tissue by HE staining, oil red O staining, and Masson staining, and detect the expression of glypican-3 (a marker of HCC) by immunohistochemical staining. RESULTS: The model group had significantly higher levels of fasting blood glucose and total cholesterol than the control group (P < 0.01). Serum levels of alanine aminotransferase, aspartate aminotransferase, and total triglyceride gradually increased with time in the model group; at week 20, there were significant differences in above three indices between the two groups (P < 0.05). HE staining showed that compared with the control group at the corresponding time point, the model group developed sequential histological changes: NASH at week 10, dysplastic nodules at week 16, and early HCC at week 20. Oil red O staining showed that in the model group, the degree of liver steatosis increased within 10 weeks and gradually decreased later. Masson staining demonstrated that the model group developed pathological changes: mild perisinusoidal fibrosis at week 16 and bridging fibrosis around tumors at week 20. HE staining, oil red O staining, and Masson staining showed that no histological or pathological changes were found in the control group. Glypican-3 was detected in the nodules at week 16 and in the cytoplasm of HCC cells at week 20 in the model group. CONCLUSION: The mouse model of NASH-related HCC can be developed by giving STZ injection to neonatal ApoE(-/-)/LDLR(-/-) mice and feeding them with HFHC diet after weaning for 20 weeks. Early HCC may develop directly from NASH.

Downregulation of miR-361-5p associates with aggressive clinicopathological features and unfavorable prognosis in non-small cell lung cancer.

OBJECTIVE: To assess the impact of miR-361-5p expression levels on non-small-cell lung cancer (NSCLC) survival. PATIENTS AND METHODS: A total of 183 patients with NSCLC who underwent surgery between October 2007 and April 2010 were included in this study. Expression levels of miR-361-5p were detected by using qRT-PCR. The association of miR-361-5p expression with clinicopathologic characteristics of NSCLC patients was analyzed. Kaplan-Meier Plotter was performed to identify the prognostic roles of miR-361-5p in NSCLC patients. Finally, multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Results indicated that miR-361-5p was lowly expressed in NSCLC compared with adjacent non-malignant tissues (p < 0.01). And low miR-361-5p expression in NSCLC was significantly correlated with TNM stage (p = 0.000), lymph node metastasis (p = 0.001) and lymphatic invasion (p = 0.032). Kaplan-Meier analysis with the log-rank test indicated that low miR-361-5p expression had a significant impact on overall survival (p < 0.001). Furthermore, Multivariate analyses indicated that miR-361-5p represented an independent predictor for overall survival of NSCLC (p = 0.007). CONCLUSIONS: Our work revealed that miR-361-5p played critical roles in NSCLC progression and could represent a novel prognostic marker in NSCLC patients.

Extra-articular tenosynovial chondromatosis of the left ring finger in a 23-year-old man: A case report and literature review.

Tenosynovial chondromatosis is an extra-articular version of articular synovial chondromatosis and a relatively rare condition that can affect the tendon sheath, bursa, or joint synovial tissue. Tenosynovial chondromatosis is rarely reported in the literature and is often misdiagnosed. In the present study, a case of extra-articular tenosynovial chondromatosis of the left ring finger in a 23-year-old man is reported. Three different-sized nodules were identified upon surgery and all were removed via synovectomy. The patient was symptom free 6 months postoperatively, and there were no signs of recurrence after 1.5 years of follow-up. The literature describing tenosynovial chondromatosis in the fingers is also reviewed.