BackgroundHepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines—most importantly interleukin (IL)-6—to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear.MethodsWe analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation.ResultsPeripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis.ConclusionsOur findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.

Objective: To evaluate, using multislice computed tomography (MSCT), the morphologic changes in the upper airway after large incisor retraction in adult bimaxillary protrusion patients. Materials and Methods: Thirty adult patients with bimaxillary protrusion had four first premolars extracted, and then miniscrews were placed to provide anchorage. A CT scan was performed before incisor retraction and again posttreatment. Three-dimensional (3D) reconstruction of the pre-(T1) and post-(T2) CT data was used to assess for morphological changes of the upper airway. A paired t-test was used to compare changes from T1 to T2. The relationship among the three variables (upper incisor retraction amount, upper airway size, and hyoid position) was analyzed by Pearson correlation coefficient. Results: The amounts of upper incisor retraction at the incisal edge and apex were 7.64 6 1.68 mm and 3.91 6 2.10 mm, respectively. The hyoid was retracted 2.96 6 0.54 mm and 9.87 6 2.92 mm, respectively, in the horizontal and vertical directions. No significant difference was observed in the mean cross-sectional area of the nasopharynx (P . .05) between T1 and T2, while significant differences between T1 and T2 were found in the mean cross-sectional areas of the palatopharynx, glossopharynx, and hypopharynx (P , .05); these mean cross-sectional areas were decreased by 21.02% 6 7.89%, 25.18% 6 13.51%, and 38.19% 6 5.51%, respectively. The largest change in the cross-sectional area is always noted in the hypopharynx. There was a significant correlation among the retraction distance of the upper incisor at its edge, the retraction distance of the hyoid in the horizontal direction, and the decrease of the hypopharynx. Conclusion: Large incisor retraction leads to narrowing of the upper airway in adult bimaxillary protrusion patients. (Angle Orthod. 2012;82:964-970.)

Human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells (MSCs) derived from dental and craniofacial tissues that exhibit high potential for differentiation into osteoblasts. Recently, microRNAs (miRNAs) have been established to play important roles in MSC osteogenesis. In the current study, we report that miR-21 was down-regulated in osteogenically differentiated PDLSCs. Overexpression of miR-21 significantly inhibited osteogenesis of hPDLSC, whereas its inhibition demonstrated the opposite effects. Furthermore, SMAD family member 5 (Smad5) was predicted to be a downstream target of miR-21 and was shown to undergo up-regulation in PDLSCs induced toward osteogenesis. Moreover, Smad5 and Runx2, which are the critical transcription factors in osteogenic differentiation, were predicted to be targets of miR-21. Suppression of miR-21 expression increased the level of Smad5 in vitro and during in vivo transplantation experiments. Furthermore, suppression of Smad5 inhibited osteogenic differentiation and decreased the protein level of Runx2. Taken together, these results suggested that miR-21 be mechanistically implicated in the regulation of osteogenic differentiation of hPDLSCs by targeting Smad5.

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There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra-and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.