Three-Dimensional-Printed Template-Guided Radioactive Seed Brachytherapy via a Submental Approach for Recurrent Base of Tongue and Floor of Mouth Cancer.

Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Untangling determinants of gut microbiota and tumor immunologic status through a multi-omics approach in colorectal cancer.

The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

Bladder perforation injury after percutaneous peritoneal dialysis catheterization: A case report.

BACKGROUND: Insertion of a catheter into the bladder is a rare complication of peritoneal dialysis (PD), and is mainly related to surgical injury. This paper reports a case of bladder perforation that was caused by percutaneous PD catheterization. CASE SUMMARY: A 64-year-old man underwent percutaneous PD catheterization for end-stage renal disease. On the second day after the operation, urgent urination and gross hematuria occurred. Urinalysis showed the presence of red and white blood cells. Empirical anti-infective treatment was given. On the third day after the operation, urgent urination occurred during PD perfusion. Ultrasound showed that the PD catheter was located in the bladder, and subsequent computed tomography (CT) showed that the PD catheter moved through the anterior wall into the bladder. The PD catheter was withdrawn from the bladder and catheterization was retained. Repeat CT on the fourth day after the operation showed that the PD catheter was removed from the bladder, but there was poor catheter function. The PD catheter was removed and the patient was changed to hemodialysis. CT cystography showed that the bladder healed well and the patient was discharged 14 d after the operation. CONCLUSION: Bladder perforation injury should be considered and treated timeously in case of bladder irritation during and after percutaneous PD catheterization. The use of Doppler ultrasound and other related technologies may reduce the incidence of such complications.

A real-world 1:1 propensity-matched study revealed unmarried status was independently associated with worse survival for patients with renal clear cell carcinoma.

Background: Marital status has been reported as an independent prognostic factor for survival in various cancers, but it has been rarely studied in renal clear cell carcinoma (ccRCC). In this study, we aimed to assess the impact of marital status on the survival of ccRCC patients. Methods: We retrospectively investigated the Surveillance, Epidemiology, and End Results (SEER) database and identified 68599 of ccRCC patients between 1973 and 2015. These patients were divided into married, single, divorced and widowed groups. The survival differences among these groups were assessed by Kaplan-Meier method and log-rank test. Multivariate Cox regression analyses were performed to identify the overall survival (OS) and cancer-specific survival (CSS) independent factors. Furthermore, 1:1 propensity score matching (PSM) analysis was performed to minimize the potential confounding factors. Results: Of the 68599 ccRCC patients, 44553 (64.95%) patients were married, 7410 (10.80%) were divorced, 10663 (15.54%) were single, and 5973 (8.71%) were widowed. The 5-year OS was 79.0%, 73.8%, 77.3%, and 66.4 % in the married, divorced, single, and widowed groups, respectively (p = 0.001) and the corresponding 5-year CSS rates were 85.5%, 83.3%, 80.8%, 76.5%, respectively. Multivariate Cox regression analysis marital status was the independent prognostic factor for OS and CSS. Compared with the married patients, the divorced, single, and widowed patients faced increased higher mortality risks for OS and CSS. In stratified analyses by sex, surgery conditions and cancer stages, those unmarried patients still had worse prognosis. The results were further confirmed in the 1: 1 matched group. Conclusion: Unmarried ccRCC patients experienced worse survival than their married counterparts. Among the unmarried patients, the widowed suffered the highest mortality risks for OS and CSS.

The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3ß (GSK3ß) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3ß, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3ß inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3ß activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection.

BACKGROUND: Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments. PURPOSE: To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. STUDY TYPE: Retrospective. POPULATION: In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. FIELD STRENGTH/SEQUENCES: 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences. ASSESSMENT: Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. STATISTICAL TESTS: Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses. RESULTS: MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. DATA CONCLUSION: MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409.

Assessing performance of augmented reality-based neurosurgical training.

This paper presents a novel augmented reality (AR)-based neurosurgical training simulator which provides a very natural way for surgeons to learn neurosurgical skills. Surgical simulation with bimanual haptic interaction is integrated in this work to provide a simulated environment for users to achieve holographic guidance for pre-operative training. To achieve the AR guidance, the simulator should precisely overlay the 3D anatomical information of the hidden target organs in the patients in real surgery. In this regard, the patient-specific anatomy structures are reconstructed from segmented brain magnetic resonance imaging. We propose a registration method for precise mapping of the virtual and real information. In addition, the simulator provides bimanual haptic interaction in a holographic environment to mimic real brain tumor resection. In this study, we conduct AR-based guidance validation and a user study on the developed simulator, which demonstrate the high accuracy of our AR-based neurosurgery simulator, as well as the AR guidance mode's potential to improve neurosurgery by simplifying the operation, reducing the difficulty of the operation, shortening the operation time, and increasing the precision of the operation.

Stenting of the Portal Vein Combined with Different Numbers of Iodine-125 Seed Strands: Dosimetric Analyses.

BACKGROUND:: Portal-vein stent combined with one iodine-125 (125I) seed strand has become a new treatment for portal vein tumor thrombosis. However, dosimetric aspects of this irradiation stent have not been reported. Therefore, we aimed to undertake dosimetric analyses comparing portal-vein stents combined with different numbers of 125I seed strands. METHODS:: A water cylinder was created by a treatment-planning system to simulate a portal-vein stent. The stent was combined with one, two, or three 125I seed strands (Groups I, II, and III, respectively). At different prescribed doses (PDs), 125I seeds of identical activities were loaded on Groups I-III. Conformation number (CN), external volume index, and homogeneity index were calculated. Linear regression analyses were used to evaluate the obtained data. RESULTS:: For identical 125I seed activity, when the 125I seed strand increased from one chain to two, D90 (dose delivered to 90% of the target volume) increased by ≥184%; when it increased from two chains to three, D90 increased by ≥63%. When the PD was 105 Gy and 125I seed strands increased from one chain to two, V100 (percentage of the target volume receiving ≥90% of the PD) increased by 158-249%; when it increased from two chains to three, V100 increased by 7-175%. CN was correlated positively with 125I seed activity (B = 0.479, P < 0.001) and number of 125I seed strands (B = 0.201, P < 0.001) and was independent of PD (B = -0.002, P = 0.078). CONCLUSIONS:: A portal-vein stent combined with a single 125I seed strand could not meet dosimetry requirements. For a stent combined with two 125I seed strands, when the PD was 105 Gy and seed activity was 0.7 mCi, the dose distribution could satisfy dosimetry requirements. For a stent combined with three 125I seed strands, if the PD was 105, 125, or 145 Gy, the recommended seed activities were 0.5, 0.5, and 0.6 mCi, respectively.

[Immunomodulatory effects of human amniotic versus bone marrow-derived mesenchymal stem cells on peripheral blood T lymphocytes in vitro].

OBJECTIVE: To compare the immunomodulatory effects of human amniotic mesenchymal stem cell (hAMSCs) and human bone marrow mesenchymal stem cells (hBMSCs) on peripheral blood T lymphocytes in an in vitro co-culture system. METHODS: hAMSCs and hBMSCs isolated using enzymatic digestion and Ficoll-Hypaque density gradient centrifugation, respectively, were culture-expanded in vitro to obtain the 4th-generation cells. The two MSCs were co-cultured separately with human peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA-PBMSC) to investigate the changes in T lymphocyte subsets using flow cytomety and the production of interleukin-2 (IL-2) and IL-10 by the T lymphocytes using enzyme-linked immunosorbent assay (ELISA). RESULTS: Co-culture with either hAMSCs or hBMSCs significantly increased the proportions of Treg, Th2 and Tc2 and decreased Th1 and Tc1 cell subsets in the PBMCs as compared with the PBMCs cultured alone (P<0.05), and the changes in the PBMCs were similar between the two co-culture systems (P>0.05). In both of the two co-culture systems, IL-2 production by the lymphocytes was significantly lowered (P<0.05) and IL-10 production was significantly increased (P<0.05) as compared with their levels in the PBMCs cultured alone; no significant difference was found in IL-2 or IL-10 levels between the two co-culture systems (P>0.05). CONCLUSION: The MSCs derived from human amnion and bone marrow have similar immunomodulatory effects on the T lymphocytes, suggesting the possibility of using hAMSCs in the treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

In vitro Dosimetric Study of Biliary Stent Loaded with Radioactive 125I Seeds.

BACKGROUND: A novel radioactive 125I seed-loaded biliary stent has been used for patients with malignant biliary obstruction. However, the dosimetric characteristics of the stents remain unclear. Therefore, we aimed to describe the dosimetry of the stents of different lengths - with different number as well as activities of 125I seeds. METHODS: The radiation dosimetry of three representative radioactive stent models was evaluated using a treatment planning system (TPS), thermoluminescent dosimeter (TLD) measurements, and Monte Carlo (MC) simulations. In the process of TPS calculation and TLD measurement, two different water-equivalent phantoms were designed to obtain cumulative radial dose distribution. Calibration procedures using TLD in the designed phantom were also conducted. MC simulations were performed using the Monte Carlo N-Particle eXtended version 2.5 general purpose code to calculate the radioactive stent's three-dimensional dose rate distribution in liquid water. Analysis of covariance was used to examine the factors influencing radial dose distribution of the radioactive stent. RESULTS: The maximum reduction in cumulative radial dose was 26% when the seed activity changed from 0.5 mCi to 0.4 mCi for the same length of radioactive stents. The TLD's dose response in the range of 0-10 mGy irradiation by 137Cs γ-ray was linear: y = 182225x - 6651.9 (R2=0.99152; y is the irradiation dose in mGy, x is the TLDs' reading in nC). When TLDs were irradiated by different energy radiation sources to a dose of 1 mGy, reading of TLDs was different. Doses at a distance of 0.1 cm from the three stents' surface simulated by MC were 79, 93, and 97 Gy. CONCLUSIONS: TPS calculation, TLD measurement, and MC simulation were performed and were found to be in good agreement. Although the whole experiment was conducted in water-equivalent phantom, data in our evaluation may provide a theoretical basis for dosimetry for the clinical application.

[Research progress of miRNAs targeting GSK-3ß in regulation of hepatocellular carcinoma invasion and metastasis].

Invasion and metastasis are key factors contributing to the high mortality rate of patients with hepatocellular carcinoma (HCC) involving a complex mechanism. In the invasion and metastasis of HCC, miRNAs can serve as either oncogenes or tumor suppressor genes to regulate the differentiation and proliferation of tumor cells being and play important roles in tumorigenesis, angiogenesis, invasion and metastasis. This review summarizes the recent progress in research of the molecular mechanisms by which miRNAs targeting GSK-3ß regulate HCC invasion and metastasis and examines the roles of miRNAs in hepatocellular carcinoma cell proliferation, apoptosis, invasion, metastasis, and GSK-3ß regulation.

[Comparison of Biological Characteristics and Immunosuppressive Activity between Human Amniotic Mesenchymal Stem Cells and Human Bone Marrow Mesenchymal Stem Cells].

OBJECTIVE: To compare the biological characteristics and immunosuppressive activity between human amniotic mesenchymal stem cells (hAMSC) and human bone marrow mesenchymal stem cells (hBMMSC). METHODS: MSC from human amnion and bone marrow were isolated using enzymatic digestion and Ficoll-Hypaque density gradients, respectively. Their biological characteristics were compared by morphology, cell growth curves, cell cycle profile analysis, immunophenotype and immunofluorescence assay. Their immunosuppressive activities were studied on total activated T-cells with phytohemagglutinin (PHA-PBMSC). An in vitro co-culture was performed to compared the lymphocyte proliferation and the supernatant level of IFN-γ were measured by CCK-8 method and ELISA, respectively. RESULTS: Both hAMSC and hBMMSC demonstrated fibroblast-like morphology. The hAMSC were able to be amplified for at least 15 passages, while the hBMMSC only for 6-7 passages. There was no significant difference in the proportion of G2/M phase cells of the 2 cells types (P>0.05). By FACS analysis for immunophenotype, both MSC were shown to be positive for CD105, CD90, CD73 and negative for CD34, CD45, CD11b, CD19, HLA-DR, but hAMSC were positive for Oct-3/4, which was in contrast to hBMMSC. Both of them expressed vimentin. Both the cells exhibited a inhibitory role on the lymphocyte proliferation induced by PHA in co-culture conditions, that was increased with the increase MSC proportion and both the suppressing effecs were enhanced. The supernatant IFN-γ levels of hAMSC co-cultured with lymphocyte at a ratio of 1:1 after 72 hours were measured by ELISA, and the level of IFN-γ was significantly lower than that in the same co-culture system of hBMMSC. In contrast to the IFN-γ in the PHA-stimulated group, the IFN-γ level in both co-culture groups was significantly lower. CONCLUSION: MSC from amnion displayed a higher proliferative capacity and stem cell properties, compared with hBMMSC. Both MSC can inhibit lymphocyte proliferation and suppress IFN-γ secretion induced by PHA in vitro.

[Inhibitory effect of Biejiajian pills on HepG2 cell xenograft growth and expression of ß-catenin and Tbx3 in nude mice].

OBJECTIVE: To explore the molecular mechanism by which Biejiajian pills inhibit hepatocellular carcinoma in a nude mouse model bearing HepG2 cell xenograft. METHODS: The inhibitory effect of Biejiajian pills on the growth of HepG2 cell xenograft in nude mice was observed. Immunohistochemical method was used to examine proliferating cell nuclear antigen (PCNA) expression in HepG2 cell xenograft, and TUNEL method was employed to detect the cell apoptosis; the expression levels of ß-catenin and Tbx3 were measured by Western blotting. RESULTS: Biejiajian pills significantly suppressed the growth of HepG2 cell xenograft in nude mice. The tumor-bearing mice treated with a high and a moderate dose of Biejiajian pills showed significantly increased apoptosis rate of the tumor cells [(22.9±1.220)% and (14.7±0.50)%, respectively] compared with the control group [(5.5±0.90)%, P<0.05]. Treatment with Biejiajian pills significantly decreased the expressions of PNCA, ß-catenin, and Tbx3 in the cell xenograft (P<0.05). CONCLUSIONS: Biejiajian pills can inhibit the growth of HepG2 cell xenograft in nude mice and promote tumor cell apoptosis possibly by inhibiting PNCA expression and the Wnt/ß-catenin signaling pathway.

[Effects of Biejiajian Pill on Proliferation and Apoptosis of Hepatic Stellate Cells in Mice].

Objective To observe the possible mechanism of Biejiajian Pill (BP) in fighting a- gainst hepatic fibrosis of hepatic stellate cell T6 ( HSC-T6) by studying effect of BP containing serum on inhibiting proliferation and inducing apoptosis of HSC-T6. Methods Forty Wistar rats were randomly di- vided into the negative control group (NC) , the positive drug control group (P) , high, middle, and low dose groups (H, M, L) , 8 in each group. BP suspension was administered by gastrogavage to rats in Group H, M, L at 21. 87, 43. 75, and 87. 50 mg/mL, respectively. Rats in Group NC were administered with equal volume of normal saline. Rats in Group P were administered with 0. 01 mg/mL colchicine solu- tion by gastrogavage. Each rat received 2 mL corresponding solution, twice per day, with an interval of 12 h gastrogavage, a total of 7 successive times to prepare drug containing serum. HSC-T6 cells were then randomly divided into drug containing serum groups (group H/M/L/NC) , colchicine positive control group (group P) , and the blank control group (BC). Cells in Group H/M/L/NC/P were fed with correspond- ing drug containing serums, while those in-Group BC were cultured with free drug serum. The proliferation inhibition rate of HSC-T6 was detected using CCK8 method at 24, 48, and 72 h, respectively. The apop- totic rate and cell cycle were detected using flow cytometry. Protein expressions of B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using Western blot. Results Compared with Group NC, 24-h proliferation inhibition rate of HSC-T6 was obviously elevated in Group M, H, P (P < 0. 05). Compared with Group NC, 48- and 72-h proliferation inhibition rate of HSC-T6 was obviously ele- vated in Group L, M, H, P (P <0. 05). But there was no statistical difference in 24-, 48-, and 72-h prolif- eration inhibition rate of HSC-T6 among Group L, M, H, P (P >0. 05). Compared with Group NC and BC, early-and late-stage apoptosis rates of HSC-T6 obviously increased in Group M, H, P (P<0. 05) ; G,/G1 phase cell number obviously increased in Group M, H, P (P <0. 05) ; S phase and G2/M phase cell num- bers obviously decreased in Group L, M, H, P (P <0. 05). There was no statistical difference in Bcl-2 protein expression among each group (P>0. 05). Compared with Group NC, Bax protein expression ob- viously increased Group L, M, H, P (P <0. 01). Conclusion The mechanism of BP for fighting against hepatic fibrosis might be associated with inhibiting proliferation of HSC-T6 and inducing apoptosis.

Changes of inflammation and apoptosis in adrenal gland after experimental injury in rats with acute necrotizing pancreatitis.

We hypothesize that adrenal insufficiency in acute necrotizing pancreatitis (ANP) is attributable to hemorrhagic inflammation, necrosis, and apoptosis of the adrenal cortex. Arguments to support this view are presented in the study that investigated morphological and functional changes of adrenal and the distinct roles of inflammatory mediator secretory phospholipase A(2) (sPLA(2)) and apoptosis-related genes Bax and Bcl-2 played in acute adrenal injury in ANP. After ANP model was induced, pancreatic histology, serum amylase, sPLA(2), and corticosterone were analyzed. The adrenal morphology, apoptotic cells by TUNEL assay, and ultrastructures were observed. sPLA(2)-IIA and Bcl-2 and Bax expressions were detected by immunohistochemistry. Histopathologic grading of adrenal was higher in ANP group than in controls. Serum corticosterone was stimulated to maximal level at 3 h, then dropped to the bottom at 24 h (P<0.05). Apoptotic index, sPLA2-IIA, and Bax expression were increased steeply after pancreatitis, and the Bax/Bcl-2 ratio was elevated gradually (P<0.05). Sustained decrease in serum corticosterone level following adrenal injury during ANP appears to be, in part, due to the crucial roles of inflammation and apoptosis in adrenal cortex. These findings could suggest that sPLA2, Bax, and Bcl-2 may be involved in the course of adrenal injury after ANP.

[Influence of pressure on cricoid on insertion ProSeal laryngeal mask airway and ventilation function].

OBJECTIVE: To assess the influence of cricoid pressure (CP) on insertion and ventilation function of ProSeal laryngeal mask airway (PLMA). METHODS: Fifty adult patients with American Society of Anesthesiologists (ASA) physical status category I, scheduled for elective plastic surgery were studied. After induction of intravenous anesthesia, the PLMA was inserted using an introducer under CP and the intracuff pressure was set to 60 cm H(2)O (1 cm H(2)O=0.098 kPa) with the introducer in place. The content degree of lung ventilation, airway seal pressure and anatomic position of the cuff were assessed. Then CP was temporary terminated, the PLMA was further advanced to the ideal position and the intracuff pressure was readjusted to 60 cm H(2)O. The above-mentioned assessments were re-performed, and the expiratory tidal volume and peak inspiratory pressure during positive-pressure ventilation (PPV) with and without CP were recorded. The gastric tube placement through the PLMA was observed, anatomical position of the drain tube was also scored by fiberoptic examination. RESULTS: After the PLMA was further advanced to the ideal position under temporary termination of CP, lung ventilation content degree (good: acceptable=50:14 cases), airway seal pressure [(27+/-7) cm H(2)O vs. (21+/-7) cm H(2)O] and fiberoptic score of anatomical position of cuff were significantly improved compared with those after PLMA insertion under CP (P<0.05). The expiratory tidal volume during PPV was not significantly different between with and without CP, but the peak inspiratory pressure increased from (14+/-2) cm H(2)O without CP to (28+/-5) cm H(2)O with CP, and there was statistically significant difference (P<0.05). In all patients, gastric tube placement through the PLMA was successful with single attempt and correct anatomical position of the drain tube was confirmed by fiberoptic examination. CONCLUSION: The CP can impede the insertion of PLMA into the ideal position. The PLMA is still able to be advanced to the ideal position with a special introducer under temporary termination of CP. After the PLMA is advanced to the ideal position, the CP produces a significant increase in the peak inspiratory pressure during PPV.