A comparison of behavioral paradigms assessing spatial memory in tree shrews.

Impairments in spatial navigation in humans can be preclinical signs of Alzheimer's disease. Therefore, cognitive tests that monitor deficits in spatial memory play a crucial role in evaluating animal models with early stage Alzheimer's disease. While Chinese tree shrews (Tupaia belangeri) possess many features suitable for Alzheimer's disease modeling, behavioral tests for assessing spatial cognition in this species are lacking. Here, we established reward-based paradigms using the radial-arm maze and cheeseboard maze for tree shrews, and tested spatial memory in a group of 12 adult males in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and task performance improved gradually until reaching a plateau in all 3 mazes. However, spatial learning was compromised post-lesion in the 2 newly developed tasks, whereas memory retrieval was impaired in the water maze task. These results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring progressive cognitive decline in aged or genetically modified tree shrews that develop Alzheimer's disease-like symptoms. This study may facilitate the utilization of tree shrew models in Alzheimer's disease research.

Association of Apoptosis-Mediated CD4+ T Lymphopenia With Poor Outcome After Type A Aortic Dissection Surgery.

Background: Many patients with type A aortic dissection (AAD) show low lymphocyte counts pre-operatively. The present study investigated the prognostic values of lymphopenia and lymphocyte subsets for the postoperative major adverse events (MAEs) in AAD patients undergoing surgery, and explore mechanisms of lymphopenia. Methods: We retrospectively analyzed pre-operative lymphocyte counts in 295 AAD patients treated at two hospitals, and evaluated their correlation with MAEs. We prospectively recruited 40 AAD patients and 20 sex- and age-matched healthy donors (HDs), and evaluated lymphocyte subsets, apoptosis, and pyroptosis by flow cytometry. Results: Multivariable regression analysis of the retrospective cohort revealed pre-operative lymphopenia as a strong predictor of MAEs (odds ratio, 4.152; 95% CI, 2.434-7.081; p < 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4+ and CD8+ T cells as compared with HDs (CD4+ T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/µl, p < 0.0001; CD8+ T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/µl, p = 0.0036). The apoptosis rates of CD4+ and CD8+ T cells were significantly higher in AAD patients relative to HDs (both p < 0.0001). Furthermore, the pre-operative CD4+ T cells count at a cut-off value of 357.96 cells/µl was an effective and reliable predictor of MAEs (area under ROC curve = 0.817; 95% CI, 0.684-0.950; sensitivity, 74%; specificity, 81%; p < 0.005). Pre-operative lymphopenia, mainly due to CD4+ T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery. Conclusion: Pre-operative lymphopenia in particular CD4+ T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.

Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4.

BACKGROUND: The metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide. Growing evidence showed that aspirin could effectively inhibit liver metastasis of colorectal cancer. However, the potential mechanism has not been fully understood. METHODS: Mouse splenic vein metastasis assay was used to examine the metastatic ability of colon cancer cells in vivo. And wound healing and transwell assay were applied to detect the metastasis potential of C26 and HCT116 colon cancer cell lines in vitro. RT-PCR and western blotting were used to explore Toll-like receptor 4 (TLR4) expression in colon cancer cell lines. The functions of TLR4 in the migration of the colon cancer cell line were analyzed by infecting cells with lentivirus containing TLR4 siRNA. RESULTS: We demonstrated that lipopolysaccharides (LPS) could enhance the metastasis potential of C26 and HCT116 colon cancer cell lines. However, aspirin effectively decreased the metastasis capacity of colon cancer cells in vitro and in vivo. We found that the enhancement of LPS on the migration of colon cancer cells by inducing epithelial-mesenchymal transition (EMT) phenotype demonstrated a TLR4-dependent manner. Aspirin treatment lead to the downregulation of TLR4 on C26 cells which resulted in the decrease of C26 cells migration and EMT phenotype that induced by LPS. Additionally, the inhibitory effect from aspirin on the expression of TLR4 on C26 cells leads to the downregulation of NF-κB. CONCLUSION: The results of our study indicate that LPS origin from intestinal flora may promote the metastasis of colon cancer to liver and aspirin may inhibit the metastasis of colon cancer by inhibiting the expression of TLR4.

Current treatment status and barriers for patients with chronic HCV infection in mainland China: A national multicenter cross-sectional survey in 56 hospitals.

Chronic hepatitis C virus (HCV) infection is a serious public health problem worldwide. China, as the country with the largest number of HCV infections in the world, plays a significant role in eliminating hepatitis C. Due to different financial situations and education background, hepatitis C patients take different actions for their disease treatment and management. Therefore, antiviral treatment status should be attached great importance to learn the medical demand of patients. A nationwide, multicenter survey was conducted from July 2015 to June 2016. Of 1798 inpatients and outpatients with chronic HCV from 56 hospitals participated in the survey. Each patient completed the questionnaire with questions about his/her antiviral therapy status, perception of treatment barriers, and expectations for future treatment. In total 1622 patients, including 1241 with chronic hepatitis C, 344 with cirrhosis, and 37 patients with hepatocellular carcinoma, fulfilled data collection requirements and finally were included in analysis. Overall, up to 30.7% of the patients had not or currently does not intend to receive antiviral therapy. The main reason was expecting more potent and well-tolerance medication (31.5%), followed by the fear of interferon related side effects (27.5%). Multiple regression analysis showed that the patient's annual income, the severity of HCV, and comorbidity were independent predictors of not receiving antiviral therapy. The whole patients were expecting more potent and well tolerance medication available soon. In summary, Peg-IFN/RBV treatment regimen cannot meet the need of patients well, and safe and efficient direct-acting antivirals are urgently needed in mainland China.

Structural distortions, orbital ordering and physical properties of double perovskite R2CoMnO6 calculated by first-principles.

The structural distortions, orbital ordering, magnetic and electronic properties of double perovskite R2CoMnO6 (R = rare-earth element) have been systematically calculated by first-principles. Structural distortions, including Co-O and Mn-O bond length splitting, the antiferroelectric motions of R ions, the tilting of octahedral (the resulted Co-O-Mn bond angle) are obviously affected by the rare-earth ions' radius. The bond length splitting behavior of Co-O and Mn-O are rather different because of the Jahn-Teller active ion Co2+ and the Jahn-Teller nonactive ion Mn4+. Taking Gd2CoMnO6 as an example, the t 2g orbitals of Co ions are predicted to be orbital ordered. That is, the spin down channel of d xz orbital for one Co ion and d yz orbital for another Co ion are basically vacant. Finally, the physical properties, including the magnetic Curie temperature and electronic band gap of R2CoMnO6 are almost linear dependent on the average value of cos2 θ (θ is the Co-O-Mn exchange-angle).

Perfusion-decellularized skeletal muscle as a three-dimensional scaffold with a vascular network template.

There exists a great need for repair grafts with similar volume to human skeletal muscle that can promote the innate ability of muscle to regenerate following volumetric muscle loss. Perfusion decellularization is an attractive technique for extracellular matrix (ECM) scaffold from intact mammalian organ or tissue which has been successfully used in tissue reconstruction. The perfusion-decellularization of skeletal muscle has been poorly assessed and characterized, but the bioactivity and functional capacity of the obtained perfusion skeletal muscle ECM (pM-ECM) to remodel in vivo is unknown. In the present study, pM-ECM was prepared from porcine rectus abdominis (RA). Perfusion-decellularization of porcine RA effectively removed cellular and nuclear material while retaining the intricate three-dimensional microarchitecture and vasculature networks of the native RA, and many of the bioactive ECM components and mechanical properties. In vivo, partial-thickness abdominal wall defects in rats repaired with pM-ECM showed improved neovascularization, myogenesis and functional recellularization compared to porcine-derived small intestinal submucosa (SIS). These findings show the biologic potential of RA pM-ECM as a scaffold for supporting site appropriate, tissue reconstruction, and provide a better understanding of the importance maintaining the tissue-specific complex three-dimensional architecture of ECM during decellularization and regeneration.

Coverage of different health insurance programs and medical costs associated with chronic hepatitis C infection in mainland China: a cross-sectional survey in 20 provinces.

BACKGROUND: Hepatitis C virus (HCV) imposes a considerable disease burden in China, with at least 10 million people chronically infected. Little is known about the financial impact of the HCV epidemic, nor about the extent to which various forms of insurance are providing HCV patients with financial protection. A cross-sectional multi-site study was conducted to acquire data that will aid policy-makers and other stakeholders in developing effective strategies to address this situation. METHODS: At 29 hospitals across China, inpatients and outpatients with chronic HCV were surveyed about their insurance coverage and medical costs. Percentages, means and medians were calculated, and differences in continuous variables among multiple groups were analyzed using the Kruskal-Wallis test or Wilcoxon two-sample test. RESULTS: Many inpatients (N = 593) and outpatients (N = 523) reported being covered by one of three major types of government health insurance, but 13 % of inpatients and 43 % of outpatients reported having no insurance. Among inpatients, the total median cost per hospitalization per patient was 8212 Renminbi (RMB). The category of expenditure with the highest median cost per hospitalization was Western medicine, followed by lab tests and Chinese medicine. The median cost per hospitalization was far higher for patients who had hepatocellular carcinoma than for those with less severe forms of liver disease. Outpatient antiviral therapy costs ranged from a median of 377 RMB for ribavirin to a median of 37,400 RMB for pegylated interferon-alpha for up to one year of treatment. CONCLUSIONS: For uninsured chronic HCV patients in China, inpatient and outpatient costs may be financially devastating. Research is needed on how different approaches to financing HCV treatment and care might improve health outcomes as well as achieve cost savings by enabling more people to be cured of HCV.

Effect of autologous platelet-rich plasma on the chondrogenic differentiation of rabbit adipose-derived stem cells in vitro.

This study aimed to isolate rabbit adipose-derived stem cells (ADSCs) and explore the potential of platelet-rich plasma (PRP) in the chondrogenic differentiation of ADSCs, thereby potentially providing a new approach for the repair and regeneration of cartilage injury. Rabbit ADSCs were isolated and characterized by induction towards adipogenic, osteogenic and chondrogenic lineages in vitro. The isolated ADSCs were also cultured with or without 10% PRP. Immunofluorescence staining, toluidine blue staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect type II collagen (Col II) and aggrecan (AGC) expression. Col II immunofluorescence staining and toluidine blue staining indicated that following induction by autologous PRP, ADSCs manifested Col II and AGC expression. The expression of Col II and AGC mRNA was significantly upregulated in the PRP-treated cells when compared with that in control cells. Autologous PRP produced by laboratory centrifugation was able to promote the chondrogenic differentiation of rabbit ADSCs in vitro.

Retrograde vs Conventional Dissection Technique in Pancreaticoduodenectomy: A Pilot Study.

IMPORTANCE: A retrograde dissection technique of pancreaticoduodenectomy in a caudocranial direction has been described recently. OBSERVATIONS: Fifteen consecutive patients who underwent retrograde pancreaticoduodenectomy were compared with 15 consecutive patients operated on through a conventional approach. The mean (SD) intraoperative blood loss was 407 (202) mL in the retrograde group compared with 423 (253) mL in the conventional group (P = .84). The mean (SD) operative duration was 255 (57) minutes in the retrograde group compared with 264 (54) minutes in the conventional group (P = .66). The overall morbidity was 7 of 15 patients (47%) in the retrograde group and 6 of 15 (40%) in the conventional group (P > .99). Neither group had a positive resection margin or a perioperative death. CONCLUSIONS AND RELEVANCE: The retrograde dissection technique had no significant difference in perioperative outcomes compared with the conventional dissection technique and could serve as an alternative dissection approach in pancreaticoduodenectomy.

Association of perioperative allogeneic blood transfusions and prognosis of patients with gastric cancer after curative gastrectomy.

BACKGROUND: The relationship between perioperative allogeneic blood transfusions (PABTs) and prognosis in patients with gastric cancer remains controversial. METHODS: Six hundred five consecutive patients with gastric cancer who underwent curative gastrectomy from a single center were enrolled in this retrospective study. Clinical and pathologic variables were prospectively collected. The effect of PABT on the long-term survival of patients with gastric cancer after curative gastrectomy was evaluated by univariate and multivariate analyses. RESULTS: The overall 5-year survival rate was 65.0%. On univariate analyses, PABT had a statistically significant negative impact on 3-year and 5-year survival rates (66.3% vs 80.5% [P = .005] and 38.7% vs 76.4% [P < .001], respectively). However, multivariate analyses revealed that duration of operation (P = .009), tumor size (P = .001), and tumor stage (P < .001), instead of PABT, were independent prognostic factors. CONCLUSIONS: Our study indicates that PABT is not an independent prognostic factor for long-term survival in patients with gastric cancer after curative gastrectomy.

Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45.

OBJECTIVE: Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissues have demonstrated the presence of SP cells, including several gastric cancer cell lines. This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45. METHODS: We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells. RESULTS: This study found that the SP cells had higher clone formation efficiency than major population (MP) cells. Five stemness-related gene expression profiles, including OCT-4, SOX-2, NANOG, CD44, and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2, were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Western blot was used to show the difference of protein expression between SP and MP cells. Both results show that there was significantly higher protein expression in SP cells than in MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells show higher tumorigenesis tendency than MP cells. CONCLUSIONS: These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

[Repair of deep wound on the head due to high-voltage electrical burn].

OBJECTIVE: To explore the methods for repairing deep wound on the head due to high-voltage electrical burn (HEB). METHODS: Twenty-six patients with deep wounds on the head due to HEB were hospitalized from June 2002 to May 2012. They were all injured by high-voltage (voltage ranged from 380 V to 300 kV) electric current, involving head and several other parts over the body. The total burn area ranged from 1% to 75% TBSA, and the depth ranged from deep partial-thickness to full-thickness (including muscle or even bone). Scalp defect area ranged from 3 cm×2 cm to 20 cm×18 cm, and the maximum size of skull exposure was 12 cm×9 cm and the maximum size of skull defect was 7 cm×6 cm. The wounds of 26 patients were repaired with 7 local advance flaps, 4 bilateral rotation flaps, 18 local rotation flaps combined with thin split-thickness skin grafts in donor site, and 3 free anterolateral thigh flaps with vascular anastomosis. In four of the 26 patients, expander was used in the early stage after burn and 5 after wound healing (with thin split-thickness grafts). RESULTS: All flaps and skin grafts survived, except for one flap which was complicated by wound infection, and it was healed after dressing and secondary suturing. The implanted expander expanded smoothly. Patients were followed up for 15 days to three years after surgery. Satisfactory results were obtained, and wounds of 15 patients were repaired completely. CONCLUSIONS: Deep wound on the head due to HEB should be repaired with suitable flap combined with skin graft in donor site, and implantation of expander according to the injury area and condition of patient.

Improving the antibacterial property of porcine small intestinal submucosa by nano-silver supplementation: a promising biological material to address the need for contaminated defect repair.

OBJECTIVE: We hypothesize that introduction of nano-silver particles to porcine-derived small intestinal submucosa (NS-PSIS) would lead to significant enhancement in antibacterial property in repairing contaminated abdominal defect. BACKGROUND: Porcine-derived small intestinal submucosa (PSIS) is an acellular and xenogenic biological material intensively used in repairing and regenerating wounded and dysfunctional tissues. Surgical site infection (SSI) remains so far a serious problem and major challenge, particularly in contaminated tissue-deficient repairing. METHODS: Self-assembly was used to fabricate NS-PSIS. The antibacterial property was evaluated in vitro and in vivo by means of repairing full-thickness contaminated abdominal defect in rats. The native PSIS and polypropylene-oxidized regenerated cellulose were served as controls. In addition, changes in biomechanical resistance, morphology and immunohistochemistry for inflammatory reaction and neovasculation in the repaired abdominal wall were analyzed. Biosafety was investigated by pyrogen test, skin irritation test and silver measurement in vivo. RESULTS: NS-PSIS exhibited strong antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa on agar diffusion, with mean diameters of inhibition zone ranging from 11.9 to 23.5 mm. There were significantly lower SSI incidence and a tendency of better abdominal wall resistance in the NS-PSIS group as compared with the PSIS or polypropylene-oxidized regenerated cellulose group after repairing contaminated abdominal defect in rats. Nano-silver modified PSIS did not change the native PSIS property in the tissue recolonization, remodeling and neovascularization. NS-PSIS was not pyrogenic or skin irritated, without silver residual in vivo after repairing contaminated abdominal defect. CONCLUSION: Nano-silver particles to PSIS lead to significant enhancements in antibacterial property in vitro and in vivo without decreasing its biomechanical resistance and biocompatibility. This study provides proof of concept for the use of nano-silver modified naturally derived PSIS as an ideal scaffold for SSI prevention in the contaminated tissue-deficient repair.

[Experience in the treatment of severe pressure sore].

OBJECTIVE: To summarize the experience in the treatment of severe pressure sore. METHODS: From Aug. 2007 to Jun. 2011, 21 cases of severe pressure sore with 43 III-IV degree lesions were treated with combination treatment, including vacuum sealing drainage technique, local fascia flaps, upper or lower gluteus maximus island myocutaneous flaps, lower gluteus maximus myocutaneous flap, neurocutaneous femoris posterior flaps, tensor fascia lata island myocutaneous flaps, free latissimus dorsi myocutaneous flaps, and skin graft, combined with stryker frame and nursing tracking guidance. 13 of 21 cases had multiple pressure sore. Among them, 5 III degree pressure sores were covered by skin grafting and 3 non-caudal III degree pressure sores (< 2 cm in width) were directly closed after debridement. 8 of 21 cases had single IV degree pressure sore. RESULTS: All the 43 wounds healed completely. 5 wounds in 3 cases had effusion under flap which healed after re-drainage. The wounds were not healed in 3 cases with flap transposition which were also healed after re-debridement. All the flaps survived completely. 16 cases were followed up for 2-26 months. Recurrence happened in 4 cases after discharge because of not following the required nursing care. CONCLUSIONS: Comprehensive application of vacuum sealing drainage technique, multiple myocutaneous flaps and skin grafting, combined with stryker frame and nursing tracking guidance after discharge can be used for the treatment of severe pressure sore with satisfactory results.

Characterization of human embryonic stem cell-derived hematopoietic progenitor phenotype.

Differentiation of human embryonic stem cells (hESCs) into hematopoietic lineages using various methods has been reported. However, the phenotype that precisely defines the hematopoietic progenitor compartment with clonogenic activities has yet to be determined. Here, we measured and characterized progenitor function of subfractions of cells prospectively isolated from human embryoid bodies (hEBs) during hematopoietic differentiation basing on surface markers CD45, CD34, CD43, and CD38. We report that hematopoietic progenitors predominantly resided in the CD45(+) subset. CD43(+) cells lacking CD45 expression were largely devoid of progenitor activity. However, progenitor activity and multipotentiality was more enriched in CD45(+) cells co-expressing CD43. CD45(+) subset co-expressing CD34 but lacking CD38 expression (CD45(+)CD34(+)CD38(-)) were further enriched for CFU capacity compared to the CD45(+)CD34(+)CD38(+) subset. Our study demonstrates a role of CD43 in enriching hematopoietic progenitors derived from hEBs and reveals a hierarchical organization of hESC-derived hematopoietic progenitor compartments defined by phenotypic markers.

[Glycyrrhiznatis ameliorates rabbit myocardial ischemia-reperfusion injury through P38MAPK pathway].

OBJECTIVE: To investigate the role of p38MAPK pathway in the protective effect of glycyrrhiznatis against myocardial ischemia-reperfusion in rabbits. METHODS: Thirty rabbits were randomly divided into control group, I/R group, and glycyrrhiznatis group. In the latter two groups, the left anterior descending branch of the coronary artery was ligated for 40 min followed by 120 min of reperfusion, and in glycyrrhiznatis group, glycyrrhiznatis was given intravenously at 2.5 mg/kg before the occlusion. Blood samples were taken to measure the plasma levels of TNF-alpha, IL-6, and IL-8 at 20 min before (T(0)) and 20 min (T(1)) and 40 min (T(2)) after the occlusion, and at 1 h (T(3)) and 2 h (T(4)) after the reperfusion. At the end of the reperfusion, the infarct size and the area at risk were defined by Evams and TTC staining. The heart was harvested and the levels of the p38 MAPK measured by Western blotting. The ultrastructures of the cardiac myocytes were observed under electron microscope. RESULTS: The p38MAPK activity and the plasma levels of the inflammatory factors were significantly lower in gtycyrrhiznatis group than in I/R group (P<0.05). Glycgrrhiznatis significantly reduced the infarct size as compared with that in I/R group. CONCLUSIONS: lycyrrhiznatis can reduce myocardial ischemia-reperfusion injury by inhibiting p38MAPK activity and modulating the cytokine expression.

[Repair of high-voltage electric burn in jaw and neck region with insular pectoralis major myocutaneous flap].

OBJECTIVE: To evaluate the effect of insular pectoralis major myocutaneous flap on repair of jaw and neck tissue defect as a result of high-voltage electric burn. METHODS: Eighteen patients with large area tissue defect in jaw and neck caused by high-voltage electric burn hospitalized from August 2001 to December 2007 were repaired with insular pectoralis major myocutaneous flap. The flaps (from 12 cm x 10 cm to 16 cm x 13 cm) was transplanted in 8 patients after early wound debridement, and in 10 patients on infected wounds. RESULTS: All flaps survived wells except in 4 patients necrotic area (length 2-5 cm, width 1-2 cm) appeared in the distal wound edge, localized dehiscence of wound edge in 2 cases, which were healed after dressing change or secondary suturing. Patients were followed up from 6 months to 3 years, and the appearance and function were satisfactory. CONCLUSIONS: Pectoralis major muscle island myocutaneous flap has the advantage of large tissue mass, with thin and flat muscle belly, and rich blood supply, which is suitable for repair of large deep tissue defect in jaw and neck.