Prognostic Value of an Immune Long Non-Coding RNA Signature in Liver Hepatocellular Carcinoma.

In recent years, there has been a growing recognition of the important role that long non-coding RNAs (lncRNAs) play in the immunological process of hepatocellular carcinoma (LIHC). An increasing number of studies have shown that certain lncRNAs hold great potential as viable options for diagnosis and treatment in clinical practice. The primary objective of our investigation was to devise an immune lncRNA profile to explore the significance of immune-associated lncRNAs in the accurate diagnosis and prognosis of LIHC. Gene expression profiles of LIHC samples obtained from TCGA database were screened for immune-related genes. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate Cox analysis. Then, the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were performed to evaluate the capability of the immune lncRNA signature as a prognostic indicator. Six long non-coding RNAs were identified via correlation analysis and Cox regression analysis considering their interactions with immune genes. Subsequently, tumor samples were categorized into two distinct risk groups based on different clinical outcomes. Stratification analysis indicated that the prognostic ability of this signature acted as an independent factor. The Kaplan-Meier method was employed to conduct survival analysis, results showed a significant difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Additionally, data obtained from gene set enrichment analysis (GSEA) revealed several potential biological processes in which these biomarkers may be involved. To summarize, this study demonstrated that this six-lncRNA signature could be identified as a potential factor that can independently predict the prognosis of LIHC patients.

Identification of a novel 5-methylcytosine-related signature for prognostic prediction of kidney renal papillary cell carcinoma and a Putative target for drug repurposing.

BACKGROUND: Many studies have demonstrated the crucial roles of 5-methylcytosine (m5C) RNA methylation in cancer pathogenesis. METHODS: Two datasets, including TCGA-KIRP and ICGC, and related clinical information were downloaded, where the expression of 13 m5C regulators was examined. We applied LASSO regression to construct a multi-m5C-regulator-based signature in the TCGA cohort, which was further validated using the ICGC cohort. Univariate and multivariate Cox regressions were applied to evaluate the independent prognostic value of our model. The differences in biological functions and immune characterizations between high and low-risk groups divided based on the risk scores were also investigated via multiple approaches, such as enrichment analyses, mutation mining, and immune scoring. Finally, the sensitivities of commonly used targeted drugs were tested, and the connectivity MAP (cMAP) was utilized to screen potentially effective molecules for patients in the high-risk group. Experimental validation was done following qPCR tests in Caki-2 and HK-2 cell lines. RESULTS: 3 m5C regulators, including ALYREF, DNMT3B and YBX1, were involved in our model. Survival analysis revealed a worse prognosis for patients in the high-risk group. Cox regression results indicated our model's superior predictive performance compared to single-factor prognostic evaluation. Functional enrichment analyses indicated a higher mutation frequency and poorer tumor microenvironment of patients in the high-risk group. qPCR-based results revealed that ALYREF, DNMT3B, and YBX1 were significantly up-regulated in Caki-2 cell lines compared with HK-2 cell lines. Molecules like BRD-K72451865, Levosimendan, and BRD-K03515135 were advised by cMAP for patients in the high-risk group. CONCLUSION: Our study presented a novel predictive model for KIRP prognosis. Furthermore, the results of our analysis provide new insights for investigating m5C events in KIRP pathogenesis.

LncRNA LUCAT1 as a Plasma Biomarker for Assessing Disease Activity in Adult Patients with Crohn's Disease.

AIM: To explore the expression of long noncoding RNA (LncRNA) LUCAT1 in adult patients with Crohn's disease (CD) and evaluate the relationship between LncRNA LUCAT1 and the disease activity in Chinese patients with CD. METHODS: Patients with CD and healthy participants (≥18 years old) were enrolled in this study between January 2018 and December 2019. The expression of LncRNA LUCAT1 in plasma samples was evaluated by quantitative reverse transcription-polymerase chain reaction. Basic characteristics of patients with CD were collected, including gender, age, clinical stage, disease behavior, disease location, C-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) score, and simplified Crohn's disease endoscopic score (SES-CD). RESULTS: In total, 168 patients with CD and 65 healthy participants (≥18 years old) were enrolled in this study. Among them, ninety patients with clinically active CD, seventy-eight patients with CD in clinical remission, forty-eight patients with endoscopically active CD, thirty patients with endoscopically inactive CD, and sixty-five healthy participants. LncRNA LUCAT1 was increased in plasma of patients with CD compared with the control group. The plasma LncRNA LUCAT1 level of patients with CD both in the clinical and endoscopic active phase was higher than that of both the clinical and endoscopic remission phase. The plasma level of LncRNA LUCAT1 in patients with CD was positively correlated with ESR, CRP, FC, CDAI, and SES-CD. There was no significant correlation between the level of LUCAT1 and platelets. The plasma LncRNA LUCAT1 level in patients with CD had significant differences between severe active patients and mild/moderate active patients. CONCLUSION: The plasma LncRNA LUCAT1 is positively associated with the disease activity in patients with CD, and it may act as a noninvasive biomarker to identify the degree of disease activity.

Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation.

Parkinson's disease (PD) is a neurodegenerative disorder and 70-80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

RTA-408 protects against propofol-induced cognitive impairment in neonatal mice via the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.

OBJECTIVE: To explore the effect of RTA-408 on the propofol-induced cognitive impairment of neonatal mice via regulating Nrf2 and NF-κB p65 nuclear translocation. METHODS: C57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA-408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT-PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits. RESULTS: Propofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA-408 treatment improved the above-mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF-κB p65 nuclear translocation, which was reversed by RTA-408. Meanwhile, RTA-408 decreased the apoptosis of neurons accompanying with the down-regulation of Caspase-3 and the up-regulations of neuronal-specific nuclear protein (NeuN), microtubule-associated protein 2 (Map2), Ca2+ /Calmodulin-dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol-induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA-408. CONCLUSION: RTA-408 improved propofol-induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.

[Carbon and nitrogen stable isotopes technology in the researches on alpine meadow ecosystem in Qinghai-Tibet Plateau: Progress and prospect]. / ç¢³æ°®ç¨³å®šåŒä½ç´ æŠ€æœ¯åœ¨é’è—é«˜åŽŸé«˜å¯’è‰ç”¸ç”Ÿæ€ç³»ç»Ÿç ”ç©¶ä¸­çš„åº”ç”¨: 进展与展望.

Carbon and nitrogen stable isotopic technique has been widely used in research of glassland ecosystems. Here, we summarized studies using carbon and nitrogen stable isotopes in the alpine meadow ecosystem on the Qinghai-Tibet Plateau. Firstly, we reviewed the environmental factors which influenced carbon and nitrogen isotope composition (δ13C and δ15N) of plants and soils in alpine meadow, such as altitude, moisture, fertilization, grassland degradation, and temperature. The values of plant δ13C were positively correlated with altitude, and negatively correlated with atmospheric pressure, grassland degradation and temperature. The relationship between plant δ13C and precipitation was non-linear. The values of soil δ13C were positively correlated with altitude and grassland degradation. The values of plant δ15N were positively correlated with soil moisture and fertilization, and negatively correlated with grassland degradation. Secondly, we reviewed the current application and progresses of 13C and 15N in the identification of plant photosynthetic type, water use, nutrient transport along food chain and carbon and nitrogen cycle in the alpine meadow. Finally, we prospected the 13C and 15N isotopes application in researches on soil organic carbon and soil respiration in the alpine meadow, transitions of vegetation type, and climate change, soil N2O trace, exploration of vegetation degradation, identification of the origin of Tibetan medicine and animal food, etc. 13C and 15N isotopes could be widely used and play important roles in researches on the alpine ecosystems.

Evaluation of three pumpkin species: correlation with physicochemical, antioxidant properties and classification using SPME-GC-MS and E-nose methods.

To ascertain the most discriminant variables for three pumpkin species principal component analysis (PCA) was performed. Twenty-four parameters (pH, conductivity, sucrose, glucose, total soluble solids, L*, a*, b*, individual weight, edible rate, firmness, citric acid, fumaric acid, l-ascorbic acid, malic acid, PPO activity, POD activity, total flavonoids, vitamin E, total phenolics, DPPH, FRAP, ß-carotene, and aroma) were considered. The studied pumpkin species were Cucurbita maxima, Cucurbita moschata, and Cucurbita pepo. Three pumpkin species were classified by PCA based on aroma, physicochemical and antioxidant properties because the sum of PC1 and PC2 were both greater than 85% (85.06 and 93.64% respectively). Results were validated by the PCA and showed that PPO activity, total flavonoid, sucrose, glucose, TSS, a*, pH, malic acid, vitamin E, DPPH, FRAP and ß-carotene, and aroma are highly useful parameters to classify pumpkin species.

A novel non­contact communication between human keratinocytes and T cells: Exosomes derived from keratinocytes support superantigen­induced proliferation of resting T cells.

It is widely accepted that keratinocytes act as non­professional antigen­presenting cells and support superantigen­induced proliferation of resting T cells; however, it remains unknown whether keratinocytes function in situ with T cells via a non­contact mechanism. The current study used a transwell co­culture system and demonstrated, for the first time to the best of the authors' knowledge, that HaCaT cells (the human keratinocyte cell line) did induce T cell proliferation via indirect contact. The data further indicated that exosomes, small membrane vesicles that transfer antigens to recipient cells, are also involved in the superantigen­associated immunity of keratinocytes. The current study provided experimental evidence that HaCaT­exosomes contained MHC I and II, and could interact with T cells. In addition, following interferon γ stimulation, Staphylococcal aureus enterotoxin B­loaded HaCaT cells secreted exosomes to induce the proliferation of CD4+ and CD8+ T cells in vitro. This novel biological function of exosomes reveals a new mechanism of how keratinocytes participate in bacterial superantigen­induced immune responses.

Propofol Suppresses Esophageal Squamous Cell Carcinoma Cell Migration and Invasion by Down-Regulation of Sex-Determining Region Y-box 4 (SOX4).

BACKGROUND This study was done to verify whether propofol could inhibit esophageal squamous cell carcinoma (ESCC) cell line EC9706 cell migration and invasion by targeting SOX4. MATERIAL AND METHODS Different concentrations of propofol were co-incubated with EC9706 cells. The pcDNA-SOX4 or SOX4 siRNA plasmid was transfected into cells before the treatment with propofol 5 µg/L. The migratory and invasion ability of EC9706 cells were tested by wound-healing assay and Transwell chambers. Western blotting was used to investigate the expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, and SOX4. Gelatin zymography was employed to detect the activity of MMP2 and MMP-9. RESULTS Compared with the control, the migration and invasion activity of EC9706 cells were decreased after incubation with different concentrations of propofol (P<0.01). The expression of MMP-2, MMP-9, and SOX4 was decreased and that of TIMP-1 was increased in the propofol-treated EC9706 cells (P<0.01). Down-regulation of SOX4 by SOX4-siRNA had the same effect as propofol on EC9706 cells, including suppressing cell migration and invasion, inhibiting the expression and activity of MMP-2/9, and increasing the expression TIMP-1. Over-expression of SOX4 could partly abrogated propofol-mediated inhibition of EC9706 cell migration and invasion. CONCLUSIONS Propofol inhibits EC9706 cell migration and invasion by down-regulation of SOX4.

Optimized microwave-assisted extraction of 6-gingerol from Zingiber officinale Roscoeand evaluation of antioxidant activity in vitro.

BACKGROUND: 6-Gingerol is one of the most pharmacologically active and abundant components in ginger, which has a wide array of biochemical and pharmacologic activities. In recent years, the application of microwave-assisted extraction (MAE) for obtaining bioactive compounds from plant materials has shown tremendous research interest and potential. In this study, an efficient microwave-assisted extraction (MAE) technique was developed to extract 6-gingerol from ginger. The extraction efficiency of MAE was also compared with conventional extraction techniques. MATERIAL AND METHODS: Fresh gingers (Zingiber officinale Rose.) were harvested at commercial maturity (originally from Shandong, laiwu, China). In single-factor experiments for the recovery of 6-gingerol, proper ranges of ratio of liquid to solid, ethanol proportion, microwave power, extraction time were determined. Based on the values obtained in single-factor experiments, a Box-Behnken design (BBD) was applied to determine the best combination of extraction variables on the yield of 6-gingerol. RESULTS: The optimum extraction conditions were as follows: microwave power 528 W, ratio of liquid to solid 26 mL·g(-1), extraction time 31 s and ethanol proportion 78%. Furthermore, more 6-gingerol and total polyphenols contents were extracted by MAE than conventional methods including Maceration (MAC), Stirring Extraction (SE), Heat reflux extraction (HRE), Ultrasound-assisted extraction (UAE), as well as the antioxidant capacity. CONCLUSION: Microwave-assisted extraction showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract within shortest extraction time. Scanning electron microscopy (SEM) images of ginger powder materials after different extractions were obtained to provide visual evidence of the disruption effect. To our best knowledge, this is the first report about usage of MAE of 6-gingerol extraction from ginger, which could be referenced for the extraction of other active compounds from herbal plants.

Short-term study of infliximab treatment for Crohn's disease in China.

OBJECTIVE: To determine the effectiveness and safety of short-term treatment of infliximab (IFX) in a group of Chinese patients with active Crohn's disease (CD). METHODS: Patients with established diagnosis of active CD were treated with IFX intravenously with a dose of 5 mg/kg at week 0, 2, 6. Clinical assessments were performed at baseline (week 0) and every week after IFX infusion until 8 weeks after the induction dose. RESULTS: Fourteen patients (nine male, five female) with a mean age of 29.7 years (range from 15 to 65 years) were included in the analysis. The mean subjective scores were decreased from 2.85 ± 0.57 at baseline to 1.3 ± 0.4 at week 14 (P < 0.05). The mean Harvey-Bradshaw index was 7.9 ± 1.5 at baseline and 2.3 ± 1.0 at week 14. The levels of erythrocyte sedimentation rate, serum C-reactive protein, total protein (TP) and albumin (ALB) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement. Mild and transient adverse events including skin itching, headache and elevation of serum alanine aminotransferase and aspartate transaminase were each observed in one patient. Severe anemia, leucopenia and thrombocytopenia at week 27 after three infusions of IFX were observed in one patient. CONCLUSIONS: Treatment with three infusions of IFX at a dose of 5 mg/kg was effective for induction of remission for active CD patients who failed to respond to conventional therapies. Study of long-term efficacy and safety of IFX therapy is warranted for further investigations.

[Induction of oral immune tolerance in systemic lupus erythematosus-like murine model by recombinant nucleosomal universal Th cell epitope].

OBJECTIVE: To explore the feasibility of oral immune tolerance of systemic lupus erythematosus (SLE)-like model induced by nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. METHODS: SLE-like murine model was established by immunization with apoptotic syngeneic lymphocytes. The recombinant strains were orally administrated to induce immune tolerance. The levels of serum autoantibodies, such as anti-ANA, ds-DNA, and antinucleosome antibody, leukopenia, proteinuria and kidney injuries were evaluated. RESULTS: SLE-like murine model was successfully established. Compared with controls, it was shown that CTLA4-Ig-H2B group could dramatically reduce the levels of serum autoantibodies, such as anti-ANA, ds-DNA and antinucleosome antibody and ameliorate leukopenia and proteinuria (all P < 0.05). Immune complex deposits of IgG in glomeruli were lower in CTLA4-Ig-H2B (1.35 +/- 0.16) than in CTLA4-Ig (1.66 +/- 0.23) and H2B (1.69 +/- 0.24) (both P < 0.05). The score of glomeruli lesion of CTLA4-Ig-H2B (1.26 +/- 0.14) was significantly lower than those of CTLA4-Ig (1.73 +/- 0.25) and H2B (1.71 +/- 0.20) (both P < 0.05). CONCLUSION: Combined with CTLA4-Ig, it is feasible to induce oral immune tolerance of SLE models with nucleosomal Th cell epitope via the attenuated Salmonella typhimurium. This may provide a novel way to prevent and treat SLE by oral immune tolerance.

[A study of efficiacy of infliximab treatment for Crohn's disease.].

OBJECTIVE: To investigated the potential and safety of the monoclonal antibody to TNFalpha infliximab (IFX) in the treatment of active Crohn's disease (CD). METHODS: Patients who were confirmed diagnosis of CD and were unresponsive to the conventional treatments, or recurred after surgeries, or discontinued treatment due to drug intolerance, were treated with IFX intravenously in a dose of 5 mg/kg at week 0, 2, 6 (IFX infusion continued at an interval of every 8 weeks if respond to initial dosing). Clinical assessments, including disease activity, blood biological markers and colonoscopic findings, were performed at baseline (week 0) and each week (4 weeks or later for colonoscopy) after IFX infusion were conducted until the week before 4(th) infusion from initiated. RESULTS: Ten patients (8 male, 2 female) with mean age of 31.4 years (ranged from 15 to 65 years old) were included in the analysis. The mean subjective score from baseline to week 14 was decreased from 2.2 +/- 0.6 to 1.2 +/- 0.4 (P < 0.05). The mean Harvey-Bradshaw index was 6.6 +/- 1.6 at baseline and 2.1 +/- 1.0 at week 14. The levels of ESR, CRP, serum total protein (TP) and albumin (Alb) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement of Crohn's Disease Endoscopic Index of Severity (CDEIS). No infusion-related reaction was observed in all patients during the treatment. Mild or transient skin itching and headache were respectively reported in two patients. Transient elevation of serum ALT and AST after 3(rd) infusion in one patient, and severe anemia including leucopenia and thrombocytopenia at week 35 after 1(st) infusion in one male patient were observed. CONCLUSIONS: Treatment with three infusions of IFX in a dose of 5 mg/kg was effective for induction of remission for active and complex CD patients who failed to respond to conventional treatment. Long-term safety of the therapy effect was warranted in further investigations.

[Effects of HS1-associated protein X-1 on the lupus activities: experiment with MRL/lpr lupus-like mice].

OBJECTIVE: To investigate the effects of HS1-associated protein X-1 (HAX-1) on the lupus activity of MRL/lpr lupus-like mice. METHODS: Fifteen MRL/lpr mice were divided into 3 equal groups: Group A, injected with phosphate-buffered saline, Group B, injected intraperitoneally with control virus AdEGFP and Group C, injected intraperitoneally with recombinant AdHAX-1 twice a week for 4 weeks. Peripheral blood samples were collected before the injection, and 2 and 4 weeks after the injection to be detected the white blood cell count, antinuclear antibody (ANA), anti-double strand-DNA antibodies, circulating immune complex (CIC), anti-histone antibodies, and interferon (IFN)-gamma. The level of urine protein was measured, too. Then the mice were killed, a kidney underwent direct immunofluorescence (DIF) to observe the deposition of Immune complexes, and the other kidney underwent periodic acid-Schiff (PAS) staining and pathological examination. MTT method was used to detect the proliferation of the lymphocytes in the spleen. Splenocytes were isolated from the other 15 MRL/lpr mice and then divided into 4 groups: Group, transfected with DMRIE-C without plasmid; Group E, as negative control group; Group F, transfected with blank plasmid pGenesil-1; and Group G, transfected with pGenesil-HAX-1. Forty-eight hours later MTT method was used to detect the proliferation rateof the spleen lymphocytes. RESULTS: The urine protein level of Group C was significantly higher than those of Groups A and B (both P < 0.01). Four weeks later the levels of ANA, anti-double strand DNA antibodies, and IFN-gamma were all significantly higher than those of Groups A and B (all P < 0.01). Hypercellularity and increased deposition of IgG in glomeruli were also observed in Group C. The score of glomeruli lesion of Group C (1.50 +/- 0.34) was significantly higher than those of Groups A (0.67 +/- 0.14) and Groups B (0.81 +/- 0.26) (both P < 0.01). MTT method showed that the growth curve of the spleen lymphocytes of Group C was higher than those of Groups A and B. The spleen lymphocyte proliferation rate and the levels of IFN-gamma of Group G was significantly lower than that of Group F (both P < 0.05). CONCLUSION: One of the important factors in apoptosis regulation of SLE, HAX-1 may be involved in the pathogenesis of SLE, and the silence of HAX-1 may be beneficial for the improvement of SLE.

Efficacy and safety of azathioprine maintenance therapy in a group of Crohn's disease patients in China.

OBJECTIVE: To evaluate the efficacy and the safety of long-term azathioprine maintenance therapy in a group of Chinese patients with Crohn's disease. METHODS: The efficacy of azathioprine (2.0 mg/kg/day) in controlling the disease relapse in 13 patients with Crohn's disease following clinical remission by prednisone or surgery were investigated. The Crohn's disease activity index (CDAI) and the Harvey-Bradshaw index, the reduction of steroid dosage and side-effects for an average of 18 months follow up were analyzed. RESULTS: Azathioprine was effective in controlling the disease relapse in 10 (by CDAI scores) or 11 (by Harvey -Bradshaw index) of 13 patients (76.9% and 84.6%, respectively) for at least 6 months. Azathioprine was not discontinued in a patient who experienced a temporary and mild elevation of aminotransferases 14 months after the initiation of therapy. However one patient who was co-administered with azathioprine and mesalamine (Pentasa) developed an episode of bone marrow suppression that ultimately required the withdrawal of both medications. CONCLUSION: Azathioprine is an effective agent which controls the relapse of Crohn's disease in most patients. Long-term remission can be achieved. Side-effects, including severe leukopenia, myelo-suppression and the mild elevation of hepatic enzymes, may occur in a small number of patients.

Vesicles from Pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery.

The morphologies of poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-F127-PLA) aggregates in aqueous solutions were reported previously to be vesicular nano-particles by our group. In the present study, we seek to investigate the feasibility of using PLA-F127-PLA vesicles as oral delivery carrier for insulin. Both in vitro and in vivo release behavior of insulin loaded in PLA-F127-PLA vesicles were studied. A biphasic release behavior was observed for the in vitro release of insulin from PLAF127-29 vesicles. More importantly, it was found in the diabetic mice tests that the blood glucose concentration of oral insulin-loaded PLAF127-29 vesicles decreased from 18.5 to 5.3 mmol/L within 4.5 h and the minimum blood glucose concentration (about 4.5 mmol/L) was achieved after about 5 h. Furthermore, the blood glucose concentration was maintained at this level for at least an additional 18.5 h. These results proved that PLA-F127-PLA vesicles could be promising polymeric carriers for oral insulin delivery application due to their prolonged hypoglycemic effect.

[Importance of colonoscopy combined with biopsy in the diagnosis of colonic Crohn's disease].

OBJECTIVE: An attempt was made to provide a better insight into endoscopic and histological features and/or problems encountered when establishing a diagnosis of colonic Crohn's disease (Crohn's colitis). METHODS: As presented in our 27 cases with Crohn's colitis, the endoscopic findings and histological changes of biopsy specimens were summarized. As collated with correspondent results of biopsy and surgical specimens, the diagnostic accuracy of endoscopy was evaluated. RESULTS: twenty-six involvements of the large intestine (combined with other sites of the intestine) was found (96.3%). However, involvement limited to the colon alone was seen in only 4 cases (14.8%). Endoscopically, overlapped lesions with multistaged-segmental distributed and multi-sited diverse patterns (destructive and proliferative/regenerative) of inflammatory changes were observed. Endoscopic accuracy was 66.7%. The characteristic features of mucosal biopsy include focal distribution of the lesions, a thickened and edematous submucosa, deep fissuring ulcers, lymphoid aggregate, and hyperplasia, fibrosis and granulomas (detected in 30% of the group), etc. CONCLUSIONS: Colonic involvement of Crohn's disease is common. Colonoscopy may be valuable in establishing the diagnosis and in assessing the extent and severity of colonic involvement, and CDEIS was value in the follow up of patients. Colonoscopic biopsies are helpful for verification of the diagnosis in difficult cases. Colonoscopy has replaced radiology as the initial test of choice in many clinical situations.