[Clinical and endoscopic characteristics of adult celiac disease].

Objective: The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment. Methods: In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed. Results: A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant (P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD (P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions: Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

[Study on the difference of curative effect of conventional mercury displacement treatment on mercury in brain and kidney].

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.

[Determination of platinum anticancer drugs in occupational settings by ICP-MS].

Objective: To establish an inductively coupled plasma mass spectrometry (ICP-MS) for platinum antineoplastic drugs in the environment. Methods: The platinum antineoplastic drugs in the environmental table were eluted by wiping and collecting pure water, and the supernatant was taken by centrifugation and inductively coupled plasma mass spectrometry for detection. Results: The concentration range of 0-8.0 µg/L was good, the correlation coefficient was 1.000, the detection limit was 0.0006 µg/L, the lower quantitative limit was 0.002 µg/L, the method precision was between 0.9%-1.3%, and the sample standard recovery rate was between 97.0%-98.5%. Conclusion: This method has low detection limit, high accuracy and precision, and simple sample pretreatment, which is suitable for the determination of platinum antineoplastic drugs in environmental tables.

Delivery of allergen powder for safe and effective epicutaneous immunotherapy.

BACKGROUND: More effective and safer immunotherapies to manage peanut allergy are in great demand despite extensive investigation of sublingual/oral immunotherapy and epicutaneous immunotherapy (EPIT) currently in the clinics. OBJECTIVE: We sought to develop a powder-laden, dissolvable microneedle array (PLD-MNA) for epidermal delivery of powdered allergens and to evaluate the efficacy of this novel EPIT in peanut-sensitized mice. METHODS: PLD-MNA was packaged with a mixture of powdered peanut allergen (PNA), 1,25-dihydroxyvitamin D3 (VD3), and CpG. Its epidermal delivery and therapeutic efficacy were evaluated alongside PNA-specific forkhead box P3-positive regulatory T cells and IL-10+ and TGF-ß1+ skin-resident macrophages. RESULTS: PLD-MNA was successfully laden with PNA/VD3/CpG powder and capable of epidermal delivery of most of its content 1 hour after application onto intact mouse skin concomitant with no significant leakage into the circulation or skin irritation. PLD-MNA-mediated EPIT substantially reduced clinical allergy scores to 1 from 3.5 in sham control mice (P < .001) after 6 treatments accompanied by lower levels of PNA-specific IgE and intestinal mucosal mast cells and eosinophils over sham treatments. Moreover, in comparison with allergens administered intradermally, powdered allergens delivered by means of PLD-MNA preferentially attracted immunoregulatory macrophages and stimulated the cells to produce IL-10, TGF-ß, or both at the immunization site, which might account for increased numbers of regulatory T-like cells in lymph tissues in association with systemic tolerance. PNA/VD3/CpG-laden PLD-MNA was safe and required only 6 treatments and one fifth of the PNA adjuvant dose, with improved outcomes when compared with 12 conventional intradermal immunotherapies. CONCLUSIONS: PLD-MNA holds great promise as a novel, safe, effective, and self-applicable modality to manage IgE-mediated allergies.

[Proximal incisal edge length and recent clinical observation of Siewert type â ¡ advanced esophagogastric junction adenocarcinoma].

Objective: To investigate the clinical effect of the radical resection with a proximal incisal edge length of 20-25 mm and 30-35 mm in Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma, to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm. Methods: A retrospective cohort study method was used. The clinical data of 166 patients with Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma who underwent total gastrectomy from January 2017 to August 2020 in the Department of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College were retrospectively collected. According to the proximal incisal edge length, the patients were divided into two groups: the proximal incisal edge length of 20-25 mm group (69 cases) and 30-35 mm group (97 cases). The perioperative conditions and the 6-month follow-up after the operation were compared between the two groups. Results: There was no statistically significant difference in baseline information between the patients in the two groups (P>0.05). The operations of both groups were completed. The intraoperative operation time of the proximal incisal edge length of 20-25 mm group was shorter than that in the proximal incisal edge length of 30-35 mm group ((172±24)and(206±27)min, P<0.001). There were no significant differences in the amount of intraoperative blood loss, the treatment of the diaphragm during the operation and the positive rate of intraoperative freezing of the upper incisal edge between the patients in the two groups (all P>0.05). And there was no significant differences in the first exhaust time, gastric tube removal time, first feeding time and hospital stay after the operation of the two groups (all P>0.05). There was no significant differences in the incidence of anastomotic leakage, anastomotic stenosis, reflux esophagitis and intestinal obstruction after the operation between the patients in the two groups (all P>0.05). And there was no anastomotic leakage case among the 69 cases in the proximal incisal edge length of 20-25 mm group. Postoperative pathological treatment showed no significant differences in the vascular tumor thrombus and nerve infiltration between the two groups (both P>0.05). During the 6-month follow-up, there was no death or tumor recurrence in the two groups, and there was no significant difference in body weight loss at 6 months after the operation between the two groups (P=0.178). Conclusion: When radical resection of Siewert type Ⅱ advanced esophagogastric junction adenocarcinoma is performed, it is feasible to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm under the premise of ensuring R0 resection. The operation time is shortened. Due to the shortening the incisal edge distance, the anastomotic tension is decreased, and the incidence of postoperative anastomotic leakage is also reduced.

[Analysis of baseline liver biochemical parameters in 324 cases with novel coronavirus pneumonia in Shanghai area].

Objective: To summarize the clinical characteristics and liver biochemical parameters of 324 cases admitted with novel coronavirus pneumonia in Shanghai area. Methods: Clinical data and baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia admitted to the Shanghai Public Health Clinical Center from January 20, 2020 to February 24, 2020 were retrospectively analyzed. Patients were divided into two groups based on the status of illness: mild type (mild and typical) and severe type (severe and critical).The differences in clinical data and baseline liver biochemical parameters of the two groups were described and compared. The t-test and Wilcoxon rank-sum test were used for measurement data. The enumeration data were expressed by frequency and rate, and chi-square test was used. Results: Of the 324 cases with novel coronavirus pneumonia, 26 were severe cases (8%), with median onset of 5 days, 20 cases were HBsAg positive (6.2%), and 70 cases (21.6%) with fatty liver, diagnosed with X-ray computed tomography. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bilirubin (TBil), albumin(ALB) and international normalized ratio (INR) of 324 cases at baseline were 27.86 ± 20.02 U/L, 29.33 ± 21.02 U/L, 59.93 ± 18.96 U / L, 39.00 ± 54.44 U/L, 9.46 ± 4.58 µmol / L, 40.64 ± 4.13 g / L and 1.02 ± 0.10. Of which, ALT was > than the upper limit of normal (> ULN), accounting for 15.7% (51/324). ALT and AST > ULN, accounting for 10.5% (34/324). ALP > ULN, accounting for 1.2% (4/324). ALP and GGT > ULN, accounting for 0.9% (3/324). INR > ULN was lowest, accounting for 0.6% (2/324). There were no statistically significant differences (P > 0.05) in ALT [(21.5 vs. 26) U / L, P = 0.093], ALP [(57 vs.59) U/L, P = 0.674], and GGT [(24 vs.28) U/L, P = 0.101] between the severe group and the mild group. There were statistically significant differences in AST (23 U/L vs. 34 U/L, P < 0.01), TBil (10.75 vs. 8.05 µmol / L, P < 0.01), ALB (35.79 ± 4.75 vs. 41.07 ± 3.80 g/L, P < 0.01), and INR (1.00 vs. 1.04, P < 0.01). Conclusion: The baseline liver biochemical parameters of 324 cases with novel coronavirus pneumonia in Shanghai area was comparatively lower and the liverinjury degree was mild, and the bile duct cell damage was rare.

[Quality evaluation of different Berberidis Cortex species based on ~1H-NMR metabolomics and anti-diabetic activity].

To evaluate the quality differences of four mainstream species of Berberidis Cortex,~1H-NMR metabolomics was applied to detect its primary and secondary metabolites, and the partial least squares discriminant analysis and analysis of variance were integrated to screen differential metabolites between species. Furthermore, diabetic rat model was established by high fat diet and streptozotocin to assess differences in antidiabetic activities among the four species. Sixteen compounds were simultaneously detected and identified, including alkaloids, organic acids, carbohydrates and amino acids. Interspecific difference markers were revealed as magnoflorine, jateorhi-zine, bufotenidine and saccharose for the first time. Berberis vernae and B. kansuensis presented superior activities on reducing blood glucose level, improving insulin resistance, increasing insulin sensibility and anti-inflammation. B. dictyophylla showed moderate antidiabe-tic effect, while B. diaphana rendered inferior antidiabetic capacity. Based on the contents of four differential markers and the results of antidiabetic activity evaluation, the quality of four Berberidis Cortex species was ranked as B.vernae≈B.kansuensis>B. dictyophylla>B. diaphana. These results provided references for species collation, quality standard establishment and exploitation of Berberidis Cortex. The antidiabetic activities of B. vernae and B. kansuensis as well as their mechanisms of action merit further study in the future.

Engineering the Protein Corona Structure on Gold Nanoclusters Enables Red-Shifted Emissions in the Second Near-infrared Window for Gastrointestinal Imaging.

The application of NIR-II emitters for gastrointestinal (GI) tract imaging remains challenging due to fluorescence quenching in the digestive microenvironment. Herein, we report that red-shifting of the fluorescence emission of Au nanoclusters (AuNCs) into NIR-II region with improved quantum yields (QY) could be achieved by engineering a protein corona structure consisting of a ribonuclease-A (RNase-A) on the particle surfaces. RNase-A-encapsulated AuNCs (RNase-A@AuNCs) displayed emissions at 1050 nm with a 1.9 % QY. Compared to rare earth and silver-based NIR-II emitters, RNase-A@AuNCs had excellent biocompatibility, showing >50-fold higher sensitivity in GI tract, and migrated homogenously during gastrointestinal peristalsis to allow visualization of the detailed structures of the GI tract. RNase-A@AuNCs could successfully examine intestinal tumor mice from healthy mice, indicating a potential utility for early diagnosis of intestinal tumors.

The contribution of oxidative stress to platelet senescence during storage.

BACKGROUND: Platelets for transfusion become senescent and dysfunctional during storage, resulting in a markedly short shelf life (5 days). We hypothesized that oxidative stress might account for this decline. STUDY DESIGN AND METHODS: Human platelets were treated with or without antioxidants before storage, and samples were collected and analyzed at different time points. Platelet senescence was determined by senescence-associated ß-galactosidase assay, and senescence-related platelet qualities were also analyzed. RESULTS: Sign of senescence became evident after Day 3 and continued to increase over time. We also found that chemical induction of platelet activation did not affect senescence level, whereas apoptosis inducers showed a stimulative effect on platelet senescence. Moreover, this effect was not prevented by a pan-caspase inhibitor. Meanwhile, cellular and mitochondrial reactive oxygen species were found elevated during storage, and treatments with antioxidants successfully prevented this increase and also mitigated senescence levels of stored platelets. Finally, resveratrol, a natural antioxidant, was utilized as a novel storage additive to safely extend platelet shelf time. We showed that the addition of resveratrol efficiently postponed platelet senescence and ameliorated platelet storage lesion. CONCLUSIONS: Platelets during storage became senescent and dysfunctional over time, and we found that oxidative stress might account for this decline. The addition of antioxidants effectively postponed senescence and ameliorated platelet storage lesion, which might provide a valuable reference to future platelet storage methodologies.

Oral delivery of Bacillus subtilis spores expressing grass carp reovirus VP4 protein produces protection against grass carp reovirus infection.

Grass carp (Ctenopharyngodon idellus) hemorrhagic disease (GCHD), caused by grass carp reovirus (GCRV), has given rise to an enormous loss in grass carp industry during the past years. Up to date, vaccination remained to be the most effective way to protect grass carp from GCHD. Oral vaccination is of major interest due to its advantages of noninvasive, time-saving, and easily-operated. The introduction of oral vaccination has profound impact on aquaculture industry because of its feasibility of extensive application for fish in various size and age. However, the main challenge in developing oral vaccine is that antigens are easily degraded and are easy to induce tolerance. Bacillus subtilis (B. subtilis) spores would be an ideal oral vaccine delivery system for their robust specialty, gene operability, safety and adjuvant property. VP4 protein is the major outer capsid protein encoded by GCRV segment 6 (S6), which plays an important role in viral invasion and replication. In this study, we used B. subtilis spores as the oral delivery system and successfully constructed the B. subtilis CotC-VP4 recombinant spores (CotC-VP4 spores) to evaluate its protective efficacy in grass carp. Grass carp orally immunized with CotC-VP4 spores showed a survival rate of 57% and the relative percent survival (RPS) of 47% after the viral challenge. Further, the specific IgM levels in serum and the specific IgZ levels in intestinal mucus were significantly higher in the CotC-VP4 group than those in the Naive group. The immune-related genes including three innate immune-related genes (IL-4/13A, IL-4/13B, CSF1R), four adaptive immune-related genes (BAFF, CD4L, MHC-II, CD8), three inflammation-related genes (IL-1ß, TNF-α, TGF-ß) and interferon type I (IFN-I) related signaling pathway genes were significantly up-regulated in the CotC-VP4 group. The study demonstrated that the CotC-VP4 spores produced protection in grass carp against GCRV infection, and triggered both innate and adaptive immunity post oral immunization. This work highlighted that Bacillus subtilis spores were powerful platforms for oral vaccine delivery, and the combination of Bacillus subtilis spores with GCRV VP4 protein was a promising oral vaccine.

γ-Aminobutyric Acid (GABA) Induced in Vitro Differentiation of Rat Pancreatic Ductal Stem Cells into Insulin-Secreting Islet-Like Cell Clusters.

In vitro produced ß-like cells can provide promising cell therapy for curing the epidemic of diabetes. In this context, we aimed to investigate the effects of different concentrations of γ-aminobutyric acid (GABA) on the differentiation of rat pancreatic ductal epithelial-like stem cells (PDESCs) into ß-like cells. The PDESC line cells were cultured in the basal media (DMEM/F12 + 10% FBS + 1% penicillinstreptomycin) supplemented with 0 µM, 5 µM, 50 µM, 500 µM, and 5 mM of GABA for 28 days to induce their differentiation. The differentiated cells were detected by cell morphology, dithizone (DTZ) staining, immunofluorescence staining, real-time polymerase chain reaction (qPCR), and glucose-stimulated insulin secretion (GSIS) assay to validate their identity. At the end of 28 days, compared with the control group, enrichment of induced cells was high among the 5 µM, 50 µM, 500 µM, and 5 mM GABA induction groups. The formation of islet-like cell clusters (ICCs) began at 14 days, and the cell clusters showed a growth trend with the culture time. The induced ICCs were positive for DTZ staining, while the control group showed negative results for DTZ staining and the differentiated cells were also positive for ß-cell-specific markers (Ins1 and Pdx1). GSIS assay of 50 µM induction group cells at 28 days showed significantly higher levels of C-peptide and insulin secretion than the control, 5 µM, 500 µM, and 5 mM GABA-treated groups (P < 0.01). At the same time, the 50 µM induction group cells also showed significantly higher levels of Ins1, Pdx1 and Nkx6.1 mRNA as compared to the 5 µM, 500 µM and 5 mM GABA groups (P < 0.01). Thus, the addition of GABA to the basal medium effectively induced differentiation of adult rat PDESCs into insulin-secreting ß-like cells, and 50 µM was the most effective concentration for the induction.

Analysis of metabolic changes in Trichoderma asperellum TJ01 at different fermentation time-points by LC-QQQ-MS.

Trichoderma spp. are among the most widely recognized biocontrol fungi used to inhibit pathogens and promote plant growth. These functions are related to primary and secondary metabolites. This study investigated the different metabolites in Trichoderma asperellum TJ01 cultured for 24 and 72 h using liquid chromatography with triple-quadrupole mass spectrometry. Compared to the 24 h culture of T. asperellum TJ01, the 72 h culture with amino acid metabolism tended to decrease while sugar and lipid metabolisms tended to increase. Furthermore, the 72 h culture had a higher proportion of upregulated flavonoids, in combination with a higher proportion of downregulated alkaloids, and equal proportions of upregulated and downregulated polyphenols and hormones. This study also identified a few valuable medicinal substances such as trigonelline and 5-hydroxytryptophan in T. asperellum TJ01 fermentation cultures.

[Analysis on CT in diagnosis of lymph node metastasis of thoracic esophageal cancer with minimum diameter greater than 1 cm].

Objectives: To evaluate the diagnostic value of CT for lymph node metastasis of thoracic esophageal carcinoma with a diameter of more than 1 cm, and to find the optimal diagnostic index by comparing relevant CT indexes. Methods: Totally 80 patients with pathologically proved thoracic esophageal cancer with preoperative CT examination revealed lymph node diameter greater than 1 cm admitted at Department of Thoracic Surgery, the First Affiliated Hospital of University of Science and Technology of China from January 2016 to January 2018 were enrolled in this study. There were 70 males and 10 females, aging of (60±14) years (range: 40-85 years). According to the pathological result of lymph nodes, all the patients and lymph nodes were divided into two groups (N+group: 47 patients, 62 lymph nodes; N-group: 33 patients, 39 lymph nodes). The average number of dissected lymph nodes were 21±4 and 101 lymph nodes' diameter were greater than 1 cm. The clinicopathologic factors, postoperative complications, lymph node dissection and relevant CT indexes like the minimum diameter of lymph nodes (Min D), the maximum diameter of lymph node (Max D), lymph node axial ratio(LAR), the enhancement of lymph node (ELN) and the boundary of lymph node (BLN) were compared. The clinicopathological data, lymph node dessection and CT parameters of the two groups were compared by t test, χ(2) test or Wilcoxon rank sum test. Receiver operating characteristic (ROC) curve analysis was used to compare the ability to predict lymph node metastasis between Min D, Max D, LAR, ELN and BLN. Multiple Logistic regression analysis were performed to determine the independent variables for prediction of lymph node metastasis. Results: The difference of tumor segmentation, pN stage, pTNM stage, total number of metastatic lymph nodes, total number of abdominal lymph node metastases, Min D, Max D, ELN and BLN between the two groups were statistically significant. The results of univariate and multivariate analyses showed that gender (OR=0.128, 95%CI: 0.019 to 0.858, P=0.034), pTNM stage (OR=1.514, 95%CI: 1.020 to 2.247, P=0.039), Min D (OR=0.102, 95%CI: 0.010 to 0.995, P=0.050) and LAR (OR=0.195, 95%CI: 0.052 to 0.731, P=0.015) were the independent relative factors. The area under the curve of ROC curve analysis of Min D, Max D, LAR, ELN and BLN were 0.679, 0.666, 0.561, 0.650 and 0.820, respectively. BLN was the best CT index to diagnosis lymph node metastasis, while the accuracy of dignosis of lymph node metastasis of BLN was 97.0%. The Youden index of Min D, Max D and LAR were 1.25 cm, 1.64 cm and 0.77, respectively. Combining the BLN and ELN had a higher diagnostic rate (97.0%) of lymph node metastasis. Conclusions: CT has high diagnostic value for lymph node metastasis in thoracic esophagel cancer when the lymph node diameter is greater than 1 cm. BLN is the best diagnostic index for lymph node metastasis.

EFFECT OF DORSOMEDIAL HYPOTHALAMUS NEUROPEPTIDE Y KNOCKDOWN ON HEPATIC INSULIN SENSITIVITY.

OBJECTIVE: In this study we investigated the effect of dorsomedial hypothalamus (DMH) neuropeptide Y (NPY) knock-down on hepatic insulin sensitivity in high-fat (HF) diet-fed rats. METHODS: Forty-eight Sprague-Dawley rats were randomly assigned to receive bilateral DMH injections of adeno-associated virus AAVshNPY or AAVshCTL and then accessed to regular chow. Five weeks after viral injection, half rats in each group were given access to the HF diet. At 16 weeks, rat livers were collected. Insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) mRNA expression was measured by qRT-PCR. Blood glucose levels were measured by the oxidase method, serum insulin, triglyceride, and TC levels were measured by Elisa. Pathological changes in the liver were assessed by hematoxylin-eosin (HE) staining. AKT, p-AKT, and GSK-3 levels were measured by western blotting. RESULTS: Compared with AAVshCTL-injected rats, AAVshNPY-injected rats showed a significant decrease in blood glucose concentrations; serum insulin, triglyceride, and TC; HOMA-IR; and IRS-1 and PI3K mRNA levels (P<0.05). ISI, GSK-3, and p-AKT levels were significantly increased (P<0.05). HE staining showed that AAVshNPY-injected rats fed the HF diet had mild fatty degeneration. CONCLUSION: These results suggest that DMH NPY knock-down improves hepatic insulin sensitivity in HF diet-fed rats by activating the hepatic PI3K/AKT insulin signalling pathway.

Nanospikes functionalization as a universal strategy to disperse hydrophilic particles in non-polar media.

Dispersion of hydrophilic particles in non-polar media has many important applications yet remains difficult. Surfactant or amphiphilic functionalization was conventionally applied to disperse particles but is highly dependent on the particle/solvent system and may induce unfavorable effects and impact particle hydrophilic nature. Recently 2 µm size polystyrene microbeads coated with ZnO nanospikes have been reported to display anomalous dispersity in phobic media without using surfactant or amphiphilic functionalization. However, due to the lack of understanding whether this phenomenon was applicable to a wider range of conditions, little application has been derived from it. Here the anomalous dispersity phenomenons of hydrophilic microparticles covered with nanospikes were systematically assessed at various conditions including different particle sizes, material compositions, particle morphologies, solvent hydrophobicities, and surface polar groups. Microparticles were functionalized with nanospikes through hydrothermal route, followed by dispersity test in hydrophobic media. The results suggest nanospikes consistently prevent particle aggregation in various particle or solvent conditions, indicating the universal applicability of the anomalous dispersion phenomenons. This work provides insight on the anomalous dispersity of hydrophilic particles in various systems and offers potential application to use this method for surfactant-free dispersions.

Effective and lesion-free cutaneous influenza vaccination.

The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other "danger" signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies.

A clinical review of phototherapy for psoriasis.

Psoriasis is an autoimmune inflammatory skin disease. In the past several decades, phototherapy has been widely used to treat stable psoriatic lesions, including trunk, scalp, arms and legs, and partial nail psoriasis. A variety of light/lasers with different mechanisms of action have been developed for psoriasis including ultraviolet B (UVB), psoralen ultraviolet A (PUVA), pulsed dye laser (PDL), photodynamic therapy (PDT), intense pulsed light (IPL), light-emitting diodes (LED), and so on. Because light/laser each has specific therapeutic and adverse effects, it is important to adequately choose the sources and parameters in management of psoriasis with different pathogenic sites, severities, and duration of the disorder. This review aims at providing most updated clinic information to physicians about how to select light/laser sources and individual therapeutic regimens. To date, UV light is primarily for stable plaque psoriasis and PDL for topical psoriatic lesions with small area, both of which are safe and effective. On the other hand, PUVA has better curative effects than UVB for managing refractory psoriasis plaques, if its side effects can be better controlled. PDL provides optimal outcomes on nail psoriasis compared with other lasers. Although the trails of low-level light/laser therapy (LLLT) are still small, the near infrared (NIR) and visible red light with low energy show promise for treating psoriasis due to its strong penetration and encouraging photobiomodulation. IPL is rarely reported for psoriasis treatment, but PDT-IPL has been found to offer a moderate effect on nail psoriasis. In brief, various phototherapies have been used either in different combinations or as monotherapy. The modality has become a mainstay in the treatment of mild-to-moderate psoriasis without systemic adverse events in today's clinical practice.

[The impact of genetic variation of KDR on clinical outcomes of advanced colorectal cancer patients treated by first line bevacizumab based regimens].

Objective: To investigate the association between kinase insertion region receptor (KDR) gene genetic variation and the efficacy of bevacizumab in patients with advanced colorectal cancer(CRC) were investigated in this study. Methods: 118 patients with advanced colorectal cancer who were treated by bevacizumab based first line regimens were included in this study. Peripheral blood and the biopsy tissue specimens of the CRC patients were collected for the genotyping of genetic variation and KDR gene expression, respectively. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate were adjusted by Cox regression analysis. Results: Located in the coding region, the prevalence of 889 C>T in KDR among the study population were as follows: CC genotype 86 cases (72.88%), CT genotype 30 cases (25.42%), TT genotype 2 cases (1.70%), minor allele frequency of 889 C>T is 0.14. The distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium (P=0.737). There were no statistical differences in the distribution of the genotypes in baseline clinical data. TT and CT genotype patients were merged in the comparison of clinical outcomes. The clinical outcomes analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes were 34.38% and 43.02% (P=0.395), respectively. And the median progression free survival (PFS) of patients with CT/TT genotype and CC genotype were 7.5 and 9.7 months respectively, which was statistically significant (P=0.009). In terms of overall survival (OS), the median OS of the two genotypes were 19.3 and 20.1 (P=0.025), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (OR=1.88, P=0.023). Additionally, of the 57 biopsy tissue specimens, gene expression analysis was conducted. And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.001). Conclusion: Among advanced colorectal cancer patients treated by bevacizumab, the polymorphism 889 C>T of KDR may impact the clinical outcomes of bevacizumab first line treatment by influencing the mRNA expression of KDR.

[A comparative study of the short-term efficacy and long-term efficacy of systematic lymph node dissection and elective lymph node dissection in patients with early esophageal cancer].

Objective: To investigate the feasibility, safety, short-term efficacy and long-term efficacy of elective lymph node dissection in patients with early esophageal cancer. Methods: The study retrospectively evaluated 405 patients with cT1N0M0 esophageal carcinoma who received minimally invasive esophagectomy in the First Affiliated Hospital of University of Science and Technology of China between March 2007 and March 2013. Of those patients, 208 patients underwent systematic lymph node dissection (SLND) and 197 patients underwent elective lymph node dissection (ELND). The clinicopathologic factors, operational factors, postoperative complications, lymph node dissection and prognosis of patients were compared by independent sample t test, χ(2) test, or Mann-Whitney rank test. The 5-year overall survival was calculated by the Kaplan-Meier estimation method using the Log-rank test. Results: There was no significant difference in clinicopathological data between the SLND group and the ELND group. The incidence of pulmonary infection (8.2% vs. 2.9%, P=0.04) and arrhythmia (6.2% vs. 2.0%, P=0.03) of the minor postoperative complications in the SLND group were higher than the ELND group. The incidence of pulmonary infection (6.2% vs. 2.0%, P=0.03), Chylothorax (5.8% vs.1.5%, P=0.02), anastomotic or pleural hemorrhage requiring reoperation (2.9% vs.0.5%, P=0.04) of major postoperative complications in the SLND group were higher than the ELND group, the difference was statistically significant. In the perioperative data of two groups, the incidence of total postoperative complications, total pulmonary complications, operation time, intraoperative blood loss, postoperative hospitalization, postoperative thoracic drainage duration and postoperative thoracic drainage fluid volume of the SLND group were higher than the ELND group, the difference was statistically significant. The mean numbers and stations of dissected lymph node in the SLND were 30.2±4.2 and 12.1±2.7, the mean numbers and stations of dissected lymph node in the ELND were 25.7±3.8 and 8.4±3.6. The survival rates of 1, 3, 5 years of all patients were 100%, 95.9% and 82.5%, respectively. The median survival time was 87.4 months. Further analysis showed that the 1, 3 and 5 years survival rate of patients with stage Ⅰ esophageal cancer was 100%, 97.1% and 88.9%, respectively. The median survival time was 89.3 months. The 1, 3 and 5 years survival rate of patients with stage Ⅱa esophageal cancer was 100%, 93.2% and 76.8%, respectively. The median survival time was 77.2 months. There was no significant difference in survival rate between the SLND group and the ELND group in 1, 3 and 5 years. When taking a further analysis of stage Ⅰ esophageal cancer, the survival rates between 188 patients in the SLND group and 180 patients in the ELND group were no significant difference. When focus on the stage Ⅱa esophageal cancer, the 1, 3 and 5 years survival rate were higher in the SLND group than that in the ELND group (100%, 94.5%, 83.2% vs. 100%, 91.3%, 72.1%, P=0.047), the difference was statistically significant. Conclusion: ELND can be safely and effectively performed for early esophageal cancer with favorable short-term efficacy and long-term efficacy.

Genetic Polymorphisms and Mutations of 30 Y-STR Loci in Chinese Han Population.

OBJECTIVES: To investigate the genetic polymorphisms and mutations of 30 Y-STR loci in Chinese Han males and to evaluate its forensic application. METHODS: The DNA extracted from blood samples of 1 005 unrelated males and 1 008 father-son pairs （1 949 individuals in all） in Chinese Han population were typed using developed 30 Y-STR loci identification system. The parameters of population genetics and the mutation rates of each locus were analysed statistically. RESULTS: A total of 983 haplotypes were found in 1 005 unrelated males from Chinese Han population, of which 963 were unique. The overall haplotype diversity （HD） and discrimination capacity （DC） were 0.999 955 and 0.978 109, respectively. Totally 340 alleles were detected on 30 Y-STR loci, the value of gene diversity （GD） ranged from 0.410 3 to 0.952 3. The GD values of 24 out of the 30 loci were over 0.6. There were 30 269 allele transfers in 1 008 father-son pairs, one mutation in 68 father-son pairs, and the mutation of three father-son pairs occurred at two loci. On 26 Y-STR loci, 74 mutations were detected in 71 father-son pairs. The average mutation rates were 2.4×10⁻³ （95% CI： 1.9×10⁻³-3.1×10⁻³ï¼‰. Seventy-three mutation events were one-step mutation （98.6%）, 1 mutation event was two-step mutation （1.4%）. CONCLUSIONS: The multiplex PCR system with 30 Y-STR loci has high genetic polymorphism and low mutation rates in Chinese Han males. Therefore, the system shows important values in Y-STR database construction and population genetic research.