Arbuscular Mycorrhizal Fungi-Mediated Modulation of Physiological, Biochemical, and Secondary Metabolite Responses in Hemp (Cannabis sativa L.) under Salt and Drought Stress.

The increasing impact of global climate change has resulted in adversity stresses, like salt and drought, gradually becoming the main factors that limit crop growth. Hemp, which contains numerous medicinal active components and multiple bioactive functions, is widely used in the agricultural, industrial, and medical fields, hence promoting the rapid development of related industries. Arbuscular mycorrhizal fungi (AMF) can establish a symbiotic relationship with 80% of vascular plants. This symbiosis promotes host plant growth, regulates plant physiology and biochemistry, facilitates secondary metabolite synthesis, and enhances resistance to abiotic stresses. However, the effects of salt stress, drought stress, and AMF interaction in hemp are not well understood. In this study, to investigate this, we performed a study where we cultured hemp that was either inoculated or uninoculated with Funneliformis mosseae and determined changes in effective colonization rate, growth, soluble substances, photosynthesis, fluorescence, ions, and secondary metabolites by cultivating hemp under different concentrations of NaCl (0 mM, 100 mM, and 200 mM) and different soil moisture content (45%, 25%, and 15%). The results showed that salt, drought stress, or salt-drought interaction stress all inhibited colonization rate after stress, plant growth, mainly due to ion toxicity and oxidative damage. Inoculation with F. mosseae effectively alleviated plant growth inhibition under 100 mM NaCl salt stress, drought stress, and salt-drought interaction stress conditions. It also improved osmoregulation, photosynthetic properties, fluorescence properties, and ion homeostasis, and promoted the accumulation of secondary metabolites. However, under 200 mM NaCl salt stress conditions, inoculation with F. mosseae negatively affected plant physiology, biochemistry, and secondary metabolite synthesis, although it did alleviate growth inhibition. The results demonstrate that there are different effects of salt-drought interaction stress versus single stress (salt or drought stress) on plant growth physiology. In addition, we provide new insights about the positive effects of AMF on host plants under such stress conditions and the effects of AMF on plants under high salt stress.

Bioactive mesoporous silica nanoparticle-functionalized titanium implants with controllable antimicrobial peptide release potentiate the regulation of inflammation and osseointegration.

Bacterial infection and delayed osseointegration are two major challenges for titanium-based orthopedic implants. In the present study, we developed a functionalized titanium implant Ti-M@A by immobilizing antimicrobial peptide (AMP) HHC36-loaded diselenide-bridged mesoporous silica nanoparticles (MSNs) on the surface, which showed good long-term and mechanical stability. The functionalized implants can realize the sustained release of AMP over 30 days and exhibit over 95.71 % antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and MRSA), which arose from the capability to destroy the bacterial membranes. Moreover, Ti-M@A can efficiently inhibit the biofilm formation of the bacteria. The functionalized implants can also significantly promote the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) because of the Se in MSNs. Notably, it can trigger macrophages toward M2 polarization in vitro by scavenging ROS in LPS-activated macrophages. Consequently, in vivo assays with infection and non-infection bone defect models demonstrated that such bioactive implants can not only kill over 98.82 % of S. aureus, but also promote osseointegration. Hence, this study provides a combined strategy to resolve bacterial infection and delayed osseointegration for titanium implants.

Marriage of High-Throughput Gradient Surface Generation With Statistical Learning for the Rational Design of Functionalized Biomaterials.

Functional biomaterial is already an important aspect in modern therapeutics; yet, the design of novel multi-functional biomaterial is still a challenging task nowadays. When several biofunctional components are present, the complexity that arises from their combinations and interactions will lead to tedious trial-and-error screening. In this work, a novel strategy of biomaterial rational design through the marriage of gradient surface generation with statistical learning is presented. Not only can parameter combinations be screened in a high-throughput fashion, but also the optimal conditions beyond the experimentally tested range can be extrapolated from the models. The power of the strategy is demonstrated in rationally designing an unprecedented ternary functionalized surface for orthopedic implant, with optimal osteogenic, angiogenic, and neurogenic activities, and its optimality and the best osteointegration promotion are confirmed in vitro and in vivo, respectively. The presented strategy is expected to open up new possibilities in the rational design of biomaterials.

Prevalence of antibiotic resistance of Helicobacter pylori isolates in Shanghai, China.

OBJECTIVE: This study aimed to evaluate the resistance of Helicobacter pylori (H. pylori) to common antibiotics in Shanghai. METHODS: A total of 1171 eligible subjects participated in the study. Antibiotic susceptibility to six common antibiotics was examined with the disk diffusion method. Mutations in resistant-related genes were identified via Sanger sequencing analysis. RESULTS: Overall, the resistance rates of strains to amoxicillin, clarithromycin, levofloxacin, metronidazole, tetracycline, and furazolidone were 0.1%, 27.8%, 31.1%, 79.9%, 0.1%, and 0.5%, respectively. Compared with untreated patients, resistance rates of clarithromycin (P < 0.01), levofloxacin (P < 0.01), and metronidazole were significantly higher in re-treated patients (P < 0.05). The total multiple resistance rate was 40.5%. Age (levofloxacin), gender (clarithromycin, levofloxacin, and metronidazole) and endoscopic findings (clarithromycin and levofloxacin) were independent factors influencing antibiotic resistance. High correlation was observed between the drug susceptibility test and molecular test for the resistance to clarithromycin and levofloxacin. CONCLUSIONS: The resistance rates of H. pylori to amoxicillin, tetracycline, and furazolidone were low, whereas the resistance rates of H. pylori to clarithromycin, levofloxacin, and metronidazole were high, especially in re-treated patients. Our results indicate that the clinical resistance patterns of clarithromycin and levofloxacin could be guided by relevant gene mutations.

Oxidative stress is important in the pathogenesis of stress-related mucosal disease.

Stress-related mucosal disease (SRMD) is a common complication in patients in the intensive care unit (ICU). The aim of the present study was to investigate the possible mechanisms for the pathogenesis of SRMD. In total, 38 patients with SRMD were enrolled from an ICU, as well as 15 healthy volunteers. The disease severity of patients in ICU was evaluated using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Gastric mucosa with the most severe lesions were biopsied for hematoxylin and eosin staining and then assessed by pathological damage scoring. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and ischemic modified albumin (IMA) were also detected. In addition, claudin-3 and inducible nitric oxide (NO) synthase (iNOS) in the gastric mucosa were assessed by western blotting and immunohistochemistry. The average APACHE II score of the patients with SRMD was significantly higher compared with the controls. Moreover, the levels of MDA (4.74±2.89 nmol/ml) and IMA (93.61±10.78 U/ml) in patients with SRMD were significantly higher compared with the controls (P<0.001), while those of SOD (89.66±12.85 U/ml) in the patients with SRMD were significantly lower compared with the controls (P<0.001). Furthermore, compared with the control, iNOS expression was significantly higher (P=0.034), while the expression of claudin-3 was significantly lower in patients with SRMD (P<0.001). The results indicated that APACHE II score was positively correlated with pathological damage score (r=0.639, P<0.001) and levels of MDA (r=0.743, P<0.001), but negatively correlated with the level of SOD (r=-0.392, P=0.015). In addition, MDA was positively correlated with IMA (r=0.380, P=0.018), but negatively correlated with claudin-3 (r=-0.377, P=0.020). Therefore, it was speculated that oxidative stress may play an important role in the pathogenesis of SRMD, and NO levels and cell membrane permeability are altered during this process.

Development and Validation of an Automatic Image-Recognition Endoscopic Report Generation System: A Multicenter Study.

INTRODUCTION: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance. METHODS: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation. White light and chromoendoscopy images from patients with GI lesions were eligible for study inclusion. A total of 46,987 images from 9 tertiary hospitals were used to train, validate, and multicenter test (6:2:2). Moreover, 5,699 images were prospectively enrolled from Qilu Hospital of Shandong University to further assess the system in a prospective test set. The primary outcome was the diagnosis performance of GI lesions in multicenter and prospective tests. RESULTS: The overall accuracy in identifying early esophageal cancer, early gastric cancer, early colorectal cancer, esophageal varices, reflux esophagitis, Barrett's esophagus, chronic atrophic gastritis, gastric ulcer, colorectal polyp, and ulcerative colitis was 0.8841 (95% confidence interval, 0.8775-0.8904) and 0.8965 (0.8883-0.9041) in multicenter and prospective tests, respectively. The accuracy of cecum and upper GI site identification were 0.9978 (0.9969-0.9984) and 0.8513 (0.8399-0.8620), respectively. The accuracy of staining discrimination was 0.9489 (0.9396-0.9568). The relative error of size measurement was 4.04% (range 0.75%-7.39%). DISCUSSION: ISRGS is a reliable computer-aided endoscopic report generation system that might assist endoscopists working at various hospital levels to generate standardized and accurate endoscopy reports (http://links.lww.com/CTG/A485).

Correlations of Acute Cerebral Hemorrhage Complicated with Stress Ulcer Bleeding with Acute Physiology and Chronic Health Evaluation (APACHE) II Score, Endothelin (ET), Tumor Necrosis Factor-alpha (TNF-α), and Blood Lipids.

BACKGROUND This study investigated the correlations between acute cerebral hemorrhage complicated with stress ulcer bleeding and corresponding indexes, including the Acute Physiology and Chronic Health Evaluation (APACHE) II score, vascular endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-α), and blood lipid factors. MATERIAL AND METHODS A total of 53 patients with acute cerebral hemorrhage complicated with stress ulcer bleeding were selected as the observation group and 50 patients with simple acute cerebral hemorrhage were selected as the control group. The APACHE II score and the levels of ET-1, TNF-α, and blood lipid factors, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA), were detected and the correlations of were analyzed between the 2 groups of patients. RESULTS The blood lipid index TG, APACHE II score, ET-1, TNF-a, renal function indexes [blood urea nitrogen (BUN) and creatinine (Cr)], mortality rate, hemoglobin, and MDA in the observation group were significantly higher than those in the control group, while HDL-C in the observation group was obviously lower than in the control group (p<0.05). The APACHEII score had positive correlations with TG and TNF-α (r=0.8960, r=0.8563, respectively), while it was negatively correlated with TC, HDL-C, LDL-C, and ET-1 (r=-0.909, r=-0.9292, r=-0.8543, and r=-0.8899, respectively) (p<0.001 in all comparisons). APACHEII score, BUN, and Cr were all risk factors. CONCLUSIONS Stress ulcer in patients with acute cerebral hemorrhage is associated with blood lipid changes and inflammation, which provides clues for the diagnosis and treatment of acute cerebral hemorrhage.

Inducible Nitric Oxide Synthase in the Duodenal Mucosa Is Associated with Mast Cell Degranulation in Patients with Functional Dyspepsia.

AIM: Functional dyspepsia (FD) is a clinical syndrome with chronic gastroduodenal symptoms without noticeable organic or systemic diseases. According to the Rome III consensus, FD can be subdivided into PDS (postprandial distress syndrome) and EPS (epigastric pain syndrome). Neurotransmitters are involved in the development and pathology of FD. However, the expression profiles of neurotransmitters in FD patients are not clear. This study aimed to investigate the expression profile of neurotransmitters in the duodenal mucosa of FD patients. METHODS: A total of 48 FD patients treated at our hospital were included in this study: 23 patients with PDS and 25 patients with EPS. Another 21 healthy volunteers served as normal controls. The duodenal mucosa was biopsied with gastroscopy and examined with immunohistochemical staining against serotonin, substance P, inducible nitric oxide synthase (iNOS), and vasoactive intestinal peptide (VIP). Mast cells were identified with toluidine blue staining. RESULTS: The duodenal iNOS levels were significantly higher in PDS patients than the normal controls (P<0.05). The expression of serotonin, substance P, and VIP did not differ significantly among the groups. Mast cell counts and the percentage of mast cells with degranulation were significantly higher in PDS and EPS patients than normal controls (P<0.001) In addition, iNOS expression levels were positively correlated with percentage of degranulating mast cells (r=0.321, P=0.008). CONCLUSIONS: In conclusion, duodenal iNOS may be involved in the pathogenesis of PDS.

Anxiety and depression are associated with increased counts and degranulation of duodenal mast cells in functional dyspepsia.

BACKGROUND: Patients with functional dyspepsia (FD) have increased risks for psychological dysfunction than healthy peoples. This study aimed to explore the roles of psychosocial factors and duodenal mast cells in the pathogenesis of FD. MATERIAL AND METHODS: We prospectively included 48 FD patients and 21 age- and sex-match healthy volunteers. There were 23 patients with postprandial distress syndrome (PDS) and 25 patients with epigastric pain syndrome (EPS). The Hospital Anxiety Depression Scale (HADS) was administered to evaluate their psychosocial status. Upper endoscopy was performed with biopsy of the mucosa from the bulb of duodenum. Mast cells counts and degranulation rates were identified by toluidine blue staining. The relationship among the scores of HADS-A (anxiety) and HADS-D (depression) and the mast cell counts and degranulation rates were analyzed. RESULTS: The scores of HADS-A and HADS-D were significantly higher in PDS and EPS patients than the normal controls (P<0.05). The mast cell counts and degranulation rates in the duodenum were significantly increased in PDS and EPS patients than the controls (P<0.05). In either PDS or EPS patients, the HADS-A and HADS-D scores were positively correlated with the mast cell counts and degranulation rate. CONCLUSION: FD patients had significantly higher risks for anxiety and depression, which may lead to FD through the increased mast cell counts and degranulation.

Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia.

The role of duodenal eosinophils and mast cells (MCs) in the pathogenesis of functional dyspepsia (FD) remains poorly understood. This study aimed to examine the counts and degranulation of duodenal eosinophils and MCs in FD patients to explore the association between FD and both cell types. We recruited 141 FD patients and 39 healthy controls for this study. Biopsy specimens were collected from the duodenal bulb (D1) and the descending part (D2) of the duodenum of all participants. Eosinophil counts and degranulation, and MC counts and degranulation at both sites were quantitatively evaluated by hematoxylin and eosin staining, major basic protein immunostaining, and toluidine blue staining, respectively. Receiver operating characteristic analysis was applied to evaluate the diagnostic accuracy of these parameters in identifying FD cases. We found that the eosinophil counts at D2 were considerably increased in FD patients compared with healthy controls, and that the proportion of cases with eosinophil degranulation at D2 was significantly higher in the FD group. In addition, FD patients showed significantly increased MC counts and degranulation both at D1 and D2, and receiver operating characteristic analysis further demonstrated that these parameters, in particular the degranulation of MCs, appear to be highly sensitive and specific for the identification of FD patients. Our findings suggest that the increased eosinophil counts and degranulation at D2, and the increased MC counts and degranulation at D1 and D2 may be the histologic markers of FD. MC degranulation at D1 and D2 appears to be highly sensitive and specific for FD identification.

Hepatic venous pressure gradient is a useful predictor in guiding treatment on prevention of variceal rebleeding in cirrhosis.

BACKGROUND: The best therapy to prevent esophageal variceal (EV) rebleeding in cirrhotic patients who are non-responsive to pharmacological therapy have not been determined. AIMS: To evaluate efficacy of a strategy to assign different treatments according to hepatic vein pressure gradient (HVPG) values to prevent EV rebleeding in non-responders. METHODS: This study is a non-randomized controlled prospective study. 109 cirrhotic patients with EV bleeding who were non-responders based on two HVPG measurements were enrolled and divided two groups: 55 patients (EVL+ß-blocker group) were treated with endoscopic variceal ligation (EVL) and nonselective ß-blocker; 54 patients (HVPG-guided group) were treated with EVL and nonselective ß-blocker if HVPG ≤ 16 mmHg (low-HVPG), with percutaneous transhepatic variceal embolization (PTVE) if HVPG > 16 mmHg and ≤ 20 mmHg (medium-HVPG), or with transjugular intrahepatic portosystemic shunt (TIPS) if HVPG > 20 mmHg (high-HVPG). Patients were followed up for rebleeding and mortality. RESULTS: The mean follow-up period was 17.0 months; rebleeding was higher in the EVL+ß-blocker group than HVPG-guided group (25.5%, 9.3%, P = 0.026); 3-year probability of rebleeding in the EVL+Beta-blocker group increased with elevated levels of HVPG (12.5% vs 46.4% vs 64.9%, χ(2) = 11.551, P = 0.003), and 3-year probability of survival was no difference (96.6% vs 85.7% vs 90.9%, χ(2) = 2.638, P = 0.267). Rebleeding rate in PTVE group (7.7%) was lower than that in EVL+ß-blockergroup with medium-HVPG (35.7%), but there was no difference. Rebleeding rate in TIPS group (7.7%) was lower than that in EVL+ß-blockergroup with high-HVPG (45.5%), but there was no difference. CONCLUSIONS: HVPG measurement was useful for making decisions to select EVL and Beta-blocker, PTVE or TIPS in secondary prophylaxis. HVPG-guided treatment is feasible and effective in preventing esophageal varices rebleeding.

Fas -670A/G (rs1800682) polymorphism and digestive cancer risk in Asians: a meta-analysis.

OBJECTIVES: Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the Fas receptor-ligand system is a key regulator of apoptosis. The Fas -670 A/G single-nucleotide polymorphism (SNP) has been demonstrated to affect the expression of the Fas gene by altering the transcriptional activity in this gene's promoter. However, the association between the Fas -670 A/G polymorphism and digestive cancer risk is still controversial and ambiguous in the Asian population, so we conducted a meta-analysis to confirm and clarify the association between the Fas -670 A/G polymorphism and digestive cancer. MATERIALS AND METHODS: A search of PubMed, China National Knowledge Infrastructure (CNKI), and WanFang databases was conducted and encompassed all available articles that had been published up to July 20, 2013. Overall, 15 case-control studies containing 3692 cases and 4895 controls were retrieved based on search criteria for digestive cancer susceptibility related to -670A/G SNP. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. RESULTS: In the overall analysis, the country type and source of control subgroups, no association between the Fas -670 A/G polymorphism and digestive cancer risk was found. However, in the digestive cancer-type subgroups, a significant protective effect was detected between Fas -670 A/G polymorphism and hepatocellular carcinoma in Asians (AG vs. GG: OR=0.89, 95% CI=0.80-0.99; AA+AG vs. GG: OR=0.93, 95% CI=0.87-1.00). CONCLUSIONS: Our investigations demonstrated that the Fas -670 A/G polymorphism might decrease the hepatocellular carcinoma risk in Asian populations. Further studies based on larger sample sizes, other ethnicities, and gene-environment interactions should be conducted to further understand the role of Fas -670 A/G polymorphism in digestive cancer risk.