PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

XPS and NMR analyze the combined forms of Pb in Cladophora rupestris subcells and its detoxification.

In this study, the combined forms of Pb in Cladophora rupestris (L.) (C. rupestris) were investigated via X-ray photoelectron spectroscopy (XPS) and nuclear magnetic resonance (NMR), different Pb concentrations (0, 0.5, and 5.0 mg/L), and C. rupestris subcells were explored. Results showed that combined forms of Pb mainly account for Pb-polysaccharides (Pb-OH of carbohydrates) in the cell wall, Pb-protein (Pb-N= and (C-N-)2Pb) in the organelle, and Pb-organic acid (Pb-sulfates, (CO)2-Pb and (COO)2-Pb) in the soluble fraction. Pb-S-containing group (Pb-C-S) could formed in subcelluar when C. rupestris was subjected to high Pb stress. Meanwhile, Pb2+ could penetrate the C. rupestris cells via the formed chelate between GSH/MT and -OH functional groups. Results could help understand the role of subcellular fraction in the algae remediation and detoxification to heavy metal.

[Clinical Significance of Peripheral Blood EBV-DNA Determination and Genotyping in Lymphoma Patients].

OBJECTIVE: To explore the clinical significance of Epstein-Barr virus（EBV） detection and classification in peripheral blood of lymphoma patients. METHODS: 101 lymphoma patients were enrolled, the clinical characteristics of the patients were collected, including ages, sex, types of lymphoma, Ann Arbor stages, extranodal infiltration and lactate dehyhrogenase. Fluorescent quantitative PCR technology was used to detect the EBV-DNA. Polymerase chain reaction and Agarose gel electrophoresis was used for determination of EB genotyping. The difference between curative effect in EBV-DNA+ and EBV-DNA－ patients, the correlation of adverse factors and EBV infection of the patients were analyzed. RESULTS: 68.3% (69/101) of the patients showed EBV-DNA positive. EBV-positive lymphoma patients showed more adverse prognostic factors than the patients with EBV-negative, which may lead to poorer disease outcome. Among the 46 B-cell non-Hodgkin's lymphoma patients, the overall response rate of EBV-positive patients (60.7%) was lower than EBV-negative patients(88.9%) (P<0.05); For 19 patients with Hodgkin's lymphoma, the overall response rate of EBV-positive patients (46.2%) was lower than EBV-negative patients (100%), the differences were statistically significant (P<0.05). Among 69 patients with EBV-infected lymphoma, 98.6% (68/69) showed type-2 EB virus, and 1.4% (1/69) were type-1 and type-2 mixed infections. CONCLUSION: Most of EBV-positive in lymphoma patients were EBV type 2, patients with EBV-DNA+ shows poorer efficacy than EBV-DNA－ patients.

Peroral endoscopic myotomy for the treatment of achalasia after failed pneumatic dilation.

BACKGROUND AND AIMS: POEM is a rescue endoscopic therapy for patients who had previously failed surgical or endoscopic treatment. However, data regarding its effectiveness after failed pneumatic dilation (PD) and its long-term effects are limited. We aimed to retrospectively investigate the long-term outcomes in patients who had undergone POEM after failed PD. METHODS: Data from 66 achalasia patients with a 2-year follow-up period were analyzed. Intraprocedural events were compared between the first POEM group (patients without prior-endoscopic intervention) and prior PD group (patients who had pre-POEM PD). Symptom evaluation, HRM and 24 h-pH DeMeester scores between the two groups were performed at 2 years after the POEM procedure. Muscularis externa samples were obtained from the lower esophagus using POEM to assess the muscle fibrosis with Azan-Mallory staining. RESULTS: POEM was successfully performed for all achalasia patients. During the 2-year follow-up period, the success rate of POEM was 96.15% (25/26) for patients with prior PD and 95% (38/40) with primary POEM. For patients with type II achalasia and who underwent prior PD, the post-procedure DeMeester score was higher compared to patients who underwent POEM only (P < 0.05). A larger number of patients who underwent primary POEM (27.50%, 11/40) complained of mild heartburn compared to patients who underwent POEM after PD (7.69%, 2/26) (P < 0.05). With regards to fibrosis, the majority of patients who underwent POEM only were classified as F-1 (45.00%, 18/40), while the majority of patients who underwent prior PD were classified as F-2 (42.3%, 11/26). The degree of fibrosis was significantly different between the two groups (P < 0.05). Both surgical time and prior PD were correlated with the degree of fibrosis (P < 0.05). CONCLUSIONS: Despite the technical challenges, pre-POEM endoscopic treatment does not impact the safety and efficacy of POEM in achalasia patients. Longer follow-up studies using larger cohorts are needed to determine long-term outcomes and complications of POEM.

Combined forms of Pb and its detoxification and absorption in Cladophora rupestris subcells.

This study aims to analyze the combined form, detoxification, and adsorption mechanism of Pb in Cladophora rupestris subcells. The chemical form analysis at different concentrations (0, 0.5, 1.0, 2.5, 5.0, 7.5, and 10 mg/L) indicated that most of the Pb (37%-76%) were integrated with oxalate and undissolved phosphate, which were important to the detoxification of C. rupestris. The characterization of Pb (0, 0.5, and 5.0 mg/L) at the subcellular was conducted via Fourier-transform infrared spectroscopy (FTIR), Three-dimensional excitation-emission matrix spectroscopy (3D-EEM), and protein secondary structure fitting. Results revealed that Pb-polysaccharides ((C6H5)-OO-Pb-OH, C-O-Pb, and symmetric Pb-O-Pb), Pb-functional-groups ((C6H5)-COO-Pb and (C6H5)-P = O-Pb), and Pb-protein complexes (OH-C7H6-CN-Pb-COOH, C9H10-NH-CN-C = O-Pb, Pb-S-C, and Pb-S) were formed. The cell wall produced transport proteins, such as metallothionein and glutathione, which bound and helped Pb2+ enter the cell. After entering the soluble fraction, the Pb-organic acid ((C6H5)-COO-Pb, (C6H5)-O-Pb, and (C6H5)-P = O-Pb) and Pb-sulfhydryl compound (Pb-S-C/Pb-S) assumed the most important role in resisting the toxicity of Pb2+. Pb2+ was absorbed in the organelle and formed (C6H5)-C-O-Pb and (C6H5)-P = O-Pb, and complexed with protein (Pb-C-N) when treated with 5.0 mg/L Pb. Results could help understand the role of subcellular fraction in the algal adaptation to stressful heavy metal conditions.

Response of sulfhydryl compounds in subcells of Cladophora rupestris under Pb stress.

This study aimed to determine the role of sulfhydryl compounds in the subcells of C. rupestris under Pb stress. Different concentrations (0, 0.5, 1.0, 2.5, 5.0, 7.5, and 10 mg/L) and different exposure days (1, 3, 5, and 7 days) were designed to analyze the subcellular distribution of non-protein thiols (NPT), glutathione (GSH), and phytochelatins (PCs) in C. rupestris. NPT, GSH, and PCs increased significantly with increasing Pb stress in the cell wall and soluble fraction, especially NPT. NPT and GSH slowly increased, and PCs showed no significant difference in the organelle of C. rupestris at low concentrations (< 5.0 mg/L). PCs slightly increased under 5.0 mg/L of Pb stress. PCs/NPT gradually increased with Pb stress at a low Pb concentration. GSH detoxification response lagged behind those of NPT and PCs in response to time. PCs/NPT initially increased and then decreased with Pb stress duration. This study suggested that NPT, GSH, and PCs played an important role in the detoxification of the cell wall and the soluble fraction of C. rupestris under Pb stress. PCs were important in the organelle.

[Source Profiles of Industrial Emission-Based VOCs in Chengdu].

The volatile organic compound (VOC) emission characteristics of various production procedures were analyzed through GC-MS after the emissions of typical enterprises such as automobile manufacturing, petrochemical, and other industries had been sampled with SUMMA canisters. Each production procedure in the automobile manufacturing and petrochemical industries was considered. The results showed that each automobile manufacturing procedure had its own dominant species, and alkanes (32%) and aromatics (35%) were the main emission species of coating spraying. The emission characteristics of furniture manufacturing were highly correlated with the raw materials, and the VOC emission species were mainly composed of aromatics (50%) and oxygenated VOCs (OVOCs) (38%). As for the petrochemical industry, VOC concentrations in various process plant areas ranged from 49 µg·m-3 to 1387 µg·m-3. As the main products of the refining area were C5-C9 gasoline and benzene series, whereas comparatively more solvents were used in the chemical area, which would generate alkene products, VOC concentrations greatly differed in the various process plant areas. In terms of electronic manufacturing, OVOCs were the main emission species, accounting for more than 50% of total VOCs. Alkanes and OVOCs were the main contributors to VOC emissions in shoemaking, accounting for 52% and 36% on average, respectively, which was strongly related to the species of the used solvents. The VOC emission species of automobile manufacturing were quite different, predominantly including n-dodecane and 2-butanone. The emission species of furniture manufacturing mainly included styrene, ethyl acetate, m/p-xylene, etc., which are typical species of coatings and diluents. As for the differences in the emission species of process plant areas in the petrochemical industry, styrene was the main species in the refining area, 1,3-butadiene in the chemical area, C3-C5 alkanes in the storage area, and C6-C8 alkanes in the wastewater treatment area. The main emission species of electronic manufacturing were ethanol, acetone, and other aldehyde ketone species. The emission species of shoemaking enterprises are mainly C5 and C6 alkanes. According to the results of ozone formation potential (OFP), alkenes and aromatics were the main VOC emission species that contribute significantly to the OFP in the automobile manufacturing and petrochemical industries, with relatively high pollution source reaction activity. The results showed that the emission ratio (17%-96%) and OFP contributions of OVOCs were significant in various industries. Therefore, for VOC emission control, in addition to focusing on the control of aromatics and alkenes, attention should also be paid to OVOCs.

The effect of candesartan on chronic stress induced imbalance of glucose homeostasis.

OBJECTIVE: To explore whether chronic stress induces imbalance of glucose homeostasis, and to investigate the possible involvement of the renin-angiotensin system (RAS). METHODS: Male Sprague-Dawley rats were divided into four groups: control, chronic stress, chronic stress plus low dose candesartan (an angiotensin II receptor-1 blocker, ARB, 5 mg/kg/d, i.p.), chronic stress plus high dose candesartan (15 mg/kg/d, i.p.). Rats were received restraint stress for 14 days. Glucose transporter 2 (GLUT2) mRNA was quantified in liver by real-time polymerase chain reaction. The concentration of glucokinase (GK), glucose-6-phosphatase (G-6-P), glycogen synthase (GS), insulin receptor (ISR), glucocorticoid receptor (GR)-alpha and -beta in liver, hexokinase (HK), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in muscle, and serum insulin were measured by ELISA. Body weights, systolic blood pressure, heart rate and fasting blood glucose were monitored. Glucose tolerance test were performed after 14 days restraint stress. RESULTS: After 14 days restraint stress, systolic blood pressure, increase of plasma glucose concentration at 15 minutes were higher and the fasting plasma concentration of glucose was lower compared with control group (P < 0.05), which were reversed by high dose ARB treatment (P < 0.05). In addition, chronic stress decreased expression of GLUT2 and increased expression of GR beta in liver. High dose ARB treatment normalized GLUT2 and GR beta expressions in liver. CONCLUSIONS: Our present data indicate chronic stress induces the imbalance of glucose homeostasis and RAS contributes to the imbalance of glucose homeostasis induced by chronic stress.

Effect of continuous nursing interventions on valve noise-related anxiety and quality of life in patients who underwent mechanical mitral valve replacement.

OBJECTIVE: The purpose of this study was to evaluate the effect of continuous nursing interventions on valve noise-related anxiety in patients undergoing mechanical mitral valve replacement (MVR) and to analyze its impact on patient quality of life. METHODS: Ninety patients who underwent mechanical MVR were divided into two groups. All patients in group A received routine nursing care. In addition to this intervention, an assigned nurse periodically provided patients in group B with continuous nursing interventions and ongoing health consultations during a 1-year follow-up. A hospital anxiety and depression (HAD) scale, a customized questionnaire and a Short Form Health Status 36 (SF-36) score questionnaire were used as the research tools. RESULTS: The postoperative HAD scores were better in group B than in group A, but the differences in most of the data were not statistically significant between the groups, except for HA sections 0-7 and 11-21. Based on the customized questionnaire, the subjective disturbance level was significantly lower in group B than in group A (the results of Q1 and Q4 were statistically significant). With regard to the SF-36 scores, group B was superior to group A in general health, emotional function and mental health, while the other dimensions had no significant difference. CONCLUSIONS: Compared with routine care, patients who received continuous care intervention after mechanical MVR had fewer anxiety symptoms and better quality of life.

[Temporal and Spatial Variation of Mercury in the Water of the Ruxi River Estuary, a Typical Tributary of the Three Gorges Reservoir Area].

Four typical estuaries located in the Ruxi River, a tributary of the Yangtze River, were selected to investigate the possibility of mercury pollution in tributary estuaries from the Three Gorges reservoir water storage. Water samples were collected during the water storage period (September to October), the flooding period (November to December), the water withdrawal period (February to March), and the drying period (May to June) to determine the levels of mercury species including total mercury (THg), particulate mercury (PHg), dissolved mercury (DHg), reactive mercury (RHg), total methylmercury (TMeHg) and dissolved methylmercury (DMeHg). The results showed that the concentration of THg and TMeHg in the estuary of the Ruxi River was comparable with that of other reservoirs or natural waters in China. There was a significant difference in the concentration of DHg and TMeHg in the water at different depths, because DHg and TMeHg might be derived from the release of sediment to the overlying water. Comparing the concentrations of different mercury species in the four estuaries during the same period, it was found that the difference of water flow direction during the water storage period could lead to an uneven concentration distribution of THg and PHg in the estuary areas. During the water withdrawal period, the particles in the estuary water could adsorb and carry a large amount of PHg, resulting in higher THg concentration in the water in comparison with other periods. The concentration of TMeHg in the flooding and the drying periods was higher than in the other two periods, indicating that the stable water level might be conducive to the accumulation of methylmercury in the water, and the severe disturbance of the water level could significantly reduce the concentration of TMeHg in the water.

[Effects of Agricultural Activities on Soil Mercury Changes in the Water-Level-Fluctuating Zone of the Three Gorges Reservoir].

Farming in the water-level-fluctuating zone (WLFZ) of the Three Gorges reservoir, China, may result in a wide range of environment problems when the sediment is exposed to air. In this study, Qukou, Chongqing, was selected as the research site due to its large WLFZ area and significant agricultural activities. Four kinds of land use types, including rice, maize, vegetables, and grassland, were selected to investigate the distribution of mercury (Hg) in the surface soil. The results showed that the mean concentrations of soil total Hg (THg), bioavailable Hg (Hg-wh), and methylmercury (MeHg) in the surface soil were 25.80-68.74 ng ·g-1, 0.44-0.88 ng ·g-1, and 0.08-0.85 ng ·g-1, respectively. The concentrations of THg, Hg-wh, and MeHg in non-cultivated soil were higher than those in cultivated soil, indicating that farming disturbances could accelerate soil Hg loss. The MeHg concentrations in both non-cultivated and cultivated soil increased up to the maximum value 1-2 months after drying, and then gradually decreased to a relatively stable level. The peak value was approximately four times higher than that at the end of flooding. The percentage of MeHg to THg (% MeHg) was similar to the distribution of soil MeHg, and the peak value occurred at 1 month after drying. However, when% MeHg decreased to the stable level, no significant difference was found compared to the value at the end of flooding (P>0.05). Furthermore, the soil% MeHg had a significantly positive correlation with Hg-wh (r=0.642, P<0.01), while there was no significant correlation with THg (P>0.05), suggesting that Hg methylation was mainly affected by the bioavailability of Hg in the seasonally inundated soil of the WLFZ.

[Distribution Characteristics and Risk Assessment of Heavy Metals in the Sediments of the Estuary of the Tributaries in the Three Gorges Reservoir, SW China].

To investigate the pollution status of sediments at the junction of the Three Gorges Reservoir area, sediment samples were collected over four seasons from the junction of the estuary located at a tributary of the Ruxi River and the Yangtze River. The content of eight heavy metals (HMs), including Cr, Zn, Mn, Ni, Cu, As, Cd, and Pb, in sediments was determined by ICP-MS. The results showed the average levels of investigated HMs (in mg·kg-1) were Cr (45.24), Zn (46.46), Mn (406.14), Ni (20.885), Cu (12.49), As (7.02), Cd (0.253), and Pb (11.042). The distribution analysis indicated that the levels of HMs at the river mouth were higher than that of the tributaries of the middle reaches and the two sections nearby. The seasonal distribution shows that the heavy metal content in the spring sediment is higher than in summer, autumn and winter. In addition, the correlation analysis indicated that the eight HMs possessed similar homologous characteristics and had common exogenous inputs. The assessment of the Geo Accumulation Index showed slight Cd pollution in the estuary of Ruxi River, and the Potential Ecological Risk index showed that Cd presented moderate ecological risks. The toxic effect of benthonic organisms was possibly correlated to Ni contamination at the intersection of the tributary and main stream, which was supported by the evidence from the sediment quality criteria. In conclusion, the rating of ecological risk at the mouth of the Ruxi River tributary is slight.

Misdiagnosis and Mistherapy of Crohn's Disease as Intestinal Tuberculosis: Case Report and Literature Review.

The differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) remains difficult as the clinical symptoms of the 2 digestive diseases are so similar. Here we report a case where a patient was initially misdiagnosed with ITB prior to the correct CD diagnosis. The 46-year-old male patient was hospitalized elsewhere for pain in the right lower abdomen and underwent an appendectomy. The pathological diagnosis was ITB and the patient was administered antituberculosis therapy for 1 year. Afterward, the patient was readmitted to the hospital for a right lower abdominal mass. A computed tomography scan revealed intestinal gas, fistula, and abdominal mass. We performed a right hemicolectomy on the patient. Postoperatively, we diagnosed the patient with CD, based on patient history and pathological examination. According to the CD active index (CDAI), the patient was at high risk and began treatment with infliximab. The patient has remained in complete remission and made a good recovery after 8-months follow-up. We compared this case with the results of a literature review on the misdiagnosis between CD and ITB (26 previously reported cases) to determine the characteristics of misdiagnosed cases. We found that distinguishing between ITB and CD is difficult because of their varied clinical presentation, nonspecific investigative tools, and profound similarities even in pathological specimens. Although a CT scan to determine the morphology of the bowel wall is a key for correct diagnosis, each case still poses challenges for diagnosis and administrating the appropriate treatment.

Induction of inflammatory cell accumulation by TM-N49 and promutoxin, two novel phospholipase A(2).

Local inflammation is a prominent characteristic of snakebite wound. Snake venom phospholipase A(2)s (PLA(2)s) are one of the main components which contribute to accumulation of inflammatory cells. We have isolated TM-N49 and promutoxin from Protobothrops mucrosquamatus venom and investigated their ability in induction of cell accumulation by using an in vivo mouse model. The results showed that both TM-N49 and promutoxin are potent stimuli for induction of neutrophil, lymphocyte, macrophage and eosinophil accumulation in the mouse peritoneum. The TM-N49- and promutoxin-induced inflammatory cell accumulation was inhibited by pretreatment of animals with cyproheptadine, terfenadine and Ginkgolide B, indicating that histamine and PAF is likely to contribute to the cells accumulation. Pre-injection of antibodies against adhesion molecules ICAM-1, CD18, CD11a and L-selectin showed that ICAM-1 is a key adhesion molecule of TM-N49- and promutoxin-induced lymphocyte, macrophage and eosinophil accumulation; CD18 and CD11a plays an important role in the migration of neutrophils, eosinophils and macrophages; and L-selectin is involved in the neutrophil and eosinophil accumulation. In conclusion, induction of inflammatory cell accumulation by TM-N49 and promutoxin confirms that group II PLA(2)s is pivotal stimulus for cell infiltration, through which they participate in the formation of snakebite inflammation.

Purification, characterization and cytokine release function of a novel Arg-49 phospholipase A(2) from the venom of Protobothrops mucrosquamatus.

Group IIA phospholipase A(2) (PLA(2)) are major components in Viperidae/Crotalidae venom. In the present study, a novel PLA(2) named promutoxin with Arg at the site 49 has been purified from the venom of Protobothrops mucrosquamatus by chromatography. It consists of 122 amino acid residues with a molecular mass of 13,656 Da assessed by MALDI-TOF. It has the structural features of snake venom group IIA PLA(2)s, but has no PLA(2) enzymatic activity. Promutoxin shows higher amino acid sequence identity to the K49 PLA(2)s (72-95%) than to D49 PLA(2)s (52-58%). Promutoxin exhibits potent myotoxicity in the animal model with as little as 1 microg of promutoxin causing myonecrosis and myoedema in the gastrocnemius muscle of mice. Promutoxin is also able to stimulate the release of IL-12, TNFalpha, IL-6 and IL-1beta from human monocytes, and induce IL-2, TNFalpha and IL-6 release from T cells, indicating that this snake venom group IIA PLA(2) is actively involved in the inflammatory process in man caused by snake venom poisoning.

N49 phospholipase A2, a unique subgroup of snake venom group II phospholipase A2.

A novel phospholipase A2 (PLA2) with Asn at its site 49 was purified from the snake venom of Protobothrops mucrosquamatus by using SP-Sephadex C25, Superdex 75, Heparin-Sepharose (FF) and HPLC reverse-phage C18 chromatography and designated as TM-N49. It showed a molecular mass of 13.875 kDa on MALDI-TOF. TM-N49 does not possess enzymatic, hemolytic and hemorrhagic activities. It fails to induce platelet aggregation by itself, and does not inhibit the platelet aggregation induced by ADP. However, it exhibits potent myotoxic activity causing inflammatory cell infiltration, severe myoedema, myonecrosis and myolysis in the gastrocnemius muscles of BALB/c mice. Phylogenetic analysis found that that TM-N49 combined with two phospholipase A2s from Trimeresurus stejnegeri, TsR6 and CTs-R6 cluster into one group. Structural and functional analysis indicated that these phospholipase A2s are distinct from the other subgroups (D49 PLA2, S49 PLA2 and K49 PLA2) and represent a unique subgroup of snake venom group II PLA2, named N49 PLA2 subgroup.