[Regulative effects of endogenous sulfur dioxide on oxidant stress in myocardium of rat with sepsis].

OBJECTIVE: To explore the modulating effect of endogenous sulfur dioxide (SO2) on the ba-lance of oxidation/reduction in the cecal-ligation-and-puncture-induced septic rat myocardium. METHODS: Forty male Sprague Dawley rats were randomized into control group, SO2group, sepsis group and sepsis + SO2group. The levels of procalcitonin (PCT), creatine kinase isoenzyme (CK-MB), cardiac troponin Ⅰ (cTn Ⅰ) and fatty acid binding protein (FABP) in plasma in each group of the rats were measured; The level of hydrogen peroxide (H2O2), level of nitric oxide (NO), activity of myeloperoxidase (MPO), activity of hydroxyl free radical (·OH) and level of malondialdehyde (MDA) in myocardial tissue were measured; Total antioxidant capacity (T-AOC), activity of catalase (CAT), level of cytochrome oxidase (CO), level of glutathione (GSH), level of glutathione oxidase (GSH-px) and activity of superoxide dismutase (SOD) in myocardial tissue were measured. RESULTS: The level of PCT in plasma in the rats with sepsis increased from (0.93±0.26) µg/L to (2.45±0.52) µg/L (P < 0.01), and decreased to (1.58±0.36) µg/L after the intervention of sulfur dioxide donor (P < 0.01). In sepsis, the plasma CK-MB, cTn Ⅰ and FABP levels in the rats increased respectively from (14.46±6.48) µg/L, (151.25±30.14) ng/L and (2.72±0.65) µg/L to (23.72±7.72) µg/L, (272.78±52.70) ng/L and (5.22±1.01) µg/L (P all < 0.01), and decreased to (16.74±3.63) µg/L, (184.86±37.72) µg/L and (3.31±0.84) µg/L (all P < 0.05) after the intervention of sulfur dioxide donor. The level of H2O2, level of NO, activity of MPO, activity of ·OH and level of MDA in myocardial tissue in the rats with sepsis increased respectively from (67.26±8.77) mmol/g, (38.39±6.93) µmol/g, (358.25±68.12) U/g, (648.42±93.69) U/ mg and (4.55±0.96) µmol/g to (111.45±17.35) mmol/g, (51.04±5.91) µmol/g, (465.88±76.76) U/g, (873.75±123.47) U/mg and (7.25±0.86) µmol/g (all P < 0.01), and decreased respectively to (75.99±10.52) mmol/g, (39.39±7.80) µmol/g, (393.17±51.5) U/g, (710.54±106.33) U/mg and (5.16±0.65) µmol/g after the intervention of the sulfur dioxide donor (all P < 0.05). The activity of T-AOC, activity of CAT, level of CO, level of GSH, level of GSH-px and activity of SOD in myocardial tissue in the rats with sepsis increased respectively from (2.07±0.37) U/mg, (169.25±36.86) U/g, (1.35±0.32) µmol/g, (103.51±16.62) µmol/g, (38.40±7.97) µmol/g and (38.50±8.30) U/mg to (1.42±0.39) U/mg, (98.44±26.56) U/g, (0.96±0.21) µmol/g, (68.05±7.35) µmol/ g, (23.83±5.04) µmol/g and (23.11±4.63) U/mg (P all < 0.01), and increased respectively to (1.83±0.37) U/mg, (146.14±31.63) U/g, (1.28±0.20) µmol/g, (92.10±11.84) µmol/g, (37.16±3.01) µmol/g and (37.29±2.62) U/mg (P all < 0.05) after the intervention of the sulfur dioxide donor. CONCLUSION: Endogenous SO2 can protect rat myocardium in sepsis by modulating the ba-lance of oxidation and reduction.

[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

[Early childhood development and risk factors in rural China: a cohort study].

Objective: To investigate the development status and risk factors of infants and toddlers in rural China. Methods: In this cohort study, 603 infants (6-12 months of age, Phase Ⅰ) in the rural areas of QinLing-Bashan (Qin-Ba) in Shaanxi were recruited in the control group that received no intervention from April 2013 to October 2015. Three follow-up visits were performed every six months (Phase Ⅱ(12-18 months of age), Phase Ⅲ (18-24 months of age) and Phase Ⅳ(24-30 months of age)). In all the 4 phases (Ⅰ-Ⅳ), general data of the children and the families were collected by questionnaires, early childhood growth and development were assessed by door to door visits, children's hemoglobin levels were determined by laboratory tests, and the cognitive and motor development screening was conducted by the Bayley Scales of Infant and Toddler Development. Logistic regression was used to analyze the risk factors affecting the development of infants and toddlers in rural areas and the data were analyzed in terms of risk factors from infants, guardians and family. Results: Phase Ⅱ, Phase Ⅲ and Phase Ⅳ survey recruited 497, 483 and 486 participants respectively. The incidences of cognitive impairment (mental development scores<80) in rural areas of southern Shaanxi were 13.4% (81/603) in Phase Ⅰ(6-12 months), 20.1%(100/497) in PhaseⅡ(12-18 months), 42.9% (207/483) in Phase Ⅲ(18-24 months) and 50.4%(245/486) in Phase Ⅳ(24-30 months) respectively, which showed a significant increase with age (χ(2)=233.40, P<0.01); the incidences of psychomotor impairment (psychomotor development scores<80) of Phase Ⅰ, Phase Ⅱ, Phase Ⅲ and Phase Ⅳ were 25.0% (151/603), 26.8% (133/497), 8.3% (40/483) and 11.9% (58/486), which showed a significant decrease with age (χ(2)=87.08, P<0.01). Multivariate logistic regression analysis showed that the leading risk factor of the cognitive development of 24-30-month-old children was the mothers' poor education background (≤9 years of school education) (OR=2.56, P<0.01), and the main risk factors affecting psychomotor development were the mothers' poor education background (≤9 years of school education) (OR=2.64, P<0.05) and growth retardation (OR=2.95, P=0.07). Conclusions: The early childhood development (especially cognitive development) in the rural areas of Qin-Ba in Shaanxi of China is not optimistic. More attention should be paid to the early childhood development in rural China, especially to the development of children from the mothers with poor education background.

[Application of benchmark dose on renal injury in people chronically exposed to lead].

Objective: To screen sensitive indicators of renal injury in lead workers using benchmark dose method. Methods: Of the 486 subjects,116 did not occupationally contact to lead as a control. The blood lead was considered as exposure biomarker, while Uß2-MG and UNAG as effect biomarkers for renal injury. The BMD and BMDL of blood lead were estimated at the 10% benchmark response using BMDS Version 2.6. Results: There was statistical rise in blood lead between the lead group and control group (P<0.05) ; and the blood lead level was divided into four groups by quarterback spacing method, among which UNAG was statistically different (P<0.05) . There was an increased prevalence of abnormal rates of Uß2-MG and UNAG with increasing blood lead concentration (P<0.05) , after trend chi-square test. BMD and BMDL of UNAG and Uß2-MG were 602.784/431.838 µg/L and 130.398/100.981 µg/L caculated by Log-Probit model, respectively. Conclusions: Occupational lead exposure may cause kidney damage, and UNAG could be as a more sensitive marker for monitoring early renal injury than Uß2-MG.

A review on equivalent magnetic noise of magnetoelectric laminate sensors.

Since the turn of the millennium, multi-phase magnetoelectric (ME) composites have been subject to attention and development, and giant ME effects have been found in laminate composites of piezoelectric and magnetostrictive layers. From an application perspective, the practical usefulness of a magnetic sensor is determined not only by the output signal of the sensor in response to an incident magnetic field, but also by the equivalent magnetic noise generated in the absence of such an incident field. Here, a short review of developments in equivalent magnetic noise reduction for ME sensors is presented. This review focuses on internal noise, the analysis of the noise contributions and a summary of noise reduction strategies. Furthermore, external vibration noise is also discussed. The review concludes with an outlook on future possibilities and scientific challenges in the field of ME magnetic sensors.

A study of glycogen storage disease with 99Tcm-MIBI gated myocardial perfusion imaging.

OBJECTIVE: Gated myocardial perfusion imaging (G-MPI) is regularly performed using single-photon emission computed tomography. The objective of this study was to evaluate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) myocardial imaging in glycogen storage disease (GSD). METHODS: 99Tcm-MIBI G-MPI was performed in nine patients with clinically proven GSD. QGS quantitative software was used for processing and interpretation. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were automatically generated. The myocardium was divided into seven segments, 20 sub-segments and a five-point scoring system was used. RESULTS: Seven out of nine cases were abnormal and the positive rate of G-MPI was 77.8 %. Sixty-two sub-segments of injured myocardium were detected in 140 sub-segments of seven abnormal patients. One injured segment was observed in one patient (14.3 %), two segments were detected in two patients (28.6 %) and three or more abnormal segments were observed in four patients (57.1 %). CONCLUSION: 99Tcm-MIBI G-MPI can detect myocardial damage in GSD as a non-invasive method. It plays an important role in the clinic.

Enhanced removal of chemical oxygen demand, nitrogen and phosphorus using the ameliorative anoxic/anaerobic/oxic process and micro-electrolysis.

Synthetic wastewater was treated using a novel system integrating the reversed anoxic/anaerobic/oxic (RAAO) process, a micro-electrolysis (ME) bed and complex biological media. The system showed superior chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) removal rates. Performance of the system was optimised by considering the influences of three major controlling factors, namely, hydraulic retention time (HRT), organic loading rate (OLR) and mixed liquor recirculation (MLR). TP removal efficiencies were 69, 87, 87 and 83% under the HRTs of 4, 8, 12 and 16 h. In contrast, HRT had negligible effects on the COD and TN removal efficiencies. COD, TN and TP removal efficiencies from synthetic wastewater were 95, 63 and 87%, respectively, at an OLR of 1.9 g/(L·d). The concentrations of COD, TN and TP in the effluent were less than 50, 15 and 1 mg/L, respectively, at the controlled MLR range of 75-100%. In this system, organics, TN and TP were primarily removed from anoxic tank regardless of the operational conditions.

Current targeting strategies for adenovirus vectors in cancer gene therapy.

Adenovirus vectors (Adv) are the most frequently used vectors in gene therapy research, especially in cancer gene therapy. However, despite encouraging preclinical and early clinical results, the successful clinical utility of gene therapy has not yet been fully realized. Challenges to clinical trial success for targeted Adv include inefficient Adv-mediated gene transfer (because many tumor cells lack Adv receptors), poor transduction in tumor tissues after systemic administration, accumulation and undesirable transgene expression in the liver. This review summarizes current targeting strategies for Adv to overcome these obstacles. Strategies include transductional selectivity through genetic modification of viral coat proteins, transcriptional selectivity by means of tumor-specific promoters, and selective biodistribution from conjugation with targeting ligands or polymers such as polyethylene glycol (PEG). Furthermore, combining selective biodistribution and active targeting ligands such as proteins, antibodies and peptides is an intriguing and promising approach that will also be covered in this review. These studies have provided new insights into our understanding of the utility of Adv in cancer gene therapy.

Composite microspheres induce the sustained release and the control of the initial release of water soluble drugs.

Although epidural analgesia may provide adequate pain relief and minimize systemic side effects, long-term, even permanent placement of epidural catheter for chronic or cancer-related pain management carries a potential risk of both superficial and deep infection. The development of antibiotics microspheres that could be dwelled in epidural drug-delivery devices is likely to achieve a significant advance allowing antibiotics given by the intradiscal route to control catheter-related infections. In the present study, the composite microspheres composed of double-walled microcapsules and PLGA were constructed for encapsulating water-soluble antibiotics, cefazolin. The results show that these microspheres could efficiently control the initial release of drug, which was only 3.0% at 2 h. Cefazolin encapsulated in the composite microspheres released gradually nearly in a constant rate in the first 16 days, and still maintained a relative fast rate in the next 14 days, indicating that composite microspheres could improve the incomplete release of entrapped drugs.

Prediction of plasma protein binding of cephalosporins using an artificial neural network.

An artificial neural network model is developed to predict the fraction of cephalosporins bound to plasma proteins (f(b)) from their molecular structural parameters. These molecular structural parameters are the molecular weight (MW), the surface area occupied by oxygen and nitrogen atoms (S(O),N), and the surface area occupied by hydrogen atoms attached to oxygen or nitrogen atoms (S(H)). For a training set of 20 cephalosporins and a test set of 3 cephalosporins, root mean squared errors (RMSE) between experimental fb values and calculated/predicted fb values are 0.036 and 0.045, respectively.

Cotransduction of CCL27 gene can improve the efficacy and safety of IL-12 gene therapy for cancer.

Interleukin-12 (IL-12) is a potent antitumoral cytokine, but high doses are toxic. Herein, we demonstrate that combinational transduction of IL-12 and CC-chemokine ligand-27 (CCL27) genes into pre-existing murine OV-HM ovarian carcinoma and Meth-A fibrosarcoma, by using RGD fiber-mutant adenoviral vectors, could induce tumor regression and relieve systemic side effects more effectively than either treatment alone. The antitumor activity of the IL-12 and CCL27 combination treatment was T-cell-dependent, and development of long-term specific immunity was confirmed in rechallenge experiments. Immunohistochemical analysis of tumors transduced with CCL27 gene alone or cotransduced with IL-12 and CCL27 genes showed significant increases in numbers of infiltrating CD3(+) T cells, which included both CD4(+) and CD8(+) cells. Additionally, cotransduction with IL-12 and CCL27 genes could more efficiently activate tumor-infiltrating immune cells than transduction with CCL27 alone, as determined by the frequency of perforin-positive cells and expression levels of IFN-gamma. Furthermore, mice treated with the IL-12 and CCL27 combination compared with those treated with IL-12 alone showed milder pathological changes, for example, lymphocyte infiltration and extramedullary hematopoiesis, in lung, liver and spleen. Our data provide evidence that combinational in vivo transduction with IL-12 and CCL27 genes is a promising approach for the development of cancer immunogene therapy that can simultaneously recruit and activate tumor-infiltrating immune cells.

Pluronic F127 gel effectively controls the burst release of drug from PLGA microspheres.

To investigate the controlled release effect of a thermo-sensitive gel, Pluronic F127 (PF127) on microspheres, poly[D,L-lactic-co-glycolic acid] (PLGA) microspheres were coated with Pluronic F127 gel and the in vitro release was evaluated. The results demonstrated that PF127, which gelled at 37 degrees C, inhibited the initial burst release of drug from microspheres effectively.

High gene expression of the mutant adenovirus vector, both in vitro and in vivo, with the insertion of integrin-targeting peptide into the fiber.

In the present study, a first-generation adenovirus (Ad) vector was modified with the RGD peptide inserted into the fiber. The insertion of an integrin-targeting sequence into the Ad vector notably enhanced the luciferase expression in the Coxsackie virus and Adenovirus Receptor-deficient A2058 and B16BL6 melanoma cells. The results of an in vivo study with tumor-bearing mice also showed that Ad-RGD-Luc had enhanced gene expression in many organs and in the B16BL6 tumor compared to that induced by a conventional Ad vector after intravenous injection.

Tumor-suppressive activities by chemokines introduced into OV-HM cells using fiber-mutant adenovirus vectors.

In this study, fiber-mutant adenovirus vectors encoding chemokines, Ad-RGD-mCCL17, Ad-RGD-mCCL21 and Ad-RGD-mCCL22 were constructed. The insertion of integrin-targeting RGD sequence into fiber knob of adenovirus vectors notably enhanced the infection efficiency into tumor cells. Among three chemokine-encoding vectors evaluated, Ad-RGD-mCCL22 showed significant tumor-suppressive activity via transduction into OV-HM cells.

[Solvent extraction-flow injection analysis for determination of trimethoprim in compound preparations].

Trimethoprim (TMP) in four pharmaceutical preparations (compound sulfamethoxazol tablets, compound tetracycline tablets, compound trimethoprim and sulfamethoxazol tablets; and compound berberine injection) is determined by solvent extraction-flow injection spectrophotometry. It can be extracted into chloroform directly, and the absorbance at a wavelength of 280 nm of the organic phase is measured after phase separation. The manifold comprises two streams. The sample is injected into a 0.2 mol/L NaOH carrier stream, and extracted with chloroform in a 200-cm coil (ID 0.7 mm) after a 50 cm reaction tube (ID 1.0 mm). Calibration graph is linear in the range of 25-150 micrograms/ml. The average recovery is 101.4% with a relative standard deviation of 1.1%. The proposed system permits the analysis of about 50 samples per hour. Precise results in agreement with those obtained with official methods are achieved.