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Background: Acute respiratory failure (ARF) is still one of the most severe complications in immunocompromised patients. Our previous systematic review showed noninvasive mechanical ventilation (NIV) reduced mortality, length of hospitalization and ICU stay in AIDS/hematological malignancy patients with relatively less severe ARF, compared to invasive mechanical ventilation (IMV). However, this systematic review was based on 13 observational studies and the quality of evidence was low to moderate. The efficacy of NIV in more severe ARF and in patients with other causes of immunodeficiency is still unclear. We aim to determine the efficacy of the initial ventilation strategy in managing ARF in immunocompromised patients stratified by different disease severity and causes of immunodeficiency, and explore predictors for failure of NIV., Methods and Analysis: The VENIM is a multicentre randomized controlled trial (RCT) comparing the effects of NIV compared with IMV in adult immunocompromised patients with severe hypoxemic ARF. Patients who meet the indications for both forms of ventilatory support will be included. Primary outcome will be 30-day all-cause mortality. Secondary outcomes will include in-hospital mortality, length of stay in hospital, improvement of oxygenation, nosocomial infections, seven-day organ failure, adverse events of intervention, et al. Subgroups with different disease severity and causes of immunodeficiency will also be analyzed., Discussion: VENIM is the first randomized controlled trial aiming at assessing the efficacy of initial ventilation strategy in treating moderate and severe acute respiratory failure in immunocompromised patients. The result of this RCT may help doctors with their ventilation decisions., Trial Registration: ClinicalTrials.gov NCT02983851 . Registered 2 September 2016.

A cascade visible-light photocatalytic difluoroalkylation and intramolecular cyclization reaction has been developed for the synthesis of difluoroalkylated oxygen heterocycles. The reaction was carried out under very mild conditions, affording fluorinated isobenzofuran-1-ones, lactone, and cyclic ethers with up to 97% chemical yields. Furthermore, several types of bromofluoroalkane precursors bearing ester, keto, amido, and phosphate groups could all work very well in this reaction, which provides an easy method for the preparation of functionalized difluoroalkylated oxygen heterocycles.

This work describes, for the first time, Michael addition reactions of tertiary fluoro-enolates in situ generated by detrifluoroacetylation with 1-(1-(phenylsulfonyl) vinylsulfonyl)benzene. Excellent enantioselectivity and chemical yields were achieved with application of catalysts (10 mol %) derived from Cu(OTf) 2 and (1S,2S)-1,2-diphenylethane-1,2-diamine. These reactions show a considerable degree of structural generality and allow the preparation of new types of biologically relevant molecules that contain quaternary C-F stereogenic carbon atoms and feature five-, six-, or seven-membered rings as well as heterocyclic 3-fluoro-2,3-dihydrochromen-4-one moieties., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the feasibility and indication of free grafting of split big toe nail bed for defects of fingernail bed., Methods: From September 2008 to September 2011,13 cases (4 females and 9 males) with fingernail bed defects(aged 17-38,average,32) were treated with split big toe nail bed. The split big toe nail was harvested according to the defects size without bone exposure at donor site., Results: Three grafted nail beds were necrotic completely and reconstructed with flaps. The 2 grafted nail bed was partial loss and healed after dressing. All the other grafted nail bed survived completely with primarily healing both in donor sites and recipient sites. The patients were followed up for 6-30 months(average,14 months).The therapeutic effect was graded as excellent in 8 cases, good in 2 cases and poor in 14 cases(good rate,76.9％).The nail matrix was excellent in 8 cases,good in 1 case and poor in 1 case(good rate,90％).The toe nails in donor sites grew well., Conclusions: The single fingernail defect with intact nail matrix can be reconstructed by split toe nail bed graft with good cosmetic and functional effect. There is no malfunction at donor site. The indication should be selected.

Objective: To explore the efficacy and the mechanism of Bisacodyl in treating slow transit constipation model rats., Methods: A total of 30 healthy rats were enrolled. Twenty rats received intragastric diphenoxylate to develop slow transit constipation (STC) model, and 10 untreated rats were set as blank control. STC rats were subdivided into two groups: STC Bisacodyl group (fed with Bisacodyl) and STC control group (common feed). Body weight, number and dry weight of faeces, and intestinal transit time were compared among 3 groups. Interstitial cells of Cajal(ICC) and c-Kit protein expression were measured by immunohistochemical staining. Restults Compared to blank control rats, at 100-day of receiving intragastric diphenoxylate, above 20 rats presented the decrease of body weight and feces number, the increase of dry weight of faeces, and the delay of intestinal transit time, indicating the successful establishment of STC rat model. One month after feeding, compared to STC control group, STC Bisacodyl grap had an increased feces number[(36.6±6.8) pill/day vs. (26.8±6.0) pill/day], decreased dry weight of feces [(150.6±10.5) mg/pill vs. (171.6±16.3) mg/pill] and shortened intestinal transit time [(416.9±50.6) minutes vs. (495.3±66.8) minutes], and the differences were statistically significant(all P<0.05). Dissolution of ICC basement membrane, damage of connection between ICC and surrounding cells, and atrophy of ICC nucleus structure were found in STC control rats. ICC (8.20±1.92 per field] and c-Kit expression (12.68%±2.59% ) in STC control rats were significantly lower than those in blank control rats(36.00±6.25 per field and 71.50 %±8.27%) (P=0.000). Compared to STC control group, the connection between ICC and surrounding cells enhanced obviously, ICC (18.80±3.70 per field) and c-Kit expression (45.91%±6.80%) were significantly higher in STC Bisacodyl group (all P=0.000)., Conclusion: Bisacodyl treatment can relieve STC symptoms, which may be associated with increased ICC number and c-Kit protein expression.

Objective: To investigate the effect of lateral arm free-flaps for hand thermal-crush injury., Methods: 15 patients with hand thermal-crush injury were treated with emergency debridement and one-staged coverage with lateral arm free-flaps pedicled with deep brachial artery between January 2010 and December 2013. ., Results: Good results were achieved. All 15 flaps survived, Conclusions: Emergency debridement and reconstruction with lateral arm free-flap is a very effective method for hand thermal-crush injuries. Meanwhile, it also can reduce complications, shorten the duration of hospitalization and reduce health care costs.

The aim of the present study was to observe the protective effect of exogenous human insulin-like growth factor-1 (hIGF-1) on spinal motor neurons, following its local transfection into an area of peripheral nerve injury. A total of 90 male Wistar rats that had been established as sciatic nerve crush injury models were randomly divided into three groups: hIGF-1 treatment, sham-transfected control and blank control groups. The different phases of hIGF-1 expression were observed in the spinal cord via postoperative immunostaining and the apoptosis of motor neurons was observed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Pathological changes of the motor neurons and Nissl bodies within cell bodies were observed via Marsland and Luxol fast blue double staining, while changes in the neuropil of the spinal cord anterior horn were investigated via ultrastructural observation. It was found that hIGF-1, locally transfected into an area of peripheral nerve injury, was expressed in the spinal anterior horn following axoplasmic transport; the peak hIGF-1 expression occurred approximately a week following transfection. The number of apoptotic spinal cord motor neurons observed in the hIGF-1 treatment group was fewer than that in the sham-transfected and blank control groups at days 7, 14 and 21 following transfection (P<0.01). Furthermore, the quantity of motor neuron cells in the anterior horn of the spinal cord in the hIGF-1 treatment group was higher compared with those in the sham-transfected and blank control groups at days 2, 7, 14 and 28 following transfection (P<0.01). The degenerative changes of Nissl bodies within the cytoplasm of the hIGF-1 treatment group were less severe compared with those of the sham-transfected and blank control groups. At day 56 following transfection, the spinal anterior horn neuropil ultrastructure in the hIGF-1 treatment group was generally normal, while the sham-transfected and blank control groups exhibited an increased number of protruding gaps and local cavities. These results indicate that the application of exogenous hIGF-1 is capable of protecting spinal cord motor neurons following peripheral nerve injury.

The purpose of the current study was to examine the relation between apomorphine (APO) induced rotational behavior and the pre- and post-synaptic dopaminergic function in a parkinsonian rat model induced by medial forebrain bundle (MFB) axotomy. The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the MFB. Behavioral studies were carried out by APO challenge prior to and 1, 3, and 5 weeks after MFB axotomy. MicroPET scans with [(11)C]CFT and [(11)C]raclopride were performed 2 days after the behavioral test. The two PET scans were separated by an interval of 24-48 h. Immunohistochemistry was conducted 4 days after the last PET scan. Our data showed that [(11)C]CFT binding decreased progressively 1, 3, and 5 weeks postlesion, and there was a significant nonlinear correlation between [(11)C]CFT uptake ratio (right/left) and APO induced rotations. In contrast, [(11)C]raclopride binding only increased significantly 3 weeks postlesion, and there was a positive linear correlation between [(11)C]raclopride uptake ratio (right/left) and APO induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. These findings not only demonstrate the relation between APO induced rotational behavior and the pre- and post-synaptic dopamine function but also indicate the utility and validity of in vivo PET imaging in understanding disease mechanisms and progression, which should in turn lead to development of new therapies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To investigate the oxidative damage of mice induced by diisobutyl phthalate (DiBP) and the mechanism of free radical oxidative damage caused by DiBP., Methods: Sixty KunMing mice were divided by weight into 5 groups after accommodation to the experimental animal room for 3 days. The control group and 4 DiBP groups, group I, II, III and IV, were given DiBP in corn oil by gavages at the dosage of 0, 50, 250, 500 and 1000 mg/kg respectively. The mice were fed with normal diets and drinking water freely for 8 weeks. By the end of the experiment, the comet assay of blood and SOD, GSH-Px, MDA and 8-OHdG of liver were tested., Results: The activities of SOD and GSH-Px in DiBP groups were significantly lower than the control group (P < 0.05); the MDA contents of DiBP group III and group IV were significantly higher than the control group (P < 0.05) and the 8-OHdG content of group II was significantly higher than the control group (P < 0.01). The comet assay showed that the oxidative damage of DNA in DiBP groups was significant in comparison with the control group (P < 0.05)., Conclusion: Oxidative stress induced by diisobutyl phthalate can decrease the activities of antioxidative enzymes and result in oxidative damage of tissues.

Objective: To study the feasibility of C3H/HeJ mice as the food allergenicity rodent model and explore the appropriate period of two different routes of exposure and the change of helper T lymphocyte cell., Methods: Allergenic protein ovalbumin (OVA) was administered intraperitoneally or orally to female C3H/HeJ mice for 35 days. Blood samples were taken on the 14th, 28th and 35th days from the orbital plexus and sera were obtained to determine OVA specific IgE (OVA sIgE). Spleen samples were obtained on the 35th day to detect the mRNA expression of Th2-type cytokines IL-4 and Th1-type cytokines IFN-gamma by real-time RT-PCR., Results: Compared with the control group, the concentration of OVA sIgE on 28th and 35th days were significantly increased in OVA group by gavage (P < 0.05). The concentration of OVA sIgE on 14th, 28th and 35th days were significantly higher than the control group when OVA was given intraperitoneally (P < 0.05). Compared with the control group, the mRNA expression of IL-4 of OVA group and OVA + Al(OH)3 group were significantly increased. The mRNA expression of IFN-gamma of OVA group and OVA + Al(OH) group were significantly lower than the control group., Conclusion: C3H/HeJ mice might be used as a rodent model for the assessment of allergenicity of food. The appropriate period is the 14th day for the route of intraperitoneal injection and the 28th day for oral gavage, respectively.

Objective: The study aimed to investigate the endocrine disruptive toxicity of isoflavone in vivo, through comparing with genistein, to study main active parts of isoflavone in estrogenic active, also., Methods: Uterotrophic assay was carried out. 0.1, 0.2, 0.5, 1.5 g/kg bw isoflavone, 0.05, 0.10, 0.25, 7.50 g/kg bw genistein, 3.0 microg/kg estradiol as positive control, water and oil as control were respectively administered orally to the animal for 3 consecutive day. In the end of the test, uterine wet and blotted weight, histopathology of ovary, uterus and vaginal were measured. Finally, all the effects caused by isoflavone and geinistein were compared., Results: Both isoflavone and genistein induce uterine weight increase significantly; histopathology of uterus and vagina showed that both isoflavone and genistein induce proliferation; there are dose-response relationship; in the related dose level, isoflavone and genistein caused similar effects., Conclusion: In uterotrophic assay, genistein was the main active part of isoflavone; via oral administration to immature prepuberty rat, isoflavone had endocrine disruptive effects which had obviously dose-response relationship.

To examine effects of lactational exposure to soy isoflavones on female reproductive system, soy isoflavones, 0 (control), 10, 50, 100, 150 or 200 mg/kg body weight, were administered to maternal rats by gavage daily during postnatal days 5-10. Ten female litters were killed on day 11. Uterine and ovary weights, serum oestradiol and progesterone concentrations, proliferating cell nuclear antigen, mRNA expressions of oestrogen receptor, androgen receptor and progesterone receptor in uterus or ovary were measured. When compared to the control group, litters in the 150 and 200 mg/kg body weight groups had significantly higher ovary and uterine weights (P < 0.05). Endometrial thickness was also significantly increased. Isoflavone-treated groups had increased proliferating cell nuclear antigen staining in comparison to the control group. Litters in the 50, 150 and 200 mg/kg body weight groups had significantly higher oestradiol concentration while lower progesterone concentrations than those in the control group (P < 0.05 or P < 0.01). All soy isoflavone-treated groups had androgen receptor mRNA expressions in ovary and uterus comparable to the control group. Progesterone receptor mRNA expression in the 150 and 200 mg/kg body weight groups was significantly lower than that in control group (P < 0.01). However, ovaries in the 150 and 200 mg/kg body weight groups had significantly higher oestrogen receptor mRNA expression while the uterus in these two treatment groups had significantly lower expressions, when compared to the control group (P < 0.05 or P < 0.01). In conclusion, lactational exposure to isoflavones could result in oestrogen-like actions on the reproductive system of neonate female rats, which mechanisms may be, at least, involved with modifications of hormone production and steroid receptor transcription in the reproductive system.

Smoking increases the risk of several chronic diseases associated with elevated oxidative stress status. Almonds are a good source of antioxidant nutrients and may diminish smoking-related biomarkers of oxidative stress. We investigated whether almond consumption decreases biomarkers of oxidative stress in young male smokers. We conducted a randomized, crossover clinical trial with 60 healthy male soldiers (18-25 y) who were habitual smokers (5-20 cigarettes/d) and supplemented their diet with 84 g almonds or 120 g pork (to control for calories) daily for 4 wk with a 4-wk washout period between treatment periods. In addition, 30 healthy nonsmoking men were provided the same daily serving of pork as reference comparison. Blood and urine were collected and assessed for biomarkers of oxidative stress. Baseline values of urinary 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) and peripheral lymphocyte DNA strand breaks were significantly higher by 185, 64, and 97% in smokers than nonsmokers, whereas activities of plasma superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase were significantly lower by 15, 10, and 9%, respectively. After the almond intervention, serum alpha-tocopherol, SOD, and GPX increased significantly in smokers by 10, 35, and 16%, respectively and 8-OHdG, MDA, and DNA strand breaks decreased significantly by 28, 34, and 23%. In smokers, after almond supplementation, the concentration of 8-OHdG remained significantly greater than in nonsmokers by 98%. These results suggest almond intake can enhance antioxidant defenses and diminish biomarkers of oxidative stress in smokers.

Objective: To study the effects of lactational exposure to soy isoflavones (SIF) on ovary development in neonate rats., Methods: Virgin Sprague-Dawley female and male rats were fed with soy and alfalfa free diets (SAFD). The pregnant rats were randomly divided into six groups with seven animals in each group. Dams in different treatment groups received 0, 10, 50, 100, 150 and 200mg/kg bw of SIF from postnatal day 5 to 10 (PND5-10) by gavage, respectively. On PND11, female litters were killed and ovaries were removed for pathological evaluation and detection of estrogen receptor (ER), andron receptor (AR), progesterone receptor (PR), proliferating cell nuclear antigen (PCNA) protein expression by immunohistochemistry as well as ER, AR, PR mRNA expression by RT-PCR., Results: The ratios of ovary weight to body weight increased significantly in 100, 150 and 200 mg/kg bw groups than that in control group. And the ovary follicles developed more quickly in offsprings exposed to SIF. In 150 and 200 mg/kg bw groups, ER, PCNA protein and ER mRNA expression in ovaries increased significantly, while PR mRNA expression decreased significantly. Other receptor expressions had no significant difference from the control group., Conclusion: Lactational exposure to soy isoflavones could induce adverse effects on ovary development in neonate rats, which mechanisms may, at least, partically involved with modification of mRNA transcription for ER and PR.

trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the cardiovascular system in a number of studies. It is, however, unclear whether this naturally occurring compound can protect against cardiac hypertrophy. The aim of the present study was to investigate the effects of resveratrol on cardiac hypertrophy in vivo and the potential underlying mechanisms involving endothelin (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague-Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation controls were simultaneously established in the present study. The systolic blood pressure (SBP) of rats was measured at baseline and, along with heart weight, after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined. In the present study, it was shown that, compared with rats in the sham-operated group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg), heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7 +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/- 26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO concentration had increased to 40.1 +/- 14.6 micromol/L. These values were significantly different from those obtained for the PNX group. In conclusion, trans-resveratrol appears to be able to protect against the increase in SBP and subsequent cardiac hypertrophy in vivo and the mechanisms responsible may involve, at least in part, modulation of NO, AngII and ET-1 production.

In order to explore the relationship between polymorphism of matrix gamma-carboxyglutamic acid protein (MGP) gene and blood lead level in children and to screen the gene which associated with lead poisoning, three hundreds and fifty-five children aged at 6 to 12 years old living in lead pollution area were recruited in this study. The blood lead level were measured. The T-138C polymorphism of MGP gene was analyzed with the method of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The blood lead level in children with wild type homozygotes(TT) was higher than those with mutated homozygotes(CC) (468.24 micrograms/L. vs. 430.31 micrograms/L, P < 0.05). The results indicated that the T-138C polymorphism of MGP gene in promoter region influenced blood lead level in children lived in lead pollution area.

Objective: The relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead., Method: Four hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP., Results: The subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028)., Conclusions: It was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.