Objective To explore the levels and the significance of IL-11 and soluble glycoprotein 130(sgp130) in the treatment of new-diagnosed acute leukemia(AL) during the induced remission. Methods The levels of IL-11 and sgpl30 in 47 patients with acute leukemia were determined by ELISA respectively before treatment and after completed remission(CR), and the number of white blood cell (WBC) and platelet (Plt) were valued by hametometry. Results Plasma IL-11 level of AL patients was significantly lower than normal (P ＜0.05), and increased obviously to the normal level when complete remission was achieved. And it correlated with PLT counts. While sgp130 level was higher than normal (P＜0.05),and declined after CR and correlated with WBC counts. Conclusion The plasma IL-11 and sgp130 levels can be helpful for confirming the diagnosis,evaluating the efficiency and predicting the prognosis of AL.

Objective To investigate the value of prenatal diagnosis in identifying the etiology and predicting the prognosis of fetal pleural effusion (FPE).Methods Forty-two cases of FPE were recruited in this study from January 2012 to September 2016.Ultrasound scan and genetic tests were performed on all fetuses.Seven fetuses with severe FPE were given pleurocentesis.Pregnancy outcomes of all the fetuses were followed up.Results FPE was commonly accompanied with other abnormalities,such as ascites,hydrops,hydramnion,hygroma colli,abnormal posturing,joint contractures,arrhythmia and micromandible.Chromosomal abnormality was detected in 11 fetuses (26.2％),of which ten were further confirmed by karyotype analysis,including six with 45,X,three trisomy 21 and one trisomy 18,and one was detected with a 9.83 Mb uniparental disomy (UPD) located at 12q24.21q24.31 by gene chip.One fetus was diagnosed with--SEA/--SEA thalassemia.All of the 12 families decided to terminate the pregnancies after genetic counseling.Among the other 30 fetuses,seven with severe FPE and normal karyotype underwent pleurocentesis.Five of the seven cases were with favorable outcomes,one with progressive hydrops was aborted and one neonate with severe hydrops died after birth.Spontaneous regression of FPE with good outcome was found in two cases.Parents of the other 21 fetuses chose to terminate the pregnancies.Conclusions Prenatal diagnosis is important to identify the etiology and predict the outcome of FPE.Chromosomal abnormality is a relatively common cause of FPE,and 45,X and trisomy 21 are the most common abnormalities.Intrauterine intervention is beneficial for FPE without chromosomal or other definite genetic abnormalities.Genetic test may be of great value for pregnant counseling.

Objective:To survey the first-aid ability of general practitioners (GPs) and the emergency service capacity of primary health institutions in southern Zhejiang province.Methods:The questionnaire of first-aid ability of GPs in primary care institution was developed on the basis of the Delphi method during August to October 2018. The questionnaire was employed in a survey on the first-aid ability among 480 GPs from 169 community health service centers of three regions in southern Zhejiang province. The survey covered basic information and first-aid skills and emergency response ability of GPs, and the emergency facilities of primary health institutions.Results:A total of 480 questionnaires were distributed and 447 were retrieved with an recovery rate of 93. 1%(447/480). Among the 447 responders, 55.9% (250/447) were males, 70.9% (317/447) had bachelor′s degree or above, and 60.2% (269/447) had middle and senior professional titles. There were 99.6% (445/447), 86.6% (387/447), 76.1% (340/447) and 69.8% (312/447) responders considered cardiopulmonary resuscitation(CPR), electrical defibrillation, respiratory balloon and endotracheal intubation as important first-aid skills, and corresponding mastery rates were 84.3% (377/447), 32.0% (143/447), 55.2% (247/447) and 12.9% (58/447), respectively. The 92.4% (413/447) responders thought that the rescue ability of common emergency and critical illness was the most important, while only 32.4% (145/447) responders mastered it. Least responders [41.4%(185/447)] thought that ability of using bedside ultrasound was important, and the corresponding mastery rate was only 3.8%(17/447); 77.4%(346/447) of general practitioners believed that CPR machines was important, while the available rate of CPR machines in primary health care institutions was only 16.0%(27/169).Conclusion:The GPs in southern Zhejiang province have a good grasp of cardiopulmonary resuscitation skills, but have a low mastery rate of first-aid skills such as electrical defibrillation, tracheal intubation, and emergency rescue capabilities, which are quite different from their perceived importance evaluation.

OBJECTIVETo observe the effects of the intervention with fire needling therapy on the uterine microenvironment at the specific time points of menstrual cycle and evaluate the effects on the assisted reproduction.

METHODSSixty-eight patients of in vitro fertilization and embryo transplantation (IVF-ET) were randomized into an observation group (35 cases) and a control group (33 cases). The patients in the two groups all received post-IVF-ET corpus luteum support of the microstimulation scheme in the Clinical Reproduction Center of Jiangsu People's Hospital. In the control group, the regular sequential therapy of acupuncture was used. In the observation group, on the basis of the treatment as the control group, the intervention of fire needling therapy was applied after ovulation (the 1st time point, on the 1st day after ovulation) and at the end of premenstrual stage (the 2nd time point, 3 days before the menstruation). At the 1st time point, Shenshu (BL 23), Mingmen (GV 4) and Yaoyangguan (GV 3) were selected and at the 2nd time point, Shenshu (BL 23) and Ciliao (BL 32) were selected. The acupoints were stimulated from up to down and from the left to the right. The changes in TCM syndrome during the preparation, the endometrial thickness and types on the day of transplantation, the biochemical pregnant rate after transplantation and clinical pregnant rate were observed and compared in the patients of the two groups.

RESULTSAfter treatment, TCM syndrome scores were all reduced in the two groups (both<0.05). In the observation group, the biochemical pregnant rate and clinical pregnant rate were slightly higher than those in the control group, without significant difference in comparison (both>0.05). In the observation group, the endo-metrial thickness on the day of transplantation was higher than that in the control group (<0.05). After treatment, the differences in TCM syndrome score and endometrial type were not significant statistically between the two groups (all>0.05).

CONCLUSIONSThe intervention of fire needling therapy at the specific time points of menstrual cycle relieves menstrual symptoms and increases endometrial thickness so as to assist embryo implantation in the patients of infertility.

Objective To investigate the value of local myocardial blood flow and myocardial function parameters in monitoring the dynamic changes of radiation induced heart disease (RIHD) using 13NNH3 PET gated myocardial perfusion imaging(GMPI).Methods Six healthy male Beagle dogs underwent 13N-NH3 PET GMPI 1 week before irradiation and 3,6 and 12 months after irradiation in the anterior wall of the left ventricle with a single dose of 20 Gy.Global myocardial function parameters including left ventricular ejection fraction (LVEF),end-diastolic volume (EDV),end-systolic volume (ESV),and regional myocardial function parameters including wall motion (WM),wall thickening (WT),end-diastolic perfusion (EDP),end-systolic perfusion (ESP) before and after irradiation were compared by repeated measures analysis of variance and paired t test.Results There were no significant changes between EDV,ESV and LVEF at baseline and those at 3 months after irradiation.EDV at 6 months after irradiation still had no change,compared with baseline value and EDV at 3 months after irradiation,but ESV was increased and LVEF was decreased.Twelve months after irradiation,ESV was further expanded,LVEF was further reduced,and EDV began to increase (F values:20.974-177.846,all P＜0.05).Compared with the baseline,WM,WT,EDP and ESP were increased in 10％(2/20),20％(4/20),10％(2/20) and 15％(3/20) of myocardial segments at 3 months after irradiation (t values:14.446-672.315,all P＜0.05);those parameters were decreased in 15％(3/20),20％(4/20),15％(3/20) and 25％(5/20) of myocardial segments at 6 months after irradiation (t values:18.171-723.156,all P＜0.05),and were decreased in 35％(7/20),45％(9/20),40％(8/20) and 60％ (12/20) of myocardial segments at 12 months after irradiation (t values:14.783-711.259,all P＜0.05).Conclusions 13N-NH3 PET GMPI could be used to detect RIHD early and monitor the dynamic development of RIHD.Compared with the global left ventricular function parameters,regional myocardial function parameters (WM,WT,EDP and ESP) are more sensitive,which may be served as the early monitoring indicators for RIHD.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of microRNA-146a (miR-146a) with clinical features of rheumatoid arthritis (RA). METHODS: In 126 patients with RA and 102 matched healthy controls, SNPs of miR-146a rs2910164 locus were determined with a high-resolution melting method. The association of such polymorphisms with disease activity score in 28 joints (DAS28) and clinical features of RA was assessed. RESULTS: The distribution of SNPs of miR-146a rs2910164 among RA patients did not differ from that of the control group. No significant association was found between miR-146a rs2910164 polymorphism with DAS28. However, RA patients with a GG genotype had a greater chance to develop extra-articular manifestations (P<0.01). CONCLUSION Polymorphisms of miR-146a rs2910164 locus is not an independent risk factor for RA, though its GG genotype may be associated with extra-articular manifestations of RA.
Arthritis, Rheumatoid ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; MicroRNAs ; genetics ; Polymorphism, Single Nucleotide

Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.

Antimicrobial peptides (AMPs) are a class of peptides widely existing in nature with broad-spectrum antimicrobial activity. It is considered as a new alternative to traditional antibiotics because of its unique mechanism of antimicrobial activity. The development and application of natural AMPs are limited due to their drawbacks such as low antimicrobial activity and unstable metabolism. Therefore, the design and optimization of derived peptides based on natural antimicrobial peptides have become recent research hotspots. In this paper, we focus on ribosomal AMPs and summarize the design and optimization strategies of some related derived peptides, which include reasonable primary structure modification, cyclization strategy and computer-aided strategy. We expect to provide ideas for the design and optimization of antimicrobial peptides and the development of anti-infective drugs through analysis and summary in this paper.
Antimicrobial Cationic Peptides/chemistry* ; Antimicrobial Peptides ; Drug Design ; Anti-Infective Agents/pharmacology* ; Anti-Bacterial Agents

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

OBJECTIVE: To investigate the effects of nicotinamide adenine dinucleoside phosphate oxidases 1(NOX1) and nuclear factor-kappa B(NF-κB) in tumor necrosis factor-α(TNF-α)-induced oxidative damage in A549 cells. METHODS: i) TNF-α was used to stimulated A549 cells at the concentrations of 0.0, 10.0, 25.0 and 50.0 μg/L. Cell inhibition rate in each group was tested by CCK-8 assay to select the appropriate concentration. ii) A549 cells in logarithmic growth phase were divided into blank control group, solvent control group, TNF-α group, diphenylene iodine(DPI) group and TNF-α+DPI group for NOX1 inhibitor experiment. Logarithmic growth phase A549 cells were divided into blank control group, TNF-α group, BAY11-7082 group and TNF-α+BAY11-7082 group for NF-κB inhibitor experiment. The relative expression of NOX1 and p65 protein in each group was detected by Western blot method. The relative expression of intracellular reactive oxygen species(ROS) were detected by flow cytometry. RESULTS: i) The inhibition rate of A549 cells increased with the increase of TNF-α dose(P<0.05), and 25.0 μg/L was selected as the stimulation dose of TNF-α in subsequent experiments. ii) The relative expression of NOX1, p65 protein and ROS in the TNF-α group was higher than that in the blank control group, solvent control group and DPI group, respectively(P<0.05). The above indexes in TNF-α+DPI group were lower than that in TNF-α group(P<0.05), but higher than that in DPI group(P<0.05). The relative expression of NOX1, p65 protein and ROS in the TNF-α group were higher than that in the blank control group and the BAY11-7082 group(P<0.05), while the above indicators in the TNF-α+BAY11-7082 group were lower than that in the TNF-α group(P<0.05). CONCLUSION: Inhibition of NOX1 or NF-κB can alleviate the oxidative damage induce by TNF-α in A549 cells.