LC-MS/MS法定量分析人血清中多黏菌素B的浓度

目的开发一种简单灵敏的液相色谱串联质谱法(LC-MS/MS)用于人血清中多黏菌素B(PB)的浓度测定。方法用多黏菌素E_(2)(PE_(2))作为内标,使用乙腈(含0.1%甲酸)沉淀蛋白质法处理样品。采用Hypersil GOLD^(TM)C_(18)色谱柱进行色谱分析。流动相A为0.1%甲酸-水,流动相B为纯甲醇,梯度洗脱;流速:0.4 mL·min^(-1),进样量:2μL,分析时间:3.3 min,柱温:40℃。采用多反应监测模式,电喷雾离子源正离子模式进行定量分析。定量离子对分别为m/z 402.10>101.10(PB_(1)),m/z 397.45>101.10(PB_(2)),m/z 578.50>101.10(PE_(2))。结果人血清中PB_(1)在22~15000 ng·mL^(-1),PB_(2)在5~1700 ng·mL^(-1)范围内线性关系良好,相关系数均大于0.9990。PB_(1)和PB_(2)的定量下限分别为22,5 ng·mL^(-1)。PB_(1)的准确度为95.98%~104.60%,PB_(2)的准确度为98.11%~105.59%;批内和批间精密度的RSD均小于15%。PB_(1)和PB_(2)的提取回收率分别为97.26%~103.31%和95.81%~101.22%;基质效应分别为96.52%~109.54%和93.29%~109.95%。样品稳定性试验的RSD均小于15%。应用本方法测定的6例患者平均AUC_(0-24h)为(72.85±17.87)mg·h·L^(-1)。结论建立的测定人血清中PB浓度的LC-MS/MS方法符合生物样本检测分析的要求,适用于临床上PB血药浓度检测。

胆宁片预防内镜保胆取石术后胆囊结石复发的研究

目的探讨中成药胆宁片在内镜保胆取石术(CGPC)后预防胆囊结石复发的作用,及其与牛磺熊去氧胆酸(TUDCA)的差异。方法纳入2016年11月-2020年1月在北京大学首钢医院符合条件的CGPC后患者1868例,按取出结石的类型分为两个队列,A队列为取出胆固醇为主的结石,B队列为取出胆色素为主的结石,将每个队列中的患者随机分为两组,DN组口服胆宁片(1.8 g/次,3次/d),TU组口服TUDCA(500 mg/次,1次/d),疗程为180 d,随访时间为36个月,记录胆囊结石复发及胆囊壁厚度的变化情况。结果两种药物相互比较,在A队列,A-DN组与A-TU组的胆囊结石复发率无明显差异;在B队列,B-DN组的胆囊结石复发率明显低于B-TU组。在两个队列中,DN组术后半年的平均胆囊壁厚度均明显薄于TU组。结论CGPC后应用胆宁片有助于缓解术后胆囊炎症,能够有效地降低胆囊结石复发率,在预防胆色素为主的胆囊结石复发方面优于TUDCA。

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Relationship between gene expression and the accumulation of catechin during spring and autumn in tea plants (Camellia sinensis L.)

The tea plant(Camellia sinensis L.)is an important commercial crop with remarkably high catechin concentrations.Tea is popular worldwide given the plant's health benefits.Catechins are the main astringent substance in tea and are synthesized mainly via the phenylpropanoid pathway.In this study,eight cultivars of tea plants harvested both in spring and autumn were used to investigate differences in catechin concentrations by using high-performance liquid chromatography.The expression levels of genes associated with catechin biosynthesis were investigated using reverse transcription-quantitative polymerase chain reaction.The results indicated that the total catechin(TC)concentrations were significantly higher in tea plants harvested in autumn than in those harvested in spring,based on higher concentrations of epigallocatechin(EGC)in autumn tea(P<0.01).The expression of the genes phenylalanine ammonia-lyase(PAL),flavanone 3-hydroxylase(F3H),flavonoid 3′,5′-hydroxylase(F3′5′H),dihydroflavonol 4-reductase(DFR),and anthocyanidin synthase(ANS)is closely related to the TC content of tea plants in both spring and autumn.Positive correlations between PAL,cinnamate 4-hydroxylase(C4H),F3H,and DFR expression and EGC accumulation in autumn tea were identified,with correlation coefficients of 0.710,0.763,0.884,and 0.707,respectively.A negative correlation between ANS expression level and EGC concentrations in tea plants harvested in spring was noted(r=−0.732).Additionally,negative correlations between F3H and ANS expression levels and the catechin content were identified in spring tea,whereas the correlations were positive in autumn tea.Significant differences in the F3H and ANS expression levels between spring and autumn tea indicate that F3H and ANS are potentially key genes affecting catechin accumulation in tea plants.

Characteristics of AZ31 Mg alloy joint using automatic TIG welding

The automatic tungsten-inert gas welding（ATIGW） of AZ31 Mg alloys was performed using a six-axis robot. The evolution of the microstructure and texture of the AZ31 auto-welded joints was studied by optical microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and electron backscatter diffraction. The ATIGW process resulted in coarse recrystallized grains in the heat affected zone（HAZ） and epitaxial growth of columnar grains in the fusion zone（FZ）. Substantial changes of texture between the base material（BM） and the FZ were detected. The {0002} basal plane in the BM was largely parallel to the sheet rolling plane, whereas the c-axis of the crystal lattice in the FZ inclined approximately 25° with respect to the welding direction. The maximum pole density increased from 9.45 in the BM to 12.9 in the FZ. The microhardness distribution, tensile properties, and fracture features of the AZ31 auto-welded joints were also investigated.

The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats

Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer.

New devices and techniques for endoscopic closure of gastrointestinal perforations

Gastrointestinal perforations,which need to be managed quickly,are associated with high morbidity and mortality. Treatments used to close these perforations range from surgery to endoscopic therapy. Nowadays,with the development of new devices and techniques,endoscopic therapy is becoming more popular. However,there are different indications and clinical efficacies between different methods,because of the diverse properties of endoscopic devices and techniques. Successful management also depends on other factors,such as the precise location of the perforation,its size and the length of time between the occurrence and diagnosis. In this study,we performed a comprehensive review of various devices and intro-duced the different techniques that are considered effective to treat gastrointestinal perforations. In addition,we focused on the different methods used to achieve successful closure,based on the literature and our clinical experiences.

Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implanta- tion. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.

Energy dissipation of slot-type flip buckets

The energy dissipation is a key index in the evaluation of energy dissipation elements.In the present work,a flip bucket with a slot,called the slot-type flip bucket,is theoretically and experimentally investigated by the method of estimating the energy dissipation.The theoretical analysis shows that,in order to have the energy dissipation,it is necessary to determine the sequent flow depth h1 and the flow speed V1 at the corresponding position through the flow depth h2 after the hydraulic jump.The relative flow depth h2/ho is a function of the approach flow Froude numberFro,the relative slot widthb/Bo,and the relative slot angleθ/β.The expression for estimating the energy dissipation is developed,and the maximum error is not larger than 9.21%.

Improved wear resistance of biodegradable Mg-1.5Zn-0.6Zr alloy by Sc addition

Magnesium alloys exhibit significant potential for use in next-generation biodegradable materials.Implanted magnesium alloys are expected to exhibit good wear resistance.In this work,the effects of rare earth metal Sc on the wear resistance of biodegradable magnesium alloys were studied.The average grain sizes of Mg-1.5 Zn-0.6 Zr-x Sc(ZK21-x Sc,x=0,0.2,0.5,1.0;wt%)alloys decreased with Sc content increasing.Unlike other rare earth metals,the grain refinement mechanism of Sc belongs to the heterogeneous nucleation mechanism.The yield tensile strengths and Vickers hardness of the ZK21-x Sc alloys markedly improved with the addition of Sc increasing.This could be due to the grain refinement and enhanced bond energy resulting from Sc addition.Moreover,the friction and wear tests showed that the friction coefficient of the alloys decreased and the weight loss reduced with Sc addition increasing.This implies that Sc addition could enhance the wear resistance of magnesium alloys.With the addition of Sc increasing,the peeling phenomenon weakened gradually and the worn surfaces of samples became smoother.The major wear mechanisms of the as-cast ZK21-x Sc alloys were abrasion wear and delamination wear.

Air entrainment of hydraulic jump aeration basin

In order to avoid the cavitation damage and the decrease of the energy dissipation of the stepped spillways with a large unit discharge, the air entrainments of the hydraulic jump aeration basin （HJAB） are theoretically and experimentally investigated for the hydraulic-jump-stepped spillway developed by the authors. It is shown that the submerged degree of the hydraulic jump and the air concentration in the measuring section are all functions of the dimensionless discharge, the length and the end sill height of the H JAB. The submerged degree odecreases with the increase of the dimensionless discharge or the dimensionless length of the H JAB, but increases with the increase of the dimensionless height of the end sill of the HJAB. The flow regimes near the critical hydraulic jump, namely, at or= 1.0, have the best effect of the air entrainment for the flow at the measuring section and then that of the stepped spillway.

Fin performance of 3-D aerator devices with backward lateral deflectors

In the present work,a 3-D aerator device with backward lateral deflectors,called BLD-3-D aerator device,is developed,and the lateral cavity and fin performance of the BLD-3-D aerator device are experimentally investigated.The findings show that,the relative lateral cavity length with backward lateral deflectors is shorter than that with current lateral deflectors under the same approach flow conditions,and on the basis of the results of the relative cavity length ratio between the lateral and bottom aerators the BLD-3-D aerator device is of remarkable performance for the water fin control thanks to the decrease of the relative lateral cavity length.

Local scour by multiple slit-type energy dissipaters

Energy dissipation and scour control are all the key issues for the design of hydraulic structures.On the basis of the high energy dissipation for the multiple slit-type energy dissipaters(M-STED)developed by the authors,in this work,the characteristics of the scour hole for the M-STED were experimentally investigated through three sets of those physical models with five cases and a scour hole form index was proposed.The results show that,the M-STED results in not only the high energy dissipation but also the mild upstream slope of the scour hole thanks to the scour hole form index of larger than 0.5,which is in favor of the safety of the release works.

Flow regime and energy dissipation of SFS-type flip buckets

In the present work,a slot-type flip bucket with separated flows,called SFS-type flip bucket,is developed,and flow regime and energy dissipation are experimentally investigated.Comparing with the circular-shaped or slot-type flip bucket buckets,the present SFS-type flip bucket has better flow regime and larger energy dissipation since the three branches of the flows are separated through the outlet of the flip bucket.Meanwhile,the energy dissipation for this flip bucket is estimated.

Enhanced mechanical properties in Al/diamond composites by Si addition

Diamond particles reinforced aluminum–silicon matrix composites,abbreviated as Al（Si）/diamond composites,were fabricated by squeeze casting.The effect of Si content on the microstructure and mechanical properties of the composites were investigated.The mechanical properties are found to increase monotonically with Si content increasing up to 7.0 wt%.The Al-7.0 wt% Si/diamond composite exhibits tensile strength of 78 MPa,bending strength of 230 MPa,and compressive strength of426 MPa.Al–Si eutectic phases are shown to connect with Al matrix and diamond particles tightly,which is responsible for the enhancement of mechanical properties in the Al（Si）/diamond composites.

Photocrosslinkable Polynorbornene-based Block Copolymers with Enhanced Dielectric and Thermal Properties

Block copolymers poly（endo-N-3,5-bis（trifluoromethyl）biphenyl-norbornene-pyrrolidine）-block-poly（exo-N-（cinnamoyloxyethyl）-7-oxanorborn-5-ene-2,3-dicarboximide）（endo-PTNP-b-exo-PCONBI） and poly（exo-N-3,5-bis（trifluoromethyl）biphenyl-norbornene-pyrrolidine）-block-poly（exo-N-（cinnamoyloxyethyl）-7-oxanorborn-5-ene-2,3-dicarboximide）（exo-PTNP-b-exo-PCONBI） were synthesized by ring-opening metathesis polymerization. The endo- or exoPTNP served as the high dielectric functional chain, and exo-PCONBI acted as the crosslinking segment. The endo-PTNPb-exo-PCONBI, in which endo-PTNP has a high content of trans double bond and adopts isotactic configuration, shows a dielectric constant（？） of 15.5, whereas exo-PTNP-b-exo-PCONBI, in which exo-PTNP has 67% trans double bonds and atactic microstructure, displays relatively low ？ of 7.1. The cinnamate groups in exo-PCONBI were crosslinked to form three-dimensional network by cycloaddition reaction under UV irradiation. Exposed to UV-light for 10 min, the cinnamate group in polymer films has a crosslinking conversion of 36%, as determined by UV-Vis absorption measurements. By photocrosslinking, the polymer film has an increased ？ of 16.6, a dielectric loss of 0.03, an elevated glass-transition temperature of 137 ？C, and an enhanced decomposition temperature of 405 ？C, compared to those of polymer films without irradiation.