Tailoring MXene Thickness and Functionalization for Enhanced Room‑Temperature Trace NO_(2) Sensing

In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Regulatory potential of soil available carbon,nitrogen,and functional genes on N_(2)O emissions in two upland plantation systems

Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Functionally graded structure of a nitride-strengthened Mg_(2)Si-based hybrid composite

The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N_(2) gas during laser powder bed fusion.This is substantialized based on both the thermal diffusion-and chemical reactionbased metallurgy of the Mg_(2)Si–SiC/nitride hybrid composite.This study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive manufacturing.This strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg_(2)Si–SiC/nitride hybrid composite.Consequently,the coefficient of friction of the hybrid composite exhibits a 309.3%decrease to–1.67 compared to–0.54 for the conventional nonreinforced Mg_(2)Si structure,while the tensile strength exhibits a 171.3%increase to 831.5 MPa compared to 485.3 MPa for the conventional structure.This outstanding mechanical behavior is due to the(1)the complementary and synergistic reinforcement effects of the SiC and nitride compounds,each of which possesses an intrinsically high hardness,and(2)the strong adhesion of these compounds to the Mg_(2)Si matrix despite their small sizes and low concentrations.

丛枝菌根真菌对褐土玉米氮素吸收和土壤N_(2)O排放的影响

探究不同氮肥水平下丛枝菌根(AM)真菌对褐土玉米土壤N_(2)O排放和氮转化功能基因的影响,为阐明AM真菌在褐土N_(2)O排放中的作用和效应提供理论依据。设置氮肥用量(NⅠ:105 mg/kg;NⅡ:210 mg/kg)、AM真菌(M0:不接种AM真菌;M1:接种根内根孢囊霉(Rhizophagus intraradices);M2:接种摩西斗管囊霉(Funneliformis mosseae);M3:接种Rhizophagus intraradices+Funneliformis mosseae等比例混合)双因素盆栽试验。测定植株地上部全氮含量、土壤铵态氮、硝态氮含量和N_(2)O排放量,采用实时荧光定量聚合酶链式反应(PCR)法分析土壤硝化功能基因(amoA-AOA和amoA-AOB)和反硝化功能基因(nirS、nirK和nosZ)的丰度。结果表明,两种施氮水平下,接种AM真菌均可显著降低土壤N_(2)O排放通量和累积排放量,不同AM真菌处理下N_(2)O累积排放量表现为:M0>M2>M1>M3。相同AM真菌处理的土壤N_(2)O排放通量和累积排放量在NⅡ施氮水平高于NⅠ施氮水平;相同AM真菌处理的玉米菌根侵染率在NⅡ施氮水平低于NⅠ施氮水平。与M0相比,NⅠ条件下M1、M2和M3处理土壤铵态氮含量分别降低24.5%、20.8%和45.3%,硝态氮含量分别降低19.7%、14.9%和30.2%,植株地上部全氮含量分别增加16.3%、35.2%和59.6%;与M0相比,NⅡ条件下M1、M2和M3处理土壤铵态氮含量分别降低20.9%、24.8%和40.0%,硝态氮含量分别降低36.3%、25.6%和45.2%,植株地上部全氮含量分别增加33.2%、43.9%和95.4%。两种施氮水平下,AM真菌可显著降低土壤硝化功能基因(amoA-AOA和amoA-AOB)丰度,增加反硝化功能基因(nirS、nirK和nosZ)丰度。AM真菌与N_(2)O排放通量呈极显著负相关。本盆栽试验条件下,接种AM真菌均可增强两种氮肥用量玉米植株氮素吸收能力,调节硝化、反硝化相关功能基因的丰度,减少土壤N_(2)O气体的排放,且两种AM真菌混合处理的N_(2)O减排效应强于单一AM真菌接种。

达格列净联合水飞蓟宾治疗2型糖尿病合并非酒精性脂肪肝患者疗效分析

目的探讨达格列净联合水飞蓟宾对2型糖尿病合并非酒精性脂肪肝(NAFLD)患者的治疗效果。方法收集2021年1月—2022年12月新疆医科大学第五附属医院内分泌科诊治2型糖尿病合并NAFLD患者104例作为研究对象,按随机数字表法分为对照组52例和研究组52例,2组患者均给予常规治疗及二甲双胍降血糖治疗,研究组在此基础上给予达格列净联合水飞蓟宾治疗,治疗6个月后,比较2组患者治疗前后糖脂代谢指标、肝功能、肝脏硬度、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)以及脂联素(APN)水平变化。结果治疗后2组患者糖化血红蛋白、空腹血糖、餐后2 h血糖以及胰岛素抵抗指数(HOMA-IR)较治疗前下降,且研究组低于对照组(t/P=3.411/<0.001,2.926/0.005,3.578/<0.001,2.672/0.015),研究组患者治疗后体质量指数(BMI)、腰臀比、内脏脂肪面积、总胆固醇(TC)、三酰甘油(TG)以及低密度脂蛋白胆固醇(LDL-C)明显低于治疗前,且低于对照组(t/P=2.873/0.008,2.435/0.013,4.878/<0.001,3.997/<0.001,2.265/0.025,1.997/0.038);研究组患者治疗后天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)以及总胆红素较治疗前明显下降,且研究组患者低于对照组(t/P=5.737/<0.001,4.971/<0.001,3.258/<0.001);治疗后研究组患者TNF-α降低,SOD及APN升高,且研究组降低/升高幅度大于对照组(t/P=2.453/0.021,3.842/<0.001,3.927/<0.001);治疗期间2组患者恶心呕吐、腹泻、腹胀、便秘、体质量增加、贫血以及低血糖等不良反应发生率比较,差异均无统计学意义(P>0.05)。结论在二甲双胍降糖治疗基础上给予达格列净联合水飞蓟宾可明显改善2型糖尿病合并NAFLD患者胰岛素抵抗水平以及肝功能,降低炎性因子水平和氧化应激损伤,提高APN水平。

玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病气阴两虚证患者临床疗效观察

目的:对玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病(T2DM)气阴两虚证患者的临床疗效进行探讨。方法:将60例T2DM患者随机分为对照组(n=30)和观察组(n=30),对照组采用二甲双胍联合德谷门冬双胰岛素治疗,观察组在此基础上应用玉液汤加减治疗,比较2组治疗后的中医证候积分、糖化血红蛋白(Hb Alc)、空腹血糖(FPG)、餐后2 h血糖(2h PG)、日内平均血糖波动幅度(MAGE)、胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-IS)。结果:治疗后,观察组总有效率显著高于对照组(93.33%vs 86.67%);观察组中医证候积分、Hb Alc、FPG、2h PG、MAGE和HOMA-IR等指标均低于对照组,HOMA-IS高于对照组(均P<0.05)。结论:玉液汤加减联合二甲双胍和德谷门冬双胰岛素对2型糖尿病气阴两虚证患者疗效显著,可有效控制患者的血糖并改善胰岛功能。

7元旋转对称2-弹性函数的构造

基于旋转对称轨道的数对分布矩阵的性质,给出了所有7元旋转对称2-弹性函数的具体构造。结果表明,在F_(2)^(7)上有且仅有280个非线性旋转对称2-弹性函数。进一步地,对于任意的奇数k,在F_(2)^(7k)上至少有280个非线性旋转对称2-弹性函数。

多模态超声心动图技术综合评估2型糖尿病患者左心房结构及功能

目的基于心肌斑点追踪技术及实时三维超声技术探讨2型糖尿病患者左心房容积、功能及心肌应变及其与血清炎性指标的相关性研究。方法收集2018年9月至2021年12月于我院就诊的2型糖尿病患者328例,其中单纯2型糖尿病患者220例,早期糖尿病肾病患者108例,选取同期于我院就诊134例健康体检者为对照组。应用二维心肌斑点追踪技术评估患者左心房应变,分别得到三腔心切面左房峰值纵向应变(PALS-LAX)、四腔心切面左房峰值纵向应变(PALS-A4C)、两腔心切面左房峰值纵向应变(PALS-A2C)、左房平均峰值纵向应变(LA-PALS)。应用三维超声评估左心房容积及收缩功能,得到左房最大容积指数(LAVImax)、左房收缩前容积指数(LAVIp)、左房最小容积指数(LAVImin)及左房总排空分数(LATEF);同时记录受试者炎性相关血清学指标。结果3组LAVImin及左心房应变指标:PALS-LAX、PALS-A2C、LA-PALS比较,差异均有统计学意义(P<0.05)。与对照组比较,单纯糖尿病组患者LAVImin增大,PALS-LAX、PALS-A2C、LA-PALS减小(P<0.05);与单纯糖尿病组比较,早期糖尿病肾病组患者LAD、EDT、E/e′、LAVImax、LAVImin增大,E/A和LATEF降低,左心房应变指标:PALS-LAX、PALS-A4C、PALS-A2C、LA-PALS进一步减小(P均<0.05)。相关性研究发现,餐后2 h血糖与LAVImin、LA-PALS、E/e′呈负相关(r=-0.583、-0.788,-0.414,P<0.05);糖化血红蛋白与LAVImin、E/e’呈负相关(r=-0.439、-0.551,P<0.05);IL-6及IL-8与LA-PALS呈负相关(r=-0.541、-0.429,P<0.05);IL-6及IL-8与LAVImin呈负相关(r=-0.572、-0.517,P<0.05);血清β2微球蛋白与LAVImin、LA-PALS呈负相关(r=-0.614、-0.568,P<0.05)。结论2型糖尿病患者随病程进展逐渐出现左心房心肌应变减低、左心房增大及排空功能减低;LA-PALS及LAVImin与患者餐后2 h血糖水平、血清β2微球蛋白IL-6、IL-8水平呈负相关。

螺内酯对射血分数轻度降低心力衰竭合并2型糖尿病患者的临床疗效观察及预后研究

目的 探究螺内酯对射血分数轻度降低的心力衰竭合并2型糖尿病患者的临床疗效及预后观察。方法 纳入2019年2月至2022年12月于北京朝阳医院治疗的射血分数轻度降低的心力衰竭合并2型糖尿病患者共409例。所有患者在试验前均未服用过螺内酯,已接受其他心衰标准药物治疗及降糖药物治疗至少半年。通过随机分组将纳入患者分为试验组及对照组,试验组在对照组治疗基础上加用螺内酯10~20 mg/d。比较两组患者治疗前后的糖化血红蛋白(glycated hemoglobin, HbA1c)、体质量指数、血浆N末端B型利钠肽原(NT-proBNP)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、舒张期二尖瓣峰值流速与二尖瓣环舒张早期运动峰速度的比值(E/e’)、血清肌酐(Scr)、血清尿酸(SUA)、肌酐清除率(Ccr)、血钾水平等指标的变化,观察治疗相关不良反应、心血管死亡或心衰恶化再住院复合终点事件发生率,评估临床治疗效果。结果 两组患者于治疗前的一般资料比较差异无统计学意义(P>0.05);治疗后试验组患者的HbA1c水平较对照组下降[(7.2±0.5)vs.(7.9±0.7),P<0.05],NT-proBNP水平较对照组降低[(423±155)vs.(640±157),P<0.05];试验组治疗后的心功能及肾功能多项指标的改善情况优于对照组(均P<0.05),心功能Ⅱ~Ⅳ级的试验组患者于治疗期间血钾水平相对稳定(均P>0.05)。治疗后试验组的临床显效率及总有效率高于对照组(均P<0.05),复合终点事件发生率及药物治疗相关不良反应在两组中差异无统计学意义(均P>0.05)。结论 螺内酯有助于射血分数轻度降低的心力衰竭合并2型糖尿病患者的血糖管理,并能进一步改善心脏功能及肾功能,同时具有良好的药物使用安全性。

新诊断的2型糖尿病患者血管内皮功能与甲状腺激素敏感性相关性的研究

目的探讨新诊断的2型糖尿病(type 2 diabetes mellitus,T2DM)患者血管内皮功能与甲状腺激素敏感性指数的相关性。方法选取2019年6月至2020年11月,于首都医科大学附属北京朝阳医院内分泌门诊就诊的新诊断T2DM患者100例,测定空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin A1c,HbA1c)、空腹胰岛素(fasting insulin,FIns)以及游离三碘甲状腺原氨酸(free thiiodothyronine,FT3)、游离甲状腺素(free thyroxine,FT4)、促甲状腺激素(thyroid stimulating hormone,TSH)和血脂等其他代谢指标。根据FT4和TSH水平,由公式计算出甲状腺反馈分位指数(thyroid feedback quantile index,TFQI)、TSH指数(TSH index,TSHI)、促甲状腺素抵抗指数(thyrotroph thyroxine resistance index,TT4RI)作为中枢甲状腺激素敏感性指数,数值越高,代表中枢甲状腺激素敏感性越低;FT3/FT4表示外周甲状腺激素敏感性,数值越低敏感性越低。计算稳态模型评估胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)。同时,所有受试者测定血管内皮反应性充血指数(reactive hyperemia index,RHI)作为评价血管内皮功能的指标,并按照RHI结果分为合并内皮功能损害组(T2DM-ED组,RHI<1.67,43例)和不合并内皮功能损害组(T2DM-NED组,RHI≥1.67,57例)。结果T2DM-ED组的RHI为1.41±0.21,T2DM-NED组RHI为1.91±0.26;T2DM-ED组低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)、FBG、HbA1c均明显高于T2DM-NED组(P<0.05);TSH、TFQI、TSHI、LnTT4RI亦高于T2DM-NED组(P<0.05);Pearson相关分析显示,RHI与LDL-C、FBG、LnHOMA-IR、HbA1c以及TSH、TFQI、TSHI、LnTT4RI均呈负相关,与FT3/FT4呈正相关。多元线性回归分析显示,HbA1c、LDL-C、TFQI、LnTT4RI、TSHI、TSH是新诊断T2DM患者RHI降低的影响因素。结论在新诊断的T2DM患者中,甲状腺激素敏感性可能参与了血管内皮功能损害的发生。

纳米SiO_(2)复合粒子/有机硅低聚物透明超疏水复合涂层的制备及其性能

将Stöber法制备的胶体SiO_(2)粒子溶液与粉体SiO_(2)粒子进行物理共混得到SiO_(2)复合粒子溶液,以三乙氧基甲基硅烷(MTES)与正硅酸乙酯(TEOS)为前驱体制备的酸性有机硅低聚物为黏结剂,使用3-氨丙基三甲氧基硅(KH540)与全氟癸基三甲基氧硅(PFDT)对其进行改性,通过喷涂法在玻璃基底上制备出SiO_(2)复合粒子/酸性有机硅低聚物复合透明超疏水涂层。考察了SiO_(2)复合粒子、酸性有机硅低聚物、KH540及PFDT对复合涂层的影响。结果表明,当SiO_(2)复合粒子溶液由粒径为110 nm的胶体SiO_(2)粒子溶液与粒径为50 nm的粉体SiO_(2)粒子(其用量为胶体SiO_(2)粒子溶液质量的1%)组成、SiO_(2)复合粒子溶液与酸性有机硅稀释液质量比为4∶1、KH540与PFDT的添加量(以混合液总质量计,下同)均为1%时,制备的复合涂层在可见光波长范围内透光率可达88%,静态接触角达155°,在800目砂纸上磨损60 cm后仍能保持超疏水性能,具有良好的自清洁性。

华蟾素对肝癌患者介入术后外周血Bcl-2和cyclinD1蛋白表达水平的影响

目的观察华蟾素对肝癌患者介入术后外周血Bcl-2和细胞周期蛋白(cyclinD1)表达水平的影响。方法本次研究对象在2020年5月—2021年5月于医院进行介入术治疗的肝癌患者中选择100例,随机分为两组,50例患者给予患者常规介入治疗(常规介入组),50例患者在常规化疗的基础上加用华蟾素治疗(华蟾素组)。检测患者的Bax、Bcl-2、cyclinD1水平及肝功能指标[甲胎蛋白(AFP)、谷丙转氨酶(ALT)、总胆红素(TBIL)、谷草转氨酶(AST)]、免疫功能指标[免疫球蛋白G(IgG)、自然杀伤(NK)细胞、T淋巴细胞亚群(CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+))],比较两组卡氏(KPS)评分、肝功能分级标准(Child-Pugh)评分,评价疗效,观察两组不良反应发生情况。结果华蟾素组患者治疗后的Bax水平高于常规介入组(P<0.05),Bcl-2、cyclinD1水平低于常规介入组(P<0.05);华蟾素组患者治疗后的AFP、TBIL、AST水平低于常规介入组(P<0.05),ALT水平高于常规介入组(P<0.05);华蟾素组患者治疗后的IgG、NK细胞、CD_(4)^(+)水平高于常规介入组(P<0.05),CD_(4)^(+)/CD_(8)^(+)水平低于常规介入组(P<0.05);华蟾素组患者治疗后的KPS评分高于常规介入组(P<0.05),Child-Pugh评分低于常规介入组(P<0.05);华蟾素组患者治疗有效率为92.00%,高于常规介入组的74.00%(P<0.05);华蟾素组患者的不良反应发生率为20.00%,低于常规介入组的44.00%(P<0.05)。结论华蟾素可以下调肝癌患者介入术后外周血Bcl-2和cyclinD1蛋白表达水平,上调Bax水平,促进肿瘤细胞凋亡;同时可以增强患者的肝功能和免疫功能,提高生活质量,改善预后;还能提高肝癌介入治疗疗效,降低发生不良反应的风险。

PGE_(2)在环氧合酶-2抑制剂保护脓毒症肠屏障功能中的作用

目的探讨PGE_(2)在环氧合酶-2抑制剂保护脓毒症肠屏障功能中的作用及机制。方法按随机数字表法将大鼠分为六组,假手术组、帕瑞昔布钠对照组、脓毒症组、帕瑞昔布钠治疗组、COX-2抑制剂组和帕瑞昔布钠-COX-2抑制剂组,每组8只。采用盲肠结扎穿孔术(CLP)制备脓毒症模型,ELISA检测大鼠血清和肠组织中TNF-α、IL-6水平和抗炎细胞因子IL-10水平,蛋白质免疫印迹试验(Western Blot)检测前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达,于假手术或CLP术后24 h取四组大鼠肠组织,RT-PCR法检测PGE_(2)、mPGES-1、EP4的mRNA表达水平。结果与假手术组比较,脓毒症大鼠血清和肠组织中TNF-α、IL-6和IL-10增加(P<0.05),帕瑞昔布钠治疗后能够降低TNF-α、IL-6水平(P<0.05),IL-10水平增加(P<0.05);术后24 h时脓毒症组大鼠肠组织PGE_(2)、mPGES-1、EP4和EP2 mRNA表达水平比假手术组明显升高,差异有统计学意义(P<0.05);与脓毒症组比较,帕瑞昔布钠治疗脓毒症大鼠后,肠组织PGE_(2)、mPGES-1、EP4的mRNA水平明显降低,差异有统计学意义(P<0.05);大鼠肠组织前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达水平比假手术组明显升高,差异有统计学意义(P<0.05),帕瑞昔布钠治疗后,肠组织前列腺素E_(2)(PGE_(2))、前列腺素合酶-1(mPGES-1)和前列腺素受体EP4的蛋白表达水平明显降低,差异有统计学意义(P<0.05);术后24h时,与假手术组比较,脓毒症组、帕瑞昔布钠治疗组、COX-2抑制剂组及帕瑞昔布钠-COX-2抑制剂组肠组织TNF-α、IL-10和IL-6的水平明显升高,差异有统计学意义(P<0.05);与脓毒症组比较,帕瑞昔布钠治疗组、COX-2抑制剂组及帕瑞昔布钠-COX-2抑制剂组肠组织TNF-α、IL-6的水平明显降低,IL-10的水平明显升高,差异有统计学意义(P<0.05);与帕瑞昔布钠治疗组比较,COX-2抑制剂组及帕瑞昔布钠-COX-2抑制剂组肠组织TNF-α、IL-6的水平降低,IL-10的水平明显升高,差异有统计学意义(P<0.05)。结论帕瑞昔布钠可通过抑制炎症反应来减轻脓毒症时肠屏障功能的损伤,其机制可能通过COX-2-mPGES-1-PGE_(2)-EP4通路发挥抗炎的作用。

功能化氮杂环卡宾聚合树脂对Cu^(2+)的吸附研究

该研究制备了功能化氮杂环卡宾聚合树脂(PNO),旨在去除废水中Cu^(2+);基于静态和动态吸附实验,研究了PNO对废水中Cu^(2+)的吸附效果。结果表明:PNO对Cu^(2+)的最佳吸附条件为吸附剂投加量100 mg、吸附时间30 min、pH值4.0~5.9、温度298 K、转速150 r/min,最大吸附量为51.55 mg/g。PNO对Cu^(2+)的吸附过程符合Langmuir、Freundlich等温吸附模型和准二级动力学模型。动态吸附量随柱高增加、流速降低和进水Cu^(2+)浓度增加而增大。使用Thomas和Bohart-Adams模型拟合,相关系数R^(2)均大于0.92,预测值与实验值相符。经过5次静态吸附-解吸和3次动态循环再生后,PNO对Cu^(2+)的去除率仍达到第一次循环的96%以上,去除效果和再生性能良好。PNO对含铜废水高效处理具有广泛的应用前景。