Clinical efficacy and changes of serum VEGF-A,VEGF-B,and PLGF after conbercept treating neovascular agerelated macular degeneration

AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal injections for the neovascular age-related macular degeneration(AMD).METHODS:Thir ty-five patients(35 eyes)with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol.Bestcorrected visual acuity(BCVA)and central retinal thickness(CRT)were detected before the intravitreal injection and at 1,3,and 12mo after conbercept treatment.The levels of serum VEGF-A,VEGF-B,and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.RESULTS:At baseline,the mean BCVA score was 39.89±14.64 letters.The mean BCVA scores were 51.03±15.78,56.71±14.38,and 52.49±10.16 letters at 1,3,and 12mo after conbercept treatment,and the BCVA improvements were all significant,respectively(P<0.05).At baseline,the mean CRT was 436.7±141.9μm.At 1,3,and 12mo after conbercept treatment,the mean CRT values were 335.1±147.8,301.1±116.5,and 312.2±98.22μm,and the CRT improvements were all significant,respectively(P<0.05).At baseline,1 and 12mo after conbercept treatment,the mean levels of serum VEGF-A were 1013.8±454.3,953.1±426.4,and 981.5±471.7 pg/mL,the mean levels of serum VEGF-B were 46.93±24.76,42.99±19.16,and 45.32±18.76 pg/mL,the mean levels of serum PLGF at these points were 251.7±154.9,241.3±166.7,and 245.6±147.2 pg/mL,respectively.Compared with the baseline,the levels of serum VEGF-A,VEGF-B,and PLGF did not significantly change at 1 and 12mo after conbercept treatment,respectively(P>0.05).CONCLUSION:Conbercept intravitreal injection leads to BCVA and CRT improvement,however,it does not significantly affect systemic serum VEGF-A,VEGF-B,and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.

Mercury speciation, bioavailability and risk assessment on soil–rice systems from a watershed impacted by abandoned Hg mine-waste tailings

Mercury(Hg) is a global pollutant and can be accumulated in the food chain, posing exposure risks to humans. In this study, rice plants and corresponding rhizosphere soil samples were collected from a watershed of the Wawu River Basin that is heavily impacted by historic Hg mining and retorting activities. Total mercury(THg)and methylmercury(MeHg) in rice grains, as well as other tissues and soil samples, were measured. Five soil Hg fractions, as well as soil parameters, were also determined.The results show that the average concentrations of THg and MeHg in rice grains were 14 ± 7.0 lg kg^(-1) and7.2 ± 4.0 lg kg^(-1). Soil organic-bound(Hg-o) and strong complex-bound(Hg-s) were the main Hg fractions,accounting for 44% of the total. To estimate the Hg–ligand interaction in the soils, soil-N/Hg(R = 0.451, p \ 0.05),-S/Hg(R = 0.372, p \ 0.1), and-OM/Hg ratio(R = 0.320,p \ 0.5) with MeHg_(soil) were observed with significant positive correlations, indicating that the formation of Hg–OM, Hg–N–OM or Hg–S–OM complexes could prevent Hg(II) from methylation in soils. The significant positive correlations of the-N/Hg ratio,-S/Hg ratio and-OM/Hg ratio with MeHg in rice tissues suggested that Hg methylation and MeHg demethylation occurred throughout the rice paddy ecosystem. The estimated MeHg daily intake(EDI) was 0.075 ± 0.041 lg kg^(-1) bw d^(-1) and was lower than the RfD level of 0.1 lg kg^(-1) bw d^(-1) recommended by the US EPA. However, approximately 29% of the hazardous index(HI) of MeHg in grain exceeded 1, posing a potential threat to local populations, particularly pregnant women and children.

LAL test and RPT for endotoxin detection of CPT-11/DSPE-mPEG_(2000) nanoformulation: What if traditional methods are not applicable?

Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride(CPT-11) and an amphiphilic molecule DSPE-mPEG_(2000) can interfere with the limulus amebocyte lysate assay(LAL). Furthermore, the rabbit pyrogen test(RPT) results indicated that at a relatively high dosage, the drug irinotecan hydrochloride can induce a hypothermia effect which may render the RPT results ambiguous in determination of the safety of the drug formulation.Our findings demonstrate limitations of endotoxin detection in micellar drugs,and call for the necessity of developing reliable endotoxin detection methods that can overcome the interference of nanomaterials in order to better ensure the drug safety of patients in future pharmaceutical drug development.

Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells

AIM： To clarify how the endothelial nitric oxide synthase （eNOS, NOS3） make effect on outflow facility through the trabecular meshwork （TM）. METHODS： Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control （NC） cells were determined, still were the collagen, type IV, alpha 1 （COL4A1） and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS： The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION： Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component （e.g. fibronectin 1 and COL4A1）. Reduced NOS3 restrains the TM cell cycle progression at the G2/ M-phase transition and induced cell apoptosis.

Molecular basis and mechanism of action of Albizia julibrissin in depression treatment and clinical application of its formulae

Albizzia julibrissin is empirically used as an antidepressant in clinical practice.Preclinical studies have indicated that its total extracts or bioactive constituents exerted antidepressant-like responses in animal models,providing the molecular basis to reveal its underlying mechanism of action.While attempts have been made to understand the antidepressant effect of A.julibrissin,many fundamental questions regarding its mechanism of action remain to be addressed at the molecular and systems levels.In this review,we conclusively discussed the mechanism of action of A.julibrissin and A.julibrissin formulae by reviewing recent preclinical and clinical studies conducted by using depressive animal models and depressive patients.Several representative bioactive constituents and formulae were highlighted as examples,and their mechanisms of action were discussed.In addition,some representative A.julibrissin formulae that have been shown to be compatible with conventional antidepressants in clinical practice were also reviewed.Furthermore,we discussed the future research directions to reveal the underlying mechanism of A.julibrissin at the molecular and systems levels in depression treatment.The integrated study using both the molecular and systematic approaches is required not only for improving our understanding of its molecular basis and mechanisms of action,but also for providing a way to discover novel agents or approaches for the effective and systematic treatment of depression.

高血压患者早期视网膜和脉络膜微血管结构改变的研究

目的:探讨SS-OCTA评估高血压患者早期视网膜和脉络膜微循环改变的可行性。方法:前瞻性临床研究。纳入2022-07/11于西安市第一医院心内科检查确诊的2级或3级原发性高血压病患者27例(高血压组)。其中,男性14例,女性13例;年龄(57.11±3.36)岁。选取同期年龄、性别匹配且无高血压病史的正常人27名(对照组):男性12名,女性15名;年龄(55.74±2.95)岁。均行BCVA(LogMAR)、眼压、眼轴、裂隙灯检查、眼底彩色照相及SS-OCTA检查。采用SS-OCTA对受检者右眼黄斑区6mm×6mm范围进行扫描。将视网膜及脉络膜根据ETDRS分区划分为以黄斑中心凹为中心直径分别为0~1mm、1~3mm、3~6mm的3个同心圆。分析并记录黄斑区0~1mm、1~3mm、3~6mm的视网膜浅层毛细血管丛(SCP)及深层毛细血管丛(DCP)的血管密度(VD)、灌注面积(PA)、黄斑中心凹视网膜厚度(CMT)、脉络膜厚度(CT)、脉络膜血管容积(CVV)及脉络膜血管指数(CVI)。对比观察两组之间VD、PA、CMT、CT、CVV及CVI的变化。两组之间VD、PA、CMT及CVI的比较采用独立样本t检验;CT、CVV及LogMAR视力采用独立样本的Wilcoxon符号秩和检验。结果:高血压组在黄斑区0~3mm区域内DCP的VD较对照组降低(0~1mm,t=-3.144;1~3mm,t=-3.611,P<0.05);3~6mm区域内的VD较对照组有增高的趋势(t=1.715,P>0.05)。高血压组在黄斑区0~1mm区域内CMT较对照组降低(t=-2.624,P<0.05),两组之间CT、CVV及CVI均无统计学差异(P>0.05)。结论:高血压组黄斑区0~3mm区域内DCP的VD降低,0~1mm区域内CMT降低。两组之间CT、CVV及CVI均无统计学差异。黄斑区DCP的VD及CMT可能成为评估高血压患者早期视网膜和脉络膜微循环改变的指标。

Mercury accumulation,distribution,and isotopic composition in tissues of the Collared Scops Owl(Otus lettia)

Mercury is a ubiquitous contaminant known to accumulate in wildlife,particularly bird species at higher trophic levels.Knowledge of tissue-specific Hg distributions aids our understanding of Hg bioaccumulation in organisms.In this study,one adult and three juvenile Collared Scops Owls(Otus lettia)were studied to elucidate the bioaccumulation of Hg in body tissues.Six tissues and organs(feathers,nails,heart,liver,gizzard,and muscle),as well as gastric contents,were examined for total Hg(THg)and methylmercury(MeHg)contents,Hg isotopic compositions including mass-dependent fractionation(MDF;δ202Hg)and mass-independent fractionation(MIF;Δ199Hg andΔ201Hg),and C(δ13C)and N(δ15N)isotopic compositions.Tissue-specific THg and MeHg concentrations in the adult were in the ranges of 150–1360 ng/g and17–1060 ng/g,and lower in the juveniles at 91–419 ng/g and 67–350 ng/g,respectively.Theδ^(202)Hg values in the adult were strongly negative at-1.75‰±0.17‰compared with the juveniles at-0.99‰±0.25‰.The adult exhibited lower MIF values than the juveniles,at0.23‰±0.07‰forΔ^(199)Hg and 0.2‰±0.11‰forΔ^(201)Hg,comparedwith0.81‰±0.09‰and0.66‰±0.07‰,respectively.The lower adult MDF and MIF values suggest that the adult tended to accumulate negative Hg isotopes but the juvenile's positive Hg isotopes.Differences between adult and juvenile tissue Hg concentrations indicate that metabolic processes play an important role in Hg accumulation.

A New Arg54Gly Transthyretin Gene Mutation Associated with Vitreous Amyloidosis in Chinese

Purpose:To analyse the hereditary features of a Chinese pedigree with familial vitreous amyloidosis in Liaoning Province,China,and to investigate the correlation between the clinical appearance of the disease and transthyretin(TTR)gene mutation,including the locus and type of TTR gene mutation.Methods:Five patients (10 eyes) from one Chinese family were diagnosed with vitreous amyloidosis between July 1996 and April 2009.Family members were followed up subsequently,and peripheral venous blood was obtained from 13 subjects (including 2 patients,and 11 controls without clinical signs of disease).DNA samples were extracted and 4 exons of the TTR gene were amplified by polymerase chain reaction (PCR).The gene fragments were subjected to sequencing analysis.The results were analyzed with DNAMAN Windows 5.2.2.0 and Chromas sequence chart analysis software,TTR gene exons were compared between affected patients and normal controls.Results:Family pedigree analysis revealed that patients were distributed in three generations.Male and female subjects had equal prevalence,and only one parent of affected patients had signs of disease.TTR gene exon sequencing showed that the sequence of patients was identical to that of normal individuals.No TTR gene mutations were noted in 10 unaffected family members.However,a TTR Gly-54 point mutation in the 2nd exon was detected in two patients and 1 unaffected family member (one of the patients' daughters).Vitreous samples in 4 cases (7 eyes) showed positive Congo red staining,suggesting that these family members suffered from familial vitreous amyloidosis.Conclusion:This pedigree affected with familial vitreous amyloidosis was characterized by autosomal dominant inheritance;.a TTR Gly-54 point mutation in the 2nd exon is presumed to be the cause.This Gly-54 point mutation of the TTR gene is a novel mutation in vitreous amyloidosis.

疑似病毒性心肌炎的扩张型心肌病1例

1 临床资料患者,男性,25 岁,因发热1 个月,咳嗽、咳痰伴喘憋20 余天入院。患者感冒后发热未治疗。出现咳嗽、咳痰、喘憋于诊所诊断为支气管炎,治疗后症状加重。甲院胸部CT 示支气管炎;右肺中叶炎症,予抗感染治疗,效果差。入住甲院后化验脑利钠肽(brain natriuretic peptide, BNP)5 287 pg/ml;超声心动图左心室舒张末期内径(left ventricular end diastolicdimension, LVEDD)62 mm;左心室射血分数(leftventricular ejection fraction, LVEF)20%。

高海拔地区慢性阻塞性肺疾病不同分期合并症的临床分析

目的:分析青海省高海拔地区慢性阻塞性肺疾病(COPD)患者不同分期发生合并症的临床分布,对预防高海拔地区COPD合并症的发生发展以及对COPD患者的管理提供参考。方法:收集2016年1月至2019年9月在青海省某三甲综合医院3264例COPD住院患者临床资料,男性2128例,女性1136例,回顾性分析COPD患者不同分期合并症的临床分布。结果:3264例COPD患者,出现合并症的患者3204例,其中除结核外肺部感染2345例,高血压1279例,代谢紊乱综合征964例,糖尿病443例以及结核感染406例。除高血压、肺部其他疾病、糖尿病及代谢紊乱综合征外,其他在COPD不同分期之间存在统计学差异(P<0.05)。结论:大部分COPD患者均有合并症,且大于60%的患者合并四种及以上;另外,在COPD急性加重期合并肺部感染(包括结核)、心血管系统疾病、继发性红细胞增多症和低蛋白血症的发生率比COPD稳定期高。减少患者多种合并症的发生,有针对性地对其进行综合管理,对提高其生活质量具有一定的临床意义。

Reconfigurable Vortex-like Paramagnetic Nanoparticle Swarm with Upstream Motility and High Body-length Ratio Velocity

Drug delivery systems with high-targeted doses can minimize excipients,reduce side effects,and improve efficacy.Human blood circulation is a complex circulatory system,and the motion control of microrobots in the static flow field in vitro is completely different from in vivo.How to achieve precise counterflow motion for targeted drug delivery without vascular blockage and immune rejection is the biggest challenge for micro-nano robots.Here,we propose a control method that enables vortex-like paramagnetic nanoparticle swarm(VPNS)to move upstream against the flow.By mimicking the clustering motion of wild herring schools and the rolling of leukocytes,VPNS are incredibly stable even when subjected to high-intensity jet impacts in the blood environment,can travel upstream,anchor at the target location,and dissipate when the magnetic field is withdrawn,which greatly reduces the risk of thrombosis.VPNS can also upstream along the vessel wall without an additional energy source and has a marked targeted therapeutic effect on subcutaneous tumors.

Rapid Access to Polysubstituted Tetrahydrocarbazol-4-ones via Sequential Selective C—H Functionalization from N-Nitrosoanilines

Comprehensive Summary Herein,we have developed a strategy of Rh(III)-catalyzed C—H activation of N-nitrosoanilines and iodonium ylides to construct novel tetralydrocarbzol-4-one scaffolds,which provided valuable templates for sequential C—H functionalization such as alkylation,alkenylation,amidation and(hetero)arylation at C^(5)-position of tetralydrocarbzol-4-one with different coupling partners.Gram-scale synthesis and further transformations of tetralydrocarbzol-4-one derivatives to Ondansetron and its analogues demonstrated the utility of this protocol,which enabled the concise and diverse construction of biologically active molecules.

一种多功能隔膜实现对多硫离子和锂离子的双重调控

多硫离子穿梭和锂枝晶生长严重阻碍了锂硫电池的实际应用进程,而合理的隔膜结构可以达到一石二鸟的作用.本工作设计了一种携带有分散性TiN/CoO颗粒的氮掺杂碳纳米管结构(TCCNT),并将其用于锂硫电池隔膜修饰层.TCCNT的多孔结构和表面/内部携带的TiN/CoO颗粒不但实现了对多硫化物的物理、化学吸附和快速催化转化作用,其高导电性的空腔结构和亲锂作用还能够均化锂离子流,在5 mA cm^(-2)的电流密度下实现长达2000 h的均匀锂沉积/剥离过程.TCCNT合理的结构设计有利于各材料组分之间最大限度地发挥协同效应.采用改性隔膜所组装的锂硫电池在常规和高硫载量两种情况下均表现出较好的电化学性能,表明其具有一定的实际应用潜力.

Innovative Irinotecan-Loaded Nanomicelles Will Enter Phase I Clinical Trial in 2021

Recent progress at the National Center for Nanoscience and Technology of China has enabled an extremely facile method to encapsulate irinotecan(CPT-11)into micelle-based nanoparticles(named as IH-NM).In preclinical study,compared with free CPT-11,IH-NM exhibited 1.56-fold higher maximum tolerance dose(MTD),-2.45-fold higher antitumor efficacy at 80%of MTD dosage,higher plasma exposure,and slower clearance from the plasma.The IH-NM technology received Clinical Trial Permission from the National Medical Products Administration(NMPA)of China on Mar 6,2019.The Phase I clinical trial is under preparation.

Recent advances in carbonized non-noble metal–organic frameworks for electrochemical catalyst of oxygen reduction reaction

The non-noble metal oxygen reduction reaction(ORR) catalysts prepared by carbonization of metal–organic framework(MOF) have attracted more and more attentions in the fields of fuel cells and metal-air batteries due to their unique intrinsic advantages such as high catalytic activity, low price, simple synthesis and good adaptability. Different from the study of traditional high active noble metal catalysts, this review systematically summarizes recent developments on non-noble metal(Fe,Co, Cu, Ni, Mn and Mo) ORR catalysts prepared by various MOFs carbonization in different metal centers. The effects of synthesis strategies and pyrolysis conditions on the catalyst properties are discussed. Meanwhile, the key parameters of catalytic performances(including active sites, dispersed state and specific surface area) are discussed and the prospect is presented. It is expected that this review will provide effective guidance for future studies on carbonized non-noble MOFs for ORR electrochemical catalyst.

柳氮磺吡啶通过铁死亡途径增强结直肠癌细胞放射敏感性研究

目的探究低剂量柳氮磺吡啶(SAS)对结直肠癌细胞的放疗增敏作用。方法CCK-8检测不同浓度SAS对结直肠癌细胞的增殖抑制作用,采用凋亡、自噬等抑制剂联合SAS处理结直肠癌细胞,CCK-8法比较细胞活力。采用锥虫蓝染色、平板克隆形成、细胞生长曲线等实验评价低浓度SAS联合放疗对结直肠癌细胞的体外放疗增敏作用。通过检测细胞内脂质过氧化物、铁死亡蛋白标志物(GPX4、PTGS2)等,探究低浓度SAS联合放疗对细胞铁死亡的促进作用。利用小鼠皮下移植瘤模型,明确SAS的体内放疗增敏效应。结果高浓度SAS可诱导结直肠癌细胞凋亡与铁死亡。低浓度SAS增强结直肠癌细胞放疗敏感性,该效应可被铁死亡抑制剂(Fer-1)阻断。低浓度SAS联合放疗显著增加细胞内脂质过氧化物含量与PTGS2表达,降低GPX4表达。皮下移植瘤模型中SAS亦显示显著的放疗增敏效应。结论低浓度SAS通过铁死亡途径增强结直肠癌细胞放疗敏感性。

Effects of dexmedetomidine on the expression of inflammatory factors in children with congenital heart disease undergoing intraoperative cardiopulmonary bypass:A randomized controlled trial

Importance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass(CPB)and protects neural function.However,the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Objective:To investigate the effect of dexmedetomidine on the cognitive level and expression of inflammatory factors in children with congenital heart disease undergoing intraoperative CPB.Methods:Ninety children with congenital heart disease were recruited and randomly divided into 3 groups of 30 children in each.In Group 1,a 1.0μg·kg-1·h-1 intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.2μg·kg-1·h-1 infusion until the surgical incision.In Group 2,a 0.5μg/kg intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia,followed by a 0.1μg·kg-1·h-1 infusion until the surgical incision.The control group was given physiological saline using the same method as in Groups 1 and 2.The serum levels of nuclear factor-kappa B(NF-κB),S-100βprotein,neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were measured before the surgery(T1),at the end of CPB(T2),2 hours after CPB(T3),6 hours after CPB(T4),and 24 hours after CPB(T5).The Wechsler Intelligence Scale for children(WISC)was measured before the operation and at 3,6,and 12 months after the operation to evaluate the neurodevelopmental state of the children.Results:The levels of the NF-κB,S-100βprotein,NSE,TNF-α,IL-6 were significantly higher at T2,T3,or T4 than before the surgery(T1)in the control group or the dexmedetomidine groups.However,the increases of NF-κB,TNF-α,IL-6,S-100βand NSE levels were significantly smaller in the dexmedetomidine groups than those in the control group(P<0.017).The WISC scores were similar among the three groups before or after the operation.Interpretation:The increases in NF-κB,TNF-α,and IL-6 levels indicated aggravation of the inflammatory reaction and the increase S-100βprotein and NSE levels indicated that the nervous system was damaged.Administration of dexmedetomidine to children with congenital heart disease undergoing intraoperative CPB can inhibit the inflammatory response and may ameliorate the neurodevelopmental damage caused by CPB.

P45 technology reveals bow-and-arrow sign in human ankle

To the Editor:Recent studies have shown that the morphology of bone in vivo,including the shape,diameter,length,curve,and alignment of the bone,adapt to longterm loads both before and after skeletal maturity.The deformation and rate are different according to the magnitude of strain,the mode of action,position and the quality of bone of the strain,which is named by law of dynamic deformation of bone.[1]Here,we found that the existence of circular bone trabecula in the calcaneus by P45 plastination technology.It might be caused by the force conduction to the flexor digitorum brevis during the contraction of the triceps surae according to this law.

Correlated tunneling in high-order above threshold dissociative ionization of H_(2)

Comprehension of photon-triggered molecular processes is essential in the study of various important topics in physics,chemistry,and biology.Here we propose a correlated tunneling picture to understand the dissociative ionization process of molecules in intense laser fields based on a quantum model developed in the framework of many-body S-matrix theory including nuclear vibrational motion.In this quantum correlation picture,the single ionization of H_(2)and the subsequent electron-ion recollisioninduced dissociation are considered as an entangled correlated process.It enables us to attribute the interference pattern in the joint-energy spectra to combined effects of single-slit diffraction and multi-slit interference of correlated electron-nuclear wave packets in the time domain.Our work opens a new avenue to understanding molecular dissociative ionization processes in external fields.