Introducing hydroxyl groups to tailor the d-band center of Ir atom through side anchoring for boosted ORR and HER

Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.

Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial

Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer.This study was to compare the efficacy and safety of a weekly taxaneanthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer.Methods:Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide(FEC) regimen or weekly paclitaxel-epirubicin(PE) regimen.The primary endpoint was the pathologic complete response(pCR) rate.Other endpoints included the clinical tumor response,breast-conserving surgery rate,and adverse events.Results:Between March 2010 and September 2013,293 patients were randomized to the FEC(n=151) and PE(n=142) arms.The overall clinical response rate was significantly higher in the PE arm than in the FEC arm(76.06%vs.59.95%,P=0.001).Consistently,the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm(P<0.001).However,the pCR rate was similar in the two arms(10.61%vs.12.31%,P=0.665).Overall,36(27.27%) patients in the FEC arm and 6(35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms,with more severe neutropenia in the PE arm than in the FEC arm(11.97%vs.5.96%,P=0.031).Conclusions:In patients with locally advanced breast cancer,weekly PE was not superior to FEC in terms of pCR.However,weekly PE has a higher response rate and superior down-staging effects.On this account,the PE regimen may be considered an alternative option for locally advanced breast cancer.Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer.Trial registration Chinese clinical trial registry,ChiCTR-TRC-10001043,September 21。

A universal elliptical disc(UED)model to represent natural rock fractures

Since natural fractures are often non-equidimensional,the circular disc model still has great limitations.By contrast,the elliptical disc model is more applicable to representing natural fractures,especially for slender ones.This paper developed a universal elliptical disc(UED)model by incorporating the center point,size,and azimuth of fractures as variables.Specifically,with respect to the azimuth of elliptical fractures in three-dimensional(3D)space,we proposed a paradigm to construct its probability density function(PDF)by coupling the orientation and rotation angle of long axis based on three coordinate transformations.To illustrate the construction process of the PDF of the fracture azimuth,we took the orientation following the Fisher distribution and the rotation angle following Von Mises distribution as an example.A rock slope is used to show the use of the developed UED model,and the 3D DFNs for the slope rock mass are generated by Monte Carlo simulation.In addition,the DFNs for the rock mass are also generated based on the existing circular disc model and non-universal elliptical disc model.The comparison results from the three models clearly illustrate the superiority of the UED model over the existing circular and non-universal elliptical disc models.

Increased pathologic complete response are expected in HER2-positive and triple-negative locally advanced breast cancers

To The Editor I want to congratulate Dr.Tan and colleagues for their article entitled'Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial'[1].The pathologic complete response(pCR)rate was similar in the two arms(10.61%vs.12.31%,P=0.665).However,the

Identification of Two Mutations in PCDHGA4 and SLFN14 Genes in an Atrial Septal Defect Family

Atrial septal defect (ASD)is a common acyanotic congenital cardiac disorder associated with genetic mutations.The objective of this study was to identify the genetic factors in a Chinese family with ASD patients by a whole exome sequencing approach.Causative ASD gene mutations were examined in 16 members from a three-generation family,among which 6 individuals were diagnosed as having ASD.One hundred and eighty-three unrelated healthy Chinese were recruited as a normal control group.Peripheral venous blood was collected from every subject for genetic analysis.Exome sequencing was performed in the ASD patients.Potential causal mutations were detected in non-ASD family members and normal controls by polymerase chain reaction and sequencing analysis.The results showed that all affected family members carried two novel compound mutations,c.1187delT of PCDHGA4 and c.2557insC of SLFN14,and these two mutations were considered to have synergetic function on ASD.In conclusion,the mutations of c.1187delT of PCDHGA4 and c.2557insC of SLFN14 may be pathogenic factors contributing to the development of ASD.

每周一次的紫杉烷–蒽环类联合方案与3周一次的以蒽环类为基础方案治疗局部晚期乳腺癌的随机对照研究

背景与目的已有大量研究证实了紫杉烷与蒽环类联合化疗治疗乳腺癌的疗效。然而,很少有研究评价每周一次紫杉烷–蒽环类治疗方案对局部晚期乳腺癌的疗效。本研究旨在比较每周一次紫杉烷–蒽环类治疗方案和3周一次以蒽环类为基础的治疗方案在治疗局部晚期乳腺癌上的疗效和安全性。方法局部晚期乳腺癌患者随机分组,接受4–6周期的3周一次的5-氟尿嘧啶–表柔比星–环磷酰胺(5-fluorouracil–epirubicin–cyclophosphamide,FEC)或每周一次的紫杉醇–表柔比星(paclitaxel–epirubicin,PE)的新辅助化疗方案。主要终点是病理完全缓解(pathologic complete response,pCR)率。其他终点包括临床肿瘤反应、保乳手术率和不良事件。结果从2010年3月至2013年9月,293例患者被随机分为FEC(n=151)组和PE(n=142)组。PE组的总临床反应率显著高于FEC组(76.06%vs. 59.95%,P=0.001)。一致的是,PE组化疗后病理性T和N分期显著低于FEC组(P <0.001)。但两组的pCR率是相似的(10.61%vs. 12.31%,P=0.665)。总体而言,FEC组36例(27.27%)和PE组6例(35.28%)适合进行保乳手术。两个治疗组中患者的大多数不良事件相似,其中PE组患者的中性粒细胞减少症比FEC组更严重(11.97%vs. 5.96%,P=0.031)。结论:在局部晚期乳腺癌患者中,每周一次PE方案在pCR方面并不优于每3周一次FEC方案。然而,每周一次PE方案具有较高的应答率和较好的肿瘤降级效果。因此,PE方案可能为治疗局部晚期乳腺癌的可选方案。还需要长期随访数据来证实这种方案对治疗局部晚期乳腺癌患者的疗效。

A new estimation method and an anisotropy index for the deformation modulus of jointed rock masses

The deformation modulus of a rock mass is an important parameter to describe its mechanical behavior.In this study,an analytical method is developed to determine the deformation modulus of jointed rock masses,which considers the mechanical properties of intact rocks and joints based on the superposition principle.Due to incorporating the variations in the orientations and sizes of joint sets,the proposed method is applicable to the rock mass with persistent and parallel joints as well as that with nonpersistent and nonparallel joints.In addition,an anisotropy index AIdmfor the deformation modulus is defined to quantitatively describe the anisotropy of rock masses.The range of AIdmis from 0 to 1,and the more anisotropic the rock mass is,the larger the value of AIdmwill be.To evaluate the proposed method,20 groups of numerical experiments are conducted with the universal distinct element code(UDEC).For each experimental group,the deformation modulus in 24 directions are obtained by UDEC(numerical value)and the proposed method(predicted value),and then the mean error rates are calculated.Note that the mean error rate is the mean value of the error rates of the deformation modulus in 24 directions,where for each direction,the error rate is equal to the ratio of numerical value minus predicted value to the numerical value.The results show that(i)for different experimental groups,the mean error rates vary between 5.06%and 22.03%;(ii)the error rates for the discrete fracture networks(DFNs)with two sets of joints are at the same level as those with one set of joints;and(iii)therefore,the proposed method for estimating the deformation modulus of jointed rock masses is valid.

Impact of Coronary Artery Anatomy in Arterial Switch Operation:In-hospital and Post-discharge Outcomes

Objective The influence of the coronary artery anatomy on the prognosis of patients receiving an arterial switch operation(ASO)is currently controversial,and the risk factors for this operation may change in more complicated patients.This study aimed to investigate the influence of coronary artery anomalies on the in-hospital and post-discharge outcomes of ASO in patients with transposition of the great arteries(TGA)and Taussig-Bing anomaly(TBA).Methods We retrospectively reviewed 206 patients who underwent ASO from January 2007 to December 2019.The median age at operation was 33[interquartile range(IQR):20–71]days.Median follow-up time was 7.2 years(IQR:4.0–10.3 years).Results Coronary anomalies were present in 86 patients(41.7%),with 9(4.4%)of them having a single coronary artery.Additional coronary features included intramural courses in 5(2.4%)patients,ostial stenosis in 1(0.5%)patient,and accessory coronary artery orifices in 5(2.4%)patients.There were 32(15.5%)in-hospital deaths and 8(4.6%)post-discharge deaths,yielding an overall survival of 81.3%,80.7%and 79.9%at 1,5 and 10 years,respectively.Mortality due to ASO has been drastically decreased since 2013.Patients with a single coronary artery had higher rate of in-hospital mortality,but this finding was not statistically significant.The earlier surgical era(OR:2.756)and a longer cardiopulmonary bypass time(OR:2.336)were significantly associated with in-hospital mortality,while coronary patterns were not.An intramural coronary artery(HR:10.034)and a patient age of older than 1 year at the time of ASO(HR:9.706)were independent predictors of post-discharge mortality.Conclusion ASO remains the procedure of choice for TGA with coronary anomalies with acceptable in-hospital and post-discharge outcomes in terms of overall survival and freedom of reoperation.However,intramural coronary artery is an independent risk factor for post-discharge mortality.Timely surgery within the 1st year of life helps improve overall midterm survival of ASO.

Association between childhood obesity and gut microbiota:16S rRNA gene sequencing-based cohort study

BACKGROUND This study aimed to identify characteristic gut genera in obese and normal-weight children(8-12 years old)using 16S rDNA sequencing.The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity.Thirty normal-weight and thirty age-and sex-matched obese children were included.Questionnaires and body measurements were collected,and fecal samples underwent 16S rDNA sequencing.Significant differences in body mass index(BMI)and body-fat percentage were observed between the groups.Analysis of gut microbiota diversity revealed lowerα-diversity in obese children.Differences in gut microbiota composition were found between the two groups.Prevotella and Firmicutes were more abundant in the obese group,while Bacteroides and Sanguibacteroides were more prevalent in the control group.AIM To identify the characteristic gut genera in obese and normal-weight children(8-12-year-old)using 16S rDNA sequencing,and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity.METHODS Thirty each normal-weight,1:1 matched for age and sex,and obese children,with an obese status from 2020 to 2022,were included in the control and obese groups,respectively.Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children.Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis.RESULTS Significant differences in BMI and body-fat percentage were observed between the two groups.The Ace and Chao1 indices were significantly lower in the obese group than those in the control group,whereas differences were not significant in the Shannon and Simpson indices.Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children(P<0.01),suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups.Prevotella,Firmicutes,Bacteroides,and Sanguibacteroides were more abundant in the obese and control groups,respectively.Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children.CONCLUSION Obese children exhibited lowerα-diversity in their gut microbiota than did the normal-weight children.Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

MicroRNAs通过调节自噬影响乳腺癌的耐药性

自噬是一种保守的分解代谢过程,其特征在于通过溶酶体依赖性途径降解和再循环胞质成分或细胞器。它与乳腺癌的耐药性有着复杂而密切的关系。小分子核糖核酸(micro RNA,mi RNA)是小的非编码分子,可通过基因表达的转录后调控来影响众多细胞过程,包括自噬。许多蛋白质和途径能调节自噬,而其中一些反过来又被mi RNA调节。另外,这些mi RNA可能会影响乳腺癌的耐药性。耐药性是乳腺癌患者远处复发、转移和死亡的主要原因。在这篇综述中,我们总结了乳腺癌自噬与药物耐药性之间的因果关系,同时还讨论了自噬相关蛋白和途径及其相关的mi RNA在乳腺癌耐药性中的作用。

Application of the concept of continuous dopaminergic stimulation for the management of Parkinson's disease

Continuous dopaminergic stimulation(CDS)is a prominent therapeutic concept for the treatment of Parkinson’s disease(PD),which proposes that continuous brain dopamine-receptor stimulation,rather than intermittent doses of oral L-dopa,prevents or manages L-dopa-induced dyskinesias(LIDs).In the normal situation,dopaminergic neurons in the substantia nigra pars compacta fire tonically to keep the dopamine receptor stimulation at a steady-state level.But when the dopaminergic pathway is impaired,the dopamine receptor stimulation becomes intermittent or pulsatile.This pulsatile stimulation causes a series of gene and protein changes in striatal neurons,leading to alterations in the firing patterns of basal ganglia neurons that result in LIDs.Studies in animal models and clinical trials of PD have shown that approaches providing CDS,currently including patches,extended-release formulations of L-dopa or dopamine agonists,continuous delivery of apomorphine and duodenal L-dopa infusion,are associated with a decreased risk of LIDs.In this review,we summarize both preclinical and clinical evidence for the five methods that may provide CDS in theory and compare the advantages and disadvantages of these methods.

Gastric carcinoma with osteoclast-like giant cells:a case report and review of the literature

Gastric carcinoma with osteoclast-like giant cells(OGCs) is an extremely rare tumor. So far,only six cases have been reported in the literature. Here we report an additional case of this tumor in a Chinese 78-year-old man presented with abdominal pain,vomiting,and hematemesis. Physical examination and gastroscopy revealed a tumor in the gastric antrum. The biopsy and pathological findings indicated a gastric adenocarcinoma with OGCs,which were present in both the tumor and the metastatic lymph nodes. Further immunohistochemical staining indicated that OGCs were reactive with CD68,CD45,and vimentin protein,but not with pancytokeratin,carcinoembryonic antigen,or epithelial membrane antigen,suggesting the monocytic/histiocytic derivation of these OGCs. In situ hybridization for Epstein-Barr virus showed no nuclear positivity in either adenocarcinoma or OGCs. Postoperative follow-up showed that the patient had survived for at least 6 months without recurrence. Further investigation is warranted to clearly define the prognostic significance of OGCs in gastric carcinoma.

Use of anti-tuberculosis drugs among newly diagnosed pulmonary tuberculosis inpatients in China: a retrospective study

Background:China’s national tuberculosis control program(NTP)provides free,first-line anti-tuberculosis(TB)drugs to pulmonary TB patients.This treatment regimen follows the World Health Organization’s(WHO)guideline.The objective of this paper is to evaluate the current status of anti-TB drug use for newly diagnosed pulmonary TB inpatients treated in prefecture-and county-level designated hospitals.Methods:Three prefecture-level hospitals and nine county-level hospitals were selected for the study.All newly diagnosed pulmonary TB inpatient medical records from 2012 were reviewed and doubly examined by two national senior physicians.The rational use of anti-TB drugs was evaluated based on criteria in line with WHO’s guideline.Results:Of the 2,060 total treatment regimens for TB,53.1%were found to be rational(1093/2060).The percentages in prefecture-level and county-level hospitals were 50.3%(761/1513)and 60.7%(332/547),respectively.The difference between the two levels of hospitals was statistically significant(Chi-square value=17.44,P<0.01).The percentages of rational treatment regimens for first-time hospitalizations and for two or more hospitalizations were 59.5%(983/1653)and 27.0%(110/407),respectively,with a statistically significant difference(Chi-square value=138.00,P<0.01).The overall use of second-line drugs(SLD)was 54.9%(1131/2060).The percentages for prefecture-level and county-level hospitals were 50.6%(766/1513)and 66.7%(365/547),respectively.A statistically significant difference was found(Chi-square value=42.06,P<0.01).The use of SLD for inpatients hospitalized once and inpatients hospitalized twice or more was 58.4%(966/1653)and 40.5%(165/407),respectively,with a statistically significant difference(Chi-square value=42.26,P<0.01).Conclusions:Half of inpatients might be treated with irrational regimens,and the use of SLD was more appropriately dispensed in city-level hospitals than in county-level hospitals.Trainings and guidelines for health personnel,supervision led by health authorities and increased investment to designated hospitals may help to improve the rational use of anti-TB drugs.

Assessment of global and regional left ventricular twistand displacement in anterior myocardial infarction using2-dimensional strain imaging

The recent development of 2-dimensional strain(2D strain)imaging can provide a powerful alternative for assessing left ventricular(LV)torsion.This study was conducted to evaluate the global and regional left ventricular twist by 2D strain in patients with anterior wall myocardial infarction(AMI).A total of 55 AMI patients were divided into two groups according to their ejection fraction(EF)values(group A:LVEF≥50%;group B:LVEF<50%),and 35 normal people served as the control group.Using 2-dimensional strain software,global and regional LV rotation and displacement were obtained at two planes.Compared with the control group,patients of group A showed reduced peak LV twist of the anterior and anterior-septal wall(9.26�1.89 vs 10.74�2.67;9.71�1.71 vs 11.36�2.29,both P<0.05),but the radial displacement and global twist were maintained(P>0.05).Differently,regional and global LV twist and radial displacement in patients of group B deceased significantly,especially in the anterior and anterior-septal wall,as compared with patients in the control or group A(both P<0.05).Moreover,a strong correlation was noted between peak twist and radial displacement;the twist-displacement loop was markedly distorted in patients of group B.This study demonstrated that 2D strain has a potential ability for quantification of left ventricular global and segment twist and radial displacement in patients with coronary artery disease.

The value of ultrasound elastography in differential diagnosisof superficial lymph nodes

The study evaluated the value of ultrasound elastography in differentiating the benign and malignant superficial lymph nodes.A total of 112 subjects,including 82 patients with enlarged lymph nodes and 30 healthy volunteers,were recruited.All the subjects were examined by B-mode ultrasonography,power Doppler ultrasonogra-phy and elastography.Most of the patients were histo-pathologically confirmed by needle aspiration cytology and some patients were diagnosed by clinical data combined with follow-upfindings.The sensitivity,speci-ficity and accuracy of B-mode ultrasonography were 59.8%,76.5%and 67.1%,those of the bloodflow classification by power Doppler ultrasonography 77.0%,82.3%and 79.4%and those of elastographic classification 74.7%,97.1%and 84.5%,respectively.The elasticity of the lymph nodes was quantitatively measured and defined as stiffness value.When the stiffness value of 2.395 was taken as the cutoff point,the sensitivity and specificity of elastography were 78.41%and 98.51%,and the Youden index reached the highest,with the value being 0.7692.The stiffness values of two indeterminate benign lymph nodes,the elastrographicfindings of which were rated as patterns 2 and 3,were below the cutoff point.The elastographicfindings of 10 malignant lymph nodes were also classified as pattern 2 or 3.Only one of them had the stiffness values below the cutoff point.It was concluded that ultrasound elastography is a novel,noninvasive and convenient tool for the differentiation of the nature of the superficial lymph nodes in clinical practice.