Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

社区空巢老人健康服务与教育管理研究

近些年人口老龄化问题日益凸显,由人口老龄化所导致的一系列社会矛盾更是愈发突出,养老难已然成为当今社会面临的一个公共问题。据了解,我国老龄人口早已过亿,且未来空巢老人队伍会日渐庞大,社区作为空巢老人的主要活动阵地,必须要以高瞻远瞩之视角,科学审视空巢老人的健康服务与教育管理问题,进一步对空巢老人负责任,给予空巢老人更多关注和照顾。

Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis

BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.

Serum inflammatory markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for mycoplasma severity

BACKGROUND Mycoplasma pneumoniae pneumonia(MPP)significantly impacts pediatric health,necessitating markers for early severe disease identification.AIM To investigate the correlation between serum inflammatory marker and the severity of MPP in children.METHODS A prospective study was carried out from January 2023 to November 2023.A total of 160 children with MPP who underwent treatment were selected:80 had severe MPP and 80 had mild MPP.Clinical and laboratory data were collected at the time of hospital admission and during hospitalization.Receiver operating characteristic curves were utilized to assess the diagnostic and prognostic for severe MPP.RESULTS Fever duration and length of hospitalization in pediatric patients with severe MPP exceeded those with mild MPP.The incidence of pleural effusion,lung consolidation,and bronchopneumonia on imaging was markedly elevated in the severe MPP cohort compared to the mild MPP cohort.In contrast to the mild cohort,there was a notable increase in C-reactive protein(CRP),procalcitonin(PCT),erythrocyte sedimentation rate,lactic dehydrogenase,D-dimer,and inflammatory cytokines[interleukin(IL)-6,IL-8,IL-10 and tumor necrosis factor(TNF)-α]in the severe MPP group were significantly higher.CONCLUSION Serum inflammatory markers(CRP,PCT,IL-6,D-dimer,IL-10 and TNF-α)were considered as predictors in children with severe MPP.

Effects of three-dimensional quality assessment nursing intervention on efficacy and disease management of patients undergoing esophageal cancer surgery

BACKGROUND Esophageal cancer is one of the most common malignant tumors.The three-dimensional quality structure model is a quality assessment theory that includes three dimensions:Structure,process,and results.AIM To investigate the effects of nursing interventions with three-dimensional quality assessment on the efficacy and disease management ability of patients undergoing esophageal cancer surgery.METHODS In this prospective study,the control group received routine nursing,and the intervention group additionally received a three-dimensional quality assessment intervention based on the above routine care.Self-efficacy and patient disease management abilities were evaluated using the General Self-Efficacy Scale(GSES)and Exercise of Self-Care Agency scale,respectively.IBM SPSS Statistics for Windows,version 17.0,was used for the data processing.RESULTS This study recruited 112 patients who were assigned to the control and experi-mental groups(n=56 per group).Before the intervention,there was no significant difference in GSES scores between the two groups(P>0.05).After the inter-vention,the GSES scores of both groups increased,with the experimental group showing higher values(P<0.05).At the time of discharge and three months after discharge,the scores for positive attitudes,self-stress reduction,and total score of health promotion in the experimental group were higher than those in the control group(P<0.05).CONCLUSION The implementation of a three-dimensional quality structure model for postoperative patients with esophageal cancer can effectively improve their self-management ability and self-efficacy of postoperative patients.

Variable and Invariable,Explore the Value-Creation Techniques of Management Accounting by Benchmarking the Financial Management of Large Enterprises

With the development of information technology such as ChatGPT,artificial intelligence,5G,and so on,technological innovation brings about a qualitative change in the economic business.This change is embodied in breakthroughs in the field of science and technology and the iterative upgrading process of products.The traditional business model undoubtedly fails to adapt to the management needs of modern enterprises,while traditional financial practices and knowledge reserves cannot meet these needs.Faced with sudden technological changes and the emergence of financial sharing,financial robots,etc.,there is an urgent need for financial practitioners to transform from traditional financial accounting to value-creating management accounting.In the future,financial professionals with the ability to embrace uncertainty,adapt to environmental changes,and find breakthroughs in uncertain environments will be the most sought-after by enterprises.This paper aims to benchmark the excellent financial management models of large enterprises and conduct thematic research on financial management in large enterprises.It seeks to explore,in the era of big data management accounting,the road and art of creating value in enterprises.The objective is to provide references for colleagues in the financial field and to explore effective ways to generate value for enterprise management ideas,thus serving as a reference point in the financial transformation journey.

Resequencing-based QTL mapping for yield and resistance traits reveals great potential of Oryza longistaminata in rice breeding

As a natural genetic reservoir, wild rice contains many favorable alleles and mutations conferring high yield and resistance to biotic and abiotic stresses. However, there are few reports describing favorable genes or QTL from the AA genome wild rice O. longistaminata, which is characterized by tall and robust habit and long tassels and anthers and shows high potential for use in cultivated rice improvement. We constructed a stable BC_(2)F_(20) backcross inbred line(BIL) population of 152 lines from the cross of 9311 × O.longistaminat. Some BILs showed large panicles, large seeds, and strong resistance to rice false smut, bacterial leaf blight, rice blast spot, and brown planthopper. Genomic resequencing showed that the 152 BILs covered about 99.6% of the O. longistaminata genome. QTL mapping with 2432 bin markers revealed 13QTL associated with seven yield traits and eight with resistance to brown planthopper and to four diseases. Of these QTL, 12 for grain yield and 11 for pest and disease resistance are novel in Oryza species.A large-panicle NIL1880 line containing QTL qPB8.1 showed a nearly 50% increase in spikelet number and27.5% in grain yield compared to the recurrent parent 9311. These findings support the potential value of O. longistaminata for cultivated rice improvement.

“绿色电力”理念的应用化学人才培养研究与实践

能源电力的可持续发展是支撑我国未来经济社会高质量发展的首要任务,因此电力行业的人才培养不可或缺。在新工科建设背景下,华北电力大学作为电力行业卓越人才培养的摇篮,以电力产业需求为导向,率先提出并构建了基于“绿色电力”理念的复合型应用化学人才培养模式,并成功应用于本科教学改革与实践。使学生既掌握电力环保技术的应用背景和工程实践技能,又具备协同分析及解决复杂多污染物控制的创新能力,以培养新时代应用化学高素质人才,服务国家发展。

干性年龄相关性黄斑变性现代医药与中医药研究新进展

年龄相关性黄斑变性(ARMD)是中老年人不可逆性视力损害的一种主要原因,严重影响个人生活质量并加重社会卫生经济负担。晚期ARMD在临床上有两种表现类型,即干性ARMD(dARMD)和湿性ARMD(nARMD)。nARMD以抗血管内皮生长因子作为一线药物已取得显著疗效,而dARMD尚无确切的治疗方法。本文就dARMD在临床试验中取得显著进展、可望上市的潜在药物、生物疗法和中医中药进行综述,包括抗炎药(强力霉素和FHTR2163)、抗氧化药(利舒尼布和依来米普瑞肽)、补体抑制剂(APL-2和滋目若)、视觉周期调节剂(ALK-001)、神经保护剂(溴莫尼定)、干细胞移植(MA09-hRPE和BMMF)、基因疗法(HMR59)和中医中药(藏红花、姜黄素、槲皮素和白藜芦醇)等。这些药物临床试验疗效显著,应用前景广阔,为ARMD改善与治疗带来巨大希望。

中药单体治疗糖尿病视网膜病变的研究进展

糖尿病视网膜病变(DR)是一种常见的糖尿病慢性并发症,可导致视网膜中微血管的不可逆性损伤,是糖尿病患者首要致盲性眼病。DR的发病机制主要涉及氧化应激、炎症反应与新生血管形成等因素。临床上多以视网膜激光光凝术、玻璃体切割术或药物治疗为主。我国传统中药组方与中药单体在DR治疗,特别是视网膜保护方面具有独特功效,为DR治疗提供有益补充。本文综述了代表性中药组方与中药单体在DR治疗中的应用实践与作用机制,以期为DR的临床治疗与新药研发提供参考。

中药单体治疗青光眼的研究进展

青光眼(glaucoma)是一组进行性视神经损害,导致视力损伤的疾病,是人类首要不可逆致盲性眼病,病理性眼压升高是其危险因素。临床上常用降眼压类与保护视神经类药物治疗,以对症治疗为主,疗效不理想。中药单体兼有中药与化药双重优势,我国传统中药与中药单体在青光眼治疗,特别是视神经保护方面具有独特优势,可供研发的空间很大。本文综述了代表性组方与单味中药,尤其是代表性中药单体在青光眼治疗中的应用与机制,以期为青光眼临床治疗与新药研发提供参考。

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Objective: To discuss the expression of long noncoding RNA TUG1 (IneRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods: Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of IncRNA-TUG I in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between IncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using IncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA-transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after IncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western -blot test. Results: The expression level of lneRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P<0.05) and the high expression level of IncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (/'<0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by IncRNA-TUG1 specific siRNA (P<0.05). The results of qRT-PCR and western -blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after IncRNA-TUG1 was silenced (P<0.05). Conclusions: IncRNA-TUG1 shows an up -regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. IncRNATUGI can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met.

Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01(a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma

Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.

Nitrate in the Changjiang diluted water:an isotopic evaluation on sources and reaction pathways

A cruise covering two transects in the Changjiang(Yangtze)estuary in July 2017 was conducted,aiming to explore the sources for riverine NOˉ3 and identify reactions involved in the NO_(3)^(-)transformations along the transport of the Changjiang diluted water(CDW).In the river water,NO_(3)^(-)was fundamentally contributed by chemical fertilizer leakage in the watershed according to isotope signals.Sewage discharge may also be significant on riverine NO_(3)^(-)inventory,while the isotope signal was masked by nitrification.Together with the transport of the CDW,NO_(3)^(-)production was observed in waters with low salinities(<20)and high turbidities.Nitrification resulted from the mineralization of riverine organic nitrogen;therefore,the high turbidity was linked to active production.In the outer plume,coupled with stratification,a significant decrease in NO_(3)^(-)concentration was observed in the surface water.In parallel,enrichment inδ^(15)N-NO_(3)^(-)andδ^(18)O-NO_(3)^(-)was found,indicating biological consumption by phytoplankton.The difference in the stratification intensity between two transects led to variations in NO_(3)^(-)concentrations and isotope compositions.In the benthic water,denitrification(sediment-water interface)and nitrification(bottom water)coexisted.Furthermore,accumulations of NH4+and dissolved organic nitrogen in the bottom water were observed,indicating that nitrification was constrained by oxidant(mainly dissolved oxygen)supplies.

Ninety-four thousand-case retrospective study on antibacterial drug resistance of Helicobacter pylori

BACKGROUND The resistance rate to antibacterial drugs is the key inhibitor of Helicobacter pylori(H.pylori)eradication treatment.AIM To evaluate the prevalence and drug resistance of H.pylori based on big data.METHODS Gastric mucosal specimens were collected from naive patients undergoing upper gastrointestinal endoscopy for H.pylori culture and antimicrobial susceptibility testing(AST),including clarithromycin,levofloxacin,metronidazole and amoxicillin.Every 10 years of age was grouped as an age group.The H.pylori infection and resistance were explored based on the age group and gender.RESULTS The number of H.pylori-positive specimen was 94509 in 283823 gastric mucosal specimens,with an infection rate of 33.30%.The infection rate increased with age,and males had a higher infection rate than females.The average resistance rate of H.pylori to amoxicillin and metronidazole was 0.21%and 93.72%,which remained stable.The average resistance rate to clarithromycin was 23.99%with an increasing trend from 14.43%to 38.24%.The average resistance rate to levofloxacin was 30.29%,which increased from 17.07%to 39.42%and mostly stabilized after 2017.The resistance rate of H.pylori increased with age,except amoxicillin.H.pylori in females are at higher risk of resistance to metronidazole but not to amoxicillin,regardless of the age group.Meanwhile,H.pylori in females are at higher risk of resistance to levofloxacin and clarithromycin in the 21-50 age group.The single,dual,triple and quadruple-drug resistance rate was 54.59%,29.03%,11.71%and 0.11%,respectively.CONCLUSION The resistance of H.pylori in Taizhou city is serious.Guided by the consensus report,individualized treatment based on AST is recommended.

180例黏膜相关淋巴瘤患者的临床特征和预后分析

目的:对黏膜相关淋巴组织(mucosa associated lymphoid tissue,MALT)进行较大样本的单中心回顾性分析,获取其临床特征及生存相关影响因素数据。方法:回顾性分析2012年9月至2019年5月陆军军医大学大坪医院经病理活检确诊的180例MALT淋巴瘤患者。结果:全组180例患者,其中男性99例(55.0%),女性81例(45.0%),发病年龄31~84岁,中位年龄57岁。原发部位为胃肠59例(32.8%),眼66例(36.7%),其他结外原发部位包括肺、咽淋巴环、甲状腺、腮腺和睾丸等,共55例(30.6%)。临床分期Ⅰ~Ⅱ期173例(96.1%),Ⅲ~Ⅳ期7例(3.9%)。胃肠组、眼部组和其他组5年生存率(overall survival,OS)分别为96.7%、95.5%和86.4%,差异无统计学意义(P=0.118);5年无进展生存率(progression-free survival,PFS)分别为82.4%、86.6%和86.4%,差异无统计学意义(P=0.862)。预后单因素相关分析提示,低血红蛋白水平(P=0.006)、β2-微球蛋白(β2-MG)升高(P=0.013)为影响患者OS的相关因素;β2-MG升高(P=0.004)为影响患者OS及PFS的相关因素。多因素分析表明低血红蛋白水平与生存期有关(P=0.015)。结论:MALT淋巴瘤可起源于全身不同部位,其临床过程进展缓慢,复发晚,OS较长。低血红蛋白水平、β2-MG可作为MALT淋巴瘤重要的临床预后指标。

A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.

Vorolanib,an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors:An open-label,phaseⅠdose escalation and dose expansion trial

Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.

Correlations between microbial communities in stool and clinical indicators in patients with metabolic syndrome

AIM To analyze the bacterial community structure and distribution of intestinal microflora in people with and without metabolic syndrome and combined these data with clinical indicators to determine relationships between selected bacteria and metabolic diseases. METHODS Faecal samples were collected from 20 patients with metabolic syndrome and 16 controls at Cangnan People's Hospital, Zhejiang Province, China. DNA was extracted and the V3-V4 regions of the 16 S rRNA genes were amplified for high throughput sequencing. Clear reads were clustered at the 97% sequence similarity level. α and β diversity were used to describe the bacterial community structure and distribution in patients. Combined with the clinical indicators, further analysis was performed.RESULTS Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria were the dominant phyla, and Prevotella, Bacteroides and Faecalibacterium was the top three genera in faecal samples. α diversity analysis showed that the species richness of metabolic syndrome samples(group D) was significantly higher than the control(group C)(P < 0.05), and the microbial diversity of group C was greater than that of group D. According to the principal co-ordinates analysis, the samples of group C clustered more tightly, indicating that the distribution of bacteria in healthy patients was similar. The correlation analysis showed that alkaline phosphatase was negatively correlated with the abundance of Prevotella(P < 0.05). There was a negative correlation between low-density lipoprotein and the abundance of Ruminococcus(P < 0.05) and a positive correlation between the high-density lipoprotein and the abundance of Ruminococcus(P < 0.05). The total protein and the alanine aminotransferase was positively correlated with the abundance of Peptostreptococcus(P < 0.05). CONCLUSION The changes microbial communities can be used as an indicator of metabolic syndrome, and Prevotella may be a target microorganism in patients with metabolic syndrome.

The morphological characteristics of gully systems and watersheds in Dry-Hot Valley, SW China

Gully systems and watersheds are geomorphic units with clear boundaries that are relatively independent of basin landscapes and play an important role in natural geography. In order to explore the morphological characteristics of gully systems and watersheds in the Dry-Hot Valley [South West(SW) China], gullies are interpreted from online Google images with high resolution and watersheds are extracted from digital elevation model at a scale of 1:50,000. The results show that:(1) There are17,382 gullies(with a total area of 1141.66 km2) and 42 watersheds in the study area.(2) The average gully density of the study area(D) is 4.29 km/km2, gully frequency(F) is 14.39 gullies/km2, the branching ratio(B) is 5.13, the length ratio(L) is 3.12, and the coefficient of the main and tributary gullies(M) is 0.06. The degree of gully erosion isstrong to extremely strong, the main development intensity of gully erosion ranges from intense to moderate, and the type of gully system is tributary.(3) The watershed areas(A) are between 0.39 and 96.43 km2, the relief ratio(R) is from 0.10 to 0.19, the circularity ratio(C) is from 0.30 to0.83, the texture ratio(T) is from 0.82 to 39.35, and the dominant geomorphological texture type is fine.(4) There is a quantitative relationship between F and D:F = 0.624 D2(R =0.84) and T is closely related to D, F, M(R2[ 0.7). A,R and C are related to M(R2[ 0.5). The development of gully systems is the result of coupling effects between multiple factors. In this area, the degree of erosion and the condition of the main and tributary gullies can be controlled by the degree of topographic breakage in the watershed, which provides some theoretical basis for the evaluation of gully erosion by the latter. In addition, the scale, relief, and shape have a significant impact on the locations of the main and tributary gullies. For tributary gullies, attention should be paid to the interception and control of runoff and sediment in the small confluence branches in order to prevent gully expansion and head advance. These features can inform the development of targeted measures for the control of soil erosion.