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| 1 | Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy显示文摘CD8^+T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1,an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance.Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes.Unfortunately,only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity.Antitumor immunity depends on the activation of the cGAS-STING pathway,as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells(DCs)to activate CD8^+T cells.STING agonists also enhance natural killer(NK)cells to mediate the clearance of CD8^+T cell-resistant tumors.Therefore STING agonists have been intensively sought after.We previously discovered that manganese(Mn)is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING.Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors.Mn-insufficient mice had significantly enhanced tumor growth and metastasis,with greatly reduced tumor-infiltrating CD8^+T cells.Mechanically,Mn^2+promoted DC and macrophage maturation and tumor-specific antigen presentation,augmented CD8^+T cell differentiation,activation and NK cell activation,and increased memory CD8^+T cells.Combining Mn^2+with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice.Importantly,a completed phase 1 clinical trial with the combined regimen of Mn^2+and anti-PD-1 antibody showed promising efficacy,exhibiting type I IFN induction,manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors.We propose that this combination strategy warrants further clinical translation. | Mengze Lv Meixia Chen Rui Zhang Wen Zhang Chenguang Wang Yan Zhang Xiaoming Wei Yukun Guan Jiejie Liu Kaichao Feng Miao Jing Xurui Wang Yun-Cai Liu Qian Mei Weidong Han Zhengfan Jiang | 2020 | Cell Research2020，30，11： | 27 |
| 2 | Combination of 'low-dose' ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy显示文摘AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a 'low dose' of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed. | Perdita Wietzke-Braun Volker Meier Felix Braun Giuliano Ramadori | 2001 | World Journal of Gastroenterology2001，7，2： | 19 |
| 3 | Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke:an updated systematic review显示文摘The optimal dose of recombinant tissue plasminogen activator(rtPA)for acute ischaemic stroke(AIS)remains controversial,especially in Asian countries.We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA.We performed a systematic literature search across MEDLINE,Embase,Cochrane Central Register of Controlled Trials(CENTRAL),PsycINFO and Cumulative Index to Nursing and Allied Health Literature(CINAHL)from inception to 22 August 2016 to identify all related studies.The outcomes were death or disability(defined by modified Rankin Scale 2-6),death,and symptomatic intracerebral haemorrhage(sICH).Where possible,data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis.We included 26 observational studies and 1 randomised controlled trial with a total of 23210 patients.Variable doses of rtPA were used for thrombolysis of AIS in Asia.Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability(OR 1.13,95% CI 0.95 to 1.33),or death(OR 0.86,95% CI 0.74 to 1.01),or decreased risk of sICH(OR 1.06,95% CI 0.65 to 1.72).The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies.Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS.Low-dose rtPA was not associated with lower risk of death or disability,death alone,or sICH. | Xia Wang Shoujiang You Shoichiro Sato Jie Yang Cheryl Carcel Danni Zheng Sohei Yoshimura Craig S Anderson Else Charlotte Sandset Thompson Robinson John Chalmers Vijay K Sharma | 2018 | Stroke & Vascular Neurology2018，3，1： | 10 |
| 4 | Influence of BOL on hyaluronic acid,laminin and hyperplasia in hepatofibrotic rats显示文摘AIM: To study the anti-hepatofibrosis mechanism of Bie Jie Jian oral liquid (BOL).METHODS: The model was induced by subcutaneous injection of CCl4. BOL was administered and the change of serum hyaluronic acid (HA) and laminin (LN) was observed and the degeneration of liver cells and the degree of fibre hyperplasia analyzed. Changes of ultra micro-structure in liver cells were observed in some samples.RESULTS: HA was reduced in both the groups with Iow and high dosage of BOL, which showed a remarkable difference as compared with that of the model group ( Iow dosage group: 376.15 μg/L ± 35.48 μg/L vs 806.07 μg/L ± 98.49 μg/L, P < 0.05; high dosage group: 340.14 μg/L ± 30.18 μg/L vs 806.07μg/L± 98.49 μg/L, P<0.05). The LN content of Iow and high dosage group of BOL was lower than that of model group (Iow dosage group: 71.99 μg/L± 8.15 μg/L vs 133.94μg/L± 14.45 μg/L, P< 0.01; high dosage group: 71.68 ig/L± 11.62 μg/L vs 133.94 μg/L ± 14.45 μg/L, P<0.01) and colchicine group (Iow dosage group: 71.99 μg/L ± 8.15 μg/Lvs 118.28 μg/L ± 16.13 μg/L, P< 0.05; high dosage group:71.68 μg/L ± 11.62 μg/L vs 118.28 μg/L ± 16.13 μg/L,P<0.05). Examined by Ridit, BOL could reduce the degeneration and necrosis of liver cells (X2 = 11.99P<0.05), the degree of fibre hyperplasia (X2 = 13.24P<0.05) and the pathological change of ultra micro-structure as well.CONCLUSION: The BOL has certain therapeutic effect on the experiment hepatofibrosis. Its mechanisms might include:protecting the function of liver cells, inhibiting excessive synthesis and secretion of extraceiluar matrix from hepatic stellate cells, relieving the cepillarization of hepatic sinueoid, improving liver micro-circulation, and regulating immune function. | Li Yao~1 Zhen-Min Yao~2 Tao Yu~2 1 Pharmacology Department of Zhejiang College of Traditional Chinese Medicine(TCM),Hangzhou 310053,Zhejiang Province,China2 Basic Medicine Department of Zhejiang College of TCM,Hangzhou 310053,Zhejiang Province,China | 2001 | World Journal of Gastroenterology2001，7，6： | 9 |
| 5 | Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex显示文摘Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018. | Zongqin Xiang Liang Xu Minhui Liu Qingsong Wang Wen Li Wenliang Lei Gong Chen | 2021 | Neural Regeneration Research2021，16，4： | 9 |
| 6 | Kinetic studies of gas hydrate formation with low-dosage hydrate inhibitors显示文摘Pipeline blockage by gas hydrates is a serious problem in the petroleum industry.Low-dosage inhibitors have been developed for its cost-effective and environmentally acceptable characteristics.In a 1.072-L reactor with methane,ethane and propane gas mixture under the pressure of about 8.5 MPa at 4 °C,hydrate formation was investigated with low-dosage hydrate inhibitors PVP and GHI1,the change of the compressibility factor and gas composition in the gas phase was analyzed,the gas contents in hydrates were compared with PVP and GHI1 added,and the inhibition mechanism of GHI1 was discussed.The results show that PVP and GHI1 could effectively inhibit the growth of gas hydrates but not nucleation.Under the experimental condition with PVP added,methane and ethane occupied the small cavities of the hydrate crystal unit and the ability of ethane entering into hydrate cavities was weaker than that of methane.GHI1 could effectively inhibit molecules which could more readily form hydrates.The ether and hydroxy group of diethylene glycol monobutyl ether have the responsibility for stronger inhibition ability of GHI1 than PVP. | TANG CuiPing 1,2,DAI XingXue 1,2,DU JianWei 1,2,LI DongLiang 1,2,ZANG XiaoYa 1,2,YANG XiangYang 1 & LIANG DeQing 1 1 Guangzhou Institute of Energy Conversion,Key Laboratory of Renewable Energy and Gas Hydrate,Chinese Academy of Sciences,Guangzhou 510640,China 2 Graduate University of the Chinese Academy of Sciences,Beijing 100039,China | 2010 | Science China Chemistry2010，53，12： | 9 |
| 7 | Treatment of the later stages of Parkinson’s disease – pharmacological approaches now and in the future显示文摘The problems associated with the pharmacological treatment of the later stages of Parkinson’s disease(PD)remain those seen over many years.These centre on a loss of drug effect(‘wearing off’)with disease progression,the occurrence of dyskinesia,notably with L-dopa use and the appearance of non-motor symptoms that are largely refractory to dopaminergic medication.Treatment strategies in late PD have been dominated by the use of drug combinations and the subtle manipulation of drug dosage.However,change is occurring as the understanding of the basis of motor complications and fluctuations and non-motor symptoms improves.New pharmacological options are expanding with the advent of longer acting versions of existing dopaminergic drugs,new drug delivery systems and the introduction of non-dopaminergic agents able to manipulate motor function both within the basal ganglia and in other brain regions.Non-dopaminergic agents are also being investigated for the treatment of dyskinesia and for the relief of non-motor symptoms.However,while therapy continues to improve,the treatment of late stage PD remains problematic with non-motor symptoms dominating the unmet need in this patient group. | Peter Jenner | 2015 | Translational Neurodegeneration2015，4，1： | 8 |
| 8 | Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China(CLASS-China):results from a prospective double-blind randomised clinical trial显示文摘Aim The role of clopidogrel in treating patients with acute ischaemic stroke is unclear.We have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non-cardiogenic acute ischaemic stroke.Method Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China(CLASS-China)was a prospective,randomised,double-blind and placebo-controlled clinical trial in China.Patients with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were excluded.Enrolled patients were divided into two treatment groups:loading dose and routine dose.The primary outcome was the incidence of stroke recurrence or progression within 7 days.Primary safety outcome was measured by life-threatening haemorrhage.An intent-to-treat analysis was used for the statistical analysis.results From March 2008 to March 2010,a total of 303 patients from 16 centres were recruited into this study;six were excluded because of lack of basic information.Since the enrolment was slow and the study drug expired in March 2010,this clinical trial was stopped earlier than planned.No significant baseline and demographic differences were seen between the two groups.There was no difference in primary outcome between the loading dosage group 16.1%(24/149)and control group 14.9%(22/148),respectively(p=0.782).The mortality and disability rate within 90 days in loading dose group(19.6%)was slightly lower than that in controlled group(23.4%),p=0.444.Loading dose group had two(1.3%)cases of fatal haemorrhage and control group had four(2.7%)within 90 days,p=0.674.No significant difference was detected in other adverse events between the groups.conclusion In our study stopped early due to slow enrolment,loading dose of clopidogrel does not reduce the risk of recurrent stroke.Future trials with sufficient number of patients enrolled are needed to re-examine this hypothesis. | Ying Zhao Wanyong Yang Zefeng Tan Wenmin Wang Weimin Xiao Jinsheng Zeng Anding Xu | 2017 | Stroke & Vascular Neurology2017，2，3： | 7 |
| 9 | Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1显示文摘Multisystem manifestations in myotonic dystrophy type 1(DM1)may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK,including DMPK,its neighboring genes(SIX5 or DMWD)and downstream MBNLh However,direct evidence is lacking.Here,we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem cells with mutant Dmpk,Six5 and Mbnll into oocytes.The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes.With the additional mutation in Dmwd,the quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1.Moreover,muscle stem cells in both models display reduced sternness,providing a unique model for screening small molecules for treatment of DM1.Our results suggest that the complex symptoms of DM1 result from the reduced dosage of multiple genes. | Qi Yin Hongye Wang Na Li Yifu Ding Zhenfei Xie Lifang Jin Yan Li Qiong Wang Xinyi Liu Liuqing Xu Qing Li Yongjian Ma Yanbo Cheng Kai Wang Cuiqing Zhong Qian Yu Wei Tang Wanjin Chen Wenjun Yang Fan Zhang Chen Ding Lan Bao Bin Zhou Ping Hu Jinsong Li | 2020 | Cell Research2020，30，2： | 7 |
| 10 | High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6. | Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders | 2016 | Horticulture Research2016，3，1： | 6 |
| 11 | Risk factors of hyperprolactinemia induced by risperidone and olanzapine and their correlations with plasma glucose and lipids显示文摘Background Hyperprolactinemia is a common adverse reaction in patients with schizophrenia who take antipsychotic drugs;it often leads to treatment noncompliance in patients and has an adverse effect on their prognosis.Aims This study aimed to explore the risk factors of elevated prolactin(PRL)caused by risperidone(RIS)and olanzapine(OLZ)and the relationship between PRL and fasting plasma glucose and lipids.Methods Patients with schizophrenia were divided into two groups:264 patients who were taking RIS and 175 patients who were taking OLZ.These two groups were further divided according to serum PRL levels:an elevated PRL group(>30ng/mL)and a normal PRL group(PRL<30ng/mL).The demographics,medication dosage,fasting plasma glucose,total cholesterol and triglycerides were compared in the two groups.Logistic regression analysis was performed to explore the risk factors of elevated PRL levels.Results Compared with the OLZ group,the RIS group had a greater number of patients with elevated PRL(155/264 vs 58/175).Either the RIS or the OLZ group,the proportion of elevated PRL was greater in female patients(RIS:x^2=6.76,p=0.009;OLZ:x^2=12.98,p<0.001)and with higher doses of the related drugs(RIS:U=-3.73,p<0.001;OLZ:U=-2.31,p=0.021).In patients taking RIS,the elevated PRL subgroup took the drug for a longer period(U=-2.76,p=0.006)and had lower triglyceride levels(U=2.76,p=0.006).In patients taking OLZ,the elevated PRL subgroup had lower fasting plasma glucose levels(U=2.29,p=0.022).Logistic regression analysis showed that gender,dose and fasting glucose levels were significantly associated with elevated PRL levels(RIS:p=0.001,OLZ:p<0.001;RIS:p<0.001;OLZ:p=0.003;RIS:p=0.020,OLZ:p=0.001,respectively).Conclusion Compared with OLZ,RIS had a greater effect on PRL in patients with schizophrenia,and in patients with schizophrenia taking RIS or OLZ,gender and dose were significantly correlated with the PRL value.Moreover,the plasma glucose level of the group with elevated PRL was lower than that of the group with normal PRL.The results also showed that high serum PRL may be associated with a favourable glucose metabolic profile in patients with schizophrenia taking RIS or OLZ.Further studies are warranted to confirm this association. | Sidi He Wen Juan Yu Xiaoliang Wang Lei Zhang Nan Zhao Guanjun Li Yi Feng Shen Huafang Li | 2020 | General Psychiatry2020，33，4： | 5 |
| 12 | TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: Further evidence supporting the compound inheritance andTBX6gene dosage model显示文摘With the support by the National Natural Science Foundation of China,the research team directed by Prof.Qiu GuiXing(邱贵兴)and Dr.Wu Nan(吴南)at the Department of Orthopedic Surgery,Beijing Key Laboratory for Genetic Research of Skeletal Deformity,Peking Union Medical College Hospital,recently reported that TBX6-associated congenital scoliosis(TAGS)is a clinically distinguishable subtype of congenital scoliosis as further evidence supporting the compound inheritance and TBX6 gene dosage model. | | 2019 | Science Foundation in China2019，27，1： | 5 |
| 13 | Effects of high voltage discharge on the human bodies of workers显示文摘In this paper,as it is reported,through mechanism analysis,calculation,testing,measuring in the site and the observation ofbiologic effect on workers as well as the peripheral blood test in vitro,there are low energy X-ray and so forth produced due to high volt-age discharge which are harmful physical and chemical factors.Theexistence of these harmful factors affect workers’ health to a certaindegree.The observed biologic indexes are those of peripheral bloodcell effect,lymphocyte,micronuclear,chromosomal aberration,sisterchromatid exchange,blood serum immune globulin,electroen-cephalogram and brain blood current gram. The vitro peripheralblood test indexes are including those of chromosmal aberration,sister chromatid exchange and blood serum immune globulin.Theresults obtained from the said observation and testing express thatthe above mentioned indexes have obvious significance after thecomparison of those between test group and control group treated bystatistics (i.e.P<0.05).Further,the test results also point out that theenvironment of high voltage discharge will creat injury to the workers,therefore a detail research should be taken. | Yang Baochu Chongqing UniversityZao Wenzhen Radiative medical Science Research Institute,Medical Science Academy of ChinaZhang Maohua Hygienic and Antiepidemic Station of Qijiang | 1991 | Electricity1991，，2： | 4 |
| 14 | Diagnosis of the accurate genotype of HKαα carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction显示文摘Background:Patients carrying the HongKongαα(HKαα)allele and-α3.7/αααanti-4.2 could be misdiagnosed as-α3.7/ααby the current conventional thalassemia detection methods,leading to inaccurate genetic counseling and an incorrect prenatal diagnosis.This study was aimed to accurately analyze the genotypes of HKααcarriers and-α3.7/αααanti-4.2.Methods::Samples were collected in our hospital from July 2017 to October 2019.Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction(Gap-PCR)and reverse dot blot(RDB).Anti-4.2 multiplex-PCR was used to confirm carriers of theαααanti-4.2 duplication with-α3.7 deletion.Two-round nested PCR and multiplex ligation-dependent probe amplification(MLPA)were applied to accurately identify and confirm their genotypes.For data analysis,we used descriptive statistics and Fisher’s exact tests.Results::Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples.The results showed thatα,β,andαβcompound thalassemia were identified in 1190(46.78%),1286(50.55%),and 68(2.67%)cases,respectively.A total of 227 samples from thalassemia patients were identified as-α3.7/ααby Gap-PCR,and the genotypes of two samples were uncertain.There was a difference between Gap-PCR and combined groups(Gap-PCR combined with nested PCR and MLPA)in detecting HKαα(P<0.05).Among the 229 patients,20 patients were identified as HKααcarriers and one was identified as-α3.7/ααα anti-4.2 by two-round nested PCR and MLPA,including 15 patients with HKαα/αα,three with HKαα/αα and β-thalassemia coinheritance,one with HKαα/-SEA,one with HKαα/-α4.2 andβ-thalassemia coinheritance,and one with-α3.7/αααanti-4.2 and β-thalassemia coinheritance.Conclusions::αααanti-4.2 and HKααgenotypes of patients carrying-α3.7 need to be detected to reduce the misdiagnosis rate of patients carrying HKααand-α3.7/αααanti-4.2 alleles.More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA. | Dong-Mei Chen Shi Ma Xiang-Lan Tang Ji-Yun Yang Zheng-Lin Yang | 2020 | Chinese Medical Journal2020，，10： | 4 |
| 15 | Biological Intelligence of Rare Earth Elements in Animal Cells显示文摘Recent progress in bioinorganic chemistry studies of rare earth elements (REE) in animal cells was outlined, and the definition of REE′s biological intelligence as well as their mechanism were also explained. The migration of REE from weathering rocks to the environment is accelerated by various anthropogenic activities, which can eventually result in the entrance of REE into animal and human bodies via food chain. REE can be found in body tissues such as brain, blood, muscle as well as bone. Based on their geochemical properties, REE in low dose show their unique biological intelligence by intervening in the process of signal transduction and its regulation, arteriosclerosis and blood clotting prevention, anticancer, and the promotion of cellular defense enzymes′ activities, nucleic acid metabolism enzymes as well as ATPases, etc. The meaning of REE′s biological intelligence refers to physicochemical properties-based capability to choose the targets (e.g., biometals) in biomolecules for the chelation or replacement of REE, and change the structures and functions of biomolecules, and consequently impact or control the biological functions or behaviors in living organisms. The regulation of various cellular processes caused by REE is mainly via antagonism or replacement of essential target biometals like calcium or via chelation of organic molecules, thereby embodying the unparalleled biological intelligence of REE. Additionally, the dosage effect of REE was also discussed from the angles of yin-yang dichotomy, bioavailability, entropy and evolution. In order to make full use of REE′s biological intelligence in the application for medicine, more detailed studies concerning dosage effect of REE and REE bioaccumulation in organisms should be conducted in future research. | 邱关明 李伟 李喜坤 周威 杨春生 | 2005 | Journal of Rare Earths2005，23，S1： | 4 |
| 16 | Magnitude of modulation of gene expression in aneuploid maize depends on the extent of genomic imbalance显示文摘Aneuploidy has profound effects on an organism,typically more so than polyploidy,and the basis of this contrast is not fully understood.A dosage series of the maize long arm of chromosome 1(1L)was used to compa re relative global gene expression in diffe rent types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression.While previously available methods require a selective examination of specific genes,RNA sequencing provides a whole-genome view of gene expression in aneuploids.Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms.The genetic toolkit of maize allows the examination of multiple ploidies and 1-4 doses of chromosome arms.Thus,a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible,in both hypoploids and hyperploids,compared with euploid controls.Previous studies observed the inverse trans effect,in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region.This response was also the major type of changes found globally in this study.Many genes varied in dosage showed proportional expression changes,though some were seen to be partly or fully dosage compensated.It was also found that the effects of aneuploidy were progressive,with more severe aneuploids producing effects of greater magnitude. | Adam F·Johnson Jie Hou Hua Yang Xiaowen Shi Chen Chen Md Soliman Islam Tieming Ji Jianlin Cheng James A·Birchler | 2020 | Journal of Genetics and Genomics2020，47，2： | 3 |
| 17 | Who may benefit from lower dosages of intravenous tissue plasminogen activator? Results from a cluster data analysis显示文摘background The risk of symptomatic intracranial haemorrhage(sICH)after thrombolysis is low but severe.Lower dose of alteplase may reduce the risk of sICH.We aim to identify subsets of patients who could benefit from lower dose of alteplase compared with standard dose.Methods Data from two observational registries were pooled together.A total of 3479 patients who had acute ischaemic stroke were entered into the interaction tree model.The response variable was the rate of sICH per the definition of the National Institute of Neurological Disorders and Stroke Study.Clinical improvement was measured by the National Institutes of Health Stroke Scale(NIHSS)and defined as NIHSS 0 or 1 or an improvement of more than 4 points(within 7 days or at discharge).Rare event logistic regression was performed to analyse the OR of safety outcome.results To optimise the interaction effect between tissue plasminogen activator(tPA)dosage(standard/lower)and patient subgroups,three subgroups based on the severity of stroke were identified:(1)NIHSS≤4,(2)NIHSS between 5 and 14,and(3)NIHSS≥15.The estimated difference of OR of having sICH was 2.71(95%CI 0.80 to 7.69,p=0.10)for mild,0.13(95%CI 0.02 to 0.68,p=0.01)for moderate,and 0.65(95%CI 0.19 to 2.55,p=0.52)for severe,respectively.In addition,patients who had moderate stroke treated with lower dose had comparable efficacy outcome(OR 1.23,95%CI 0.71 to 2.13,p=0.45).Conclusion Our analysis demonstrated that in patients who had moderate stroke,lower doses of alteplase are associated with significant sICH reduction and non-inferior performance in efficacy,compared with those in the standard dose group. | Yi Dong Ye Han Haipeng Shen Yilong Wang Frank Ma Hao Li Yongjun Wang Qiang Dong | 2020 | Stroke & Vascular Neurology2020，5，4： | 3 |
| 18 | Effects of different loading rates and types of biochar on passivations of Cu and Zn via swine manure composting显示文摘Pollution of arable land caused by heavy metals in livestock and poultry manure has become a potential threaten to human health in China.Safe disposal of the contained toxic pollution with animal manure by co-composting with biochar is one of the alternative methods.Biochars from different sources(wheat straw,peanut shells and rice husks)amended with different loading rates were investigated for passivations of copper and zinc(Cu and Zn)in swine manure composting.Results showed that the passivation effects of the three types of biochar on Cu and Zn were enhanced with increasing biochar dose.Contents of Cu and Zn measured by diethylenetriaminepentaacetic acid(DTPA)and Community Bureau of Reference(CBR)showed that wheat straw biochar with the loading rates of 10%–13%(w/w)was superior to the other two types of biochar in this study.Compared with the control,sample from wheat straw biochar was more favorable for the bacterial growth of Proteobacteria,Firmicutes and Actinobacteria.In addition,pot experiment showed that organic fertilizer amended with wheat straw biochar could significantly improve the growth of Chinese pakchoi and enzyme activities(superoxide dismutase,peroxidase,polyphenol oxidase and catalase)as compared with the control.Cu and Zn contents of Chinese pakchoi in the organic fertilizer group containing wheat straw biochar reduced by 73.2%and 45.2%,65.8%and 33.6%,respectively,compared with the group without loading biochar.There was no significant difference in the contents of vitamin C and reducing sugar between the groups of organic fertilizer amended with/without wheat straw biochar,however,there was significant difference compared with the heavy metal addition group.The application of organic fertilizer formed by adding biochar can effectively reduce the adverse effects of heavy metals on crops. | CHEN Yan XU Yongping QU Fangjing HOU Fuqin CHEN Hongli LI Xiaoyu | 2020 | Journal of Arid Land2020，12，6： | 3 |
| 19 | Rhabdomyolysis and respiratory insufficiency due to the common ETFDH mutation of c.250G>A in two patients with late-onset multiple acyl-CoA dehydrogenase deficiency显示文摘To the Editor:Late-onset multiple acyl-CoA dehydrogenase deficiency(MADD)is clinically characterized by a fluctuating or progressive proximal myopathy,exercise intolerance but good responsive to riboflavin.ETFDH mutations are a major cause of late-onset MADD.We analyzed the clinical course,biochemical studies,and muscle magnetic resonance imaging(MRI)and pathologies of two late-onset MADD adult male patients who were misdiagnosed as polymyositis and presented with serious clinical symptoms of rhabdomyolysis and respiratory insufficient after using large dosage of intravenous glucocorticoids.Our current report broadens the clinical phenotypes spectrum of MADD and reminds clinicians to be cautious about using large dosage glucocorticoids in metabolic compromised patients. | Hai-Zhu Chen Ming Jin Nai-Qing Cai Xiao-Dan Lin Xin-Yi Liu Liu-Qing Xu Min-Ting Lin Feng Lin Ning Wang Zhi-Qiang Wang Guo-Rong Xu | 2019 | Chinese Medical Journal2019，，13： | 3 |
| 20 | Antidotal effects of calcium folinate against high-dose methotrexate-induced damages to mouse matured oocytes显示文摘Methotrexate(MTX)is a common folate antagonist and it blocks the dihydrofolate reductase,thereby causing tetrahydrofolate for mation disorder.Tetrahydrofolate is the active folate form and its related metabolic products are required for DNA synthesis and DNA methylation modification.The effects of MTX have been demonstrated by DNA methylation aberrations,DNA damage,and DNA synthesis obstruction,causing cell replication disorder and apoptosis[1,2].Since MTX passes through blood-brain,blood-testis,and blood-ocular barriers,high-dose MTX is commonly used to treat malignancies in clinic(the high dose generally is the total dosage of MTX>1 g once or single dose>20 mg/kg)[3],The main defect of MTX treatment is its insufficient tumor targeting because MTX kills cancer cells and at the same time also destroys the normal cells[2].Additionally,MTX has also been reported to reduce the oocyte quality[4]. | Ning Tian Wanyun Ma | 2020 | Acta Biochimica et Biophysica Sinica2020，52，1： | 3 |
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