To the Editor:Pediatric liver transplantation is the only treatment option for end-stage liver disease in children,and the 5-year and 20-year survival rates after living donor liver transplantation(LDLT)can reach 91.5...To the Editor:Pediatric liver transplantation is the only treatment option for end-stage liver disease in children,and the 5-year and 20-year survival rates after living donor liver transplantation(LDLT)can reach 91.5% and 84.2%[1].Many Asian countries,including China,have begun to develop LDLT and achieved good progress.However,the shortage of donor livers in children remains a serious problem.展开更多
AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all partic...AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all participants into three distinct groups:1)control group(n=61),2)mild DE group(n=56),and 3)moderate-to-severe DE group(n=82).Schirmer’s tear secretion strips were used,and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS:The three groups had significant differences in alpha diversity:the control group had the highest richness(Chao1,Faith’s phylogenetic diversity),the mild DE group showed the highest diversity(Shannon,Simpson),and the moderate-to-severe DE group had the lowest of the above-mentioned indices.DE severity was positively correlated with a reduction in beta diversity of the microbial community,with the moderate-to-severe DE group exhibiting the lowest beta diversity.Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each.Furthermore,the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria,as determined by random forest analysis.CONCLUSION:As DE severity worsens,microbial community diversity tends to decrease.DE development corresponds with changes in microbial constituents,primarily characterized by reduced microbial diversity and a more homogenous species composition.展开更多
Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
In this paper,^(99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with ...In this paper,^(99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia.Pigmented guinea pigs aged 3 weeks were derided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6).The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4^(th) week after injection of ^(99m)Tc-TRODAT-1.The retinas were clearly resolved in the images.The ratio of ^(99m)Tc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98),and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04).The results showed that ^(99m)Tc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina,and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes.Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.展开更多
Background:Electrical impedance myography(EIM)is a non-invasive,painless,and easy-to-perform technique for assessing neuromuscular disorders.We evaluated the potential of EIM for quantitatively characterizing carpal t...Background:Electrical impedance myography(EIM)is a non-invasive,painless,and easy-to-perform technique for assessing neuromuscular disorders.We evaluated the potential of EIM for quantitatively characterizing carpal tunnel syndrome(CTS).Methods:Healthy subjects and patients with differing severity of CTS underwent EIM measurement of their small hand muscles.A bioelectrical impedance vector analysis(BIVA)method was first applied to display 50-kHz EIM data in a single plot.Results:Patients with more severe CTS had smaller EIM values in the affected muscle.The reactance and phase parameters differed significantly between any two groups(P<0.05).Their accuracy for differentiating between any two adjacent groups was approximately 80%and for other groups was approximately 90%.There was a strong association between EIM and electrophysiology results.Conclusion:BIVA is convenient and helpful for indicating the differences between healthy subjects and CTS patients.These results demonstrate EIM’s potential for quantitatively characterizing patients with CTS.展开更多
Although new drugs and intervention strategies have emerged from recent studies of neuroprotection, compared with haemodynamic and hemorheologic factors, knowledge of vascular factors of ischemic stroke is rather limi...Although new drugs and intervention strategies have emerged from recent studies of neuroprotection, compared with haemodynamic and hemorheologic factors, knowledge of vascular factors of ischemic stroke is rather limited. In practical terms, any strategy shown to reduce the incidence of fatal and nonfatal vascular events can be termed "vascular protection", including anti-thrombotic and anti-hypertensive therapies, as well as agents that directly benefit vascular endothelium. Vascular events include myocardial infarction, stroke, and claudication. Factors involved in these events include statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. In traditional Chinese medicine, the principles of "activating blood circulation to remove stasis", "tonifying the kidney and replenishing the essence", "dispelling pathogenic wind and removing obstruction from the meridians", and "warming Yang and promoting water metabolism" are possibly related to vascular protection. However, more evidence is needed to correlate these positive effects with vascular protection.展开更多
Objective Restoring the blood perfusion of ischemic heart tissues is the main treatment for myocardial ischemia.However,the accompanying myocardial ischemia reperfusion injury(IRI)would aggravate myocardial damage.Pre...Objective Restoring the blood perfusion of ischemic heart tissues is the main treatment for myocardial ischemia.However,the accompanying myocardial ischemia reperfusion injury(IRI)would aggravate myocardial damage.Previous studies have confirmed that aryl hydrocarbon receptor(AhR)is closely correlated to kidney and intestinal IRI.The present study aimed to explore the relationship between AhR and myocardial IRI.Methods An oxygen glucose deprivation/reoxygenation(OGD/R)model of H9c2 cells and an ischemia/reperfusion(I/R)model of Sprague-Dawley rat myocardium were established.OGD/R cells and myocardial IRI rats were treated with different concentrations of the AhR antagonist CH-223191 or agonist 6-formylindolo[3,2-b]carbazole(FICZ).Under the conditions of normoxia and hypoxia/reoxygenation,the activity of cardiomyocytes,lactate dehydrogenase(LDH)and cell reactive oxygen species(ROS)were detected.In rats,myocardial pathological damage and markers of myocardial injury were detected.Results According to the results of the cell viability,LDH and ROS tests in vitro,both CH-223191 and FICZ showed no myocardial protection under OGD/R conditions.However,the histological staining and analysis of myocardial injury marker LDH in vitro revealed that CH-223191 could significantly reduce the myocardial IRI.Conclusion AhR exhibited a different effect on myocardial IRI in vitro and in vivo.In vivo,CH-223191 could significantly alleviate the myocardial IRI,suggesting that inhibition of AhR may play a role in myocardial protection,and AhR may serve as a potential treatment target for myocardial IRI.展开更多
Dear Editor, We reported the first case of acute exogenous postoperative endophthalmitis caused by a normal human microbiota in the nasopharynx, Streptococcus anginosus. The patient had a successful cataract surgery, ...Dear Editor, We reported the first case of acute exogenous postoperative endophthalmitis caused by a normal human microbiota in the nasopharynx, Streptococcus anginosus. The patient had a successful cataract surgery, but he felt uncomfortable in the surgery eye 4 d post-surgery. Besides.展开更多
End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent ne...End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent nerve(donor nerve).However,the motor-sensory specificity after end-to-side neurorrhaphy remains unclear.This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy.Thirty rats were randomized into three groups:(1) end-to-side neurorrhaphy using the ulnar nerve(mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve;(2) the sham group:ulnar nerve and cutaneous antebrachii medialis nerve were just exposed;and(3) the transected nerve group:cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied.At 5 months,acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group,and none of the myelinated axons were stained in either the sham or transected nerve groups.Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%.In contrast,no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment.These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.展开更多
Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appe...Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appelbaum et al.1999;Saba 2007).However,drug resistance causing treatment failure and disease relapse is an unresolved problem to date.Certain cancer cells rely on the salvage enzymes cytidine deaminase(CDA)and dCMP deaminase(DCTD)to inactivate these cytidine derivative drugs by deamination(Jamieson et al.1987;Ebrahem et al.2012).It is imperative to develop new categories of chemotherapeutic nucleosides to overcome the drug resistance caused by such increased cellular deamination activity.展开更多
Background Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases,differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and th...Background Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases,differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal.The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs.Methods Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation.Perfusion was calculated using the Patlak method.The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively.CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively.The correlations between CBV, PS of tumoral parenchyma and MVD were examined.Results The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P〈0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P 〉0.05).MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P〈0.05).There were positive correlations between CBV and MVD (r=0.648, P〈0.05), PS and MVD (r=0.541, P〈0.05) respectively.Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P〈0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P〈0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not significantly different with that of contrallateral normal white matter (P 〉0.05).Conclusions CT perfusion imaging can provide critical information on the vascuiarity of HPC and benign meningiomas.Determination of maximal CBV and corresponding PS values in the parenchyma may be useful in the preoperative differentiating HPC from benign meningiomas.展开更多
Background Previous studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, alterations in intrinsic brain activity patterns in mild cogniti...Background Previous studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, alterations in intrinsic brain activity patterns in mild cognitive impairment (MCI) patients are poorly understood. This study aimed to explore the differences in regional intrinsic activities throughout the whole brain between aMCI patients and controls. Methods In the present study, resting-state functional magnetic resonance imaging (fMRI) was performed on 18 amnestic MCI (aMCI) patients, 18 mild AD patients and 20 healthy elderly subjects. And amplitude of low-frequency fluctuation (ALFF) method was used. Results Compared with healthy elderly subjects, aMCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex, and right ventral medial prefrontal cortex (vMPFC) and increased ALFF in the left temporal-parietal junction (TPJ) and inferior parietal Iobule (IPL). Mild AD patients showed decreased ALFF in the left TPJ, posterior IPL (plPL), and dorsolateral prefrontal cortex compared with aMCI patients. Mild AD patients also had decreased ALFF in the right posterior cingulate cortex, right vMPFC and bilateral dorsal MPFC (dMPFC) compared with healthy elderly subjects. Conclusions Decreased intrinsic activities in brain regions closely related to episodic memory were found in aMCI and AD patients. Increased TPJ and IPL activity may indicate compensatory mechanisms for loss of memory function in aMCI patients. These findings suggest that the fMRI based on ALFF analysis may provide a useful tool in the study of aMCI patients.展开更多
Background Endothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1 was observed after intracerebral hemorrhage (ICH); howe...Background Endothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1 was observed after intracerebral hemorrhage (ICH); however, ET-1 changes and their relationship with BBB disruption within 24 hours of ICH have not been thoroughly investigated. The aim of the present study was to observe the changes in perihematomal ET-1 levels in various phases of ICH and their correlation with the BBB integrity in a rabbit model of ICH. Methods Twenty-five rabbits (3.2-4.3 kg body weight) were randomly divided into a normal control group (five rabbits) and a model group (20 rabbits). Animals in the model group were equally divided into four subgroups (five rabbits each to be sacrificed at 6, 12, 18, and 24 hours following ICH establishment). An ICH model was prepared in the model group by infusing autologous arterial blood into the rabbit brain. ET-1 expression in perihematomal brain tissues was determined using immunohistochemistry and color image analysis, and the permeability of the BBB was assayed using the Evan's Blue (EB) method. A repeated measures analysis of variance was used to make comparisons of the ET-1 and EB content across the entire time series. Results The number of perihematomal endothelial cells with ET-1 positive expressions following 6, 12, 18, and 24 hours ICH model establishment was 9.32, 13.05, 15.90, and 20.44, respectively, but as low as 6.67 in the control group. The average transmittance of ET-1-positive cell bodies at 6, 12, 18, and 24 hours after ICH was 99.10, 97.40, 85.70, and 80.80, respectively, but 100.12 in the control group. These data reveal that the expression of ET-1 was significantly increased at 6, 12, 18, and 24 hours after ICH compared with the control group, and a marked decrease in the average transmittance of ET-l-positive cell bodies was noted (P 〈0.05). Similarly, the perihematomal EB content at 6, 12, 18, and 24 hours after ICH was 29.39±1.16, 32.20±0.73, 33.63±1.08, and 35.26±1.12, respectively, in the model group and 28.06±0.80 in the control group. The results indicate that a significant increase in the EB content in the model group was observed compared with that of the control group (P 〈0.05). Moreover, a positive correlation between the number of ET-1-positive endothelial cells and BBB permeability was observed (t=0.883, P 〈0.05). Conclusions High levels of ET-1 are closely associated with BBB disruption. ET-1 may play an important role in the pathogenesis of secondary brain injury after ICH.展开更多
Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective inve...Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma(HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients,81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein(AFP) level, and other 35% had an AFP level lower than 400 ng mL^(-1). In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was(191.7±105.6) min,the blood loss was(546.0±562.8) m L, and blood transfusion was(543.0±1,035.2) m L. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules,tumor thrombosis and high AFP level were risk factors that affect postoperative survival.展开更多
Background Previous studies have shown that the functional brain activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, most studies focused on the relationship between different b...Background Previous studies have shown that the functional brain activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, most studies focused on the relationship between different brain areas, rather than the amplitude or strength of the regional brain activity. The purpose of this study was to explore the functional brain changes in AD patients by measuring the amplitude of the blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals.展开更多
This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multis...This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.展开更多
Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patient...Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patients, the status of chromosome 1 p/19q deletion, the methylation of O6-methylguanine-DNA methyltransferase (MGMT), and the expression of p53 protein were evaluated and investigated in relation to patients' outcomes.Methods Methylation of MGMT in 73 cases was analyzed by nested methylation-specific PCR (MSP). The levels of MGMT and p53 protein were tested with immunohistochemistry. Pearson's chi-square test and Fisher's exact test were used. Multivariate and Kaplan-Meier analysis were performed to determine patients' outcomes.Results Both oligodendrogliomas and astrocytic gliomas exhibited frequent methylation of MGMT. However, the results of MSP did not completely correspond to that of the immunohistochemical staining for MGMT. The expression of p53 protein was more frequently observed in patients without a 1 p or 19q deletion in anaplastic oligodendrogliomas (=0.032,0.025). In low-grade oligodendrogliomas, methylation of MGMT was more frequent in patients with 1 p/19q deletion than in patients with 1p/19q intact (P=0.038). Patients with oligodendrogliomas with 1p/19q loss of heterozygosity and p53-negative showed a longer progression-free survival.Conclusion Detection of chromosome 1p/19q status combined with p53 protein immunohistochemistry might be beneficial to improve the pathological diagnosis and to determine the prognosis of patients with oligodendrogliomas.展开更多
ABSTRACT Objective: To observe the effect of Lidan Granule (利胆冲剂, LDG) on bile lithogenic tendency and biliary 33.5 kd vesicular protein (VP) and to explore its mechanism. Methods: Sixty patients with choled...ABSTRACT Objective: To observe the effect of Lidan Granule (利胆冲剂, LDG) on bile lithogenic tendency and biliary 33.5 kd vesicular protein (VP) and to explore its mechanism. Methods: Sixty patients with choledocholithiasis combined with cholecystolithiasis were randomly assigned to the LDG treated group, the sodium cholate treated group for positive control, and the untreated control group, 20 patients in each group. The 4 bile lithogenic trend indexes, including lithogenic index (LI), unconjugated bilirubin percent (UCB%), unconjugated bilirubin saturation index (BSI) and Z-value, were determined before and after treatment. The content of VP in bile was determined as well. Results: Before treatment, the LI, UCB%, BSI and Z-value in the LDG treated group were 1.298 ± 0.265, 34.72 ± 2.96, 0.353± 0.093 and 0.556 ± 0.499, respectively, which was decreased after the 2-week treatment to 0.926± 0.208, 8.93± 1.19, 0.154 ± 0.056 and 0.257± 0.211, respectively (all P〈0.05). Meantime, the content of VP was also lowered from 0.050 ± 0.005 g/L to 0.032 ± 0.005 g/L. However, no significant change in any of the above-mentioned indexes was found in the other two groups. Conclusion: LDG could effectively suppress bile lithogenic trend and reduce 33.5 kd VP in bile.展开更多
To study the changes of adhesion molecules' expressions during the recombinant h u man granulocyte colony stimulating factor (rhG CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to...To study the changes of adhesion molecules' expressions during the recombinant h u man granulocyte colony stimulating factor (rhG CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to confirm the influence of rhG CSF on hematopoietic stem cells, which are proposed to guide mobilization in PBS CT Methods Mice were injected subcutaneously with diluted rhG CSF or normal saline for 7 d ays The blood Sca 1 + stem cell count and bone marrow (BM) nucleated cell co unt were enumerated The expressions of CD49d and CD44 and the adhesive ability of mononuclear cells to bone marrow matrix (fibronectin) were examined by flow c ytometry and 51 Cr adhesive assay, respectively Results The mobilizing effect of rhG CSF on mice was the same as on humans The number of Sca 1 + cells in peripheral blood reached the peak on the seventh day, the BM nucleated cell count was reduced, and the expressions of CD49d and the cells ' adhesive ability in BM and PB declined Conclusions rhG CSF can reduce some cell adhesion molecules' expressions and the adhesive a bility of hematopoietic stem cells to BM matrix, therefore mobilizing hematopoie tic stem cells (HSC) from the BM to the peripheral blood展开更多
基金supported by grants from the National Natural Science Foundation of China(82071797 and 81873874)Clinical Research Plan of SHDC(SHDC2020CR2021B and SHDC2020CR5012)。
文摘To the Editor:Pediatric liver transplantation is the only treatment option for end-stage liver disease in children,and the 5-year and 20-year survival rates after living donor liver transplantation(LDLT)can reach 91.5% and 84.2%[1].Many Asian countries,including China,have begun to develop LDLT and achieved good progress.However,the shortage of donor livers in children remains a serious problem.
基金Supported by Shanghai Municipal Health Commission(No.201940243).
文摘AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all participants into three distinct groups:1)control group(n=61),2)mild DE group(n=56),and 3)moderate-to-severe DE group(n=82).Schirmer’s tear secretion strips were used,and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS:The three groups had significant differences in alpha diversity:the control group had the highest richness(Chao1,Faith’s phylogenetic diversity),the mild DE group showed the highest diversity(Shannon,Simpson),and the moderate-to-severe DE group had the lowest of the above-mentioned indices.DE severity was positively correlated with a reduction in beta diversity of the microbial community,with the moderate-to-severe DE group exhibiting the lowest beta diversity.Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each.Furthermore,the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria,as determined by random forest analysis.CONCLUSION:As DE severity worsens,microbial community diversity tends to decrease.DE development corresponds with changes in microbial constituents,primarily characterized by reduced microbial diversity and a more homogenous species composition.
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
文摘In this paper,^(99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia.Pigmented guinea pigs aged 3 weeks were derided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6).The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4^(th) week after injection of ^(99m)Tc-TRODAT-1.The retinas were clearly resolved in the images.The ratio of ^(99m)Tc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98),and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04).The results showed that ^(99m)Tc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina,and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes.Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.
基金This study was supported by the National Natural Science Foundation of China(Grant No.6137607261334008).
文摘Background:Electrical impedance myography(EIM)is a non-invasive,painless,and easy-to-perform technique for assessing neuromuscular disorders.We evaluated the potential of EIM for quantitatively characterizing carpal tunnel syndrome(CTS).Methods:Healthy subjects and patients with differing severity of CTS underwent EIM measurement of their small hand muscles.A bioelectrical impedance vector analysis(BIVA)method was first applied to display 50-kHz EIM data in a single plot.Results:Patients with more severe CTS had smaller EIM values in the affected muscle.The reactance and phase parameters differed significantly between any two groups(P<0.05).Their accuracy for differentiating between any two adjacent groups was approximately 80%and for other groups was approximately 90%.There was a strong association between EIM and electrophysiology results.Conclusion:BIVA is convenient and helpful for indicating the differences between healthy subjects and CTS patients.These results demonstrate EIM’s potential for quantitatively characterizing patients with CTS.
基金funded by the Shanghai Municipal Commission of Health and Family Planning“Effect of cognitive psychological intervention on the anxiety of the postpartum pregnant women at high risk”project.Project number:2009107
文摘Although new drugs and intervention strategies have emerged from recent studies of neuroprotection, compared with haemodynamic and hemorheologic factors, knowledge of vascular factors of ischemic stroke is rather limited. In practical terms, any strategy shown to reduce the incidence of fatal and nonfatal vascular events can be termed "vascular protection", including anti-thrombotic and anti-hypertensive therapies, as well as agents that directly benefit vascular endothelium. Vascular events include myocardial infarction, stroke, and claudication. Factors involved in these events include statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. In traditional Chinese medicine, the principles of "activating blood circulation to remove stasis", "tonifying the kidney and replenishing the essence", "dispelling pathogenic wind and removing obstruction from the meridians", and "warming Yang and promoting water metabolism" are possibly related to vascular protection. However, more evidence is needed to correlate these positive effects with vascular protection.
基金supported by the Natural Science Foundation of Hubei Science and Technology Commission(No.2018CFB585).
文摘Objective Restoring the blood perfusion of ischemic heart tissues is the main treatment for myocardial ischemia.However,the accompanying myocardial ischemia reperfusion injury(IRI)would aggravate myocardial damage.Previous studies have confirmed that aryl hydrocarbon receptor(AhR)is closely correlated to kidney and intestinal IRI.The present study aimed to explore the relationship between AhR and myocardial IRI.Methods An oxygen glucose deprivation/reoxygenation(OGD/R)model of H9c2 cells and an ischemia/reperfusion(I/R)model of Sprague-Dawley rat myocardium were established.OGD/R cells and myocardial IRI rats were treated with different concentrations of the AhR antagonist CH-223191 or agonist 6-formylindolo[3,2-b]carbazole(FICZ).Under the conditions of normoxia and hypoxia/reoxygenation,the activity of cardiomyocytes,lactate dehydrogenase(LDH)and cell reactive oxygen species(ROS)were detected.In rats,myocardial pathological damage and markers of myocardial injury were detected.Results According to the results of the cell viability,LDH and ROS tests in vitro,both CH-223191 and FICZ showed no myocardial protection under OGD/R conditions.However,the histological staining and analysis of myocardial injury marker LDH in vitro revealed that CH-223191 could significantly reduce the myocardial IRI.Conclusion AhR exhibited a different effect on myocardial IRI in vitro and in vivo.In vivo,CH-223191 could significantly alleviate the myocardial IRI,suggesting that inhibition of AhR may play a role in myocardial protection,and AhR may serve as a potential treatment target for myocardial IRI.
基金National Natural Science Foundation of China (No.81900879)。
文摘Dear Editor, We reported the first case of acute exogenous postoperative endophthalmitis caused by a normal human microbiota in the nasopharynx, Streptococcus anginosus. The patient had a successful cataract surgery, but he felt uncomfortable in the surgery eye 4 d post-surgery. Besides.
文摘End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve.It involves suturing the distal stump of the disconnected nerve(recipient nerve) to the side of the intimate adjacent nerve(donor nerve).However,the motor-sensory specificity after end-to-side neurorrhaphy remains unclear.This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy.Thirty rats were randomized into three groups:(1) end-to-side neurorrhaphy using the ulnar nerve(mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve;(2) the sham group:ulnar nerve and cutaneous antebrachii medialis nerve were just exposed;and(3) the transected nerve group:cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied.At 5 months,acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group,and none of the myelinated axons were stained in either the sham or transected nerve groups.Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%.In contrast,no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment.These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.
基金supported by the National Natural Science Foundation of China(Nos.32000894,32000420)the Ministry of Science and Technology of China(No.2018YFA0800302)+5 种基金the China postdoctoral Science Foundation(No.2019M651357)the Shanghai Sailing Program(No.18YF1412200)the Chinese Academy of Sciences Interdisciplinary Innovation Team(No.JCTD-2018-14)the Natural Science Foundation of Shanghai(NO.20ZR1408000)Fudan University Start-up Research Grant(Nos.IDH1340038,IDH1340045,IDH1340046,IDH1340059)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS,No.2019-I2M-5-077).
文摘Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appelbaum et al.1999;Saba 2007).However,drug resistance causing treatment failure and disease relapse is an unresolved problem to date.Certain cancer cells rely on the salvage enzymes cytidine deaminase(CDA)and dCMP deaminase(DCTD)to inactivate these cytidine derivative drugs by deamination(Jamieson et al.1987;Ebrahem et al.2012).It is imperative to develop new categories of chemotherapeutic nucleosides to overcome the drug resistance caused by such increased cellular deamination activity.
文摘Background Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases,differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal.The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs.Methods Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation.Perfusion was calculated using the Patlak method.The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively.CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively.The correlations between CBV, PS of tumoral parenchyma and MVD were examined.Results The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P〈0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P 〉0.05).MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P〈0.05).There were positive correlations between CBV and MVD (r=0.648, P〈0.05), PS and MVD (r=0.541, P〈0.05) respectively.Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P〈0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P〈0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not significantly different with that of contrallateral normal white matter (P 〉0.05).Conclusions CT perfusion imaging can provide critical information on the vascuiarity of HPC and benign meningiomas.Determination of maximal CBV and corresponding PS values in the parenchyma may be useful in the preoperative differentiating HPC from benign meningiomas.
基金grants from the Natural Science Foundation of China,the Shanghai High Technology Research Program
文摘Background Previous studies have shown that brain functional activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, alterations in intrinsic brain activity patterns in mild cognitive impairment (MCI) patients are poorly understood. This study aimed to explore the differences in regional intrinsic activities throughout the whole brain between aMCI patients and controls. Methods In the present study, resting-state functional magnetic resonance imaging (fMRI) was performed on 18 amnestic MCI (aMCI) patients, 18 mild AD patients and 20 healthy elderly subjects. And amplitude of low-frequency fluctuation (ALFF) method was used. Results Compared with healthy elderly subjects, aMCI patients showed decreased ALFF in the right hippocampus and parahippocampal cortex, left lateral temporal cortex, and right ventral medial prefrontal cortex (vMPFC) and increased ALFF in the left temporal-parietal junction (TPJ) and inferior parietal Iobule (IPL). Mild AD patients showed decreased ALFF in the left TPJ, posterior IPL (plPL), and dorsolateral prefrontal cortex compared with aMCI patients. Mild AD patients also had decreased ALFF in the right posterior cingulate cortex, right vMPFC and bilateral dorsal MPFC (dMPFC) compared with healthy elderly subjects. Conclusions Decreased intrinsic activities in brain regions closely related to episodic memory were found in aMCI and AD patients. Increased TPJ and IPL activity may indicate compensatory mechanisms for loss of memory function in aMCI patients. These findings suggest that the fMRI based on ALFF analysis may provide a useful tool in the study of aMCI patients.
文摘Background Endothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1 was observed after intracerebral hemorrhage (ICH); however, ET-1 changes and their relationship with BBB disruption within 24 hours of ICH have not been thoroughly investigated. The aim of the present study was to observe the changes in perihematomal ET-1 levels in various phases of ICH and their correlation with the BBB integrity in a rabbit model of ICH. Methods Twenty-five rabbits (3.2-4.3 kg body weight) were randomly divided into a normal control group (five rabbits) and a model group (20 rabbits). Animals in the model group were equally divided into four subgroups (five rabbits each to be sacrificed at 6, 12, 18, and 24 hours following ICH establishment). An ICH model was prepared in the model group by infusing autologous arterial blood into the rabbit brain. ET-1 expression in perihematomal brain tissues was determined using immunohistochemistry and color image analysis, and the permeability of the BBB was assayed using the Evan's Blue (EB) method. A repeated measures analysis of variance was used to make comparisons of the ET-1 and EB content across the entire time series. Results The number of perihematomal endothelial cells with ET-1 positive expressions following 6, 12, 18, and 24 hours ICH model establishment was 9.32, 13.05, 15.90, and 20.44, respectively, but as low as 6.67 in the control group. The average transmittance of ET-1-positive cell bodies at 6, 12, 18, and 24 hours after ICH was 99.10, 97.40, 85.70, and 80.80, respectively, but 100.12 in the control group. These data reveal that the expression of ET-1 was significantly increased at 6, 12, 18, and 24 hours after ICH compared with the control group, and a marked decrease in the average transmittance of ET-l-positive cell bodies was noted (P 〈0.05). Similarly, the perihematomal EB content at 6, 12, 18, and 24 hours after ICH was 29.39±1.16, 32.20±0.73, 33.63±1.08, and 35.26±1.12, respectively, in the model group and 28.06±0.80 in the control group. The results indicate that a significant increase in the EB content in the model group was observed compared with that of the control group (P 〈0.05). Moreover, a positive correlation between the number of ET-1-positive endothelial cells and BBB permeability was observed (t=0.883, P 〈0.05). Conclusions High levels of ET-1 are closely associated with BBB disruption. ET-1 may play an important role in the pathogenesis of secondary brain injury after ICH.
基金supported by the State Key Project on Inflectional Disease of China(2012ZX10002016-004,2012ZX 10002010-001-004)the Chinese Ministry of Public Health for Key Clinical Projects(439,2010)to Prof.Xiaoping Chenthe National Natural Science Foundation of China(81502524)to Dr.Binhao Zhang
文摘Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma(HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients,81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein(AFP) level, and other 35% had an AFP level lower than 400 ng mL^(-1). In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was(191.7±105.6) min,the blood loss was(546.0±562.8) m L, and blood transfusion was(543.0±1,035.2) m L. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules,tumor thrombosis and high AFP level were risk factors that affect postoperative survival.
基金This work was supported by grants from the National Natural Science Foundation of China (No. 30970818), and the National High-Tech Research and Development Program of China (No. 2008AA02Z302).
文摘Background Previous studies have shown that the functional brain activity in the resting state is impaired in Alzheimer's disease (AD) patients. However, most studies focused on the relationship between different brain areas, rather than the amplitude or strength of the regional brain activity. The purpose of this study was to explore the functional brain changes in AD patients by measuring the amplitude of the blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals.
基金supported by the National Health Commission of the People’s Republic of China (201302002,Clinical Trial NCT02200679)。
文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
文摘Background Our previous study confirmed that oligodendrogliomas had higher frequency of chromosome 1p/19q deletion. In order to improve the diagnostic criteria and to predict the prognosis of oligodendroglioma patients, the status of chromosome 1 p/19q deletion, the methylation of O6-methylguanine-DNA methyltransferase (MGMT), and the expression of p53 protein were evaluated and investigated in relation to patients' outcomes.Methods Methylation of MGMT in 73 cases was analyzed by nested methylation-specific PCR (MSP). The levels of MGMT and p53 protein were tested with immunohistochemistry. Pearson's chi-square test and Fisher's exact test were used. Multivariate and Kaplan-Meier analysis were performed to determine patients' outcomes.Results Both oligodendrogliomas and astrocytic gliomas exhibited frequent methylation of MGMT. However, the results of MSP did not completely correspond to that of the immunohistochemical staining for MGMT. The expression of p53 protein was more frequently observed in patients without a 1 p or 19q deletion in anaplastic oligodendrogliomas (=0.032,0.025). In low-grade oligodendrogliomas, methylation of MGMT was more frequent in patients with 1 p/19q deletion than in patients with 1p/19q intact (P=0.038). Patients with oligodendrogliomas with 1p/19q loss of heterozygosity and p53-negative showed a longer progression-free survival.Conclusion Detection of chromosome 1p/19q status combined with p53 protein immunohistochemistry might be beneficial to improve the pathological diagnosis and to determine the prognosis of patients with oligodendrogliomas.
文摘ABSTRACT Objective: To observe the effect of Lidan Granule (利胆冲剂, LDG) on bile lithogenic tendency and biliary 33.5 kd vesicular protein (VP) and to explore its mechanism. Methods: Sixty patients with choledocholithiasis combined with cholecystolithiasis were randomly assigned to the LDG treated group, the sodium cholate treated group for positive control, and the untreated control group, 20 patients in each group. The 4 bile lithogenic trend indexes, including lithogenic index (LI), unconjugated bilirubin percent (UCB%), unconjugated bilirubin saturation index (BSI) and Z-value, were determined before and after treatment. The content of VP in bile was determined as well. Results: Before treatment, the LI, UCB%, BSI and Z-value in the LDG treated group were 1.298 ± 0.265, 34.72 ± 2.96, 0.353± 0.093 and 0.556 ± 0.499, respectively, which was decreased after the 2-week treatment to 0.926± 0.208, 8.93± 1.19, 0.154 ± 0.056 and 0.257± 0.211, respectively (all P〈0.05). Meantime, the content of VP was also lowered from 0.050 ± 0.005 g/L to 0.032 ± 0.005 g/L. However, no significant change in any of the above-mentioned indexes was found in the other two groups. Conclusion: LDG could effectively suppress bile lithogenic trend and reduce 33.5 kd VP in bile.
基金ThisstudywassupportedbyShanghaiScience TechnologyDevelopingFoundationofChina (No .9741 1 90 0 6)
文摘To study the changes of adhesion molecules' expressions during the recombinant h u man granulocyte colony stimulating factor (rhG CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to confirm the influence of rhG CSF on hematopoietic stem cells, which are proposed to guide mobilization in PBS CT Methods Mice were injected subcutaneously with diluted rhG CSF or normal saline for 7 d ays The blood Sca 1 + stem cell count and bone marrow (BM) nucleated cell co unt were enumerated The expressions of CD49d and CD44 and the adhesive ability of mononuclear cells to bone marrow matrix (fibronectin) were examined by flow c ytometry and 51 Cr adhesive assay, respectively Results The mobilizing effect of rhG CSF on mice was the same as on humans The number of Sca 1 + cells in peripheral blood reached the peak on the seventh day, the BM nucleated cell count was reduced, and the expressions of CD49d and the cells ' adhesive ability in BM and PB declined Conclusions rhG CSF can reduce some cell adhesion molecules' expressions and the adhesive a bility of hematopoietic stem cells to BM matrix, therefore mobilizing hematopoie tic stem cells (HSC) from the BM to the peripheral blood