Objective:To determine the causes of COVID-19 deaths at home.Methods:This descriptive cross-sectional study was conducted on confirmed COVID-19 deaths,which were confirmed to occur at home using the“Electronic Death ...Objective:To determine the causes of COVID-19 deaths at home.Methods:This descriptive cross-sectional study was conducted on confirmed COVID-19 deaths,which were confirmed to occur at home using the“Electronic Death Registration System(EDRS)”database,from February 20,2020,to September 23,2021,in the Fars province,south of Iran.A semi-structured,face-to-face survey consisting of 29 items was filled by the family caregivers,and the information was confirmed based on medical records.Results:One hundred and ninety-three deaths were included,with 60.1%male and 39.9%female.More than 75%of cases had at least one comorbid condition.Death was unexpected for 65.8%of the families and 45.1%of the deceased cases had been medically managed at home during the disease.According to the family caregivers’opinion,the most frequent causes of death at home in their COVID-19 patients were early discharge/release from the hospital(28.5%),physician's reassurance to continue home quarantine/supportive care(14.5%),hopeless/oldest-old patient(11.9%),and family/relative recommendation to not to hospitalize their patient due to fears,myths,etc.(8.8%).Conclusions:In family caregivers’belief,deaths at home might be related to healthcare system preparedness,physicians’knowledge,and public education and empowerment.展开更多
INIRODUCIIONA newly discovered DNA virus,transfusiontransmitted virus (TTV),was reported as a cause ofpost-transfusion hepatitis of unknown etiology inJapan.In order to investigate TTV prevalence insouthern China,a st...INIRODUCIIONA newly discovered DNA virus,transfusiontransmitted virus (TTV),was reported as a cause ofpost-transfusion hepatitis of unknown etiology inJapan.In order to investigate TTV prevalence insouthern China,a study was carried out amongblood donors,patients with liver diseases andhemodialysis to determine the epidemiologicalcharateristics.展开更多
Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity...Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.展开更多
AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy bl...AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 ± 12.58 U/L (normal range 5-35 U/L), 33.13 ± 22.98 (normal range 5-35 U/L), and 25.11 ± 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P < 0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B = 6.988, P = 0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B = 15.763, P < 0.001), (B = 32.345, P < 0.001), (B =24.415, P < 0.001), respectively.CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.展开更多
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the hig...The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.展开更多
AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran. METHODS: A total of 2292 (1376 female, aged 18-75 year), were s...AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran. METHODS: A total of 2292 (1376 female, aged 18-75 year), were selected by systematic clustered random sampling from the cities and villages of Gonbad and Kalaleh in Golestan Province and invited to participate in the study. A comprehensive history regarding alcohol drinking and medication was taken. Body mass index (BMI), viral markers and ALT levels were measured. If ALT level was ≥ 40 U/L, it was rechecked twice within 6 mo. Those with ≥ 2 times elevation of ALT were considered as having persistently elevated ALT level. Non-alcoholic fatty liver disease (NAFLD) was diagnosed based on evidence of fatty liver upon sonography and excluding other etiology. RESULTS: A total of 2049 (1351 female) patients participated in the study, 162 (7.9%) had elevated ALT level at the first measurement. Persistently elevated ALT level was detected in 64 (3.1%) participants, with51 (79.6%) with no obvious etiology, six (9.3%) with Hepatitis B, four (6.2%) with Hepatitis C virus (HCV) infection and three (4.6%) with alcoholic hepatitis. The prevalence of NAFLD and alcoholic hepatitis was 2.04% (42 patients) and 0.1% (three), respectively. There was correlation between NAFLD and male gender, overweight, diabetes and living in an urban area [odds ratio = 3.03 (95% CI: 1.6-5.72), 4.21 (95% CI: 1.83-9.68), 2.86 (95% CI: 1.05-7.79) and 2.04 (95% CI: 1.00-4.16) respectively]. CONCLUSION: NAFLD is the most common cause of persistently elevated serum ALT level among the general population of Iran.展开更多
Bone marrow microenvironment (BMM) is the main sanctuary of leukemic stem cells (LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the clo...Bone marrow microenvironment (BMM) is the main sanctuary of leukemic stem cells (LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the close connection between LSCs and the BMM. The elimination of LSCs is of high importance, since they follow cancer stem cell theory as a part of this population. Based on cancer stem cell theory, a cell with stem cell-like features stands at the apex of the hierarchy and produces a heterogeneous population and governs the disease. Secretion of cytokines, chemokines, and extracellular vesicles, whether through autocrine or paracrine mechanisms by activation of downstream signaling pathways in LSCs, favors their persistence and makes the BMM less hospitable for normal stem cells. While all details about the interactions of the BMM and LSCs remain to be elucidated, some clinical trials have been designed to limit these reciprocal interactions to cure leukemia more effectively. In this review, we focus on chronic myeloid leukemia and acute myeloid leukemia LSCs and their milieu in the bone marrow, how to segregate them from the normal compartment, and finally the possible ways to eliminate these cells.展开更多
Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisininbased combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is esse...Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisininbased combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications.展开更多
AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis C referred t...AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type ofpegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a(Pegaferon®) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus(HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes.RESULTS: A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men(92.8%). The most frequent HCV genotype was type-1, infecting 93/152(61.2%) patients. Sustained virologic response(SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2%(52/57) of patients with the IFNL rs12979860 CC genotype and 82.1%(78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT(39/45; 86.7%) and non-TT(61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR(OR = 6.2; 95%CI: 1.2-31.9; P = 0.03).CONCLUSION: The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.展开更多
Umbilical cord blood(UCB) is a valuable source of hematopoietic stem cells(HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen(HLA)-matched donors. The main pr...Umbilical cord blood(UCB) is a valuable source of hematopoietic stem cells(HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen(HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation(UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together,complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.展开更多
Objective:To investigate the protective effect of IL-22 and IL-12 on cutaneous leishmaniasisin BALB/c mice.Methods:The protective effect of IL-22 and IL-I2 on cutaneous leishmanias in BALB/c mice was evaluated by meas...Objective:To investigate the protective effect of IL-22 and IL-12 on cutaneous leishmaniasisin BALB/c mice.Methods:The protective effect of IL-22 and IL-I2 on cutaneous leishmanias in BALB/c mice was evaluated by measurement of IL-4.INF-γ.total IgG,IgG1 and IgG2 a after challenge with Leishamania major.Clinical evaluations were performed by measurement of lesion diameter,and survival rate of the mice.Results:In week 27 post infection,the mortality rates for control groups were 100%.While the survival rates for the IL-12.IL-12 + IL-22.and IL-22(5 ng/g) groups were 100%.The size of lesions decreased in the presence IL-22(5 ng/g) of mice weight,which was statistically significant in comparison with other groups(P<0.05).Mean of total IgG,IgG1 and IgG2 a for IL-22(5 ng/g) group was more than other groups.In IL-22 group(5 ng/g).INF—γ production was significantly higher than other groups and IL-4 was significantly lower than other groups.Conclusions:The results obtained indicate the effectiveness of IL-22 and its effect on IL-12 in protection of cutaneous leishmaniasis.展开更多
The current pandemic SARS-CoV-2(also known as 2019-nCoV and COVID-19)viral infection is growing globally and has created a disastrous situation all over the world.One of the biggest challenges is that no drugs are ava...The current pandemic SARS-CoV-2(also known as 2019-nCoV and COVID-19)viral infection is growing globally and has created a disastrous situation all over the world.One of the biggest challenges is that no drugs are available to treat this life-threatening disease.As no drugs are available for definitive treatment of this disease and the mortality rate is very high,there is an utmost need to cure the infection using novel technologies.This study will point out some new antimicrobial technologies that have great potentials for eradicating and preventing emerging infections.They can be considered as treatments of choice for viral infections in the future.展开更多
The efficient differentiation of adult gastric stem cells into specific epithelial cell types is crucial for gastric homeostasis.Although it is well appreciated that the niche plays a critical role in gastric epitheli...The efficient differentiation of adult gastric stem cells into specific epithelial cell types is crucial for gastric homeostasis.Although it is well appreciated that the niche plays a critical role in gastric epithelium cell differentiation,the relevant molecular factors and the underlying regulatory mechanisms remain poorly understood.In this study,by combining the knowledge of the niche cells obtained from single-cell RNA sequencing and manipulation of signaling pathways,we achieved effective differentiation of various gastric epithelial cell types in mouse and human gastric organoids.These in vitro differentiated cells showed a similar gene expression profile to those in gastric tissues.Specifically,BMP4 signaling stimulates pit cell and parietal cell differentiation.Furthermore,BMP4 and EGF signaling cooperate to enhance pit cell differentiation,whereas inhibition of TGF-βand BMP4 signaling promotes chief cell differentiation.We demonstrated that Zbtb7b is a novel regulator controlling pit cell differentiation.In addition,BMP4,together with the small molecule Isoxazole 9,promotes parietal and enteroendocrine cell differentiation.Our data also revealed the different requirements of parietal and chief cell differentiation between mouse and human.Together,our findings provide a mechanistic insight into gastric epithelial cell differentiation and uncover its similarities and differences between mouse and human,laying a foundation for future investigation and potential clinical use of gastric organoids.展开更多
Background:Given the controversial reports on the effect of convalescent plasma(CP)on coronavirus disease 2019(COVID-19)patients,this study aimed to clarify the efficacy of early CP administration,improve the understa...Background:Given the controversial reports on the effect of convalescent plasma(CP)on coronavirus disease 2019(COVID-19)patients,this study aimed to clarify the efficacy of early CP administration,improve the understanding of its impact on clinical outcomes,guide future research,address safety concerns,and inform public health policies.Methods:In this prospective,multicenter,randomized controlled trial conducted at Razi Hospital(Ahvaz)and Bouali Hospital(Zahedan)in Iran,232 confirmed COVID-19 patients were randomly assigned into two groups using a computer-generated randomization method.The treatment group(n=116)received CP with anti-severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)IgG titer≥1/160 on the first day of admission,along with routine antiviral medications,while the control group received only routine medications(n=116).Recruitment occurred from 1 March to 30 July 2020,with two months of post-intervention follow-up.The primary outcome was two-month mortality,and secondary outcomes included CP-related side effects and various clinical and laboratory parameters.Results:No significant differences were observed between the groups in terms of age(P=0.119),sex(P=0.418),comorbidities(P>0.05),or pre-and post-treatment changes in temperature,lymphocyte count,erythrocyte sedimentation rate,or platelet count(all P>0.05).Despite a higher CT severity score at admission in the treatment group(P<0.001),improvements in respiratory rate,C-reactive protein,and lactate dehydrogenase occurred earlier and were more pronounced compared to the control group(P<0.05).No side effects related to CP therapy were observed during infusion or follow-up.However,no significant differences were observed between the groups in the mortality rate or length of hospitalization.The mortality rate in the treatment group was 11.2%(13/116),compared to 17.2%(20/116)in the control group(P=0.130).The median hospital stay was 7 days(95%CI:6-8 days)for the treatment group and 6 days(95%CI:5-7 days)for the control group(P=0.560).Conclusion:While administering CP with a high titer of anti-SARS-CoV-2 IgG early in infection may improve vital signs and laboratory parameters in COVID-19 patients,it does not significantly reduce mortality risk or length of hospitalization compared to routine medications.Overall,the treatment appears to have few side effects,suggesting it may be a safe option for further evaluation in managing early COVID-19 symptoms.展开更多
Dendritic cells （DCs） are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous ...Dendritic cells （DCs） are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous population of cells that differ in their development, surface phenotype and function. The study of human blood and spleen has shown the presence of two subsets of conventional DC including the CDlb/c＋ and CD141＋CLEC9A＋ conventional DC （cDC） and a plasmacytoid DC （pDC） that is CD304＋CD123＋. Studies on these subpopulations have revealed phenotypic and functional differences that are similar to those described in the mouse. In this study, the three DC subsets have been generated in vitrofrom human CD34＋ precursors in the presence of fins-like tyrosine kinase 3 ligand （FIt3L） and thrombopoietin （TPO）. The DC subsets so generated, including the CDlb/c＋ and CLEC9A＋ cDCs and CD123 ＋ pDCs, were largely similar to their blood and spleen counterparts with respect to surface phenotype, toll-like receptor and transcription factor expression, capacity to stimulate T cells, cytokine secretion and cross-presentation of antigens. This system may be utilized to study aspects of DC development and function not possible in vivo.展开更多
BACKGROUND： Bone marrow mesenchymal stromal cells （BM-MSCs） are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abn...BACKGROUND： Bone marrow mesenchymal stromal cells （BM-MSCs） are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type. METHODS： A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used： ＂cytogenetic,＂ ＂leukemia,＂ ＂bone marrow,＂ and ＂mesenchymal stromal cells.＂ RESULTS： Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells. CONCLUSIONS： Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.展开更多
BACKGROUND： Recurrent pregnancy loss （RPL） is a heterogeneous condition and thrombophilias have been considered as a probable cause. OBJECTIVE： The aim of this study was to investigate the prevalence of the coagul...BACKGROUND： Recurrent pregnancy loss （RPL） is a heterogeneous condition and thrombophilias have been considered as a probable cause. OBJECTIVE： The aim of this study was to investigate the prevalence of the coagulation factor XIII Va134Leu polymorphism among women with unexplained RPL. METHODS： A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Va134Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. RESULTS： Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls （P〈 0.05）： 33.5% vs. 15%, and 9.2% vs. 2%, respectively. CONCLUSION： These results indicate a significant association between FXIII Va134Leu polymorphism and unexplained RPL in the Iranian patient.展开更多
文摘Objective:To determine the causes of COVID-19 deaths at home.Methods:This descriptive cross-sectional study was conducted on confirmed COVID-19 deaths,which were confirmed to occur at home using the“Electronic Death Registration System(EDRS)”database,from February 20,2020,to September 23,2021,in the Fars province,south of Iran.A semi-structured,face-to-face survey consisting of 29 items was filled by the family caregivers,and the information was confirmed based on medical records.Results:One hundred and ninety-three deaths were included,with 60.1%male and 39.9%female.More than 75%of cases had at least one comorbid condition.Death was unexpected for 65.8%of the families and 45.1%of the deceased cases had been medically managed at home during the disease.According to the family caregivers’opinion,the most frequent causes of death at home in their COVID-19 patients were early discharge/release from the hospital(28.5%),physician's reassurance to continue home quarantine/supportive care(14.5%),hopeless/oldest-old patient(11.9%),and family/relative recommendation to not to hospitalize their patient due to fears,myths,etc.(8.8%).Conclusions:In family caregivers’belief,deaths at home might be related to healthcare system preparedness,physicians’knowledge,and public education and empowerment.
文摘INIRODUCIIONA newly discovered DNA virus,transfusiontransmitted virus (TTV),was reported as a cause ofpost-transfusion hepatitis of unknown etiology inJapan.In order to investigate TTV prevalence insouthern China,a study was carried out amongblood donors,patients with liver diseases andhemodialysis to determine the epidemiologicalcharateristics.
基金supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065),the Innovation Groups of NSFC(81721001),and the Young Scientists Fund(82102279).
文摘Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
文摘AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 ± 12.58 U/L (normal range 5-35 U/L), 33.13 ± 22.98 (normal range 5-35 U/L), and 25.11 ± 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P < 0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B = 6.988, P = 0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B = 15.763, P < 0.001), (B = 32.345, P < 0.001), (B =24.415, P < 0.001), respectively.CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
基金Digestive Disease Research Center, Medical Sciences/University of Tehran and Iranian Blood Transfusion Research Center, Tehran, Iran. No. 1384/4
文摘AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran. METHODS: A total of 2292 (1376 female, aged 18-75 year), were selected by systematic clustered random sampling from the cities and villages of Gonbad and Kalaleh in Golestan Province and invited to participate in the study. A comprehensive history regarding alcohol drinking and medication was taken. Body mass index (BMI), viral markers and ALT levels were measured. If ALT level was ≥ 40 U/L, it was rechecked twice within 6 mo. Those with ≥ 2 times elevation of ALT were considered as having persistently elevated ALT level. Non-alcoholic fatty liver disease (NAFLD) was diagnosed based on evidence of fatty liver upon sonography and excluding other etiology. RESULTS: A total of 2049 (1351 female) patients participated in the study, 162 (7.9%) had elevated ALT level at the first measurement. Persistently elevated ALT level was detected in 64 (3.1%) participants, with51 (79.6%) with no obvious etiology, six (9.3%) with Hepatitis B, four (6.2%) with Hepatitis C virus (HCV) infection and three (4.6%) with alcoholic hepatitis. The prevalence of NAFLD and alcoholic hepatitis was 2.04% (42 patients) and 0.1% (three), respectively. There was correlation between NAFLD and male gender, overweight, diabetes and living in an urban area [odds ratio = 3.03 (95% CI: 1.6-5.72), 4.21 (95% CI: 1.83-9.68), 2.86 (95% CI: 1.05-7.79) and 2.04 (95% CI: 1.00-4.16) respectively]. CONCLUSION: NAFLD is the most common cause of persistently elevated serum ALT level among the general population of Iran.
文摘Bone marrow microenvironment (BMM) is the main sanctuary of leukemic stem cells (LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the close connection between LSCs and the BMM. The elimination of LSCs is of high importance, since they follow cancer stem cell theory as a part of this population. Based on cancer stem cell theory, a cell with stem cell-like features stands at the apex of the hierarchy and produces a heterogeneous population and governs the disease. Secretion of cytokines, chemokines, and extracellular vesicles, whether through autocrine or paracrine mechanisms by activation of downstream signaling pathways in LSCs, favors their persistence and makes the BMM less hospitable for normal stem cells. While all details about the interactions of the BMM and LSCs remain to be elucidated, some clinical trials have been designed to limit these reciprocal interactions to cure leukemia more effectively. In this review, we focus on chronic myeloid leukemia and acute myeloid leukemia LSCs and their milieu in the bone marrow, how to segregate them from the normal compartment, and finally the possible ways to eliminate these cells.
基金funded by the National Natural Science Foundation of China(31260508,U1202226)grants of Doctor Newcomer Scholarship from Yunnan province
文摘Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisininbased combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications.
基金Supported by Pooyesh Darou which is the local manufacturer of pegylated interferon alpha-2a in Iran(Pegaferon)
文摘AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ(IFNL) polymorphisms. METHODS: This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type ofpegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a(Pegaferon®) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus(HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes.RESULTS: A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men(92.8%). The most frequent HCV genotype was type-1, infecting 93/152(61.2%) patients. Sustained virologic response(SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2%(52/57) of patients with the IFNL rs12979860 CC genotype and 82.1%(78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT(39/45; 86.7%) and non-TT(61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR(OR = 6.2; 95%CI: 1.2-31.9; P = 0.03).CONCLUSION: The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.
文摘Umbilical cord blood(UCB) is a valuable source of hematopoietic stem cells(HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen(HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation(UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together,complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.
文摘Objective:To investigate the protective effect of IL-22 and IL-12 on cutaneous leishmaniasisin BALB/c mice.Methods:The protective effect of IL-22 and IL-I2 on cutaneous leishmanias in BALB/c mice was evaluated by measurement of IL-4.INF-γ.total IgG,IgG1 and IgG2 a after challenge with Leishamania major.Clinical evaluations were performed by measurement of lesion diameter,and survival rate of the mice.Results:In week 27 post infection,the mortality rates for control groups were 100%.While the survival rates for the IL-12.IL-12 + IL-22.and IL-22(5 ng/g) groups were 100%.The size of lesions decreased in the presence IL-22(5 ng/g) of mice weight,which was statistically significant in comparison with other groups(P<0.05).Mean of total IgG,IgG1 and IgG2 a for IL-22(5 ng/g) group was more than other groups.In IL-22 group(5 ng/g).INF—γ production was significantly higher than other groups and IL-4 was significantly lower than other groups.Conclusions:The results obtained indicate the effectiveness of IL-22 and its effect on IL-12 in protection of cutaneous leishmaniasis.
文摘The current pandemic SARS-CoV-2(also known as 2019-nCoV and COVID-19)viral infection is growing globally and has created a disastrous situation all over the world.One of the biggest challenges is that no drugs are available to treat this life-threatening disease.As no drugs are available for definitive treatment of this disease and the mortality rate is very high,there is an utmost need to cure the infection using novel technologies.This study will point out some new antimicrobial technologies that have great potentials for eradicating and preventing emerging infections.They can be considered as treatments of choice for viral infections in the future.
基金supported by grants from the Beijing Science and Technology Plan(Z231100007223006)the Natural Science Foundation of China(92354306,31988101)+2 种基金the National Key Research and Development Program of China(2023YFA1800603)the Shenzhen Medical Research Fund(B2302022)the Natural Science Foundation of Jiangxi Province(20224 ACB209001).
文摘The efficient differentiation of adult gastric stem cells into specific epithelial cell types is crucial for gastric homeostasis.Although it is well appreciated that the niche plays a critical role in gastric epithelium cell differentiation,the relevant molecular factors and the underlying regulatory mechanisms remain poorly understood.In this study,by combining the knowledge of the niche cells obtained from single-cell RNA sequencing and manipulation of signaling pathways,we achieved effective differentiation of various gastric epithelial cell types in mouse and human gastric organoids.These in vitro differentiated cells showed a similar gene expression profile to those in gastric tissues.Specifically,BMP4 signaling stimulates pit cell and parietal cell differentiation.Furthermore,BMP4 and EGF signaling cooperate to enhance pit cell differentiation,whereas inhibition of TGF-βand BMP4 signaling promotes chief cell differentiation.We demonstrated that Zbtb7b is a novel regulator controlling pit cell differentiation.In addition,BMP4,together with the small molecule Isoxazole 9,promotes parietal and enteroendocrine cell differentiation.Our data also revealed the different requirements of parietal and chief cell differentiation between mouse and human.Together,our findings provide a mechanistic insight into gastric epithelial cell differentiation and uncover its similarities and differences between mouse and human,laying a foundation for future investigation and potential clinical use of gastric organoids.
文摘Background:Given the controversial reports on the effect of convalescent plasma(CP)on coronavirus disease 2019(COVID-19)patients,this study aimed to clarify the efficacy of early CP administration,improve the understanding of its impact on clinical outcomes,guide future research,address safety concerns,and inform public health policies.Methods:In this prospective,multicenter,randomized controlled trial conducted at Razi Hospital(Ahvaz)and Bouali Hospital(Zahedan)in Iran,232 confirmed COVID-19 patients were randomly assigned into two groups using a computer-generated randomization method.The treatment group(n=116)received CP with anti-severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)IgG titer≥1/160 on the first day of admission,along with routine antiviral medications,while the control group received only routine medications(n=116).Recruitment occurred from 1 March to 30 July 2020,with two months of post-intervention follow-up.The primary outcome was two-month mortality,and secondary outcomes included CP-related side effects and various clinical and laboratory parameters.Results:No significant differences were observed between the groups in terms of age(P=0.119),sex(P=0.418),comorbidities(P>0.05),or pre-and post-treatment changes in temperature,lymphocyte count,erythrocyte sedimentation rate,or platelet count(all P>0.05).Despite a higher CT severity score at admission in the treatment group(P<0.001),improvements in respiratory rate,C-reactive protein,and lactate dehydrogenase occurred earlier and were more pronounced compared to the control group(P<0.05).No side effects related to CP therapy were observed during infusion or follow-up.However,no significant differences were observed between the groups in the mortality rate or length of hospitalization.The mortality rate in the treatment group was 11.2%(13/116),compared to 17.2%(20/116)in the control group(P=0.130).The median hospital stay was 7 days(95%CI:6-8 days)for the treatment group and 6 days(95%CI:5-7 days)for the control group(P=0.560).Conclusion:While administering CP with a high titer of anti-SARS-CoV-2 IgG early in infection may improve vital signs and laboratory parameters in COVID-19 patients,it does not significantly reduce mortality risk or length of hospitalization compared to routine medications.Overall,the treatment appears to have few side effects,suggesting it may be a safe option for further evaluation in managing early COVID-19 symptoms.
文摘Dendritic cells （DCs） are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous population of cells that differ in their development, surface phenotype and function. The study of human blood and spleen has shown the presence of two subsets of conventional DC including the CDlb/c＋ and CD141＋CLEC9A＋ conventional DC （cDC） and a plasmacytoid DC （pDC） that is CD304＋CD123＋. Studies on these subpopulations have revealed phenotypic and functional differences that are similar to those described in the mouse. In this study, the three DC subsets have been generated in vitrofrom human CD34＋ precursors in the presence of fins-like tyrosine kinase 3 ligand （FIt3L） and thrombopoietin （TPO）. The DC subsets so generated, including the CDlb/c＋ and CLEC9A＋ cDCs and CD123 ＋ pDCs, were largely similar to their blood and spleen counterparts with respect to surface phenotype, toll-like receptor and transcription factor expression, capacity to stimulate T cells, cytokine secretion and cross-presentation of antigens. This system may be utilized to study aspects of DC development and function not possible in vivo.
文摘BACKGROUND： Bone marrow mesenchymal stromal cells （BM-MSCs） are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type. METHODS： A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used： ＂cytogenetic,＂ ＂leukemia,＂ ＂bone marrow,＂ and ＂mesenchymal stromal cells.＂ RESULTS： Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells. CONCLUSIONS： Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.
文摘BACKGROUND： Recurrent pregnancy loss （RPL） is a heterogeneous condition and thrombophilias have been considered as a probable cause. OBJECTIVE： The aim of this study was to investigate the prevalence of the coagulation factor XIII Va134Leu polymorphism among women with unexplained RPL. METHODS： A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Va134Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. RESULTS： Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls （P〈 0.05）： 33.5% vs. 15%, and 9.2% vs. 2%, respectively. CONCLUSION： These results indicate a significant association between FXIII Va134Leu polymorphism and unexplained RPL in the Iranian patient.
