Gene expression of cytokines after allogeneic peripheral stem cell transplantation and its relationship with acute graft-versus-host disease

Objective: To investigate the role of cytokines IL-2, IL-4, IL-10, IL-12, and IFN-γ in pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: Forty-two patients undergoing allo-PBSCT were included in this study. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to analyze gene expression of cytokines IL-2, IL-4, IL-10, IL-12, and IFN-γ. Results: All patients achieved engraftment, 18 patients developed grade ⅠGVHD, 6 patients developed grade Ⅱ-Ⅳ GVHD. The gene expression of IL-2, IL-12, and IFN-γ increased, the gene expression of IL-4 and IL-10 decreased. Conclusion: Cytokines IL-2, IL-12, and IFN-γ lead to a positive regulation of the development in human aGVHD, and IL-4 and IL-10 play negative regulatory roles.

Diagnosis and treatment of acute graft-versus-host disease after liver transplantation:Report of six cases

BACKGROUND Graft-versus-host disease(GVHD)following liver transplantation(LT)is an unpredictable complication with poor outcome.However,consensus regarding the diagnosis and therapeutic regimen for the disease is yet lacking.The present study summarized the clinical experience on the diagnosis and treatment of acute GVHD(aGVHD)following LT and reviewed the pertinent literature.CASE SUMMARY Between January 1^(st),2000 and December 31^(st),2020,a total of 1053 LT were performed in the First Affiliated Hospital of Xi’an Jiaotong University.Six recipients developed aGVHD with clinical symptoms of fever,rash,diarrhea,and pancytopenia.The incidence of aGVHD was 0.57%.The median time from LT to the clinical presentation of aGVHD was 22.17 d.The median time from the beginning of the clinical symptom to histopathological diagnosis was 7.5 d.All six cases underwent treatment of immunosuppressant adjustment,corticosteroids,human normal immunoglobulin,and antithymocyte globulin/IL-2 antagonists.Despite intensive treatment strategies,4 patients were deceased due to sepsis,multiple organ failure,and cerebral hemorrhage.The remaining two cases were discharged as treatment successfully.However,one died because of tuberculosis infection on the 6 th month of follow-up,the other one was alive healthy during 30 mo of follow-up.CONCLUSION The rapid diagnosis of aGVHD is mainly based on the time from the first symptom,histopathological features,and the donor T-lymphocyte chimerism.Our cases report highlights massive corticosteroid therapy and age difference between donors and recipients could accelerate to aGVHD.Moreover,gut microbial interventions and donor-targeted serotherapy may provide novel therapeutics.

Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease

The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.

Expressions of Tissue Factor and Tissue Factor Pathway Inhibitor in Patients with Acute Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

This study examined the expressions of human serum tissue factor （TF） and tissue factor pathway inhibitor （TFPI） in patients with acute graft-versus-host disease （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplanta-tion and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipi-ents in the absence of aGVHD or with gradeⅠaGVHD before and after the transplantation. The lev-els of serum TF and TFPI were substantially increased in the patients with gradeⅡ aGVHD at the peak of aGVHD （P〈0.05） and they were even higher in the patients with grade Ⅲ–Ⅳ aGVHD （P〈0.01）. When the conditions became stable after treatment with immunosuppressive agents, the serum TFPI level was decreased to the baseline level （P〉0.05） and the TF level was lowered but still higher than the baseline level （P〈0.05）. It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade Ⅱ–Ⅳ aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.

Pathophysiology of acute graft-versus-host disease from the perspective of hemodynamics determined by dielectric analysis

BACKGROUND Numerous reports have demonstrated that the pathophysiology of graft-versushost disease(GVHD)during hematopoietic stem cell transplantation(HSCT)is closely related to vascular endothelial disorders and coagulation abnormalities.We previously presented the discovery of a principle and the development of a novel instrument for measuring whole blood coagulation.This was achieved by assessing the variations in the dielectric properties of whole blood.AIM To investigate how GVHD affects the changes of dielectric properties of whole blood in patients with HSCT.METHODS We examined the changes of dielectric properties of whole blood and erythrocyte proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis sequentially in patients with HSCT and compared it with clinical symptoms and inflammatory parameters of GVHD.RESULTS During severe GVHD,the dielectric relaxation strength markedly increased and expression of band3 decreased.The dielectric relaxation strength normalized with the improvement of GVHD.In vitro analysis confirmed that the increase of relaxation strength was associated with severe erythrocyte aggregates,but not with decreased expression of band3.CONCLUSION Severe erythrocyte aggregates observed in GVHD may cause coagulation abnormalities and circulatory failure,which,together with the irreversible erythrocyte dysfunction we recently reported,could lead to organ failure.

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are lacking.Methods:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology,the First Affiliated Hospital of USTC,between August 2018 and June 2021.IR differences were compared between the patients with and without aGVHD.Results:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of lymphocytes.DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation.Importantly,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow.In addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization

This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.

Correlation of neutrophil to lymphocyte ratio to severity of coronary artery disease and in-hospital clinical outcomes in patients with acute coronary syndrome: A prospective observational study

Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease(AECOPD)is often combined with respiratory failure,which increases the patient's morbidity and mortality.Diaphragm ultrasound(DUS)has developed rapidly in the field of critical care in recent years.Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator.Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important.AIM To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD.METHODS Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed,and they were divided into a successful ventilation group(68 cases)and a failed ventilation group(26 cases)according to the outcome of ventilation.The clinical data of patients with successful and failed noninvasive ventilation were compared,and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis.RESULTS There were no significant differences in gender,age,body mass index,complications,systolic pressure,heart rate,mean arterial pressure,respiratory rate,oxygen saturation,partial pressure of oxygen,oxygenation index,or time of inspiration between patients with successful and failed mechanical ventilation(P>0.05).The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide(PaCO_(2))than those with failed treatment,while potential of hydrogen(pH),diaphragm thickening fraction(DTF),diaphragm activity,and diaphragm movement time were significantly higher than those with failed treatment(P<0.05).pH[odds ratio(OR)=0.005,P<0.05],PaCO_(2)(OR=0.430,P<0.05),and DTF(OR=0.570,P<0.05)were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients.CONCLUSION The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.

Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Effects of Wuwei Xiaodu Decoction on Uterine Energy Metabolism and Serum Inflammatory Factors in Rats with Acute Pelvic Inflammatory Disease

[Objectives]To observe the effects of Wuwei Xiaodu Decoction on uterine energy metabolism and serum inflammatory factors in the acute pelvic inflammatory disease(APID)model.[Methods]75 Wistar rats(females)were randomly divided into control group,model group and Wuwei Xiaodu Decoction low,medium and high dose groups(n=15).Except for the control group,the rat APID model was established by right uterine inoculation.On the fifth day after inoculation,the low,medium and high dose groups of Wuwei Xiaodu Decoction were administered at 4,8 and 16 g/kg,and the control group and model group received normal saline.Rats were killed 12 h after nondose administration,blood was collected from the abdominal aorta and measured by ELISA for serum interleukin-6(interleukin-6,IL-6),IL-8,and C-reactive proteins(CRP);the right uterus of rats was tested for high-energy phosphate adenosine phosphate(AMP),adenosine diphosphate(ADP),adenosine triphosphate(ATP)and total adenine nucleotides(TAN)level to evaluate the uterine energy metabolism.[Results]AMP,ADP,ATP and TAN were significantly higher in the Wuwei Xiaodu Decoction of low,medium and high dose than the model group,while the serum IL-6,IL-8 and CRP were significantly lower than the model group,and the difference between the low,medium and high doses(P<0.05).[Conclusions]The Wuwei Xiaodu Decoction can dose-dependent promote uterine energy metabolism and inhibit inflammatory response in APID model rats.

Palliative care for end-stage liver disease and acute on chronic liver failure:A systematic review

BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.

Adult-Onset Still's Disease Misdiagnosed as Acute Fibrinous and Organizing Pneumonia: A Case Report and Literature Review

Adult-onset Stil's disease(AOSD)is a rare condition that lies between autoinflammatory syndrome and autoimmune disease.The main clinical manifestations include fever,chills,rash,joint swelling and pain,peripheral blood leukocytosis,splenomegaly,etc.It is a systemic disease affecting between 1 and 34 people per million.The average age of onset is 35 years old,with a slightly higher prevalence rate in women.Since AOSD lacks early specific symptoms and signs,non-specialist doctors have limited understanding of the disease,and patients are prone to clinical misdiagnosis,mistreatment,and delayed disease progression.This paper reports a patient whose AOSD was misdiagnosed as acute fibrinous and organizing pneumonia.

Clinical Efficacy and Safety Analysis of Tigecycline in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Combined with Multidrug-Resistant Acinetobacter baumannii Infection

Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infection.Methods:113 patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection were recruited between January 2021 and January 2023,and given tigecycline treatment.The total effective rate,lung function indexes,related biochemical index levels,and the incidence rate of adverse reactions were observed after the treatment.Results:After the treatment,100 patients were cured,1 case with apparent effect,2 cases were effective,10 cases were ineffective,and the total effective rate was 91.15%.The post-treatment CRP(21.22±3.35 mg/L),PCT(3.18±1.11 ng/L),CRE(76.36±9.24μmol/L),and ALT(37.76±6.99 U/L)were significantly improved as compared to the pre-treatment(P<0.05).After treatment,10 cases of vomiting(8.85%),13 cases of nausea(11.50%),4 cases of diarrhea(3.53%),1 case of abdominal pain(0.88%),and 2 cases of allergy(1.77%)were observed in 113 patients.Conclusion:Tigecycline therapy for patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection not only has significant therapeutic efficacy but also has a high degree of safety.

《Controlled,randomized,open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation》解读——临床实践与基础研究的相互转化

本文最初发表于2016年的《Journal of Clinical Oncology》杂志上,文章题录为:Chang YJ,Xu LP,Wang Y,et al.Controlled,randomized,open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation[J].J Clin Oncol,2016,34:1855-1863。本研究证实在单倍型相合骨髓/外周血混合移植模式下,危险分层指导的小剂量激素预防不仅降低了移植后Ⅱ~Ⅳ度急性移植物抗宿主病发生率,而且促进了血小板重建,降低了激素相关的股骨头坏死和继发性高血压的发生率,使单倍型相合移植更安全。经通信作者允许,再次以佳文解读的形式来阐释这一发现。

Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

Background In haploidentical hematopoietic stem cell transplantation （HSCT）, the duration of graft-versus-host disease （GVHD） prophylaxis after modified donor lymphocyte infusion （DLI） was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia （GVL） effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease （MRD）-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients （26.6% vs. 69.0%, P 〈0.001）. Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant （P=0.018） and in 49 patients developing MRD-positive status post-transplant （P 〈0.001）. Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD （P 〈0.05）, reduced the therapeutic application of immunosuppressive agents （P=0.019）, but increased the incidence of chronic GVHD （P〈0.05）. Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant （P 〈0.05）. Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks. This strategy will probably improve the safety and efficacy of modified DLI further.

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

Transplantation of primary and reversibly immortalized human liver cells and other gene therapies in acute liver failure and decompensated chronic liver disease

Studies performed in experimental small animalswith hepatic-based metabolic disorders but nostructural liver disease,including Gunn andanalbuminaemic rats and rabbits with inherited low-density lipoprotein receptor deficiency,have shownthat up to 95% of hepatocytes transplanted into thespleen or liver remain in these sites,withimprovement in metabolic function

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.