BACKGROUND: Although regulatory T cells(Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to r...BACKGROUND: Although regulatory T cells(Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis.DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and Pub Med. Articles on the role of Tregs in immune dysfunction during sepsis were identified.RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function.CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.展开更多
Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has ...Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.展开更多
Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in th...Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in the“Curcumin”panel instead of the original“Curcumin”panel.The corrected version of Figure 4 is shown below as the revised Figure 4.The figure legend remains the same.展开更多
To the Editor:Lung cancer,specifically lung adenocarcinoma(LUAD),is one of the primary cause of cancer-related mortality globally.[1,2]Nevertheless,only a small subset of individuals with LUAD have derived clinical be...To the Editor:Lung cancer,specifically lung adenocarcinoma(LUAD),is one of the primary cause of cancer-related mortality globally.[1,2]Nevertheless,only a small subset of individuals with LUAD have derived clinical benefits from chemoimmunotherapy in either first-line or subsequent treatment settings.Both programmed death-ligand 1(PDL1)expression and tumor mutational burden(TMB)have proven inadequate in accurately predicting treatment outcomes in these scenarios.[3]Consequently,there exists a pressing necessity to identify a reliable biomarker to inform treatment decisions.展开更多
Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body.Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity,due to defects in the local immunity o...Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body.Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity,due to defects in the local immunity of liver as well as in systemic immunity.Cirrhosis-associated immune dysfunction is a dynamic phenomenon,comprised of both increased systemic inflammation and immunodeficiency,and is responsible for 30%mortality.It also plays an important role in acute as well as chronic decompensation.Immune paralysis can accompany it,which is characterized by increase in antiinflammatory cytokines and suppression of proinflammatory cytokines.There is also presence of increased gut permeability,reduced gut motility and altered gut flora,all of which leads to increased bacterial translocation.This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome,sepsis,multiorgan failure and death.The gut microbiota of cirrhotic patients has more pathogenic microbes than that of noncirrhotic individuals,and this disturbs the homeostasis and favors gut translocation.Prompt diagnosis and treatment of such infections are necessary for better survival.We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis.Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates.展开更多
Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The es...Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The estimated case fatality rate is approximately 3.4%in China.However,some patients experience dyspnea within 1 week and develop rapidly to organ injury and even death within 2 weeks after dyspnea.1 In addition,early organ injury could lead to higher risks of mortality.Thus,early identification of patients at risk of organ injury and death is crucial,which saves the patients from classified and invasive treatment,improving clinical outcome and prognosis.The human immune system plays significant roles in the resistance of foreign pathogens and the progress of pneumonia.Recent studies have mentioned that T cells were decreased in COVID-19 patients,excessive activated immune response was caused by pathogenic Th1 cells,and inflammatory CD14+CD16+monocytes may connect to pulmonary immunopathology,leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections.2 SARS-CoV-2 might damage lymphocytes,especially T lymphocytes,and the immune system was impaired during the period of disease to cause tissue injury.展开更多
Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global...Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest（CA） and resuscitation.Methods：Thirty pigs were randomly divided into the sham（n=6） and 3 returns of spontaneous circulation（ROSC） groups（n=24）.After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups（n=8 per group）,which received central venous injection of SFI（SFI group）,epinephrine（EP group）,or saline（SA group）.Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results：Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin（IL）-6,IL-8and tumor necrosis factor α（TNF-α,P〈0.05）,and increased the anti-inflammatory cytokine levels of IL-4 and IL-10（P〈0.05）.Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions：SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.展开更多
Objective： To investigate whether Shen-Fu Injection（参附注射液, SFI） reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes（Treg） in...Objective： To investigate whether Shen-Fu Injection（参附注射液, SFI） reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes（Treg） in the spleen. Methods： After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine（EP） group, and saline（SA） group（8 in each group）, which received central venous injection of SFI（1.0 m L/kg）, EP（0.02 mg/kg） and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated（sham） group（n=6）. After successful return of spontaneous circulation（ROSC）, apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor（Foxp3） of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4（IL-4） and interferon-γ（IFN-γ） in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay（ELISA）. Results： Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group（P〈0.05 or P〈0.01）. Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4（P〈0.05）. Conclusions： SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.展开更多
This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction(IUGR)newborn piglets and relieve this dysfunction via dimethylglycine sodium salt(DMG-Na)suppleme...This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction(IUGR)newborn piglets and relieve this dysfunction via dimethylglycine sodium salt(DMG-Na)supplementation during the suckling period.Thirty sows(Duroc×[Landrace×Yorkshire])were selected,and 1 male newborn piglet with normal birth weight(NBW)and 1 male newborn piglet with IUGR were obtained from each sow.Among them,10 NBW and 10 IUGR newborns were euthanized without suckling.The other 20 NBW newborns were allocated to the group named NCON,which means NBW newborns fed a basic milk diet(BMD)(n=10),and the group named ND,which means NBW newborns fed BMD supplemented with 0.1%DMG-Na(n=10);the other 20 IUGR newborns were assigned to the group named ICON,which means IUGR newborns fed BMD(n=10),and the group named ID,which means IUGR newborns fed BMD supplemented with 0.1%DMG-Na(n=10).The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples.The growth performance,small intestinal histological morphology and sub-organelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,inflammatory cytokine level,and jejunum mRNA and protein expression of the toll-like receptor 4(TLR4)/nucleotide-binding oligomerization domain protein(NOD)/nuclear factor-k B(NF-k B)network deteriorated in the ICON group compared to that in the NCON group.The small intestinal histological morphology and suborganelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,and inflammatory cytokine level improved(P<0.05)in the ID group compared to those in the ICON group.The jejunum mRNA and protein expression of the TLR4/NOD/NF-k B network improved(P<0.05)in the ID group compared to that in the ICON group.In conclusion,the activity of the TLR4/NOD/NF-k B pathway was inhibited in the IUGR newborns,which in turn led to their jejunum immune dysfunction and reduced their performance.By ingesting DMG-Na,the IUGR newborns activated the TLR4/NOD/NF-k B pathway,thereby improving their unfavorable body state during the suckling period.展开更多
BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to ...BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.METHODS:A prospective observational study was carried out in Zhongshan Hospital,Fudan University,enrolling septic patients admitted between July 2016 and December 2018.Blood samples were collected at days 1 and 3.Serum cytokine levels(e.g.,tumor necrosis factor-α[TNF-α],interleukin-10[IL-10])and CD14+monocyte human leukocyte antigen-D-related(HLA-DR)expression were measured to serve as immune markers.Classifi cation of each immune status,namely systemic inflammatory response syndrome(SIRS),compensatory anti-inflammatory response syndrome(CARS),and mixed antagonistic response syndrome(MARS),was defined based on levels of immune markers.Changes of immune status were classifi ed into four groups which were stabilization(SB),deterioration(DT),remission(RM),and non-remission(NR).RESULTS:A total of 174 septic patients were enrolled including 50 non-survivors.Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors.Patients with MARS had the highest mortality rate.Immune status of 46.1%patients changed from day 1 to day 3.Among four groups of immune status changes,DT had the highest mortality rate,followed by NR,RM,and SB with mortality rates of 64.7%,42.9%,and 11.2%,respectively.CONCLUSIONS:Severe immune disorder defi ned as MARS or deterioration of immune status defi ned as DT lead to the worst outcomes.The preliminary model of the classifi cation and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.展开更多
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated...Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.展开更多
AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list...AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1<sup>st</sup> February 2014. RESULTSCirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM P = 0.01) for infection. A very low QFM P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSIONQFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.展开更多
Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently...Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.展开更多
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure(ACLF). The...The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure(ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts(evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.展开更多
Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ...Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.展开更多
In modern warfare,therapy for combat injury is a critical issue to improve personnel survival and battle effectiveness.Be limited to the severe circumstance in the distant battlefield,quick and effective treatment can...In modern warfare,therapy for combat injury is a critical issue to improve personnel survival and battle effectiveness.Be limited to the severe circumstance in the distant battlefield,quick and effective treatment cannot be supplied that leads infections,sepsis,multiple organ dysfunction syndrome(MODS)and high mortality.To get a better therapy for combat injury,we summarized several reports that associated with the mechanisms of sepsis and MODS,those published on MMR recently.Chaudry and colleagues reported gender difference in the outcomes of trauma,shock and sepsis.The advantageous outcome in female is due to their hormone milieu.Their accumulating reports indicated estrogen as a beneficial factor for multiple system and organs,including the central nervous system,the cardiopulmonary system,the liver,the kidneys,the immune system,and leads to better survival from sepsis.Thompson et al.reviewed the underlying mechanisms in trauma induced sepsis,which can be concluded as an imbalance of immune response triggered by damage-associated molecular patterns(DAMPs)and other immune modifying agents.They also emphasize immunomodulation as a better therapeutic strategy that might be a potential benefit in regulating the host immune response.Fan et al.have revealed a crucial mechanism underlying lung epithelial and macrophage crosstalk,which involves IL-25 as a mediator.After the injury,lung epithelial secreted IL-25 promotes TNF-αproduction in macrophage leading to acute lung injury(ALI).In addition to a mountain of cytokines,mitochondrial dysfunction in immune cell is another critical risk factor for immune dysfunction during sepsis.Both morphology and function alterations in mitochondria are closely associated with inadequate ATP production,insufficient metabolism process and overloaded ROS production,which lead harm to immune cells and other tissues by triggering oxidative stress.All the above reports discussed mechanisms of sepsis induction after trauma and provided evidence to improve better therapy strategies targeting diverse risk factors.展开更多
Patients suffering from liver cirrhosis(LC) frequently require non-hepatic abdominal surgery,even before liver transplantation.LC is an important risk factor itself for surgery,due to the higher than average associate...Patients suffering from liver cirrhosis(LC) frequently require non-hepatic abdominal surgery,even before liver transplantation.LC is an important risk factor itself for surgery,due to the higher than average associated morbidity and mortality.This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors,such as coagulopathy,poor nutritional status,adaptive immune dysfunction,cirrhotic cardiomyopathy,and renal and pulmonary dysfunction,which all lead to poor outcomes.Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery.In the emergency setting,with the presence of decompensated LC,alcoholic hepatitis,severe/advanced LC,and significant extrahepatic organ dysfunction conservative management is preferred.A multidisciplinary,individualized,and specialized approach can improve outcomes;preoperative optimization after risk stratification and careful management are mandatory before surgery.Laparoscopic techniques can also improve outcomes.We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before,during,and after surgery.展开更多
BACKGROUND Colon cancer is associated with a higher incidence among residents in highaltitude areas.Hypoxic environment at high altitudes inhibits the phagocytic and oxygen-dependent killing function of phagocytes,the...BACKGROUND Colon cancer is associated with a higher incidence among residents in highaltitude areas.Hypoxic environment at high altitudes inhibits the phagocytic and oxygen-dependent killing function of phagocytes,thereby increasing the inflammatory factors,inhibiting the body’s innate immunity and increasing the risk of colon cancer.AIM To examine the effect of minimally invasive surgery vs laparotomy in patients with colon cancer residing in high-altitude areas.METHODS Ninety-two patients with colon cancer in our hospital from January 2019 to February 2021 were selected and divided into the minimally invasive surgery and laparotomy groups using the random number table method,with 46 patients in each group.Minimally invasive surgery was performed in the minimally invasive group and laparotomy in the laparotomy group.Operative conditions,inflammatory index pre-and post-surgery,immune function index and complication probability were measured.RESULTS Operative duration was significantly longer and intraoperative blood loss and recovery time of gastrointestinal function were significantly less(all P<0.05)in the minimally invasive group than in the laparotomy group.The number of lymph nodes dissected was not significantly different.Before surgery,there were no significant differences in serum C-reactive protein,interleukin-6 and tumor necrosis factor-αlevels between the groups,whereas after surgery,the levels were significantly higher in the minimally invasive group(26.98±6.91 mg/L,146.38±11.23 ng/mL and 83.51±8.69 pg/mL vs 41.15±8.39 mg/L,186.79±15.36 ng/mL and 110.65±12.84 pg/mL,respectively,P<0.05).Furthermore,before surgery,there were no significant differences in CD3+,CD4+and CD4+/CD8+levels between the groups,whereas after surgery,the levels decreased in both groups,being significantly higher in the minimally invasive group(55.61%±4.39%,35.45%±3.67%and 1.30±0.35 vs 49.68%±5.33%,31.21%±3.25%and 1.13±0.30,respectively,P<0.05).Complication probability was significantly lower in the minimally invasive group(4.35%vs 17.39%,P<0.05).CONCLUSION Laparoscopic minimally invasive procedures reduce surgical trauma and alleviate the inflammatory response and immune dysfunction caused by invasive operation.It also shortens recovery time and reduces complication probability.展开更多
BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cel...BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cells,and the rapidly proliferating tumour cells are powered by aerobic glycolysis.Lipid metabolism reprogramming enables tumour cells to meet their needs for highly proliferative growth and is an important driving force for the development of hepatocellular carcinoma(HCC).AIM To explore the influence of different metabolic subtypes of HCC and analyse their significance in guiding prognosis and treatment based on the molecular mechanism of glycolysis and fatty acid oxidation(FAO).METHODS By downloading related data from public databases including the Cancer Genome Atlas(TCGA),the Molecular Signatures Database,and International Cancer Genome Consortium,we utilised unsupervised consensus clustering to divide TCGA Liver Hepatocellular Carcinoma samples into four metabolic subgroups and compared single nucleotide polymorphism,copy number variation,tumour microenvironment,and Genomics of Drug Sensitivity in Cancer and Tumour Immune Dysfunction and Exclusion between different metabolites.The differences and causes of survival and the clinical characteristics between them were analysed,and a prognostic model was established based on glycolysis and FAO genes.Combined with the clinical features,a Norman diagram was created to compare the pros and cons of each model.RESULTS In the four metabolic subgroups,with the increase in glycolytic expression,the median survival of patients showed the worst results,while FAO showed the best.When comparing the follow-up analysis of each group,we considered that the differences between them might be related to reactive oxygen species,somatic copy number variation of key genes,and immune microenvironment.It was also found that the FAO group and the low-risk group had better efficacy and response to immune checkpoint blockade treatment and anti-tumour drugs.CONCLUSION There are obvious differences in genes,chromosomes,and clinical characteristics between metabolic subgroups.The establishment of a prognostic model could predict patient prognosis and guide clinical treatment.展开更多
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related ...The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.展开更多
基金supported by the National Natural Science Foundation of China(81170296)
文摘BACKGROUND: Although regulatory T cells(Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis.DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and Pub Med. Articles on the role of Tregs in immune dysfunction during sepsis were identified.RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function.CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.
文摘Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.
文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in the“Curcumin”panel instead of the original“Curcumin”panel.The corrected version of Figure 4 is shown below as the revised Figure 4.The figure legend remains the same.
基金National Natural Science Foundation of China(Nos.82373425 and 82372722)Medical Innovation Research Special Project of the Science and Technology Commission of Shanghai Municipality(No.23Y11904200)+3 种基金Shanghai Innovative Medical Device Application Demonstration Project 2023(No.23SHS02600)"Science and Technology Innovation Action Plan"Medical Innovation Research Special Project of Shanghai(No.21Y11913500)key project of the Medical and Health Technology Development Research Center of the National Health Commission(No.WKZX2023CX030003)Shanghai Key Laboratory Open Project(No.STCSM 22DZ2229005)
文摘To the Editor:Lung cancer,specifically lung adenocarcinoma(LUAD),is one of the primary cause of cancer-related mortality globally.[1,2]Nevertheless,only a small subset of individuals with LUAD have derived clinical benefits from chemoimmunotherapy in either first-line or subsequent treatment settings.Both programmed death-ligand 1(PDL1)expression and tumor mutational burden(TMB)have proven inadequate in accurately predicting treatment outcomes in these scenarios.[3]Consequently,there exists a pressing necessity to identify a reliable biomarker to inform treatment decisions.
文摘Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body.Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity,due to defects in the local immunity of liver as well as in systemic immunity.Cirrhosis-associated immune dysfunction is a dynamic phenomenon,comprised of both increased systemic inflammation and immunodeficiency,and is responsible for 30%mortality.It also plays an important role in acute as well as chronic decompensation.Immune paralysis can accompany it,which is characterized by increase in antiinflammatory cytokines and suppression of proinflammatory cytokines.There is also presence of increased gut permeability,reduced gut motility and altered gut flora,all of which leads to increased bacterial translocation.This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome,sepsis,multiorgan failure and death.The gut microbiota of cirrhotic patients has more pathogenic microbes than that of noncirrhotic individuals,and this disturbs the homeostasis and favors gut translocation.Prompt diagnosis and treatment of such infections are necessary for better survival.We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis.Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates.
文摘Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The estimated case fatality rate is approximately 3.4%in China.However,some patients experience dyspnea within 1 week and develop rapidly to organ injury and even death within 2 weeks after dyspnea.1 In addition,early organ injury could lead to higher risks of mortality.Thus,early identification of patients at risk of organ injury and death is crucial,which saves the patients from classified and invasive treatment,improving clinical outcome and prognosis.The human immune system plays significant roles in the resistance of foreign pathogens and the progress of pneumonia.Recent studies have mentioned that T cells were decreased in COVID-19 patients,excessive activated immune response was caused by pathogenic Th1 cells,and inflammatory CD14+CD16+monocytes may connect to pulmonary immunopathology,leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections.2 SARS-CoV-2 might damage lymphocytes,especially T lymphocytes,and the immune system was impaired during the period of disease to cause tissue injury.
基金Supported by the National Natural Science Foundation of China(No.81372025)
文摘Objective：To investigate the action of Shen-Fu Injection（参附注射液,SFI） in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest（CA） and resuscitation.Methods：Thirty pigs were randomly divided into the sham（n=6） and 3 returns of spontaneous circulation（ROSC） groups（n=24）.After 8-min untreated ventricular fibrillation and 2-min basic life support,24 pigs of the ROSC groups were randomized into three groups（n=8 per group）,which received central venous injection of SFI（SFI group）,epinephrine（EP group）,or saline（SA group）.Hemodynamic status and blood samples were obtained at 0,0.5,1,2,4,6,12,and 24 h after ROSC.Results：Serum concentrations of specific activation markers of the complement system C3,C4 and C5b-9 were increased during cardiopulmonary resuscitation th rough1 24 h after ROSC.There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA.Compared with the EP and SA groups,SFI treatment reduced the proinflammatory cytokines levels of interleukin（IL）-6,IL-8and tumor necrosis factor α（TNF-α,P〈0.05）,and increased the anti-inflammatory cytokine levels of IL-4 and IL-10（P〈0.05）.Further,SFI treatment decreased the values of C3,C4 and C5b-9 compared with the EP and SA groups.Conclusions：SFI,derived from the ancient Chinese medicine,has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels.The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.
基金Supported by the National Natural Science Foundation of China(No.81372025)Basic and Clinical Research Cooperation Project of Capital Medical University(No.15JL42)Beijing Municipal Administration of Hospitals Incubating Program(No.Px2016022)
文摘Objective： To investigate whether Shen-Fu Injection（参附注射液, SFI） reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes（Treg） in the spleen. Methods： After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine（EP） group, and saline（SA） group（8 in each group）, which received central venous injection of SFI（1.0 m L/kg）, EP（0.02 mg/kg） and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated（sham） group（n=6）. After successful return of spontaneous circulation（ROSC）, apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor（Foxp3） of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4（IL-4） and interferon-γ（IFN-γ） in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay（ELISA）. Results： Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group（P〈0.05 or P〈0.01）. Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4（P〈0.05）. Conclusions： SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.
基金National Key Research and Development Program of China(No.2018YFD0501101)the National Natural Science Foundation of China(No.31802094)。
文摘This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction(IUGR)newborn piglets and relieve this dysfunction via dimethylglycine sodium salt(DMG-Na)supplementation during the suckling period.Thirty sows(Duroc×[Landrace×Yorkshire])were selected,and 1 male newborn piglet with normal birth weight(NBW)and 1 male newborn piglet with IUGR were obtained from each sow.Among them,10 NBW and 10 IUGR newborns were euthanized without suckling.The other 20 NBW newborns were allocated to the group named NCON,which means NBW newborns fed a basic milk diet(BMD)(n=10),and the group named ND,which means NBW newborns fed BMD supplemented with 0.1%DMG-Na(n=10);the other 20 IUGR newborns were assigned to the group named ICON,which means IUGR newborns fed BMD(n=10),and the group named ID,which means IUGR newborns fed BMD supplemented with 0.1%DMG-Na(n=10).The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples.The growth performance,small intestinal histological morphology and sub-organelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,inflammatory cytokine level,and jejunum mRNA and protein expression of the toll-like receptor 4(TLR4)/nucleotide-binding oligomerization domain protein(NOD)/nuclear factor-k B(NF-k B)network deteriorated in the ICON group compared to that in the NCON group.The small intestinal histological morphology and suborganelle ultrastructure,serum immunoglobulin,small intestinal digestive enzyme activity,and inflammatory cytokine level improved(P<0.05)in the ID group compared to those in the ICON group.The jejunum mRNA and protein expression of the TLR4/NOD/NF-k B network improved(P<0.05)in the ID group compared to that in the ICON group.In conclusion,the activity of the TLR4/NOD/NF-k B pathway was inhibited in the IUGR newborns,which in turn led to their jejunum immune dysfunction and reduced their performance.By ingesting DMG-Na,the IUGR newborns activated the TLR4/NOD/NF-k B pathway,thereby improving their unfavorable body state during the suckling period.
基金the National Natural Science Foundation of China(81471840,81171837)the Shanghai Traditional Medicine Development Project(ZY3-CCCX3-3018,ZHYY-ZXYJH-201615)the Key Project of Shanghai Municipal Health Bureau(2016ZB0202).
文摘BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.METHODS:A prospective observational study was carried out in Zhongshan Hospital,Fudan University,enrolling septic patients admitted between July 2016 and December 2018.Blood samples were collected at days 1 and 3.Serum cytokine levels(e.g.,tumor necrosis factor-α[TNF-α],interleukin-10[IL-10])and CD14+monocyte human leukocyte antigen-D-related(HLA-DR)expression were measured to serve as immune markers.Classifi cation of each immune status,namely systemic inflammatory response syndrome(SIRS),compensatory anti-inflammatory response syndrome(CARS),and mixed antagonistic response syndrome(MARS),was defined based on levels of immune markers.Changes of immune status were classifi ed into four groups which were stabilization(SB),deterioration(DT),remission(RM),and non-remission(NR).RESULTS:A total of 174 septic patients were enrolled including 50 non-survivors.Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors.Patients with MARS had the highest mortality rate.Immune status of 46.1%patients changed from day 1 to day 3.Among four groups of immune status changes,DT had the highest mortality rate,followed by NR,RM,and SB with mortality rates of 64.7%,42.9%,and 11.2%,respectively.CONCLUSIONS:Severe immune disorder defi ned as MARS or deterioration of immune status defi ned as DT lead to the worst outcomes.The preliminary model of the classifi cation and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.
基金the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)and 81601084(to YC)+3 种基金the National Key Research and Development Program of China,No.2017YFA0104304(to BW)the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science of China,No.201803024(to TYG)Innovation Platform,No.ZDX16005(to BW)。
文摘Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.
文摘AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1<sup>st</sup> February 2014. RESULTSCirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM P = 0.01) for infection. A very low QFM P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSIONQFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.
基金Supported by Grants from Wonkwang University in 2013
文摘Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-α agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.
文摘The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure(ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts(evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.
文摘Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.
文摘In modern warfare,therapy for combat injury is a critical issue to improve personnel survival and battle effectiveness.Be limited to the severe circumstance in the distant battlefield,quick and effective treatment cannot be supplied that leads infections,sepsis,multiple organ dysfunction syndrome(MODS)and high mortality.To get a better therapy for combat injury,we summarized several reports that associated with the mechanisms of sepsis and MODS,those published on MMR recently.Chaudry and colleagues reported gender difference in the outcomes of trauma,shock and sepsis.The advantageous outcome in female is due to their hormone milieu.Their accumulating reports indicated estrogen as a beneficial factor for multiple system and organs,including the central nervous system,the cardiopulmonary system,the liver,the kidneys,the immune system,and leads to better survival from sepsis.Thompson et al.reviewed the underlying mechanisms in trauma induced sepsis,which can be concluded as an imbalance of immune response triggered by damage-associated molecular patterns(DAMPs)and other immune modifying agents.They also emphasize immunomodulation as a better therapeutic strategy that might be a potential benefit in regulating the host immune response.Fan et al.have revealed a crucial mechanism underlying lung epithelial and macrophage crosstalk,which involves IL-25 as a mediator.After the injury,lung epithelial secreted IL-25 promotes TNF-αproduction in macrophage leading to acute lung injury(ALI).In addition to a mountain of cytokines,mitochondrial dysfunction in immune cell is another critical risk factor for immune dysfunction during sepsis.Both morphology and function alterations in mitochondria are closely associated with inadequate ATP production,insufficient metabolism process and overloaded ROS production,which lead harm to immune cells and other tissues by triggering oxidative stress.All the above reports discussed mechanisms of sepsis induction after trauma and provided evidence to improve better therapy strategies targeting diverse risk factors.
文摘Patients suffering from liver cirrhosis(LC) frequently require non-hepatic abdominal surgery,even before liver transplantation.LC is an important risk factor itself for surgery,due to the higher than average associated morbidity and mortality.This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors,such as coagulopathy,poor nutritional status,adaptive immune dysfunction,cirrhotic cardiomyopathy,and renal and pulmonary dysfunction,which all lead to poor outcomes.Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery.In the emergency setting,with the presence of decompensated LC,alcoholic hepatitis,severe/advanced LC,and significant extrahepatic organ dysfunction conservative management is preferred.A multidisciplinary,individualized,and specialized approach can improve outcomes;preoperative optimization after risk stratification and careful management are mandatory before surgery.Laparoscopic techniques can also improve outcomes.We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before,during,and after surgery.
基金the People’s Hospital of Tibet Autonomous Region Institutional Review Board(Approval No.METBHP-21-KJ-025).
文摘BACKGROUND Colon cancer is associated with a higher incidence among residents in highaltitude areas.Hypoxic environment at high altitudes inhibits the phagocytic and oxygen-dependent killing function of phagocytes,thereby increasing the inflammatory factors,inhibiting the body’s innate immunity and increasing the risk of colon cancer.AIM To examine the effect of minimally invasive surgery vs laparotomy in patients with colon cancer residing in high-altitude areas.METHODS Ninety-two patients with colon cancer in our hospital from January 2019 to February 2021 were selected and divided into the minimally invasive surgery and laparotomy groups using the random number table method,with 46 patients in each group.Minimally invasive surgery was performed in the minimally invasive group and laparotomy in the laparotomy group.Operative conditions,inflammatory index pre-and post-surgery,immune function index and complication probability were measured.RESULTS Operative duration was significantly longer and intraoperative blood loss and recovery time of gastrointestinal function were significantly less(all P<0.05)in the minimally invasive group than in the laparotomy group.The number of lymph nodes dissected was not significantly different.Before surgery,there were no significant differences in serum C-reactive protein,interleukin-6 and tumor necrosis factor-αlevels between the groups,whereas after surgery,the levels were significantly higher in the minimally invasive group(26.98±6.91 mg/L,146.38±11.23 ng/mL and 83.51±8.69 pg/mL vs 41.15±8.39 mg/L,186.79±15.36 ng/mL and 110.65±12.84 pg/mL,respectively,P<0.05).Furthermore,before surgery,there were no significant differences in CD3+,CD4+and CD4+/CD8+levels between the groups,whereas after surgery,the levels decreased in both groups,being significantly higher in the minimally invasive group(55.61%±4.39%,35.45%±3.67%and 1.30±0.35 vs 49.68%±5.33%,31.21%±3.25%and 1.13±0.30,respectively,P<0.05).Complication probability was significantly lower in the minimally invasive group(4.35%vs 17.39%,P<0.05).CONCLUSION Laparoscopic minimally invasive procedures reduce surgical trauma and alleviate the inflammatory response and immune dysfunction caused by invasive operation.It also shortens recovery time and reduces complication probability.
基金Supported by the Project of National Natural Science Foundation of China,No.81802365 and 81802385the Special Project of Clinical Key Diseases Treatment Technology in Suzhou,No.LCZX2019003+2 种基金the City-Level Scientific Research Projects in Jiangsu Province,No.SLT201907Major Projects of Provincial Universities in Jiangsu Province,No.19KJA170002Soochow University Horizontal Research Project,No.H190168.
文摘BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cells,and the rapidly proliferating tumour cells are powered by aerobic glycolysis.Lipid metabolism reprogramming enables tumour cells to meet their needs for highly proliferative growth and is an important driving force for the development of hepatocellular carcinoma(HCC).AIM To explore the influence of different metabolic subtypes of HCC and analyse their significance in guiding prognosis and treatment based on the molecular mechanism of glycolysis and fatty acid oxidation(FAO).METHODS By downloading related data from public databases including the Cancer Genome Atlas(TCGA),the Molecular Signatures Database,and International Cancer Genome Consortium,we utilised unsupervised consensus clustering to divide TCGA Liver Hepatocellular Carcinoma samples into four metabolic subgroups and compared single nucleotide polymorphism,copy number variation,tumour microenvironment,and Genomics of Drug Sensitivity in Cancer and Tumour Immune Dysfunction and Exclusion between different metabolites.The differences and causes of survival and the clinical characteristics between them were analysed,and a prognostic model was established based on glycolysis and FAO genes.Combined with the clinical features,a Norman diagram was created to compare the pros and cons of each model.RESULTS In the four metabolic subgroups,with the increase in glycolytic expression,the median survival of patients showed the worst results,while FAO showed the best.When comparing the follow-up analysis of each group,we considered that the differences between them might be related to reactive oxygen species,somatic copy number variation of key genes,and immune microenvironment.It was also found that the FAO group and the low-risk group had better efficacy and response to immune checkpoint blockade treatment and anti-tumour drugs.CONCLUSION There are obvious differences in genes,chromosomes,and clinical characteristics between metabolic subgroups.The establishment of a prognostic model could predict patient prognosis and guide clinical treatment.
文摘The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.
