Blood purification for treatment of non-liquefied multiple liver abscesses and improvement of T-cell function:A case report

BACKGROUND Non-liquefied multiple liver abscesses(NMLA)can induce sepsis,septic shock,sepsis-associated kidney injury(SA-AKI),and multiple organ failure.The inability to perform ultrasound-guided puncture and drainage to eradicate the primary disease may allow for the persistence of bacterial endotoxins and endogenous cytokines,exacerbating organ damage,and potentially causing immunosuppression and T-cell exhaustion.Therefore,the search for additional effective treatments that complement antibiotic therapy is of great importance.CASE SUMMARY A 45-year-old critically ill female patient presented to our hospital’s intensive care unit with intermittent vomiting,diarrhea,and decreased urine output.The patient exhibited a temperature of 37.8℃.Based on the results of liver ultrasonography,laboratory tests,fever,and oliguria,the patient was diagnosed with NMLA,sepsis,SA-AKI,and immunosuppression.We administered antibiotic therapy,entire care,continuous renal replacement therapy(CRRT)with an M100 hemofilter,and hemoperfusion(HP)with an HA380 hemofilter.The aforementioned treatment resulted in a substantial reduction in disease severity scores and a decrease in the extent of infection and inflammatory factors.In addition,the treatment stimulated the expansion of the cluster of differentiation 8^(+)(CD8^(+))Tcells and led to the complete recovery of renal function.The patient was discharged from the hospital.During the follow-up period of 28 d,she recovered successfully.CONCLUSION Based on the entire therapeutic regimen,the early combination of CRRT and HP therapy may control sepsis caused by NMLA and help control infections,reduce inflammatory responses,and improve CD8^(+)T-cell immune function.

Lithium promotes recovery of neurological function after spinal cord injury by inducing autophagy

Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.

Value of transient ultrasonic elastography for evaluating the liver fibrosis and liver function in patients with drug-induced liver injury

Objective: To study the value of transient ultrasonic elastography for evaluating the liver fibrosis and liver function in patients with drug-induced liver injury. Methods: A total of 68 patients with drug-induced liver injury who were treated in our hospital between January 2016 and May 2017 were selected as drug-induced liver injury group, and 50 healthy volunteers who received physical examination in our hospital during the same period were selected as normal control group. The liver transient ultrasonic elastography parameter Stiffness levels as well as serum liver fibrosis index and liver function index contents of two groups of subjects were detected. Pearson test was used to evaluate the correlation of Stiffness levels with liver fibrosis and liver function damage degree in patients with drug-induced liver injury. Results:Stiffness level in drug-induced liver injury group was higher than that in normal control group;serum liver fibrosis indexes HA, LN, CⅣ, PⅢNP and CG contents were higher than those of normal control group;serum liver function indexes ALT, AST, ALP, STB and γ-GT contents were higher than those of normal control group. Conclusion: Transient ultrasonic elastography parameter Stiffness levels increase in patients with drug-induced liver injury, and the specific levels are consistent with the liver fibrosis and liver function damage degree, and can be used as the objective means to evaluate the disease severity.

Etiology and management of liver injury in patients with COVID-19

The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.

Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients

Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.

Efficacy of Jian’ganle(健肝乐) versus Hugan Pian(护肝片),Glucuronolactone and Reduced Glutathione in Prevention of Antituberculosis Drug-induced Liver Injury

Summary： Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts＇ experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian＇ganle in prevention of drug-induced liver injury （DILI） caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People＇s Republic of China and National Health and Family Planning Commission of the Peo- ple＇s Republic of China to select and renew the Essential Medicine List （EML）, the new rural cooperative medical scheme in China （NRCMS） list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian＇ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBIL）, direct bilirubin （DBIL）, total protein （TP）, albumin （A） and globulin （G） were detected at admission as baseline and after treatment. The Jian＇ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian＇ganle was more efficacious than glucuronolactone. And Jian＇ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian＇ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian＇ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.

Role of the^(13)C-methacetin breath test in the assessment of acute liver injury in a rat model

AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine(D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group(n = 8) and five model groups(each n = 8), and acute liver injury was assessed at different time points(6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green(ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT(Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman'scorrelation analysis.RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score(r = 0.493, P < 0.05; r =-0.731, P < 0.01; r =-0.618, P < 0.01; r =-0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection(3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.

COVID-19 combined with liver injury:Current challenges and management

Coronavirus disease 2019(COVID-19)combined with liver injury has become a very prominent clinical problem.Due to the lack of a clear definition of liver injury in patients with COVID-19,the different selection of evaluation parameters and statistical time points,there are the conflicting conclusions about the incidence rate in different studies.The mechanism of COVID-19 combined with liver injury is complicated,including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines,ischemia and hypoxia,and drugs.In addition,underlying diseases,especially chronic liver disease,can aggravate COVID-19 liver injury.In the treatment of COVID-19 combined with liver injury,the primary and basic treatment is to treat the etiology and pathogenesis,followed by support,liver protection,and symptomatic treatment according to the clinical classification and severity of liver injury.This article evaluates the incidence,pathogenesis and prevention and treatment of COVID-19 combined with liver injury,and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.

Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors

Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.

Madelung’s disease with alcoholic liver disease and acute kidney injury: A case report

BACKGROUND Madelung’s disease(MD)is a rare disorder of lipid metabolism,characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck,shoulders,or other sites around the body.Its pathological mechanism is not yet known.One of the most common comorbidities in MD patients is liver disease,especially chronic alcoholic liver disease(CALD);however,no reports exist of acute kidney injury(AKI)with MD.CASE SUMMARY We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d.Physical examination showed subcutaneous masses around the neck,and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking.Considering the clinical symptoms,along with various laboratory test results and imaging characteristics,a diagnosis was made of MD with acute exacerbation of CALD and AKI.The patient was treated with liver function protection and traditional Chinese medicine,without surgical intervention.He was advised to quit drinking.After 10 d,the edema had subsided,renal function indicators returned to normal,liver function significantly improved,and size of subcutaneous masses remained stable.CONCLUSION In MD,concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial.

Effects of Qingwen Baidu decoction on coagulation and multiple organ injury in rat models of sepsis

Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations of sepsis and ease inflammation,but its effects on coagulation functions and multiple organ injuries remain unclear.Methods:100 healthy,male Sprague-Dawley rats were randomly divided into the sham group,the cecal ligation and puncture(CLP)group,the low-dose QWBD group,and the high-dose QWBD group,with 25 rats in each group.The sepsis model was established using CLP.Blood was collected to measure platelet count,serum creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels,as well as coagulation function.The total protein in bronchoalveolar lavage fluid(BALF)was determined in each group of rats.The lung,liver,and kidney tissues were harvested,and statistics were calculated on the wet-to-dry(W/D)weight ratio.Changes in histopathology and thrombin level were evaluated in each group.The remaining ten rats in each group were observed daily to record the number of surviving rats.Such observation was made consecutively for 7 days to calculate survival rates.Results:After model establishment,ALT,AST,Cr,and BUN levels were significantly elevated(P<0.01).The BALF protein content and lung W/D weight ratio were significantly increased(P<0.01).Furthermore,the survival rate of rats was significantly reduced in the CLP group compared with the sham group.After the treatment,rats in the high-dose QWBD group had lower ALT(P<0.05),AST(P<0.01),Cr(P<0.05),BUN(P<0.01)levels,lower BALF protein content(P<0.05)and lower lung W/D weight ratio(P<0.01)than the CLP group.However,rats in the high-dose QWBD group had significantly better pathological changes in the lung,liver,and kidney compared to the sham group.After the treatment,the platelet level in the peripheral blood was elevated(P<0.05)and both activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.01).The fibrinogen level was significantly increased(P<0.01).Finally,thrombin positive expression areas in the lung,liver,and kidney were significantly decreased in the high-dose QWBD group.Conclusion:QWBD can improve coagulation disorders caused by sepsis and has a protective effect on multiple organ injuries in rats.

Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury and represents a potential therapeutic target

AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of shamoperation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histologicalalterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150' groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60' R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60' R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates in he-patic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

Targeting the mitochondrial permeability transition pore in traumatic central nervous system injury

The mitochondrion serves many functions in the central nervous system （CNS） and other organs beyond the well-recognized role of adenosine triphosphate （ATP） production. This includes calcium-dependent cell signaling, regulation of gene expression, synthesis and release of cytotoxic reactive oxygen species, and the release of cytochrome c and other apoptotic cell death factors. Traumatic injury to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial function. One consequence of compromised mitochondrial function is induction of the mitochondrial permeability transition （mPT） state due to formation of the cyclosporine A sensitive permeability transition pore （mPTP）. In this mini-review, we summarize evidence supporting the involvement of the mPTP as a mediator of mitochondrial and cellular demise following CNS traumatic injury and discuss the beneficial effects and limitations of the current ex- perimental strategies targeting the mPTP.

Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury

Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.

GUT BARRIER FUNCTION DAMAGE FOLLOWING MULTIPLE FIREARM INJURIES IN A PORCINE MODEL

Objective. To study the characteristics and pathogenesis of gut barrier damage following multiple firearm injuries in a porcine model. Methods. Twenty four small pigs were divided into 4 groups: control group (n=6, group C), group H (n=6, gunshot induced tangential fracture of parietal bone), group L (n=6, gunshot induced comminuted fracture of bilateral femora) and group M (n=6, combined group H+L). Gastric intramucosal pH (pHi), plasma endotoxin levels in portal vein, and plasma D lactate levels were measured and blood samples were cultured at different intervals after trauma. The animals were sacrificed at 72 h following trauma and intestinal tissues were harvested for pathological examination and diamine oxidase (DAO) activity measurement. Results. In group M at 72 h, pHi was significantly lower than that of group H and L (P< 0.01), and plasma endotoxin level was significantly higher than that of group H (P< 0.01) and group L (P< 0.05). Simultaneously, in groupM, D lactate level was markedly higher than that of group H (P< 0.01), and incidence of positive blood culture was much higher than that of group H and L (P<0.05). Necrosis and exfoliation were revealed at ileum villus top in all traumagroups, especially in group M, in which ileum DAO activity declined most significantly as well. Conclusion. Multiple trauma is prone to cause gastrointestinal ischemia even without hemorrhagic shock. The damage of gut barrier in multiple trauma appears to be more severe than that in one site trauma, thereby promoting gut derived endotoxemia and bacterial translocation and contributing to the development of endogenous infection.SURGICAL TREATMENT OF MALIGNANTESOPHAGEAL TUMORS IN PUMC HOSPITAL Guo Huiqin,Li Zejian ,Zhang Fan1 ,Zhang Zhiyong,Xu Letian ,Li Weidong2,Wang Xiuqin2and Wu Min2Department of Thoracic Surgery, PUMC Hospital, CAMS &PUMC, Beijing 100730Key words malignant esophageal tumors; early diagnosis; FHIT geneTo study how to prolong the postoperative survival time of the patientswith malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet (FHIT) gene (a tumor suppressor gene) in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2%in esophageal cancer and 20%in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.

Current status and recent advances of liver transplantation from donation after cardiac death

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.

Better therapy for combat injury

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.

Liver function in COVID-19 infection

Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver function.In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease.Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients,severity of liver injury,presence of comorbidity and pre-treatment.The method of antiviral treatment can also impact on liver function,which manifests as increasing values in liver function tests.Therefore,analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.

Liver dysfunction during COVID-19 pandemic:Contributing role of associated factors in disease progression and severity

In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.

Time of Liver Function Abnormal Identification on Prediction of the Risk of Anti-tuberculosis-induced Liver Injury

Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.