With the gradual development and popularization of extracorporeal membrane oxygenation (ECMO) in China, some prefecture-level medical institutions in China have carried out and formed their own pre-hospital extracorporeal cardiopulmonary resuscitation (ECPR) model. Although the development levels of various prefecture-level cities are uneven and the start times vary, at present, the prefecture-level hospitals in China generally go through the development process of ECMO-in-hospital ECPR-pre-hospital ECPR-professional medical recovery center. Among them, in-hospital ECPR has the advantages of timely resuscitation, guaranteed quality of resuscitation, and fast activation speed of the ECPR team, and currently has a high success rate, with a low proportion of patients with neurological complications. However, pre-hospital ECPR is more challenging, requiring the coordination between pre-hospital and in-hospital emergency forces, multidisciplinary cooperation, and the quality of resuscitation before ECPR cannot be fully guaranteed, the long duration of patient's low perfusion, and other factors make the survival rate of patients without neurological damage obviously lower than that of in-hospital ECPR. China has a large population base, and comprehensive domestic and foreign data show that there should be no less than several million cases of out-of-hospital cardiac arrest under the age of 60 every year, so there is much to be done to improve the survival rate of pre-hospital ECPR. Pre-hospital ECPR is a project of concentrated resources and technology, which has high requirements for the multidisciplinary diagnosis and treatment capabilities of medical institutions. The optimization of the implementation process of in-hospital and pre-hospital ECPR teams, the advancement of the timing of ECPR intervention, the selection of patients, the support and construction of multidisciplinary diagnosis and treatment capabilities after ECPR, and the management of related complications and risk factors are closely related to the prognosis of ECPR patients. The recoverability of the brain and heart is currently the key factor restricting the further improvement of the survival rate of patients after ECPR. Considering that the recovery of neurological function mainly depends on the duration of the early low perfusion, the in-hospital treatment after the implementation of ECPR is mainly the low-temperature brain protection strategy, the effect of which is still controversial, so the recovery of cardiac function is the key that seriously restricts the survival of patients after ECPR in addition to neurological prognosis. The recoverability of the heart after ECPR can be implemented from multiple angles: the research on pathophysiological issues such as the matching of the heart itself after the implementation of ECPR, and the matching between the heart and ECMO, and the proposal of corresponding countermeasures will help to improve the survival rate of patients after ECPR. The large population and the potential salvageable population make the development of ECPR technology in China's tertiary hospitals urgent and necessary, with challenges and opportunities coexisting.
Humans ; Cardiopulmonary Resuscitation/methods* ; China ; Extracorporeal Membrane Oxygenation/methods* ; Emergency Medical Services ; Risk Factors ; Prognosis

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.
Adoptive Transfer ; methods ; Carcinoma, Hepatocellular ; immunology ; therapy ; Humans ; Immunotherapy, Adoptive ; methods ; Liver Neoplasms ; immunology ; therapy ; Lymphocytes, Tumor-Infiltrating ; cytology ; Randomized Controlled Trials as Topic ; Receptors, Chimeric Antigen ; T-Lymphocytes ; cytology

Objective To explore whether Rho kinase inhibitor protects endotoxemia mice from kidney injury,and to investigate the mechanism underlying this effect. Methods Adult male C57BL/6 mice were randomly divided into three groups (n = 8 for each group): control,lipopolysaccharide (LPS),and LPS+ Y-27632 (Rho kinase inhibitor). For induction of acute kidney injury,mice were administered 30 mg/kg LPS intraperitoneally. Y-27632 (10 mg/kg body weight) was injected intraperitoneally 18 h and 1 h before injection of LPS,and an equal volume of sterile saline was administered at the corresponding time point in each group. The mice were killed 8 h after LPS administration. Blood samples and kidney tissues were taken and preserved for subsequent analysis. Results Pretreatment with Y-27632 significantly attenuated LPS-induced kidney injury;pretreatment with Y-27632 markedly reduced renal expression of inflammatory cytokines (TNF-α and IL-1β) in endotoxemia mouse,and also significantly inhibited LPS-induced caspase-3 expression in the kidney; and Y-27632 pretreatment dramatically reduced TLR4 protein expression and NF-κBp65 phosphorylation in kidney tissues of endotoxemia mouse. Conclusion Rho kinase inhibitor may inhibit TLR4 and NF-κB signaling pathway to reduce the inflammatory response in the kidneys of endotoxemia mice and alleviate acute renal injury induced by LPS.

Objective To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU).Methods This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital,China Medical University from Jan 2012 to Jun 2016.Subjects were classified by ventilator status:early-onset VAP (＜ 5 d ventilation,E-VAP) or late-onset VAP (≥ 5 d ventilation,L-VAP).Potential risk factors and pathogen were evaluated.Results A total of 4 179 patients in adult ICU were screened,3 989 (95.5％) of whom were mechanically ventilated,962 patients with mechanical ventilation time ≥ 48 h.VAP developed in 142 patients.E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male (OR =1.825,95％ CI 1.006-3.310),chronic obstructive pulmonary disease (COPD;OR =3.746,95％ CI 1.795-7.818),emergency intubation (OR =1.932,95％ CI 1.139-3.276),aspiration (OR =3.324,95％ CI 1.359-8.130).Whereas independent risk factors for L-VAP were coma (OR =2.335,95％ CI 1.300-4.194),renal dysfunction (OR =0.524,95％ CI O.290-O.947),emergency intubation (OR =2.184,95％ CI 1.334-3.574).Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2％(19/63)vs 19.8％ (162/820),P=0.044;29.1％ (23/79) vs 19.8％(162/820),P=0.046].The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups,which the most common ones were acinetobacter baumannii,pseudomonas aeruginosa and klebsiella pneumoniae.Conclusion E-VAP and L-VAP have different risk factors,however related pathogens are similar.Different specific preventive strategies are suggested based on different onset of VAP.

After the concept of "chronic critical illness (CCI)" was proposed, the new concept persistent inflammation immunosuppression catabolism syndrome (PICS) is present recently. Patients with PICS are manifested by fast decreasing body weight, poor nutritional status, long-term immunosuppression and repeated nosocomial infections. These patients are faced with great challenges of persistent inflammation, acquired immunosuppression and high catabolism, which finally results in repeated nosocomial infections, prolonged hospital stay and increased mortality. At present, main problems of PICS diagnosis standard include varying length of ICU stay, difference in normal C reactive protein value, poor value of nutrition indexes, absence of clinical verification. Though associated pathophysiology mechanism is not clear, PICS is preventable and magageable with certain therapy, including early comprehensive prevention and treatment focused on infection control for CCI patients to stop the progression of PICS, application of immune modulator to improve immune function and prognosis of patients, and reasonable nutritional support and treatment. Besides, through the analysis of the association between PICS and CCI, authors draw a conclusion that PICS is a new phenotype of CCI, and immune paralysis is its main feature.
Chronic Disease ; Critical Illness ; Cross Infection ; Humans ; Immunosuppression ; Inflammation ; Length of Stay ; Nutrition Assessment ; Nutritional Support ; Prognosis ; Syndrome