Survival and neurological function in patients treated with extracorporeal membrane oxygenation and therapeutic hypothermia: a protocol for updating a systematic review.

INTRODUCTION: The widespread application of extracorporeal membrane oxygenation (ECMO) has enhanced clinical outcomes for patients experiencing cardiac arrest. However, its effectiveness is still limited and falls short of the desired level. Therapeutic hypothermia, which maintains body temperatures between 32°C and 36°C in cardiac arrest patients treated with ECMO, has been proposed as a potential means of neuroprotection and increased survival rates. Nevertheless, it remains controversial, and its impact on patient complications has yet to be fully understood. Thus, this paper aims to update the protocol for a systematic review of patients treated with ECMO and therapeutic hypothermia, in order to explore its effects on survival and neurological function. METHOD AND ANALYSIS: This protocol has been developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be systematically searched: PubMed, Web of Science, Cochrane Library, Embase, Ovid, CNKI, Wanfang and China Biology Medicine Disc. The database search strategy will use a combination of subject terms and free-text keywords. The search will encompass articles from the inception of each database up to 15 June 2023. Inclusion criteria encompass randomised controlled trials, cohort studies, case-control studies and quasi-experimental studies. Two researchers will independently review articles and extract relevant data based on these criteria. Any disagreements will be resolved through discussion. Data analysis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Since no patient data were collected in this study, ethical approval was not required. Research findings will be released in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023435353.

SULFORAPHANE ALLEVIATES POSTRESUSCITATION LUNG PYROPTOSIS POSSIBLY VIA ACTIVATING THE NRF2/HO-1 PATHWAY.

ABSTRACT: Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 mL of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase, the contents of malondialdehyde, IL-1ß, and IL-18, and the expression levels of NOD-like receptor pyrin domain 3, cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal, Nrf2, and HO-1. Results: During CPR, spontaneous circulation was achieved in six and seven pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1ß, IL-18), downregulated pyroptosis-related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.

A new coumarin isolated from the roots of Heracleum dissectum Ledeb.

A new coumarin named (9 R, 10 R)-9, 10-dihydro-10-hydroxy-9-methoxy-bergapten (1) and 13 known compounds (2-14) were isolated from the roots of Heracleum dissectum Ledeb., in which compounds (2-13) were obtained from H. dissectum for the first time. Their structures were illuminated by HR-ESI MS, 1 D and 2 D NMR, optical rotation and comparison with literatures. All compounds were evaluated against hepatocellular carcinoma HepG2 cell lines and the results showed that candinol C (8) had moderate cytotoxic activity against HepG2 cells with IC50 value at 57.6 ± 1.1 µM.

Do-not-resuscitate decision making for terminally ill older patients in the emergency department: An explorative, descriptive inquiry of Chinese family members.

Many terminally ill older adults depend on family members to make medical decisions in China. Many family members find it difficult to make do-not-resuscitate (DNR) decisions in emergency departments (ED). Currently, factors that affect DNR decision making by family members for older adults needing emergency care have not been well studied. This qualitative inquiry explores factors influencing DNR decision-making among family members of terminally ill older adults in ED. Semi-structured in-depth interviews were conducted for a 12-family member of terminally ill older adults at ED in China. Results of the conventional content analysis showed that family members made DNR decisions based on a wide of reasons: (a) subjective perception of family members, (b) conditions of the terminally ill older adults, (c) external environmental factors, and (d) internal family factors. The findings of this study expand our knowledge and understanding of factors influencing DNR decision-making by family members of terminally ill older adults in ED.

Role of Estrogen Receptor-Mediated Anti-Tumor Effects in U2OS Cells.

OBJECTIVE: This study aimed to investigate the effects of 17ß-estradiol and estrogen receptors (ERs) in U2OS cells. METHODS: Osteosarcoma U2OS cells were divided into six groups, and cell proliferation was determined using the cell counting kit-8 growth test. Furthermore, U2OS cell migration and invasion were examined by cell scratch test and Transwell invasion assays, respectively. RESULTS: At 48 h of 17ß-estradiol exposure, U2OS cell viability decreased (p<0.001); however, ERα siRNA and ERß siR-NAs significantly increased cell viability (p<0.01). Considering the cell positions at 0 h, the cell migration distance at 24 h significantly reduced in the presence of 17ß-estradiol (p<0.001); however, ERα and ERß siRNAs significantly increased cell migration distance (p<0.01). The number of invasive cells significantly decreased upon exposure to 17ß-estradiol (p<0.001); however, ERα and ERß siRNAs significantly increased the number of invasive cells (p<0.01 and p<0.05, respectively). CONCLUSIONS: 17ß-estradiol exhibited significant anti-tumor effects on U2OS cells that were mediated by ERs and reduced cell proliferation, migration, and invasion.

Death and do-not-resuscitate order in the emergency department: A single-center three-year retrospective study in the Chinese mainland.

BACKGROUND: Consenting to do-not-resuscitate (DNR) orders is an important and complex medical decision-making process in the treatment of patients at the end-of-life in emergency departments (EDs). The DNR decision in EDs has not been extensively studied, especially in the Chinese mainland. METHODS: This retrospective chart study of all deceased patients in the ED of a university hospital was conducted from January 2017 to December 2019. The patients with out-of-hospital cardiac arrest were excluded. RESULTS: There were 214 patients' deaths in the ED in the three years. Among them, 132 patients were included in this study, whereas 82 with out-of-hospital cardiac arrest were excluded. There were 99 (75.0%) patients' deaths after a DNR order medical decision, 64 (64.6%) patients signed the orders within 24 hours of the ED admission, 68 (68.7%) patients died within 24 hours after signing it, and 97 (98.0%) patients had DNR signed by the family surrogates. Multivariate analysis showed that four independent factors influenced the family surrogates' decisions to sign the DNR orders: lack of referral (odds ratio [OR] 0.157, 95% confidence interval [CI] 0.047-0.529, P=0.003), ED length of stay (ED LOS) ≥72 hours (OR 5.889, 95% CI 1.290-26.885, P=0.022), acute myocardial infarction (AMI) (OR 0.017, 95% CI 0.001-0.279, P=0.004), and tracheal intubation (OR 0.028, 95% CI 0.007-0.120, P<0.001). CONCLUSIONS: In the Chinese mainland, the proportion of patients consenting for DNR order is lower than that of developed countries. The decision to sign DNR orders is mainly affected by referral, ED LOS, AMI, and trachea intubation.

Estrogen receptor ß induces autophagy of osteosarcoma through the mTOR signaling pathway.

BACKGROUND: Estrogen receptor beta (ERß) was considered as a tumor-inhibiting factor in estrogen-sensitive malignant tumors. In this study, we intended to investigate whether ERß was involved in inducing autophagy in osteosarcoma. METHODS: This is an experimental study. The associations between ERß and autophagy were detected in osteosarcoma U2-OS cells which were treated with E2, E2 + 2,3-Bis (4-hydroxyphenyl) propionitrile (DPN, ERß agonists), E2 + DPN + water, E2 + DPN + 3-Methyladenine (3-MA, autophagy inhibitor), respectively. Cell viability and death were detected using cell counting kit 8 assay and flow cytometry, respectively. In addition, the expression of autophagy marker LC3II/I, sequestosome 1 (P62), mammalian target of rapamycin (mTOR), and phosphorylated-mTOR (p-mTOR) was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RESULTS: Cell viability was significantly decreased with DPN treatment, while was reversed with 3-MA treatment. DPN treatment decreased living cells proportion and increased cell apoptosis proportion, while 3-MA treatment reversed those changes. However, there were significant differences between the E2 group and the E2 + DPN + 3-MA group for the living cell proportion and cell apoptosis proportion, suggesting apoptosis and autophagy all were induced. In addition, DPN treatment upregulated the LC3II/I expression level and downregulated P62 and mTOR (mRNA level) and p-mTOR (protein level) expression levels. CONCLUSION: ERß inhibited the cell viability and mediated cell death by inducing apoptosis and autophagy in osteosarcoma. ERß-induced autophagy in osteosarcoma was associated with downregulating the P62 expression level and inhibiting mTOR activation.

The diagnosis and treatment of tibial intercondylar chondroblastoma.

OBJECTIVES: To investigate the diagnosis and treatment of tibial intercondylar chondroblastoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 12 patients with tibial intercondylar chondroblastoma admitted to the orthopedics department from May 2011 to February 2016; among them were 4 males and 3 females aged 10-19 years, with an average age of 15.7 years. Tibial intercondylar chondroblastoma was on the left and right side in 7 and 5 cases, respectively. The preoperative average Lysholm score of the knee joint was 68 (42-87). A posteromedial approach was applied in all cases. The incisions were approximately 5-8 cm in length. Complete curettage and inactivation were performed after fenestration, and allogeneic bone grafts were transplanted. Then, the posterior cruciate ligament insertion was fixed with 5.0 suture anchors. All patients were followed up with regularly to monitor for tumor recurrence, observe bone graft healing, and reassess the Lysholm score of the knee. RESULTS: Patients were followed for 7-55 months, and the median follow-up time was 19 months. One patient experienced tumor relapse 4 months after the operation. Incision, inactivation and cementation were performed. Then, the bone was fixed with anchors. In the other 11 patients, the bone graft healed over an average period of 6.2 months (4-10 months), with good functional recovery postoperatively. The average postoperative Lysholm score of the knee was 91 (81-95). CONCLUSION: Tibial intercondylar chondroblastoma has unique clinical and imaging characteristics and can effectively be treated by curettage followed by the inactivation, transplantation and fixation of allogeneic bone grafts with suture anchors through a posteromedial approach.

The diagnosis and treatment of tibial intercondylar chondroblastoma

OBJECTIVES: To investigate the diagnosis and treatment of tibial intercondylar chondroblastoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 12 patients with tibial intercondylar chondroblastoma admitted to the orthopedics department from May 2011 to February 2016; among them were 4 males and 3 females aged 10-19 years, with an average age of 15.7 years. Tibial intercondylar chondroblastoma was on the left and right side in 7 and 5 cases, respectively. The preoperative average Lysholm score of the knee joint was 68 (42-87). A posteromedial approach was applied in all cases. The incisions were approximately 5-8 cm in length. Complete curettage and inactivation were performed after fenestration, and allogeneic bone grafts were transplanted. Then, the posterior cruciate ligament insertion was fixed with 5.0 suture anchors. All patients were followed up with regularly to monitor for tumor recurrence, observe bone graft healing, and reassess the Lysholm score of the knee. RESULTS: Patients were followed for 7-55 months, and the median follow-up time was 19 months. One patient experienced tumor relapse 4 months after the operation. Incision, inactivation and cementation were performed. Then, the bone was fixed with anchors. In the other 11 patients, the bone graft healed over an average period of 6.2 months (4-10 months), with good functional recovery postoperatively. The average postoperative Lysholm score of the knee was 91 (81-95). CONCLUSION: Tibial intercondylar chondroblastoma has unique clinical and imaging characteristics and can effectively be treated by curettage followed by the inactivation, transplantation and fixation of allogeneic bone grafts with suture anchors through a posteromedial approach.

Estrogen receptor ß exhibited anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kB/BCL-2 and PI3K/Akt signal pathway.

This study aimed to investigate the effects of Estrogen receptor ß (ERß) on osteosarcoma cells, and explore the regulatory mechanisms involved in this process. Osteosarcoma U2-OS cells consisted four groups, and treated by E2, E2 + LY294002 (ERß agonists), E2 + ERß siRNA, E2 + ERß siRNA + LY294002, respectively. Cell counting kit 8 (CCK-8) assay was performed to detect the cell viability of U2-OS cells in each group. The effects of ERß on the migration and invasion ability of U2-OS cells were examined by wound healing assay and transwell cell culture chamber, respectively. The expression of Inhibitor of apoptosis protein (IAP) and integrin α5 in U2-OS cells of each group was detected by quantitative RT-PCR, and the expression of phosphorylated p65 (p-p65), p-AKT and Bcl-2 was detected by western blotting. The cell viability, migration and invasion ability of U2-OS cells were significantly increased by ERß siRNA, but inhibited by ERß agonists LY294002 (p < 0.05). ERß siRNA significantly downregulated Integrin α5 and unregulated IAP in U2-OS cells (p < 0.05). The expression of p-p65, p-AKT and Bcl-2 was significantly reduced by LY294002, but increased by ERß siRNA (p < 0.05). In conclusion, ERß exhibited obvious anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kBBCL-2 and PI3K/Akt signal pathway.

Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng is a well-known traditional Chinese medicine and has been used for treatment of various diseases for more than four thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents are reported to possess antidiabetic activity, but their antihyperglycemic mechanisms are not fully elucidated. In the present study, the mechanisms of action of ginsenoside Re were investigated in vitro models. MATERIALS AND METHODS: 3T3-L1 cells were chosen as the model to investigate the molecular mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by insulin in the absence or presence of ginsenoside Re were quantified by measuring (3)H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-α were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-γ and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-α. And western blot analysis was performed to determine the translocation of GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes and in macrophages were investigated through measurement of nitrite concentration by Griess reagent. RESULTS: Ginsenoside Re induced adipogenesis of 3T3-L1 adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR-γ2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also increased production and release of adiponectin. Although having no effects on GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the membranes. In addition, Re inhibited the expression and release of TNF-α. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-α and IFN-γ and in LPS-stimulated mouse peritoneal macrophages. CONCLUSIONS: Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-γ pathway by directly increasing the expressions of PPAR-γ2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-α production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes.