Circ-IP6K2 suppresses tumor progression by modulating the miR-1292-5p/CAMK2N1 signal in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor originating from the epithelial cells of the renal tubules. The clear cell RCC subtype is closely linked to a poor prognosis due to its rapid progression. Circular RNA (circRNA) is a novel class of regulatory RNA molecules that play a role in the development of ccRCC, although their functions have not been fully elucidated. In this study, we identified a significant downregulation of circ-IP6K2 in ccRCC tissues based on data from the GSE100186 dataset. The decreased expression of circ-IP6K2 correlated with the progression of TNM stage and histological grade, and was also associated with decreased overall survival rates in ccRCC patients. Moreover, our findings revealed that circ-IP6K2 expression suppressed proliferation, migration, and invasion capabilities in vitro, and inhibited xenograft growth in vivo. Mechanistically, circ-IP6K2 acted as a sponge for miR-1292-5p in ccRCC cells, which in turn targeted the 3'UTR of CAMK2N1, leading to a decrease in its expression. CAMK2N1 was identified as a tumor suppressor that negatively regulated the ß-catenin/c-Myc oncogenic signaling pathway. Additionally, we confirmed a positive correlation between the expression of circ-IP6K2 and CAMK2N1 in ccRCC. Circ-IP6K2 functions to impede the progression of ccRCC by modulating the miR-1292-5p/CAMK2N1 axis. These findings shed new light on the molecular mechanisms driving ccRCC progression and suggest potential therapeutic targets for the treatment of ccRCC.

DUSP3 regulates phosphorylation-mediated degradation of occludin and is required for maintaining epithelial tight junction.

BACKGROUND: Tight junctions (TJ) are multi-protein complexes that hold epithelial cells together and form structural and functional barriers for maintaining proper biological activities. Dual specificity phosphatase 3 (DUSP3), a suppressor of multiple protein tyrosine (Tyr) kinases, is decreased in lung cancer tissues. Here we demonstrated the role of DUSP3 in regulation of epithelial TJ. METHODS: Barrier functions of TJ were examined in wild-type or DUSP3-deficient lung epithelial cells. Animal and clinical data were analyzed for the association between DUSP3 deficiency and lung cancer progression. Proximity ligation assay, immunoblotting, and phosphatase assay were performed to study the effect of DUSP3 on the TJ protein occludin (OCLN). Mutations of Tyr residues on OCLN showed the role of Tyr phosphorylation in regulating OCLN. RESULTS: Compared to those of the DUSP3-expressing cells, we found the expression and distribution of ZO-1, a TJ-anchoring molecule, were abnormal in DUSP3-deficient cells. OCLN had an increased phosphorylation level in DUSP3-deficient cells. We identified that OCLN is a direct substrate of DUSP3. DUSP3 regulated OCLN ubiquitination and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion kinase, the OCLN kinase. CONCLUSION: Our study revealed that DUSP3 is an important TJ regulatory protein and its decrease may be involved in progression of epithelial cancers.

Analgesic efficacy of postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane block for laparoscopic colorectal cancer surgery: a randomized, prospective, controlled study.

BACKGROUND: We assessed whether a postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane (TAP) block could reduce 24 h rescue tramadol requirement compared with placebo in patients undergoing elective laparoscopic colorectal cancer surgery. METHODS: Patients scheduled to undergo elective laparoscopic surgery following the diagnosis of colorectal cancer were included in this study and randomized into Group and Group Control. The patients received a postoperative bilateral, ultrasound-guided, posterior TAP block in either 20 mL of 0.5% ropivacaine (Group TAP) per side or an equivalent volume of normal saline (Group Control). The primary outcome was the cumulative consumption of rescue tramadol within 24 h after the surgery. Secondary endpoints included (1) resting and movement numerical rating scale (NRS) pain scores at 2, 4, 6, 12, 24, 48, and 72 h; (2) incidences of related side effects; (3) time to the first request for rescue tramadol; (4) patient satisfaction regarding postoperative analgesia; (5) time to restoration of intestinal function; (6) time to mobilization; and (7) the length of hospital stay. RESULTS: In total, 92 patients were randomized, and 82 patients completed the analysis. The total rescue tramadol requirement (median [interquartile range]) within the first 24 h was lower in Group TAP (0 [0, 87.5] mg) than in Group Control (100 [100, 200] mg), P < 0.001. The posterior TAP block reduced resting and movement NRS pain scores at 2, 4, 6, 12, and 24 h after surgery (all P < 0.001) but showed similar scores at 48 h or 72 h. A higher level of satisfaction with postoperative analgesia was observed in Group TAP on day 1 (P = 0.002), which was similar on days 2 (P = 0.702) and 3 (P = 0.551), compared with the Group Control. A few incidences of opioid-related side effects (P < 0.001) and a lower percentage of patients requiring rescue tramadol analgesia within 24 h (P < 0.001) were observed in Group TAP. The time to the first request for rescue analgesia was prolonged, and the time to mobilization and flatus was reduced with a shorter hospital stay in Group TAP as compared with Group Control. CONCLUSIONS: A postoperative bilateral, ultrasound-guided, posterior TAP block resulted in better pain management and a faster recovery in patients undergoing laparoscopic colorectal cancer surgery, without adverse effects. TRIAL REGISTRATION: The study was registered at http://www.chictr.org.cn ( ChiCTR-IPR-17012650 ; Sep 12, 2017).

[Evidence-Based Nursing Care of Older Adult Patient With Postoperative Delirium and Hip Fracture].

Hip fracture commonly occurs in adult patients over 65 years old at a prevalence rate that is estimated to be 756 per 100 thousand cases. Thus, hip fracture surgery is one of the most common emergency operations in older adult populations. In addition, the incidence rate in older adults of post-operative delirium, which leads to symptoms of disturbance related to cognition, attention, perception, logic, memory, psychological activities, mood, and sleep, has been reported as 5%-61%. The many possible complications of post-operative delirium, including death, increase medical costs and family burdens if not managed properly. Proper management involves healthcare providers initiating early assessments, reducing accelerated factors, and providing appropriate care. As diagnosing and differentiating post-operative delirium in clinical practice is difficult, this condition is easily neglected by healthcare teams, resulting in adequate care not being provided to this population. The aim of this paper was to review the definition, relevant physiological and pathological mechanisms and etiologies, and medical management and nursing care of post-operative delirium using an evidence-based literature review. Suggestions for healthcare providers to improve the detection and management of post-operative delirium include using appropriate evaluation tools to detect and diagnose high-risk patients as early as possible, implementing older-adult life planning strategies, and conducting medical consultations. Furthermore, healthcare providers may initiate pain control, nutrient and body fluid supplementation, and sensory/cognition enhancement therapies to reduce the incidence of delirium, length of hospital stay, complications, and in-hospital mortality, thereby improving the quality of care provided to older adult patients with hip fractures and their caregivers.

Subgaleal Hematoma at the Contralateral Side of Scalp Trauma in an Adult.

BACKGROUND: Subgaleal hematoma (SGH), an abnormal accumulation of blood under the galeal aponeurosis of the scalp, is more commonly observed in newborns and children. According to previous cases, the etiology of SGH includes mild head trauma, vacuum-assisted vaginal delivery, contusion, and hair braiding or pulling. CASE REPORT: A 39-year-old healthy worker came to our emergency department (ED) due to scalp lacerations from an accident that caused severe twisting of his hair. He denied head contusion and was conscious upon arrival. Physical examination showed three lacerations over his right temporal area. The wounds depth extended to the skull, with a 10-cm subperiosteal pocket beneath the lacerations. Primary sutures were performed immediately under local anesthesia, not only for wound closure but also for hemostasis. However, he returned to our ED 3 h after the first visit for a newly developed soft lump over the left side of his forehead. Computed tomography scan of brain illustrated a huge and diffuse SGH in the left temporal region with extension to periorbital region. Although the option of incision and drainage was discussed with a neurosurgeon and a search for some case reports was done, most of the hematoma could be self-limited. Conservative management with non-elastic bandage packing direct compression was applied. The patient was then admitted for close observation and conservative treatment for 1 week. There was no recurrence of SGH in the following 3 months. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: SGH is an uncommon phenomenon that is caused by tearing of the emissary veins in the loose areolar tissue located beneath the galeal aponeurosis. Conservative treatment with bandage compression is recommended for SGH. Surgery is reserved for cases where non-invasive management fails or severe complications.

EGFR over-expression in non-small cell lung cancers harboring EGFR mutations is associated with marked down-regulation of CD82.

Epidermal growth factor receptor (EGFR) gene mutations are strongly associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor. The mutated EGFR proteins (EGFRs) are hyper-phosphorylated and refractory to receptor down-regulation. To address the discrepancy between hyper-phosphorylation and lack of down-regulation of mutant EGFRs, we have examined the expression of EGFR negative regulators in non-small cell lung cancer (NSCLC) cell lines. We found that NSCLC cell lines expressing mutant EGFRs often had low expression of various negative regulators for EGFR. Among them, tumor suppressor CD82 was up-regulated by wild type (WT) EGFR but down-regulated by mutant EGFRs. Reconstitution of CD82 exerted stronger suppressive effects on mutant EGFRs than on WT EGFR. Active exportation of CD82 through the exosome was one of the mechanisms involved in achieving the overall CD82 down-regulation in mutant EGFR-expressing lung cancer cell lines. Over-expression of mutant EGFR protein frequently occurred in the lung cancer tissues of mutant EGFR-transgenic mice and also associated with CD82 down-regulation. Immunoblot analyses on the tumor tissues from 23 lung adenocarcinoma patients (12 with WT EGFR, and 11 with mutant EGFRs) also identified significantly stronger down-regulation of CD82 in tumors with mutant EGFRs than WT. Our data indicate that CD82 down-regulation could be a critical step involved in the EGFR over-expression and the stronger tumorigenic activity triggered by EGFR mutations. Up-regulation of the CD82 level may become a promising new treatment strategy for lung adenocarcinoma.

[The effectiveness of a cold application for pain associated with chest tube removal: a systematic review].

BACKGROUND: Several previous studies have investigated the effectiveness of cold applications for pain associated with chest tube removal (CTR). However, the results of these studies are mutually contradictory. PURPOSE: The aim of this study was to determine the evidence related to the effectiveness of using a cold application to reduce the pain associated with CTR. METHODS: This review focused on studies published before June 2014 that were indexed in the following databases: Cochrane Library, PubMed, MEDLINE, CINAHL, ProQuest, Airiti Library, and National Digital Library of Theses and Dissertations in Taiwan. Keywords that were searched included: chest tube removal, cold application, and pain within a search design based on the PICO (patient, intervention, comparion, outcome) structure. Only randomized controlled trials (RCTs) that evaluated the efficacy of cold application in patients before CTR were included in analysis. Study quality was assessed using the Modified Jadad scale. RESULTS: Five RCTs that enrolled a total of 426 patients were included in the analysis. The mean age of participants ranged from 48.7 (SD = 16.5) to 60.2 (SD = 6.2) years. Ice packs were most widely used and applied to an area approximately 5-15 cm in diameter, with the chest tube entry point at the center. The findings of the effectiveness of the cold application were inconsistent among the studies. The researchers terminated the cold application when patients' skin temperature reached 13°C or after 20 min, which showed that the cold application immediately reduced the pain associated with CTR. It was also observed that the cold application prolonged the duration of time between the CTR and the administration of analgesics. Additionally, two studies in which analgesics were administered to participants 60 min before CTR showed that cold application in combination with analgesics administration reduced patient pain due to the enhancement affects of CTR, which obtained results that were better than analgesics administration alone. CONCLUSIONS: The results of this study may be used as a reference for reducing pain associated with CTR in clinical practice. However, further studies with larger sample sizes are required to support these results.

Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway.

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling.

DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer.

Vaccinia H1-related phosphatase is a phosphatase of ErbB receptors and is down-regulated in non-small cell lung cancer.

Vaccinia H1-related phosphatase (VHR) is classified as a dual specificity phosphatase. Unlike typical dual specificity phosphatases, VHR lacks the MAPK-binding domain and shows poor activity against MAPKs. We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. Decreasing VHR expression by RNA interference caused higher EGFR phosphorylation at Tyr-992. In addition to EGFR, VHR also directly dephosphorylated ErbB2. Consistent with these results, suppression of VHR augmented the foci formation ability of H1299 non-small cell lung cancer (NSCLC) cells, whereas overexpression of VHR suppressed cell growth in both two- and three-dimensional cultures. Expression of VHR also suppressed tumor formation in a mouse xenograft model. Furthermore, VHR expression was significantly lower in NSCLC tissues in comparison to that in normal lung tissues. Collectively, this study shows that down-regulation of VHR expression enhances the signaling of ErbB receptors and may be involved in NSCLC pathogenesis.

CA10 is associated with HBV-related hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the main threat for the patients infected with hepatitis B virus (HBV), but the oncogenic mechanism of HBV-related HCC is still controversial. Previously, we have found that several HBV surface gene (HBS) non-sense mutations are oncogenic. Among these mutations, sW182* was found to have the most potent oncogenicity. In this study, we found that Carbonic Anhydrase X (CA10) level was specifically increased in sW182* mutant-expressing cells. CA10 overexpression was also associated with HBS nonsense mutation in HBV-related HCC tumor tissues. Transformation and tumorigenesis assays revealed that CA10 had significant oncogenic activity. In addition, CA10 overexpression resulted in dysregulation of apoptosis-related proteins, including Mcl-1, Bcl-2, Bcl-xL and Bad. While searching for the regulatory mechanism of CA10, miR-27b was found to downregulate CA10 expression by regulating its mRNA degradation and its expression was decreased in sW182* mutant cells. Moreover, CA10 overexpression was associated with down-regulation of miR-27b in human HBV-related HCC tumor tissues with sW182* mutation. Therefore, induction of the expression of CA10 through repression of miR-27b by sW182* might be one mechanism involved in HBS mutation-related hepatocarcinogenesis.

EGFR Mutation-Harboring Lung Cancer Cells Produce CLEC11A with Endothelial Trophic and Tumor-Promoting Activities.

The formation of new blood vessels in solid tumors is regulated by various endothelial trophic factors. We identified that CLEC11A, an extracellular C-type lectin, was over-expressed in lung cancer cell lines harboring mutated EGFR. CLEC11A expression was also frequently elevated in lung adenocarcinoma (LAC) tissues with EGFR mutation. CLEC11A-expressing H1299 cells formed larger tumors in nude mice than did the control cells. The CLEC11A-expressing tumors contained more CD31-positive cells, suggesting that they had a higher angiogenic activity. CLEC11A per se did not induce blood vessel formation, but enhanced angiogenesis triggered by VEGF-A or basic FGF in vivo. Additionally, the expression of small hairpin RNA against CLEC11A (shCLEC11A) in HCC827 LAC cells suppressed their tumorigenic ability. Purified CLEC11A exhibited a chemotactic ability, which is dependent on its integrin-binding RGD and LDT motifs, toward endothelial cells. This chemotactic activity was not affected by the presence of a VEGFR inhibitor. Conditioned medium produced by HCC827-shCLEC11A cells had diminished chemotactic ability toward endothelial cells. CLEC11A treatments increased the levels of active integrin ß1 that were not associated with activation of focal adhesion kinases in endothelial cells. Our results indicated that CLEC11A was a factor of angiogenic potential and was involved in lung cancer tumorigenesis.

JNK pathway-associated phosphatase dephosphorylates focal adhesion kinase and suppresses cell migration.

JNK pathway-associated phosphatase (JKAP, also named DUSP22) is expressed in various tissues, indicating that JKAP may have an important biological function. We showed that JKAP localized in the actin filament-enriched region. Expression of JKAP reduced cell migration, whereas a JKAP mutant lacking catalytic activity promoted cell motility. JKAP efficiently removed tyrosine phosphorylation of several proteins. We have identified focal adhesion kinase (FAK) as a substrate of JKAP. Overexpression of JKAP, but not JKAP mutant lacking catalytic activity, decreased FAK phosphorylation at tyrosines 397, 576, and 577 in H1299 cells. Consistent with these results, decreasing JKAP expression by RNA interference promoted cell migration and Src-induced FAK phosphorylation. Taken together, this study identified a new role for JKAP in the modulation of FAK phosphorylation and cell motility.

[Dutasteride in the treatment of benign prostatic hyperplasia: an update].

Benign prostatic hyperplasia (BPH) is a common disease in older men. At present, 5alpha reductase inhibitor-based medication, preferred by most BPH patients as the first-choice therapy, is taking place of traditional transurethral resection of the prostate. This article presents an update of the researches on the treatment of BPH with dutasteride--a novel 5 alpha-reductase inhibitor.

Complete maternal mitochondrial genome of the freshwater mussel Cuneopsis celtiformis (Bivalvia: Unionidae).

The genus Cuneopsis Simpson, 1900 comprises seven valid species, and Cuneopsis celtiformis (Heude, 1874) is the type species of this genus. Previous phylogenetic studies using complete mitochondrial genomes showed that Cuneopsis was not monophyletic, but the result was hampered by incomplete species sampling and lack of the type species of this genus. In this study, we collected C. celtiformis from the type locality and determined its complete maternal mitochondrial genome. This mitogenome is 15,922 bp in length and contains 14 protein-coding genes (including one F-orf), two rRNA genes, 22 tRNA genes, and 1 putative control region. Our mitochondrial phylogenomic analysis confirms that currently recognized genus Cuneopsis is polyphyletic, and C. celtiformis is the closest to C. heudei with high maximum likelihood bootstrap support value. Comprehensive sampling of all Cuneopsis species is needed for phylogenetic analysis to erect new genera in future studies.

Effect of Temporal Difference on Clinical Outcomes of Patients with Out-of-Hospital Cardiac Arrest: A Retrospective Study from an Urban City of Taiwan.

Circadian pattern influence on the incidence of out-of-hospital cardiac arrest (OHCA) has been demonstrated. However, the effect of temporal difference on the clinical outcomes of OHCA remains inconclusive. Therefore, we conducted a retrospective study in an urban city of Taiwan between January 2018 and December 2020 in order to investigate the relationship between temporal differences and the return of spontaneous circulation (ROSC), sustained (≥24 h) ROSC, and survival to discharge in patients with OHCA. Of the 842 patients with OHCA, 371 occurred in the daytime, 250 in the evening, and 221 at night. During nighttime, there was a decreased incidence of OHCA, but the outcomes of OHCA were significant poor compared to the incidents during the daytime and evening. After multivariate adjustment for influencing factors, OHCAs occurring at night were independently associated with lower probabilities of achieving sustained ROSC (aOR = 0.489, 95% CI: 0.285-0.840, p = 0.009) and survival to discharge (aOR = 0.147, 95% CI: 0.03-0.714, p = 0.017). Subgroup analyses revealed significant temporal differences in male patients, older adult patients, those with longer response times (≥5 min), and witnessed OHCA. The effects of temporal difference on the outcome of OHCA may be a result of physiological factors, underlying etiology of arrest, resuscitative efforts in prehospital and in-hospital stages, or a combination of factors.

Patients' and Caregivers' Attitudes Toward Deprescribing in Singapore.

BACKGROUND: Knowledge of decision-making preference of patients and caregivers is needed to facilitate deprescribing. This study aimed to assess the perspectives of caregivers and older adults towards deprescribing in an Asian population. Secondary objectives were to identify and compare characteristics associated with these attitudes and beliefs. METHOD: A cross-sectional survey of two groups of participants was conducted using the Revised Patients' Attitudes Towards Deprescribing questionnaire. Descriptive results were reported for participants' characteristics and questionnaire responses from four factors (belief in medication inappropriateness, medication burden, concerns about stopping, and involvement) and two global questions. Correlation between participant characteristics and their responses was analyzed. RESULTS: A total of 1,057 (615 older adults; 442 caregivers) participants were recruited from 10 institutions in Singapore. In which 511 (83.0%) older adults and 385 (87.1%) caregivers reported that they would be willing to stop one or more of their medications if their doctor said it was possible, especially among older adults recruited from acute-care hospitals (85.3%) compared with older adults in community pharmacies (73.6%). Individuals who take more than five medications and those with higher education were correlated with greater agreement in inappropriateness and involvement, respectively. CONCLUSIONS: Clinicians should consider discussing deprescribing with older adults and caregivers in their regular clinical practice, especially when polypharmacy is present. Further research is needed into how to engage older adults and caregivers in shared decision making based on their attitudes toward deprescribing.

The Effect of Implementing Mechanical Cardiopulmonary Resuscitation Devices on Out-of-Hospital Cardiac Arrest Patients in an Urban City of Taiwan.

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195-2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427-3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.

Chimeric mouse models for lung adenocarcinomas.

Evaluation of: Zhou Y, Rideout WM 3rd, Zi T et al.: Chimeric mouse tumor models reveal differences in pathway activation between ERBB family- and KRAS-dependent lung adenocarcinomas. Nat. Biotechnol. 28(1), 71-78 (2010). EGFR and KRAS mutations are among the most frequent oncogenic mutations in non-small-cell lung cancer. However, these two mutations are associated with distinct clinical presentations. The underlying mechanisms for these differences are unclear. This study by Zhou et al. examines lung cancer formation induced by oncogenic mutants of ERBB, EGFR and HER2, as well as KRAS, using a novel chimeric mouse approach. They demonstrate that the PI3K/Akt pathway is preferentially activated in ERBB-induced tumors while KRAS-induced lung cancer demonstrates strong activation of the c-Jun N-terminal kinase pathway. This result suggests that, despite the involvement of KRAS and ERBB receptors in the same signaling pathway, oncogenic KRAS and ERBB mutants utilize different cellular signals to induce cancer formation.