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Crowding refers to impaired object recognition of peripheral visual targets caused by nearby flankers. It has been shown that the response to a word was faster when it was preceded by a semantically related than unrelated crowded prime, demonstrating that semantic priming survives crowding. This study examines neural correlates of semantic priming under visual crowding using magnetoencephalography with four conditions: prime (isolated, crowded) x prime-target relationship (related, unrelated). Participants judged whether the target was a word or a nonword. We found significant differences in θ activity at the left inferior frontal gyrus (IFG) for both isolated and crowded primes when comparing the unrelated and related conditions, although the activation was delayed with the crowded prime compared to the isolated prime. The locations within the IFG were also different: theta-band activation was at BA 45 in the isolated condition and at BA 47 in the crowded condition. Phase-locking-value analysis revealed that bilateral IFG was more synchronized with unrelated prime-target pairs than related pairs regardless of whether the primes were isolated or crowded, indicating the recruitment of the right hemisphere when the prime-target semantic relationship was remote. Finally, the distinct waveform patterns found in the isolated and crowded conditions from both the source localization and PLV analysis suggest different neural mechanisms for processing semantic information with isolated primes versus crowded primes.

Lead contamination in the environment tends to enter the food chain and further into the human body, causing serious health issues. Herein, we proposed a Csm6-DNAzyme tandem assay (termed cDNAzyme) using CRISPR/Cas III-A Csm6 and GR-5 DNAzyme, enabling one-pot and sensitive detection of lead contamination. We found that Pb

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

The heterogeneity and drug resistance of colorectal cancer (CRC) often lead to treatment failure. Isocitrate dehydrogenase 1 (IDH1), a rate-limiting enzyme in the tricarboxylic acid cycle, regulates the intracellular redox environment and mediates tumor cell resistance to chemotherapeutic drugs. The aim of this study was to elucidate the mechanism underlying the involvement of IDH1 acetylation in the development of CRC drug resistance under induction of TNFα. We found TNFα disrupted the interaction between SIRT1 and IDH1 and increased the level of acetylation at K115 of IDH1. Hyperacetylation of K115 was accompanied by protein ubiquitination, which increased its susceptibility to degradation compared to IDH1 K115R. TNFα-mediated hyperacetylation of K115 sensitized the CRC cells to 5FU and reduced the NADPH/NADP ratio to that of intracellular ROS. Furthermore, TNFα and 5FU inhibited CRC tumor growth in vivo, while the K115R-expressing tumor tissues developed 5FU resistance. In human CRC tissues, K115 acetylation was positively correlated with TNFα infiltration, and K115 hyperacetylation was associated with favorable prognosis compared to chemotherapy-induced deacetylation. Therefore, TNFα-induced hyperacetylation at the K115 site of IDH1 promotes antitumor redox homeostasis in CRC cells, and can be used as a marker to predict the response of CRC patients to chemotherapy.

Objective Lupus nephritis (LN) is the main complication of systemic lupus erythematosus (SLE), causing huge financial burden and poor quality of life. Due to the low compliance of renal biopsy, we aim to find a non-invasive biomarker of LN to optimize its predictive, preventive, and personalized medical service or management. Method Herein, we provided a bioinformatic screen combined clinical validation strategy for rapidly mining exosomal miRNAs for LN diagnosis and management. We screened out differentially expressed miRNAs (DEMs) and differentially expressed mRNAs (DEGs) in LN database and performed a miRNA-mRNA integrated analysis to select out reliable changed miRNAs in LN tissues by using R and Cytoscape. Urinary exosomes were collected by ultracentrifugation and analyzed by nano-tracking analysis and western blotting. Detection of aquaporin-2 showed the tubular source of urinary exosomes. Urinary exosomal miRNAs were detected by RT-qPCR and the target of miR-195-5p was verified by using bioinformatic, dual-luciferase, and western blotting. Result 15 miRNAs and their 60 target mRNAs were contained in miRNA-mRNA integrated map. Bioinformatic analysis showed these miRNAs were involved in various cellular biological process. Exosomal miR-195-5p, miR-25-3p, miR-429, and miR-218-5p were verified in a small clinical group (n = 47). Urinary exosomal miR-195-5p, miR-25-3p, and miR-429 were downregulated in patients and miR-195-5p could recognize LN patients from SLE with good sensitivity and specificity, showing good potential in LN disease monitoring and diagnosis. Conclusion We analyzed and obtained a series of differential miRNAs in LN kidney tissues and suggested that urinary exosomal miR-195-5p could serve as a novel biomarker in LN. Further, miR-195-5p-CXCL10 axis could be a therapeutic target of LN.

To identify the significant predictors of overall survival for patients living with diffused large B-cell lymphoma (DLBCL) in the central nervous system and establish a novel decision tree model to help predict survival status at several time points.Patients diagnosed with DLBCL were identified from the SEER database and randomly divided into training and test samples (6:4). Dichotomous decision trees were developed for survival status at 3, 12, 24, and 60 months. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and area under the receiver operating characteristic curve were calculated to evaluate the model performance.A total of 2998 patients were included, with 1799 and 1199 patients divided into the training and testing groups. Decision trees for 3, 12, 24, and 60 months survival status were generated. Chemotherapy and patient's age were of the primary importance for prognosis in the novel models. Favorable consistency between the predicted and actual survival status was presented. The accuracy rates were 0.79, 0.71, 0.68, and 0.86 for training sample at 3, 12, 24, and 60 months, respectively, and 0.75, 0.69, 0.58, and 0.84 for test sample at 3, 12, 24, and 60 months, respectively. The area under the receiver operating characteristic curve values ranged between 0.645 and 0.721 for the training sample and between 0.607 and 0.712 for the test sample.Novel decision tree models were established for predicting the 3, 12, 24, and 60 months survival status of patients with DLBCL. The newly developed models were verified using training and test samples, showing favorable accuracy and predictive value on overall survival.

Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord injury (SCI) in the neurotrauma field, which provides a promising strategy in neural regeneration. Olfactory ensheathing cells (OECs), a specialized type of glial cells, is considered as the excellent candidate due to its unique variable and intrinsic regeneration-supportive properties. In fact, OECs could support olfactory receptor neuron turnover and axonal extension, which is essential to maintain the function of olfactory nervous system. Hitherto, an increasing number of literatures demonstrate that transplantation of OECs exerts vital roles in neural regeneration and functional recovery after neural injury, including central and peripheral nervous system. It is common knowledge that the deteriorating microenvironment (ischemia, hypoxia, scar, acute and chronic inflammation, etc.) resulting from injured nervous system is adverse for neural regeneration. Interestingly, recent studies indicated that OECs could promote neural repair through improvement of the disastrous microenvironments, especially to the overwhelmed inflammatory responses. Although OECs possess unusual advantages over other cells for neural repair, particularly in SCI, the mechanisms of OEC-mediated neural repair are still controversial with regard to anti-inflammation. Therefore, it is significant to summarize the anti-inflammation property of OECs, which is helpful to understand the biological characteristics of OECs and drive future studies. Here, we mainly focus on the anti-inflammatory role of OECs to make systematic review and discuss OEC-based therapy for CNS injury.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-β-cyclodextrin inclusion (SHβCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-β-CD. The solubility of SLN was increased by generating SHβCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHβCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHβCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHβCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HβCD on drug absorption and gut microbial homeostasis.

Indoleamine 2.3-dioxygenases (IDO1/2) and tryptophan 2.3-dioxygenase (TDO) are the initial and rate-limiting enzymes in tryptophan metabolism, which play an essential role in mediating immunosuppression in tumor microenvironment. Accumulating evidence has indicated that both IDO1 and TDO are highly expressed in many malignant tumors, and their expression is generally associated with reduced tumor-infiltrating immune cells, increased regulatory T-cell infiltration, as well as cancer progression and poor prognosis for malignancies. A large number of IDO1 and TDO inhibitors have been screened or synthesized in the last two decades. Thus far, at least 12 antagonists targeting IDO1 and TDO have advanced to clinical trials. In this account, we conducted a comprehensive review of the development of IDO1 and TDO inhibitors in cancer immunotherapy, particularly their clinical research progress, and presented the current challenges and corresponding solutions.

Peri-intubation cardiac arrest is an uncommon, serious complication following endotracheal intubation in the emergency department. Although several risk factors have been previously identified, this study aimed to comprehensively identify risk factors associated with peri-intubation cardiac arrest.This retrospective, nested case-control study conducted from January 1, 2016 to December 31, 2020 analyzed variables including demographic characteristics, triage, and pre-intubation vital signs, medications, and laboratory data. Univariate analysis and multivariable logistic regression models were used to compare clinical factors between the patients with peri-intubation cardiac arrest and patients without cardiac arrest.Of the 6983 patients intubated during the study period, 5130 patients met the inclusion criteria; 92 (1.8%) patients met the criteria for peri-intubation cardiac arrest and 276 were age- and sex-matched to the control group. Before intubation, systolic blood pressure and diastolic blood pressure were lower (104 vs. 136.5 mmHg, p0.01; 59.5 vs. 78 mmHg, p0.01 respectively) and the shock index was higher in the patients with peri-intubation cardiac arrest than the control group (0.97 vs. 0.83, p0.0001). Cardiogenic pulmonary edema as an indication for intubation (adjusted odds ratio [aOR]: 5.921, 95% confidence interval [CI]: 1.044-33.57, p = 0.04), systolic blood pressure90 mmHg before intubation (aOR: 5.217, 95% CI: 1.484-18.34, p = 0.01), and elevated lactate levels (aOR: 1.012, 95% CI: 1.002-1.022, p = 0.01) were independent risk factors of peri-intubation cardiac arrest.Patients with hypotension before intubation have a higher risk of peri-intubation cardiac arrest in the emergency department. Future studies are needed to evaluate the influence of resuscitation before intubation and establish airway management strategies to avoid serious complications.

This study aimed to observe the analgesic effect of the cocktail formulation with diprospan during total hip arthroplasty (THA).From September 2018 to April 2019, 120 patients undergoing primary unilateral THA were included in this prospective, randomized, observer-blinded study. Patients were randomized into three groups, according to the different local infiltration analgesia (LIA) strategies: LIA with ropivacaine (the ropivacaine group, n = 40), LIA with a new cocktail containing ropivacaine, diprospan, and morphine (the cocktail group, n = 40), and the control group (n = 40). The primary outcomes included postoperative pain scores. The resting visual analogue scale (VAS) scores were measured at 2, 6, and 12 h after the surgery (a.m. and p.m.) on postoperative day (POD) 1, POD2, and the day of discharge. Movement VAS scores were assessed at 6 h, 12 h after the operation (a.m. and p.m.) on POD1, POD2, and the day of discharge. The secondary outcomes included opioid consumption, postoperative hospital stay, range of motion of the hip at discharge, patient satisfaction, and the results of the follow-up.After the screening, 120 patients were randomized into three groups (40 patients in each group). All of the patients completed the trial. The resting VAS scores in the ropivacaine group and cocktail group at 2 h were lower than those in the control group (P 0.001 and P 0.001, respectively, F = 17.054), and the same trend was also postoperatively found at 6 h (p = 0.005 and P = 0.002, F = 6.212). Twelve hours after the operation, the pain score in the cocktail group was lower than that in the other two groups, but only the difference between the cocktail group and the control group was statistically significant (P = 0.018, F = 3.144). From the morning of the first postoperative day to the a.m. on POD 2, the VAS scores in the cocktail group were significantly lower than those in the ropivacaine group and the control group. Furthermore, the movement VAS scores in the ropivacaine group and the cocktail group were better than those in the control group at 6 and 12 h post-operation (P 0.05). The per capita opioid consumption in the cocktail group was less than that in the ropivacaine group and the control group within 24 h post-operation. There were no significant differences in the comparison of additional indicators among the three groups.The new cocktail with diprospan had a better result and longer duration time for early postoperative pain control in primary THA via the posterolateral approach under general anesthesia, especially for treating resting pain.

High-grade neuroendocrine tumors (NETs) of the lung consist of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Both exhibit aggressive malignancy with poor prognosis. The transformation of lung adenocarcinoma (ADC) to SCLC or LCNEC also contributes to acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Despite initially being responsive to chemotherapy, high-grade NET patients inevitably develop drug resistance; thus, novel therapeutic targets are urgently needed for these patients. Our study reported that VGF (nerve growth factor inducible), a factor mainly expressed in neurons during neural development, is highly expressed in SCLC and LCNEC as well as in a subset of ADCs, whereas targeting VGF attenuates cancer cell growth and tumor formation. High VGF expression was associated with advanced stage SCLC and predicted poor prognosis in lung ADC. In addition, EGFR-TKI selection enriched VGF expression in TKI-resistant ADC under epigenetic control. The VGF locus possessed the HDAC1 binding site, and treatment of ADC cells with the HDAC1 inhibitor induced VGF expression. High VGF expression was associated with chemoresistance, and silencing VGF induced BMF and BCL2L11 expression and rendered lung cancer cells sensitive to chemotherapy drugs. These findings suggested the potential of VGF as a prognostic factor and therapeutic target in lung cancers with neuroendocrine feature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The central pathogenesis is an explosive cytokine storm characterized by a significant increase in proinflammatory cytokines, including IL-1β, IL-6, IL-18, IFN-γ, and TNF-α. Meanwhile, negative regulatory factors, such as IL-10 and TGF-β, are also related to the production of HLH. Exploring the specific mechanism of cytokine storms could provide ideas regarding targeted therapy, which could be helpful for early treatment to reduce the mortality of HLH. Although some research has focused on the advantages of targeted therapies, there is still a lack of a comprehensive discourse. This article attempts to summarize the mechanisms of action of various cytokines and provide a therapeutic overview of the current targeted therapies for HLH.

Cervical spondylotic myelopathy (CSM) is a common cause of neurological morbidity, which can have an impact on quality of life. Symptomatic postoperative spinal epidural hematoma (SPSEH) is a rare condition, but can cause permanent neurological deficits and disability if not managed properly. However, there are limited studies on the outcomes of SPSEH after anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) were performed for 2-level CSM. Therefore, the aim of the present study was to compare the clinical outcomes and incidence of SPSEH after ACDF compared with SPSEH after anterior cervical corpectomy and ACCF for 2-level CSM to reduce surgical complications of 2 level CSM.A total of 551 patients (261 males and 290 females) who underwent ACDF or ACCF for 2-level CSM from January 2009 to February 2015 were retrospectively reviewed. Preoperative indexes (age, sex, body mass index, bone mineral density, preoperative coagulation, and past medical history), perioperative indexes (length of hospital admission, blood loss, and operation times), preoperative and postoperative neurological statuses, complications, fusion rate, and the SPSEH incidence for ACDF or ACCF were compared simultaneously.With the exception of blood loss (P0.001), no significant differences were observed between the 2 groups in terms of sex, prothrombin time, activated partial thromboplastin time, platelet count, length of hospital admission, operation time, the final follow-up Japanese Orthopedic Association score, visual analog scale score, fusion rate, and complications. The overall incidence rate for SPSEH after ACDF was 1.9%, while the rate for SPSEH after ACCF was 0.4%. Following hematoma removal, only one patient showed any improvement in neurological function, despite treatment with hyperbaric oxygen and neurotrophic drugs.The findings indicated that surgical management of 2-level CSM using ACDF or ACCF showed similar clinical outcomes, fusion rate, complications, and perioperative parameters, with the exception of blood loss. However, SPSEH preferentially occurs after surgery with ACDF. Therefore, whether ACCF surgery for 2-stage CSM is the superior treatment modality.

Multidrug resistance (MDR), which is common in colorectal cancer (CRC), induces high mortality in patients. Due to its robust and selective apoptosis induction in some CRC cells with MDR, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is attractive as a novel tool for CRC therapy. However, TRAIL is limited by its poor tumor-homing ability and inefficient apoptosis induction in CRC cells expressing low levels of death receptor (DR). Here, the tumor-homing RGR peptide (CRGRRST) was fused to TRAIL to produce RGR-TRAIL. Compared with TRAIL, RGR-TRAIL showed greater cell binding and cytotoxicity in CRC cells. In addition, RGR-TRAIL exerted significantly enhanced tumor uptake and growth suppression in mice bearing CRC tumor xenografts. Notably, RGR-TRAIL eradicated all tumor xenografts of DR-overexpressing COLO205 cells. However, TRAIL only showed mild tumor growth suppression under the same conditions, indicating that RGR fusion significantly increased the antitumor effect of TRAIL in DR-overexpressing CRC cells by improving tumor homing. Nevertheless, RGR fusion did not significantly enhance the antitumor effect of TRAIL in HT29 cells expressing low levels of DR. We found that DR expression in HT29 cells was enhanced by epidermal growth factor receptor (EGFR)-targeted photodynamic therapy (PDT). Moreover, both the in vitro and in vivo antitumor effects of RGR-TRAIL were significantly improved by combination with PDT. HT29 tumor xenografts (∼20%) were even eradicated by combination therapy. These results indicate that it is valuable to further evaluate the combination therapy of RGR-TRAIL and tumor-targeted PDT for clinical therapy of CRC with MDR.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells.

PURPOSE Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, –4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

To investigate the relationship between different CYP4V2 disease-causing variants and disease severity in Bietti crystalline dystrophy (BCD).Twenty-one subjects from 19 unrelated families with a clinical diagnosis of BCD were enrolled. A novel severity prediction score for BCD based on the predicted molecular impact of CYP4V2 variants was applied for grouping and subsequent analyses. The more severe variants led to less CYP4V2 protein function preservation and a higher severity prediction score.All subjects harbored two alleles of CYP4V2 disease-causing variants, of which c.802-8_810del17insGC was the most prevalent (14/21, 66.67%) and c.1507GC was novel. According to the severity score, the subjects were categorized into severe, moderate, and mild groups with different preservation of central vision (mean logMAR visual acuity 0.95 ± 0.82, 0.89 ± 1.22, and 0.56 ± 0.64, respectively). The patients with a lower severity score had slower disease progression.This is the first cohort study of BCD in Taiwan, and we established a novel BCD severity index based on the molecular impact of different CYP4V2 variants. More severe impairment of CYP4V2 protein led to a more severe disease course with earlier progression. Our results could be helpful in identifying a therapeutic window for patients with BCD.

The optimal extent of surgery for older patients with early-stage pulmonary carcinoid tumour (PC) remains controversial.To compare prognostic differences between sublobar resection versus lobectomy in older patients with early-stage PC.The SEER database was searched for stage T1N0M0 PC patients aged ≥ 65 years who underwent lobectomy or sublobar resection from 2000 to 2017. Propensity score matching (PSM) was used to determine intergroup covariate differences. Kaplan-Meier curves and the log-rank test were used for intergroup comparison of overall survival (OS). A Cox proportional hazard model was used to evaluate independent risk factors.Among 1023 participants, 650 and 373 underwent lobectomy and sublobar resection, respectively. Before PSM, the 5- and 10-year OS in the sublobar resection group were lower than that of the lobectomy group (5-year OS 84.12% vs. 91.16%; 10-year OS 57.43% vs. 64.77%; p = 0.014); after PSM, no significant prognostic difference existed between lobectomy and sublobar resection (5-year OS 88.17% vs. 89.23%; 10-year OS 58.32% vs. 62.75%; p = 0.811). Subgroup analysis included tumour size, age, number of lymph nodes examined and histological type, and showed no statistically significant survival differences between the lobectomy and sublobar resection groups. Multivariable Cox analysis indicated that age ≥ 77 years, male sex, inadequate lymph node assessment ( 7), and atypical carcinoid were associated with reduced OS.Sublobar resection showed a similar long-term survival rate for early-stage PC patients aged ≥ 65 years as with lobectomy, thereby providing a basis for the selection of surgical methods for PC.

Background and Hypothesis Social competition affects human behaviors by inducing psychosocial stress. The neural and genetic mechanisms of individual differences of cognitive-behavioral response to stressful situations in a competitive context remain unknown. We hypothesized that variation in stress-related brain activation and genetic heterogeneity associated with psychiatric disorders may play roles towards individually differential responses under stress. Study Design A total of 419 healthy subjects and 66 patients with schizophrenia were examined functional magnetic resonance imaging during working memory task including social competition stressors. We explored the correlation between stress-induced brain activity and individual working memory performance. The partial least squares regression was performed to examine the genetic correlates between stress-related activity and gene expression data from Allen Human Brain Atlas. Polygenic risk score (PRS) was used to assess individual genetic risk for schizophrenia. Study Results Greater suppression of bilateral striatal activity was associated with better behavioral improvement in working memory manipulation under social competition (left: rPearson = −0.245, P = 4.0 × 10−6, right: rPearson = −0.234, P = 1.0 × 10−5). Genes transcriptionally related to stress-induced activation were linked to genetic risk for schizophrenia (PFDR < 0.005). Participants with decreased accuracy under social competition exhibited higher PRS of schizophrenia (t = 2.328, P = .021). Patients with schizophrenia showed less suppressed striatal activity under social stress (F = 13.493, P = 3.5 × 10−4). Conclusions Striatal activity change and genetic risk for schizophrenia might play a role in the individually behavioral difference in working memory manipulation under stress.

The soluble fms-like tyrosine kinase 1 (sFlt1)/placental growth factor (PlGF) ratio is a useful parameter for the diagnosis of preeclampsia. However, a comprehensive comparison of the ratio in preeclampsia and other hypertensive disorders of pregnancy was still missing and the dynamic levels of PlGF in the process of these diseases needed more clinical evidence.This retrospective study included participants tested for serum sFlt1 and PlGF levels at a national hospital in China throughout 2020. Diagnostic performance of the sFlt1/PlGF ratio and blood pressure was assessed by the receiver operating characteristic (ROC) analysis. The correlation of the sFlt1/PlGF ratio with pregnancy outcomes was evaluated using Kaplan-Meier curves. Besides, the circulating levels of PlGF were monitored in the time course of different hypertensive disorders' progress.The sFlt1/PlGF ratios were significantly elevated in the women with preeclampsia. The results of ROC analysis showed that, compared with blood pressure, the ratio is reliable for preeclampsia diagnosis from healthy control and shows better performance in distinguishing preeclampsia from other hypertensive disorders of pregnancy. A higher ratio than 85 could be used as an indicator of developing severe preeclampsia with adverse outcomes such as preterm delivery. Besides, our results suggested that using PlGF to predict preeclampsia should after 20 weeks of pregnancy.The PlGF and sFlt1/PlGF ratio are worth implementing in clinical management of women with preeclampsia rather than other hypertensive disorders of pregnancy.

Oncolytic virus therapy is a promising novel immunotherapy. In this report, we engineered a novel oncolytic influenza virus (IV) carrying an antihuman programmed cell death 1 (PD-1) monoclonal antibody utilizing reverse genetics. A reassortant chimeric IV, named rFlu-huPD1, was synthesized as follows: the heavy chain of the PD-1 antibody was encoded on the PB1 fragment, and the light chain of the PD-1 antibody was encoded on the polymerase acid protein fragment. rFlu-huPD1 antibodies were produced in infected ovalantoic eggs and could replicate to high titers. Moreover, selective cytotoxicity of rFlu-huPD1 was upregulated in multiple hepatocellular carcinoma (HCC) cell lines compared with a control, as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the activation of T cells in the spleen of tumor-bearing BALB/c mice treated with rFlu-huPD1 was observed, especially cytotoxic CD8

BackgroundEpidemiological evidence suggests an association between rheumatoid arthritis (RA) and myocardial infarction (MI). However, causality remains uncertain. Therefore, this study aimed to explore the causal association between RA and MI.MethodsUsing publicly available genome-wide association study summary datasets, bidirectional two-sample Mendelian randomization (TSMR) was performed using inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods.ResultsThe MR results for the causal effect of RA on MI (IVW, odds ratio [OR] = 1.041, 95% confidence interval [CI]: 1.007–1.076, P = 0.017; weighted median, OR = 1.027, 95% CI: 1.006–1.049, P = 0.012) supported a causal association between genetic susceptibility to RA and an increased risk of MI. MR results for the causal effect of MI on RA (IVW, OR = 1.012, 95% CI: 0.807–1.268, P = 0.921; weighted median, OR = 1.069, 95% CI: 0.855–1.338, P = 0.556) indicated that there was no causal association between genetic susceptibility to MI and an increased risk of RA.ConclusionBidirectional TSMR analysis supports a causal association between genetic susceptibility to RA and an increased risk of MI but does not support a causal association between genetic susceptibility to MI and an increased risk of RA.

Alzheimer type of dementia is accompanied with progressive loss of cognitive function that directly correlates with accumulation of amyloid beta plaques. It is known that Fibroblast growth factor 21 (FGF21), a metabolic hormone, with strong neuroprotective potential, is induced during oxidative stress in Alzheimer's disease. Interestingly, FGF21 cross-talks with autophagy, a mechanism involved in the clearance of abnormal protein aggregate. Moreover, autophagy activation by Rapamycin delivers neuroprotective role in Alzheimer's disease. However, the synergistic neuroprotective efficacy of overexpressed FGF21 along with Rapamycin is not yet investigated. Therefore, the present study examined whether overexpressed FGF21 along with autophagy activation ameliorated neurodegenerative pathology in Alzheimer's disease. We found that cognitive deficits in rats with intracerebroventricular injection of Amyloid beta

Antagonistic antibodies targeting the inhibitory immune-checkpoint receptor PD-1 or its ligand PD-L1 are used to treat a wide range of cancer types and can substantially improve patient survival. Nevertheless, strategies to overcome intrinsic and acquired resistance are required to respectively increase response rates and durations. PD-L1 is often upregulated in various malignancies, and emerging evidence suggests numerous underlying mechanisms involving distinct oncogenic signalling pathways. Thus, specific small-molecule inhibitors have the potential to simultaneously suppress not only a key oncogenic signalling pathway but also PD-L1 expression and/or activity in particular cancers, thereby presenting attractive candidate drugs for combination with existing immune-checkpoint inhibitors and/or other targeted agents. Herein, we summarize advances in understanding the mechanisms regulating PD-L1 expression at the transcriptional, post-transcriptional, translational and post-translational levels in cancers. We describe the roles of the diverse post-translational modifications of PD-L1, including phosphorylation, palmitoylation, glycosylation, acetylation and ubiquitination. Moreover, we discuss the potential use of small-molecule agents to modulate these mechanisms as well as of predictive biomarkers to stratify patients for optimal treatment, and provide our perspective on potential therapeutic strategies to circumvent resistance to conventional anti-PD-1/PD-L1 antibodies.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

To investigate the presence and clinical relevance of hyperreflective foci (HRFs) in retinitis pigmentosa.Seventy seven retinitis pigmentosa cases were retrospectively reviewed. The 10-mm wide cross-line macular scans in optical coherence tomography were acquired. Hyperreflective foci were classified according to the location in optical coherence tomography: outer layers within the macula (HRF-outer-central), macular border beyond the central 3 mm (HRF-outer-perifoveal), and choroid (HRF-choroidal). The visual acuity at baseline, at 12 months, and other fundus characteristics were collected.The mean logMAR best-corrected visual acuity decreased from 0.59 ± 0.66 (20/78 in Snellen) to 0.74 ± 0.81 (20/106 in Snellen) in 1 year. Sixty-six (42.9%), 105 (68.2%), and 98 (63.6%) eyes were classified to HRF-outer-central, HRF-outer-perifoveal, and HRF-choroidal group, respectively. Hyperreflective foci were positively correlated with poorer vision, central macular thinning, and ellipsoid zone disruption (all P0.001). Worse vision was associated with older age, macular involvement, and the coexistence of two or three HRF groups (P = 0.014, 0.047, 0.019,0.001, respectively). Hyperreflective foci developed more frequently in patients with thick choroid than in those with thin choroid. The coexistence of three HRF groups was correlated with quicker visual deterioration (P = 0.034).Hyperreflective foci are common in retinitis pigmentosa and can be a negative prognostic indicator of macular thickness and visual preservation. Thick choroid was associated with all groups of HRFs, especially HRF-choroidal.

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti-LINGO-1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO-1. In this study, we aim to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10-month-old male amyloid-β (Aβ) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti-LINGO-1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y-maze tests, and Aβ deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti-LINGO-1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO-1 positive cells, decreased Aβ deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO-1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO-1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aβ deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO-1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO-1 might be a potential therapeutic strategy for AD.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu

Optimal regimen using intravitreal aflibercept injections for diabetic macular edema (DME) in clinical practice remains to be elucidated. The purpose of this study is to evaluate a treat-and-extend (TAE) approach using intravitreal aflibercept in participants with center-involved DME.A 52-week open-label, prospective, multicenter, interventional study was conducted between August 2015 and November 2017 in Taiwan. Adults with diabetes mellitus and center-involved DME who have best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (CRT)300 μm were included. Participants received five monthly loading doses of 2 mg intravitreal aflibercept, followed by a TAE regimen with a four-week increment/decrement interval over 48 weeks; the maximum interval was 12 weeks. Main outcomes included changes in BCVA and CRT from baseline to week 52, additional anatomical outcomes, and treatment burden parameters.Forty-five participants with mean (SD) age of 63.7 (8.3) years were analyzed. At baseline, mean (SD) BCVA and CRT were 58.3 (11.9) letters and 434.4 (116.8) μm, respectively. Changes from baseline in BCVA and CRT were +8.3 (9.3) letters and -138.2 (150.0) μm (both p0.001) at week 52, respectively. In addition, 22% (10/45) of patients gained ≥15 letters, 14% (6/44) of participants achieved ≥2-level improvement in diabetic retinopathy severity, and 51% (23/45) demonstrated dry retina at week 52 compared with 13% (6/45) at baseline. In total, 87% (39/45) of patients reached disease stability, entering TAE at week 20. Subsequently, 89% (40/45) of patients reached maximum interval at week 52. Mean (SD) number of injections was 7.7 (1.5) over a period of 52 weeks.This straightforward and practical TAE regimen using intravitreal aflibercept injections resulted in favorable clinical outcomes with minimal treatment burden for DME at week 52.

Propionic acidemia (PA) is a severe autosomal recessive metabolic disease caused by deficiency of propionyl-CoA carboxylase (PCC). We studied PA transgenic (Pat) mice that lack endogenous PCC but express a hypoactive human PCCA cDNA, permitting their survival. Pat cohorts followed from 3 to 20 weeks of age showed growth failure and lethal crises of lethargy and hyperammonemia, commoner in males (27/50, 54%) than in females (11/52, 21%) and occurring mainly in Pat mice with the most severe growth deficiency. Groups of Pat mice were studied under basal conditions (P-Ba mice) and during acute crises (P-Ac). Plasma acylcarnitines in P-Ba mice, compared to controls, showed markedly elevated C3- and low C2-carnitine, with a further decrease in C2-carnitine in P-Ac mice. These clinical and biochemical findings resemble those of human PA patients. Liver acyl-CoA measurements showed that propionyl-CoA was a minor species in controls (propionyl-CoA/acetyl-CoA ratio, 0.09). In contrast, in P-Ba liver the ratio was 1.4 and in P-Ac liver, 13, with concurrent reductions of the levels of acetyl-CoA and other acyl-CoAs. Plasma ammonia levels in control, P-Ba and P-Ac mice were 109 ± 10, 311 ± 48 and 551 ± 61 μmol/L respectively. Four-week administration to Pat mice, of carglumate (N-carbamyl-L-glutamic acid), an analogue of N-carbamylglutamate, the product of the only acyl-CoA-requiring reaction directly related to the urea cycle, was associated with increased food consumption, improved growth and absence of fatal crises. Pat mice showed many similarities to human PA patients and provide a useful model for studying tissue pathophysiology and treatment outcomes.

Patients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/β-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.

Background: Current management guidelines for gallbladder polyps (GBPs) focus on a diameter more than 1 cm as an indication for cholecystectomy. Since most GBPs are not malignant, unnecessary cholecystectomies can lead to unnecessary complications and costs. We developed a score to identify true polyps focusing on their cross-sectional area (CSA). Methods: We retrospectively analyzed the demographic, clinical, laboratory, and sonographic characteristics of 522 patients with GBPs who had undergone cholecystectomy at our hospital between January 2010 and July 2020 (reference group). We used univariate analysis to compare these parameters between 88 true polyps and 434 pseudopolyps and multivariate logistic regression analysis to identify parameters to include in our scoring model. Receiver operating characteristics and area under the curve were used to identify cut-off values. The model was tested on a validation group of 98 patients. Results: In the multivariate analysis, a CSA >123 mm2, positive blood flow signal, age >55.5 years, alanine aminotransferase (ALT) levels > 50 U/L, and an ALT/aspartate aminotransferase ratio > 0.77 were significantly associated with true polyps (odds ratio 6.528, 2.377, 2.617, 2.445, and −0.372, respectively). A prediction model based on cut-off values was used to distinguish a low-risk and high-risk GBP group; true polyps accounted for 6.54% and 58.72%, respectively (p

Objective The purpose of the present study was to estimate complications and other outcomes associated with staple and suture closure after hip arthroplasty through meta-analysis techniques and a systematic review. Methods We searched for articles in EMBASE, PubMed, Medline, Web of Science and the Cochrane Library. To determine the eligibility of the searched trials, Cochrane Collaboration's Review Manager software was used to perform the meta-analysis. Results Five randomized controlled trials and one retrospective cohort trial were included in our study. Our study indicated that for skin closure after hip arthroplasty, the risks of superficial infection and prolonged discharge were higher with staples than with sutures. There was no significant difference between the two groups in terms of allergic reaction, dehiscence, inflammation, abscess formation, the Hollander Wound Evaluation Scale or patient's satisfaction with skin closure methods. However, suturing required a longer operating time. Conclusions Closure with sutures is associated with lower risks of superficial infection and prolonged discharge than closure with staples following hip arthroplasty, but it may take more time.

In order to evaluate the stability of neonatal parenteral nutrition solution, in this paper, the prescription of neonatal parenteral nutrition solution was investigated and analyzed. The formula of neonatal parenteral nutrition solution used, particularly the one utilized in this study, is commonly used in clinical practice. All the neonatal parenteral nutrition solution required for the test was prepared on the purification workbench in a sterile environment. The time points of stability of parenteral nutrient solution were 0, 12, and 24 hours, respectively, and three parallel samples were taken at each time point. Likewise, to investigate the stability of two kinds of fat milk injection in parenteral nutrition solution of neonates and provide a reference for subsequent experiments and to investigate the influence of electrolyte, amino acid, temperature, pH value, mixing sequence, and the final concentration of glucose on the stability of neonatal parenteral nutrition solution, the stability indexes of neonatal parenteral nutrition liquid mainly include appearance, pH, insoluble particles, fat milk particle size, and particle size distribution. Neonatal parenteral nutrition solution prescriptions from the First Affiliated Hospital of Jinan University, specifically from January to June 2019, were collected and statistically processed. The experimental data were processed by SPSS 19.0 software and data mining technology. The results were expressed as mean ± standard deviation and statistically processed by ANOVA. P < 0.05 was considered statistically significant. The results showed that the stability of neonatal parenteral nutrient solution was influenced by many factors. The formula of neonatal parenteral nutrition solution is generally reasonable, but there are unreasonable phenomena which are needed to be improved further if feasible.

As a selective estrogen receptor modulator (SERM), raloxifene is used in healthy postmenopausal women to prevent bone loss and reduce fractures. However, the benefit of raloxifene is uncertain in the treatment of osteoporosis among patients with end-stage renal disease (ESRD) or those who require maintenance dialysis. We assessed the safety and efficacy of raloxifene in this particular population. Studies were selected from PubMed, Springer, CNKI (Chinese National Knowledge Infrastructure) and Wanfang Database. Randomized controlled trials (RCTs) and prospective studies with control/placebo groups were included. Five studies were included with a total of 244 participants (121 patients in the raloxifene group and 123 patients in the placebo/control group). The median duration of treatment was 12 months. The incidence rate of side effects of raloxifene was 0/121 (0%). There was a significant improvement of lumbar spine bone mineral density (BMD) levels in the raloxifene group compared with the placebo group (MD: 33.88, 95% CI: 10.93, 56.84, p=0.004). There was no significant difference concerning the improvement of femoral neck BMD (MD: 8.42, 95% CI: –10.21, 27.04, p=0.38), intact parathyroid hormone (iPTH) (MD: –12.62, 95% CI: –35.36, 10.13, p=0.28), calcium (MD: -0.08, 95% CI: –0.61, 0.44, p=0.76), phosphorus (MD: 0.18, 95% CI: –0.12, 0.48, p=0.23) or bone alkaline phosphatase (BAP) (MD: –4.33, 95% CI: –14.44, 5.79, p=0.40). Raloxifene seems to be effective in improving the lumbar spine BMD in postmenopausal women with ESRD. More large RCTs are necessary to evaluate the long-term safety of raloxifene in uremic patients.

BACKGROUND Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival. METHODS This retrospective cohort study included 419 patients aged 0 to 14 years at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival. RESULTS The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL. CONCLUSIONS These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.

To provide real-world experiences of treating polypoidal choroidal vasculopathy (PCV) patients with photodynamic therapy (PDT) plus intravitreal injection of ranibizumab or intravitreal injection of aflibercept alone. Retrospective chart review of patients with PCV in a single tertiary referral center in Taiwan. Chart review of PCV patients treated with PDT and injection of ranibizumab or injection of aflibercept. A total of 101 eyes of 101 patients (38 females and 63 males) were reviewed. Of those, 48 and 53 eyes received primary/adjunctive PDT along with injections of ranibizumab or intravitreal injections of aflibercept only, respectively. Initial visual acuity (VA) and central subfield choroidal thickness were similar between the two groups (p > 0.05). In addition, changes in VA at 3, 6, and 12 months post treatment were similar. The central retinal thickness decreased with either treatment (p p > 0.05). In the subgroup analysis of pachychoroid and non-pachychoroid patients, better initial VA and post-treatment VA at 3 months and 6 months was noted in the latter group of patients treated with anti-vascular endothelial growth factor monotherapy (p

Aim This study aimed to develop an AI model for detecting a caller’s emotional state during out-of-hospital cardiac arrest calls by processing audio recordings of dispatch communications. Methods Audio recordings of 337 out-of-hospital cardiac arrest calls from March-April 2011 were retrieved. The callers’ emotional state was classified based on the emotional content and cooperative scores. Mel-frequency cepstral coefficients extracted essential information from the voice signals. A support vector machine was utilised for the automatic judgement, and repeated random sub-sampling cross validation (RRS-CV) was applied to evaluate robustness. The results from the artificial intelligence classifier were compared with the consensus of expert reviewers. Results The audio recordings were classified into five emotional content and cooperative score levels. The proposed model had an average positive predictive value of 72.97%, a negative predictive value of 93.47%, sensitivity of 38.76%, and specificity of 98.29%. If only the first 10 seconds of the recordings were considered, it had an average positive predictive value of 84.62%, a negative predictive value of 93.57%, sensitivity of 52.38%, and specificity of 98.64%. The artificial intelligence model’s performance maintained preferable results for emotionally stable cases. Conclusion Artificial intelligence models can possibly facilitate the judgement of callers’ emotional states during dispatch conversations. This model has the potential to be utilised in practice, by pre-screening emotionally stable callers, thus allowing dispatchers to focus on cases that are judged to be emotionally unstable. Further research and validation are required to improve the model's performance and make it suitable for the general population.

Repetitive transcranial magnetic stimulation (rTMS) of the brain is an effective clinical treatment for psychiatric disorders. Noninvasive neuroimaging during rTMS allows visualization of cortical brain activations and responses, and it is a potential tool for investigating the neurophysiological response occurring actively during stimulation. In this paper, we present a fast diffuse optical tomography (DOT) approach for three-dimensional brain mapping of hemodynamics during rTMS. Eight healthy subjects were enrolled in the study. These subjects received 10 Hz stimulation with 80%and 100%of resting motor threshold (rMT), respectively, for 4 seconds for each stimulation. Significant hemodynamic activation was observed in all cases with the strongest response when 100%rMT stimulation was applied. This work demonstrates that fast DOT has the potential to become a powerful tool for noninvasive three-dimensional imaging of the brain during rTMS.

To investigate the effect of CT image acquisition parameters on the performance of radiomics in classifying benign and malignant pulmonary nodules (PNs) with respect to nodule size. We retrospectively collected CT images of 696 patients with PNs from March 2015 to March 2018. PNs were grouped by nodule diameter: T1a (diameter ≤ 1.0 cm), T1b (1.0 cm

Long non–coding RNA AC020978 (lncRNA AC020978) is an oncogenic regulator of non–small cell lung cancer (NSCLC). However, the function of AC020978 in regulating NSCLC metastasis and the potential molecular mechanism remains largely unknown. In this study, we evaluated the expression levels of AC020978 in a series of NSCLC tissues using FISH assays and found that higher AC020978 expression levels were closely associated with metastasis and unfavorable prognosis. Functional studies showed that AC020978 promoted NSCLC migration and invasion both in vitro and in vivo. Further investigation demonstrated that AC020978 interacted with malate dehydrogenase 2 (MDH2) and maintained MDH2 stability. Knockdown of MDH2 weakened the facilitating effect on cell metastasis and 2‐hydroxyglutarate (2‐HG) metabolism in AC020978‐overexpressed NSCLC cells. RNA sequencing, bioinformatic analysis, and western blotting revealed that AC020978 was associated with the AKT signaling pathway. Taken together, our findings revealed that AC020978 might serve as a prognostic biomarker and activate the AKT pathway by stabilizing MDH2, leading to metastasis and progression of NSCLC., We identified the metastasis‐related function of lncRNA AC020978 in NSCLC, which directly interacts with MDH2 and promotes migration and invasion of lung cancer through the AC020978/MDH2/AKT axis.

Objective This research was performed to investigate the correlation between acute kidney injury (AKI) and systemic immune-inflammation index (SII) in severe acute pancreatitis (SAP) patients. Methods The study included 218 SAP patients from Chongqing Jiangjin Center Hospital during January 2016 to October 2020. The SII was defined as platelet × neutrophil/lymphocyte ratio. After univariate analysis, logistic regression analysis was used for analyzing independent risk factors of AKI in SAP patients. Receiver operating characteristic (ROC) curve was used for analyzing the prognostic value of the SII. Results AKI occurred in 74 cases and its incidence rate was 33.9%. The median SII value of AKI patients was higher than that of patients without AKI. After multivariate analysis, SII, age, triglyceride (TG), neutrophil ratio (NEU-R), C-reactive protein (CRP), aspartate aminotransferase (AST), and serum albumin (ALB) were independent predictors of AKI. Serum ALB was an independent protective factor. The optimum threshold truncation value of SII was 2880.1*10^9/L. Compared with other inflammatory factors, SII had a better prediction efficiency. Conclusion The SII, TG, NEU-R, CRP, and ALB were significant independent predictors of AKI in SAP patients. Serum TG, NEU-R, CRP, and SII were risk factors. Serum ALB was a protective factor. The SII may be a novel, simple, and strong marker for the accurate early prediction of AKI in SAP patients.

Background Out-of-hospital cardiac arrest (OHCA) is a critical condition with poor outcomes. Although the survival rate increases in those who undergo defibrillation, the utility of on-time defibrillation among bystanders remained low. An evaluation of the deployment strategy for public access defibrillators (PADs) is necessary to increase their use and accessibility. This study was to conduct a systematic review for deployment strategies of PADs. Methods Two authors independently searched for articles published before October 2019 from PubMed, Embase, Web of Science, and Cochrane Library. An independent librarian provided the search strategy and assisted the literature research. We included articles that were focused on the main topic, but excluded those which were missing results or that used an unclear definition. The qualitative outcomes were the utility and OHCA coverage of PADs. We performed a qualitative analysis across the studies, but a quantitative analysis was not available due to the studies' heterogeneity in design and variety of outcomes. Results We eventually included 15 studies. Three strategies were presented: guidelines-based, grid-based, and landmark-based. The guidelines-based deployment was common fit for OHCA events. The grid-based method increased the use of bystander defibrillation 3-fold, and 30-day survival doubled. The top 3 landmarks in the landmark-based strategy were offices (18.6%), schools (13.3%), and sports facilities (12.9%). Utility of PADs might increase if we optimize PAD location by mathematical modeling and evaluation feedback. Conclusion Three deployment strategies were presented. Although the optimal method could not be fully identified, a more efficient PAD deployment could benefit the population in terms of OHCA coverage and survival among patients with OHCA.

This study highlights the clinical features and treatment response of polypoidal choroidal vasculopathy (PCV) among three different branching vascular network (BVN) morphologies in optical coherence tomography angiography (OCTA), and further correlates the BVN features with those under fluorescent angiography (FA) and indocyanine green angiography (ICGA). In total, we reviewed 70 eyes with PCV followed up for > 12 months. OCTA, ICGA and FA images were obtained at baseline and post-treatments. BVN was assessed using OCTA and divided into three types by a previously described BVN classification: type 1 (trunk), type 2 (glomeruli), and type 3 (stick). At baseline, type 1 BVN had the poorest vision and thinnest subfoveal choroidal thickness (SFCT), whereas type 3 had the best vision and thickest SFCT. The aforementioned trend sustained after treatments. Each BVN morphology in OCTA showed typical features in FA + ICGA and encompassed significant correlation (p = 0.004). In conclusion, OCTA is an innovative imaging tool for the detection and classification of BVN in PCV. Furthermore, OCTA has advantages of being noninvasive and free of systemic toxicities. The BVN can be divided into three types based on morphological characteristics in OCTA, which play crucial roles in clinical presentations and treatment outcomes.

We aimed to evaluate the prognostic impact of the number of examined lymph nodes (ELNs) in resected early‑stage pulmonary typical carcinoid tumors (TC).Patients who underwent sublobar resection and lobectomy for stage T1N0M0 TC between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results database and enrolled in the ELNs≥4 or ELNs4 groups (optimal cutoff using X-tile). Propensity score matching balanced baseline intergroup characteristics. Kaplan-Meier curve and log-rank test were used to calculate and compare overall survival (OS) rates. Cox proportional hazard model analysis was used to identify independent prognostic factors.Among 2234 participants, 961 (43.02%) and 1273 (56.98%) had ELNs4 and ≥4, respectively. The 5-year OS was significantly higher in the ELNs≥4, compared with ELNs4, group, both before and after propensity score matching (95.41% vs. 89.71%, P0.001 and 95.24% vs. 90.28%, P=0.004), respectively. Surgical subgroup analysis confirmed this survival trend in the lobectomy and sublobar resection groups. Tumor size-based subgroup analysis revealed superior OS with ELNs≥4 than ELNs4 for tumors measuring 1.1-3.0 cm but not for tumors1.0 cm. Multivariate Cox analysis showed that ELN≥4 contributed to improved OS.The higher the ELNs, the greater the long-term survival rate in patients with early‑stage TC. Therefore, we recommend at least 4 ELNs as the cutoff value for evaluating the prognosis of early‑stage TCs, especially for patients with a tumor size of 1.1 to 3.0 cm.

Background and objective The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates. Purpose The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide. Methods and materials Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland–Altman plots were used to examine SPC-guided agreements for CBT screw placement. Results A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland–Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip. Conclusions Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.

BackgroundAlterations in lipid metabolism promote tumor progression. However, the role of lipid metabolism in the occurrence and development of gastric cancer have not been fully clarifiedMethodHere, genes that are related to fatty acid metabolism and differentially-expressed between normal and gastric cancer tissues were identified in the TCGA-STAD cohort. The intersection of identified differentially-expressed genes with Geneset was determined to obtain 78 fatty acid metabolism-related genes. The ConsensusClusterPlus R package was used to perform differentially-expressed genes, which yielded divided two gastric cancer subtypes termed cluster 1 and cluster 2.ResultsPatients in cluster 2 was found to display poorer prognosis than patients in cluster 1. Using machine learning method to select 8 differentially expressed genes among subtypes to construct fatty acid prognostic risk score model (FARS), which was found to display good prognostic efficacy. We also identified that certain anticancer drugs, such as bortezomib, elesclomol, GW843682X, and nilotinib, showed significant sensitivity in the high FARS score group. RGS2 was selected as the core gene upon an analysis of the gastric cancer single-cell, and Western blotting and immunofluorescence staining results revealed high level of expression of this gene in gastric cancer cells. The results of immunohistochemical staining showed that a large amount of RGS2 was deposited in the stroma in gastric cancer. A pan-cancer analysis also revealed a significant association of RGS2 with TMB, TIDE, and CD8+ T-cell infiltration in other cancer types as well. RGS2 may thus be studied further as a new target for immunotherapy in future studies on gastric cancer.ConclusionIn summary, the FARS model developed here enhances our understanding of lipid metabolism in the TME in gastric cancer, and provides a theoretical basis for predicting tumor prognosis and clinical treatment.