Estimation and Inference for High-Dimensional Generalized Linear Models with Knowledge Transfer.

Transfer learning provides a powerful tool for incorporating data from related studies into a target study of interest. In epidemiology and medical studies, the classification of a target disease could borrow information across other related diseases and populations. In this work, we consider transfer learning for high-dimensional generalized linear models (GLMs). A novel algorithm, TransHDGLM, that integrates data from the target study and the source studies is proposed. Minimax rate of convergence for estimation is established and the proposed estimator is shown to be rate-optimal. Statistical inference for the target regression coefficients is also studied. Asymptotic normality for a debiased estimator is established, which can be used for constructing coordinate-wise confidence intervals of the regression coefficients. Numerical studies show significant improvement in estimation and inference accuracy over GLMs that only use the target data. The proposed methods are applied to a real data study concerning the classification of colorectal cancer using gut microbiomes, and are shown to enhance the classification accuracy in comparison to methods that only use the target data.

Hotspots lurking underwater: Insights into the contamination characteristics, environmental fates and impacts on biogeochemical cycling of microplastics in freshwater sediments.

The widespread presence of microplastics (MPs) in aquatic environments has become a significant concern, with freshwater sediments acting as terminal sinks, rapidly picking up these emerging anthropogenic particles. However, the accumulation, transport, degradation and biochemical impacts of MPs in freshwater sediments remain unresolved issues compared to other environmental compartments. Therefore, this paper systematically revealed the spatial distribution and characterization information of MPs in freshwater (rivers, lakes, and estuaries) sediments, in which small-size (<1 mm), fibers, transparent, polyethylene (PE), and polypropylene (PP) predominate, and the average abundance of MPs in river sediments displayed significant heterogeneity compared to other matrices. Next, the transport kinetics and drivers of MPs in sediments are summarized, MPs transport is controlled by the particle diversity and surrounding environmental variability, leading to different migration behaviors and transport efficiencies. Also emphasized the spatio-temporal evolution of MPs degradation processes and biodegradation mechanisms in sediments, different microorganisms can depolymerize high molecular weight polymers into low molecular weight biodegradation by-products via secreting hydrolytic enzymes or redox enzymes. Finally, discussed the ecological impacts of MPs on microbial-nutrient coupling in sediments, MPs can interfere with the ecological balance of microbially mediated nutrient cycling by altering community networks and structures, enzyme activities, and nutrient-related functional gene expressions. This work aims to elucidate the plasticity characteristics, fate processes, and potential ecological impact mechanisms of MPs in freshwater sediments, facilitating a better understanding of environmental risks of MPs in freshwater sediments.

Palmitoylation at a conserved cysteine residue facilitates gasdermin D-mediated pyroptosis and cytokine release.

Gasdermin D (GSDMD)-mediated pyroptotic cell death drives inflammatory cytokine release and downstream immune responses upon inflammasome activation, which play important roles in host defense and inflammatory disorders. Upon activation by proteases, the GSDMD N-terminal domain (NTD) undergoes oligomerization and membrane translocation in the presence of lipids to assemble pores. Despite intensive studies, the molecular events underlying the transition of GSDMD from an autoinhibited soluble form to an oligomeric pore form inserted into the membrane remain incompletely understood. Previous work characterized S-palmitoylation for gasdermins from bacteria, fungi, invertebrates, as well as mammalian gasdermin E (GSDME). Here, we report that a conserved residue Cys191 in human GSDMD was S-palmitoylated, which promoted GSDMD-mediated pyroptosis and cytokine release. Mutation of Cys191 or treatment with palmitoyltransferase inhibitors cyano-myracrylamide (CMA) or 2-bromopalmitate (2BP) suppressed GSDMD palmitoylation, its localization to the membrane and dampened pyroptosis or IL-1ß secretion. Furthermore, Gsdmd-dependent inflammatory responses were alleviated by inhibition of palmitoylation in vivo. By contrast, coexpression of GSDMD with palmitoyltransferases enhanced pyroptotic cell death, while introduction of exogenous palmitoylation sequences fully restored pyroptotic activities to the C191A mutant, suggesting that palmitoylation-mediated membrane localization may be distinct from other molecular events such as GSDMD conformational change during pore assembly. Collectively, our study suggests that S-palmitoylation may be a shared regulatory mechanism for GSDMD and other gasdermins, which points to potential avenues for therapeutically targeting S-palmitoylation of gasdermins in inflammatory disorders.

Angiogenesis in heterotopic ossification: From mechanisms to clinical significance.

Heterotopic ossification (HO) refers to the formation of pathologic bone in nonskeletal tissues (including muscles, tendons or other soft tissues). HO typically occurs after a severe injury and can occur in any part of the body. HO lesions are highly vascularized. Angiogenesis, which is the formation of new blood vessels, plays an important role in the pathophysiology of HO. Surgical resection is considered an effective treatment for HO. However, it is difficult to completely remove new vessels, which can lead to the recurrence of HO and is often accompanied by significant problems such as intraoperative hemorrhage, demonstrating the important role of angiogenesis in HO. Here, we broadly summarize the current understanding of how angiogenesis contributes to HO; in particular, we focus on new insights into the cellular and signaling mechanisms underlying HO angiogenesis. We also review the development and current challenges associated with antiangiogenic therapy for HO.

Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma.

BACKGROUND: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. METHODS: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. RESULTS: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.

A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors.

Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)-based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid-based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNß than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy. Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors.

Development and validation of prognostic nomograms for adult with papillary renal cell carcinoma: A retrospective study.

OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.

Compilation of a self-management assessment scale for postoperative patients with aortic dissection.

Objective: The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods: The initial version of the "postoperative self-management assessment scale for patients with aortic dissection" was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the "postoperative self-management assessment scale for patients with aortic dissection." A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results: The formal version of the scale had 6 dimensions and 35 entries. The Cronbach's α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test-retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker-Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2/df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion: We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Utilizing physician modified fenestration on the castor branched stent technique for reconstruction of an isolated left vertebral artery on the aortic arch.

The study aimed to provide physician modified fenestration (PMF) on a single-branched stent for the aortic arch (Castor) to protect the isolated left vertebral artery (ILVA) during thoracic endovascular aortic repair (TEVAR). Patients who underwent TEVAR involving ILVA reconstruction through PMF performing on the Castor branched stent were included in a retrospective, multi-centre study from June 2018 to December 2022. In these patients, all proximal landing zones of "Castor" were positioned in Ishimaru zone 2a. A total of twenty-five patients met the inclusion criteria and the achievement rate showed 25/25 (100%) success in them. The twenty-five patients had a median follow-up length of 28.5 ± 14.6 months. One patient (4.0%) suffered from postoperative ischemic stroke before discharge. One patient (4.0%) died from a hemodialysis-related brain hemorrhage before discharge on the 29th day after the procedure. One patient died of advanced liver cancer in the 33th month after discharge. Aortic rupture, stroke or spinal cord injury did not occur throughout the follow-up period after discharge. Two patients (8.0%) experienced endoleak at the fenestration, however, resulting in only one's necessity for reintervention. Notably, the procedure effectively maintained ILVAs patency for all patients during follow up. According to our preliminary findings, performing a TEVAR under local anaesthesia using PMF on a Castor branched stent for ILVA preservation appeared practical, secure, and effective.

circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression.

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Investigating the correlation of delirium after cardiac surgery with memories and posttraumatic stress disorder consequences of intensive care unit: A prospective cohort study.

OBJECTIVES: To explore the differences in post-intensive care unit memory and posttraumatic stress disorder symptoms between patients with and without delirium, and assess the correlations between the two. DESIGN: Prospective cohort observation study. SETTING: A cardiac intensive care unit of a tertiary hospital in China. We enrolled 318 consecutive patients after cardiac surgery between December 2017 and March 2019. MAIN OUTCOME MEASURES: Delirium was assessed using the Confusion Assessment Method for the ICU from intensive care unit admission to discharge. Intensive care unit memory was assessed using the ICU-Memory Tool through face-to-face interviews one week after discharge. Posttraumatic stress disorder was measured telephonically using the Impact of Events Scale-revised questionnaire at three months post-discharge. RESULTS: Eighty patients each in the delirium and non-delirium groups were enrolled for follow-up interviews. Patients with delirium had vaguer memories of pre-intensive care unit admission and of their stay, and recollected more memories of feelings (vs. without delirium). Posttraumatic stress disorder was diagnosed in 14 patients with and in seven without delirium, with non-significant differences between groups. Delirium did not influence post-intensive care unit factual, feeling, and delusional memories, nor posttraumatic stress disorder and hyperarousal, intrusion, and avoidance. The memories of feelings were positively correlated with the last three (r = 0.285, r = 0.390 and r = 0.373, respectively). CONCLUSION: Patients with delirium had vague intensive care unit memories. Memories of feelings were positively correlated with symptoms of hyperarousal, intrusion, and avoidance. Delirium did not influence factual, feeling, or delusional memories nor posttraumatic stress disorder incidence and symptoms. IMPLICATIONS FOR CLINICAL PRACTICE: Interventions are needed to reduce the impact of vague memory in patients with post-intensive care unit delirium. Memories of feelings should be focused on because of their correlation with hyperarousal, intrusion, and avoidance. Delirium prevention and early recognition measures are suggested.

Analysis of serum calcium change trajectories and prognostic factors in patients with acute type A aortic dissection.

OBJECTIVES: This study aimed to analyze the correlation between serum calcium changes and short-term prognosis of patients with acute type A aortic dissection. METHODS: Patients who underwent acute type A aortic dissection surgery at Fujian Heart Medical Center between June 2019 and June 2021 were retrospectively analyzed. RESULTS: A total of 383 patients were enrolled. According to the changing track of serum calcium in patients after acute type A aortic dissection, three potential category tracks were determined: high-level (n = 85), medium-level (n = 259), and continuous low-level groups (n = 39). Using the medium-level group as the control, regression analysis showed that poor prognosis risk was increased in the group with continuous low serum calcium (odds ratio = 2.454, P < 0.05) and in the group with continuous low serum calcium > 48 h (odds ratio = 3.595, P < 0.05). Age (odds ratio = 1.063, P < 0.001), body mass index (odds ratio = 1.138, P < 0.05), hypertension (odds ratio = 3.697, P < 0.05), and the highest lactic acid within 72 h after surgery(odds ratio = 1.093, P < 0.05) were independent risk factors for poor prognosis after aortic dissection. CONCLUSION: Continuous low serum calcium was an independent predictor of poor prognosis in patients with acute type A aortic dissection.

Preoperative Nutritional Status of Infants with Non-Restricted Ventricular Septal Defect and Its Influence on Postoperative Recovery.

PURPOSE: This study described the preoperative nutritional status of infants with nonrestricted ventricular septal defects (VSDs) and evaluated its effect on postoperative recovery. METHODS: We retrospectively collected data from infants with nonrestricted VSD who received surgical treatment in our hospital from January 2020 to December 2021 and analyzed their preoperative nutritional status and postoperative recovery. RESULTS: Fifty (53.8%) patients were underweight (weight for age Z score (WAZ) ≤-1), and 31 (33.3%) patients were malnourished (WAZ ≤-2). The mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery of patients with WAZ ≤-2 were significantly longer than those of patients with WAZ >-2 (p < 0.05). The results of linear correlation analysis showed that age, WAZ and prealbumin were negatively correlated with mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery, respectively. Multiple linear regression analysis showed that mechanical ventilation time = 7.080 - 0.668 WAZ - 0.013 prealbumin - 0.618 age (R2: 0.729, F: 79.773, p: 0.001); duration of intensive care unit admission = 11.775 - 1.385 WAZ - 0.018 prealbumin - 0.102 age (R2: 0.714, F: 74.072, p: 0.001); and hospital stay time = 17.663 - 1.673 WAZ - 0.017 prealbumin - 1.07 age (R2: 0.711, F: 72.842, p: 0.001). CONCLUSION: The incidence of malnutrition in infants with nonrestricted VSD was very high, and malnutrition had a significant adverse effect on postoperative recovery. Malnutrition significantly prolonged mechanical ventilation time, duration of intensive care unit stay and hospital stay after surgery.

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study.

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ∼5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

RNA-sequencing-based detection of human viral pathogens in cerebrospinal fluid and serum samples from children with meningitis and encephalitis.

Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the Anelloviridae was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.

Online dynamic nomogram for predicting pain recurrence after microvascular decompression in trigeminal neuralgia.

Trigeminal neuralgia (TN) is one of the most common causes of facial pain. Microvascular decompression (MVD) is the first-choice surgical treatment. The present study aimed to develop a novel practical assessment system based on preoperative clinical and imaging factors for clinicians to predict the likelihood of pain recurrence following MVD in TN. A total of 56 patients with primary unilateral TN who underwent MVD were retrospectively analyzed. Patients were followed up to observe pain recurrence 1 year after MVD. An online dynamic nomogram was constructed for predicting the probability of pain recurrence after MVD in patients with TN based on multivariate logistic model. The concordance index (C-index) and receiver operating characteristic (ROC) were used to measure model discrimination. Bootstrap resampling was used for internal validation of the model and calibration curve was constructed. Decision curve analysis (DCA) was used to assess clinical applicability. Factors such as numeric rating scale (to score pain degree of patients with TN), response to neuroanalgesic drugs and neurovascular contact on magnetic resonance imaging were independent risk factors affecting the pain recurrence rate (all P<0.05). C-index was 0.973 (95%CI, 0.938-1.000) and the area under the ROC was 0.973 (95%CI, 0.938-1.000). Calibration curve with a 1,000 bootstrap resampling showed a good fit between dynamic nomogram prediction and actual observations. The DCA showed that at a threshold probability between 0 and 100%, this model can achieve a greater net benefit than if all patients had surgery or none had surgery. In conclusion, this online dynamic nomogram reliably predicted risk of pain recurrence in patients with TN following MVD.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear. AIM: To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients. METHODS: High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1. RESULTS: EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance. CONCLUSION: This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

Regulation of gasdermins in pyroptosis and cytokine release.

Gasdermins are effectors of pyroptosis downstream of diverse signaling pathways. Emerging evidence suggests that a number of post-translational modifications regulate the function of gasdermins in pyroptosis, a highly inflammatory form of cell death, and lytic or non-lytic secretion of intracellular contents. These include processing by different caspases and other proteases that may activate or suppress pyroptosis, ubiquitination by a bacterial E3 ligase that suppresses pyroptosis as an immune evasion mechanism, modifications at Cys residues in mammalian or microbial gasdermins that promote or inhibit pyroptosis, and potential phosphorylation that represses pyroptosis. Such diverse regulatory mechanisms by host and microbial proteases, ubiquitin ligases, acyltransferases, kinases and phosphatases may underlie the divergent physiological and pathological functions of gasdermins, and furnish opportunities for therapeutic targeting of gasdermins in infectious diseases and inflammatory disorders.