Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/p53 signaling pathway.

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Efficacy and safety of robotic vs. laparoscopic gastrectomy for patients with gastric cancer: systematic review and meta-analysis.

BACKGROUND: The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer is still unclear but increasingly drawing attention. MATERIALS AND METHODS: In this systematic review and meta-analysis, we searched the PubMed, EMBASE, Web of Science, and Cochrane Library as of January 20, 2024 and referenced list of eligible articles for all published studies comparing RG and LG for patients with gastric cancer, Data on study characteristics, individual characteristics, and outcome parameters were extracted. The quality of studies was assessed using the Revised Cochrane risk-of-bias 2 tool and the risk of bias in non-randomized studies of interventions tool. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 3641 articles, of which 72 studies (30081 patients) were included in the meta-analysis. Compared with LG, RG was associated with higher OS [hazard ratio (HR)=0.89, 95% CI=0.83 to 0.96), lower rate of overall postoperative complications [odds ratio (OR)=0.77, 95% CI=0.71 to 0.84], longer operating time [mean difference (MD)=35.53, 95% CI=29.23 to 41.83], less estimated blood loss (MD=-37.45, 95% CI=-46.24 to -28.67), a higher number of retrieved lymph nodes (MD=1.88, 95% CI=0.77 to 3.00), faster postoperative recovery, and lower rate of conversion (OR=0.44, 95% CI=0.36 to 0.55). Mortality and DFS were not significantly different between the two groups. The subgroup of meta-analysis results also showed the advantages of robotic surgery over laparoscopic surgery in intracorporeal reconstruction, total gastrectomy, Ⅰ/Ⅱ stage, and BMI≥25, especially for patients with stage Ⅰ/Ⅱ, there is better overall survival and disease-free survival. CONCLUSION: Our findings point to robotic surgery having great benefits compared with laparoscopic surgery in gastric cancer. Our study may help inform decision-making in applying robotic surgical systems to clinical treatment.

Enhanced Recovery Protocol Versus Conventional Care in Patients Undergoing Esophagectomy for Cancer: Advantages in Clinical and Patient-Reported Outcomes.

BACKGROUND: This study was designed to compare the clinical and patient-reported outcomes (PROs) between the enhanced recovery after surgery (ERAS) protocol and conventional care in patients undergoing esophagectomy for cancer, which have not previously been compared. METHODS: This single-center retrospective study included prospective PRO data from August 2019 to June 2021. Clinical outcomes included perioperative complications and postoperative length of stay (PLOS). Patient-reported outcomes were assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and esophagus-specific module (QLQ-OES18) preoperatively to 6 months postoperatively. Mixed-effects models were used to longitudinally compare quality of life (QOL) scores between the two modes. RESULTS: Patients undergoing conventional care and ERAS were analyzed (n = 348 and 109, respectively). The ERAS group had fewer overall complications, pneumonia, arrhythmia, and a shorter PLOS than the conventional group, and outperformed the conventional group in five functional QLQ-C30 domains and five symptom QLQ-OES18 domains, including less dysphagia (p < 0.0001), trouble talking (p = 0.0006), and better eating (p < 0.0001). These advantages persisted for 3 months postoperatively. For the cervical circular stapled anastomosis, the initial domains and duration of benefit were reduced in the ERAS group. CONCLUSIONS: The ERAS protocol has significant advantages over conventional care in terms of clinical outcomes, lowering postoperative symptom burden, and improving functional QOL in patients who have undergone esophagectomy. Selection of the optimal technique for cervical anastomosis is a key operative component of ERAS that maintains the symptom domains and duration of the advantages of PROs.

The role of adenoid immune phenotype in polysensitized children with allergic rhinitis and adenoid hypertrophy.

BACKGROUND: There is increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children with AH and AR remains unclear. METHODS: Patients aged 2-8 years (recruited from January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size, and respiratory viral infection history. The serum total immunoglobulin E (IgE) and specific IgE levels were measured, and flexible nasal endoscopy was performed. The relationship between AH, aeroallergen sensitization patterns, and lymphocyte subpopulations in adenoid samples was analyzed using flow cytometry. RESULTS: In total, 5281 children were enrolled (56.5% with AR; and 48.6% with AH). AH was more prevalent in children with AR. Compared to nonsensitized individuals, those polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95% CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in adenoidectomy patients. The percentages and corrected absolute counts of regulatory T (Treg) cells, activated Tregs, class-switched memory B cells (CSMBs), natural killer (NK) T cells, and NK cell subpopulations were reduced in the adenoid tissues of children with both AH and AR (AH-AR) compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB percentages. CONCLUSION: Polysensitivity to molds is associated with an increased risk of AH in children with AR. Fewer B cells, NK cells, and Treg cells with an effector/memory phenotype were detected in the adenoids of AR children, and these lower percentages of immune cells, particularly CSMBs, were closely linked to aeroallergen sensitization models and respiratory viral infection.

Akkermansia muciniphila ameliorates colonic injury in mice with DSS-induced acute colitis by blocking macrophage pro-inflammatory phenotype switching via the HDAC5/DAB2 axis.

Akkermansia muciniphila (A. muciniphila), a probiotic, has been linked to macrophage phenotypic polarization in different diseases. However, the role and mechanisms of A. muciniphila in regulating macrophage during ulcerative colitis (UC) are not clear. This research aimed to examine the impact of A. muciniphila on dextran sulfate sodium (DSS)-induced acute colitis and elucidate the underlying mechanism related to macrophage phenotypic polarization. A. muciniphila inhibited weight loss, increased disease activity index, and ameliorated inflammatory injury in colonic tissues in mice induced with DSS. Furthermore, A. muciniphila reduced macrophage M1 polarization and ameliorated epithelial barrier damage in colonic tissues of DSS-induced mice through inhibition of histone deacetylase 5 (HDAC5). In contrast, the effect of A. muciniphila was compromised by HDAC5 overexpression. HDAC5 deacetylated H3K9ac modification of the disabled homolog 2 (DAB2) promoter, which led to repressed DAB2 expression. DAB2 overexpression blocked HDAC5-induced pro-inflammatory polarization of macrophages, whereas knockdown of DAB2 resulted in the loss of effects of A. muciniphila against colonic injury in DSS-induced mice. Taken together, A. muciniphila-induced loss of HDAC5 hampered the deacetylation of DAB2 and enhanced the expression of DAB2. Our findings propose that A. muciniphila may be a possible probiotic agent for alleviating DSS-induced acute colitis.

Effect of smoking cessation medications on intracranial aneurysm risk: A Mendelian randomization study.

INTRODUCTION: We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. METHODS: Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. RESULTS: Cigarettes smoked per day (OR=2.89; 95% CI:1.85-4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64-8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10-2.8) and smoking cessation (OR=6.80; 95% CI: 0.01-4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/day could be a main mediator of HYKK's effect on IA risk. CONCLUSIONS: This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

Droplet digital PCR: An effective method for monitoring and prognostic evaluation of minimal residual disease in JMML.

Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)-monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1- to 3-month window post-HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post-HSCT was observed, as 65% (13/20) of non-relapse patients took over 6 months to achieve ddPCR-MRD negativity. Furthermore, bone marrow ddPCR-MRD levels at 1-month post-HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR-MRD levels at this time point (p = 0.026), with a cut-off of 0.465% effectively stratifying overall survival (p = 0.007), event-free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR's superiority in JMML MRD monitoring post-HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML.

Ultrahigh-Q Polarization-Independent Terahertz Metamaterial Absorber Using Pattern-Free Graphene for Sensing Applications.

In contrast to noble metals, graphene exhibits significantly lower loss, especially useful for optical sensing applications that require ultrahigh Q factors, and offer wide range tunability via an adjustable Fermi level. However, precise graphene patterning is difficult, especially for large areas, severely limiting its applications. Here, a tunable terahertz metamaterial absorber (TMMA) with ultrahigh Q factors consisting of a continuous, pattern-free graphene is demonstrated. A graphene sheet is overlaid on an Al metal array, forming a structure that supports strong localized surface plasmon polaritons (LSPPs) with fields tightly confined in the graphene, minimizing loss. Theoretical results show that this TMMA exhibits an ultrahigh Q factor of 1730, a frequency sensitivity of 2.84 THz/RIU, and an excellent figure of merit (FoM) of 365.85 RIU-1, independent of polarization. A tunability from ~2.25 to ~3.25 THz is also achieved by tuning Ef of graphene from 0.3 to 0.7 eV. The proposed graphene-based TMMA holds many potential applications, particularly in the field of sensing.

Concave Version Printing of High-Performance Polymer THz Filters.

The development of high Q and tunable narrowband filters that can efficiently manipulate THz beams is critical for various THz applications, such as imaging and sensing. However, for filters made of metals and dielectrics, issues such as high losses, limited tunability, and lengthy process flows exist. Here, a scalable concave version reprinting technique to mass produce high-performance microstructured polymer filters is presented. The technique is extremely simple, eliminating the demand for the use of any large equipment including injection molding and thermal press printing machines, and is reliable; in the reprinted structures, there are no defects including gaps and air bubbles. The produced narrowband filters exhibit a high Q factor of 57 with wide tunability over the THz band from ∼80 to 160 µm in wavelength. The presented technique can be adopted to realize other devices as well using polymer materials with simplicity and high precision.

Esophageal cancer screening, early detection and treatment: Current insights and future directions.

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease.

Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687.

Light sheet fluorescence microscopy with active optical manipulation.

We present a light sheet fluorescence microscopy (LSFM) with active optical manipulation by using linear optical tweezers (LOTs). In this method, two coaxially transmitting laser beams of different wavelengths are shaped using cylindrical lenses to form a linear optical trapping perpendicular to the optical axis and an excitation light sheet (LS) parallel to the optical axis, respectively. Multiple large-sized polystyrene fluorescent microspheres are stably captured by LOTs, and their rotation angles around specific rotation axes are precisely controlled. During a sample rotation, the stationary excitation LS scans the sample to obtain fluorescence sectioning images of the sample at different angles.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Dynamic speckle illumination wide-field fluorescence microscopy with actively optical manipulation of rotational angles.

We present a dynamic speckle illumination wide-field fluorescence microscopy (DSIWFM) combined with a line optical tweezers (LOTs) for rotational fluorescence sectioning imaging. In this method, large polystyrene fluorescent microspheres are stably trapped with LOTs, and precisely manipulated to rotate around a specific rotation axis. During the rotation process, multiple raw fluorescence images of trapped microspheres are obtained with dynamic speckle illumination. The root-mean-square (RMS) algorithm is used to extract the drastically changing fluorescent signals in the focal plane to obtain the fluorescence sectioning images of the samples at various angles. The influence of speckle granularity on the image quality of fluorescence sectioning images is experimentally analyzed. The rotational fluorescence sectioning images obtained by DSIWFM with LOTs could provide an alternative technique for applications of biomedical imaging.

[Diagnosis of a Chinese pedigree affected with Treacher-Collins syndrome due to a novel variant of TCOF1 gene through whole exome sequencing].

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Treacher-Collins syndrome (TCS) through whole exome sequencing (WES). METHODS: A TCS pedigree which was diagnosed at the Women and Children's Hospital Affiliated to Qingdao University on February 5, 2020 was selected as the study subject. Following collection of clinical data, WES was carried out. Candidate variant was validated through Sanger sequencing and bioinformatic analysis. RESULTS: The WES results showed that the proband has harbored a heterozygous c.3337C>T variant of the TCOF1 gene, and Sanger sequencing confirmed that his mother and brother also carried the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.3337C>T variant of the TCOF1 gene probably underlay the pathogenesis of TCS in this pedigree.

VirGrapher: a graph-based viral identifier for long sequences from metagenomes.

Viruses are the most abundant biological entities on earth and are important components of microbial communities. A metagenome contains all microorganisms from an environmental sample. Correctly identifying viruses from these mixed sequences is critical in viral analyses. It is common to identify long viral sequences, which has already been passed thought pipelines of assembly and binning. Existing deep learning-based methods divide these long sequences into short subsequences and identify them separately. This makes the relationships between them be omitted, leading to poor performance on identifying long viral sequences. In this paper, VirGrapher is proposed to improve the identification performance of long viral sequences by constructing relationships among short subsequences from long ones. VirGrapher see a long sequence as a graph and uses a Graph Convolutional Network (GCN) model to learn multilayer connections between nodes from sequences after a GCN-based node embedding model. VirGrapher achieves a better AUC value and accuracy on validation set, which is better than three benchmark methods.

Idiopathic multicentric Castleman disease (iMCD)-idiopathic plasmacytic lymphadenopathy: A distinct subtype of iMCD-not otherwise specified with different clinical features and better survival.

Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD-thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD-not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD-NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed-type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD-NOS identified 103 (45.2%) patients with iMCD-IPL. The clinical features and outcomes of patients with iMCD-IPL and iMCD-NOS without IPL were compared. Patients with iMCD-IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non-severe patients in the iMCD-IPL group according to the CDCN severity classification. Compared with lymphoma-like treatments, multiple myeloma-like and IL-6-blocking treatment approaches in the iMCD-IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD-IPL and suggest that it should be considered a new subtype of iMCD-NOS.