Per- and polyfluoroalkyl substances (PFAS) exposure in plasma and their blood-brain barrier transmission efficiency-A pilot study.

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.

Small nucleolar RNA host gene 5 plays a role in orthodontic tooth movement by inhibiting osteoclast differentiation.

BACKGROUND AND OBJECTIVES: The alveolar bone remodelling promoted by reasonable mechanical force triggers orthodontic tooth movement (OTM). The generation of osteoclasts is essential in this process. However, the mechanism of mechanical force mediating osteoclast differentiation remains elusive. Small nucleolar RNA host gene 5 (SNHG5), which was reported to mediate the osteogenic differentiation of bone marrow mesenchymal stem cells in our previous study, was downregulated in human periodontal ligament cells (hPDLCs) under mechanical force. At the same time, the RANKL/OPG ratio increased. Based on this, we probed into the role of SNHG5 in osteoclast formation during OTM and the relevant mechanism. MATERIALS AND METHODS: SNHG5 and the RANKL/OPG ratio under different compressive forces were detected by western blotting (WB) and qRT-PCR. Impact of overexpression or knockdown of SNHG5 on osteoclast differentiation was detected by qRT-PCR, WB and transwell experiments. The combination of SNHG5 and C/EBPß was verified by RNA immunoprecipitation and RNA pull-down assays. The expression of SNHG5 and osteoclast markers in gingiva were analysed by qRT-PCR and the paraffin sections of periodontal tissues were used for histological analysis. RESULTS: Compressive force downregulated SNHG5 and upregulated the RANKL/OPG ratio in hPDLCs. Overexpression of SNHG5 inhibited RANKL's expression and osteoclast differentiation. SNHG5 combined with C/EBPß, a regulator of osteoclast. The expression of SNHG5 in periodontal tissue decreased during OTM. CONCLUSION: SNHG5 inhibited osteoclast differentiation during OTM, achieved by affecting RANKL secretion, which may provide a new idea to interfere with bone resorption during orthodontic treatment.

Characteristic structures of liquid crystal monomers in EI-MS analysis and the potential application in suspect screening.

Liquid crystal monomers (LCMs) are of emerging concern due to their ubiquitous presence in indoor and outdoor environments and their potential negative impacts on human health and ecosystems. Suspect screening approaches have been developed to monitor thousands of LCMs that could enter the environment, but an updated suspect list of LCMs is difficult to maintain given the rapid development of material innovations. To facilitate suspect screening for LCMs, in-silico mass fragmentation model and quantitative structure-activity relationship (QSPR) models were applied to predict electron ionization (EI) mass spectra of LCMs. The in-silico model showed limited predictive power for EI mass spectra, while the QSPR models trained with 437 published mass spectra of LCMs achieved an acceptable absolute error of 12 percentage points in predicting the relative intensity of the molecular ion, but failed to predict the mass-to-charge ratio of the base peak. A total of 41 characteristic structures were identified from an updated suspect list of 1606 LCMs. Multi-phenyl groups form the rigid cores of 85% of LCMs and produce 154 characteristic peaks in EI mass spectra. Monitoring the characteristic structures and fragments of LCMs may help identify new LCMs with the same rigid cores as those in the suspect list.

A rare KMT2A::CBL transcript in an acute monoblastic leukemia patient with an unfavorable outcome.

BACKGROUND: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified. METHODS AND RESULTS: We report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes. CONCLUSIONS: This report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear. METHODS: We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored. RESULTS: After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100). CONCLUSIONS: Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

Promyelocytic leukemia zinc finger controls type 2 immune responses in the lungs by regulating lineage commitment and the function of innate and adaptive immune cells.

Type 2 immune responses are critical for host defense, mediate allergy and Th2-high asthma. The transcription factor, promyelocytic leukemia zinc finger (PLZF), has emerged as a significant regulator of type 2 inflammation in the lung; however, its exact mechanism remains unclear. In this review, we summarized recent findings regarding the ability of PLZF to control the development and function of innate lymphoid cells (ILCs), iNKT cells, memory T cells, basophils, and other immune cells that drive type 2 responses. We discussed the important role of PLZF in the pathogenesis of Th2-high asthma. Collectively, prior studies have revealed the critical role of PLZF in the regulation of innate and adaptive immune cells involved in type 2 inflammation in the lung. Therefore, targeting PLZF signaling represents a promising therapeutic approach to suppress Th2-high asthma.

Anti-inflammatory roles of type I interferon signaling in the lung.

Excessive or persistent inflammation may have detrimental effects on lung structure and function. Currently, our understanding of conserved host mechanisms that control the inflammatory response remains incompletely understood. In this study, we investigated the role of type I interferon signaling in the inflammatory response against diverse clinically relevant stimuli. Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. The elevated inflammatory response in IFNAR1-/- mice was manifested as elevated myeloid cells, such as macrophages and neutrophils, in the bronchoalveolar lavage. The inflammatory cell response in the IFNAR1-/- mice persisted to 14 days and there is impaired recovery and fibrotic remodeling of the lung in IFNAR1-/- mice after bleomycin injury. In the Pseudomonas infection model, the elevated inflammatory cell response led to improved bacterial clearance in IFNAR1-/- mice, although there was similar lung injury and survival. We performed RNA sequencing of lung tissue in wild-type and IFNAR1-/- mice after LPS and bleomycin injury. Our unbiased analysis identified differentially expressed genes between IFNAR1-/- and wild-type mice, including previously unknown regulation of nucleotide-binding oligomerization domain (NOD)-like receptor signaling, retinoic acid-inducible gene-I (RIG-I) signaling, and necroptosis pathway by type I interferon signaling in both models. These data provide novel insights into the conserved anti-inflammatory mechanisms of the type I interferon signaling.NEW & NOTEWORTHY Type I interferons are known for their antiviral activities. In this study, we demonstrate a conserved anti-inflammatory role of type I interferon signaling against diverse stimuli in the lung. We show that exacerbated inflammatory response in the absence of type I interferon signaling has both acute and chronic consequences in the lung including structural changes.

Interference Morphology of Free-Growing Tendrils and Application of Self-Locking Structures.

Organisms can adapt to various complex environments by obtaining optimal morphologies. Plant tendrils evolve an extraordinary and stable spiral morphology in the free-growing stage. By combining apical and asymmetrical growth strategies, the tendrils can adjust their morphology to wrap around and grab different supports. This phenomenon of changing tendril morphology through the movement of growth inspires a thoughtful consideration of the laws of growth that underlie it. In this study, tendril growth is modeled based on the Kirchhoff rod theory to obtain the exact morphological equations. Based on this, the movement patterns of the tendrils are investigated under different growth strategies. It is shown that the self-interference phenomenon appears as the tendril grows, allowing it to hold onto its support more firmly. In addition, a finite element model is constructed using continuum media mechanics and following the finite growth theory to simulate tendril growth. The growth morphology and self-interference phenomenon of tendrils are observed visually. Furthermore, an innovative class of fluid elastic actuators is designed to verify the growth phenomena of tendrils, which can realize the wrapping and locking functions. Several experiments are conducted to measure the end output force and the smallest size that can be clamped, and the output efficiency of the elastic actuator and the optimal working pressure are verified. The results presented in this study could reveal the formation law of free tendril spiral morphology and provide an inspiring idea for the programmability and motion control of bionic soft robots, with promising applications in the fields of underwater rescue and underwater picking.

Relapsed/Refractory Peripheral T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis With UNC13D and CD27 Germline Mutations.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms. Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as CD27 and UNC13D and other germline heterozygous variants (NOTCH2, NOTCH3, IL2RA, TYK2, AGL, CFD, and F13A1). CD107a analyses consistently demonstrated impaired degranulation of cytotoxic T-lymphocytes and natural killer (NK) cells. Examination of the patient's family pedigree revealed that his father and mother harbored UNC13D and CD27 mutations, respectively; his brother carried the same CD27 heterozygous mutation. However, none of them manifested the disease. Despite the missense mutation of CD27 (c.779C>T; p.Pro260Leu) lacking previous documentation in databases, comprehensive analysis suggested non-pathogenic mutations in the CD27 variant, indicating minimal impact on T- and NK-cell functions. These results ultimately supported the option of hematopoietic stem cell transplantation (HSCT) as a successful curative therapeutic approach. As of this report, the patient has remained free of lymphoma and quiescent HLH 15.2 months post-HSCT. This study underscores the efficacy of genetic tests in identifying significant mutations and confirming their etiologies, providing an early basis for treatment decisions and the selection of suitable transplant donors.

The Impact of Parental Myopia and High Myopia on the Hyperopia Reserve of Preschool Children.

INTRODUCTION: The aim of this study was to explore the association between parental myopia and high myopia with children's refraction and ocular biometry in large-scale Chinese preschool children from the Beijing Hyperopia Reserve Study. SUBJECTS/METHODS: This cross-sectional kindergarten-based study enrolled children aged 3-6 years. Cycloplegic refraction, axial length (AL), and corneal radius (CR) were measured for all children. Parents were asked to complete a questionnaire about refractive status (no myopia, mild myopia <-3 D, moderate myopia ≥-3 D and ≤-6, and high myopia >-6 D). RESULTS: The study enrolled 2,053 children (1,069 boys and 984 girls), with a mean age of 4.26 ± 0.96 years and mean spherical equivalent refraction (SER) of 1.11 ± 0.97 diopter. Of the children, 90.7% had at least one myopic parent, and 511 children (24.9%) had at least one highly myopic parent. SER decreased significantly with increasing severity of parental myopia (p < 0.001). Preschool children's myopia was independently associated with parental myopia (OR, 10.4 and 11.5 for one and two highly myopic parent[s]). Age (OR = 1.1), gender (OR = 1.7; girls as references), near work time (OR = 1.2), and both maternal (OR, 1.4 and 2.0 for moderate and high myopia) and paternal myopia (OR, 1.6 and 1.9 for moderate and high myopia) were independent risk factors for lacking hyperopia reserve. CONCLUSION: Severe parental myopia was associated with a lower SER, longer AL, and higher AL/CR ratio in preschool children. Parental myopia and near work may predispose children to faster elimination of hyperopia reserves before exposure to higher educational stress.

Pancreatic Cancer: An Exocrine Tumor with Endocrine Characteristics.

OBJECTIVE: To examine the characteristics of pancreatic cancer patients with long-term survival. BACKGROUND: Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified. METHODS: An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤ 37 U/mL) subgroup. RESULTS: A normal A19-9 level was an independent variable for overall survival (median survival, 18.1 vs. 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs. 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose (P < 0.001) and increased expression of insulin (P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients. CONCLUSIONS: CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.

Hydrogel-based molecular tension fluorescence microscopy for investigating receptor-mediated rigidity sensing.

Extracellular matrix (ECM) rigidity serves as a crucial mechanical cue impacting diverse biological processes. However, understanding the molecular mechanisms of rigidity sensing has been limited by the spatial resolution and force sensitivity of current cellular force measurement techniques. Here we developed a method to functionalize DNA tension probes on soft hydrogel surfaces in a controllable and reliable manner, enabling molecular tension fluorescence microscopy for rigidity sensing studies. Our findings showed that fibroblasts respond to substrate rigidity by recruiting more force-bearing integrins and modulating integrin sampling frequency of the ECM, rather than simply overloading the existing integrin-ligand bonds, to promote focal adhesion maturation. We also demonstrated that ECM rigidity positively regulates the pN force of T cell receptor-ligand bond and T cell receptor mechanical sampling frequency, promoting T cell activation. Thus, hydrogel-based molecular tension fluorescence microscopy implemented on a standard confocal microscope provides a simple and effective means to explore detailed molecular force information for rigidity-dependent biological processes.

HLA Fully-Mismatched Sibling-Derived CD7 CAR-T Therapy Bridging to Haploidentical Hematopoietic Stem Cell Transplantation for Hepatosplenic γδ T-cell Lymphoma.

While chimeric antigen receptor (CAR)-T-cell therapy has demonstrated remarkable effectiveness in the treatment of B-cell lymphomas and leukemias, research on T-cell malignancies is still limited. Here, we reported a patient with hepatosplenic γδ T-cell lymphoma refractory to multiple lines of chemotherapy, who eventually achieved first complete remission with flow cytometry-confirmed minimal residual disease negativity after human leukocyte antigen (HLA) fully-mismatched sibling-derived CD7 CAR-T therapy. However, given the allogeneic nature, CAR-T cells dropped rapidly after a peak of 83.4% of circulating T-cells. Cytokine release syndrome, cytopenia, and infections occurred but were manageable after treatments. After the consolidative haploidentical hematopoietic stem cell transplantation (HSCT), the patient remained in remission at the end of the follow-up (13 months post-CAR-T infusion). This is the first case of relapsed/refractory hepatosplenic γδ T-cell lymphoma who achieved lasting CR after HLA fully-mismatched sibling-derived CD7 CAR-T therapy bridging to haploidentical HSCT.

Systems pharmacology approach to explore the mechanisms of shufeng Jiedu Capsule on treating H1N1 infection.

BACKGROUND: Influenza caused by the H1N1 virus still affects human health. There is currently no effective strategy against H1N1 virus infection. The present study is to evaluate the mechanism of Shufeng Jiedu Capsule (SFJDC) in the treatment of H1N1 infection using an integrated systems pharmacology approach and experimental validation. SFJDC is recommended for the treatment of H1N1 infection in traditional Chinese medicine (TCM), whose mechanism of action is not precise. METHODS: We systematically analyzed SFJDC using a systematic pharmacology and ADME screening model, and predicted effective targets using systematic drug targeting (SysDT) algorithm. Subsequently, the network of interactions between compounds and targets was built to help in the discovery of new drugs. In addition, the pathway of molecular action was determined by using enrichment analysis from the predicted targets. what is more, molecular docking also applied to predict the specific binding sites and binding capacity of active compounds and related targets, which validated the results of the compounds-targets network (C-T network). Finally, the mechanism of SFJDC effect on autophagy and virus replication in H1N1 virus-infected RAW264.7 mouse macrophage cells was experimentally verified. RESULTS: The systematic pharmacology results suggested that 68 candidate compounds were obtained from SFJDC, which interacted with 74 different targets related to inflammation and the immune system. The CCK-8 results showed that different concentrations of SFJDC serum had no significant inhibitory effect on the viability of RAW264.7 cells. LC3-II was significantly increased after virus infection compared to the control group, while it was inhibited by different concentrations of SFJDC serum. H1N1 virus nucleocapsid protein (NP protein) was significantly reduced in the high concentration group, Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), and viral M1 gene were significantly reduced compared to the H1N1 group. CONCLUSIONS: The integrated systemic pharmacological approach and experimental validation not only provide a precise explanation of the molecular mechanism of SFJDC in the treatment of H1N1 infection but also provide valuable clues for the development of novel drug strategies to control the H1N1 infection.

Characterization of quinoa starch nanoparticles as a stabilizer for oil in water Pickering emulsion.

Quinoa starch nanoparticles (QSNPs) prepared by nanoprecipitation had a uniform particle size of 191.20 nm. QSNPs with amorphous crystalline structure had greater contact angle than QS with orthorhombic crystalline structure, which can therefore be utilized to stabilize Pickering emulsions. QSNPs-based Pickering emulsions prepared by suitable formulations (QSNPs concentration of 2.0-2.5 %, oil volume fraction of 0.33-0.67) exhibited good stability against pH of 3-9 and ionic strength of 0-200 mM. The oxidative stability of the emulsions increased with increasing starch concentration and ionic strength. Microstructural and rheological results indicated that the structure of the starch interfacial film and the thickening effect of the water phase affected the emulsion stability. The emulsion had excellent freeze-thaw stability and can be produced as a re-dispersible dry emulsion using the freeze-drying technique. These results implied that the QSNPs had great potential for application in the preparation of Pickering emulsions.

Retrospective analysis of cataract surgery outcomes in China from 2009 to 2018: from a national registry system data.

OBJECTIVE: To evaluate patients' benefits after cataract surgery and to form recommendations for Chinese national health policy decision makers and administration departments based on the quality of cataract treatments. METHOD: An observational study based on real-world data source from the National Cataract Recovery Surgery Information Registration and Reporting System. RESULTS: A total of 14 157 463 original records were reported from 1 July 2009 to 31 December 2018. The factors that influenced the 3-day postsurgical best-corrected visual acuity (BCVA), the primary outcome, were analysed by logistic regression analysis. We found that a history of hypertension (OR=0.916) or diabetes (OR=0.912), presurgical pupil abnormality (OR=0.571) and high intraocular pressure (OR=0.578) were harmful to the postsurgical BCVA improvement (BCVA ≥6/20), while male sex (OR=1.113), better presurgical BCVA level (OR=5.996 for ≥6/12-<6/7.5 and OR=2.610 for >6/60-<6/12 taken ≤6/60 as reference), age-related cataract (OR=1.825) and intraocular lens implantation (OR=1.886) were statistically beneficial to the postsurgical BCVA improvement. Compared with extracapsular cataract extraction (ECCE) with large incision, the ECCE with small incision (OR value=1.810) and the phacoemulsification (OR=1.420) significantly improved the benefit probability. CONCLUSION: ECCE with small incision has comparable effects on postsurgical BCVA improvement of phacoemulsification. Therefore, ECCE could be an alternative cataract surgical treatment in economically underdeveloped areas in China, provided the surgeons are adequately trained.

Enrichment of Circulating Tumor Cells of Lung Cancer and Correlation With Serum Leukomonocyte and Tumor Biomarkers: A Retrospective Study.

STUDY DESIGN: Circulating tumor cells is important in the clinical diagnosis of cancer and there are a number of circulating tumor cell detection systems associated with different isolation strategies being validated. There is a novel platform, the CytoBot 2000, which utilizes a combination of physical and immunological technologies to isolate and capture circulating tumor cells. METHODS: In this retrospective study, 39 lung cancer patients and 11 normal healthy individuals were enrolled and performed circulating tumor cell tests and immunofluorescence staining with CytoBot 2000. The performance of this device was assessed by receiver operating characteristic curve. The clinical relevance of circulating tumor cells was assessed by Chi-square. The correlations between circulating tumor cell number and blood lymphocytes and tumor biomarkers were analyzed by Pearson correlation coefficient. RESULTS: The number of circulating tumor cell is significantly increased in lung cancer patients (3.74 > 0.45, P < .0001). The CytoBot 2000 presented a 100% (39/39) circulating tumor cell detection rate in lung cancer patients and 36% (4/11) in healthy individual blood samples, the sensitivity and specificity were 89.7% and 90.9%, respectively, and with the area under curve of 0.966. Further, there was a positive correlation between circulating tumor cell count and carcinoembryonic antigen 211 (R2 = 0.125, P = .027), but not blood lymphocytes (P = .089). CONCLUSIONS: This automatic platform showed excellent performance of circulating tumor cell detection by clinical sample. The tumor biomarkers increased with the number of circulating tumor cell in the lung cancer patients.

Effect of muscle activation on dynamic responses of neck of pilot during emergency ejection: a finite element study.

To determine the effect of muscle activation on the dynamic responses of the neck of a pilot during simulated emergency ejections. A complete finite element model of the pilot's head and neck was developed and dynamically validated. Three muscle activation curves were designed to simulate different activation times and levels of muscles during pilot ejection: A is the unconscious activation curve of the neck muscles, B is the pre-activation curve, and C is the continuous activation curve. The acceleration-time curves obtained during ejection were applied to the model, and the influence of the muscles on the dynamic responses of the neck was investigated by analyzing both angles of rotation of the neck segments and disc stresses. Muscle pre-activation reduced fluctuations in the angle of rotation in each phase of the neck. Continuous muscle activation caused a 20% increase in the angle of rotation compared to pre-activation. Moreover, it resulted in a 35% increase in the load on the intervertebral disc. The maximum stress on the disc occurred in the C4-C5 phase. Continuous muscle activation increased both the axial load on the neck and the posterior extension angle of rotation of the neck. Muscle pre-activation during emergency ejection has a protective effect on the neck. However, continuous muscle activation increases the axial load and rotation angle of the neck. A complete finite element model of the pilot's head and neck was established and three neck muscle activation curves were designed to investigate the effects of muscle activation time and level on the dynamic response of the pilot's neck during ejection. This increased insights into the protection mechanism of neck muscles on the axial impact injury of the pilot's head and neck.

Transfer of miR-4755-5p through extracellular vesicles and particles induces decitabine resistance in recipient cells by targeting CDKN2B.

Decitabine (5-aza-2-deoxycytidine, DAC), a DNA-hypomethylating agent, has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome and acute myeloid leukemia, but DAC-resistance often occurs and leads to treatment failure. Therefore, elucidating the mechanisms of DAC resistance is important for improving its therapeutic efficacy. The extracellular vesicles and particles (EVPs) have been reported to be involved in mediating drug resistance by transporting diverse bioactive components. In this study, we established the DAC-resistant cell line (KG1a-DAC) from its parental human leukemia-derived cell line KG1a and observed that EVPs released from KG1a-DAC can promote DAC-resistant in KG1a cells. Moreover, treatment with KG1a-DAC EVPs reduced the expression of cyclin-dependent kinase inhibitor 2B (CDKN2B) in KG1a cells. miRNA-Seq analysis revealed that miR-4755-5p is overexpressed in EVPs from KG1a-DAC. Dual-luciferase reporter assay and flow cytometry analysis confirmed that miR-4755-5p rendered KG1a cells resistant to the DAC by targeting CDKN2B gene. Taken together, miR-4755-5p in EVPs released from the DAC-resistant cells plays an essential role in inducing DAC-resistance, and is a potential therapeutic target for suppression of DAC resistance.