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Sleep insufficiency is associated with various disorders; the molecular basis is unknown until now. Here, 14 males and 18 females were subjected to short-term (24 h) sleep deprivation, and donated fasting blood samples prior to (day 1) and following (days 2 and 3) short-term sleep deprivation. We used multiple omics techniques to examine changes in volunteers' blood samples that were subjected to integrated, biochemical, transcriptomic, proteomic, and metabolomic analyses. Sleep deprivation caused marked molecular changes (46.4% transcript genes, 59.3% proteins, and 55.6% metabolites) that incompletely reversed by day 3. The immune system in particular neutrophil-mediated processes associated with plasma superoxidase dismutase-1 and S100A8 gene expression was markedly affected. Sleep deprivation decreased melatonin levels and increased immune cells, inflammatory factors and c-reactive protein. By disease enrichment analysis, sleep deprivation induced signaling pathways for schizophrenia and neurodegenerative diseases enriched. In sum, this is the first multiomics approach to show that sleep deprivation causes prominent immune changes in humans, and clearly identified potential immune biomarkers associated with sleep deprivation. This study indicated that the blood profile following sleep disruption, such as may occur among shift workers, may induce immune and central nervous system dysfunction.
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Introduction: Traditional DBS is usually conducted under local anesthesia (LA) which is intolerable to some patients, DBS under general anesthesia (GA) was opted to extended surgical indication. This study aimed to compare the efficacy and safety of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) under asleep and awake anesthesia state in 1-year postoperative follow-up. Methods: Twenty-one PD patients were assigned to asleep group and 25 patients to awake group. Patients received bilateral STN-DBS under different anesthesia state. The PD participants were interviewed and assessed preoperatively and at 1-year postoperative follow-up. Results: At 1-year follow-up, compared surgical coordinate in two groups, the left-side Y of asleep group showed more posterior than awake group (Y was-2.39 ± 0.23 in asleep group, -1.46 ± 0.22 in awake group, p = 0.007). Compared with preoperative OFF MED state, MDS-UPDRS III scores in OFF MED/OFF STIM state remained unchanged, while in OFF MED/ON STIM state were significantly improved in awake and asleep groups, yet without significant difference. Compared with preoperative ON MED state, MDS-UPDRS III scores in ON MED/OFF STIM, and ON MED/ON STIM state remained unchanged in both groups. In non-motor outcomes, PSQI, HAMD, and HAMA score significantly improved in asleep group compared to awake group at 1-year follow-up (PSQI, HAMD, and HAMA score in 1-year follow-up were 9.81 ± 4.43; 10.00 ± 5.80; 5.71 ± 4.75 in awake group, 6.64 ± 4.14; 5.32 ± 3.78; 3.76 ± 3.87 in asleep group, p = 0.009; 0.008; 0.015, respectively), while there was no significant difference in PDQ-39, NMSS, ESS, PDSS score, and cognitive function. Anesthesia methods was significantly associated with improvement of HAMA and HAMD score (p = 0.029; 0.002, respectively). No difference in LEDD, stimulation parameters and adverse events was observed between two groups. Discussion: Asleep STN-DBS may be considered a good alternative method for PD patients. It is largely consistent with awake STN-DBS in motor symptoms and safety. Yet, it showed higher improvement in terms of mood and sleep compared to awake group at 1-year follow-up.
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Wiegand wires are unique ferromagnetic materials that display rapid magnetization reversal and a large Barkhausen jump under an applied field. This stable reversal can be used to induce a periodic pulse voltage in a pickup coil wrapped around the Wiegand wire. To unlock the full potential of Wiegand wires for magnetic sensors and devices, the magnetic structure and magnetization state of the Wiegand wire must be fully elucidated. In this study, hysteresis loops were used to reveal the magnetic structure of Wiegand wires. Wiegand wires of different diameters magnetized under different applied magnetic field strengths were analyzed in detail. Our results show that Wiegand wires 0.06 mm in diameter are composed solely of a hard magnetic core. Wiegand wires above 0.10 mm in diameter have a hard magnetic core, a middle layer, and a soft layer that decreases in thickness but increases in coercivity as the wire diameter decreases. Then, theoretical models were built to predict the magnetic structure of Wiegand wires under an applied field for the first time. The magnetization process of Wiegand wires with different diameters under different applied magnetic fields was also analyzed.
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Fighting intracellular bacteria with strong antibiotics evading remains a long-standing challenge. Responding to and regulating the infectious microenvironment is crucial for treating intracellular infections. Sophisticated nanomaterials with unique physicochemical properties exhibit great potential for precise drug delivery towards infection sites, along with modulating infectious microenvironment via their instinct bioactivity. In this review, we first identify the key characters and therapeutic targets of intracellular infection microenvironment. Next, we illustrate how the nanomaterials physicochemical properties, such as size, charge, shape and functionalization affect the interaction between nanomaterials, cells and bacteria. We also introduce the recent progress of nanomaterial-based targeted delivery and controlled release of antibiotics in intracellular infection microenvironment. Notably, we highlight the nanomaterials with unique intrinsic properties, such as metal toxicity and enzyme-like activity for the treatment of intracellular bacteria. Finally, we discuss the opportunities and challenges of bioactive nanomaterials in addressing intracellular infections.
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Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.
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ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. AIM OF THE STUDY: To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. MATERIALS AND METHODS: Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. RESULTS: Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. CONCLUSION: Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.
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Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , PPAR gama/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Quercetina/metabolismo , Leucócitos Mononucleares/metabolismo , Camundongos Endogâmicos C57BL , Colo , Colite/tratamento farmacológico , Macrófagos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Fator de Transcrição STAT1/metabolismoRESUMO
Guanylate binding protein 5 (GBP5) is a member of the interferon (IFN)-inducible large guanosine triphosphate hydrolases (GTPase) family that regulates cell-autonomous immunity and malignant tumor transformation. However, its specific roles and underlying mechanisms GBP5 in gastric cancer (GC) remain unknown. In this study, we aimed to determine the role GBP5 and underlying mechanism of GBP5 in GC cell progression. Potential oncogenic roles of GBP5 in GC as well as its relationship with the tumor immune microenvironment (TIME) were comprehensively evaluated using bioinformatics analysis. Protein expression levels of GBP5 and their correlation with clinicopathological features of patients were assessed using immunohistochemistry. In addition, diverse in vitro functional experiments were performed to identify the functions of GBP5 in GC. Downstream targets of GBP5 were identified using RNA-sequencing analysis and verified using western blotting or quantitative polymerase chain reaction analysis in different cell lines. GBP5 expression is commonly upregulated and promotes the proliferation and migration of GC cells. Mechanistically, GBP5 was regulated by the IFNγ-Janus kinase (JAK1)-signal transducer and activator of transcription 1 (STAT1) axis and induced CXCL8 expression. Interestingly, GBP5-induced CXCL8 regulated the JAK1-STAT1 signaling pathway to form a positive feedback loop. Moreover, GBP5 is closely related to the TIME and may be used as a biomarker for predicting the efficacy of immunotherapy. Our findings revealed a new JAK1-STAT1/GBP5/CXCL8 pathway and highlighted the value of GBP5 as a predictive biomarker and novel target for GC intervention.
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OBJECTIVES: Pancreatic trauma and subsequent pancreatic operation result in early pathophysiologic alterations. Understanding changes in energy expenditure and body composition is essential for optimal management. This study aims to observe changes in energy expenditure and body composition in patients during the early postoperative days (PODs) after pancreatic trauma. METHODS: This is a retrospective review of patients who underwent surgery for blunt pancreatic trauma in a single trauma center. Data of body composition by bioimpedance spectroscopy and energy expenditure by indirect calorimetry were collected and analyzed in patients during the early PODs. The association of body composition parameters with major complications was analyzed. RESULTS: Forty-one patients were included. Compared with POD-3, the total body water, extracellular water, fat-free mass, and skeletal muscle mass on POD-7 and -14 decreased significantly (all P < 0.05). The phase angle (PhA) increased significantly from POD-3 to -14 (P < 0.05). Resting energy expenditure was significantly higher than predicted and remained high throughout the study period. Over the 14-d study period, delivered energy was escalated to the level of resting energy expenditure. The PhA was significantly lower in patients with severe morbidity than in those without (3.6 [3.3-4.2] versus 4.5 [4.2-5.0]; P < 0.001). A multivariate analysis found that PhA was the independent variable for severe complications, with an odds ratio of 0.069 (95% CI, 0.011-0.427; P = 0.004). The predictive ability of PhA revealed an area under the receiver operating characteristic curve of 0.837, with an optimal threshold of 4.23. CONCLUSIONS: Changes in body composition and hypermetabolism state were observed from POD-3 to -14 after pancreatic trauma. A postoperative value of PhA < 4.23 is associated with severe complications.
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The purpose of this study was to introduce the surgical process of Sommerlad-Furlow modified (S-F) palatoplasty and compare its surgical and functional outcomes with conventional Sommerlad (S) palatoplasty. Patients with non-syndromic cleft palate who had undergone either S-F palatoplasty or S palatoplasty were retrospectively reviewed. Data on the outcomes of velopharyngeal function and postsurgical palatal fistula incidence were collected for all patients. Data for preselected factors, including gender, age at palatoplasty, and cleft type, were also collected. Chi-square tests were conducted. 1254 patients were included. The postsurgical velopharyngeal competence (VPC) rate after S-F palatoplasty was significantly higher than after S palatoplasty (total, 70.5% vs 57.9%, p < 0.0001; age ≤ 1, 87.0% vs 69.2%, p < 0.0001; 1 < age ≤ 2, 78.3% vs 69.3%, p = 0.0479). With regard to different types of cleft palate, the postsurgical VPC rates after S-F palatoplasty were all significantly higher than for S palatoplasty in all patients younger than 2 years of age (complete cleft palate, 78.7% vs 62.4%, p = 0.0016; hard and soft palate cleft, 84.4% vs 74.8%, p = 0.0172; submucosal cleft and soft palate cleft, 96.6% vs 68.4%, p = 0.0114). The postoperative fistula rate after S-F palatoplasty was 4.3%. This modified palatoplasty technique provided adequate cleft palate closure, with satisfactory speech outcomes and low fistula rates, while older age at palatoplasty may affect the postsurgical outcomes. Within the limitations of the study it seems that the Sommerlad-Furlow modified technique is an option for cleft palate repair.
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Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1ß and anti-IL-36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10-month-old. Results of whole-exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame-shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti-TNF-α inhibitor etanercept treatment. Results of further RNA sequencing (RNA-seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil-related genes, while most genes associated with neutrophil activation, neutrophil-mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.
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BACKGROUND: Breast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR-433-3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear. METHODS: RT-qPCR was used to analyze circ_0002496, miR-433-3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl-2, and PI3K/AKT-related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays. RESULTS: Circ_0002496 was enhanced and MiR-433-3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR-433-3p and miR-433-3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR-433-3p inhibitor reversed the impact of si-circ_0002496 on the BC process. Re-expression of YWHAZ weakened the influence of miR-433-3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR-433-3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway. CONCLUSION: Circ_0002496 participated in the malignant procession of BC by miR-433-3p/YWHAZ regulation cascade.
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[This corrects the article DOI: 10.1016/j.gendis.2018.02.001.].
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Objectives: Infection is one of the important causes of death in intensive care unit (ICU) patients. At present, there are few articles focused on the detailed analysis of pathogenic microorganisms detected in different therapy periods of critically ill patients supported by extracorporeal membrane oxygenation (ECMO). Methods: From October 2020 to October 2022, ECMO-assisted patients who underwent multiple times of both metagenomic next-generation sequencing (mNGS) test and conventional culture were enrolled continuously in the First Affiliated Hospital of Zhengzhou University. The baseline data, laboratory test results, and pathogenic microorganisms detected by mNGS and traditional culture in different time periods were recorded and analyzed. Results: In the present study, 62 patients were included finally. According to whether the patients survived at discharge, they were divided into the survivor group (n = 24) and the non-survivor group (n = 38). Then, according to the different types of ECMO support, they were divided into the veno-venous ECMO (VV ECMO) group (n = 43) and the veno-arterial ECMO (VA ECMO) group (n = 19). The summit period of specimens of traditional culture and mNGS detection of ECMO patients was 7 days after admission, and the largest number of specimens of surviving patients appeared after ECMO withdrawal. The total number of traditional culture specimens was 1,249, the positive rate was 30.4% (380/1,249), and the positive rate of mNGS was 79.6% (82/103). A total of 28 kinds of pathogenic microorganisms were cultured from conventional culture, and 58 kinds of pathogenic microorganisms were detected by mNGS, including Mycobacterium, Rickettsia, and Chlamydia psittaci. In conventional culture, the most frequent Gram-negative bacteria, Gram-positive bacteria, and fungi were Klebsiella pneumoniae, Corynebacterium striatum, and Candida glabrata, and those with the highest frequency of occurrence in mNGS detection were Acinetobacter baumannii, Enterococcus faecium, and Aspergillus flavus. Conclusions: Throughout the whole treatment process, different kinds of suspicious biological specimens of high-infection-risk ICU patients supported by ECMO should undergo both mNGS detection and traditional culture early and repeatedly.
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Acinetobacter baumannii , Oxigenação por Membrana Extracorpórea , Humanos , Estado Terminal/terapia , Sequenciamento de Nucleotídeos em Larga Escala , Aspergillus flavus , Estudos RetrospectivosRESUMO
PURPOSE: While crudely quantified lipoproteins have been reported to affect the risk of breast cancer, the effects of subclass lipoproteins characterized by particle size, particle number, and lipidomes remain unknown. METHODS: Utilizing nuclear magnetic resonance-based GWAS of 85 lipoprotein traits, we performed two-sample univariable Mendelian randomization (MR) to evaluate the causal relationship between each trait with breast cancer (Ncase/control = 133,384/113,789) and with its estrogen receptor (ER) subtypes. Then, we applied multivariable MR to investigate the independent effects considering both general and central obesity. RESULTS: In univariable MR, a heterogeneous effect of subclass high-density lipoproteins (HDL) was observed, in which small HDL traits (ORs ranged from 0.89 to 0.94) were associated with a decreased risk of breast cancer while non-small HDLs traits (OR ranged from 1.04 to 1.08) were associated with an increased risk of breast cancer. Very-low-density lipoproteins (VLDL) traits and serum total triglycerides (TG) were associated with a decreased risk of breast cancer (ORs ranged from 0.88 to 0.94). Similar association patterns were found for ER + subtype. In multivariable MR, only the protective effects of small HDL, VLDL and TG on ER + subtype remained significant. CONCLUSION: We identified a heterogeneous effect of subclass HDLs and a consistent protective effect of VLDL on breast cancer. Only the effects of small HDL and VLDL on ER + subtype remained robust after controlling for obesity. These findings provide new insight into the causal pathway underlying lipoproteins and breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Análise da Randomização Mendeliana , Lipoproteínas/genética , Lipoproteínas HDL , Lipoproteínas VLDL , Triglicerídeos , Espectroscopia de Ressonância Magnética , ObesidadeRESUMO
Non-alcoholic fatty liver disease (NAFLD) is gradually becoming one of the most common and health-endangering diseases. Flaxseed powder (FLA) is rich in α-linolenic acid, dietary fiber, lignans, and other active ingredients, which have lipid-lowering and anti-inflammatory effects. Here, we investigated whether the FLA improves host metabolism by gut bacteria modulation and further bile acid modulation in mice fed a high-fat diet. At the end of the experiment, we found that FLA can significantly reduce the body weight, body fat content, and serum TG, LDL-C, and TNF-α levels of mice, and improve liver steatosis. FLA intervention has a significant effect on preventing and regulating the gut flora disturbance caused by HFD. FLA intervention affects bile acid metabolism in the intestine and causes significant changes in functional bile acids, which can play a lipid-lowering and anti-inflammatory role by activating the intestinal Fxr- Fgfr4-Cyp7a1 and Tgr5-Tlr4-Tnfα pathways.
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Linho , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácidos e Sais Biliares/metabolismo , Pós/farmacologia , Dieta Hiperlipídica/efeitos adversos , Redes e Vias Metabólicas , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , Fígado/metabolismoRESUMO
Background: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference (p<0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p<0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p<0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis. Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.
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Fraturas por Compressão , Cifoplastia , Cifose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/efeitos adversos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Fraturas por Compressão/etiologia , Estudos Retrospectivos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Resultado do Tratamento , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/etiologia , Cimentos ÓsseosRESUMO
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) refers to cerebral hypoxic-ischemic injury caused by asphyxia during perinatal period, which is one of the important causes of neonatal death and sequelae. Early and accurate diagnosis of HIE is of great significance for the prognostic evaluation of patients. The purpose of this study is to explore the efficacy of diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) in the diagnosis of early HIE. METHODS: Twenty Yorkshire newborn piglets (3-5 days) were randomly divided into control group and experimental group. DWI and DKI scanning were performed at timepoints of 3, 6, 9, 12, 16, and 24 h after hypoxic-ischemic exposure. At each timepoint, the parameter values obtained by each group scan were measured, and the lesion area of the apparent diffusion coefficient (ADC) map and mean diffusion coefficient (MDC) map were measured. (For better interpretation of this study, we replaced the description of MD with MDC). Then, we completely removed the brain for pathological examination, and observed the state of cells and mitochondria in the ADC/MDC matching area (the actual area of the lesion), and the mismatch area (the area around the lesion). RESULTS: In the experimental group, the ADC and MDC values decreased with time, but the MDC decreased more significantly and the change rate was higher. Both MDC and ADC values changed rapidly from 3 to 12 h and slowly from 12 to 24 h. The MDC and ADC images showed obvious lesions at 3 h for the first time. At this time, the area of ADC lesions was larger than that of MDC. As the lesions developed, the area of ADC maps was always larger than that of the MDC maps within 24 h. By observing the microstructure of the tissues by light microscopy, we found that the ADC and MDC matching area in the experimental group showed swelling of neurons, infiltration of inflammatory cells, and local necrotic lesions. Consistent with the observation under light microscope, pathological changes were observed in the matching ADC and MDC regions under electron microscopy as well, including collapse of mitochondrial membrane, fracture of partial mitochondrial ridge, and emergence of autophagosomes. In the mismatching region, the above pathological changes were not observed in the corresponding region of the ADC map. CONCLUSIONS: DKI's characteristic parameter MDC is better than ADC (parameter of DWI) to reflect the real area of the lesion. Therefore, DKI is superior to DWI in diagnosing early HIE.
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Edema Encefálico , Hipóxia-Isquemia Encefálica , Animais , Encéfalo/diagnóstico por imagem , Edema Encefálico/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/patologia , SuínosRESUMO
[This corrects the article DOI: 10.1021/acsmedchemlett.2c00537.].
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Goji berries (Lycium barbarum L.) were rich in flavonoids, showing high nutritional and medicinal value. However, a thorough evaluation and comparison of the flavonoids in goji berries from various regions and the possible biological regulation pathways with differences are scanty. Here, we investigated the flavonoid metabolites and gene expression levels of goji berries from three major production areas in China using transcriptomics sequencing and metabolomics. The total flavonoid content and total polyphenol content of goji berry in Ningxia (57.87 µg/g and 183.41 µg/g, respectively) were higher than in Qinghai (50.77 µg/g and 156.81 µg/g) and Gansu (47.86 µg/g and 111.17 µg/g). We identified the 105 differentially accumulated flavonoids (DAFs) and 1858 differentially expressed genes (DEGs) from the goji berries in three habitats. Interestingly, gossypetin-3-O-rutinoside and isorhamnetin were significantly expressed between Ningxia and Qinghai berries. The chalcone isomerase (CHI), chalcone synthase (CHS), and flavonol synthase (FLS) genes also played key roles in the regulation of flavonoid synthesis. In addition, MYB1 positively regulated the expression of quercetin-3-O-glucoside, quercetin-7-O-glucoside and isohyperoside. As a result, we speculated that CHI, CHS, FLS genes, and related transcription factors jointly controlled the variation of flavone accumulation in goji berries. These findings may provide a new perspective for understanding the accumulation and molecular mechanisms of goji flavonoids.
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Lycium , Lycium/genética , Transcriptoma/genética , Flavonoides/metabolismo , Polifenóis/metabolismo , Metaboloma , Frutas/genéticaRESUMO
Diarrheal cases caused by non-toxigenic Vibrio cholerae have been reported globally. Lineages L3b and L9, characterized as ctxAB-negative and tcpA-positive (CNTP), pose the highest risk and have caused long-term epidemics in different regions worldwide. From 2001 to 2018, two waves (2001-2012 and 2013-2018) of epidemic caused by non-toxigenic V. cholerae occurred in the developed city of Hangzhou, China. In this study, through the integrated analysis of 207 genomes of Hangzhou isolates from these two waves (119 and 88) and 1573 publicly available genomes, we showed that L3b and L9 lineages together caused the second wave as had happened in the first wave, but the dominant lineage shifted from L3b (first wave: 69%) to L9 (second wave: 50%). We further found that the genotype of a key virulence gene, tcpF, in the L9 lineage during the second wave shifted to type I, which may have enhanced bacterial colonization in humans and potentially promoted the pathogenic lineage shift. Moreover, we found that 21% of L3b and L9 isolates had changed to predicted cholera toxin producers, providing evidence that gain of complete CTXφ-carrying ctxAB genes, rather than ctxAB gain in pre-CTXφ-carrying isolates, led to the transition. Taken together, our findings highlight the possible public health risk associated with L3b and L9 lineages due to their potential to cause long-term epidemics and turn into high-virulent cholera toxin producers, which necessitates a more comprehensive and unbiased sampling in further disease control efforts.
