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OBJECTIVE: Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. MATERIAL AND METHODS: We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. RESULTS: Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32-0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26-0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. CONCLUSION: In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.
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Síndrome do Ovário Policístico , Receptores para Leptina , Feminino , Humanos , Povo Asiático , Predisposição Genética para Doença , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/genéticaRESUMO
PURPOSE: To investigate changes in relative peripheral refraction (RPR) associated with myopia progression in children who wore single-vision (SV) lenses for 2 years and switched to Defocus Incorporated Multiple Segments (DIMS) lenses in the third year versus children who wore DIMS lenses for 3 years. METHODS: In the first 2 years, children were allocated randomly to wear either DIMS or SV lenses. In the third year, children in the DIMS group continued to wear these lenses, while those in the SV group were switched to DIMS lenses (Control-to-DIMS group). Central and peripheral refraction and axial length were monitored every 6 months. RESULTS: Over 3 years, the DIMS group (n = 65) showed good myopia control and maintained a relatively constant and symmetrical RPR profile without significant changes. In the first 2 years, children who wore SV lenses (n = 55) showed asymmetrical RPR changes, with significant increases in hyperopic RPR at 20° nasal (N) (mean difference: 0.88 ± 1.06 D, p < 0.0001) and 30N (mean difference: 1.07 ± 1.09 D, p < 0.0001). The Control-to-DIMS group showed significant myopia retardation after wearing DIMS lenses in the third year. When compared with the RPR changes in the first 2 years, significant reductions in hyperopic RPR were observed at 20N (mean difference: -1.14 ± 1.93 D, p < 0.0001) and 30N (mean difference: -1.07 ± 1.17 D, p < 0.0001) in the third year. However, no significant difference between the RPR changes found in the nasal retina and temporal retina (p > 0.05) was noted in the third year. CONCLUSION: Symmetrical changes in RPR were found in children switching from SV to DIMS lenses, and a symmetrical pattern of RPR was noted in children who wore DIMS for 3 years. Myopia control using myopic defocus in the mid-periphery influenced the RPR changes and retarded myopia progression by altering the eye's growth pattern.
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Óculos , Hiperopia , Miopia , Criança , Humanos , Progressão da Doença , Miopia/terapia , Refração Ocular , RetinaRESUMO
Lipid metabolic dysregulation and liver inflammation have been reported to be associated with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unclear. Hepatitis B virus x protein (HBx) is a risk factor for NASH. Based on metabolomic and transcriptomic screens and public database analysis, we found that HBx-expressing hepatocyte-derived prostaglandin E2 (PGE2) induced macrophage polarization imbalance via prostaglandin E2 receptor 4 (EP4) through in vitro, ex vivo, and in vivo models. Here, we revealed that the M1-type polarization of macrophages induced by endoplasmic reticulum oxidoreductase-1-like protein α (ERO1α)-dependent endoplasmic reticulum stress was associated with the HBx-related hepatic NASH phenotype. Mechanistically, HBx promoted Niemann-Pick type C1 (NPC1)/oxysterol-binding protein-related protein 5 (ORP5)-mediated cholesterol transport from the lysosome to the endoplasmic reticulum via mammalian target of rapamycin (mTOR) activation. This study provides a novel basis for screening potential biomarkers in the macrophage mTOR-cholesterol homeostasis-polarization regulatory signaling pathway and evaluating targeted interventions for HBx-associated NASH.
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Hepatopatia Gordurosa não Alcoólica , Oxisteróis , Colesterol/metabolismo , Dinoprostona/metabolismo , Retículo Endoplasmático/metabolismo , Hepatócitos/metabolismo , Humanos , Lisossomos/metabolismo , Macrófagos/metabolismo , Proteína C1 de Niemann-Pick/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Oxirredutases/metabolismo , Oxisteróis/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transativadores , Proteínas Virais Reguladoras e AcessóriasRESUMO
BACKGROUND: Cysticercosis is an emerging and neglected tropical disease (NTD) that poses a serious public health concern worldwide. Disseminated cysticercosis (DCC) is an uncommon manifestation of cysticercosis, also found in China. CASE PRESENTATION: We report three cases of DCC in patients living in China, with different clinical and radiological presentations. All three patients had DCC with active ocular cysticercosis, including one patient with widespread DCC caused by direct ingestion of Taenia solium eggs. The intravitreal cysticercus cyst in this patient was completely extracted entirely by 23-gauge pars plana vitrectomy, and the cyst was oval in shape on the flat mount preparation. CONCLUSION: The clinical presentation of DCC is highly sophisticated. The diagnosis depended on the typical radiological presentations, biopsy and flat mount preparations of the cyst.
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Cisticercose/diagnóstico , Adolescente , Adulto , Albendazol/uso terapêutico , Animais , Anticorpos/sangue , Anticorpos/líquido cefalorraquidiano , Antiprotozoários/uso terapêutico , Encéfalo/diagnóstico por imagem , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Feminino , Humanos , Larva/fisiologia , Imageamento por Ressonância Magnética , Masculino , Taenia solium/crescimento & desenvolvimento , Taenia solium/isolamento & purificação , Vitrectomia , Adulto JovemRESUMO
OBJECTIVE: To confirm the benefits of whole-body vibration exercise for pain intensity and functional disability in patients with non-specific chronic low back pain. DESIGN: Single-blind randomized controlled trial. SETTING: Outpatient. SUBJECTS: Eighty-nine patients with non-specific chronic low back pain met the inclusion criteria, they were randomly allocated to either the intervention group (n = 45) or the control group (n = 44). INTERVENTION: The intervention group received whole-body vibration exercises three times a week for 12 weeks. The control group received general exercise protocol three times a week for 12 weeks. MAIN OUTCOMES: The primary outcome measures were pain intensity and functional disability measured by the visual analog scale scores and Oswestry Disability Index. The secondary outcome measures included lumbar joint position sense, quality of life (Short Form Health Survey 36) and overall treatment effect (Global Perceived Effect). RESULTS: A total of 84 subjects completed the 12-week study program. After 12 weeks, compared with the control group, the mean visual analog scale and Oswestry Disability Index scores decreased by additional 1 point (95% confidence interval (CI) = -1.22 to -0.78; P < 0.001), 3.81 point (95% CI, -4.98, -2.63; P < 0.001) based on adjusted analysis in the intervention group. And the intervention group provided additional beneficial effects for in terms of lumbar joint position sense (P < 0.05), quality of life (P < 0.05), and Global Perceived Effect (P = 0.012). CONCLUSION: The study demonstrated that whole-body vibration exercise could provide more benefits than general exercise for relieving pain and improving functional disability in patients with non-specific chronic low back pain.
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Dor Crônica/terapia , Dor Lombar/terapia , Vibração/uso terapêutico , Adulto , Avaliação da Deficiência , Feminino , Humanos , Masculino , Qualidade de Vida , Método Simples-Cego , Escala Visual Analógica , Adulto JovemRESUMO
Premna microphylla Turczaninow, an erect shrub, was widely used in Chinese traditional medicine to treat dysentery, appendicitis, and infections. In this study, the essential oil from P. microphylla Turcz. was obtained by hydrodistillation and analyzed by GC (Gas Chromatography) and GC-MS (Gas Chromatography-Mass Spectrometer). Fifty-six compounds were identified in the oil which comprised about 97.2% of the total composition of the oil. Major components of the oil were blumenol C (49.7%), ß-cedrene (6.1%), limonene (3.8%), α-guaiene (3.3%), cryptone (3.1%), and α-cyperone (2.7%). Furthermore, we assessed the in vitro biological activities displayed by the oil obtained from the aerial parts of P. microphylla, namely the antioxidant, antimicrobial, and cytotoxic activities. The antioxidant activity of the essential oil was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. For this, the IC50 value was estimated to be 0.451 mg/mL. The essential oil of P. microphylla exhibited considerable antibacterial capacity against Escherichia coli with an MIC (Minimum Inhibitory Concentration) value of 0.15 mg/mL, along with noticeable antibacterial ability against Bacillus subtilis and Staphylococcus aureus with an MIC value of 0.27 mg/mL. However, the essential oil did not show significant activity against fungus. The oil was tested for its cytotoxic activity towards HepG2 (liver hepatocellular cells) and MCF-7 Cells (human breast adenocarcinoma cell line) using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, and exerted cytotoxic activity with an IC50 of 0.072 and 0.188 mg/mL for 72 h. In conclusion, the essential oil from P. microphylla is an inexpensive but favorable resource with strong antibacterial capacity as well as cytotoxic activity. Thus, it has the potential for utilization in the cosmetics and pharmaceutical industries.
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Anti-Infecciosos/química , Antioxidantes/química , Lamiaceae/química , Óleos Voláteis/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Componentes Aéreos da Planta/química , Óleos de Plantas/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.
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Cloreto de Cádmio , Senescência Celular , Degradação Associada com o Retículo Endoplasmático , Neurônios , Receptores sigma , Animais , Senescência Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Cloreto de Cádmio/toxicidade , Receptores sigma/metabolismo , Degradação Associada com o Retículo Endoplasmático/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Camundongos , Proteínas tau/metabolismo , Masculino , Doença de Alzheimer/metabolismo , Humanos , Melatonina/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.
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Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Ferroptose/genética , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.
Assuntos
DNA Helicases , RNA Helicases , DNA Helicases/metabolismo , RNA Helicases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Separação de Fases , Grânulos Citoplasmáticos/metabolismoRESUMO
Tumor immunotherapy has become an important means of tumor therapy by enhancing the immune response and triggering the activation of immune cells. However, currently, only a small number of patients respond to immunotherapy alone, and patients may experience immune-related adverse events (irAEs) during the course of treatment. Sonodynamic therapy (SDT) can produce cytotoxic substances to tumor tissue, induce apoptosis and enhance immunity. SDT combined with immunotherapy is considered a promising strategy for cancer treatment. In this mini review, we summarize the role of SDT in immunotherapy in recent years, including the application of SDT-triggered immunotherapy and the combination of SDT and immunotherapy.
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Neoplasias , Terapia por Ultrassom , Humanos , Terapia Combinada , Apoptose , Imunoterapia/efeitos adversos , Neoplasias/terapia , Linhagem Celular Tumoral , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Bacteremia, which is a major cause of mortality in patients with acute cholangitis, induces hyperactive immune response and mitochondrial dysfunction. Presepsin is responsible for pathogen recognition by innate immunity. Acylcarnitines are established mitochondrial biomarkers. AIM: To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage. METHODS: Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018. Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry, respectively. RESULTS: The concentrations of presepsin, procalcitonin, short- and medium-chain acylcarnitines increased, while long-chain acylcarnitines decreased with the severity of acute cholangitis. The areas under the receiver operating characteristic curves (AUC) of presepsin for diagnosing moderate/severe and severe cholangitis (0.823 and 0.801, respectively) were greater than those of conventional markers. The combination of presepsin, direct bilirubin, alanine aminotransferase, temperature, and butyryl-L-carnitine showed good predictive ability for biliary drainage (AUC: 0.723). Presepsin, procalcitonin, acetyl-L-carnitine, hydroxydodecenoyl-L-carnitine, and temperature were independent predictors of bloodstream infection. After adjusting for severity classification, acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality (hazard ratio 14.396; P < 0.001) (AUC: 0.880). Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine. CONCLUSION: Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage. Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis. Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.
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Colangite , Sepse , Humanos , Pró-Calcitonina , Acetilcarnitina , Biomarcadores , Sepse/diagnóstico , Carnitina , Colangite/diagnóstico , Colangite/complicações , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Drenagem , Proteína C-Reativa/análiseRESUMO
This study evaluated the long-term myopia control effect and safety in children wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses. Participants who completed the 2-year RCT were followed for a total of 6 years; their cycloplegic refractions and axial length were measured. Group 1 (n = 36) wore DIMS spectacles for 6 years; Group 2 (n = 14) wore DIMS lens for the first 3.5 years and SV spectacles afterwards; Group 3 (n = 22) wore SV spectacles in the first 2 years and switched to DIMS; Group 4 (n = 18) wore SV spectacles in the first 2 years, switched to DIMS for 1.5 years and then SV spectacles again. Group 1 showed no significant differences in myopia progression (- 0.52 ± 0.66 vs. - 0.40 ± 0.72D) and axial elongation (0.32 ± 0.26 vs. 0.28 ± 0.28 mm, both p > 0.05) between the first and the later 3 years. In the last 2.5 years, DIMS lens groups (Groups 1 and 3) had less myopia progression and axial elongation than the single vision groups (Groups 2 and 4). There was no evidence of rebound after stopping the treatment. Post-wear visual functions in all groups were within norms. The results supported that DIMS lenses provided sustained myopia control without adverse effects over the 6-year study period.Trial registration: clinicaltrials.gov; NCT02206217.
Assuntos
Óculos , Miopia , Humanos , Criança , Refração Ocular , Miopia/terapia , Testes VisuaisRESUMO
BACKGROUND: Biliary decompression is well known to greatly decrease the risks of mortality in acute cholangitis (AC). Although early biliary drainage is recommended by the treatment guidelines for AC, the best time for performing this procedure is yet to be established. Furthermore, since the clinical outcomes of patients with severe AC vary dramatically, screening for patients that could benefit the most from early drainage would be more beneficial than the drainage performed based on the severity grade criteria. AIM: To investigate the optimal drainage timing for AC patients with each disease severity grade and organ dysfunction. METHODS: In this retrospective monocenter cohort analysis, we reviewed 1305 patients who were diagnosed with AC according to the Tokyo guidelines 2018 at a Chinese tertiary hospital between July 2016 and December 2020. Demographic characteristics including age and sex, clinical and laboratory characteristics, and imaging findings of each patient were obtained from electronic medical records. We investigated the all-cause in-hospital mortality (IHM), hospital length of stay (LOS), and hospitalization costs associated with the timing of biliary drainage according to the severity grading and different dysfunctioning organs and predictors [age, white blood cell (WBC) count, total bilirubin, albumin, lactate, malignant obstruction, and Charlton comorbidity index (CCI)]. RESULTS: Biliary drainage within 24 or 48 h in Grade III AC patients could dramatically decrease IHM (3.9% vs 9.0%, P = 0.041; 4% vs 9.9%, P = 0.018, respectively), while increasing LOS and hospitalization costs. Multivariate logistic analysis revealed that neurological, respiratory, renal, and cardiovascular dysfunctions, hypoalbuminemia, and malignant obstruction were significantly associated with IHM (odds ratio = 5.32, 2.541, 6.356, 4.021, 5.655, and 7.522; P < 0.001, P = 0.016, P < 0.001, P = 0.012, P < 0.001, and P < 0.001; respectively). Biliary decompression performed within 12 h of admission significantly decreased the IHM in AC patients with neurological dysfunction (0% vs 17.3%, P = 0.041) or with serum lactate > 2 mmol/L (0% vs 5.4%, P = 0.016). In the subgroup of AC patients with renal dysfunction, abnormal WBC count, hyperbilirubinemia, or hypoalbuminemia, early drainage (< 24 h) reduced the IHM (3.6% vs 33.3%, P = 0.004; 1.9% vs 5.8%, P = 0.031; 1.7% vs 5.0%, P = 0.019; 0% vs 27%, P = 0.026; respectively). The IHM was lower in patients with AC combined with hepatic dysfunction, malignant obstruction, or a CCI > 3 who had undergone biliary drainage within 48 h (2.6% vs 20.5%, P = 0.016; 3.0% vs 13.5%, P = 0.006; 3.4% vs 9.6%, P = 0.021; respectively). CONCLUSION: Biliary drainage within 12 h is beneficial for AC patients with neurological or cardiovascular dysfunction, while complete biliary decompression within 24 h of admission is recommended for treating patients with Grade III AC.
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Colangite , Hipoalbuminemia , Doença Aguda , Albuminas , Bilirrubina , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangite/complicações , Colangite/terapia , Drenagem/métodos , Humanos , Hipoalbuminemia/etiologia , Lactatos , Estudos RetrospectivosRESUMO
Background and objective: Radioiodine therapy (RAI) is one of the most common treatment solutions for Graves' disease (GD). However, many patients will develop hypothyroidism as early as 6 months after RAI. This study aimed to implement machine learning (ML) algorithms for the early prediction of post-RAI hypothyroidism. Methods: Four hundred and seventy-one GD patients who underwent RAI between January 2016 and June 2019 were retrospectively recruited and randomly split into the training set (310 patients) and the validation set (161 patients). These patients were followed for 6 months after RAI. A set of 138 clinical and lab test features from the electronic medical record (EMR) were extracted, and multiple ML algorithms were conducted to identify the features associated with the occurrence of hypothyroidism 6 months after RAI. Results: An integrated multivariate model containing patients' age, thyroid mass, 24-h radioactive iodine uptake, serum concentrations of aspartate aminotransferase, thyrotropin-receptor antibodies, thyroid microsomal antibodies, and blood neutrophil count demonstrated an area under the receiver operating curve (AUROC) of 0.72 (95% CI: 0.61-0.85), an F1 score of 0.74, and an MCC score of 0.63 in the training set. The model also performed well in the validation set with an AUROC of 0.74 (95% CI: 0.65-0.83), an F1 score of 0.74, and a MCC of 0.63. A user-friendly nomogram was then established to facilitate the clinical utility. Conclusion: The developed multivariate model based on EMR data could be a valuable tool for predicting post-RAI hypothyroidism, allowing them to be treated differently before the therapy. Further study is needed to validate the developed prognostic model at independent sites.
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AIMS: To determine myopia progression in children who continued to wear the defocus incorporated multiple segments (DIMS) lenses or switched from single vision (SV) to DIMS lenses for a 1-year period following a 2-year myopia control trial. METHODS: 128 children participated in this study. The children who had worn DIMS lenses continued to wear DIMS lenses (DIMS group), and children who had worn SV lenses switched to wear DIMS lenses (Control-to-DIMS group). Cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at 6-month interval. Historical controls were age matched to the DIMS group at 24 months and used for comparing the third-year changes. RESULTS: Over 3 years, SER and AL changes in the DIMS group (n=65) were -0.52±0.69D and 0.31±0.26 mm; these changes were not statistically significant over time (repeated measures analysis of variance, p>0.05).SER (-0.04±0. 38D) and AL (0.08±0.12 mm) changes in the Control-to-DIMS group (n=55) in the third year were less compared with the first (mean difference=0.45 ± 0.30D, 0.21±0.11 mm, p<0.001) and second (0.34±0.30D, 0.12±0.10 mm, p<0.001) years.Changes in SER and AL in both groups over that period were significantly less than in the historical control group (DIMS vs historical control: mean difference=-0.18±0.42D, p=0.012; 0.08±0.15 mm, p=0.001; Control-to-DIMS versus historical control: adjusted mean differences=-0.30±0.42D, p<0.001; 0.12±0.16 mm, p<0.001). CONCLUSIONS: Myopia control effect was sustained in the third year in children who had used the DIMS spectacles in the previous 2 years and was also shown in the children switching from SV to DIMS lenses.
Assuntos
Óculos , Miopia , Criança , Pré-Escolar , China/epidemiologia , Progressão da Doença , Seguimentos , Humanos , Miopia/terapia , Refração OcularRESUMO
Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by lacking oxygen and photosynthesis-derived nutrients. Most animals acquire nutrition in cold seeps or hydrothermal vents by maintaining epi- or endosymbiotic relationship with chemoautotrophic microorganisms. Although several seep- and vent-dwelling animals hosting symbiotic microbes have been well-studied, the genomic basis of adaptation to deep-sea reducing environment in nonsymbiotic animals is still lacking. Here, we report a high-quality genome of Chiridota heheva Pawson & Vance, 2004, which thrives by extracting organic components from sediment detritus and suspended material, as a reference for nonsymbiotic animal's adaptation to deep-sea reducing environments. The expansion of the aerolysin-like protein family in C. heheva compared with other echinoderms might be involved in the disintegration of microbes during digestion. Moreover, several hypoxia-related genes (Pyruvate Kinase M2, PKM2; Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase, LHPP; Poly(A)-specific Ribonuclease Subunit PAN2, PAN2; and Ribosomal RNA Processing 9, RRP9) were subject to positive selection in the genome of C. heheva, which contributes to their adaptation to hypoxic environments.
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Fontes Hidrotermais , Aclimatação/genética , Adaptação Fisiológica/genética , Animais , Genoma , SimbioseRESUMO
Based on atmospheric monitoring data and the WRF-CAMx model, this study analyzed the characteristics of air pollution and performed a quantitative assessment of PM2.5 cross-border transport in the Beijing-Tianjin-Hebei (BTH) region in January 2016. The results showed that the average concentrations of PM2.5, PM10, SO2, NO2, and CO were 89.5 µg·m-3, 135.61µg·m-3, 57.55µg·m-3, 60.79µg·m-3, and 2.12 mg·m-3, respectively, indicating severe PM2.5 pollution. During the study period, surface-level PM2.5 in each city of BTH region was dominated by local emissions, which accounted for 45.4% to 69.9%. The regional transport contribution was supplemented by transport from within and outside of the BTH region, accounting for 4.8% to 49.7% and 4.9% to 29.6%, respectively. In addition, high wind speeds promoted the diffusion of local PM2.5 pollution and cities with high upwind pollution enhance regional-scale transport to downwind cities. The total inflow, outflow, and net flux of PM2.5 in Beijing (Shijiazhuang) in January 2016 were 1582.96 t·d-1 (2036.89 t·d-1), -1171.09 t·d-1 (-1879.12 t·d-1), and 411.87 t·d-1 (157.77 t·d-1), respectively, indicating that PM2.5 inputs from surrounding cities per unit time were higher than external inputs to the surrounding cities. Furthermore, net PM2.5 flux showed notable vertical evolution; the total net flux of PM2.5 in Beijing and Shijiazhuang below 1782 m ranged from 17.86 to 64.18 t·d-1 and -2.95 to 134.81 t·d-1, respectively, and both peaked 817 m above the ground at 64.18 and 134.81 t·d-1. Moreover, a significant increase the net PM2.5 inflow flux in Zhangjiakou and Shanxi explained the observed net flux peaks in these two cities.
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BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder affecting many parts of the body with café au lait spots, skeletal deformity, and scoliosis. A familial case of NF1 with scoliosis and a painless mass had not yet been reported. CASE SUMMARY: We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis. His right shoulder was about 5 cm lower than the left, the left side of his face was deformed, and the left submandibular skin was relaxed. The folding and drooping were obvious and movement was poor. Computed tomography revealed the involvement of the neck, upper chest wall, and surrounding left shoulder, accompanied by bone changes and scoliosis. Histological evaluation showed subepidermal pale blue mucoid degeneration, fibrous fusiform cells in the dermis in a fascicular, woven arrangement. His mother had the same medical history. The diagnosis was neurofibromatosis of the left neck. Various parts of the tumor tissue were serially resected during several visits. Eight months after surgery, there was a slight tendency to regrow. CONCLUSION: This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient's growth and development.
RESUMO
A 20-year-old female resident of Beijing intended to consume the eggs of the parasitic worm, Taenia saginata, for weight loss; however, she apparently inadvertently ingested Taenia solium (pork tapeworm) eggs, which resulted in disseminated cysticercosis. Cysticerci developed in the brain, tongue, muscles, liver, peritoneum, and subcutaneous tissues. She was administered oral albendazole and praziquantel. After four 10-day courses of treatment, most of the cysts disappeared and she recovered. After 3 years, the patient remains in good health.
Assuntos
Anti-Helmínticos/uso terapêutico , Encéfalo/patologia , Cisticercose/patologia , Taenia solium/patogenicidade , Língua/patologia , Albendazol/uso terapêutico , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Cisticercose/diagnóstico por imagem , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/parasitologia , Fígado/patologia , Músculos/diagnóstico por imagem , Músculos/parasitologia , Músculos/patologia , Peritônio/diagnóstico por imagem , Peritônio/parasitologia , Peritônio/patologia , Praziquantel/uso terapêutico , Tela Subcutânea/diagnóstico por imagem , Tela Subcutânea/parasitologia , Tela Subcutânea/patologia , Taenia saginata , Taenia solium/crescimento & desenvolvimento , Língua/diagnóstico por imagem , Língua/parasitologia , Resultado do Tratamento , Redução de Peso , Adulto Jovem , Zigoto/crescimento & desenvolvimento , Zigoto/patologiaRESUMO
BACKGROUND: Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk. The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage. With the introduction of white blood cell (WBC) count, C-reactive protein (CRP), and total bilirubin (T-Bil) into the diagnostic criteria and severity grading for acute cholangitis, the diagnosis rate and grading have significantly improved. However, early risk stratification assessments are challenging in the emergency department. Therefore, we hope to find an ideal predictive biomarker for cholangitis grade. Presepsin is a promising biomarker for the early diagnosis, severity, and prognosis of acute bacterial infections. AIM: To assess the grading value of presepsin in patients with acute cholangitis. METHODS: This clinical study was conducted at the Beijing Friendship Hospital, a 2000-bed teaching hospital with approximately 200000 emergency admissions per year. In this prospective observational study, 336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed. WBC count, CRP, procalcitonin (PCT), presepsin, T-Bil, and blood culture results were collected. The values were compared using the Pearson χ 2 test, Fisher's exact test, or Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) of the value was examined using the Delong test. The correlations among the key research indicators were determined using Pearson correlation. RESULTS: In total, 336 patients were examined, which included 107, 106, and 123 patients classified as having mild, moderate, and severe cholangitis, respectively. WBC count, CRP, PCT, presepsin, T-Bil, direct bilirubin, and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients (P = 0.000). The AUC of presepsin in predicting moderate acute cholangitis was 0.728, which was higher than that of CRP (0.631, P = 0.043) and PCT (0.585, P = 0.002), and same as that of WBC count (0.746, P = 0.713) and T-Bil (0.686, P = 0.361). The AUC of presepsin in predicting severe acute cholangitis was 0.715, which was higher than that of WBC count (0.571, P = 0.008), CRP (0.590, P = 0.009), PCT (0.618, P = 0.024), and T-Bil (0.559, P = 0.006). The presepsin levels in the positive blood culture group were higher (2830.8pg/mLvs1987.8pg/mL, P = 0.000), and the AUC of presepsin (0.688) proved that it was a good biomarker for predicting positive bacterial culture. CONCLUSION: Presepsin can predict positive blood culture in patients with acute cholangitis. It is superior to WBC count, CRP, PCT, and T-Bil for the risk stratification of acute cholangitis.