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BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Pirroles/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Helicobacter pylori/efectos de los fármacos , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento , Adulto , AncianoRESUMEN
Acovenosigenin A ß-glucoside (AAG) is a cardiac glycoside derived from Streptocaulon juventas (Lour.) Merr, which exhibited the potential in treating lung cancer in our previous research. However, the action mechanism remains unclear. In this research, JAK2-STAT3 signaling pathway was predicted to be the critical regulation pathway based on the integrative analysis of transcriptome and proteome. Western blotting and qPCR assays were performed to identify that AAG can regulate JAK2-STAT3 signaling pathway and its downstream genes, such as c-Myc, Survivin, Cyclin B1, CDK1, Bcl-2. And this action of AAG depended on the suppression of STAT3 phosphorylation and its nuclear translocation through the experiments of Immunofluorescence, transient transfection and cryptotanshinone treatment. Additionally, AAG was discovered to mediate the JAK2-STAT3 pathway in IL-6-driven A549 and H460 cells, which in turn inhibited cell proliferation, promoted mitochondria-related apoptosis, and arrested the cell cycle progression. By molecular docking analysis, CETSA and SIP experiments, the protein of GP130 was identified as the specific target of AAG in A549 and H460 cells. Further studies suggested that AAG inhibited JAK2-STAT3 pathway and its downstream genes by targeting GP130 in nude mice xenograft model in vivo. This research presented that AAG exhibits the promising potential in the treatment of NSCLC.
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Proliferación Celular , Glucósidos , Janus Quinasa 2 , Factor de Transcripción STAT3 , Transducción de Señal , Humanos , Factor de Transcripción STAT3/metabolismo , Janus Quinasa 2/metabolismo , Transducción de Señal/efectos de los fármacos , Glucósidos/farmacología , Glucósidos/química , Proliferación Celular/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Proteoma/metabolismo , Animales , Ratones , Estructura Molecular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Ratones Desnudos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Línea Celular TumoralRESUMEN
Chemical investigation on the 80% EtOH extract of the air dried aerial parts of Hypericum sampsonii resulted in the isolation of two new polycyclic polyprenylated derivatives, hypersampines A and B (1 and 2). The structures of the new compounds were elucidated by spectroscopic data (NMR, IR, and UV) and high resolution mass analysis. The two isolated polyprenylated acylphloroglucinols were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1 and 2 possessed modest cytotoxic activities against all the tested tumor cell lines with IC50 values less than 40 µM.
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Water permeability of reinforced concrete is essential for transportation of ingress ions inside concrete structures. The coupling effect of permeability and loading presents a challenge for the experimental simulation of water-permeate reinforced concrete subjected to tension. This renders the development of the model based on dimensionless analysis, using a series of experimental tests from an innovative experimental system that allows simultaneous measurement of permeability and crack width. The experiments focused on both ordinary concrete and high strength concrete under tension. The relationship between permeability and variables such as deformation, diameter of rebars, tensile load, and crack width under tension was formulated through multiple regression analysis using the testing data. The load to deformation characteristics determines the permeability of the concrete under tension. The proposed model accounts for the influence of continuous loading on permeability, as demonstrated by the robust analysis and proposed yield effective point. The robust analysis demonstrates that the diameter of the rebar, load, and crack width exert minimal influence on the permeability of concrete at lower significance levels. However, permeability variations become pronounced from 0.5 threshold, with significant changes observed between 0.5 and 0.9 thresholds. The findings indicate a differential impact of the variables on the permeability of concrete under tension. The yield-effective points delineate the relationship between the rebar diameter, load, and crack-width on the permeability of concrete with a threshold of 0.5, 0.5, and 0.58, respectively. At a threshold of 0.78, higher permeability will occur in the concrete, attributed to the prevalence of deformation. This deformation highlights the parameters with the most significant influence on the permeability of concrete under tension. The robust analysis and yield effective point derivative are useful parameters to measure concrete permeability and evaluate the behavior of the permeability model under tension.
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INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.
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Iodate crystal materials are some of the important candidates for mid-infrared nonlinear optical (NLO) crystals. Almost all the structures and NLO properties of monometallic iodates have been studied, except for a few difficult to synthesize crystalline phases. In this work, crystalline Cr(IO3)3 was synthesized and its optical properties were studied. Cr(IO3)3 has a strong powder second-harmonic generation (SHG) effect (1.3 × AgGaS2) and a large birefringence (0.24) at 2100 nm. Theoretical calculations indicate that the 3d orbital of Cr3+ is strongly involved in the SHG process, and the contribution of the metal cation centered unit CrO6 to the SHG response is much greater than that of the non-metal cation centered unit IO3. This study provides a new case among the few NLO materials in which the SHG response is dominated by metal cation centered groups.
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Exploring materials that balance the second harmonic generation (SHG) effect and laser-induced damage threshold (LIDT) is the frontier of nonlinear optical (NLO) crystal research at present. In this work, the NLO property of anhydrous aluminum iodate is extensively explored and discussed first. It exhibits a strong SHG intensity of 18.3 × KH2PO4 (KDP) and a high-powder LIDT of 1.4 × KDP at 1064 nm. Combining experimental and theoretical studies at the atomic level and electronic levels, it is found that the cations in the structure are replaced by cations with small radius and high valence, enabling the production of materials with large SHG responses. Unbonded and antibonding orbitals play a crucial positive role in the SHG response of the structure, whereas bonding orbitals produce a large negative contribution. This provides a scarce example of materials in which bonding orbitals make significant negative contributions.
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BACKGROUND: Preoperative teres minor insufficiency has been identified as a risk factor for poor restoration of external rotation (ER) after reverse total shoulder arthroplasty (RTSA). However, there has been little investigation regarding muscle activation patterns generating ER. This prospective study sought to determine the timing and activation levels of the shoulder girdle musculature during ER in well-functioning RTSAs with an intact teres minor using a lateralized design. METHODS: Patients who underwent RTSA ≥1 year previously with functional ER, an American Shoulder and Elbow Surgeons (ASES) score >70, superior rotator cuff deficiency, and an intact teres minor were identified. Electrophysiological and kinematic analyses were performed during ER in the modified neutral position (arm at side with 90° of elbow flexion) and in abduction (AB) (shoulder abducted 90° with 90° of elbow flexion). Dynamometer-recorded torque and position were pattern matched to electromyography during ER. The root-mean-square and integrated electromyography (in microvolts × milliseconds with standard deviation [SD]), as well as median frequency (MF) (in hertz with SD), were calculated to determine muscle recruitment. Pair-wise t test analysis compared muscle activation (P < .05 indicated significance). RESULTS: After an a priori power analysis, 16 patients were recruited. The average ASES score, visual analog scale pain score, and ASES subscore for ER in AB ("comb hair") were 87.7, 0.5, and 2.75 of 3, respectively. In AB, muscle activation began with the upper trapezius, middle trapezius, and latissimus dorsi, followed by the anterior deltoid activating to neutral. With ER beyond neutral, the teres major (9.6 µV × ms; SD, 9.2 µV × ms) initiated ER, followed by the teres minor (14.1 µV × ms; SD, 18.2 µV × ms) and posterior deltoid (11.1 µV × ms; SD, 9.3 µV × ms). MF analysis indicated equal contributions of the teres major (1.1 Hz; SD, 0.5 Hz), teres minor (1.2 Hz; SD, 0.4 Hz), and posterior deltoid (1.1 Hz; SD, 0.4 Hz) in ER beyond neutral. In the modified neutral position, the upper trapezius and middle trapezius were not recruited to the same level as in AB. For ER beyond neutral, the teres major (9.5 µV × ms [SD, 9 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), teres minor (11.4 µV × ms [SD, 15.1 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), and posterior deltoid (8.5 µV × ms [SD, 8 µV × ms]; MF, 1.2 Hz [SD, 0.3 Hz]) were activated in similar sequence and intensity as AB. No differences in muscle activation duration or intensity were noted among the teres major, teres minor, and posterior deltoid (P > .05). CONCLUSION: Active ER after RTSA is complex and is not governed by a single muscle-tendon unit. This study establishes a sequence, duration, and intensity of muscle activation for ER in well-functioning RTSAs. In both tested positions, the teres major, teres minor, and posterior deltoid function equally and sequentially to power ER.
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Artroplastía de Reemplazo de Hombro , Articulación del Hombro , Humanos , Manguito de los Rotadores/cirugía , Estudios Prospectivos , Hombro/cirugía , Rango del Movimiento Articular/fisiologíaRESUMEN
Cholesterol metabolism is a hot topic in exploration of cancer treatment in recent years,and its complex mechanism of action potentially lays a molecular foundation related to lipid-cancer.However,most studies focus only on cholesterol as a product to understand and analyze the progress of cancer,ignoring the phased effects of related derivatives,regulatory proteins and immune cells in its metabolic process,so whether to find targets to regulate colorectal cancer(CRC)from the cholesterol metabolic pathway has become a research focus.This paper reviews the molecular mechanism and the role of signaling pathways in metabolic reprogramming of CRC starting from the abnormal intracellular cholesterol metabolic pathway in order to provide new ideas for the targeted cholesterol therapy of CRC.
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Background@#and Purpose Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. @*Methods@#We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. @*Results@#We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. @*Conclusions@#This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.
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Objective To understand the HIV/AIDS burden and the disease burden attributed to various risk factors in four countries with different socio-demographic index (SDI) (China, United States, Russia, and Afghanistan) from 1990 to 2019, and to predict the HIV/AIDS attributable disease burden from 2020 to 2029. Methods The 2019 Global Burden of Disease Study data was used to describe and compare the incidence, prevalence, death, and DALYs of HIV/AIDS in the four countries. The standardized DALYs attributed to various risk factors in different age groups of HIV/AIDS in the four countries in 1990 and 2019 were compared. R4.3.0 was used to construct an autoregressive moving average mixed model to predict the attributable disease burden in each country over the next decade. Results Compared with 1990, in 2019, the standardized incidence rate, standardized prevalence rate, standardized mortality rate, and standardized DALYs rate in China and the other two countries, except the United States, showed an increase. People aged 10 to 49 years old were a key group for disease burden, and the main risk factors for disease burden varied among different countries and age groups. The autoregressive moving average mixed model predicted that the main risk factor for Russia in the next decade would be injecting drugs, while unsafe sexual behavior would occur in the other three countries. Conclusion There are differences in disease burden and risk factors among different genders and age groups globally and in the four different SDI countries. Therefore, differences should be fully considered to determine the focus of HIV/AIDS prevention and control and rationally allocate health resources.
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BACKGROUND: Changes in circulating pregnancy-associated plasma protein A (PAPP-A) have been observed in women with a placenta accreta spectrum (PAS). However, no consensus has been reached according to the previous studies. Our study investigated the relationship between circulating PAPP-A and PAS risk through a systematic review and meta-analysis. METHODS: Studies comparing the circulating level of PAPP-A between pregnant women with and without PAS were obtained by searching the Medline, Cochrane Library, Embase, CNKI, and Wanfang databases from the inception of the databases until February 12, 2023. Heterogeneity was considered in the pooling of results via a random-effects model. RESULTS: Eight observational studies were obtained for the meta-analysis, which included 243 pregnant women with PAS and 1599 pregnant women without PAS. For all these women, the first-trimester circulating level of PAPP-A was measured by immunoassay and reported as multiples of the median (MoM) values. The pooled results showed that compared to those who did not develop PAS, women with PAS had significantly higher first-trimester serum level PAPP-A (mean difference: 0.43 MoM, 95% confidence interval [CI]: 0.30 to 0.56, Pâ <â .001; I2â =â 32%). Furthermore, a high first-trimester serum PAPP-A level was related to a high PAS risk (odds ratio: 2.89, 95% CI: 2.13 to 3.92, Pâ <â .001; I2â =â 0%). Sensitivity analysis which excluded one study at a time, also obtained similar results (p allâ <â 0.05). CONCLUSION: Pregnant women with a high serum PAPP-A level in the first trimester may be at an increased risk for PAS.
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Placenta Accreta , Proteína Plasmática A Asociada al Embarazo , Humanos , Femenino , Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Placenta Accreta/diagnóstico , Primer Trimestre del EmbarazoRESUMEN
This study aimed to develop an ultraminiature pressure sensor array to measure the force exerted on teeth. Orthodontic force plays an important role in effective, rapid, and safe tooth movement. However, owing to the lack of an adequate tool to measure the orthodontic force in vivo, it remains challenging to determine the best orthodontic loading in clinical and basic research. In this study, a three-dimensional (3D) orthodontic force detection system based on piezoresistive absolute pressure sensors was designed. The 3D force sensing array was constructed using five pressure sensors on a single chip. The size of the sensor array was only 4.1 × 2.6 mm, which can be placed within the bracket base area. Based on the barometric calibration, conversion formulas for the output voltage and pressure of the five channels were constructed. Subsequently, a 3D linear mechanical simulation model of the voltage and stress distribution was established using 312 tests of the applied force in 13 operating modes. Finally, the output voltage was first converted to pressure and then to the resultant force. The 3D force-detection chip was then tested to verify the accuracy of force measurement on the teeth. Based on the test results, the average output force error was only 0.0025 N (0.7169%) (p = 0.958), and the average spatial positioning error was only 0.058 mm (p = 0.872) on the X-axis and 0.050 mm (p = 0.837) on the Y-axis. The simulation results were highly consistent with the actual force applied (intraclass correlation efficient (ICC): 0.997-1.000; p < 0.001). Furthermore, through in vivo measurements and a finite element analysis, the movement trends generated when the measured orthodontic forces that acted on the teeth were simulated. The results revealed that the device can accurately measure the orthodontic force, representing the first clinical test of an orthodontic-force monitoring system. Our study provides a hardware basis for clinical research on efficient, safe, and optimal orthodontic forces, and has considerable potential for application in monitoring the biomechanics of tooth movement.
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Omipalisib (GSK2126458), a potent dual PI3K/mTOR inhibitor, is reported to exhibit anti-tumor effect in several kinds of cancers. More than 50% of acute myeloid leukemia (AML) patients display a hyperactivation of PI3K/AKT/mTOR signaling. We investigated the anti-proliferative effect of omipalisib in AML cell lines with varied genetic backgrounds. The OCI-AML3 and THP-1 cell lines had a significant response to omipalisib, with IC50 values of 17.45 nM and 8.93 nM, respectively. We integrated transcriptomic profile and metabolomic analyses, and followed by gene set enrichment analysis (GSEA) and metabolite enrichment analysis. Our findings showed that in addition to inhibiting PI3K/AKT/mTOR signaling and inducing cell cycle arrest at the G0/G1 phase, omipalisib also suppressed mitochondrial respiration and biogenesis. Furthermore, omipalisib downregulated several genes associated with serine, glycine, threonine, and glutathione metabolism, and decreased their protein and glutathione levels. In vivo experiments revealed that omipalisib significantly inhibited tumor growth and prolonged mouse survival without weight loss. Gedatolisib and dactolisib, another two PI3K/mTOR inhibitors, exerted similar effects without affecting mitochondria biogenesis. These results highlight the multifaceted anti-leukemic effect of omipalisib, revealing its potential as a novel therapeutic agent in AML treatment.
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Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-akt , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Biogénesis de Organelos , Serina-Treonina Quinasas TOR/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Glutatión/farmacología , Glutatión/uso terapéutico , Línea Celular Tumoral , Proliferación CelularRESUMEN
The reaction condition for purifying carbonic anhydrase from Sulfurihydrogenibium yellowstonense (SspCA) by direct heating without prior cell lysis was optimized; heating at 70 °C for 5 min resulted in the highest total activity of 23,460 WAU (Wilbur-Anderson unit) from a 50 mL culture. Heat-purified SspCA was examined for its capability to increase the rate of the mineralization of CO2; compared with an uncatalyzed control, the onset time of CaCO3 formation was shortened by up to 71%. Cyanase can be used to degrade toxic cyanate; however, one of the limitations of this biomimetic process is that the reaction needs HCO3- as a substrate. Heat-purified SspCA was combined with heat-purified cyanase from Thermomyces lanuginosus to alleviate the HCO3- dependence; in industrial wastewater, the HCO3- required was reduced by 50% when 0.75 WAU of SspCA was added. Heat-purified SspCA is stable at 4 °C; 88% of the initial activity was retained for up to five weeks. Partially purified SspCA can be obtained with ease and applied to a variety of applications.
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BACKGROUND: Cutaneous melanomas (CMs) are more frequently found on the trunk in men, and on the hip and lower extremities (legs) in women. This discrepancy has been attributed to greater exposure to ultraviolet (UV) radiation of women's legs due to their dressing habits. OBJECTIVES: To understand the sex difference in the bodily distribution of CMs, especially those on the legs. METHODS: This was a cancer registry-based cohort study. CM incidences, relative tumour density and tumour mutational burdens (TMBs) were compared among different body sites in different sex and racial groups using the SEER (Surveillance, Epidemiology, and End Results) and TCGA SKCM (The Cancer Genome Atlas skin cutaneous melanoma) databases. RESULTS: White men had lower rates and lower relative tumour density (RTD) of CMs on their legs compared with the rest of their body sites, or compared with White women. Men classified by SEER into racial groups other than White did not show such a trend. White women had comparable RTDs among different body sites. The ratios between the 'White' and the 'other' groups were used to evaluate the approximate effect of sun exposure at different body sites, which further validated a distinct protective effect of men's legs in melanoma. TMB on leg melanomas was lower than on other sites in both sexes. CONCLUSIONS: The legs of both sexes in White patients show lower RTDs and lower levels of TMB, suggesting a weaker association with UV exposure. Furthermore, White men are especially protected against CM on their legs, suggesting an unknown intrinsic protective factor as compared with women.
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Melanoma , Neoplasias Cutáneas , Femenino , Humanos , Masculino , Melanoma/patología , Neoplasias Cutáneas/patología , Incidencia , Estudios de Cohortes , Extremidad Inferior/patologíaRESUMEN
In this study, we designed and manufactured a posterior lumbar interbody fusion cage for osteoporosis patients using 3D-printing. The cage structure conforms to the anatomical endplate's curved surface for stress transmission and internal lattice design for bone growth. Finite element (FE) analysis and weight topology optimization under different lumbar spine activity ratios were integrated to design the curved surface (CS-type) cage using the endplate surface morphology statistical results from the osteoporosis patients. The CS-type and plate (P-type) cage biomechanical behaviors under different daily activities were compared by performing non-linear FE analysis. A gyroid lattice with 0.25 spiral wall thickness was then designed in the internal cavity of the CS-type cage. The CS-cage was manufactured using metal 3D printing to conduct in vitro biomechanical tests. The FE analysis result showed that the maximum stress values at the inferior L3 and superior L4 endplates under all daily activities for the P-type cage implantation model were all higher than those for the CS-type cage. Fracture might occur in the P-type cage because the maximum stresses found in the endplates exceeded its ultimate strength (about 10 MPa) under flexion, torsion and bending loads. The yield load and stiffness of our designed CS-type cage fall into the optional acceptance criteria for the ISO 23089 standard under all load conditions. This study approved a posterior lumbar interbody fusion cage designed to have osteoporosis anatomical curved surface with internal lattice that can achieve appropriate structural strength, better stress transmission between the endplate and cage, and biomechanically tested strength that meets the standard requirements for marketed cages.
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In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.
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Degeneración Macular , Modelos Genéticos , Humanos , Fenotipo , Degeneración Macular/genética , Simulación por Computador , Modelos LinealesRESUMEN
BACKGROUND: Rectal distension increases regulatory burden to autonomic nervous system in the brain. PURPOSE: To determine the effect of rectal defecation on endurance performance and blood supply to the prefrontal brain and sub-navel regions of elite triathletes. METHODS: Thirteen elite triathletes completed a cycling time trial (80% VO2max) under defecated and non-defecated conditions, using a counterbalanced crossover design. Oxygenation and blood distribution in prefrontal brain and sub-navel regions were monitored by near-infrared spectroscopy (NIRS) during cycling. RESULTS: Defecation moderately decreased systolic blood pressure (-4 mmHg, p < 0.05, d = 0.71), suggesting an alleviation of autonomic nervous activity. During the exercise trials, fatigue (cycling time to exhaustion) occurred when cerebral oxygenation decreased to ~ 5 % below baseline regardless of treatment conditions, suggesting a critical deoxygenation point for sustaining voluntary exertions. Cerebral blood (estimated by total hemoglobin) increased progressively throughout the entire exercise period. Defecation decreased sub-navel oxygenation levels below the non-defecated level, suggesting an increased sub-navel oxygen consumption. Exercise also decreased sub-navel blood distribution, with minimal difference between non-defecated and defecated conditions. Defecation improved blood pooling in the prefrontal brain during exercise (p < 0.05) and enhanced cycling performance in triathletes (Non-defecated: 1624 ± 138 s vs. defecated: 1902 ± 163 s, d = 0.51, p < 0.05). CONCLUSION: Our results suggest that improved exercise performance after defecation is associated with greater blood availability to compensate deoxygenation in the prefrontal brain region during exercise. Further investigation is needed to examine the role of increasing sub-navel oxygen consumption in the performance improvement after defecation.
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Defecación , Ejercicio Físico , Humanos , Ejercicio Físico/fisiología , Consumo de Oxígeno/fisiología , Fatiga , Circulación CerebrovascularRESUMEN
AIMS: To explore the university students' attitude and the potential influencing factors to receive the coronavirus disease 2019 (COVID-19) vaccine in Sichuan Province, China. DESIGN: A cross-sectional study. METHODS: The self-designed questionnaire was distributed among university students online in June 2021. SPSS software was used for statistical analysis of the data. Descriptive statistics, Chi-square, two independent samples t-tests, one-way analysis of variance (ANOVA), multivariate linear regression, and content analysis were performed. RESULTS: A total of 397 questionnaires were analysed, involving 316 (79.6%) respondents have received at least one dose of a COVID-19 vaccine and 81 (20.4%) have not taken the vaccine. The total mean score of university students' vaccination attitude was 25.97 (standard deviation [SD] = 3.720), and the total scoring rate was 74.2%. Main factors influencing students' attitude included education level, major, living style, with chronic disease or not, self-reported vaccination status, and number of medical units that can provide vaccination within 3 km of residence. Students were more willing to choose Chinese-manufactured vaccines (66.8%) and participate in collective vaccination programs organized by the school (71.3%). The desired vaccine protection period was 5-10 years (42.1%). The top three reasons for refusing the vaccine or vaccine hesitancy were as follows: concern about the side effects of vaccine (44.8%), lack of information about vaccine (31.0%), and concern about the efficacy of vaccine (29.3%). CONCLUSION: In general, most of the participants had relatively high level of positive attitude to receive the COVID-19 vaccine. Nevertheless, more attention should be paid to postgraduate students, non-medical students, those living alone, those with chronic disease, those have not received the COVID-19 vaccine, and those living far away from the vaccination medical units. Findings of this study can help educational institutions in developing effective interventions to improve the vaccination rate in the university student population.