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BACKGROUND Over the past decades, total knee arthroplasty (TKA) in China has increased substantially. Owing to a lack of a joint registry, there is restricted information concerning the epidemiology of TKA failures in China. We aimed to (1) investigate the etiology of TKA failures in a cohort of Chinese patients and (2) determine the related demographic and anthropometric risk factors in Jilin, China, to have a look at the actual situation. MATERIAL AND METHODS A total of 1927 primary and 109 revision TKAs performed between April 2014 and May 2022 were analyzed in this retrospective study. Patient demographics and anthropometric measures, the interval from primary TKA to revision procedures, and the mechanisms for primary TKA failure were evaluated. A chi-square test, unpaired t test, and multivariate logistic regression were used to investigate the relationships between different factors and TKA failures. RESULTS The leading failure mechanism was infection (53.3%), followed by aseptic loosening (21.5%), stiffness (15.0%), instability (3.7%), malposition (2.8%), periprosthetic fractures (2.8%), and extensor mechanism disruption (0.9%). Infection (59.7%) was the main reason for early revision. Aseptic loosening (43.3%) was the leading cause of late revision. The male ratio in infection patients was higher (35.1% vs 20.6%). The smoking rate in patients with revision and infection was higher (18.9%, 23.9% vs 7%) than in primary patients. There was no difference in BMI between groups. CONCLUSIONS The leading cause of revision TKA in Jilin, China, was infection, followed by aseptic loosening and stiffness. Sex and smoking history were associated with TKA failures in this region.
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Artroplastia de Reemplazo de Rodilla , Reoperación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artroplastia de Reemplazo de Rodilla/efectos adversos , China/epidemiología , Pueblos del Este de Asia , Prótesis de la Rodilla/efectos adversos , Falla de Prótesis , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Identification of unique and specific biomarkers to better detect and quantify senescent cells remains challenging. By a global proteomic profiling of senescent human skin BJ fibroblasts induced by ionizing radiation (IR), the cellular level of pregnancy zone protein (PZP), a presumable pan-protease inhibitor never been linked to cellular senescence before, was found to be decreased by more than 10-fold, while the level of PZP in the conditioned medium was increased concomitantly. This observation was confirmed in a variety of senescent cells induced by IR or DNA-damaging drugs, indicating that high-level secretion of PZP is a novel senescence-associated secretory phenotype. RT-PCR examination verified that the transcription of the PZP gene is enhanced in various cells at senescence or upregulated following DNA damage treatment in a p53-independent manner. Moreover, pretreatment with late pregnancy serum containing a high level of PZP led to inhibition of doxorubicin-induced senescence in A549 cells, and depletion of PZP in the pregnancy serum could enhance such inhibition. Finally, the addition of immuno-precipitated PZP complexes into tissue culture attenuated the growth of A549 cells and promoted the spontaneous senescence. Therefore, we revealed that high-level secretion of PZP is a novel and unique feature associated with DNA damage-induced senescence, and secreted PZP is a positive regulator of cellular senescence, particularly during the late stage of gestation.
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Senescencia Celular , Daño del ADN , Proteínas Gestacionales , Humanos , Biomarcadores/metabolismo , Senescencia Celular/genética , Proteómica , Piel/metabolismo , Proteínas Gestacionales/metabolismo , Fibroblastos , Células A549RESUMEN
Plant growth regulators are a class of physiologically active substances that could modify or regulate basic physiological processes in the plant and defense against abiotic and biotic stresses, including natural plant growth regulators and synthetic ones. Different from natural plant growth regulators with low content and high cost of extraction in plants, synthetic ones can be produced in large-scale production and widely used in agriculture for increasing and securing yield and quality of the harvested produce. However, like pesticides, the abuse of plant growth regulators will have negative impacts on human beings. Therefore, it is important to monitor plant growth regulators residues. Due to the low concentration of plant growth regulators and complex matrices of food, it is necessary to isolate and extract plant growth regulators by appropriate adsorbents in sample preparation for obtaining satisfactory results. In the last decade, several advanced materials as adsorbents have shown superiority in sample preparation. This review briefly introduces the recent application and progress of advanced materials as adsorbents in sample preparation for extraction of plant growth regulators from the complex matrix. In the end, the challenge and outlook about the extraction of plant growth regulators of these advanced adsorbents in sample preparation are presented.
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Plaguicidas , Reguladores del Crecimiento de las Plantas , Humanos , Reguladores del Crecimiento de las Plantas/química , PlantasRESUMEN
It is possible to develop new chemopreventive compounds so that cancer cells can be targeted in an exclusive manner. Bioactive natural compounds have demonstrated to be efficient chemotherapeutic agents, safe and cost-effective. Majority of anti-cancer medications are derived from natural sources, particularly of plant origins. Betanin (betanidin-5-O-ß-glucoside) is the most common betacyanin with antioxidant, anti inflammatory and anticancer properties. The present study therefore investigated the effect of betanin onosteosarcoma MG-63 cells. The mechanistic pathway of inflammatory responses, cell proliferation and apoptosis were investigated. The MG-63 cells were treated with betanin for 24 h. Betanin actions on the appearance of cell arrangements, morphological changes, ROS induced Δψm , cell migration, cell adhesion and proliferative mechanistic marker expression of PI3K/AKT/mTOR/S6were analyzed. Betanin inhibited MG-63 cells at IC50 concentrations between 9.08 and 54.49 µM and induced apoptosis by triggering the ROS mechanism. Betanin inhibited proliferation and migration of MG-63 cells and induced DNA fragmentation. Betanin also modified the key mediator expression levels of PI3K/AKT/mTOR/S6 signaling pathways. Betanin can potentially be utilized in bone carcinoma therapeutics to inhibit, reverse or delay osteosarcoma.
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Neoplasias Óseas , Osteosarcoma , Humanos , Betacianinas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Especies Reactivas de Oxígeno , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular , Osteosarcoma/metabolismo , Neoplasias Óseas/patología , Apoptosis , Línea Celular TumoralRESUMEN
The accurate prediction of vehicle speed is crucial for the energy management of vehicles. The existing vehicle speed prediction (VSP) methods mainly focus on road vehicles and rarely on off-road vehicles. In this paper, a double-layer VSP method based on backpropagation neural network (BPNN) and long short-term memory (LSTM) for off-road vehicles is proposed. First of all, considering the motion characteristics of off-road vehicles, the VSP problem is established and the relationship between the variables in the problem is carefully analyzed. Then, the double-layer VSP framework is presented, which consists of speed prediction and information update layers. The speed prediction layer established by using LSTM is to predict vehicle speed in the horizon, and the information update layer built by BPNN is to update the prediction information. Finally, with the help of mining truck and loader operation scenarios, the proposed VSP method is compared with the analytical method, BPNN prediction method, and recurrent neural network (RNN) prediction method in terms of speed prediction accuracy. The results show that, under the premise of ensuring the real-time prediction performance, the average prediction error of the proposed BPNN-LSTM prediction method under two operation scenarios reduces by 48.14%, 35.82% and 30.09% compared with the other three methods, respectively. The proposed speed prediction method provides a new solution for predicting the speed of off-road vehicles, effectively improving the speed prediction accuracy.
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Lithium-promoted hydroboration of alkynes and alkenes using commercially available hexamethyldisilazane lithium as a precatalyst and HBpin as a hydride source has been developed. This method will be appealing for organic synthesis because of its remarkable substrate tolerance and good yields. Mechanistic studies revealed that the hydroboration proceeds through the in situ-formed BH3 species, which acts to drive the turnover of the hydroboration of alkynes and alkenes.
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BACKGROUND: Femoral neck fractures in young people are usually Pauwels Type III fractures. The common treatment method are multiple parallel cannulated screws or dynamic hip screw sliding compression fixation. Due to the huge shear stress, the rate of complications such as femoral head necrosis and nonunion is still high after treatment. The aim of our study was to compare the stabilities of two fixation methods in fixating pauwels type III femoral neck fractures. METHODS: All biomimetic fracture samples are fixed with three cannulated screws combined with a medial buttress plate. There were two fixation groups for the buttress plate and proximal fracture fragment: Group A, long screw (40 mm); Group B, short screw (6 mm). Samples were subjected to electrical strain measurement under a load of 500 N, axial stiffness was measured, and then the samples were axially loaded until failure. More than 5 mm of displacement or synthetic bone fracture was considered as construct failure. RESULTS: There were no significant differences in failure load (P = 0.669), stiffness (P = 0.842), or strain distribution (P > 0.05) between the two groups. CONCLUSIONS: Unicortical short screws can provide the same stability as long screws for Pauwels Type III Femoral Neck Fractures.
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Fracturas del Cuello Femoral , Adolescente , Fenómenos Biomecánicos , Placas Óseas , Tornillos Óseos , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas , Humanos , Estrés MecánicoRESUMEN
Temperature, salinity, and pressure (TSP) are essential parameters for the ocean. Optical fiber sensors (OFSs) have rapidly come into focus as an ocean detection technology in recent years due to their advantages of electromagnetic interference, light weight, low cost, and no waterproof requirement. In this paper, the most recently developed TSP sensors for single parameter and multi-parameter TSP sensing and measurement based on different OFSs are reviewed. In addition, from the practical point of view, encapsulation methods that protect fibers and maintain the normal operation of OFSs in seawater, and the response time of the OFS, are addressed. Finally, we discuss the prospects and challenges of OFSs used in marine environments and provide some clues for future work.
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Fibras Ópticas , Salinidad , Tecnología de Fibra Óptica , Agua de Mar , TemperaturaRESUMEN
A practical, convenient, and highly selective method of synthesizing ß-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.
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BACKGROUND: Femoral neck fracture combined with anterior dislocation of the femoral head is very rare. To our knowledge, there is no classification system yet for this rare form of injury, and the injury mechanism of femoral neck fracture combined with obturator head dislocation has not been described in the literature. In this study, we systematically reviewed the literature and the cases treated in our hospital, and identified and classified all injury types according to the injury mechanism of femoral neck fracture combined with anterior dislocation of the femoral head. Further, based on the experience of treating a patient with femoral neck fracture and obturator dislocation of the femoral head, a theoretical hypothesis was proposed for the injury mechanism of this rare type of injury. METHODS: A comprehensive search was conducted on PubMed, WOS, CNKI database. These fractures were classified according to the dislocation site and injury mechanism (one injury or two injuries). RESULTS: 1891 articles were initially identified through PubMed and other databases, and after bibliographic research, study screening, and removing duplicates, 1455 articles were selected. After applying the exclusion criteria, a total of 18 full-text articles describing femoral neck fractures combined with anterior dislocation of the femoral head. Different dislocation sites have different injury mechanisms. Our classification system, to the best of the authors' knowledge, allowed us to include all types of femoral neck fractures combined with anterior dislocation of the femoral head from the literature. According to the proposed classification system, the morphological features of femoral neck fracture combined with anterior dislocation of the femoral head can be accurately conveyed between doctors. CONCLUSIONS: All injury patterns can likely be identified using the proposed classification system. This can help avoid confusion in the nomenclature of femoral neck fractures combined with anterior dislocation of the femoral head and help surgeons to more accurately detect lesions, thereby guiding surgical treatment.
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Fracturas del Cuello Femoral , Luxación de la Cadera , Luxaciones Articulares , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Fijación Interna de Fracturas , Luxación de la Cadera/diagnóstico por imagen , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugía , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/etiología , Luxaciones Articulares/cirugíaRESUMEN
BACKGROUND: Endocrine disrupting chemicals (EDCs), proved to be potential carcinogenic threats to human health, have received great concerns in food field. It was essential to develop effective methods to detect EDCs in food samples. The present study proposed an efficient method to determine trace EDCs including estrone (E1), 17ß-estradiol (E2), estriol (E3) and bisphenol A (BPA) based on magnetic solid-phase extraction (MSPE) coupled high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in meat samples. RESULTS: Fe3 O4 @COF(TpBD)/TiO2 nanocomposites were synthesized via functionalization of magnetic covalent organic frameworks (COFs) with titanium dioxide (TiO2 ) nanoparticles, and used as absorbents of MSPE to enrich EDCs. The efficient EDCs enrichment relies on π-π stacking interaction, hydrogen bonding, and the interaction between titanium ions (IV, Ti4+ ) and hydroxyl groups in EDCs, which improves the selectivity and sensitivity. Under the optimized conditions, target EDCs were rapidly extracted through MSPE with 5 min. Combining Fe3 O4 @COF(TpBD)/TiO2 based MSPE and HPLC-MS/MS to determine EDCs, good linearities were observed with correlation coefficient (R2 ) ≥ 0.9989. The limits of detection (LODs) and limits of quantification (LOQs) were 0.13-0.41 µg kg-1 and 0.66-1.49 µg kg-1 , respectively. Moreover, the proposed method was successfully applied to real samples analysis. CONCLUSIONS: The established MSPE-HPLC-MS/MS method was successfully applied to determine EDCs in meat samples with rapidness, improved selectivity and sensitivity. It shows great prospects for EDCs detection in other complicated matrices. © 2020 Society of Chemical Industry.
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Cromatografía Líquida de Alta Presión/métodos , Disruptores Endocrinos/análisis , Disruptores Endocrinos/aislamiento & purificación , Contaminación de Alimentos/análisis , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodos , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/aislamiento & purificación , Estradiol/análisis , Estradiol/aislamiento & purificación , Estriol/análisis , Estriol/aislamiento & purificación , Estrona/análisis , Estrona/aislamiento & purificación , Límite de Detección , Fenoles/análisis , Fenoles/aislamiento & purificación , Extracción en Fase Sólida/instrumentaciónRESUMEN
RATIONALE: Sedatives, which are prone to cause residues in animals, have been abused in modern animal husbandry. Long-term consumption of contaminated meat products would be unfavorable to the human nervous system. Taking into account public health and food safety, it was essential to develop an effective method for the enrichment and detection of sedatives in meat. METHODS: Fe3 O4 @TbBd@ZIF-8 composites were synthesized by using Fe3 O4 nanoparticles as a magnetic core and 1,3,5-triformylbenzene (Tb) and benzidine (Bd) as two building blocks to form Fe3 O4 @TbBd. Furthermore, the zeolitic imidazolate framework-8 (ZIF-8) was modified on the surface of the Fe3 O4 @TbBd. In addition, Fe3 O4 @TbBd@ZIF-8 was used as a magnetic solid-phase extraction (MSPE) adsorbent of typical animal sedatives in pork samples. Mass spectrometry analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry in positive-ion multiple reaction monitoring mode. RESULTS: By combining the optimized MSPE approach with high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS), an accurate and sensitive method for the determination of sedatives was developed. The method exhibited good linearity in the range of 0.03-70 µg/kg with the correlation coefficient (R2 ) ranging from 0.9982 to 0.9999, high sensitivity with limits of detection (LODs) ranging from 0.04 to 0.2 µg/kg, and high precision with relative standard deviation (RSD) less than 5.5%. The adsorption behaviors of Fe3 O4 @TbBd@ZIF-8 towards sedatives were more suitably described by a pseudo-second-order kinetic and Freundlich isotherm model. CONCLUSIONS: The proposed MSPE-HPLC/MS/MS method was successfully applied to the determination of sedatives in real samples and showed excellent applicability. Several sedatives were detected in the selected meat samples. The developed method was shown to be facile, sensitive and accurate for sedative detection and also showed great prospects for determination of sedatives from other complex samples.
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Contaminación de Alimentos/análisis , Hipnóticos y Sedantes/análisis , Nanopartículas Magnéticas de Óxido de Hierro/química , Estructuras Metalorgánicas/química , Carne de Cerdo/análisis , Extracción en Fase Sólida/métodos , Adsorción , Animales , Cromatografía Líquida de Alta Presión/métodos , Humanos , Hipnóticos y Sedantes/aislamiento & purificación , Límite de Detección , Porcinos , Espectrometría de Masas en Tándem/métodosRESUMEN
Streptococcus thermophilus, one of the most important industrial lactic acid bacteria, is widely used as a starter culture in the dairy industry. Streptococcus thermophilus S-3 isolated from Chinese traditional dairy products has shown great potential for the production of larger amounts of exopolysaccharides (EPS), which significantly affect the organoleptic properties of fermented milk products. To understand the relationship between the genotype and phenotype of S. thermophilus S-3 in terms of EPS biosynthesis, its genome of strain S-3 was sequenced and the genes related to carbohydrate utilization, nucleotide sugars synthesis, and EPS biosynthesis were investigated. The genomic analysis revealed that S. thermophilus S-3 can use sucrose, mannose, glucose, galactose, and lactose. Phenotypic analysis showed that S-3 prefers fermenting lactose to fermenting glucose or galactose. The genetic analysis of nucleotide sugars and EPS biosynthesis revealed that S-3 can synthesize uridine diphosphate (UDP)-glucose, deoxythymidine diphosphate-glucose, deoxythymidine diphosphate-rhamnose, UDP-galactose, UDP-N-acetylgalactosamine, and UDP-N-acetylglucosamine. A high yield of EPS from S-3 cultivated with lactose rather than glucose as the carbon source was correlated with high transcriptional levels of the genes associated with metabolism of these nucleotide sugars and EPS biosynthesis. Our results provide a better understanding of EPS biosynthesis in S. thermophilus and can facilitate enhanced EPS production by lactic acid bacteria fermentation via genetic and metabolic engineering approaches.
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Polisacáridos Bacterianos/biosíntesis , Streptococcus thermophilus/metabolismo , Animales , Fermentación , Galactosa/metabolismo , Genoma Bacteriano , Genotipo , Glucosa/análogos & derivados , Lactosa/metabolismo , Fenotipo , Streptococcus thermophilus/genética , Nucleótidos de TiminaRESUMEN
Preclinical Research & Development The purpose of the present study is to evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The rats were pretreated with rhGLP-1 (20 µg/kg intraperitoneally, thrice a day) for 14 days. Thereafter, the rats were subjected to MCAO 90 min/reperfusion 24 hr. At 2 and 24 hr of reperfusion, the rats were assessed for neurological deficits and subsequently executed for the evaluation of cerebral infarct volume, oxidative stress parameters, and the expression of excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress parameters in ischemic penumbra were significantly alleviated in rhGLP-1-pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl-2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could significantly ameliorate neurological deficits and reduce cerebral infarct volume in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and apoptosis and the promotion of EAAT2 expression.
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Isquemia Encefálica/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Péptido 1 Similar al Glucagón/genética , Péptido 1 Similar al Glucagón/farmacología , Incretinas/farmacología , Proteínas Recombinantes/farmacología , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/complicaciones , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/fisiopatología , Transportador 2 de Aminoácidos Excitadores/metabolismo , Humanos , Infarto de la Arteria Cerebral Media , Fármacos Neuroprotectores , Estrés Oxidativo/efectos de los fármacos , Ratas , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatologíaRESUMEN
OBJECTIVE: The aim of this research was to explore quality of life (QoL), mental health status, type D personality, symptom duration, and emergency admissions of Chinese rectal cancer patients as well as the relationship between these factors. METHODS: Type D personality was measured with the 14-item Type D Personality Scale (DS14). Mental health status was measured with the Hospital Anxiety and Depression Scale (HADS). The QoL outcomes were assessed longitudinally using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires at the baseline and 6 months after diagnosis. RESULTS: Of the 852 survivors who responded (94 %), 187 (22 %) had a type D personality. The proportion of patients with duration of symptoms >1 month and being diagnosed after emergency admissions in type D group is significantly higher than that in non-type D group. At both of the time points, type D patients reported statistically significant lower scores on most of the functional scales, global health status/QoL scales, and worse symptom scores compared to patients without a type D personality. At the 6-month time point, a higher percentage of patients in the type D group demonstrated QoL deterioration. Clinically elevated levels of anxiety and depression were more prevalent in type D than in non-type D survivors. CONCLUSIONS: Type D personality was associated with poor QoL and mental health status among survivors of rectal cancer, even after adjustment for confounding background variables. Type D personality might be a general vulnerability factor to screen for subgroups at risk for longer symptom duration and emergency admissions in clinical practice.
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Calidad de Vida , Neoplasias del Recto/psicología , Sobrevivientes/psicología , Personalidad Tipo D , Anciano , Anciano de 80 o más Años , Ansiedad/complicaciones , Demografía , Depresión/complicaciones , Femenino , Humanos , Estudios Longitudinales , Masculino , Salud Mental , Persona de Mediana Edad , Neoplasias del Recto/complicaciones , Encuestas y CuestionariosRESUMEN
Background: The morphology of proximal humeral fractures (PHFs) is complex, and the fixation and selection of implants need to be guided by the fracture type and classification, which requires an accurate understanding of the fracture line. This study had three purposes. 1) Define and analyze the fracture lines and morphological features of all types PHFs by three-dimensional (3D) mapping technology. 2) Determine the osteotomy position of the biomechanical model of the PHFs according to the fracture heat map. 3) Based on the analysis of the pathological morphology and distribution of a large number of consecutive cases of PHFs, propose a novel classification of PHFs. Methods: We retrospectively collected 220 cases of PHFs and generated a 3D fracture map and heat map based on computed tomography (CT) imaging. Through analysis of the fracture morphology of the 220 PHFs, a novel classification was proposed. The primary criterion for staging was the continuity between the humeral head and the greater tuberosity and lesser tuberosity, and the secondary criterion was the relationship between the humeral head segment and the humeral shaft. Results: The fracture line was primarily found around the metaphyseal zone of region of the surgical neck, with the most extensive distribution being below the larger tuberosity and on the posterior medial side of the epiphysis. We suggest that the osteotomy gap should be immediately (approximately 5-10 mm) below the lower edge of the articular surface. The most common type of fracture was type I3 (33 cases, 15.0%), followed by type IV3 fracture (23 cases, 10.4%), and type III2 fracture (22 cases, 10.0%). Interobserver and intraobserver reliability analysis for the fracture classification revealed a k value (95% confidence interval) of 0.639 (0.57-0.71) and 0.841, P < 0.01, respectively. Conclusion: In this study, the fracture line and morphological characteristics of PHFs were clarified in detail by 3D mapping technique. In addition, a new classification method was proposed by analysis of the morphological characteristics of 220 PHFs, A two-part fracture model for PHFs is also proposed.
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Canagliflozin (CFZ) tablets was a commercially new class of anti-diabetic drug, CFZ had various anhydrate crystal forms and two hydrate crystal forms (Canagliflozin hemihydrate (Hemi-CFZ) and Canagliflozin monohydrate (Mono-CFZ) crystal form). The active pharmaceutical ingredients (APIs) of commercially available CFZ tablets were Hemi-CFZ, was easily convert to CFZ or Mono-CFZ under the influence of temperature, pressure, humidity and other factors in tablets processing, storage, and transportation, thus affected bioavailability and efficacy of tablets. Therefore, quantitative analysis of low-content CFZ and Mono-CFZ in tablets was essential to control tablets' quality. The main objective of this study was to explore the feasibility and in-depth explain its quantitative analysis mechanism of NIR for quantitative analysis of low-content CFZ/Mono-CFZ in CFZ tablets. PLSR models for low-content CFZ/Mono-CFZ were established by NIR solid-state analysis technique in different resolutions with different wavenumber regions combined with various pretreatments methods (such as Multiplicative Scatter Correction (MSC), Standard Normal Variate (SNV), Savitzky-Golay First Derivative (SG1st), Savitzky-Golay Second Derivative (SG2nd) and Wavelet Transform (WT)), and the PLSR models were verified. The feasibility of NIR spectroscopy for quantitative analysis of low-content CFZ and Mono-CFZ in CFZ tablets was discussed and analyzed from multiple perspectives, which included the distribution of effective information on the spectrum, the influence of resolution on PLSR models performance, the variance contribution/cumulative variance contribution of PLSR model principal components (PCs), the relation of PCI loadings, scores of the spectra and CFZ/Mono-CFZ content, and the mechanism of quantitative analysis was in-depth explained simultaneously. Eventually the most suitable PLSR models in 0.0000-10.0000â¯% w/wâ¯% obtained. That can provide theoretical support for quantitative analysis of low-content impurity crystal during the production, storage and transportation of CFZ tablets, thus provide reference methods for quality control of CFZ tablets and a reliable reference method for quantitative analysis of impurity crystal forms and quality control of similar drugs.
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Canagliflozina , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Comprimidos , Análisis de los Mínimos CuadradosRESUMEN
Site-directed mutagenesis for creating point mutations, sometimes, gives rise to plasmids carrying variable number tandem repeats (VNTRs) locally, which are arbitrarily regarded as polymerase chain reaction (PCR) related artifacts. Here, the alternative end-joining mechanism is reported rather than PCR artifacts accounts largely for that VNTRs formation and expansion. During generating a point mutation on GPLD1 gene, an unexpected formation of VNTRs employing the 31 bp mutagenesis primers is observed as the repeat unit in the pcDNA3.1-GPLD1 plasmid. The 31 bp VNTRs are formed in 24.75% of the resulting clones with copy number varied from 2 to 13. All repeat units are aligned with the same orientation as GPLD1 gene. 43.54% of the repeat junctions harbor nucleotide mutations while the rest don't. Their demonstrated short primers spanning the 3' part of the mutagenesis primers are essential for initial creation of the 2-copy tandem repeats (TRs) in circular plasmids. The dimerization of mutagenesis primers by the alternative end-joining in a correct orientation is required for further expansion of the 2-copy TRs. Lastly, a half-double priming strategy is established, verified the findings and offered a simple method for VNTRs creation on coding genes in circular plasmids without junction mutations.
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Gastric cancer (GC) is a malignant tumor with high incidence rate and mortality. Due to the lack of effective diagnostic indicators, most patients are diagnosed in late stage and have a poor prognosis. An increasing number of studies have proved that Peptidylprolyl isomerase A (PPIA) can play an oncogene role in various cancer types. However, the precise mechanism of PPIA in GC is still unclear. Herein, we analyzed the mRNA levels of PPIA in pan-cancer. The prognostic value of PPIA on GC was also evaluated using multiple databases. Additionally, the relationship between PPIA expression and clinical factors in GC was also examined. We further confirmed that PPIA expression was not affected by genetic alteration and DNA methylation. Moreover, the upstream regulator miRNA and lncRNA of PPIA were identified, which suggested that LINC10232/miRNA-204-5p/PPIA axis might act as a potential biological pathway in GC. Finally, this study revealed that PPIA was negatively correlated with immune checkpoint expression, immune cell biomarkers, and immune cell infiltration in GC.