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Emergency wounds are often accompanied by bacterial infection, oxidative stress, and excessive inflammation due to the inability to quickly close and stop bleeding, resulting in chronic wounds that are difficult to heal. Clinically, surgical suturing is the fastest method for wound closure, but it is only suitable for wounds with small bleeding volumes and causes unsightly scar formation. Consequently, there is a critical need for hemostatic dressings versatile enough to address a spectrum of diverse and intricate wounds, especially in emergency scenarios. In this study, we constructed a unique versatile natural gelatin-based hydrogel with hemostasis, antibacterial, and anti-inflammation properties. The hydrogel was composed of 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrylethylenediamine-modified methacrylated gelatin (GelMA-NB) and epigallocatechin gallate-grafted polylysine (EPL-EGCG), which imparts adhesion, antibacterial and antioxidant properties to the hydrogel. Simultaneously, the hydrogel was loaded with GelMA microspheres encapsulating natural resveratrol (RES@GM). This combination not only exhibited outstanding hemostatic capabilities but also preserved the anti-inflammatory potential of RES. In different animal models, the hydrogel exhibited outstanding hemostatic and wound healing effects, down-regulated the expression of IL-1ß to promote inflammatory regulation and potential for angiogenesis and anti-scar. In conclusion, unique versatile natural gelatin-based hydrogel suitable for various complex wounds provides a promising strategy for emergency wound dressing applications.
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Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.
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BACKGROUND: Microbiota dysbiosis has been reported to lead to leaky epithelia and trigger numerous dermatological conditions. However, potential causal associations between skin microbiota and skin fibrosis and whether immune cells act as mediators remain unclear. METHODS: Summary statistics of skin microbiota, immune cells, and skin fibrosis were identified from large-scale genome-wide association studies summary data. Bidirectional Mendelian randomization was performed to ascertain unidirectional causal effects between skin microbiota, immune cells, and skin fibrosis. We performed a mediation analysis to identify the role of immune cells in the pathway from skin microbiota to skin fibrosis. RESULTS: Three specific skin microbiotas were positively associated with skin fibrosis, while the other three were negative. A total of 15 immune cell traits were associated with increased skin fibrosis risk, while 27 were associated with a decreased risk. Moreover, two immune cell traits were identified as mediating factors. CONCLUSIONS: Causal associations were identified between skin microbiota, immune cells, and skin fibrosis. There is evidence that immune cells exert mediating effects on skin microbiota in skin fibrosis. In addition, some strains exhibit different effects on skin fibrosis in distinct environments.
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The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5' region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.
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Empalme Alternativo , Receptor de Muerte Celular Programada 1 , Isoformas de Proteínas , Humanos , Animales , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Ratones , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/inmunología , Progresión de la Enfermedad , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/metabolismo , Ratones Endogámicos C57BL , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
PURPOSE: This study aimed to explore the correlation between hemoglobin levels and albuminuria in US adults. METHODS: This cross-sectional investigation analyzed the National Health and Nutrition Examination Survey (NHANES) information from 2011 to 2020. Data on hemoglobin, albuminuria, and other variables were collected from all participants. The logistic-regression analyses and smoothed curves were used to substantiate the research objectives. RESULTS: The average age of the 8,868 participants was 49.5 ± 17.3 years, and 49.3% were men. The prevalence of albuminuria was 12.1%. After adjusting for potential variables in the logistic-regression analysis models, hemoglobin (per 1 g/dL increase) was inversely associated with the presence of albuminuria (odds ratio [OR], 0.92; 95% confidence interval [95%CI], 0.87-0.97). Compared with participants in quartile 3 (Q3, 14.1-15.0 g/dL) for hemoglobin levels, those in the lowest quartile 1 (Q1, 6.1-13.0 g/dL) and highest quartile 4 (Q4, 15.1-19.6 g/dL) had adjusted ORs for albuminuria of 1.48 (95% CI, 1.19-1.85) and 1.11 (95% CI, 0.9-1.38), respectively. Our observations indicated a U-shaped association between hemoglobin levels and albuminuria, with a point of inflection at approximately 15.5 g/dL. The effect sizes and CIs below and above this point were 0.853 (95% CI, 0.798-0.912) and 1.377 (95% CI, 1.055-1.797), respectively. CONCLUSION: This study indicates that the presence of albuminuria is linked to both low and high hemoglobin levels in US adults. The management of hemoglobin may benefit kidney health.
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Hematopoietic stem cells (HSCs) maintain homeostasis in the hematopoietic ecosystem, which is tightly regulated at multiple layers. Acute myeloid leukemia (AML) is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells (LSCs). Since somatic mutations in DNA methylation-related genes frequently occur in AML, DNA methylation is widely altered and functions as a starting engine for initiating AML. Additionally, RNA modifications, especially N6-methyladenosine (m6A), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of m6A modifications to facilitate cells with hallmarks of cancer. Given the complex pathogenesis and poor prognosis of AML, it is important to fully understand its pathogenesis. Here, we mainly focus on DNA methylation and RNA m6A modification in hematopoiesis and AML and summarize recent advances in this field.
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Background: Tracheo-carinal resection and reconstruction in cases of extensive malignant tumors present a significant surgical challenge, often complicated by high anastomotic tension and potential for incomplete anastomosis. Case Description: We report on a 45-year-old male with a primary adenoid cystic carcinoma. The tumor was about 3 cm in size and invaded about 1 cm of the lower trachea, 2 cm of the left main bronchus (LMB), and 1 cm of the right main bronchus (RMB), blocking about 70% of the tracheal lumen, 90% of the LMB, and 50% of the RMB. Resection of the lower trachea and part of the LMB and RMB was performed via the right chest. We used the right main bronchial flap as a bridge, suturing it separately to the lower tracheal segment and the LMB, thereby completing the carinal reconstruction. This technique was crucial for bridging the defect between the trachea and LMB, which was impossible to anastomose directly due to the tumor's extensive involvement. The elliptical-shaped lingual flap from the RMB provided a stable and tension-free foundation for the reconstruction, overcoming the limitations of conventional methods. Conclusions: The novel carinal reconstruction technique demonstrated a reliable alternative for complex tracheo-carinal defects, ensuring tension-free anastomosis and complete tumor resection with clear margins.
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INTRODUCTION AND IMPORTANCE: Fallopian tube cancer that is characterized only by inguinal lymph node metastasis without intra-abdominal widespread is rare. Here we report a patient with primary Fallopian tube cancer with bilateral inguinal metastases as the first symptom. CASE PRESENTATION: A 68-year-old patient with primary Fallopian tube cancer, with painless bilateral inguinal enlargement (7 × 6 cm on the right side, 3 × 2 cm on the left side) as the only manifestation, was confirmed by preoperative biopsy as metastatic high-grade serous denocarcinoma, consider the adnexal or peritoneal source. Pelvic MRI, abdominal CT and PET-CT showed irregular signal foci can be seen in the right adnexal area, with a maximum cross-section of about 7.5 × 7.0 × 4.0 cm, considering malignancy, ovarian cancer may be possible; bilateral pelvic wall, bilateral inguinal, right iliac vessels with hypermetabolic lymph nodes. Serum CA125 level was markedly elevated at 922.40 U/ml and HE4 at 394.50 pmol/L. No abnormality was found in gastrointestinal endoscopy. At exploratory laparotomy, the tumor was confined to the right rear of the uterus, and a solid tumor with a size of about 10 × 6 × 6 cm was seen. The surface was smooth and closely related to the uterus. There was almost no tumor spread in the pelvic abdominal cavity, but there was 50 ml of pale blood-colored peritoneal fluid. The right ovarian capsule was intact. Cytoreductive surgery was performed, postoperative pathology confirmed adenocarcinoma of the right fallopian tube, and the patient received six cycles of paclitaxel plus cisplatin combination chemotherapy were administered, with three 3-weeks intervals between cycles. And subsequent the patient participated in a clinical trial. The work has been reported in line with the SCARE criteria. CLINICAL DISCUSSION: Literature review indicates that inguinal lymph node as the first manifestation of fallopian tube cancer is not usual, and with no widespread lymphadenopathies and abdominopelvic cavity are even rarer. This case shows that rare cases with only inguinal lymph node metastasis may occur through the underlying lymphatic and/or hematogenous routes. CONCLUSION: The diagnosis of tubal cancer is sometimes complicated and delayed. For elderly women without nonspecific symptoms, especially those with obvious masses, detailed examinations, and imaging studies should be carried out in time. The treatment of tubal cancer is multi-modal. Due to the high risk of recurrence of fallopian tube cancer, the possibility of metastasis after the initial diagnosis is large, so it is very important to receive close and regular follow-up for patients with fallopian tube cancer after treatment. We suggest that more tumor centers study the possible mechanisms, metastasis patterns, biological characteristics, etc. of such patients, and at the same time efforts should be made to early differential diagnosis, and ultimately prolong the survival time of such patients.
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Introduction: Dementia and physical disability are serious problems faced by the aging population, and their occurrence and development interact. Methods: Based on data from a national cohort of Chinese people aged 60 years and above from the China Health and Retirement Longitudinal Survey from 2011 to 2018, we applied the group-based trajectory model to identify the heterogeneous trajectories of cognitive function and physical disability in participants with different physical disability levels. Next, multinomial logistic regression models were used to explore the factors affecting these trajectories. Results: The cognitive function trajectories of the Chinese older people could be divided into three characteristic groups: those who maintained the highest baseline level of cognitive function, those with a moderate baseline cognitive function and dramatic progression, and those with the worst baseline cognitive function and rapid-slow-rapid progression. The disability trajectories also fell into three characteristic groups: a consistently low baseline disability level, a low initial disability level with rapid development, and a high baseline disability level with rapid development. Compared with those free of physical disability at baseline, a greater proportion of participants who had physical disability at baseline experienced rapid cognitive deterioration. Education, income, type of medical insurance, gender, and marital status were instrumental in the progression of disability and cognitive decline in the participants. Discussion: We suggest that the Chinese government, focusing on the central and western regions and rural areas, should develop education for the older people and increase their level of economic security to slow the rate of cognitive decline and disability among this age group. These could become important measures to cope with population aging.
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Cognición , Disfunción Cognitiva , Personas con Discapacidad , Humanos , Anciano , Femenino , Masculino , China/epidemiología , Personas con Discapacidad/estadística & datos numéricos , Estudios Longitudinales , Persona de Mediana Edad , Disfunción Cognitiva/epidemiología , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Intrapancreatic fat deposition (IPFD) exerts a significant negative impact on patients with type 2 diabetes mellitus (T2DM), accelerates disease deterioration, and may lead to impaired ß-cell quality and function. AIM: To investigate the correlation between T2DM remission and IPFD. METHODS: We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023, including 40 patients with weight loss-induced T2DM remission (research group) and 40 patients with short-term intensive insulin therapy-induced T2DM remission (control group). We comparatively analyzed improvements in IPFD [differential computed tomography (CT) values of the spleen and pancreas and average CT value of the pancreas]; levels of fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and insulin; and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Correlation analysis was performed to explore the association between T2DM remission and IPFD. RESULTS: After treatment, the differential CT values of the spleen and pancreas, FBG, 2hPBG, and HOMA-IR in the research group were significantly lower than those before treatment and in the control group, and the average CT value of the pancreas and insulin levels were significantly higher. Correlation analysis revealed that the greater the T2DM remission, the lower the amount of IPFD. CONCLUSION: T2DM remission and IPFD are inversely correlated.
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Hematopoietic homeostasis is maintained by hematopoietic stem cells (HSCs), and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs. Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases, including acute myeloid leukemia (AML). Thus, understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology. N 6-methyladenosine (m6A) is a common modification in mammalian messenger RNAs (mRNAs) and plays important roles in various biological processes. In this study, we performed a comparative analysis of the dynamics of the RNA m6A methylome of hematopoietic stem and progenitor cells (HSPCs) and leukemia-initiating cells (LICs) in AML. We found that RNA m6A modification regulates the transformation of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs. Interestingly, m6A modification leads to reprogramming that promotes cellular transformation during AML development, and LIC-specific m6A targets are recognized by different m6A readers. Moreover, the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2 (ABCD2) is a key factor that promotes AML development, and deletion of ABCD2 damages clonogenic ability, inhibits proliferation, and promotes apoptosis of human leukemia cells. This study provides a comprehensive understanding of the role of m6A in regulating cell state transition in normal hematopoiesis and leukemogenesis, and identifies ABCD2 as a key factor in AML development.
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The study aimed to evaluate the association between high-altitude polycythemia and hypertension in adults residing on Anduo County's plateau, which is located 4700 meters above sea level. A total of 387 individuals participated in the cross-sectional survey conducted between April and May of 2021. Interviews, physical inspections, and laboratory tests were employed to gather information about all of the subjects. The association between high-altitude polycythemia and hypertension was assessed using multivariable logistic regression models. The average age of the 387 participants was 32.6 ± 6.3 years. Of these participants, 260 (67%) were male. The overall prevalence of hypertension was 27.1% (57/380). When stratified by gender, the prevalence was 12.6% (16/127) in females and 34.2% (89/260) in males. The overall prevalence of high-altitude polycythemia was 19.6% (76/387). When stratified by gender, the prevalence was 26.2% (68/260) in males and 6.3% (8/127) in females. During logistic regression analysis, we found that participants with elevated hemoglobin per 10 g/L had a 26% greater risk of hypertension (adjusting for odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44). Additionally, high-altitude polycythemia greatly increased the risk of hypertension in comparison to non-high-altitude polycythemia (OR, 3.01; 95% CI, 1.66-5.44, P < 0.001). The consistency of the results was further demonstrated by stratified and interaction analyses, showing that Hans individuals had a higher risk of hypertension. High-altitude polycythemia is positively associated with hypertension in adults residing at Tibetan ultrahigh altitudes. The results of the investigation may aid in the planning of future research and guide the development of targeted healthcare practices for high-altitude populations, particularly among Han Chinese residents of the Tibetan Plateau.
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Altitud , Hipertensión , Policitemia , Humanos , Masculino , Femenino , Policitemia/epidemiología , Policitemia/diagnóstico , Adulto , Estudios Transversales , Hipertensión/epidemiología , Hipertensión/diagnóstico , Tibet/epidemiología , Prevalencia , Factores de Riesgo , Persona de Mediana Edad , Adulto JovenRESUMEN
G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype. Overexpression of GPS2 promoted hemin-induced hemoglobin synthesis in K562 cells as assessed by the increased percentage of benzidine-positive cells and the deeper red coloration of the cell pellets. In contrast, knockdown of GPS2 inhibited hemin-induced erythroid differentiation of K562 cells. GPS2 overexpression also enhanced erythroid differentiation of K562 cells induced by cytosine arabinoside (Ara-C). GPS2 induced hemoglobin synthesis by increasing the expression of globin and ALAS2 genes, either under steady state or upon hemin treatment. Promotion of erythroid differentiation of K562 cells by GPS2 mainly relies on NCOR1, as knockdown of NCOR1 or lack of the NCOR1-binding domain of GPS2 potently diminished the promotive effect. Thus, our study revealed a previously unknown role of GPS2 in regulating human primitive erythropoiesis in K562 cells.
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Diferenciación Celular , Eritropoyesis , Hemina , Leucemia Eritroblástica Aguda , Co-Represor 1 de Receptor Nuclear , Humanos , 5-Aminolevulinato Sintetasa/genética , 5-Aminolevulinato Sintetasa/metabolismo , Células Eritroides/metabolismo , Células Eritroides/citología , Eritropoyesis/genética , Técnicas de Silenciamiento del Gen , Hemina/farmacología , Hemoglobinas/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Células K562 , Leucemia Eritroblástica Aguda/patología , Leucemia Eritroblástica Aguda/metabolismo , Leucemia Eritroblástica Aguda/genética , Co-Represor 1 de Receptor Nuclear/metabolismo , Co-Represor 1 de Receptor Nuclear/genéticaRESUMEN
Objective: Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis. Methods: We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results. Results: According to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis. Objective conclusion: There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.
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Objective: Despite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure. Methods: We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed. Results: We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150µg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150µg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection. Conclusion: G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.
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Implantación del Embrión , Fertilización In Vitro , Factor Estimulante de Colonias de Granulocitos , Índice de Embarazo , Humanos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Implantación del Embrión/efectos de los fármacos , Embarazo , Fertilización In Vitro/métodos , Transferencia de Embrión/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: Although low-dose computed tomography has been proven effective to reduce lung cancer-specific mortality, a considerable proportion of surgically resected high-risk lung nodules were still confirmed pathologically benign. There is an unmet need of a novel method for malignancy classification in lung nodules. METHODS: We recruited 307 patients with high-risk lung nodules who underwent curative surgery, and 247 and 60 cases were pathologically confirmed malignant and benign lung lesions, respectively. Plasma samples from each patient were collected before surgery and performed low-depth (5×) whole-genome sequencing. We extracted cell-free DNA characteristics and determined radiomic features. We built models to classify the malignancy using our data and further validated models with 2 independent lung nodule cohorts. RESULTS: Our models using one type of profile were able to distinguish lung cancer and benign lung nodules at an area under the curve metrics of 0.69 to 0.91 in the study cohort. Integrating all the 5 base models using cell-free DNA profiles, the cell-free DNA-based ensemble model achieved an area under the curve of 0.95 (95% CI, 0.92-0.97) in the study cohort and 0.98 (95% CI, 0.96-1.00) in the validation cohort. At a specificity of 95.0%, the sensitivity reached 80.0% in the study cohort. With the same threshold, the specificity and sensitivity had similar performances in both validation cohorts. Furthermore, the performance of area under the curve reached 0.97 in both the study and validation cohorts when considering the radiomic profile. CONCLUSIONS: The cell-free DNA profiles-based method is an efficient noninvasive tool to distinguish malignancies and high-risk but pathologically benign lung nodules.
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Increasing interests have been directed toward the exploitation of origami techniques in developing biomimetic soft robots. There is a need for effective design solutions to exploit the properties of origami structure with simplified assembly and improved robotic mobility. In this study, inspired by human long-standing jumps, we present a soft electrostatically driven legged accordion fold actuator made by turning a flat paper into hollow polyhedron structure with a spring like rear and capable of electrostatic pad-assisted steering and carrying loads. Without the need for integration of external actuators, the actuator is composed of the electrostatic origami actuator itself supported by a single-fold leg with fast response, easy fabrication process, and low cost. Initiated by periodic deformation around the folding hinges caused by alternating current voltage and ground reaction forces, the actuators exhibit a unique jump-slide movement outperforming other existing soft electrostatic actuators/robots in terms of relative speed. We examined the effect of different geometric and external factors on the relative speed and highlighted the significance of body scale and short-edge panels as the elastic elements, as well as operating at resonance frequency in producing effective performances. Theoretical locomotion models and finite element analysis were carried out to interpret the working principle and validate experimental results.
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Zinc oxide (ZnO) is a widely employed material for enhancing the performance of cellulose-based triboelectric nanogenerators (C-TENGs). Our study provides a novel chemical interpretation for the improved output efficiency of ZnO in C-TENGs. C-TENGs exhibit excellent flexibility and integration, achieving a maximum open-circuit voltage (Voc) of 210 V. The peak power density is 54.4 µW/cm2 with a load resistance of 107 Ω, enabling the direct powering of 191 light-emitting diodes with the generated electrical output. Moreover, when deployed as self-powered sensors, C-TENGs exhibit prolonged operational viability and responsiveness, adeptly discerning bending and motion induced by human interaction. The device's sensitivity, flexibility, and stability position it as a promising candidate for a diverse array of energy-harvesting applications and advanced healthcare endeavors. Specifically, envisaging sensitized wearable sensors for human activities underscores the multifaceted potential of C-TENGs in enhancing both energy-harvesting technologies and healthcare practices.
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Óxido de Zinc , Humanos , Fenómenos Físicos , Movimiento (Física) , Celulosa , Actividades HumanasRESUMEN
The movements of syringes and medications during an anesthetic case have yet to be systematically documented. We examine how syringes and medication move through the anesthesia work area during a case. We conducted a video-based observational study of 14 laparoscopic surgeries. We defined 'syringe events' as when syringe was picked up and moved. Medications were administered to the patient in only 48 (23.6%) of the 203 medication or syringe events. On average, 14.5 syringe movements occurred in each case. We estimate approximately 4.2 syringe movements for each medication administration. When a medication was administered to the patient (either through the IV pump or the patient port), it was picked up from one of 8 locations in the work area. Our study suggests that the syringe storage locations vary and include irregular locations (e.g., patient bed or provider's pockets). Our study contributes to understanding the complexity in the anesthesia work practices.