OBJECTIVE To explore the prognostic significance of the prognostic nutrition index(PNI)in patients with hypopharyngeal cancer undergoing surgical treatment.METHODS Clinical and pathological data of 117 patients with hypopharyngeal carcinoma who underwent surgical treatment at the center of Otolaryngology Head and Neck Surgery of Beijing Friendship Hospital,Capital Medical University from May 2014 to June 2022 were collected.The prognostic significance of hematological indicators such as PNI and neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and systemic immune inflammation index(SⅡ)were investigated.The time-dependent receiver operating characteristic(tROC)curves were used to analyze the sensitivity and specificity of various hematological indicators and to determine their optimal cutoffvalues.The Kaplan-Meier method was used to plot the postoperative survival curve,and the Cox regression model was used to analyze the correlation between PNI and overall survival(OS)and disease-free survival(DFS).RESULTS 117 patients were enrolled in this cohort,of which 109 were clinically classified as advanced stage(Ⅲ-Ⅳ).63 cases underwent surgery to preserve laryngeal function.The 5-year OS is 46.07％.According to the analysis of the tROC curve,the optimal cutoffvalue for PNI is 46.75.PNI is correlated with tumor T staging,NLR,PLR,and SⅡ.Kaplan Meier univariate analysis showed that PNI was significantly correlated with OS and DFS(P<0.05).In addition,tumor N-stage,postoperative complications,adverse pathological prognostic factors,NLR,PLR,and SⅡ were all significantly correlated with OS(P<0.05).Tumor N-stage,laryngeal preservation,postoperative complications,NLR,and SⅡ were significantly correlated with DFS(P<0.05).The Cox multivariate analysis results indicated that PNI,tumor N-stage,and postoperative complications were independent factors affecting OS and DFS.CONCLUSION Preoperative PNI,tumor N-stage,and postoperative complications are independent risk factors for OS and DFS in patients with hypopharyngeal carcinoma.PNI,as a prognostic indicator for predicting hypopharyngeal cancer patients,is superior to other hematological indicators.

BACKGROUND:Osteoporosis is a significant contributor to the global burden of disease and disability.Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets.Although existing studies have suggested an association between plasma proteins and osteoporosis,the causal nature of these associations is not fully clarified.Therefore,it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.OBJECTIVE:To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.METHODS:A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci(P<5×10-8)were obtained from the UK Biobank database and used as instrumental variables,with linkage disequilibrium excluded.Summary data on osteoporosis were collected from the FinnGen database,which included 438 872 individuals of European descent.The study was analyzed using inverse variance weighting,MR-Egger regression,weighted median,and several sensitivity analyses to ensure the robustness of the results.Further,a protein-protein interaction network was constructed,and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.RESULTS AND CONCLUSION:(1)The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis(P<0.05).Among them,20 plasma proteins,including chromosome 19 open reading frame 12(odds ratio[OR]=0.610;95%confidence interval[CI]:0.483-0.769,P=2.967×10-5)and epidermal growth factor(EGF;OR=0.877;95%CI:0.770-0.999,P=0.049),might be associated with a reduced risk of osteoporosis.In contrast,30 plasma proteins,such as C-C motif chemokine ligand(CCL)18(OR=1.091;95%CI:1.037-1.147,P=0.001)and CD209(OR=1.036;95%CI:1.003-1.070,P=0.034),might be associated with an increased risk of osteoporosis.After Bonferroni correction,only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis.(2)Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity,indicating the robustness of the results.(3)The construction of the PPI network identified core proteins such as EGF,CCL5,C-X-C motif chemokine ligand(CXCL)13,CXCL5,vascular endothelial growth factor C,CCL17,CCL18,TEK receptor tyrosine kinase,tyrosine kinase with immunoglobulin like and EGF like domains 1,and CCL23.(4)Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system,influencing osteoporosis through processes such as signal transduction,cell migration,and chemotaxis.(5)This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis,highlighting the utility of a large-scale,data-driven approach to identify new biomarkers and drug targets in diverse populations.Additionally,our findings suggest that processes such as immune signaling,cell migration,and chemotaxis play significant roles in the pathogenesis of osteoporosis,offering new directions for research under specific genetic backgrounds and environmental factors.Finally,the core proteins identified in this study(e.g.,EGF,CCL5,and CXCL13)may serve as novel biomarkers or therapeutic targets,providing a new basis for the precise prevention and treatment of osteoporosis.

This paper systematically reviews the phased development history of spacesuit technology across various nations,analyzes its core technologies and breakthroughs,points out the limitations of current spacesuit technology,and explores future directions for spacesuit development in response to deep-space exploration and commercialization demands.It clarifies that spacesuits are transitioning from passive protective gear to intelligent operational platforms,requiring interdisciplinary innovations to overcome key challenges such as lightweight design,adaptive systems,high reliability,and efficient human-machine interaction.

Objective With the development of manned space missions to the moon and space exploration,extravehicular activities become more frequent and extravehicular mission become more complex,which puts forward higher requirements for the extravehicular spacesuit.In order to ensure the ergonomics of spacesuit,the flexible joints are usually adopted in the limbs of spacesuit.The structural design of large angle of movement and low resistance joints is the basic for ensuring the ergonomics of spacesuit.Methods This study established a method of spacesuit joint structure to analysis the motion characteristic of typical joints.Firstly,the structure and activity characteristics of the spacesuit and lunar space suits were comprehensively analyzed,and the activity characteristics of different typical structure are qualitatively analyzed based on existing empirical method.Then,the dynamics of typical structure was analyzed by finite element model.By studying the change trend of motion of spacesuit joint with motion angle,and the motion characteristic curve was obtained.Finally,the model was studied according to different structural size parameters.The influence of structural parameters on the motion characteristics was analyzed,and the curves was obtained to provide a basis for design of spacesuit motion joint structure.Results Through the above analysis,the motion characteristics of different typical structure are obtained qualitatively.And the influence of different structure parameters on the motion characteristics was analyzed.This establishes the method basis for structure design.Conclusion The study was carried out a method based on finite element model for joint motion analysis,which is suitable for the design of typical joint structure of spacesuit.

When conducting extravehicular activities under low-gravity conditions like on the moon,the weight of the spacesuit is one of the loads that human body has to bear.The centroid position of the spacesuit will affect the motion control of the human-spacesuit system.In order to reveal the influence of the centroid position of the lunar spacesuit on human motion under lunar-gravity,a suspended 1/6 gravity simulation system was used for the experiment.When subjects were under different load centroids which include front and back on sagittal plane,left and right on coronal plane,up and down on cross-section plane,near to coordinate origin,the postures and plantar pressures of subjects during three typical movements:standing,single-knee standing and walking were captured.Inverse dynamics solution is adopted to analyze the joint torques of human body in above conditions.Combined with the subjective evaluation,the appropriate load centroid area was analyzed by comparative.The experiment shows that,human is non-sensitive to the up and down change of load centroid,the after is back change,the front and right load centroid are the mostly avoided.The results obtained by this study will provide a reference for the layout design of the lunar spacesuit.

Objective Maintain a sable differential pressure inside the Underwater Positive Pressure Protective Suit(UPPPS)to ensure normal breathing and safe underwater operations for the diver.Methods Utilize a pressure regulator as the UPPPS's pressure control valve to automatically maintain the differential pressure inside the suit.Results By establishing a physical model,the relationship between the steady-state differential pressure with the ventilation flow rate and the ambient pressure was obtained.(1)The ventilation flow rate is positively correlated with the steady-state differential pressure,the higher the ventilation flow rate,the greater the steady-state differential pressure.(2)At the same ventilation flow rate,the larger the ambient pressure is,the smaller the steady-state differential pressure is.Underwater unmanned and manned experiments using the UWT suit were conducted.The expermental results are in agreement with the theoretical analysis.Conclusion The performance of pressure regulator has been verified by the underwater experiments,it effectively stabilizes the differential pressure within the UPPPS.

BACKGROUND:Osteoporosis is a significant contributor to the global burden of disease and disability.Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets.Although existing studies have suggested an association between plasma proteins and osteoporosis,the causal nature of these associations is not fully clarified.Therefore,it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.OBJECTIVE:To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.METHODS:A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci(P<5×10-8)were obtained from the UK Biobank database and used as instrumental variables,with linkage disequilibrium excluded.Summary data on osteoporosis were collected from the FinnGen database,which included 438 872 individuals of European descent.The study was analyzed using inverse variance weighting,MR-Egger regression,weighted median,and several sensitivity analyses to ensure the robustness of the results.Further,a protein-protein interaction network was constructed,and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.RESULTS AND CONCLUSION:(1)The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis(P<0.05).Among them,20 plasma proteins,including chromosome 19 open reading frame 12(odds ratio[OR]=0.610;95%confidence interval[CI]:0.483-0.769,P=2.967×10-5)and epidermal growth factor(EGF;OR=0.877;95%CI:0.770-0.999,P=0.049),might be associated with a reduced risk of osteoporosis.In contrast,30 plasma proteins,such as C-C motif chemokine ligand(CCL)18(OR=1.091;95%CI:1.037-1.147,P=0.001)and CD209(OR=1.036;95%CI:1.003-1.070,P=0.034),might be associated with an increased risk of osteoporosis.After Bonferroni correction,only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis.(2)Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity,indicating the robustness of the results.(3)The construction of the PPI network identified core proteins such as EGF,CCL5,C-X-C motif chemokine ligand(CXCL)13,CXCL5,vascular endothelial growth factor C,CCL17,CCL18,TEK receptor tyrosine kinase,tyrosine kinase with immunoglobulin like and EGF like domains 1,and CCL23.(4)Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system,influencing osteoporosis through processes such as signal transduction,cell migration,and chemotaxis.(5)This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis,highlighting the utility of a large-scale,data-driven approach to identify new biomarkers and drug targets in diverse populations.Additionally,our findings suggest that processes such as immune signaling,cell migration,and chemotaxis play significant roles in the pathogenesis of osteoporosis,offering new directions for research under specific genetic backgrounds and environmental factors.Finally,the core proteins identified in this study(e.g.,EGF,CCL5,and CXCL13)may serve as novel biomarkers or therapeutic targets,providing a new basis for the precise prevention and treatment of osteoporosis.

To study the prevalence of depression, anxiety, and insomnia among social workers during the prolonged battle against the COVID-19 pandemic and explore the associated risk factors.

Objective:To study the short-term clinical outcomes of different courses of antenatal corticosteroids (ACS) for preterm twins.Methods:From January 2017 to December 2021, preterm twins with gestational age (GA) 24-34 weeks admitted to the neonatal ward of our hospital and received ACS were retrospectively studied. The infants were assigned into single-course group, partial-course group and multiple-course group according to ACS courses. The short-term clinical outcomes were compared among the groups. SPSS software version 25.0 was used for statistical analysis.Results:A total of 286 infants were enrolled in this study, including 128 in single-course group, 89 in partial-course group and 69 in multiple-course group. Compared with single-course group, the risks of neonatal respiratory distress syndrome (RDS) in both partial-course group ( OR=2.332, 95% CI 1.028-5.293, P=0.043) and multiple-course group ( OR=3.872, 95% CI 1.104-13.584, P=0.034) were higher. The birth length in multiple-course group ( β=-0.016, 95% CI -0.029 - -0.002, P=0.024) was lower than single-course group. Conclusions:The risks of neonatal RDS in preterm twins are higher in partial-course and multiple-course of ACS. A full course of ACS should be used to prevent neonatal RDS until further evidence of effectiveness is available.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*