Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective To explore the risk factors of incision complications after cerebral revasculariza-tion.Methods The patients who underwent vascular reconstruction for craniocerebral vascular diseases in the Affiliated Hospital of Xuzhou Medical University who underwent revascularization for cerebrovascular disea-ses from January 2018 to December 2022 were retrospectively included,and the patients were divided into the incision complications group and the no incision complications group.Among them,this study documented the delayed complications following incision healing after cerebral revascularization.The baseline clinical data of patients'demographics and incisional complications after cerebral revascularization were recorded,and possi-ble influencing factors were included in a binary logistic regression analysis to analyze the influencing factors that may contribute to the occurrence of incisional complications after cerebral revascularization.Results A total of 117 patients who underwent cerebral revascularization were included,including 25 cases(21.4％)in the group with incision complications,including 7 cases(28.0％)of fat liquefaction,4 cases(16.0％)of inci-sion dehiscence,7 cases(28.0％)of incision infection,and 7 cases(28.0％)of necrosis,while 92 cases(78.6％)in the group without incisional complications.Univariate analysis showed that there was no statisti-cally significant difference in gender,age,hypertension,hyperlipidemia,smoking,drinking,disease type,and vascular reconstruction type between the patients with incision complications after cerebral revascularization and those without incision complications(P＞0.05).The proportion of patients with diabetes mellitus and the frontal branches of superficial temporal artery not preserved in the incision complications group was higher than in the no incision complications group.BMI,scalp thickness,and operation time in the group with incision complications were higher than those in the no incision complications group,and the difference was statistical-ly significant(P＜0.05).Multifactorial analysis showed that scalp thickness(OR=1.484,95％CI:1.024-2.149,P=0.037),BMI(OR=1.323,95％CI:1.042-1.680,P=0.021),and the absence of the frontal branch of the superficial temporal artery(OR=3.582,95％CI:1.146-11.190,P=0.028),were the main risk factors for incisional complications(P＜0.05).Conclusion BMI,scalp thickness,and failure to preserve the frontal branch of the superficial temporal artery are independent risk factors for scalp incision complica-tions after cerebral revascularization.

Objective:To assess the enhancement characteristics of responsibility plaque of patients with intracranial artery stenosis(ICAS)and explore the correlation between that and stroke by using three dimensional high-resolution magnetic resonance imaging(3D-HR-MRI).Methods:A total of 72 ICAS patients who admitted to Beijing Huairou Hospital from April 2019 to April 2022 were retrospectively selected as the study objects,with a total of 96 atherosclerotic stenosis plaques.The plaques were divided into mild to moderate stenosis group(33 cases)and severe stenosis group(63 cases)according to the results of whole brain digital subtraction angiography.They were also were divided into sub-acute/acute plaque group(within 1 month)(47 cases)and non-acute plaque group(including chronic and non-responsible plaques)(49 cases)according to the time of occurring plaque.The imaging characteristics of the 3D-HR-MRI results were assessed by two radiologists.The degrees of plaque enhancement referred to the degrees of pituitary enhancement,and the degrees of plaque enhancement were divided into significant enhancement group(52 cases)and non-significant enhancement group that included moderate enhancement group and non-enhancement group(44 cases).The relationships between ICAS,degree of plaque enhancement and stroke were analyzed.Results:A total of 96 atherosclerotic stenosis plaques were confirmed in 72 patients.The statistical analysis of Kruskal-Wallis H test of multiple samples showed that there was a significant correlation between the time of occurring plaque and the degree of plaque enhancement(H=3.294,P＜0.05).Univariate Logistic regression analysis indicated that the difference between the acute plaque group and the non-acute plaque group was respectively significant correlations with ICAS degree[P＜0.05,OR(95%CI)=1.0(0.3-2.6)]and degree of plaque enhancement[P＜0.05,OR(95%CI)=1.0(0.4-2.0)].The multivariate Logistic regression analysis demonstrated that both severe arterial stenosis[P＜0.05,OR(95%CI)=1.0(0.3-1.9)]and significant enhancement of plaque[P＜0.05,OR(95%CI)=1.0(0.4-2.1)]were independent risk factors of stroke.Conclusion:Severe ICAS and significant plaque enhancement are the independent risk factors of stroke,which can provide effective basis for clinical prevention,diagnosis and treatment of stroke.

Objective:To investigate the characteristics and distribution of plaque of patients with mild middle cerebral artery(MCA)stenosis by using three dimensional(3D)high-resolution magnetic resonance imaging(3D HR-MRI),and the correlation between that and the occurrence of ischemic stroke.Methods:The clinical data of 64 patients with mild MCA stenosis who admitted to Beijing Huairou hospital from March 2020 to March 2022 were retrospectively analyzed.They were divided into symptomatic group(n=30)and asymptomatic group(n=34)according to whether occurred transient ischemic cerebral attack or ischemic cerebral stroke.The degree and distribution of plaque enhancement between the two groups were assessed and analyzed,and the correlation of plaque features in HR-MRI and ischemic stroke was analyzed.Results:There were a total of 71 plaques in 64 patients,including 30 responsible plaques and 41 non-responsible plaques.The enhancement degree of responsible plaques was significantly stronger than that of non-responsible plaques,and the difference was statistically significant(Z=5.645,P<0.05).Compared with non-responsible plaques,the responsible plaques more concentrated at the dorsal and upper walls of MCA,and the probability of occurring positive remodeling of responsible plaques was greater than that of non-responsible plaques,with statistical significance(x2=7.658,P<0.05).Conclusion:In patients with mild MCA stenosis,the degree enhancement and distribution location of plaque,and positively remodeling index of vessel are closely related to the occurrence of ischemic cerebral stroke.

Objective To conduct a scoping review of research on the application of mobile health(mHealth)in the management of home enteral tube feeding,so as to provide references for future research and clinical practice.Methods A literature search was performed in the PubMed,Cochrane Library,Embase,Web of Science,CINAHL,CNKI,Wanfang,and CMB databases to identify relevant studies.The search period spanned from the establishment of databases until February 18,2024.According to the scoping review framework,2 researchers independently screened the studies,extracted the data of the included studies,and collaborated on the final analysis.Results A total of 24 studies were included.9 studies were conducted with interventions based on nursing models such as discharge planning model,"Hospital to Home"nutrition management model,guided care nursing model.The management forms included application,network communication software,and website.The content elements included education,assessment,consultation,referral,self-management,electronic health archive,appointment service,peer support.The outcome indicators included patients'physical and mental health,self-management ability,caregiver competence,family burden and user assessment.Conclusion The mHealth has played a positive role in the management of home enteral tube feeding.In the future,it is recommended to establish a multidisciplinary team to conduct high-quality research and continuously improve the form and content of mHealth management.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

To investigate the therapeutic effect and mechanism of Qingwen Baiduyin on acute lung injury （ALI） in mice induced by lipopolysaccharide （LPS）. MethodA total of 144 C57BL/6 mice were randomly divided into the following groups： a normal group， a model group （LPS， 5 mg·kg^-1）， a dexamethasone group （5 mg·kg^-1）， and low-， medium-， and high-dose Qingwen Baiduyin groups （14.105， 28.21， 56.42 g·kg^-1）. The mice were treated once daily for 5 days. One hour after the final administration， the ALI model was established by intratracheal instillation of LPS， and samples were collected at 6 h and 24 h after modeling. The arterial blood gas index of mice was analyzed. The total protein content， total cell count， Evans blue dye （EBD） content， and lung tissue wet-to-dry weight ratio （W/D） of bronchoalveolar lavage fluid （BALF） were measured. Hematoxylin-eosin （HE） staining was performed to assess the pathological changes in mouse lung tissue. Western blot was used to detect the expression levels of key proteins in the Janus kinase 1/signal transducer and activator of transcription 1/interferon regulatory factor 1 （JAK1/STAT1/IRF1） signaling pathway in lung tissue. ResultCompared with the normal group， the model group showed reduced arterial oxygen pressure （pO₂）， oxygen saturation （SO₂）， and lung tissue W/D （P<0.05， P<0.01）， increased carbon dioxide pressure （pCO₂）， total protein content， total cell count， EBD content， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， chemokine CXC ligand 1 （CXCL1）， chemokine CXC ligand 2 （CXCL2）， chemokine CXC ligand 9 （CXCL9）， and chemokine CXC ligand 10 （CXCL10） content （P<0.05， P<0.01）， thickening of the alveolar walls， fusion of alveolar cavities， and infiltration of inflammatory cells in lung tissue， increased proportion of M1 macrophage polarization and lung cell apoptosis （P<0.05）， and increased protein expression levels of JAK1， phosphorylated JAK1 （p-JAK1）， inducible nitric oxide synthase （iNOS）， STAT1， phosphorylated STAT1 （p-STAT1）， IRF1， gasdermin D （GSDMD）， and mixed lineage kinase domain-like protein （MLKL） （P<0.05， P<0.01）. Compared with the model group， Qingwen Baiduyin significantly increased pO₂， SO₂， and lung tissue W/D （P<0.05， P<0.01）， improved the pathological changes in lung tissue， and reduced pCO₂， total protein content， total cell count， EBD content， IFN-γ， TNF-α， IL-1β， CXCL1， CXCL2， CXCL9， and CXCL10 content， proportion of M1 macrophage polarization， and protein expression levels of JAK1， p-JAK1， iNOS， STAT1， p-STAT1， IRF1， GSDMD， and MLKL （P<0.05， P<0.01）. ConclusionQingwen Baiduyin can improve the lung inflammatory response and reduce lung cell apoptosis in mice with ALI by inhibiting the JAK1/STAT1/IRF1 signaling pathway， thereby exerting a lung-protective effect.