BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

Evidence mapping was used to systematically analyze the clinical research evidence of oral Chinese patent medicines in the treatment of intracerebral hemorrhage(ICH), thus revealing the distribution and quality of evidence in this field. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science from inception to July 5, 2024. The distribution characteristics of evidence were presented numerically and graphically. A total of 35 Chinese patent medicines were identified, involving 261 articles. The basic information of the 35 Chinese patent medicines, publication trend, traditional Chinese medicine(TCM) syndromes, interventions, and outcome indicators were compared and analyzed, and the methodological quality of the articles was evaluated. The results indicated that the clinical scope of Chinese patent medicines in the treatment of ICH was broad. However, the available studies inadequately emphasized the advantages and characteristics of TCM, lacked the safety information and the standards for evaluating outcome indicators, and paid insufficient attention to cognitive ability and neuropsychology. In addition, these articles demonstrated low quality. It is recommended that follow-up clinical research should be standardized and highlight the characteristics of TCM. In the analysis of outcome indicators, TCM syndrome evaluation should be taken as an important outcome indicator, and the evaluation criteria should be unified. Moreover, more attention should be paid to patients' cognitive ability and neuropsychology. The holder of marketing license of Chinese patent medicines should standardize the clinical position and improve the safety information in the medicine instructions according to the relevant requirements of the National Medical Products Administration. Additionally, the proportion of Chinese patent medicines in the category A list of medical insurance should be increased, and the limited medical resources should be rationally allocated.
Cerebral Hemorrhage/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Nonprescription Drugs/administration & dosage* ; Administration, Oral

OBJECTIVE: To investigate the molecular alterations of splenocytes associated with anti-factor Ⅷ (FⅧ) immune response and the underlying mechanisms based on hemophilia A (HA) murine model via RNA sequencing (RNA-seq) technology. METHODS: Severe HA mice were immunized with recombinant human factor Ⅷ (rhF8) weekly for 4 weeks to establish an FⅧ inhibitor model. High quality raw data were obtained by using bulk RNA-seq and CASAVA base identification technology, and the differentially expressed genes (DEGs) were identified. The DEGs were statistically classified by gene ontology (GO) annotation to obtain information on the major signaling pathways and biological processes involved in anti-FⅧ immune response in HA mouse splenocytes. The cell clusters, genes, and signaling pathway datasets were comprehensively analyzed by GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and single cell RNA-seq (ScRNA-seq) analysis, respectively. Flow cytometry analysis was used to verify the changes in T follicular helper cells (Tfh) and regulatory T cells (Treg). RESULTS: A total of 3731 DEGs was identified, including 2275 genes with up-regulated expression and 1456 genes with down-regulated expression. The DEGs were enriched in helper T cell differentiation, cytokine receptor, T cell receptor signaling pathway, ferroptosis, etc. Uniform Manifold Approximation and Project (UMAP) downscaling and visualization analysis yielded a total number of 11 T/NK cell subsets, visualizing the overall expression distribution of C-X-C chemokine-specific receptor gene cxcr5 among these T/NK cell subsets. Higher expression of cxcr5 was found in activated Tfh from FⅧ inhibitor mice, in comparison to the control group. The visualization using Upset plot R language showed a close interaction between Tfh and Treg. Moreover, the increased frequencies of Tfh and the decreased frequencies of Treg in inhibitor mouse splenocytes were further verified by flow cytometry analysis. CONCLUSION Multiple immune cell subsets, signaling pathways, and characteristic genes may be involved in the process of anti-FⅧ immune response in HA mouse splenocytes. The molecules involved in the regulation of Tfh/Treg may play key roles, which provide potential biological targets and therapeutic strategies for HA patients with inhibitors in the future.
Animals ; Hemophilia A/genetics* ; Mice ; Sequence Analysis, RNA ; Disease Models, Animal ; Spleen/cytology* ; T-Lymphocytes, Regulatory/immunology* ; Humans ; Signal Transduction ; Factor VIII/immunology* ; T-Lymphocytes, Helper-Inducer/immunology*

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Objective To investigate the protective effect and mechanism of CDK4/6 inhibitor palbociclib against radiation-induced injury in rats'small intestinal crypt epithelial cell line(IEC-6).Methods(1)Using CCK-8 colorimetric assay,colony formation assay,the PI staining method,Annexin V-FITC/PI dual staining and Western blot,the impact of palbociclib on proliferation,cell cycle dynamics,apoptosis,DNA damage,as well as phosphorylation events at Rb-780 and 795 sites in irradiated IEC-6 cells was investigated.(2)An IEC-6 cell line overexpressing Rb was established,and the effects of Rb overexpression on proliferation,cell cycle,and apoptosis in the IEC-6 cell line were assessed using the CCK-8 colorimetric assay,PI staining method,Annexin V-PE/7-AAD dual staining and Western blot.Additionally,the impact of Rb overexpression on the protective effect of palbociclib against radiation damage was verified in the Rb-overexpressing IEC-6 cell line.Results(1)Administration of palbociclib was demonstrated to enhance the proliferative capacity of IEC-6 cells following exposure to 10 Gy X-ray irradiation,increase colony formation ability post 4-8 Gy X-ray exposure while concomitantly reducing the proportion of cells in the G2/M phase after 10 Gy irradiation and diminishing apoptosis in irradiated IEC-6 cells.Protein expression analysis revealed that palbociclib inhibited phosphorylation at Rb-780 and 795 sites and attenuated the production of γ-H2AX in IEC-6 cells following irradiation.(2)After transfection of IEC-6 cells with Rb overexpression lentivirus,there was a significant increase in the total protein expression of Rb.The phosphorylation levels at Rb-780 and 795 sites were markedly elevated.Consequently,cell proliferation was accelerated,the proportion of cells in the S phase of the cell cycle increased,and the apoptotic rate significantly rose after exposure to 10 Gy X-ray irradiation.(3)Treatment with a lower dose of palbociclib(0.05 μmol/L)was found to suppress the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells overexpressing Rb.Additionally,it reduced apoptosis in IEC-6 cells overexpressing Rb following exposure to 10 Gy X-ray irradiation.However,this treatment did not inhibit the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells transfected with the empty vector,nor did it exert a protective effect against radiation-induced damage in these cells.Conclusion The CDK4/6 inhibitor palbociclib demonstrates significant protective effects against radiation-induced damage in rats'intestinal crypt epithelial cell line(IEC-6),with the Rb protein potentially playing a crucial role in mediating this radioprotective response.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective To investigate the impacts of LINC00943 on proliferation,apoptosis,and invasion of esophageal squamous cell carcinoma(ESCC)cells by regulating the miR-126-5p/HOXB2 axis.Methods QRT-PCR was applied to detect the expression of LINC00943 in 45 ESCC tissues and cell lines;The effects of LINC00943 knockdown on the proliferation,apoptosis and invasion of KYSE30 cells were detected by MTT assay,flow cytometry and Transwell chamber.Western blot was applied to detect the expression of proliferating cell nuclear antigen(PCNA),Bcl-2 associated X protein(Bax),anti apoptotic factor B cell lymphomatoma-2(Bcl-2),cleaved caspase-3,matrix metalloproteinase-2(MMP-2),MMP-9,and HOXB2;dual luciferase reporter gene experiment was applied to verify the relationship between miR-126-5p and LINC00943 and HOXB2;the ESCC nude mouse in vivo model was constructed and separated into si-NC and si-LINC00943 groups,the tumor mass and volume were measured,qRT-PCR was applied to detect the expression of miR-126-5p in transplanted tumor tissue,immunohistochemistry was applied to detect the expression of HOXB2 protein in transplanted tumor tissue,and TUNEL staining was applied to detect cell apoptosis in tumor tissue.Results The expression of LINC00943 mRNA increased in ESCC tissues and cell lines(P＜0.05);Compared with the si-NC group,the proliferation activity,migration and invasion cell number,HOXB2,PCNA,MMP-2,MMP-9 and Bcl-2 protein expression of KYSE30 cells in the si-LINC00943 group were decreased,and the expression of miR-126-5 p,Bax,Cleaved Caspase-3 and apoptosis rate were increased(P＜0.05);downregulation of miR-126-5p was able to weaken the inhibitory effect of LINC00943 knockdown on the malignant behavior of KYSE30 cells(P＜0.05);dual luciferase reporter gene experiment confirmed the targeted regulatory relationship between miR-126-5p and LINC00943,and miR-126-5p and HOXB2(P＜0.05);The ESCC nude mouse model was constructed in vivo and divided into si-NC and si-LINC00943 groups.The tumor mass,tumor volume,expression of miR-126-5p and HOXB2 in transplanted tumor tissues and apoptosis rate of tumor cells were measured.(P＜0.05).Conclusion LINC00943 is highly expressed in ESCC tissues and cell lines.Knocking down LINC00943 may inhibit the expression of HOXB2 by up-regulating the expression of miR-126-5p,promote the apoptosis of ESCC cells,and inhibit their proliferation,migration and invasion.

Objective:To investigate the effectiveness and clinical efficacy of tension-free vaginal tape(TVT)surgery in treating female recurrent stress urinary incontinence(rSUI).Methods:A retrospec-tive analysis was conducted on 24 patients who experienced recurrence of mid-urethral sling failure and were treated with TVT surgery at Beijing Chao-Yang Hospital from January 2016 to June 2020.Basic pa-tient information was collected.The International Consultation on Incontinence questionnaire-short form(ICI-Q-SF)was used to record urinary incontinence symptom scores preoperatively,1-year postoperative-ly,and more than three years postoperatively.The changes in various ICI-Q-SF scores and total scores were compared.Additionally,clinical symptom severity of urinary incontinence was recorded and com-pared preoperatively and more than three years postoperatively.Results:Among the 24 patients included in the follow-up,one patient was lost to follow-up due to death from a cerebrovascular accident one year postoperatively,leaving 23 patients with a follow-up period ranging from 3.9 to 7.3 years,with an ave-rage follow-up time of(5.2±1.1)years.Preoperatively,the median ICI-Q-SF total score was 20.0(16.0,21.0);at the 1-year follow-up,the median ICI-Q-SF total score was 5.0(1.5,7.8)(P＜0.001);at an average follow-up of five years,the median ICI-Q-SF total score was 6.0(3.0,9.0),still showing a statistically significant difference compared with preoperative scores(P＜0.001).The in-dividual ICI-Q-SF scores were significantly lower at the 1-year and average five-year follow-ups compared with preoperative scores(P＜0.001).Regarding the severity of urinary incontinence,all the patients had moderate to severe urinary incontinence preoperatively;Five years postoperatively,87.0％(20/23)of the patients had no or only mild urinary incontinence,and 13.0％(3/23)had recurrent moderate to severe urinary incontinence(P＜0.001).Conclusion:TVT surgery is effective in treating female recur-rent stress urinary incontinence,with an average 5-year cure and improvement rate of 87.0％.

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.