Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective To investigate the differences in BMD,T-scores,lumbar HU values,and modified VBQ scores in patients with thoracolumbar fractures,analyze their correlations,and evaluate their predictive efficacy for thoracolumbar fractures.Methods Patients with thoracolumbar fragility fractures and hospitalized in the Department of Orthopedics at the Second Affiliated Hospital of Kunming Medical University from January 2022 to March 2025 were retrospectively enrolled.Among them,132 eligible patients were divided into the fracture group(n=63)and the non-fracture group(n=69).BMD and T-scores of L1～L4 vertebrae were measured via DEXA,lumbar HU values were obtained from CT scans,and modified VBQ scores were calculated using lumbar MRI.Intergroup comparisons were performed using independent samples t-tests.Pearson's correlation analysis was used to assess the relationships among BMD,T-scores,HU values,and modified VBQ scores.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate their predictive performance for thoracolumbar fractures.Results The fracture group exhibited significantly lower mean BMD,T-scores,and HU values in L1～L4 compared to the non-fracture group,while modified VBQ scores were significantly higher(P<0.001).Correlation analysis revealed a significant positive correlation between BMD,T-scores,and HU values in L1～L4,whereas all three parameters showed a significant negative correlation with modified VBQ scores(P<0.001).The AUC values for predicting thoracolumbar fractures were 0.826(T-score),0.836(BMD),0.759(HU value),and 0.875(modified VBQ score),with optimal cutoff thresholds of-1.65(T-score),0.836 g/cm2(BMD),68.4(HU value),and 3.01(modified VBQ score),respectively.Conclusion BMD,T-scores,HU values,and modified VBQ scores in L1～L4 vertebrae are significantly correlated and can serve as the predictive indicators for thoracolumbar fractures.Among them,the modified VBQ score demonstrates the best predictive performance,making it a valuable auxiliary tool for assessing the vertebral bone quality.

Objective:To discuss the synergistic inhibitory effect of apatinib mesylate(apatinib)combined with radiotherapy(RT)on the hepatocellular carcinoma(HepG2)cells in vitro,and to clarify its related antitumor mechanism.Methods:The HepG2 cells were cultured in vitro and treated with different concentrations of apatinib and/or varying doses of X-rays.MTT method was used to detect the survival rates of the cells in various groups;the inhibitory rates of cell proliferation and the 20％inhibitory concentration(IC20)of apatinib were calculated;the X-ray irradiation dose for subsequent experiments was detected.The HepG2 cells were divided into apatinib group,RT group,and apatinib+RT group(combined group).Flow cytometry was used to detect the apoptotic rates of the cells in various groups;wound healing assay was used to detect the migration rates of the cells in various groups;ELISA method was used to detect the levels of vascular endothelial growth factor(VEGF)in the cell culture supernatant in various groups.Results:The MTT results showed that the IC20 of apatinib was 1.32 μmol·L-1,and this concentration was used for subsequent experiments,and the X-ray irradiation dose for the follow-up experiments was 2 Gy.Compared with control group,the apoptotic rates of the cells in apatinib group and RT group had no significant differences(P＞0.05),while the apoptotic rate of the cells in combined group was increased(P＜0.05).Compared with control group,the migration rates of the cells in apatinib group,RT group,and combined group were decreased(P＜0.05);compared with apatinib group and RT group,the migration rate of the cells in combined group was decreased(P＜0.05).Compared with control group,the levels of VEGF in the cell culture supernatant in apatinib group and combined group were decreased(P＜0.05);compared with apatinib and RT group,the level of VEGF in the cell culture supernatant in combined group was decreased(P＜0.05).Conclusion:Apatinib combined with radiotherapy significantly inhibits the proliferation and migration of the HepG2 cells in vitro and induces the apoptosis;its effect may be related to the inhibition of VEGF secretion by cells.

OBJECTIVE To systematically evaluate the risk factors for cefoperazone/sulbactam-induced coagulation dysfunction in adult patients. METHODS Retrieved from CNKI， VIP， CBM， Wanfang data， PubMed， Embase and Cochrane Library， randomized controlled trial （RCT）， case-control study or cohort study about cefoperazone/sulbactam-induced coagulation dysfunction in adult patients were collected from the inception to Apr. 30th， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was carried out by using RevMan 5.3 software. RESULTS A total of 13 studies were included， among which 11 studies were case-control studies， and 2 studies were cohort studies， involving 18 387 patients in total. Meta- analysis showed that the proportion of advanced age [OR＝2.04， 95%CI （1.14， 3.64）， P＝0.02]， liver insufficiency [OR＝5.95， 95%CI （4.21， 8.40）， P＜0.000 01]， renal insufficiency [OR＝3.51， 95%CI （3.04， 4.05）， P＜0.001]， hypoproteinemia [OR＝ 1.90， 95%CI（1.37， 2.62）， P＜0.001]， poor diet [OR＝7.25， 95%CI （5.13， 10.24）， P＜0.000 01]， daily dose of cefoperazone/ sulbactam ≥9 g [OR＝3.95， 95%CI （2.45，6.37）， P＜0.001]， medication duration of cefoperazone/sulbactam ≥10 d [OR＝2.43， 95%CI （1.81， 3.28）， P＜0.001]， combined use of anticoagulant drugs [OR＝2.84， 95%CI （2.03， 3.97）， P＜0.001]， combined with malignant tumor [OR＝1.60， 95%CI （1.20， 2.15），P＜0.001] in patients with abnormal coagulation function were significantly higher than those with normal coagulation function. CONCLUSIONS Advanced age， liver insufficiency， renal insufficiency， complicated with malignant tumors and hypoalbuminemia， combined use of anticoagulant drugs， poor diet， daily dose ≥9 g， and medication duration≥10 days are risk factors for coagulation dysfunction caused by cefoperazone/sulbactam.

Objective: To investigate the mechanism of electroacupuncture (EA) for treating depression and to explore the role of brevican in the medial prefrontal cortex (mPFC) in modulating stress susceptibility and the antidepressant effects of EA in rats. Methods: Twenty-four Sprague–Dawley (SD) rats were equally divided into three groups: green fluorescent protein (GFP) + control, GFP + chronic unpredicted mild stress (CUMS), and short-hairpin RNA targeting on brevican (shBcan) + CUMS. Another 24 SD rats were equally divided into CUMS + GFP, CUMS + GFP + EA, and CUMS + shBcan + EA groups. Behavioral tests were conducted to assess depression-like behavior. Western blot analysis was used to evaluate the expression of brevican, aggrecan, GLuA1, and PSD95 in mPFC subregions. Results: Behavioral parameter evaluation show that rats in the shBcan + CUMS group exhibited a significantly reduced sucrose preference (P = .0002) and increased immobility time (P = .0011) compared to those in rats in the GFP + CUMS group. Western blotting showed that brevican expression was significantly downregulated in the PrL of the shBcan + CUMS group compared with that in the GFP + CUMS group (P = .0192). Furthermore, compared to the CUMS + GFP + EA group, the CUMS + shBcan + EA group exhibited a significantly decreased sucrose preference (P = .0334), increased immobility time (P = .0465), and increased latency to food (P = .0261). In the CUMS + shBcan + EA group, the EA-induced brevican and PSD95 overexpression was reversed, compared with that in the CUMS + GFP + EA group (P = .0454 and P = .0198, respectively). Conclusion EA exerts its antidepressant effects through the modulation of brevican expression in rats. Our findings highlight the important role for brevican in stress susceptibility, which could be a potential target for treating depression.

Objective:To analyze clinical efficacy and safety of dermabrasion for the treatment of familial benign chronic pemphigus.Methods:Clinical data were retrospectively collected from 6 patients with familial benign chronic pemphigus, who underwent dermabrasion in the Department of Dermatology, the First Affiliated Hospital of Dalian Medical University from February 2019 to July 2020. There were 3 males and 3 females, they were aged from 39 to 65 years, and their disease duration ranged from 10 to 40 years. All the patients were postoperatively followed up for 14 - 34 months. Response rates were calculated, and adverse reactions and recurrence were observed.Results:Dermabrasion was performed on the 6 patients in 55 body areas. After operation, complete recovery was observed in 36 areas (65.5%), marked improvement was noted in 13 areas (23.6%), and moderate improvement was observed in 6 areas (10.9%) ; there were no areas with no response, resulting in an overall response rate of 89.1%. Postoperatively, the patients experienced no obvious discomfort, and only slight hypopigmentation and mild scars remained. During the follow-up of 14 to 34 months, no recurrence was observed in the treated areas.Conclusion:Dermabrasion was safe and effective for the treatment of familial benign chronic pemphigus.

Objective: To investigate the effects of lactoprotein iron chelates on rats with iron deficiency anaemia (IDA), so as to provide insights into developing and utilizing novel iron supplements. Methods: Seventy weaning female SPF-graded rats of the SD strain were randomly divided into the control group (A), model group (B), ferrous sulfate group (C), lactoferrin group (D), lactoferrin iron chelate group (E), Casein oligopeptide iron chelate group (F) and whey protein oligopeptide iron chelate group (G), with 10 rats in each group. The rats in group A were fed with normal diet, and the others were fed with poor iron diet for IDA modeling. The corresponding interventions were given by intragastric administration once a day. The iron ion concentrations of group C, E, F and G were 2.0 mg/kg, and the protein and oligopeptide concentrations of group D, E, F and G were 2 000 mg/kg. Body weight and hemoglobin of rats were measured weekly during 21-day intervention. At the end, peripheral blood samples were collected, and blood routine, iron metabolism and liver function indicators were determined. Results: After the intervention, among blood routine indicators, the rats in group C, E, F and G showed elevated hemoglobin, red blood cell, mean corpuscular volume and hematocrit, and decreased free protoporphyrin and mean corpuscular hemoglobin concentration when compared with the rats in group B (all P<0.05); among iron metabolism indicators, the rats in group C, E and G showed elevated serum ferritin, the rats in group C, E, F and G showed elevated serum iron, the rats in group C, D, E, F and G showed decreased unsaturated iron binding capacity and total iron binding capacity when compared with the rats in group B (all P<0.05); among liver function indicators, the rats in group E and G showed decreased alanine transaminase when compared with the rats in group B (both P<0.05). Conclusions Lactoprotein alone could not completely improve IDA in rats compared with traditional iron supplement (ferrous sulfate). Lactoprotein iron chelate, especially whey protein oligopeptide iron chelate, could significantly improve IDA, iron reserve and liver function damage in rats.

Objective:To evaluate the safety and short-term outcomes of transfemoral transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with pure native aortic valve regurgitation (AR).Methods:A total of 16 patients with pure native AR who underwent transfemoral TAVR in the Renmin Hospital of Wuhan University from June 2019 to January 2022 were consecutively included in our study, and 24 patients with aortic stenosis (AS) who underwent transfemoral TAVR in the same period were selected as the control group. This study compared the baseline characteristics, baseline echocardiography, morphological characteristics of the aortic root, safety of the procedure and short-term outcomes between the two groups.Results:Compared with the AS group, the pure native AR group had a higher prevalence of baseline NYHA class Ⅲ or Ⅳ, a larger left ventricular end-diastolic diameter (LVEDD), a smaller relative ventricular wall thickness (RWT) (all P<0.05), a lower aortic root calcification score, and a larger sinus junction diameter, and cardiac angle (all P<0.05). During TAVR operation, the pure native AR group was treated with larger prostheses size, with a larger percentage in relation to the native annulus size and outflow tract (all P<0.05). There were 7 cases (43.8%) treated with 'valve in valve’, 2 cases (12.5%) with moderate paravalvular leak(PVL), and 2 cases (12.5%) with prostheses-migration to ascending aorta.However, no cases of death, transfer to surgery, coronary obstruction or annular rupture were observed in the pure native AR group. There were no statistical differences between the pure native AR group and AS group in device success rate (56.3% vs 62.5%, P>0.05) and 1-month all-cause mortality[0 (0/16) vs 4.2% (1/24), P>0.05]. The 6MWT, NT-proBNP, and NYHA were significantly improved at 1-month post TAVR compared with those before the procedure in the two groups (all P<0.05). Echocardiography showed significant reverse cardiac remodeling and improved left ventricular function compared with those before the procedure in the two groups. Conclusions:Transfemoral TAVR is a feasible and safe method for patients with pure native AR, and its short-term prognosis is similar to that in AS patients with well-established TAVR.

Stem cell transplantation has great potential in the treatment of ischemic stroke, and bone marrow mesenchymal stem cells (BMSCs) are the most widely studied. Studies have shown that BMSCs mainly perform their functions in a paracrine manner, and the exosomes released by BMSCs show biological activities similar to BMSCs. As a cell-free therapy, BMSCs exosomes have made a lot of progress in the field of ischemic stroke. This article reviews the research progress of BMSCs-derived exosomes in the treatment of ischemic stroke.