Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

This study was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of the cell division cycle 42 (CDC42) gene with Pulmonary artery systolic pressure (PASP) among patients with Congenital heart disease (CHD). METHODS: In this observational study, clinical data and blood samples were collected from 579 CHD patients with left-to-right shunt who presented to our hospital between January 2012 and January 2017. SNPs of the CDC42 gene were genotyped using an improved multiple ligase detection reaction. Multiple linear regression was applied to evaluate the association of CDC42 gene variants with PASP. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (Ethics No.: 20180222-102). RESULTS: Polymorphisms at rs2501256 and rs34896897 of the CDC42 gene were significantly associated with PASP. Compared with the CC genotype at rs2501256, TT and CT carriers displayed higher PASP [TT vs. CC: B (95%CI) = 4.01 (1.95, 6.07), P < 0.001; CT vs. CC: B (95%CI) = 2.91 (0.63, 5.19), P < 0.001]. Similarly, GG and GA genotypes at rs34896897 were associated with higher PASP compared to the AA genotype [GG vs. AA: B (95%CI) = 26.15 (20.45, 31.84), P < 0.001; GA vs. AA: B (95%CI) = 7.19 (4.31, 10.08), P < 0.001]. Genetic model analyses demonstrated significant differences for both rs2501256 and rs34896897 under dominant, additive, and recessive models (P < 0.05). TT carriers at rs2501256 exhibited larger left-and right-atrial diameters, whereas GG carriers at rs34896897 showed greater right-atrial and right-ventricular end-diastolic dimensions. Subgroup analyses revealed no association between rs2501256 and PASP in males, individuals younger than 18 years, Uyghur ethnicity, or those with ventricular septal defects. CONCLUSION CHD patients carrying the minor alleles of rs2501256 and rs34896897 in the CDC42 gene present higher incidence of PASP compared to those carrying the common alleles.
Humans ; Male ; Female ; Heart Defects, Congenital/physiopathology* ; Polymorphism, Single Nucleotide ; cdc42 GTP-Binding Protein/genetics* ; Adult ; Child ; Genotype ; Adolescent ; Child, Preschool ; Genetic Predisposition to Disease ; Pulmonary Artery/physiopathology*

Being a minimally-invasive surgery,the transcatheter arterial embolization treats tumor and vascular diseases mainly through the way of selective endovascular obstruction.Clinically,a variety of embolic agents are available,which include solid embolic agents,liquid embolic agents,and embolic devices.Owing to the consistency of particle size and controllable delivery,the solid embolic agents,especially microspheres-based embolic agents,can effectively achieve the accurate embolization of the tumor blood vessels.Such embolic agents can not only obstruct blood flow but also carry effective anticancer drugs which can be released at the same time of embolization procedure,thus,enhancing the therapeutic effect.Besides,embolic microspheres containing radiopaque components such as iodine,barium,and tantalum,can achieve inherent traceability and monitor the real-time location of embolic agent within body,providing timely information feedback to physicians.As the first part of the topic,this paper makes a comprehensive review about the recent advances in solid embolic agents(focusing on embolic microspheres),aiming to promote the development of this scientific research field.

Being a minimally-invasive procedure,transcatheter arterial embolization can treat tumors and vascular diseases by obstructing the lesion s blood vessels.Embolic agents have been constantly developed so as to meet the requirements in clinical practice.Compared with solid embolic agents,liquid embolic agents and new-type liquid-solid phase conversion type embolic agents have more unique physicochemical properties,which,theoretically,are capable of occluding all the fine vascular branches at the target site.Besides,the microrobot drugs emerging in recent years can be delivered to lesion sites that are difficult to reach in the human body by using multiple external driving sources(such as sound,light,magnetic,etc.),which is of a great advantage in embolization therapy.As the second part of the topic,this paper makes a comprehensive review about the research achievements in embolic equipment,liquid embolic agents and liquid-solid phase conversion type embolic agents,and discusses their characteristics,advantages,clinical application prospects and their shortcomings,aiming to promote the development of this scientific research field.