BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective: To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC). Materials and Methods: Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test. Results: The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively. Conclusion SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Objective To investigate the clinical effects of different right lung volume reduction techniques when the donor lung is oversized and mismatched with the recipient. Methods Clinical data of 10 recipients who underwent right lung volume reduction lung transplantation at the First Affiliated Hospital of Xi'an Jiaotong University from October 2022 to June 2024 were collected, including gender, age, primary disease type, and type of transplantation. A retrospective analysis was performed on postoperative complications within 90 days, duration of mechanical ventilation, hospital stay, and survival status to explore the impact of different volume reduction techniques on the survival rate of lung transplant recipients. Results A total of 10 right lung volume reduction recipients were included in this study, with 2 cases of upper lobe reduction, 7 cases of middle lobe reduction, and 1 case of lower lobe reduction. Three recipients developed airway complications (one each with upper, middle, and lower lobe reduction). The 30-day survival rate was 90% and the 1-year survival rate was 70%. One recipient with upper lobe reduction died of septic shock during the perioperative period, one with lower lobe reduction died of airway anastomotic fistula 2 months after surgery, and one with middle lobe reduction died of renal insufficiency 1 year after surgery. All 7 recipients with middle lobe reduction successfully passed the perioperative period, with one case of airway anastomotic stenosis (1/7). The average duration of mechanical ventilation was 71 hours, and the average hospital stay was 26 days. The 30-day survival rate was 7/7, and the 1-year survival rate was 6/7. Conclusions Middle lobe reduction in right lung transplantation surgery has the advantages of low incidence of airway complications, good safety, and minimal loss of lung function, and may be a better right lung volume reduction option with potential for application.

Objective To explore the efficacy of goal management training(GMT)on core symptoms and mental status in college students with attention deficit hyperactivity disorder(ADHD)inattentive type.Methods Delphi method was used to construct a GMT program for college students with inattentive ADHD.Then,totally 68 college students with inattentive ADHD were recruited through advertisements published by hospitals and universities(Second Affiliated Hospital of Army Medical University,and 3 universities in Chongqing from March to June 2024.The subjects were randomly divided into an intervention group(n=34)and a control group(n=34).The intervention group received GMT for 2 h,once a week,for 7 weeks,and the control group did not receive training for the time being.The 2 groups were evaluated within 1 week before and in 7 weeks after intervention by using Adult ADHD Self-Report Scale(ASRS),Dysregulation of Emotions Rating Scale(DERS),Generalized Anxiety Disorde-7(GAD-7),Patient Health Questionnaire-9(PHQ-9),Self-Compassion Scale(SCS),and Satisfaction with Life Scale(SWLS).Results ① The expert authority coefficient(Cr)of 2 rounds of expert consultation was 0.83,with a questionnaire recovery rate of 100%and 95%,respectively,the Kendall's coordination coefficient was 0.081(P<0.01)and 0.226(P<0.01),and the coefficient of variation was<0.3,indicating the results of the expert consultation were reliable.The constructed GMT program includes 1 first-level indicator,7 second-level indicators,and 20 third-level indicators.② After 7 weeks of GMT intervention,the interaction between the 2 groups and time showed that the experimental group obtained significant improvements than the control group in terms of inattention symptoms(Wald Chi-square=28.35,P<0.001),dysregulation of emotions(Wald Chi-square=23.81,P<0.001),anxiety(Wald Chi-square=22.79,P<0.001),depression(Wald Chi-square=20.52,P<0.001),self-compassion(Wald Chi-square=9.36,P<0.01),and life satisfaction(Wald Chi-square=3.97,P<0.05).Conclusion GMT intervention can significantly improve the core symptoms of college students with inattentive ADHD,reduce anxiety and depression levels,enhance their emotion regulation and self-compassion abilities,and improve their life satisfaction.

A matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)method was developed for simultaneous analysis of 10 kinds of aphrodisiac drugs,including sildenafil,acetildenafil,nor-acetildenafil,homosildenafil,lodenafil carbonate,sildlenafil dimer impurity,vardenafil dimer,hydroxyacetildenafil,N-desmethylsildenafil and udenafil.By using different matrices(α-cyano-4-hydroxycinnamic acid(HCCA)and sinapic acid(SA)),the effects of solvents,amount of matrices,laser intensity and spotting methods on the peak strength and signal intensity of MALDI-TOF MS for the aphrodisiac drugs were investigated.As a result,SA was chosen as the matrix,and then dispersed in methanol-water(50∶50,V/V),and spotted by matrix firstly and sample secondly approach with the reflect linear positive mode and laser power of 60%.Under optimal conditions,the proposed MALDI-TOF MS method could obtain stable signal,high intensity and well-repeated mass spectrometric results.The results of method validation showed a linear range from 10 to 100 ng/mL,and the regression coefficients(r)were all above 0.985.The limits of detection(LOD)were 0.1-1.0 ng/mL,and the recoveries were in the range of 72.9%-109.9%for health wine,soft capsule and instant coffee samples,while the relative standard deviations(RSDs)ranged from 0.7%to 11.3%(n=3).The test results of 10 kinds of aphrodisiac drugs by MALDI-TOF MS were in accordance with the results of high-performance liquid chromatography-tandem mass spectrometry.This method exhibited high sensitivity,high accuracy,good anti-interference ability,low chemical solvents consumption and environmentally friendliness,and could be used to detect drugs without standards.The developed MALDI-TOF MS method could realize the non-target screening and detection of 10 kinds of illegally added aphrodisiac drugs in foods.