BACKGROUND:Due to the very limited ability of articular cartilage to repair itself,articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own,which triggers or aggravates osteoarthritis and even leads to severe disability.Therefore,the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE:To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS:Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023,and bibliometric and visualization analyses were carried out using VOSviewer,Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION:The annual publication volume in the field of articular cartilage repair shows an overall increasing trend,with the United States,China,and Germany being the top three countries in terms of publication volume,and the research institutions focus on universities and hospitals,with Harvard University,New York Hospital for Special Surgery,and Shanghai Jiao Tong University being the top three institutions in terms of publication volume.AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field,and BIOMATERIALS is the journal with the highest number of citations in the field."Injectable hydrogels for cartilage and bone tissue engineering"is the most cited document published in the last decade,and the author with the most publications is Madry Henning,an active author in the field.The active authors in this field have formed a number of stable research teams with each other,and the cooperation between different teams needs to be further strengthened.Intra-articular injections,high tibial osteotomies,hydrogels,drug delivery,inflammation,cartilage regeneration,and scaffolds are the current hot topics of research in this field,and the application of 3D printing technology,bio-inks,silk proteins,injectable hydrogels,and exosomes in articular cartilage repair may be the frontier of research in this field.Integrating various innovative technologies and methods for more effective,durable and functional cartilage tissue regeneration and repair,and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field.

Objective To investigate the efficacy and safety of sofosbuvir/velpatasivr/voxilaprevir(SOF/VEL/VOX)in patients with HCV infection experiencing failure in previous direct-acting antiviral agent(DAA)therapy.Methods A retrospective analysis was performed for the chronic hepatitis C patients who experienced failure in previous DAA antiviral therapy and were treated with SOF/VEL/VOX(400 mg/100 mg/100 mg/tablet,1 tablet/day)for 12 weeks in Nanjing Second Hospital,Wuxi Fifth People's Hospital,and The Third People's Hospital of Zhenjiang from June 2020 to June 2023.Sustained virological response at 12 weeks(SVR12)was observed after the end of treatment,and the changes in biochemical parameters and the incidence rate of adverse reactions were assessed to evaluate drug safety.The paired t-test was used for comparison of continuous data between two groups.Results A total of 36 patients were enrolled,among whom there were 27 non-liver cirrhosis patients and 9 patients with compensated liver cirrhosis,and 4 patients experienced failure in the previous two or more sessions of DAA therapy.Two patients were lost to follow-up after treatment,and the remaining 34 patients(34/36,94.4%)achieved SVR12.Among the 36 patients enrolled,the most common adverse events were pruritus,nausea,fatigue,and headache,and one patient(2.78%)experienced serious adverse events;there were no adverse events that resulted in the discontinuation of therapeutic agents or the death of patients.Conclusion For chronic hepatitis C patients who experience failure in previous DAA therapy,SOF/VEL/VOX salvage therapy has a relatively high rate of SVR12,with good tolerability and safety.

Objective　By exploring the function of sulfakinin (SK) and sulfakinin receptor (SKR) of Aedes aegypti, it laid a certain experimental basis and theoretical basis for the research and development of new insecticides targeting neuropeptides and their receptors. Methods　This study investigated the roles of SK and its receptor gene in Ae. aegypti using bioinformatics analysis and Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/Cas9 knockout technology. Subsequently, RNA interference technology was employed to suppress the expression of SK or its receptor in adult mosquitoes. Lastly, transcriptome sequencing technology was utilized to identify and analyze differentially expressed genes between the interference group and the control group in order to gain insights into their functions. Results　It was found that there is only one SK receptor in Ae. aegypti. In addition, during the construction of mutant strains of Ae. aegypti SK and its receptor gene, it was found that only 2% of the G0 generation mutant strains mutated to form chimeras, with a large number of male chimeras dying, and only 14% of female chimeras being able to lay eggs, ultimately resulting in no effective G1 generation mutants. Transcriptome data showed, compared to the control group, 181 genes were significantly differentially expressed after interfering with the SK gene, with 62 genes significantly upregulated and 119 genes significantly downregulated. In addition, after interference with the sulfakinin receptor, 110 genes exhibited significant differential expression, including 20 upregulated and 90 downregulated genes. Cross-analysis of the two datasets identified 46 genes with significant expression changes after interference with sulfakinin or its receptor, with only 4 genes upregulated and the remaining 42 genes significantly downregulated, and the differentially expressed genes were mainly enriched in the metabolic pathway, endocrine system, and digestive system. Conclusions　The SK and its receptor gene are highly conserved and may primarily play roles in regulating the energy metabolism and digestion functions in Ae. aegypti, thus playing an important role in regulating insect growth and development.

Objective A two-sample Mendelian randomization approach was used to explore the causal relationship between im-mune cells and the risk of inflammatory joint diseases.Methods A dataset of 731 immune cells and osteoarthritis,ankylosing spondyli-tis,gout,and psoriatic arthritis was obtained from the Finngen database and the GWAS catalog database.The causal relationship between immune cells and osteoarthritis was explored using inverse variance weighting,weighted median and MR-Egger methods,and the stabili-ty and reliability of the research results were evaluated using Cochran's Q test,MR-Egger regression,MR-PRESSO,Leave one out method,and Meta-analysis.Results A total of 45 immune cells were obtained with osteoarthritis,35 immune cells with ankylosing spondylitis,29 immune cells with gout,and 36 immune cells with psoriatic arthritis in a potential causal relationship(P＜0.05).There was a significant causal relationship between HLA DR on CD14-CD16+monocyte and ankylosing spondylitis(P＜6.8 × 10-5),and the results were stable,but Meta-analysis showed that the causal relationship was not significant(OR=1.00,95％CI:1.00-1.00).Conclusion This study preliminarily reveals the causal relationship between immune cells and inflammatory joint diseases represented by ankylosing spondylitis from the perspective of genetics,and provides an important theoretical basis for future precision medicine and indi-vidualized treatment.

This study was performed to investigate the features of HBV-specific CD8+T cell reactivity in patients with chronic hepatitis B(CHB),HBV-induced liver cirrhosis(LC)or hepatocellular carcinoma(HCC).A total of 124 CHB patients,36 LC patients,and 114 HCC patients were enrolled in this study.The reactive HBV-specific CD8+T cells in peripheral blood were enumerated using an innovative ELISPOT system.In addition,19 CHB patients and 20 HCC patients were longitudinally monitored with an interval of 3-5 months.Data showed that the numbers of reactive HBV-specific CD8+T cells in CHB group were not significantly different from that in LC group,but obviously lower than that in HCC group(P=0.009 9),especially HBsAg-,HBpol-and HBe/cAg-specific CD8+T cells.In CHB group,the patients with normal ALT level,AST level,or low HBV-DNA load showed significantly more reactive HBV-specific CD8+T cells than the patients with abnormal ALT level,abnormal AST level,or high HBV-DNA load.Furthermore,the duration of NUCs treatment had an impact on the HBV-specific CD8+T cell reactivity in CHB patients,while different NUCs at the same treatment duration did not bring different reactivity of HBV-specific T cells.In LC group,the HBeAg-positive patients presented much more reactive HBV-specific CD8+T cells than the HBeAg-negative patients did.In HCC group,the numbers of reactive HBV-specific CD8+T cells in the patients with normal AFP level or normal DCP level were significantly higher than that in the patients with abnormal AFP level or abnormal DCP level.Longitudinal monitoring results showed that HBV-specific CD8+T cell reactivity displayed a slow upward trend in the CHB patients undergoing NUCs treatment,and an obvious increasing in the HCC patients undergoing combined treatment of targeted drugs and immunotherapy.Taken together,the features of HBV-specific CD8+T cell reactivity are distinct among the CHB,LC and HCC patients,and are influenced by virological indicators,tumor markers and treatment regimens.Therefore,more attention should be paid to the changes of HBV-specific CD8+T cell reactivity during clinical treatment.

Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective:This study aimed to construct a risk prediction model for obstructive sleep apnea（OSA） related hypertension based on the nomogram, and to explore the independent risk factors for OSA-related hypertension, so as to provide reference for clinical treatment decision-making. Methods:The clinical data of OSA patients diagnosed by polysomnography from October 2019 to December 2021 were collected retrospectively and randomly divided into training sets and validation sets. A total of 1 493 OSA patients with 27 variables were included. The least absolute shrinkage and selection operator（Lasso） logistic regression model was used to select potentially relevant features and establish a nomogram for OSA-related hypertension.The performance and clinical benefits of this nomogram were verified in terms of discrimination, calibration ability and clinical net benefit. Results:Multivariate logistic regression showed that body mass index（BMI）, family history of hypertension, lowest oxygen saturation（LSaO2）, age and cumulative percentage of total sleep time with oxygen saturation below 90% were independent risk factors for OSA-related hypertension. Lasso logistic regression identified BMI, family history of hypertension, LSaO2 and age as predictive factors for inclusion in the nomogram. The nomogram provided a favorable discrimination, with a C-indexes of 0.835（95% confidence interval[CI ]0.806-0.863） 0.865（95%CI 0.829-0.900） for the training and validation cohort, respectively, and well calibrated. The clinical decision curve analysis displayed that the nomogram was clinically useful. Conclusion:Compared with cumulative percentage of total sleep time with blood oxygen saturation below 90%, LSaO2 may have a greater impact on the incidence of OSA-related hypertension, and the effects of different times and degrees of hypoxia on OSA-related hypertension should be further explored in the future. Apnea hypopnea index involvement is weak in predicting OSA-related hypertension, and the blood oxygen index may be a better predictor variable. Furthermore, we established a risk prediction model for OSA-related hypertension patients using nomogram, and demonstrated that this prediction model was helpful to identify high-risk OSA-related hypertension patients. This model can provide early and individualized diagnosis and treatment plans, protect patients from the serious.
Humans ; Sleep Apnea, Obstructive/complications* ; Nomograms ; Hypertension/epidemiology* ; Male ; Female ; Risk Factors ; Middle Aged ; Retrospective Studies ; Polysomnography ; Logistic Models ; Body Mass Index ; Adult

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.
Animals ; Male ; Goats ; Stem Cells ; Spermatogonia/metabolism* ; Cell Proliferation ; Flow Cytometry ; Testis/metabolism*

Objective·To analyze the progression of children with severe coronary artery lesions due to Kawasaki disease by coronary artery angiography,and evaluate the diagnostic value of echocardiography in these children.Methods·A retrospective analysis was performed to enroll children with Kawasaki disease whose coronary artery lesions were graded Ⅳ or above from Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,from January 2013 to January 2023.The subjects were required to have received at least 2 times of coronary angiogram,and their clinical and imaging data were collected to analyze the progression of the lesions.Echocardiography results were compared with the results of the coronary angiogram.Results·A total of 21 children were included,including 15 males and 6 females,with a median age at onset of 3 years and 6 months,a median age at initial coronary angiography of 7 years and 11 months,a median interval of 4 years and 5 months between the time of onset and initial angiography,a median age at angiographic review of 9 years and 2 months,and a median interval of 1 year and 3 months between the time of initial angiography and review.Coronary stenosis or occlusion was detected in 13 children in the initial angiography,of whom 6 underwent coronary artery bypass grafting(CABG)and had their angiography reviews 1 year later.The review results showed that the bridging vessels were unobstructed and no obvious stenosis was observed.Fifteen children had progression of the lesions detected by echocardiography in the subsequent follow-up and had their angiogram reviews,of whom 8 had significant progression of the coronary lesions.Intracoronary balloon dilatation was performed in 1 case,and CABG was performed in another case.Sixteen lesions of coronary stenosis or occlusion were detected in the initial angiography in 21 children,while only 1 lesion of coronary stenosis was detected by echocardiography during the same period of time.Twenty-eight medium-to large-sized coronary aneurysms were detected in the initial angiography in the 21 children,and the diameters of the 28 aneurysms measured by echocardiography and coronary angiogram were subjected to the Bland-Altman analysis.The Bland-Altman analysis showed that the difference in maximum diameter between 2 methods was(1.63±2.33)mm,with 95％CI of-2.95-6.21 mm.Conclusion·Coronary artery lesions due to Kawasaki disease may be progressive;in the children with severe lesions,coronary artery stenosis or occlusion may be missed or misdiagnosed and some errors may exist in the measurement of diameters of aneurysms by echocardiography.Regular review of coronary angiography is needed.