Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

Objective:To explore the effect of integrating clinical situational mode into experimental teaching of Pathogenic Biology,integrate early clinical concept into experimental teaching,and enhance students'ability to analyze and solve clinical problems,so as to improve the quality of teaching.Methods:A total of 179 students from class 7 to 12 of grade 2022 majoring in clinical medicine of a medical college were enrolled as the research subjects.Among them,88 students from class 7 to 9 were selected as the control group and comprehensive experimental content teaching according to the traditional teaching mode were carried out.A total of 91 students from class 10 to 12 were selected as the experimental group and experimental teaching system of Pathogenic Biology focusing on clinical case analysis and discussion,comprehensive experimental development,and diagnosis and treatment of infectious diseases were carried out.The results of process evaluation and summative evaluation were compared between the two groups,and the effect of integrating clinical situation mode into experimental teaching on improving the learning ability of students in the experimental group was evaluated in the form of a questionnaire survey.Results:Academic performances of process evaluation and summative evaluation in the experimental group were higher than those in the control group(P＜0.01).The integration of clinical situational mode into Pathogenic Biology significantly improved students'learning interest,theoretical comprehension,and cultivation of"early clinical"thinking.Conclusion:The integration of clinical situational mode into Pathogenic Biology experiment course can effectively motivated students'learning enthusiasm and cultivate high-quality medical talents with innovative ability and clinical thinking.

Objective To investigate the relationship between biological aging and the rate of cognitive decline in middle-aged and elderly populations.Methods Longitudinal tracking data of cognitive function were obtained from the China Health and Retirement Longitudinal Study(CHARLS).We employed the Klemera and Doubal method(KDM)to estimate biological age(BA),and calculate the biological aging index(BAI)and biological aging type(BAT).A multivariate linear regression model was employed to analyze the relationships between baseline BAI,BAT,and cognitive function scores.Based on the baseline analysis,a mixed-effects model was used to examine the longitudinal associations between baseline BAI,BAT,and cognitive function during follow-up.Results A total of 5 897 participants were included in the study.BAI was found to be negatively associated with baseline cognitive function scores,with the partial regression coefficient(β)(95％CI)being-0.185(—0.231,—0.139)(P＜0.001).Compared with the lagged aging group,the premature aging group had lower cognitive function scores(β[95％CI]:—0.741[—0.966,—0.516]).For age and sex,for each additional year of baseline BAI,cognitive function scores declined by an average of 0.012(95％CI:—0.019,—0.005)points per year after adjusting for age and sex,and declined by 0.011(95％CI:—0.018,—0.004)points per year after adjusting for other covariates.Compared with participants with lagged aging,those with premature aging experienced,on average,an additional decline of 0.042(95％CI:—0.075,0.009)points per year in cognitive function scores after adjusting for age and sex alone,and by 0.039(95％CI:—0.072,—0.007)points per year after adjusting for other covariates.Conclusion Biological aging affects the rate of cognitive decline in middle-aged and elderly populations.A higher BAI is associated with a faster decline in cognitive function.Compared with those with lagged aging,individuals with premature aging exhibit a more rapid rate of cognitive decline.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male