BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVES: We propose a YOLOv11-TDSP model for improving the accuracy of dental abnormality detection on panoramic oral X-ray images. METHODS: The SHSA single-head attention mechanism was integrated with C2PSA in the backbone layer to construct a new C2PSA_SHSA attention mechanism. The computational redundancy was reduced by applying single-head attention to some input channels to enhance the efficiency and detection accuracy of the model. A small object detection layer was then introduced into the head layer to correct the easily missed and false detections of small objects. Two rounds of structured pruning were implemented to reduce the number of model parameters, avoid overfitting, and improve the average precision. Before training, data augmentation techniques such as brightness enhancement and gamma contrast adjustment were employed to enhance the generalization ability of the model. RESULTS: The experiment results showed that the optimized YOLOv11-TDSP model achieved an accuracy of 94.5%, a recall rate of 92.3%, and an average precision of 95.8% for detecting dental abnormalities. Compared with the baseline model YOLOv11n, these metrics were improved by 6.9%, 7.4%, and 5.6%, respectively. The number of parameters and computational cost of the YOLOv11-TDSP model were only 12% and 13% of those of the high-precision YOLOv11x model, respectively. CONCLUSIONS The lightweight YOLOv11-TDSP model is capable of highly accurate identification of various dental diseases on panoramic oral X-ray images.
Radiography, Panoramic/methods* ; Humans ; Algorithms ; Tooth Abnormalities/diagnostic imaging*

The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Subarachnoid Hemorrhage/complications* ; Inflammasomes/metabolism* ; Rats ; Mice ; Neuroinflammatory Diseases/metabolism* ; WNK Lysine-Deficient Protein Kinase 1/genetics* ; Male ; Humans ; Chlorides/metabolism* ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; Brain Injuries/metabolism* ; Microglia/metabolism* ; Protein Serine-Threonine Kinases

Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Anterior cruciate ligament(ACL)injury is caused by strong violence,which can destabilize the knee joint,cause joint cartilage degeneration,meniscus injury,and in severe cases,develop osteoarthropathy.The gold standard for the treatment of ACLR injuries at this stage is arthroscopic anterior cruciate ligament recon-struction(ACLR).In clinical practice,the LARS(Ligament advanced reinforcement system)artificial ligament made of polyethylene terephthalate(PET)as the material has a good effect in the short and medium term,but the long-term biological healing between the graft and the host bone is poor,and the real"ligamentization"requirement of the postoperative graft cannot be met.Coating-modified modification of artificial ligaments can improve their hydrophilicity and biocompatibility,which in turn can promote the healing of graft-bone tunnels.Tendon bone healing is a bone-derived progressive process from indirect insertion to direct insertion,which takes a relatively long time and is closely related to the prognosis and early rehabilitation effect of patients.This article reviews the progress of superficial modification of artificial ligaments to promote ACLR tendon bone healing.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?

Objective:To calculate the yield and relative biological effectiveness (RBE) of proton radiation-induced DNA damage to C. elegans germ cells using the Geant4-DNA toolkit in order to explore the biological effects of proton radiation on Caenorhabditis elegans. Methods:A DNA model for a 20-μm-diameter C. elegans germ cell was built using Hilbert curves within the Geant4-DNA toolkit. By simulating DNA damage induced by proton radiation at varying energy levels (100, 50, 20, 5 and 2 MeV), the correlations between DNA double-strand break yields (YDSBs) and different parameters such as physics constructors, energy threshold (ET) models, and free radical scavenging distances were explored, and the result were compared with biological experimental data (20 MeV proton). The DNA damage types from varying energy levels of protons were defined, and the relative biological effectiveness of DNA double-strand breaks (RBE DSB) values were calculated using the RBE DSB mathematical model. Results:The analysis of proton radiation-induced DNA damage under varying physics constructors, ET models, and free radical scavenging distances indicated that the proton radiation-induced YDSBs were the lowest when physics constructor 2 was utilized, while the YDSBs under physics constructors 4 and 6 differed slightly. The proton radiation-induced YDSBs gradually decreased with a rise in both the single ET and free radical scavenging distance. The comparison revealed that the simulation result were the closest to biological experimental data under physics constructor 4, a single ET model of 21.25 eV, and a radical scavenging distance of 9 nm, with disparities approximating 8.3%. Calculated RBE DSB values for protons spanned 1.02 to 1.85, with a lower proton energy corresponding to higher RBE DSB values. Conclusions:Proton radiation-induced YDSBs in C. elegans derived using Geant4-DNA simulations align well with relevant assessments using molecular biology. This study provides a vital means for understanding and predicting the biological effects stemming from proton radiation

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

ObjectiveTo investigate the influencing factors for the prognosis of patients with acute－on－chronic liver failure （ACLF）， and to establish a short－term prognostic model. MethodsA retrospective analysis was performed for the baseline clinical data of 247 patients with ACLF who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Xi’an Jiaotong University， from January 2011 to December 2016， and the patients were divided into survival group and death group. The two groups were compared to identify the influencing factors for prognosis； a prognostic model was established， and the receiver operating characteristic （ROC） curve was used to assess its predictive efficacy and determine the optimal cut－off value. The independent－samples t test was used for comparison of normally distributed continuous data between groups， and the Mann－Whitney U rank sum test was used for comparison of non－normally distributed continuous data between groups； the Fisher’s exact test or the Pearson’s chi－square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for 28－ and 90－day prognosis， and the Kaplan－Meier method was used to plot the 28－day survival curves. ResultsA total of 220 patients with ACLF were included based on the inclusion and exclusion criteria； there were 148 patients in the 28－day survival group and 72 patients in the 28－day death group， with a 28－day transplantation－free survival rate of 67.27%； there were 115 patients in the 90－day survival group and 105 patients in the 90－day death group， with a 90－day transplantation－free survival rate of 52.27%. The logistic regression analysis showed that female sex （odds ratio ［OR］=2.149， P=0.030）， high Model for End－Stage Liver Disease （MELD） score （OR=1.120， P<0.001）， and low lymphocyte count （OR=0.411， P=0.002） were independent risk factors for 28－day prognosis， and an LS－MELD model for 28－day prognosis was established as Logit （28－day prognosis）=－3.432+0.765×sex－0.890×lymphocyte count×10^－9+0.113×MELD（1 for male sex and 2 for female sex）. The ROC curve analysis showed that this model had an optimal cut－off value of 0.35， and then the patients were divided into low LS－MELD group （≤0.35） and high LS－MELD group （>0.35）； the low LS－MELD group had a significantly higher 28－day survival rate than the high LS－MELD group （P<0.001）. ConclusionPeripheral blood lymphocyte count combined with sex and MELD score has a certain value in predicting the short－term prognosis of ALCF patients.

Objective:To understand the prevalence of insufficient physical activity among adults aged ≥18 years in China and to explore the influencing factors.Methods:The China Chronic Disease and Risk Factor Surveillance was conducted in 298 counties/districts in China in 2018, covering 31 provinces (autonomous regions, municipalities). A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. A questionnaire including Global Physical Activity Questionnaire was used to collect information about the participants' demographic characteristics and physical activity through face-to-face interview. A total of 183 769 participants completed the survey. After complex data weighting, the prevalence of insufficient physical activity, occupation, transportation, and leisure-time physical activity time was analyzed. Multivariate logistic regression models were used to analyze the influencing factors related to insufficient physical activity.Results:The prevalence of insufficient physical activity among adults aged ≥18 years was 22.3% (95% CI: 20.9%-23.7%) in China in 2018, with males [24.4% (95% CI: 23.0%-25.8%)] significantly higher than females [20.2% (95% CI: 18.6%-21.8%)]. Adults aged 70 years and above [28.4% (95% CI: 26.9%-29.9%)] were significantly higher than adults in other age groups, followed by adults aged 18-29 years [26.4% (95% CI: 24.4%- 28.3%)] and 30-39 years [23.4% (95% CI: 21.5%-25.3%)], and tended to increase with increasing education and total sedentary behavior time ( P<0.001). The weekly occupation, transportation, and leisure-time physical activity time appeared 958.6 (95% CI: 911.4-1 005.8) minutes, 234.5 (95% CI: 224.7- 244.2) minutes, and 88.6 (95% CI: 83.5-93.7) minutes, respectively. Multivariate logistic regression analysis showed that males, adults living in rural areas or northern China, ≥70 years, with junior high school education, an annual household income per capita <6 000 yuan and institutional/clerical/ technical occupation and longer total sedentary behavior time were related to a higher prevalence of insufficient physical activity. Conclusions:In China, over one-fifth of the adults had lower physical activity levels. Adults who are male, young adults, more educated, institutional/clerical/technical occupation, and with more extended total sedentary behavior are the populations that need to be focused on to promote physical activity-related health.