ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

Objectives:Using data from the heart transplant patient dataset of our center,we aimed to develop a preoperative risk scoring model specifically suitable for the Chinese population undergoing heart transplantation.This model was established to predict the likelihood of graft failure within the first year post-surgery and classify recipients according to their risk level.Methods:A retrospective study was conducted at a single center on 1 210 consecutive heart transplant recipients between June 2004 and December 2022.Risk factor screening was performed using univariate and multivariate logistic regression analyses.Variable selection was carried out through a stepwise backward procedure based on the Akaike Information Criterion(AIC).The regression coefficients obtained from the final model were employed as weighting factors in the multifactor analysis.The study utilized the area under the receiver operating characteristic(ROC)area under curve(AUC)as a metric to evaluate the performance of the model.Patients were stratified into low,medium,and high-risk groups based on the distribution of the calculated scores.Survival analysis was conducted on the various risk groups using the Kaplan-Meier method,with statistical comparisons performed using the log-rank test.A significance level of P<0.05 was deemed statistically significant.Results:A risk scoring model,denoted as the heart transplant(HTx)score,was developed,comprising 11 variables and yielding a total score of 20.6 points.In comparison to the low-risk group,the OR for 1-year graft failure in the medium-risk group was 2.0(95%CI:1.1-3.6,P=0.02),while the high-risk group had an OR of 9.8(95%CI:5.4-17.7,P<0.01).The risk scoring model exhibited strong discriminative ability with an AUC of 0.712(95%CI:0.646-0.778)and an internally validated bias-corrected AUC of 0.713.The results of the Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model demonstrated a strong calibration ability(Hosmer-Lemeshow χ2=2.92,P=0.71).Within the cohort,the AUC values for the IMPACT score,UNOS score,RSS score,Mayo score,BO score,and TRS score models were 0.645,0.651,0.632,0.589,0.610,and 0.604,respectively.These findings suggest that the HTx scoring model exhibited superior predictive performance compared to the aforementioned models in forecasting outcomes within our cohort.The Kaplan-Meier survival analysis revealed statistically significant differences in long-term survival rates between the three risk groups,a noticeable decrease in long-term survival rates were observed with increasing levels of HTx risk stratification(P<0.05).Conclusions:Present results indicate a significant association between the developed HTx risk scores and graft failure within the initial year post-surgery,present model effectively categorizes the heart transplant recipients into low,medium,and high-risk groups and is valuable for risk stratification.

Objective:To analyze the prognostic influencing factors in patients with isocitrate dehydrogenase (IDH) wild-type glioma, and further evaluate the value of surgical resection in prognosis.Methods:The clinical data and molecular pathological information of 647 patients with IDH wild-type glioma were retrieved from the Chinese Glioma Genome Atlas (CGGA) database (from 2006 to 2019). The clinical characteristics were recorded, including gender, age, initial symptoms, preoperative Karnofsky performance status (KPS) score, tumor location, tumor laterality, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and postoperative treatment. Kaplan-Meier survival curve was plotted to calculate overall survival (OS) and progression-free survival (PFS), and comparisons were performed using the log-rank test. Multivariate Cox regression analysis was used to identify the independent influencing factors of prognosis in patients with IDH wild-type glioma.Results:Among the 647 patients with IDH wild-type glioma, there were 120 cases of WHO grade Ⅱ, 115 cases of grade Ⅲ, and 412 cases of grade Ⅳ; the median OS was 20.3 months. There were statistical differences in age, initial symptoms, tumor location, preoperative KPS score, extent of resection, MGMT promoter methylation status and postoperative treatment among patients with different WHO grades (P<0.01), but there were no statistical difference in gender and tumor laterality (P>0.05). The median OS and PFS in patients with WHO grade Ⅱ were significantly longer than those in patients with WHO grade Ⅲ and WHO grade Ⅳ (169.9 months vs. 24.7 and 14.4 months, 138.8 months vs. 17.7 and 11.4 months), the indexes in patients with WHO grade Ⅲ were significantly longer than patients with WHO grade Ⅳ, and there were statistical differences (P<0.05). The median OS and PFS in patients with total resection were significantly longer than those in patients with subtotal resection and partial resection (37.2 months vs. 20.3 and 8.5 months, 29.5 months vs. 17.6 and 6.0 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 153 patients with MGMT promoter methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (67 cases) were significantly longer than those in patients with subtotal resection (64 cases) and partial resection (22 cases): 28.8 months vs. 18.4 and 9.0 months, 25.6 months vs. 16.6 and 6.5 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 202 patients with MGMT promoter non-methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (81 cases) were significantly longer than those in subtotal resection (81 cases) and partial resection (40 cases): 31.3 months vs. 21.9 and 14.0 months, 22.7 months vs. 16.8 and 9.7 months, and there were statistical differences (P<0.05), but there were no statistical difference in the indexes between patients with subtotal and patients with partial resection (P>0.05). Multivariate Cox regression analysis result showed that age, extent of resection, WHO grade (grade Ⅲ/grade Ⅳ) and postoperative treatment were independent OS and PFS influencing factors in patients with IDH wild-type glioma (OS: HR = 1.327, 3.295, 3.406/7.964 and 1.597; 95% CI 1.079 to 1.633, 2.627 to 4.132, 2.225 to 5.216/5.339 to 11.880 and 1.288 to 1.981; P<0.01. PFS: HR = 1.282, 2.655, 3.143/6.511 and 1.477; 95% CI 1.039 to 1.583, 2.123 to 3.322, 2.049 to 4.819/4.376 to 9.690 and 1.181 to 1.849; P<0.05 or <0.01).Conclusions:The age, extent of resection, WHO grade and postoperative treatment are independent prognosis influencing factors in patients with IDH wild-type glioma. Treatment strategies should fully consider the clinical and molecular pathological characteristics to achieve maximal safe tumor resection and optimal survival benefit.

Oral fluid specimens are a new type of specimen whose clinical application value is widely evaluated. Compared with conventional pathogen detection technology, they have the advantages of non-invasive, simple operation and self-collection. They can be used for biochemical analysis, nucleic acid detection of infectious pathogens and tumor cells, and have been recommended for screening and diagnosis of certain diseases. This article mainly summarizes the collection methods of oral fluid and related samples, as well as their application in the diagnosis of infectious pathogens, providing a reference for the detection and research of clinical infectious disease etiology in China.

Objective:To investigate the dynamic changes of inflammatory biomarkers in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support after cardiac surgery, and evaluate their predictive value for in-hospital mortality.Methods:The retrospective study included 212 patients who underwent VA-ECMO support following cardiac surgery at Beijing Anzhen Hospital, Capital Medical University, from January 2021 to May 2024. Baseline characteristics and inflammatory markers during ECMO support including procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen (FBG) were collected. Univariate analysis, ROC curves, and multivariate logistic regression were performed to assess the association of these indicators with outcomes. Results:On day 3 post-ECMO, mean PCT and CRP levels were significantly higher in the deceased group (87 cases) than in the survival group (125 cases). PCT demonstrated an area under the curve ( AUC) of 0.750 (95% CI: 0.680-0.819) for predicting mortality, while CRP had an AUC of 0.701(95% CI: 0.625-0.778). No significant differences were observed in FBG, NLR, or PLR between the two groups. Lactate levels at 24 h post-ECMO ( AUC=0.723) and SOFA scores ( OR=2.511, AUC=0.713) were also significantly associated with mortality risk in the deceased group ( P<0.05). Conclusion:Dynamic increases in PCT and CRP are independent predictors of in-hospital mortality in cardiac surgery patients supported by ECMO. Elevated lactate levels and SOFA scores, aligning with previous studies, reflect severe tissue hypoperfusion and multi-organ dysfunction in non-survivors, underscoring the necessity of dynamic monitoring of inflammatory and organ function markers for prognosis assessment.

Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.

Alzheimer's disease(AD)is a multifactorial condi-tion characterized by the accumulation of toxic proteins and asso-ciated neurodegeneration.AD is distinguished by the pathologi-cal aggregation of amyloid beta(Aβ)and Tau proteins.The in-teraction between Aβ and Tau can further induce neuroinflamma-tion,mitochondrial autophagy dysfunction,and endoplasmic retic-ulum stress,exacerbating synaptic damage and neuronal death.Neuronal cells are particularly susceptible to protein misfolding due to an imbalance between protein production and degrada-tion.The ubiquitin/26S proteasome system(UPS),a major pathway for protein degradation in eukaryotic cells,plays a cruci-al role in recognizing misfolded or damaged proteins within the nervous system.In UPS,the levels of ubiquitin are tightly regu-lated by both ubiquitin ligases(E3s)and deubiquitylases(DUBs).This article reviews the involvement and mechanisms of E3s and DUBs in the pathogenesis of AD,aiming to provide novel research strategies for its treatment.

Objective To validate the diagnostic performance and risk stratification ability of an AI-based recognition system(PE-AI)for pulmonary embolism(PE)using computed tomography pulmonary angiography(CTPA)so as to analyze its diagnostic value in clinical practice.Methods A total of 416 patients with suspected PE who underwent CTPA from January 1,2023 to December 10,2023 at our hospital were included in this study.Two junior radiologists and PE-AI separately detected and diagnosed emboli in the collected cases by double-blind method,and recorded the diagnosis time respectively.Three senior radiologists reviewing with clinical follow-up results were used as the gold standard in this study.Diagnostic performance was evaluated by using the receiver operating characteristic(ROC)curve analysis and Delong-t test.For positive cases,the pulmonary artery obstruction index(PAOI)calculated by AI and manually were collected respectively and consistency analysis was performed.Results The area under the curve(AUC)of PE-AI,manual and combined diagnosis was 85.6％,90.8％and 95.1％,respectively,which differed significantly(P＜0.05).The reading time of PE-AI[(0.16±0.07)min]was significantly lower than the time of manual[(4.42±1.85)min,P＜0.001]and combined diagnosis[(4.58±1.84)min,P＜0.001].The PAOI measured by PE-AI and manually had high consistency(intraclass correlation efficient,ICC=0.80)in the subgroup analysis of confirmed cases.Conclusion AI can quickly identify pulmonary artery emboli in a short time and assist radiologists to improve diagnostic efficiency.At the same time,through the intelligent detection of PAOI,it is helpful for the risk stratification of patients with PE and optimizing the diagnosis and treatment pathway for pulmonary embolism.

BackgroundMental health issues have become increasingly prominent amid rising societal pressure. Depressive disorders， characterized as chronic and recurrent conditions， adversely affect patients' physical and mental well-being while imposing a significant economic burden. Previous studies on depressive disorders in China have relied on cross-sectional surveys， capturing prevalence at specific time points， but lacking systematic analyses across age， period， and cohort dimensions. ObjectiveTo analyze long-term trends in the disease burden of depressive disorder in the Chinese population from 1990 to 2021， and to provide references to inform prevention and treatment strategies. MethodsData on the disease burden of depressive disorders in China were obtained from the Global Burden of Disease Study 2021 （GBD 2021） database. A joinpoint regression model was used to analyze trends in the disease burden. An age-period-cohort model， implemented in Stata 17.0， was applied to assess variations in incidence and disease burden attributable to age， period and cohort effects. ResultsFrom 1990 to 2021， the disability-adjusted life year （DALY） rate for depressive disorders in China decreased by an average of 0.27% annually， while the incidence rate decreased by an average of 0.24% annually. Females had higher incidence and DALY rates than those of males. The age-period-cohort model analysis revealed that age effects on incidence and disease burden steadily increased， period effects declined over time， and cohort effects initially increased and then declined. ConclusionFrom 1990 to 2021， both the incidence and DALY rates of depressive disorders in China showed a declining trend. Females experienced a higher burden compare to males. Additionally， incidence and DALY rates increased with age but declined over time.

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*