Objective​ To evaluate the clinical characteristics and influencing factors of fatigue in patients with rheumatoid arthritis （RA）， with the aim of providing guidance for clinical treatment. Methods​ Based on the multicenter real-world cohort of the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform， patients with RA enrolled from 2019 to 2025 were included. Demographic data， disease assessment indicators， laboratory indices， and traditional Chinese medicine （TCM） syndrome patterns were collected to analyze the TCM syndromes and clinical characteristics of RA patients with fatigue. Spearman correlation analysis and logistic regression analysis were used to identify factors associated with fatigue in RA. Results​ A total of 3 021 patients with RA were included， among whom 2 007 （66.43%） had fatigue. Compared with the non-fatigue group， the fatigue group was older and had a longer disease duration， with significantly higher scores for the 28-joint Disease Activity Score （DAS28）， swollen joint count （SJC）， tender joint count （TJC）， Health Assessment Questionnaire （HAQ）， pain visual analog scale （VAS）， and patient global assessment （PGA） （P<0.01）. Among TCM syndromes， fatigue was more common in patients with dampness-heat obstruction， cold-dampness obstruction， and liver-kidney deficiency syndromes （P<0.05）. Multivariate analysis revealed that morning stiffness duration exhibited a stepwise association with fatigue， while poor appetite， insomnia with frequent dreaming， restlessness， high HAQ scores， and high pain VAS scores were identified as risk factors. ConclusionFatigue is a prominent symptom in patients with RA and is more common among those with dampness-heat obstruction， cold-dampness obstruction， and liver-kidney deficiency syndromes. It is closely associated with disease activity， pain， functional limitation， sleep， and emotional status.

ObjectiveTo investigate the risk factors for atherosclerosis （AS） in rheumatoid arthritis （RA） patients and its correlation with traditional Chinese medicine （TCM） syndromes. MethodsA cross-sectional study was conducted， enrolling 16,082 RA patients from 122 medical centers nationwide. Patient demographics， disease assessment data including disease activity （DAS-28）， tender joint count （TJC）， swollen joint count （SJC）， patient's global assessment （PGA）， evaluator's global assessment （EGA）， and visual analogue scale （VAS）， major clinical symptoms including insomnia， loss of appetite， irritability， and fatigue， and laboratory indicators including blood routine， inflammatory markers， liver and kidney function， metabolic indices， and coagulation markers were collected through questionnaire. Based on the four examinations in TCM， patients were classified into eight TCM syndromes， which were wind-damp obstruction， cold-damp obstruction， damp-heat obstruction， phlegm-stasis obstruction， blood stasis obstructing the collaterals， qi-blood deficiency， liver-kidney insufficiency， and qi-yin deficiency. Patients who experienced AS events were included in the event group （564 cases）， while those without AS events were included in the non-event group （15,518 cases）. Intergroup difference tests were used to screen potential risk factors， and binary logistic regression analysis was employed to assess the correlation between TCM syndromes and rheumatoid arthritis with atherosclerosis （RA-AS）. ResultsCompared to the non-event group， patients in the event group had longer disease duration， higher body weight， and older age （P＜0.05）， and showed significantly higher DAS28， TJC， SJC， PGA， EGA， VAS， ESR， low-density lipoprotein cholesterol （LDL-C）， triglycerides （TG）， total cholesterol （TC）， and D-dimer levels， and lower high-density lipoprotein cholesterol （HDL-C）， with more severe symptoms of insomnia， irritability， and fatigue （P＜0.05）. Damp-heat obstruction syndrome was the most prevalent in both groups， with a higher proportion in the event group （393/564， 69.68%） than in the non-event group （4578/15,518， 29.50%） showing significant difference （P＜0.05）. Logistic regression analysis showed that patients with damp-heat obstruction syndrome had a 5.326-fold higher risk of developing RA-AS compared to those without this syndrome （OR=5.326， 95%CI 4.517 to 7.089， P＜0.001）. ConclusionThe occurrence of RA-AS is associated with TCM syndromes， disease activity， inflammatory markers and lipid metabolic indices， and damp-heat obstruction syndrome is an independent risk factor for RA-AS.

Objective:To evaluate the association between the preoperative aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:In this nested case-control study, medical records from patients, aged ≥55 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, with Mini-Mental State Examination (MMSE) scale score >24 on preoperative day 1, scheduled for elective total knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital between November 2021 and December 2023, were collected. POD was assessed using the Confusion Assessment Method. Patients were categorized into POD and non-POD groups based on the occurrence of POD. Logistic regression was employed to identify protective and risk factors for POD. The predictive performance of preoperative AST/ALT ratio alone and its combination with cerebrospinal fluid (CSF) biomarker concentrations for POD was evaluated using receiver operating characteristic curves, and the clinical utility of the prediction models was assessed using decision curve analysis. Mediation analysis was conducted to examine the mediation role of CSF biomarkers in the relationship between the preoperative AST/ALT ratio and POD. Restricted cubic splines were used to assess the nonlinear relationship between the preoperative AST/ALT ratio and POD.Results:A total of 460 patients were finally included, with 49 in POD group and 411 in non-POD group. After adjustment for multiple confounding factors including age, sex, educational level, MMSE score, history of hypertension, history of diabetes, history of smoking and history of alcohol use, multivariable logistic regression identified that the higher preoperative AST/ALT ratio, CSF total tau protein (t-tau) and phosphorylated tau protein (p-tau) concentrations were independent risk factors for POD, whereas lower CSF β-amyloid 42 (Aβ 42) concentration, Aβ 42/t-tau ratio and Aβ 42/p-tau ratio served as protective factors ( P<0.05). The area under the receiver operating characteristic curve of the preoperative AST/ALT ratio combined with CSF biomarkers in predicting POD was 0.939 ( P<0.001), demonstrating high clinical efficacy. After adjusting for age, educational level, sex, MMSE score, history of hypertension, history of diabetes, history of smoking, history of alcohol use and body mass index, restricted cubic splines revealed a nonlinear relationship between preoperative AST/ALT levels and the probability of POD, and the probability of POD increased with rising ratios when the preoperative AST/ALT ratio ranged from 1.09 to 1.40 ( Poverall < 0.05, Pnonlinear <0.05). After stratification by sex, the preoperative AST/ALT ratio demonstrated a linear relationship with the probability of POD ( Poverall <0.05, Pnonlinear>0.05). Mediation analysis indicated that the relationship between the preoperative AST/ALT ratio and POD was partially mediated by CSF p-tau concentration (proportion mediated 18.1%), CSF t-tau concentration (proportion mediated 12.0%), and the Aβ 42/t-tau ratio (proportion mediated 15.4%). Conclusions:A higher preoperative AST/ALT ratio is an independent risk factor for POD in total knee/hip arthroplasty patients. The concentrations of CSF t-tau and p-tau and Aβ 42/t-tau ratio have a mediating role in the relationship between the preoperative AST/ALT ratio and POD.

Objective:To explore the impact of different blood transfusion thresholds on clinical outcomes in children with severe traumatic brain injury (TBI).Methods:A retrospective cohort study was conducted. Clinical data was collected from 64 children with severe TBI who received red blood cell transfusions and were admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children′s Hospital between January 2020 and December 2024. Data included basic clinical characteristics, mortality rate, neurological recovery (measured by Glasgow coma scale (GCS) at discharge, pediatric cerebral performance category (PCPC) score), length of stay in the PICU, duration of mechanical ventilation, and incidence of complications. Patients were divided into a liberal transfusion group (hemoglobin >70-<100 g/L at first transfusion) and a restrictive transfusion group (hemoglobin ≤70 g/L at first transfusion). Stratified analysis was performed based on age (children >5 and children ≤5 years old). Comparisons between groups were conducted using the independent samples t test, Mann-Whitney U test, χ2 test or Fisher′s exact test. Results:Among the 64 children with severe TBI (43 males and 21 females), the age was 4.9 (2.3, 10.0) years. There were 33 cases in the liberal transfusion group and 31 cases in the restrictive transfusion group. No statistically significant differences were observed in baseline data, including gender, age, trauma mechanism, GCS at admission, surgical intervention, presence of multiple injuries, or comorbidities (sepsis, shock, ventilator-associated pneumonia and acute kidney injury) between the 2 groups (all P>0.05). There were no statistically significant differences between the liberal and restrictive transfusion groups in mortality rate, GCS and PCPC score at discharge, length of PICU stay, duration of mechanical ventilation, or transfusion volume (all P>0.05). In the stratified analysis, 38 children aged over 5 years were included. The restrictive transfusion subgroup, which included 19 children, had a significantly longer PICU length of stay compared to the liberal transfusion subgroup, which also included 19 children (29.5 (18.0, 36.3) vs. 17.0 (6.3, 25.8) d, Z=2.11, P=0.035). Conclusions:There were no significant differences in PICU mortality or neurological functional recovery between the liberal and restrictive blood transfusion strategies in children with severe TBI. However, among children aged over than 5 years, a restrictive transfusion strategy might be associated with a longer length of PICU stay.

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans