ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P＜0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P＜0.05);the inhibition rate of thrombosis formation was 53.80％,23.96％,33.63％,and 32.59％,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P＜0.05),and the inhibition rate of platelet aggregation was 86.90％,26.17％,38.87％,54.48％,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective : To generate heterozygous TRAF2 knockout mice, the CRISPR/Cas9 technology was successfully employed. These mice were served as a valuable model to explore the pathological mechanisms underlying inflammatory and immune disorders mediated by abnormal TNF-α-TRAF2 signaling and to develop new therapeutic targets. Methods : A vector targeting the knockout of the TRAF2 gene was constructed. Lead RNA and Cas9 Mrna were introduced into the fertilized eggs of C57BL/6JGpt mice through microinjection to mediate the TRAF2 gene mutation in mice. The mouse tail protein was extracted and the genotype of the F0 generation was determined by PCR and Western blot. TRAF2+/- mice were successfully obtained. F0 generation mice were backcrossed with C57BL/6JGpt wild-type mice to obtain stable TRAF2+/- mice for propagation and subsequent experiments. The body weight of TRAF2+/- mice was detected; Western blot was used to detect the expression of TRAF2 in the spleen, liver and kidney tissues of TRAF2+/- mice. The development of spleen, liver and kidney tissues in TRAF2+/- mice was detected by HE staining. Results : PCR identification using specific primers demonstrated that TRAF2+/- mice exhibited a target band at 679 bp. Western blot analysis results indicated that, compared with the WT group, the expression of TRAF2 in the tail protein of TRAF2+/- mice was significantly reduced(P+/- mice had a lower body weight compared to their littermate WT mice(P+/- mice was decreased(P+/- mice and WT mice. Conclusion The successful construction of TRAF2+/- mice has provided an important animal model for exploring the role of TRAF2 in developmental regulation, revealing the mechanism of inflammatory immune diseases mediated by abnormal TNF-α-TRAF2 signaling, and screening related drug targets.

Objective:To analyze the risk factors associated with intradialytic hypotension (IDH) in patients undergoing maintenance hemodialysis (MHD).Methods:This study used a cross-sectional design and included 150 adult patients who underwent MHD at The Third Affiliated Hospital of Anhui Medical University from January 2023 to March 2024. Relevant clinical data were collected to analyze the occurrence of IDH in patients undergoing MHD over 3 months, and the associated risk factors.Results:Among the 150 patients undergoing MHD, there were 67 in the IDH group and 83 in the non-IDH group. The IDH group had a higher fibrinogen/albumin ratio (FAR) [89.41 (73.30, 114.50) vs. 76.56 (65.80, 89.60), χ2 = -3.55, P < 0.001], an older age [(68.46 ± 14.10) years vs. (61.30 ± 12.23) years, t = -3.33, P = 0.001], a longer dialysis duration [(4 (3.5, 4.0) hours vs. (4 (4.0, 4.0) hours), U = -2.11, P = 0.044], a greater ultrafiltration volume [(2.20 ± 0.74) L vs. (1.92 ± 0.82) L, t = -2.16, P = 0.032], a higher ultrafiltration rate [(8.90 ± 2.64) mL·h?1·kg?1 vs. (7.75 ± 2.91) mL·h?1·kg?1, t = -2.51, P = 0.013], and a higher ultrafiltration volume/dry body mass ratio [(33.75 ± 9.76) mL/kg vs. (30.21 ± 11.39) mL/kg, t = -2.11, P = 0.046] compared with the non-IDH group. In the IDH group, the proportion of patients with primary chronic glomerulonephritis was lower (19.4% vs. 37.3%, χ2 = 5.76, P = 0.016), fibrinogen levels were higher [(3.63 (3.15, 4.50) μg/L vs. (3.34 (2.90, 3.74) μg/L, U = -2.61, P = 0.009], albumin levels were lower [(41.26 ± 4.03) g/L vs. (43.42 ± 4.29) g/L, t = 3.15, P = 0.002], high-density lipoprotein cholesterol (HDL-C) levels were lower [0.90 (0.77, 1.09) mmol/L vs. 1.05 (0.84, 1.34) mmol/L, U = -2.77, P = 0.006], and C-reactive protein levels were higher [5.92 (2.79, 9.61) mg/L vs. 2.70 (0.99, 6.49) mg/L, U = -2.27, P = 0.023] compared with the non-IDH group. Multivariate logistic regression analysis indicated that higher FAR values ( OR = 1.030, P = 0.025), a history of chronic glomerulonephritis ( OR = 10.408, P = 0.012), older age ( OR = 1.062, P = 0.043), a high ultrafiltration volume/dry body mass ratio ( OR = 1.072, P = 0.037), and low HDL-C levels ( OR = 0.046, P = 0.015) are independent risk factors for IDH. The area under the receiver operating characteristic curve for FAR predicting IDH was 0.699 (95% CI: 0.571-0.827, P = 0.003). The combination of age, chronic glomerulonephritis, ultrafiltration volume/dry body mass ratio, HDL-C levels, and FAR for predicting IDH resulted in a receiver operating characteristic curve area of 0.839 (95% CI: 0.750-0.929, P < 0.001). Conclusions:Among the risk factors for IDH in patients undergoing MHD, FAR is independently associated with an increased risk of IDH and serves as a valuable predictor for its occurrence in these patients.

Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P＜0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P＜0.05);the inhibition rate of thrombosis formation was 53.80％,23.96％,33.63％,and 32.59％,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P＜0.05),and the inhibition rate of platelet aggregation was 86.90％,26.17％,38.87％,54.48％,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.