Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective: To comprehensively evaluate the clinical efficacy of a single dose of tranexamic acid (TXA) in reducing perioperative blood loss in patients undergoing craniomaxillofacial plastic and cosmetic surgery through meta-regression analysis. Methods: Embase, PubMed, Wanfang Data, VIP database, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect clinical studies evaluating efficacy of perioperative TXA administration in patients undergoing craniomaxillofacial plastic and cosmetic surgery, from inception to August 2024. Quality assessment of randomized controlled trials (RCTs) was performed using Cochrane Collaboration's Risk of Bias Tool. Based on the results of methodological heterogeneity, corresponding meta-analyses were conducted using either random-effects or fixed-effects models in R programming software. Results: Thirty-one articles were included, involving 2 072 patients who underwent craniomaxillofacial plastic and cosmetic surgeries. Among these patients, 1 051 were in the TXA treatment group, and 1 021 were in the control group. The paired meta-analysis showed that compared with the control group, the use of TXA significantly reduced bleeding volume in perioperative patients [standardized mean difference (SMD)=-1.13; 95%CI (-1.47, -0.80), P<0.001]. Subgroup analysis revealed that TXA significantly reduced intraoperative bleeding volume in patients across different surgeries, with the order of efficacy as follows: orthognathic surgery [SMD=-1.44; 95%CI (-2.07, -0.80), P<0.001], cleft palate repair [SMD=-1.32; 95%CI (-2.14, -0.50), P<0.001], rhinoplasty [SMD=-0.97; 95%CI (-1.63, -0.30), P<0.001], and craniosynostosis [SMD=-0.96; 95%CI (-1.40, -0.53), P=0.040]. The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) (P=0.650). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger's test indicated a certain degree of publication bias (Z=-3.40, P<0.001). Conclusion: Existing evidence suggests that TXA effectively reduces perioperative blood loss in patients undergoing craniofacial plastic surgery, regardless of its dosage administered.

In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5％,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

Objective:To the investigate the predictive value of preoperative systemic inflammatory response index (SIRI) for postoperative clinical outcome in patients with spontaneous intracerebral hemorrhage (ICH) in basal ganglia region.Methods:Patients with ICH in basal ganglia region underwent surgical treatment at the Department of Neurosurgery, the Affiliated Hospital of Qingdao University from January 2015 to December 2021 were retrospectively included. At 3 months after surgery, the modified Rankin Scale was used to evaluate the clinical outcome, with a score of 0-2 defined as good outcome and >2 defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent correlation between SIRI and poor outcome in patients with ICH. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive value of SIRI. Results:A total of 258 patients with ICH in basal ganglia region underwent surgical treatment were enrolled, including 176 males (68.22%), aged 57.00 years (interquartile range, 49.00-65.25 years); median hematoma volume was 50.00 ml (interquartile range, 40.00-70.00 ml), and median SIRI was 4.12 (interquartile range, 2.28-7.30); 143 patients (55.43%) had poor outcome. Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.070, 95% confidence interval [ CI] 1.030-1.111; P<0.001), lower Glasgow Coma Scale score ( OR 0.669, 95% CI 0.575-0.779; P<0.001), higher platelet count ( OR 1.010, 95% CI 1.003-1.017; P=0.004), and higher SIRI ( OR 1.434, 95% CI 1.255-1.638; P<0.001) were the independent predictors of poor outcome. ROC curve analysis showed that the area under the curve for predicting poor outcome by SIRI was 0.791 (95% CI 0.737-0.845; P<0.001), with an optimal cutoff value of 4.53. The predictive sensitivity and specificity were 67.8% and 81.7%, respectively. Conclusion:Preoperative SIRI can effectively predict the clinical outcome of patients with ICH in basal ganglia area at 3 months after surgery, and SIRI >4.53 indicates poor outcome.

Objective:To investigate the effectiveness and safety of endovascular therapy for patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion with early neurological deterioration (END).Methods:Patients with AIS due to anterior circulation large vessel occlusion with END underwent endovascular therapy under the multimodal imaging guidance in the Department of Neurology, Huai'an First Hospital Affiliated to Nanjing Medical University from June 2019 to April 2023 were collected retrospectively. The modified Thrombolysis in Cerebral Infarction (mTICI) grading was used to evaluate the vascular recanalization, and grade 2b or 3 was defined as successful recanalization. At 90 days after onset, the modified Rankin Scale (mRS) was used to evaluate the functional outcome, and 0-2 was defined as a good outcome. The patients with onset to femoral artery puncture time ≤24 hours and >24 hours were compared.Results:A total of 19 patients were enrolled, including 13 males, aged 61.16±11.75 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-5), and the median NIHSS score at END was 13 (interquartile range, 10-20). Twelve patients (63.2%) received intravenous thrombolysis before END. Median baseline Alberta Stroke Project Early CT Score (ASPECTS) was 8 (interquartile range, 7-9); 18 patients (94.7%) achieved successful recanalization, and 2 (10.5%) experienced symptomatic intracranial hemorrhage (sICH). At 90 days after onset, the mRS scores: 0-2 in 12 cases (63.2%), 3 in 4 cases (21.1%), 5 in 1 case (5.2%), and 6 (death) in 2 cases (10.5%). There were 10 patients (52.6%) in the group with onset time to femoral artery puncture ≤24 hours, and 9 patients (47.4%) in the group with onset time >24 hours. There was significant difference between the two groups only in the ASPECTS ( P=0.035), but there were no significant differences in the postprocedural recanalization rate, sICH incidence rate, and good outcome rate at 90 days. Conclusion:Endovascular therapy under the guidance of multimodal imaging is safe and feasible for AIS patients with END due to anterior circulation occlusion.

Objective To investigate the clinical characteristics,diagnosis,treatment,and prognosis of descending necrotizing mediastinitis(DNM)to provide a reference for the early diagnosis and timely treatment of DNM.Methods Data on DNM in China was electronically retrieved from the core databases and comprehensively reviewed from June 2012 to June 2023.The infection,pathogenic microorganisms,main symptoms,comorbidities and treatment methods of DNM were analyzed.Results The data of a total of 781 DNM patients,with an average age of(52.97±5.64)years,were retrieved,including 554 males and 227 females.Odontogenic source,tonsillitis,pharyngeal abscess,sialoadenitis,upper respiratory tract infection,foreign body injury,or iatrogenic traumatic procedures are common causes.Among these,odontogenic infection is the most common source.Streptococcus sp.(n=217)and Staphylococcus sp.(n=82)were most isolated,followed by Klebsiella pneumoniae and Pseudomonas aeruginosa(equally n=59).A total of 69.4％(542/781)of DNM patients recruited in this study were discovered to have various comorbidities,and more than one-third of these patients(n=185)had diabetes.Of the broad antibiotics,carbapenem was most frequently used as treatment,and vancomycin was the most frequently coadministered.The mediastinal drainage approach varies widely,and the optimal regimen is still unknown.Seventy-two patients were treated with video-assisted thoracoscopic/mediastinoscopic surgical drainage,22 patients were treated with percutaneous catheter drainage,30 underwent the transcervical approach,and 40 underwent thoracotomy.A total of 617 patients who were selected underwent the appropriate combined operation for surgical drainage according to the specific location of the infected focus.The overall mortality rate of all 781 DNM pa-tients included was 11.2％.Conclusion The most effective diagnosis and treatment of DNM is a high degree of clini-cal vigilance followed by prompt and adequate drainage with intensive care,including hemodynamic monitoring,nutri-tional support,computer tomographic scanning repeated as necessary,and combined use of systemic antibiotics.

Objective:To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Temporomandibular disorders (TMD) are a heterogeneous group of diseases that affect the temporomandibular joint, chewing muscle system, dental occlusion, and even various structures throughout the body, with significant characteristics of biological-psychological-social pattern. TMD related chronic pain, as the most important clinical symptom, can result in negative emotions seriously affecting patients′ quality of life and physical and mental health. Although a variety of therapies have been previously reported to treat TMD related chronic pain, there is a lack of widely recognized therapies. Professor Jason W Busse (from Michael G DeGroote National Pain Centre, McMaster University, Hamilton ON, Canada) took the lead and collaborated with multiple internationally renowned schools/hospitals of stomatology to develop an international consensus on the management of chronic pain associated with TMD, a clinical practice guideline, which took two years and was published in December 15th, 2023 in a global top journal of clinical research The British Medical Journal. This clinical practice guideline explored the comparative effectiveness of available therapies for chronic pain associated with TMD, conditionally recommended the specific intervention for different treatment or pain relief, proposed a comprehensive, agreed, and standardized clinical practice guideline. This present article describes the methodology and key elements of the clinical practice guideline to help clinicians fully understand and appropriately apply this guidance, which could provide the references for clinical practice of TMD associated chronic pain in China.