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.

AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P＜0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.

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.

AIM:This study aims to investigate the expression differences of the ultraconserved RNA gene cluster uc.102-uc.106 and its host gene Obg-like ATPase 1(OLA1)in various tissues of C57BL/6J mice.METHODS:Five healthy male C57BL/6J mice aged 8～10 weeks were selected,and under normal physiological conditions,various tis-sues and organs,including liver,testis,bone marrow,brain,kidney,blood,lung,colon,thymus,spleen,stomach,heart,lymph nodes and bladder,were collected.Simultaneously,magnetic bead separation technology was employed to extract bone marrow blood cells,including B cells,macrophages,erythroid precursor,and mature red blood cells.The ex-pression levels of uc.102-uc.106 and OLA1 mRNA were determined by RT-qPCR with GAPDH as the internal reference.RESULTS:The OLA1 mRNA exhibited high expression levels in the brain,lymph nodes,testis and thymus of C57BL/6J mice,and low expression levels in the liver,spleen,lung,colon and peripheral blood(P<0.05).The expression trend of the uc.102-uc.106 gene cluster was generally opposite to that of OLA1 mRNA,except for both exhibiting high expression levels in testicular tissue(P<0.05).In blood cells,the OLA1 mRNA and the uc.102-uc.106 gene cluster showed the highest expression levels in B cells and the lowest expression levels in mature red blood cells(P<0.05).CONCLU-SION:This study indicates that OLA1 gene and uc.102-uc.106 gene cluster are expressed in different tissues and blood cells of C57BL/6J mice.Notably,the high expression levels of OLA1 gene and uc.102-uc.106 gene cluster in the mouse testis suggest a potential association with male reproductive functions.

Objective To explore the efficacy and safety of intravenous infusion of tirofiban after mechanical thrombectomy in elderly patients with acute anterior circulation intracranial athero-sclerotic stenosis-related large vessel occlusion(ICAS-LVO).Methods A retrospective analysis was conducted on 106 elderly patients with acute anterior circulation ICAS-LVO undergoing me-chanical thrombectomy in our hospital from June 2021 to August 2023.After operation,38 pa-tients receiving 48-hour intravenous infusion of tirofiban at a drip rate of 0.1 μg/(kg·min)were assigned into experimental group,while the other 68 patients undergoing the infusion for only 24 h served as the control group.The indicators related to efficacy(90-day good prognosis rate)and to safety[intracerebral hemorrhage(ICH),symptomatic intracerebral hemorrhage(sICH),and 90-day mortality rate]were compared between the 2 groups.Multivariate logistic regression model was employed to analyze the influencing factors for good prognosis.Results The experimental group exhibited a significantly higher rate of 90-day favorable prognosis than the control group(52.6％vs 29.4％,P=0.018),but no significant differences were observed in the rates of ICH,sICH,and 90-day mortality between the 2 groups(P＞0.05).Multivariate logistic regression anal-ysis indicated that intravenous tirofiban administration for 48 h(OR=2.554,95％CI:1.067-6.116,P=0.034)and NIHSS score at admission(OR=0.887,95％CI:0.822-0.957,P=0.001)were independent influencing factors for 90-day prognosis in elderly patients undergoing mechani-cal thrombectomy due to acute anterior circulation ICAS-LVO.Conclusion In elderly acute ante-rior circulation ICAS-LVO patients receiving mechanical thrombectomy,postoperative intrave-nous tirofiban infusion for 48 h shows better improvement for 90-day prognosis than for 24 h,and has no effect on increasing the risk of sICH.

Objective:To systematically review the effect of bilateral thoracic paravertebral nerve block (TPVB) on postoperative analgesia in the patients undergoing coronary artery bypass grafting (CABG) under general anesthesia (GA) using a meta-analysis.Methods:A systematic search of PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, and VIP databases was performed, with a limited search period ending in December 2023. Randomized controlled trials regarding bilateral TPVB combined with GA versus GA alone for postoperative analgesia following CABG were included. The primary outcome was the rate of 24 h postoperative rescue analgesia. Secondary outcomes were intraoperative opioid consumption, incidence of intraoperative adverse reactions, indicators related to postoperative recovery, and incidence of postoperative adverse reactions. This meta-analysis was performed by using the " meta" package in R studio software.Results:A total of 9 papers ( n=788) were included. Compared to GA, bilateral TPVB combined with GA reduced intraoperative opioid consumption ( SMD=-1.88, 95% confidence interval [ CI] -2.80--0.96), decreased the rate of 24 h postoperative rescue analgesia ( RR=0.17, 95% CI 0.06-0.46) and the incidence of postoperative adverse reactions ( RR=0.39, 95% CI 0.25-0.60) and shortened postoperative extubation time ( MD=-1.52, 95% CI -2.01--1.03), postoperative intensive care unit stay ( MD=-4.40, 95% CI -5.29--3.51) and postoperative hospitalization time ( MD=-0.70, 95% CI -1.37--0.04). Conclusions:Bilateral TPVB can enhance the postoperative analgesic effect in the patients undergoing CABG under general anesthesia.

This article reported a male patient with neonatal onset mental retardation autosomal dominant 35 (MRD35). The boy presented with repeated convulsions, hypotonia, enlarged head circumference, congenital muscular torticollis and feeding difficulties in the neonatal period. Dynamic electroencephalogram showed paroxysmal epileptic discharges in the left central-temporal region. High-throughput whole-exome sequencing revealed a heterozygous mutation of c.139G>A (p.Glu47Lys) in the PPP2R5D gene, which was a de novo mutation not inherited from his parents. The child had significant developmental delay at the age of one year. MRD35 lacks typical clinical manifestations and requires whole-exome sequencing for definitive diagnosis. Currently, there is no specific treatment for MRD35 and symptomatic treatments, including rehabilitation training, language training and seizure control, are mostly adopted.

Objective:To analyze the epidemic characteristics and clinical key indicators of the patients infected with SARS-CoV-2 of the local Omicron variant epidemic, to understand the clinical characteristics of mild and severe patients, and to provide a scientific basis for the effective treatment and prevention of severe disease.Methods:From January 2020 to March 2022, the clinical and laboratory data of COVID-19 patients admitted to the Fifth People's Hospital of Wuxi were retrospective analyzed, including virus gene subtypes, demographic information, clinical classification, main clinical symptoms, and key indicators of clinical testing, and the changes of clinical characteristics of the patients infected with SARS-CoV-2.Results:A total of 150 patients with SARS-CoV-2 infection were admitted, 78, 52 and 20 in 2020, 2021 and 2022, including 10, 1 and 1 severe patient, and the main infected virus strains were L, Delta, and Omicron variants. The relapse rate of patients infected with the Omicron variant was as high as 15.0% (3/20), the incidence of diarrhea decreased to 10.0% (2/20), the incidence of severe disease decreased to 5.0% (1/20), and the number of hospitalization days of mild patients increased compared with 2020 (days: 20.43±1.78 vs. 15.84±1.12); respiratory symptoms were reduced, and the proportion of pulmonary lesions decreased to 10.5%; the virus titer of severely ill patients with SARS-CoV-2 Omicron variant infection (day 3) was higher than that of L-type strain (Ct value: 23.92±1.16 vs. 28.19±1.54). The acute plasma cytokines interleukin (IL-6, IL-10) and tumor necrosis factor-α (TNF-α) were significantly lower in patients with severe Omicron variant new coronavirus infection than those with mild disease [IL-6 (ng/L): 3.92±0.24 vs. 6.02±0.41, IL-10 (ng/L): 0.58±0.01 vs. 4.43±0.32, TNF-α (ng/L): 1.73±0.02 vs. 6.91±1.25, all P < 0.05], while γ-interferon (IFN-γ) and IL-17A were significantly higher than patients with mild disease [IFN-γ (ng/L): 23.07±0.17 vs. 13.52±2.34, IL-17A (ng/L): 35.58±0.08 vs. 26.39±1.37, both P < 0.05]. Compared with previous epidemics (2020 and 2021), the proportion of CD4/CD8 ratio, lymphocyte count, eosinophil and serum creatinine decreased in patients with mild Omicron infection in 2022 (36.8% vs. 22.1%, 9.8%; 36.8% vs. 23.5%, 7.8%; 42.1% vs. 41.2%, 15.7%; 42.1% vs. 19.1%, 9.8%), the proportion of patients with elevated monocyte count and procalcitonin was large (42.1% vs. 50.0%, 23.5%; 21.1% vs. 5.9%, 0). Conclusion:The incidences of severe disease in patients with SARS-CoV-2 Omicron variant infection was significantly lower than that of previous epidemics, and the occurrence of severe diseases was still related to the underlying diseases.

Gallbladder abdominal wall fistula is usually due to the acute cholecystitis with-out timely treatment, which leads the formation of abscess around the gallbladder, the gallbladder adhering to the abdominal wall and the abscess infiltrating into the skin to form a spontaneous abdominal wall fistula. Patient with gallbladder abdominal wall fistula may have the symptoms of cholecystolithiasis and acute cholecystitis. Ultrasound examination can detect the situation of gallbladder conveniently, including the internal echo after formation of abscess, the connection between the gallbladder and abdominal cavity, and the blood flow signal, to clarify the diagnosis for the subsequent treatment. The authors share the diagnosis and treatment experiences of an elderly patient with gallbladder abdominal wall fistula.

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.