BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.

Background/Aims: Cytomegalovirus (CMV) disease in the upper gastrointestinal (UGI) tract frequently occurs in immunocompromised patients. However, data regarding UGI CMV disease in non-transplant patients compared with those in transplant recipients are limited. Therefore, we compared the clinical characteristics, endoscopic findings, and outcomes of UGI CMV disease in non-transplant patients with those in transplant recipients. Methods: We reviewed the medical records of patients diagnosed with UGI CMV disease between May 1999 and January 2022. UGI CMV disease was defined as symptoms or signs of gastrointestinal disease with typical findings of CMV inclusion body and positive immunochemistry stain or CMV polymerase chain reaction from the endoscopic biopsy specimen. Results: Among the 219 eligible patients, 132 (60.3%) were transplant patients. Age, male sex, and Charlson Comorbidity Index were significantly higher in the non-transplant group than in the transplant group. The most common symptoms were pain and odynophagia (43.8%). Transplant recipients more frequently experienced UGI CMV disease in the stomach than non-transplant patients, typically presenting as erosions or mucosal hyperemia. However, non-transplant patients more commonly experienced UGI CMV disease in the esophagus than transplant recipients, typically presenting as ulcers. The transplant group had a significantly higher clinical response than the non-transplant group. Conclusions UGI CMV disease in transplant patients can be present in the stomach in various forms, including ulcers or erosions. In transplant patients suspected of UGI CMV disease, conducting an esophagogastroduodenoscopy with tissue biopsy in any area where even the slightest mucosal abnormality is observed is essential to facilitate a prompt diagnosis.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Objective: To analyze the relationship between body mass index(BMI) during pre pregnancy, maternal lipid levels during early pregnancy and childhood overweight and obesity, as well as the mediating role of maternal lipid levels during early pregnancy in pre pregnancy BMI and childhood overweight and obesity, providing scientific evidence for developing obesity prevention strategies in preschool children. Methods: Using data from Peking University Birth Cohort in Tongzhou (PKUBC-T) collected between June 2018 and September 2022, the study included 1 292 mother-child pairs. Participants were stratified into two groups based on children s BMI Z scores at age 3: an overweight/obesity risk group (BMI Z >1, n =173) and a non overweight/obesity risk group (BMI Z ≤1, n =1 119).Multivariate Logistic regression was conducted to analyze the associations between pre pregnancy BMI, maternal lipid levels[total cholesterol(TC),triglyceride（TG）,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),TC/HDL-C,TG/HDL-C,LDL-C/HDL-C] during early pregnancy and childhood overweight and obesity. The mediating effect of maternal lipid levels during early pregnancy on pre pregnancy BMI and childhood overweight and obesity was further explored. Results: There were statistically significant differences in pregnancy BMI levels, early pregnancy blood LDL-C ,TC/HDL-C,LDL-C/HDL-C levels between the overweight and obesity risk group and the non overweight and obesity risk group ( χ 2/Z =19.01, 2.48, 2.48, 2.71, all P <0.05). Multivariate Logistic regression analysis showed that pre pregnancy BMI, LDL-C, TC/HDL-C and LDL-C/HDL-C in early pregnancy were significantly associated with childhood overweight and obesity ( OR =1.09, 1.42, 1.49, 1.60, all P <0.05). LDL-C, TC/HDL-C and LDL-C/HDL-C in early pregnancy played a significant mediating role on pre pregnancy BMI and childhood obesity and the mediating effects accounted for 7.3%, 10.2%, 23.5% of the total effects, respectively (all P <0.05). Conclusions Maternal hyperlipidemia during early pregnancy partially mediated the association between pre pregnancy obesity and childhood obesity. Both pre pregnancy obesity and maternal hyperlipidemia during early pregnancy are risk factors for obesity in preschool children.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Background: Remimazolam is a novel short-acting benzodiazepine. This study compared the effects of remimazolam and propofol on cognitive function in adult patients after surgery or other procedures. Methods: We searched electronic databases, including PubMed, Embase, CENTRAL, Web of Science, and Scopus, for relevant studies. The primary outcome was the proportion of participants who experienced delirium or impaired cognitive function postoperatively. Secondary outcomes included the incidence of hypotension, bradycardia, and postoperative nausea and vomiting. We estimated the odds ratios (OR) and mean differences (MD) with 95% CIs using a random-effects model. Results: In total, 1295 patients from 11 randomized controlled trials were included. The incidence of postoperative delirium was 8.0% in the remimazolam group and 10.4% in the propofol group that was not significantly different (OR: 0.74, 95% CI [0.39–1.42], P = 0.369, I2 = 32%). More favorable cognitive function, as assessed using the Mini-Mental State Examination, was observed in the remimazolam group compared to the propofol group (MD: 1.06, 95% CI [0.32–1.80], P = 0.005, I2 = 89%). Remimazolam lowered the incidence of hypotension (OR: 0.28, 95% CI [0.21–0.37], P = 0.000, I2 = 0%) compared to propofol. Conclusions Remimazolam did not increase the risk of postoperative delirium and maintained cognitive function well, providing hemodynamic stability during surgery compared to propofol.

Background: Remimazolam is a novel short-acting benzodiazepine that has recently been used for general anesthesia. This study compared the safety and efficacy of remimazolam-based total intravenous anesthesia (TIVA) and volatile agent-based anesthesia in adults undergoing general anesthesia. Methods: We searched electronic databases including PubMed, Embase, CENTRAL, and Scopus for relevant studies. The primary outcome was the proportion of patients who experienced hypotension during surgery. Secondary outcomes included incidence of bradycardia, extubation time, duration in the post-anesthesia care unit hospital stay, and incidence of postoperative nausea and/or vomiting (PONV). We estimated the relative risk (RR) and mean difference with 95% CIs using a random-effects model. Results: A total of 969 patients from 12 randomized controlled trials were included. The incidence of hypotension was 14% and 34% in the remimazolam and volatile agent groups, respectively. Remimazolam significantly lowered the incidence of hypotension (RR: 0.43, 95% CI [0.29–0.63], P = 0.0000, I2 = 26%). The remimazolam group had a PONV incidence of 13%, compared to 28% in the volatile agent group, indicating a significant difference (RR: 0.51, 95% CI [0.37–0.72], P = 0.0001, I2 = 15%). No significant differences were observed in the other outcomes. Conclusions Remimazolam-based TIVA demonstrated favorable hemodynamic effects, with a lower incidence of hypotension and similar bradycardia rates, compared to volatile agent-based anesthesia. Furthermore, the reduction in PONV supports the use of remimazolam-based TIVA as a valuable method for general anesthesia.