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.

AIM: To investigate the relationship between Apelin and δ-like ligand 4(DLL4)expression levels and clinical stage and efficacy in patients with neovascular glaucoma(NVG).METHODS: A total of 96 NVG patients(96 eyes)who were admitted to our hospital from January 2022 to March 2024(NVG group)and 96 cataract patients(96 eyes)who underwent cataract surgery in our hospital during the same period(control group)were selected. NVG patients were divided into stage Ⅰ group(22 eyes), stage Ⅱ group(47 eyes)and stage Ⅲ group(27 eyes)according to the clinical stage; furthermore, patients were divided into ineffective group(20 eyes)and effective group(76 eyes)according to efficacy. Aqueous humor Apelin and DLL4 levels were detected by enzyme-linked immunosorbent assay. The influencing factors of the efficacy in NVG patients were analyzed by multivariate unconditional Logistic regression analysis, the evaluation efficiency of aqueous humor Apelin and DLL4 levels on the efficacy in NVG patients was analyzed by receiver operating characteristic(ROC)curve.RESULTS: Compared with the control group, aqueous humor Apelin and DLL4 levels in the NVG group were increased(all P<0.001). Aqueous humor Apelin and DLL4 levels in the stage Ⅰ, stage Ⅱ and stage Ⅲ groups increased in turn(all P<0.001). The effective rate of 96 NVG patients was 79.2%(76/96). Compared with the effective group, aqueous humor Apelin and DLL4 levels in the ineffective group increased(all P<0.001). Clinical stage III, high intraocular pressure, high Apelin and DLL4 were independent risk factors for ineffective treatment in NVG patients(all P<0.05). The area under the curve of the combined evaluation of aqueous humor Apelin and DLL4 levels in evaluating the efficacy of NVG patients was 0.874, which was greater than 0.790 and 0.786 of aqueous Apelin and DLL4 levels alone(all P<0.05).CONCLUSION: Aqueous humor Apelin and DLL4 levels in NVG patients increase, which relate to the increase of clinical stage and poor efficacy, and the combination of aqueous humor Apelin and DLL4 levels is more effective in evaluating the efficacy of NVG patients.

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

Objective To investigate the relationship between the levels of C1q/tumor necrosis factor-relat-ed protein 9(CTRP9),Klotho(Klotho)and chitinase 1(CHIT1)in aqueous humor with the disease severity and macular edema(ME)in patients with retinal vein occlusion(RVO).Methods A total of 174 in patients with ME caused by RVO who visited the hospital from January 2022 to June 2024(observation group)and 174 patients with simple RVO(RVO group)were selected.Observation group was divided into mild,moder-ate and severe subgroup according to the disease severity of ME.The levels of CTRP9,Klotho and CHIT1 in aqueous humor between RVO group and observation group were compared.The evaluation value of CTRP9,Klotho and CHIT1 levels in aqueous humor for ME in patients with RVO was analyzed by receiver operating characteristic(ROC)curve.The influencing factors of ME in patients with RVO were analyzed by univariate and multivariate Logistic regression model.The correlation between the levels of CTRP9,Klotho,CHIT1 in a-queous humor with the disease severity of ME in patients with RVO was analyzed by spearman correlation a-nalysis.Results Compared with RVO group,the levels of CTRP9 and Klotho in aqueous humor of observa-tion group were lower,and the level of CHIT1 was higher(P＜0.05).ROC analysis curve showed that,the area under the curve(AUC)of CTRP9,Klotho and CHIT1 in aqueous humor for evaluating ME in patients with RVOwere 0.757,0.773 and 0.813,respectively.The AUC of combined detection of the three was 0.939,and the efficiency of combined evaluation was higher than that of the single evaluation(Z=7.520,7.513,6.278,all P＜0.05).Multivariate Logistic regression model showed that high level of CHIT1 in aque-ous humor,hypertension and severe retinal vein tortuosity were risk factors for ME in patients with RVO(P＜0.05),and high levels of CTRP9 and Klotho in aqueous humor were protective factors(P＜0.05).Spearman correlation analysis showed that the levels of CTRP9 and Klotho in aqueous humor were negatively correlated with the disease severity of ME in patients with RVO(r=-0.584,-0.401,all P＜0.05),while level of CHIT1 in aqueous humor was positively correlated with the disease severity of ME in patients with RVO(r=0.809,P＜0.05).Conclusion The levels of CTRP9,Klotho and CHIT1 in aqueous humor have high value in the evaluation of ME in patients with RVO,and they are the influencing factors of ME in pa-tients with RVO.The level changes of the three are closely related to the disease severity of ME in patients with RVO.

In the past decades, significant progress has been achived in cartilage regeneration. The traditional techniques for constructing tissue engineering cartilage scaffold mainly include pore agent method (or template method), phase separation method, gas foaming method, freeze-drying method, electrospinning method, etc. Cartilage is heterogeneous, and it is difficult for traditional scaffolds to simulate the high anisotropy of cartilage. Therefore, functional regeneration of cartilage is challenging. With the progress of three-dimensional(3D) printing technology, it is possible to prepare functional bionic scaffolds with fine structure and gradient changes through co-deposition of biomaterials, cells and active biomolecules, so as to achieve functional cartilage regeneration. This article reviewed 3D printing technology of cartilage tissue engineering, and the application of 3D printing technology in cartilage regeneration at different anatomical positions (articular cartilage, auricle cartilage, nasal cartilage). In addition, the importance of preparing bionic constructs with regional structure gradient and regional composition gradient was discussed. 3D bioprinting technology, 4D printing techniques, smart biomaterials brought hope for the construction of bionic tissues and organs.

In the past decades, significant progress has been achived in cartilage regeneration. The traditional techniques for constructing tissue engineering cartilage scaffold mainly include pore agent method (or template method), phase separation method, gas foaming method, freeze-drying method, electrospinning method, etc. Cartilage is heterogeneous, and it is difficult for traditional scaffolds to simulate the high anisotropy of cartilage. Therefore, functional regeneration of cartilage is challenging. With the progress of three-dimensional(3D) printing technology, it is possible to prepare functional bionic scaffolds with fine structure and gradient changes through co-deposition of biomaterials, cells and active biomolecules, so as to achieve functional cartilage regeneration. This article reviewed 3D printing technology of cartilage tissue engineering, and the application of 3D printing technology in cartilage regeneration at different anatomical positions (articular cartilage, auricle cartilage, nasal cartilage). In addition, the importance of preparing bionic constructs with regional structure gradient and regional composition gradient was discussed. 3D bioprinting technology, 4D printing techniques, smart biomaterials brought hope for the construction of bionic tissues and organs.

Objective·To investigate the expression of miR-146a in peripheral blood CD4+T lymphocytes of patients with rheumatoid arthritis(RA)and its correlation with inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Methods·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua,Shenzhen from August 2019 to July 2021 were selected.Peripheral blood mononuclear cells(PBMCs)and CD4+T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls,respectively.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-146a in peripheral blood CD4+T lymphocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α and IL-6.After transfection of the peripheral blood CD4+T lymphocytes of RA patients with miR-146a mimic,the expression of miR-146a,TNF-α and IL-6 was detected again.The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients,both before and after transfection,were analyzed by using Pearson correlation coefficient.Results·Before transfection with miR-146a mimic,the expression levels of miR-146a,TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients were significantly higher than those of healthy controls(all P＜0.001).After transfection,the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients was significantly higher,and the expression of TNF-α and IL-6 was significantly lower(all P＜0.001).The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients,both before and after transfection,was positively correlated with the expression of TNF-α and IL-6,respectively(r=0.959,P＜0.001;r=0.916,P＜0.001;r=0.971,P＜0.001;r=0.861,P＜0.001).Conclusion·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients,indicating that miR-146a may play a role in the pathogenesis of RA.

Objective To explore the optimal method for preparing fresh and fixed skeletal muscle tissues,and to lay an experimental foundation for the rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.Methods The tibialis anterior muscle was extracted from C57BL/6J mice.Fresh tissue was treated by direct rapid freezing in liquid nitrogen,embedding combined with liquid nitrogen freezing,and foreign body alkane treatment combined with liquid nitrogen freezing.Fixed tissues were pre-treated by direct embedding with embedding agent combined with rapid liquid nitrogen freezing.The frozen sections were stained with hematoxylin and eosin.The cross-sectional areas of ice crystals and muscle fibers were calculated to evaluate the effects of the different pre-treatment method.Results The morphology of the muscle fiber bundles was disrupted and numerous ice crystal vacuoles were observed in fresh tissues after direct liquid nitrogen freezing and foreign body alkane treatment combined with liquid nitrogen freezing.In contrast,the muscle fiber bundles were intact and dense and there were no ice crystals in tissues treated with embedding agent combined with rapid liquid nitrogen freezing,indicating that this pre-treatment method was suitable for preparing fresh skeletal muscle tissue.Fixed tissue treated with embedding agent and liquid nitrogen freezing also showed complete muscle fiber bundles and no ice crystals.Conclusions Treatment of fresh and fixed skeletal muscle tissues with embedding agent combined with rapid liquid nitrogen freezing preserves muscle fiber bundles,with no ice crystals.Tissues prepared by this method are thus suitable for further examinations,such as immunohistochemistry and immunofluorescence.This method will therefore aid the accurate and rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.

ObjectiveTo systematically analyze the effect of therapeutic exercise on neck function and quality of life in patients with neck pain and forward head posture. MethodsRandomized controlled trials about the effects of exercise training on forward head posture and neck pain were searched from PubMed, Web of science, Embase, Medline, Science Direct, EBSCO, Springlink, CNKI, VIP, and Wanfang Data from database establishment to April, 2022. The literature was screened by two researchers independently. Cochrane bias risk assessment tool and Physiotherapy Evidence Database Scale were used to evaluate the quality of the included articles. Revman 5.4 software was used for meta-analysis. ResultsA total of 416 patients from eleven literatures were included. Level 1a evidence indicated scapula stability training could effectively improve cranial vertebral angle (MD = 3.62, 95%CI 2.41 to 4.83, P < 0.001), and relieve pain (MD = 1.32, 95%CI 0.18 to 2.46, P = 0.02). Level 1b evidence indicated scapula stability training could reduce functional disability (MD = -0.92, 95%CI -1.11 to -0.74, P < 0.001). Level 1b evidence indicated deep cervical flexor training could improve cranial vertebral angle (MD = -0.83, 95%CI -1.56 to -0.10, P = 0.03), relieve pain (MD = 0.93, 95%CI 0.54 to 1.32, P < 0.001), and improve neck functional disability (MD = 2.17, 95%CI 1.39 to 2.95, P < 0.001). ConclusionScapula stability training and deep cervical flexor training can effectively improve cranial vertebral angle, relieve neck pain, and improve neck function.

Objective:To explore the effect of Helicobacter pylori(HP)eradication on development of metachronous gastric cancer(MGC)after endoscopic submucosal dissection(ESD)in elderly patients with early gastric cancer.Methods:From January 2014 to December 2019, 748 early gastric cancer patients aged 60 years or older, receiving ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were included.According to the situation of HP infection and eradication efficacy within 1 year postoperatively, patients were divided into three groups.The patients with HP infection and successful HP-eradication were enrolled into successful eradication group, those without eradicating or with eradication failure were enrolled into eradication failure group, those with HP negative were enrolled into HP-negative group.And then the occurrence and risk factors of MGC after ESD among the three groups were statistically analyzed.Results:MGC were detected in 58 cases(7.7%)in elderly patients with early gastric cancer after ESD.The median follow-up time was 39 months.The multivariate regression analysis results of MGC showed that no HP-eradication or HP eradication of failure( HR=2.231, 95% CI: 1.054-4.722, P=0.036)and multiple lesions( HR=1.857, 95% CI: 1.076-3.204, P=0.026)were independent risk factors.Non-smoking was a protective factor for the occurrence of MGC( HR=0.409, 95% CI: 0.234-0.716, P=0.002). After adjusting for confounding factors, Cox proportional risk regression analysis showed that the incidence of MGC was significantly higher in group of no HP-eradicating or HP-eradicating of failure than in group of successful HP-eradicating group( χ2=37.877, P<0.001). Conclusions:HP eradication can effectively prevent MGC in elderly patients with early gastric cancer after ESD.Multiple lesions and smoking are independent risk factors for MGC.