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.

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 correlations of CALLY index in early pregnancy with the onset and severity of preeclampsia.Methods A total of 987 pregnant women were prospectively en-rolled as study subjects,with 42 lost during follow-up,resulting in a final inclusion of 945 subjects.Based on the occurrence and severity of preeclampsia during follow-up,the pregnant women were di-vided into preeclampsia group(n=47),severe preeclampsia group(n=49),and normal group(n=849).General information and laboratory test results were collected from all pregnant women,and the CALLY index was calculated.The Pearson correlation analysis was used to explore the correlation be-tween CALLY index and severity of preeclampsia(mean arterial pressure);the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficacy of each indicator for pre-eclampsia;Cox regression analysis was used to explore the influencing factors for the onset of preeclamp-sia.Results The mean arterial pressure and 24-hour urine protein levels were higher in the severe pre-eclampsia group than those in the preeclampsia group and normal group,and higher in the preeclampsia group than those in the normal group(P＜0.05).The CALLY index was lower in the severe preeclamp-sia group than in the preeclampsia group and normal group,and lower in the preeclampsia group than in the normal group(P＜0.05).Pearson correlation analysis showed a negative correlation between CALLY index and mean arterial pressure(r=-0.571,P＜0.001).The ROC curve showed that the area under the curve(AUC)of CALLY index for predicting preeclampsia was 0.941(95％CI,0.900 to 0.981).Multivariate Cox regression analysis showed that an increased CALLY index was an independent protective factor for the onset of preeclampsia(HR=0.185,95％CI,0.092 to 0.374,P＜0.001).Conclusion The CALLY index is negatively correlated with the severity of preeclampsia and is an independent influencing factor for the onset of preeclampsia,which can be used as an auxiliary indicator to assess the onset and severity of preeclampsia in pregnant women.

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.

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 analyze the effect of cognitive conflict in teaching practice nurses in emergency department.Methods:102 nursing students who practiced in the emergency department of Huai′an First Hospital Affiliated to Nanjing Medical University were selected as the research objects by quasi-experimental study, 52 students from December 2021 to July 2022 were set as the research group, and 50 students from March 2021 to November 2021 were set as the control group. The control group received on-site first aid sitnation teaching. The research group combined cognitive conflict teaching on the basis of on-site first aid situation teaching, and compared the emergency nursing skills, theoretical knowledge, critical thinking, clinical strain ability and teaching satisfaction of the two groups of interns.Results:After practice, the scores of emergency nursing skills, theoretical knowledge, critical thinking ability, clinical adaptability and satisfaction with the teaching mode (theoretical memory, interest in learning, practical ability) in the research group were (87.25 ± 2.66), (90.01 ± 2.74), (298.10 ± 8.27), (84.37 ± 3.45), (90.13 ± 3.26), (89.03 ± 3.37) and (91.34 ± 3.16), which were significant higher than the (83.76 ± 2.87), (85.16 ± 3.11), (290.47 ± 8.55), (80.05 ± 3.68), (85.46 ± 3.53), (86.28 ± 3.61) and (88.47 ± 3.38), the difference were significant ( t values were 3.98-8.37, all P<0.05). Conclusions:Cognitive conflict teaching can significantly improve the professional level, critical thinking and clinical adaptability of nursing interns and their satisfaction with teaching.

Objective:To investigate the clinical effect and safety of camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 24 patients with stage Ⅲ-IV A NPC were recruited prospectively to receive two cycles of camrelizumab combined with induction chemotherapy (docetaxel 75 mg/m 2+ cisplatin 25 mg/m 2 for three consecutive days) followed by concurrent chemoradiotherapy (prescription doses: 6 996 cGy in 33 fractions for PGTV and PGTV nd, 6 006 cGy in 33 fractions for PTV 1, 5 096 cGy in 28 fractions for PTV 2, and concurrent cisplatin chemotherapy with a dose of 75 mg/m 2). The short-term efficacy and adverse reactions were evaluated. Results:After induction therapy, nasopharyngeal lesions showed an objective response rate (ORR) of 91.6%, including 45.8% of complete response (CR) and 45.8% of partial response (PR); cervical lymph nodes showed an ORR of 95.8% (CR: 4.2%; PR: 91.6%). Seventeen patients accepted a reexamination under a nasopharyngoscope, and the biting biopsy result indicated that 13 patients among them had complete pathologic response. After concurrent chemoradiotherapy, nasopharyngeal lesions and cervical lymph nodes showed CR rates of 83.3% and 91.7% and PR rates of 16.7% and 8.3%, respectively. After the induction therapy, 13 patients with stage IV A NPC had ORR (PR) rates of 92.4% and 92.4%, respectively, at nasopharyngeal lesions and cervical lymph nodes. After concurrent chemoradiotherapy, the patients with stage IV A NPC had CR rates of 84.6% and 92.3% and PR rates of 15.4% and 7.7%, respectively, at nasopharyngeal lesions and cervical lymph nodes. Major adverse reactions include leukopenia, granulopenia, anemia, radioactive acute oropharyngeal mucositis and dermatitis, digestive tract reaction, fatigue, hypothyroidism, aminotransferase elevation, and reactive capillary hyperplasia. Conclusions:Camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy can achieve high short-term efficacy for patients with locally advanced nasopharyngeal carcinoma, without increasing the incidence of adverse reactions. Its long-term efficacy deserves further research.

Objective:To investigate imaging characteristics of papulopustular rosacea (PPR) by high-frequency ultrasound combined with color Doppler flow imaging.Methods:From August 2021 to August 2022, 30 patients with PPR were enrolled from the Department of Dermatology, the First Affiliated Hospital of Baotou Medical College in the Inner Mongolia Autonomous Region, and 30 healthy volunteers served as controls. The 22-MHz high-frequency ultrasound combined with color Doppler blood flow imaging was performed to measure the skin thickness, echo and blood flow parameters at the cheek, and the ultrasound results were compared between the two groups. Comparisons between groups were conducted by using t test or chi-square test. The diagnostic value was analyzed using the area under the curve (AUC) in the receiver operating characteristic (ROC) curve. Results:In the case group, there were 12 males and 18 females, and their ages ranged from 22 to 65 years (42.3 ± 12.8 years) ; in the control group, there were 10 males and 20 females, and their ages ranged from 24 to 62 years (41.0 ± 8.4 years) . The epidermal and dermal thicknesses at the cheek were significantly higher in the case group (132.64 ± 12.29 μm, 1 812.29 ± 85.52 μm, respectively) than in the control group (104.34 ± 14.45 μm, 1 671.77 ± 146.55 μm, respectively, both P < 0.05) . High-frequency ultrasound images showed that the case group was mainly characterized by irregular hypoechoic areas in the cheek dermis (80%) , while banded moderately echoic areas were common in the cheek dermis in the control group (90%) ; subepidermal low-echogenic bands and dermal irregular hypoechoic areas were more likely to appear in the case group than in the control group (93.33% vs. 43.33%, 80% vs. 10%, respectively, both P < 0.001) . Compared with the control group, the case group showed a significantly increased proportion of patients with abundant blood flow signals (93.3% vs. 10%, P < 0.05) , and significantly increased blood vessel diameters (1.60 ± 0.42 mm vs. 0.95 ± 0.32 mm, P < 0.05) ; there was no significant difference in peak systolic blood flow velocity and vascular resistance index between the two groups (both P > 0.05) . The AUC of high-frequency ultrasound combined with color Doppler flow imaging quantitative parameters (including epidermal thicknesses, dermal thicknesses, and blood vessel diameters) was 0.989 (95% CI: 0.970 - 1.000) for the diagnosis of PPR, and the sensitivity and specificity were both 96.7%, which were higher than those of single parameter-based diagnostic model. Conclusion:High-frequency ultrasound combined with color Doppler flow imaging can help improve the accuracy of the diagnosis of PPR, by accurately and non-invasively measuring skin thickness and blood flow parameters.