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.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Background: A simple superoposterior approach to thoracic transforaminal epidural injections (TFEIs) under ultrasonographic guidance was proposed to reduce zoster-associated pain (ZAP) involving multiple thoracic nerves and the likelihood of transitioning to postherpetic neuralgia (PHN). Methods: Patients were prospectively enrolled. Primary endpoints were the burden of illness (BOI) scores and epidural contrast spread. Secondary endpoints included number of needle insertion attempts, sensory blockade, hemodynamic changes, procedure time, radiation dose, adverse events, rescue analgesics, PHN incidence and EuroQoL 5-Dimension scores. Results: Thirty-five injections were performed in 27 patients. Median levels of cephalad-caudad epidural contrast spread were 3, 4, and 5 ml following injections of 2, 3, and 4 ml. Dorsal epidural spread was observed at levels 3, 4, and 5, whereas concurrent ventral spread was observed at levels 2, 3, and 4. BOI scores at 30–180 days significantly decreased (mean difference: −25.3, 95% CI [−57.4 to 6.6], P = 0.005), accounting for reduced rescue analgesic requirements and PHN occurrence and improved EuroQoL 5-Dimension scores. Median sensory blockade at 5 min post-procedure was at level 2, 3, and 4 after 2, 3, and 4 ml of therapeutic injectate. No significant hemodynamic changes were noted at 15 min post-injection. No serious adverse events were observed. Conclusions Spread of thoracic epidural contrast to all involved nerves was confirmed using this novel technique. Simplified needle placement reduced the technical difficulty and risk of complications. It might be a promising alternative approach for ZAP.

Objective To investigate the effects of Shengjiyuhong ointment on coagulation system,endothelial progenitor cells(EPCs)differentiation and Rho kinase activity in rats with thromboangiitis obliterans by inhibiting autophagy.Methods The rat model of thromboangiitis obliterans was established by injecting sodium laurate solution into the left lower limb artery.40 SD rats were randomly divided into sham operation group,model group,compound sodium aescinate gel group and Shengjiyuhong ointment group,10 per group.The pathological morphology of vascular tissue was detected by HE staining.The expression of autophagy related proteins was detected by Western blot,coagulation system parameters were detected by coagulation detector,EPCs differentiation was detected by flow cytometry,and Rho kinase activity was detected by immunohistochemistry.Results The expression of autophagy marker protein LC3Ⅱ/I,Beclin1,Rho kinase protein,the positive expression rate of CD34 in fibrinogen and EPCs of Shengjiyuhong ointment group were decreased,and the positive expression rate of serum prothrombin time,international normalized ratio,von Willebrand factor in EPCs and the expression of P62 in vascular tissue were increased(P＜0.05).The in vitro experiment showed that Shengjiyuhong ointment could reduce the expression of LC3Ⅱ/I and Beclin1,and increase the expression of P62 protein in injured endothelial cells(P＜0.05).Conclusion Shengjiyuhong ointment can effectively improve the coagulation function,promote the differentiation of EPCs and reduce the activity of Rho kinase in rats with thromboangIItis obliterans.The mechanism may be related to inhibition of autophagy.

The establishment of mother-infant bonding is closely related to maternal mental health and early growth and development of infants. This paper reviews the concept, evaluation tools, influencing factors and intervention measures of maternal-infant bonding, in order to provide a basis for promoting the normal establishment of postpartum maternal infant relationships and maternal infant health.

Objective:To construct a prognostic risk model for hepatocellular carcinoma(HCC),and elucidate the immune characteristics and immunotherapy response in patients with different prognostic stratification.Methods:RNA-seq data of TCGA-LIHC and ICGC(LIRI-JP),and gene microarray data of GSE14520 and GSE54236 in hepatocellular carcinoma,as well as clinical informa-tion of the corresponding samples were downloaded.First,screening of differentially expressed genes in tumor and non-tumor tissue samples from TCGA-LIHC,GSE14520 and GSE54236.For the common differential genes,univariate cox regression analysis was per-formed using TCGA-LIHC data to obtain HCC prognosis-related genes.Five genes were randomly selected as a panel,and the optimal prognostic marker panel was screened among 10 000 panels using Lasso-cox regression analysis combined with a five-fold cross-valida-tion method.TCGA-LIHC data were used as training set to construct the prognostic risk model,and ICGC data were used as validation set to test the model performance.Tumor immune dysfunction and exclusion(TIDE)algorithm and Immunophenotypic score(IPS)were used to predict immunotherapy efficacy in patients in different prognostic groups.Results:Overall survival was significantly lon-ger in low-risk group of HCC patients compared with high-risk group.Tumor proliferation rate,Treg and Th2 cell chemotaxis,stromal remodeling,and pro-tumor cytokines were significantly increased in high-risk patients,while NK cells,Th1 cells,effector cells and endothelial cells were significantly increased in low-risk patients.Immune checkpoint analysis showed that PDCD1,CTLA4 and CD276 were up-regulated in high-risk patients,while PDCD1LG2 was upregulated in low-risk patients.TIDE score and IPS results predicted that patients in low-risk group had better efficacy to immunotherapy.Conclusion:This study constructed a prognostic risk model containing three genes,DNASE1L3,RDH16 and DLGAP5,which can effectively predict the prognosis of HCC patients and assist in clinical decision making for individualized immunotherapy.

To evaluate the safety and efficacy of oral double-balloon enteroscopy for small intestinal bezoars with obstruction, the clinical, endoscopic, imaging, pathological and surgical data of patients with small intestinal bezoars and obstruction treated in Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from December 2021 to March 2023 were retrospectively analyzed. A total of 5 patients, all female, aged 52-83 years, were included. The clinical manifestation was mainly digestive tract obstruction. The diameter of bezoars was 30-50 mm. Three were located in the jejunum, one in the proximal ileum, and one at the jejuno-ileal junction. Three cases were diagnosed as having small intestinal bezoars by imaging examination before operation. All 5 patients achieved technical success. Four patients achieved clinical success, the symptoms of obstruction were completely relieved, and 1 patient was partially relieved due to malignant obstruction. No obvious complication occurred in 5 patients after operation. The follow-up time was 15-790 days, and there was no recurrence. The results showed that oral double-balloon enteroscopy for small intestinal bezoars was safe and effective, providing a new treatment for patients with small intestinal bezoars except for surgery.

Objective:To explore the relationship between serum urea nitrogen to creatinine ratio (UCR) and cardiac function in elderly patients with severe pneumonia.Methods:A prospective selection of 100 elderly patients with severe pneumonia admitted to Group Wanbei General Hospital of Wanbei Coal Power from May 2020 to April 2023 was conducted as the case group, and an additional 50 patients who underwent health examinations in the hospital during the same period were selected as the control group. Serum urea nitrogen (BUN), creatinine (Cr), UCR value, myocardial injury indexes: cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-ProBNP), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), and cardiac function indexes: left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume (SV) and cardiac output index (CI) were detected in the two groups. The patients in the case group were divided into two subgroups based on the occurrence of heart failure during hospitalization: the heart failure subgroup and the normal heart function subgroup. The serum UCR, myocardial injury and cardiac function indexes were compared between the case group and the control group. The general data, myocardial injury and cardiac function indexes were compared between the heart failure group and the normal heart function group. The relationship between serum UCR and cardiac function in patients with severe pneumonia was analyzed by bivariate Pearson correlation. Logistic regression model was used to analyze the influencing factors of cardiac dysfunction in patients with severe pneumonia, and using receiver operating characteristic (ROC) curve to analyze the value of serum UCR in predicting cardiac dysfunction in patients with severe pneumonia.Results:The values of BUN, UCR, cTnI, NT-ProBNP, CK and CK-MB in the case group were higher than those in the control group: (8.72 ± 1.14) μmol/L vs. (6.41 ± 0.76) μmol/L, 125.00 ± 19.75 vs. 86.12 ± 12.02, 0.04 (0.03, 0.05) μg/L vs. 0.04 (0.03, 0.05) μg/L, (185.49 ± 20.59) ng/L vs. (147.76 ± 20.85) ng/L, (104.78 ± 14.98) U/L vs. (99.33 ± 15.07) U/L, (31.59 ± 6.23) U/L vs. (29.13 ± 5.76) U/L. The values of Cr, LVEF, CO, SV and CI in the observation group were lower than those in the control group: (70.22 ± 5.76) μmol/L vs. (74.75 ± 5.12) μmol/L, (59.72 ± 2.41)% vs. (61.78 ± 2.16)%, (3.93 ± 0.43) L/min vs. (4.53 ± 0.62) L/min, (59.82 ± 6.12) ml vs. (62.23 ± 7.22) ml, (2.95 ± 0.30) L/(min·m 2) vs. (3.06 ± 0.33) L/(min·m 2), with a statistical significant difference ( P<0.05). In the case group, 21 patients had heart failure during hospitalization, accounting for 21.00%. The pneumonia severity index score on admission in the heart failure subgroup was higher than that in the normal heart function subgroup: (172.76 ± 9.18) points vs. (168.24 ± 8.81) points. The serum BUN and UCR levels were higher than those in the normal heart function subgroup: (9.51 ± 0.79) mmol/L vs. (8.51 ± 1.13) mmol/L, 141.62 ± 9.89 vs. 120.59 ± 19.39. The serum Cr level was lower than that in the normal heart function subgroup: (67.26 ± 5.34) μmol/L vs. (71.00 ± 5.65) μmol/L, with a significant statistical difference ( P<0.05). There was no significant statistical difference in other data between the two subgroups ( P>0.05). The bivariate Pearson correlation analysis showed that serum UCR was positively correlated with cardiac function indicators cTnI, NT-ProBNP, CK and CK-MB levels in severe pneumonia ( r = 0.40, 0.27, 0.32 and 0.33; P<0.05), and negatively correlated with LVEF, CO, SV and CI levels ( r = - 0.37, - 0.21, - 0.25 and - 0.21; P<0.05). Univariate and multivariate Logistic regression analysis showed that the occurrence of cardiac dysfunction in elderly patients with severe pneumonia may be related to the pneumonia severity index score on admission and the abnormal expression of serum BUN, UCR and Cr levels ( P<0.05). ROC curve analysis found that the area under the curve for predicting the occurrence of cardiac dysfunction during hospitalization in severe pneumonia patients with serum UCR on admission was 0.85 (95% CI 0.77 to 0.92), which had certain predictive value. Conclusions:Elderly patients with severe pneumonia are accompanied by a certain degree of elevated serum UCR levels, and the higher the serum UCR level, the more severe the cardiac function damage and the greater the risk of cardiac dysfunction.