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:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

ObjectiveTo improve the quality and service performance of community visual health services in Shanghai, and to establish a set of reasonable and effective evaluation index system for community visual health services. MethodsCentered on the national and Shanghai-based visual health policies and based on the current status and development trends of community visual health service program in Shanghai, the candidate indicators were formed through literature review and expert interviews, firstly. The framework of an evaluation index system was formulated through qualitative research successively, which was further revised and perfected using the Delphi method. Coefficient weights were calculated using the analytic hierarchy process (AHP), culminating in the establishment of the community visual health evaluation index system, lastly. ResultsA total of 22 visual health experts from district-level center for disease control, hospital ophthalmology and leaders in charging of visual health service in community health centers participated in the Delphi questionnaire survey, with a questionnaire recovery rate of 100% and an expert authority coefficient of 0.86, indicating high credibility. After a round of correspondence to experts’ importance ratings and discussions, a comprehensive evaluation index system comprising 3 primary indicators, 12 secondary indicators, and 47 tertiary indicators, along with 5 additional indicators, was finalized. ConclusionAn index system tailored to effective evaluation for community visual health initiatives was drawn up in this study, which can promote the capacity building in community eye health services, facilitating the high-quality development of visual health courses, and enhancing residents’ eye health.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

BACKGROUND:For non-traumatic osteonecrosis of the femoral head,if the femoral head collapses,it will have a great impact on the normal life of the patients.Thus,it is necessary to use an appropriate way to evaluate the risk of femoral head collapse and then to take targeted measures to delay the process of femoral head collapse. OBJECTIVE:To analyze the natural course of early osteonecrosis of the femoral head(without collapse)under different locations of necrotic lesions. METHODS:121 patients(191 hips)with early non-traumatic osteonecrosis of the femoral head who were treated in the Outpatient Department of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017 were enrolled in this study.The clinical data of all patients were followed up for 5 years to observe the collapse of osteonecrosis of the femoral head and the risk coefficient of femoral head collapse among different JIC types.The collapse rate of osteonecrosis of the femoral head was calculated during the follow-up. RESULTS AND CONCLUSION:(1)A total of 191 hips were included in this study.The femoral head collapsed in 86 hips during follow-up,with a total collapse rate of 45.0%.Among the influencing factors,age,ARCO stage and JIC classification were the main influencing factors of femoral head collapse(P<0.05),but body mass index,sex,incidence side and pathogenic factors were not the main influencing factors(P>0.05).(2)Among 191 hips,in JIC classification,the total collapse rates of type A,type B,type C1 and type C2 were 11.1%(2/18),30.2%(16/53),52.4%(43/82),and 65.8%(25/38),respectively.There were significant differences in the total collapse rate of the femoral head among all types(P<0.05).The collapse risk results showed that the collapse risk of type B,type C1 and type C2 was 2.41,5.22 and 7.89 times higher than that of type A,respectively.(3)Both JIC classification and ARCO stage were correlated with femoral head collapse(P<0.01).There was no significant difference in the collapse rate of the femoral head among all JIC types in ARCO I stage hips(P>0.05).In the hips with ARCO II stage,the collapse rates of the femoral head of JIC types A,B,C1 and C2 were 1.2%,19.5%,50.0%and 29.3%,respectively,and there were significant differences in the collapse rates among different types(P<0.05).(4)During follow-up,the collapse rates of the femoral head in the first to fifth years were 29.3%,7.9%,4.7%,2.6%and 0.5%,respectively.(5)Results showed that for early non-traumatic osteonecrosis of the femoral head,the risk of collapse of osteonecrosis of the femoral head is high within one year,and the location of the focus of osteonecrosis affects the risk of collapse of the femoral head.The effect of the location of the focus on the prognosis of the disease should be considered in clinical treatment.

Objective To establish a differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris using radiomics.Methods A total of 91 patients with stable angina pectoris who underwent coronary artery CT angiography in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2021 to January 2022 were collected,including 47 cases of phlegm and blood stasis pattern and 44 cases of qi deficiency and blood stasis pattern.The patients were divided into train set(64 cases)and test set(27 cases)according to the ratio of 7∶3 by stratified random sampling method.3D-slicer software was used to extract the radiomics features of pericoronary adipose tissue(PCAT)images.Principal component analysis was used to visualize the distribution of radiomics features of pattern of phlegm and blood stasis and pattern of qi deficiency and blood stasis.The least absolute shrinkage and selection operator regression analysis and support vector machine decreasing feature elimination were used for feature selection.The multinomial logistics regression was used for model construction.The receiver operating characteristic(ROC)curve was used to verify the model in the train set and the test set to evaluate the effectiveness of the radiomics features in differentiating phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.Finally,Spearman coefficient was used to analyze the correlation between the differential features and clinical physicochemical data.Results A total of 837 radiomics features were extracted from PCAT images by 3D-slicer software.In the principal component analysis,PC1 and PC2 explained 77.9%and 8.1%of the total variance,respectively,and there was a relatively obvious separation trend between the two pattern groups.After feature screening,7 radiomics features were used to construct the differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.The area under the ROC curve(AUC)of the differential model was 0.844 in the train set and 0.834 in the test set.Spearman correlation analysis showed that the differential features were significantly correlated with cTnI,neutrophil,triglyceride,total cholesterol,and leukocyte.Conclusion The CT radiomics model based on PCAT has a high discrimination efficiency for stable angina pectoris with phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.

Objective : Objective Methods : The expression levels of PATL1 in pancar- cinoma，gastric cancer and normal tissues were analyzed by TCGA database．The expression level of PATL1 in 40 human gastric cancer tissues and paired adjacent tissues was evaluated by quantitative real-time PCR (RT-qPCR) . The Kaplan-Meier Plotter database was used to analyze the prognosis of PATL1 in gastric cancer patients．The gas- tric cancer cell line AGS was transfected with PATL1 interference vector，and the interference effect was evaluated by RT-qPCR. The effects of PATL1 on the proliferation and migration of AGS were detected by cell counting kit-8 ( CCK-8) ，Transwell test and scratch healing test．The effects of interference with PATL1 on the expression of cel- lular-myelocytomatosis viral oncogene ( c-Myc) and autophagy related 7 ( ATG7) proteins in gastric cancer cells were detected by Western blot assay. Results : RT-qPCR showed that the expression of PATL1 in human gastric cancer tissue was higher than that in normal gastric tissue (P＜0. 001) ，and PATL1 was correlated with the progno- sis of patients with enteric gastric cancer (P＜0. 000 1) ．After PATL1 was knocked down，the number of prolifera- ting and migrating gastric cancer cells decreased (P＜0. 05) ．Western blot test results showed that the expression level of ATG7 protein decreased after PATL1 was knocked down (P＜0. 05) ． Conclusion PATL1 may inhibit the proliferation and migration of gastric cancer cells through crosstalk with c-Myc and ATG7 .

Objective To observe the role of dried tangerine peel in Yigong Powder improves iron metabolism and promotes red blood cell generation in anemia of chronic disease (ACD).Methods With a two-by-two factorial design,the Yigong Powder was divided into dried tangerine peel and Chenpi absent Decoction. According to the random number table method,32 zymosan-induced generalized inflammation (ZIGI) mice were randomly divided into the model group,the dried tangerine peel group,the Chenpi absent Decoction group,and the Yigong Powder group. The dried tangerine peel group,Chenpi absent Decoction group and the Yigong Powder group were given dried tangerine peel(3.083 g/kg),Chenpi absent Decoction(12.33g/kg),and Yigong Powder(15.413g/kg)by gavage to the corresponding group of mice. The model group was given an equal amount of physiological saline by gavage,and treated continuously for 7 days. After the completion of administration,the body weight of each group of mice was recorded. The hemoglobin content of each group of mice was detected using a fully automatic cell counter,the serum iron content was detected using colorimetry,the serum ferritin content was detected using enzyme-linked immunosorbent assay (ELISA),and the spleen index was calculated. The liver tissue inflammatory factors interleukin-1β (IL-1β),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),interleukin-4 (IL-4),and interleukin-10 (IL-10) levels were detected using Luminex method. The mRNA expressions of liver tissue hepcidin gene (HAMP) and membrane iron transporter ( Fpn) were detected using real-time fluorescence PCR method. Results Dried tangerine peel and Chenpi absent Decoction both showed interactive effects in regulating hemoglobin,serum iron,serum ferritin content,improving spleen index,and regulating the mRNA expressions of HAMP,Fpn,as well as IL-1β and IFN-γ (P<0.05). Compared with the model group,dried tangerine peel significantly increased hemoglobin,serum iron content,and Fpn mRNA expression in ZIGI model mice,while decreasing ferritin content,spleen index,HAMP mRNA expression,and the levels of IL-1β,IL-6,TNF-α,and IFN-γ (P<0.05). Chenpi absent Decoction significantly increased serum iron content and Fpn mRNA expression in ZIGI model mice,while reducing spleen index,ferritin content,HAMP mRNA expression,and the levels of IL-1β and IFN-γ、IL-4 (P<0.05). Conclusion The effects of dried tangerine peel on inflammatory factors (IL-6 and TNF-α) and Fpn may play a key role in the improvement effects of Yigong Powder on ACD and iron metabolism.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Chronic urticaria （CU） is a common skin disease worldwide， and its incidence is increasing year by year in various regions. Clinical manifestations such as severe itching can affect normal work， sleep， and daily life and increase the negative psychological burden caused by stress， anxiety， and depression. Mast cell activation and degranulation induced by immunoglobulin（Ig）E hypersensitivity is one of the core pathogenic mechanisms of CU， and there is no cure. Antihistamines such as cetirizine and loratadine are preferred for the clinical treatment of CU. Although they can effectively improve clinical manifestations such as itchiness， long-term application can increase the risk of adverse reactions and drug resistance. The phosphatidylinositol kinase/serine-threonine protein kinase B（PI3K/Akt） signaling pathway， as a classical signaling pathway regulated by phosphatidylinositol and tyrosine kinase receptor （RTK）， is a key target regulating the production and release of cytokines in macrophages and affecting the migration of leukocytes and the activation of mast cells and inflammation， and it can be involved in a variety of metabolic processes， such as mast cell activation and degranulation induced by IgE hypersensitivity and abnormal activation of the complement system so that the PI3K/Akt molecular pathway could be an important target for the future eradication of CU. However， the mechanism and potential role of the PI3K/Akt signaling pathway in the treatment of CU are less reported in China. Now， this paper reviewed the molecular mechanism of PI3K/Akt signaling pathway regulation in the treatment of CU and provided corroborative evidence and therapeutic strategy choices for the treatment of CU with traditional Chinese medicine （TCM） from the perspectives of molecular regulation and network pharmacology analysis.