Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis.

Objective: To investigate the relationship of interleukin (IL)-35 with sarcoidosis. Methods: We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of p35, EBI3, and GAPDH in CD19+ cells and CD4+ cells were detected by real-time PCR. Sarcoidosis granuloma mice models were established with Propionibacterium acnes (PA) and one group was treated with IL-35 antibodies. Proportions of Breg, Tfh, and Treg cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) were detected by FCM. Results: The IL-35 levels and the proportions of Breg and Tfh cells in the peripheral blood of patients with active sarcoidosis were significantly higher compared to patients with stable sarcoidosis and healthy controls. Moreover, the IL-35 level in patients with progressive disease was lower than that found at the initial visit. EBI3 and p35 mRNA levels in CD19+ cells for patients with active sarcoidosis were significantly higher as compared to patients with stable sarcoidosis and healthy controls, while there were no significant differences in p35 and EBI3 mRNA levels in CD4+ cells between the three groups. In the mouse model of sarcoidosis, there were loose granulomata (macrophage accumulation in the bronchial areas and immature granuloma) after intervention with IL-35 antibodies. Meanwhile, the proportions of Breg cells in the peripheral blood and BALF of the model were significantly increased, while the proportion of Treg cells declined significantly. After intervention with IL-35 antibodies, the proportion of Breg cells in the peripheral blood of mice decreased significantly as compared to the mice not exposed to anti-IL-35 antibodies. Conclusion: IL-35 levels increased significantly in the serum of patients with active sarcoidosis, and lower IL-35 levels were correlated with persistent disease. Serum IL-35 levels might be better correlated with Breg cell functions.

Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway / 中国实验方剂学杂志

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4+ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Analysis of disease burden and risk factors of diabetic kidney disease in China from 1990 to 2019 / 中华肾脏病杂志

Objective:To explore the changes of disease burden and risk factors of chronic kidney disease (CKD) due to type 1 and type 2 diabetes mellitus in China from 1990 to 2019, and to provide reference data for the prevention and control of diabetic kidney disease (DKD).Methods:The Chinese DKD data were obtained from the 2019 Global Burden of Disease (GBD) database. The morbidity, prevalence, mortality, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life year (DALY) were used to compare the disease burden of CKD due to type 1 and type 2 diabetes mellitus from 1990 to 2019. In addition, the risk factors of DKD were analyzed.Results:The numbers of CKD patients due to type 1 and type 2 diabetes mellitus in China were 574 (95% UI 495-665) and 31 076 (95% UI 28 152-33 909) thousand, and the numbers of new cases were 9 (95% UI 8-11) and 434 (95% UI 390-481) thousand in 2019, respectively. The numbers of death were 13 (95% UI 8-18) and 63 (95% UI 50-77) thousand, respectively. The age groups with the largest number of patients and new cases of CKD due to type 1 diabetes mellitus were 30-34 years old and <5 years old, respectively. The age group with the largest number of patients and new cases of CKD due to type 2 diabetes mellitus were 50-54 years old and 70-74 years old, respectively. From 1990 to 2019, the age-standardized prevalence rate of DKD patients in China was relatively stable, but the age-standardized incidence rate and YLD rate showed an upward trend, while the age-standardized mortality rate, YLL rate, and DALY rate showed a downward trend. The main risk factors associated with DKD death were high fasting plasma glucose, kidney dysfunction, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure. The proportions of DKD death caused by high systolic blood pressure and high body mass index in the Chinese population were still increasing. Conclusions:From 1990 to 2019, the age-standardized incidence and YLD rate of DKD in China shows an upward trend, while the age-standardized prevalence rate is relatively stable, and the age-standardized mortality rate, YLL rate, and DALY rate show a decreasing trend. High fasting glucose, renal failure, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure are risk factors associated with death in DKD patients. With the progress of aging, the disease burden of DKD in China will continuously increase. Future work should be focused on population-specific interventions, taking into consideration the risk factors identified within the study.

Alterations of hubs related to disease progression in patients with temporal lobe epilepsy: a study on topological properties of brain networks / 中华神经科杂志

Objective:To investigate the alterations of brain functional network related to disease progression in patients with temporal lobe epilepsy (TLE) and the potential neural mechanism of executive dysfunction.Methods:Nineteen temporal lobe epilepsy patients with a disease course of less than or equal to 5 years (TLE-SD group) and 24 temporal lobe epilepsy patients with a disease course of more than 5 years (TLE-LD group) were recruited from the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from December 2019 to December 2021. At the same time, 21 healthy control individuals (healthy control group) were recruited from the society and matched with gender, age, and education level. All subjects were evaluated demographic and clinical data, and performed resting state functional magnetic resonance imaging (rs-fMRI) and attention network test (ANT). The topological properties of functional brain network of 3 groups of subjects were calculated using graph theory, and then the hubs were determined. Then the inter-group comparison of hubs properties was carried out, and the correlation analysis with executive control function was performed.Results:The distribution pattern of hub nodes in TLE-SD patients was changed. Compared with the TLE-LD and healthy control groups, the TLE-SD group significantly increased the nodal degree values in brain regions such as the ventrolateral area of the left middle frontal gyrus, the left anterior central gyrus (upper limb area), the cephalic and caudal areas of the left parietal lobule, as well as the inner parietal lobe area, the caudal side of the right parietal lobule, and the right lateral occipital cortex. The nodal values of the brain areas such as the lateral and parietal inner area, the caudal side of the right upper upper lobule, and the right lateral occipital cortex were significantly increased. TLE-SD patients had a significant increase in the middle of the right upper frontal gyrus and the head of the left upper upper lobule. The node efficiency was significantly lower than that of TLE-LD patients, and the node efficiency in the middle of the right upper frontal gyrus was significantly lower than that of the healthy control group. The node network attributes of the left upper lobe were positively correlated with the execution control efficiency, and negatively correlated with the orientation efficiency. No significant difference was detected between TLE-LD patients and healthy controls.Conclusions:In TLE patients, the hubs in the middle of the right superior frontal gyrus were first damaged, and new hubs appeared in the dorsal attention network, the left anterior central gyrus and the right occipital lobe and were overloaded. With the progression of the disease, hubs tended to be redistributed to normality. The left superior parietal lobule may play an important role in the impairment of executive control function in TLE patients.

Research progress on liquid biopsy and its combination of radiology in diagnosis of pulmonary nodules / 中国胸心血管外科临床杂志

@#Lung cancer is a malignant tumor with the highest mortality worldwide, and its early diagnosis and evaluation have a crucial impact on the comprehensive treatment of patients. Early preoperative diagnosis of lung cancer depends on a variety of imaging and tumor marker indicators, but it cannot be accurately assessed due to its high false positive rate. Liquid biopsy biomarkers can detect circulating tumor cells and DNA in peripheral blood by non-invasive methods and are gradually becoming a powerful diagnostic tool in the field of precision medicine for tumors. This article reviews the research progress of liquid biopsy biomarkers and their combination with clinical imaging features in the early diagnosis of lung cancer.

Circulating tumor cells-based model for pulmonary solid nodules diagnosis: a multicenter study / 中华胸心血管外科杂志

Objective:To evaluate the clinical radiological features combined with circulating tumor cells in the diagnosis of benign and malignant pulmonary solid nodules.Methods:Clinical data of 437 patients from Shanghai Pulmonary Hospital(SPH cohort) from January to April 2021 and 82 patients from Lanzhou University First Hospital (LZH cohort) from August 2019 to May 2022 were retrospectively included. Patients in Shanghai pulmonary hospital were randomly divided into training set and internal validation set in a ratio of 4∶1 by random number table method and patients in Lanzhou University First Hospital were as external validation set. Independent risk factors were selected by regression analysis of training set constructed a Nomogram prediction model. The performance of the Nomogram prediction model was estimated by applying receiver operating curve( ROC) analysis, tested in different nodules size and intermediate risk IPSNs and tested by calibration curve. Results:Independent risk factors selected by regression analysis for solid pulmonary nodules were age, the level of CTC, pleural Indentation, lobulation, spiculation. The Nomogram prediction mode provided an area under ROC( AUC) of 0.888, 0.833 in internal validation set and external validation set, outperforming radiological features model(0.835, P=0.007; 0.804, P=0.043) Mayo clinical model(0.781, P=0.019; 0.726, P=0.033) and CTCs(0.699, P=0.002; 0.648, P=0.012) in both two validation sets, C-index of 0.888, 0.871 and corrected C-index of 0.853, 0.842 in both two validation sets . The AUC of the prediction model with internal validation set was 0.905 and 0.871 for nodule diameter of 5-20 mm and intermediate risk probability. Conclusion:The prediction model in this study has better diagnostic value and practicability, and is more effective in clinical diagnosis of diseases.

Application value of radiomics-based machine learning model in identifying the degree of pulmonary ground-glass nodule infiltration / 中国胸心血管外科临床杂志

@#Objective    To establish a machine learning model based on computed tomography (CT) radiomics for preoperatively predicting invasive degree of lung ground-glass nodules (GGNs). Methods    We retrospectively analyzed the clinical data of GGNs patients whose solid component less than 3 cm in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from March 2021 to July 2021 and the First Hospital of Lanzhou University from January 2019 to May 2022. The lesions were divided into pre-invasiveness and invasiveness according to postoperative pathological results, and the patients were randomly divided into a training set and a test set in a ratio of 7∶3. Radiomic features (1 317) were extracted from CT images of each patient, the max-relevance and min-redundancy (mRMR) was used to screen the top 100 features with the most relevant categories, least absolute shrinkage and selection operator (LASSO) was used to select radiomic features, and the support vector machine (SVM) classifier was used to establish the prediction model. We calculated the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value, positive predictive value to evaluate the performance of the model, drawing calibration and decision curves of the prediction model to evaluate the accuracy and clinical benefit of the model, analyzed the performance in the training set and subgroups with different nodule diameters, and compared the prediction performance of this model with Mayo and Brock models. Two primary thoracic surgeons were required to evaluate the invasiveness of GGNs to investigate the clinical utility of the mode. Results    A total of 400 patients were divided into the training set (n=280) and the test set (n=120) according to the admission criteria. There were 267 females and 133 males with an ……

Efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children / 中华实用儿科临床杂志

Objective:To investigate the clinical efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children.Methods:The clinical data of 50 children with moderate-to-severe allergic asthma and allergic comorbidities, who were treated with Omalizumab and completed 12-month follow-up in the Department of Pediatrics of Peking University First Hospital from July 2018 to March 2022, were retrospectively analyzed.A comparison was performed on the scale scores of childhood allergic asthma and allergic comorbidities including allergic rhinitis (AR) and chronic spontaneous urticaria (CSU), pulmonary function test indices and fractional exhaled nitric oxide (FeNO) concentration before and after treating with Omalizumab.The data were compared by ANOVA, paired t-test, chi- square test and rank sum test. Results:(1)Improvement of clinical symptoms: after 12 months of Omalizumab treatment, the childhood asthma control test score of 42 children aged ≤11 years increased from (20.98±5.03) points to (26.95±0.22) points ( F=18.189, P<0.001). The asthma control questionnaire 7 score of 50 children decreased from (0.89±0.11) points to (0.10±0.02) points ( F=5.662, P=0.006). The score of visual analogue scale of 47 children with AR decreased from (11.00±1.65) points to (0.2±0.14) points ( F=14.901, P<0.001), and the urticaria control test score of 13 children with CSU decreased from (4.82±0.88) points to (1.87±0.61) points ( F=4.329, P=0.018). (2)Improvement of quality of life: compared with those before treatment, the pediatric asthma quality of life questionnaire score in 50 children increased from (124.50±32.13) points to (159.40±6.21) points ( F=12.052, P<0.001), and global evaluation of asthma treatment effectiveness decreased from (2.23±0.70) points to (1.07±0.26) points ( F=68.865, P<0.001) after Omalizumab treatment for 12 months.(3)Improvement of pulmonary function results: after 12 months of Omalizumab treatment, the number of children with forced expiratory volume in one second/forced vital capacity< 80% decreased from 13 cases (26%) to 1 case (2%), and the values increased from (91.39±12.88)% to (96.96±8.54)%( χ2=11.960; t=2.486, all P<0.05). The peak expiratory flow of predicted value increased from (86.73±16.05)% to (94.01±13.11)% ( t=2.445, P<0.05). The number of children with two indicators among the forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled and maximal mid-expiratory flow lower than 65% decreased from 31 cases (62%) to 7 cases (14%) ( χ2=24.450, P<0.001). There was no significant difference in FeNO concentration before and after treatment ( P>0.05). Safety of Omalizumab: no obvious adverse reactions were found during treatment and follow-up. Conclusions:Omalizumab can significantly improve the clinical symptoms, small airway function and quality of life of children with allergic asthma and concomitant AR or CSU.It is a potential targeted drug for treating a variety of allergic diseases in children.

Analysis of drug resistance gene in Mycoplasma pneumoniae and 13 pathogens in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia / 中华实用儿科临床杂志

Objective:To investigate drug resistance gene in Mycoplasma pneumoniae(MP) and the distribution of 13 respiratory pathogens in bronchoalveolar lavage fluid(BALF) of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:A total of 100 BALF of children with MPP in Peking University Third Hospital and Peking University First Hospital from January 2018 to January 2019 were collected.Fluorogenic quantitative PCR was used to detect nucleic acid and it′s drug resistance gene of MP and multiple PCR method was adopted to detect influenza A virus, influenza A virus-H 1N 1, influenza A virus-H 3N 2, influenza B, human parainfluenza virus, adenovirus, human bocavirus, human rhinovirus, Chlamydia pneumoniae, human metapneumovirus, MP, human coronavirus, and respi-ratory syncytial virus gene, and the results were compared by using Chi square test. Results:In 100 BALF samples, MP and drug resistance gene were detected by fluorogenic quantitative PCR.Totally, 83 cases (83.00%) were MP positive and 78 cases (93.98%) were drug resistant.All of them had the point mutations A2063G in V region of 23S rRNA domain.A total of 13 kinds of respiratory pathogens were detected by multiplex PCR method, and 89 cases (89.00%) were positive.Totally, 79 cases (79.00%) were MP positive, of which 74 cases (74.00%) detected only MP, and 5 cases (5.00%) detected MP combined with other pathogens.Other pathogens were detected in 10 cases (10.00%). The virus detection rate of 0-4 years old group was higher than that of >4-6 years old group ( P=0.042) and >6 years old group ( P=0.002), and the differences were statistically significant. Conclusions:MP can be detected in most BALF samples of MPP children, the drug resistance phenomenon is serious, and the main point mutation is A2063G.There were other respiratory pathogens and 2 or 3 pathogens were detected in a small number of BALF samples.

The application of Whole-Mount immuno fluorescence staining technique in the study of lymphatic morphology in mice / 中华整形外科杂志

Objective@#To elaborate the characteristics and advantages of Whole-Mount immune fluorescence staining by observing the lymphatic vessels of mice.@*Methods@#The ear skin tissue, the hindlimb lymphatic vessels and the mesenteric lymphatic vessels were harvested from normal C57 mice. The tissue samples were subjected to whole-tissue immunofluorescence staining.These tissue samples were fixed by paraformaldehyde, blocked by bovine serum and incubated in primary and secondary antibodies. Then, the lymphatic vessels were observed and analyzed in these samples with a confocal laser-scanning microscope.@*Results@#The capillary lymphatic vessels and lymphatic endothelial cells can be clearly showed in the ear skin. The valves and smooth muscles can be clearly showed in the hindlimb and mesenteric lymphatic vessels by Whole-Mount immunofluorescence staining.@*Conclusions@#The whole-tissue immunofluorescence staining technique can observe the external morphology of lymphatic vessels clearly and stereoscopically, and can deeply observe the internal structure of lymphatic vessels. This technique can provide more accurate study on physiology and pathology of lymphatic vessels.

Effect of Euonymus alatus on the blood glucose and hemorheology in the rat model of Type 2 diabetes mellitus with blood stagnation / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of Euonymus alatus on the blood glucose and hemorheology in rat model of Type 2 diabetes mellitus with blood stagnation (DMBS).@*METHODS@#High fat diet with streptozocin was used to establish the rat model of Type 2 diabetes mellitus, followed by the prednisolone and adrenaline muscle injection to obtain DMBS. DMBS rats were divided into a DMBS group (treated with saline gavage), an Euonymus alatus group (treated with Euonymus alatus gavage), and a glybenzoylamide group (treated with glybenzoylamide gavage).A blank group was treated with saline gavage. The experiment lasted 4 weeks, followed by the evaluation of rats' behavior, and detection of fasting blood glucose and hemorheology.@*RESULTS@#Compared with DMBS rats, the symptoms of polydipsia and diuresis in Euonymus alatus rats were improved, with increased body weight (P<0.05), better fur and mental state, increased resistance for being caught, and reduced tongue stagnation. Compared with DMBS group, though body weight increased, resistance for being caught decreased in the glybenzoylamide group with bad fur and mental state,and tongue stagnation. As to the fasting blood glucose, there was significant difference between the Euonymus alatus group and the DMBS group (P<0.05). As to the hemorheology, including whole blood viscosity (shear rates 1,5,50, and 100 s(-1)), plasma viscosity, and hematocrit, the Euonymus alatus rats had a better efficacy than DMBS rats and glybenzoylamide rats (P<0.05 or P<0.01).@*CONCLUSION@#Euonymus alatus can reduce the fasting blood glucose of DMBS and improve blood stagnation.