Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research

Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle, which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discuss the future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.

Diagnostic utility of electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound in peripheral pulmonary lesions / 中国胸心血管外科临床杂志

@#Objective    To investigate the diagnostic value and safety of electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound in peripheral pulmonary nodules. Methods    The clinical imaging, surgical and pathological data of 60 patients with 76 peripheral pulmonary nodules who underwent electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound guided biopsy in the Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from June 2020 to June 2021 were retrospectively analyzed. The diagnosis rate and complications were analyzed and summarized. The 76 pulmonary nodules were divided into a small pulmonary nodules group (10 nodules, diameter≤1 cm) and a pulmonary nodules group (1 cm<diameter≤3 cm, 66 nodules) according to diameter. The two groups were compared in terms of operation and diagnosis rate. Results    Pulmonary nodules diameter was 1.8±0.6 cm, operation time 29.8±8.6 min, navigation 2.9±0.9 times, biopsy 9.5±1.9 pieces. In the 76 pulmonary nodules, 55 were confirmed by pathology, with a total diagnosis rate of 72.4%,  including 32 of malignant lesions and 23 of benign lesions. In the 76 pulmonary nodules, 59 had grade 0 hemorrhage, 17 had grade 1 hemorrhage, and none had grade 2 or more serious hemorrhage. Eight patients developed pneumothorax after surgery, and the degree of lung compression was less than 30%, which was improved after symptomatic treatment with oxygen inhalation. The operation time in the small pulmonary nodules group was significantly longer than that in the pulmonary nodules group, and there was no significant difference in diagnosis rate or complications between the two groups. Conclusion    Electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound is a safe and effective method for the diagnosis of periphery pulmonary nodules, and it also has a high diagnostic rate for small pulmonary nodules (≤1 cm), which is worthy of clinical promotion and application.

Symptomatic Radiation Pneumonitis in NSCLC Patients Receiving EGFR-TKIs and Concurrent Once-daily Thoracic Radiotherapy: Predicting the Value of Clinical and Dose-volume Histogram Parameters / 中国肺癌杂志

BACKGROUND@#The incidence of symptomatic radiation pneumonitis (RP) and its relationship with dose-volume histogram (DVH) parameters in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and concurrent once-daily thoracic radiotherapy (TRT) remain unclear. We aim to analyze the values of clinical factors and dose-volume histogram (DVH) parameters to predict the risk for symptomatic RP in these patients.@*METHODS@#Between 2011 and 2019, we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and once-daily TRT simultaneously (EGFR-TKIs group) and 129 patients who had received concurrent chemoradiotherapy (CCRT group). The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event (CTCAE) criteria (grade 2 or above). Statistical analyses were performed using SPSS 26.0.@*RESULTS@#In total, the incidences of symptomatic (grade≥2) and severe RP (grade≥3) were 43.5% (37/85) and 16.5% (14/85) in EGFR-TKIs group vs 27.1% (35/129) and 10.1% (13/129) in CCRT group respectively. After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching, chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group (χ2=4.469, P=0.035). In EGFR-TKIs group, univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving ≥30 Gy (ilV30) [odds ratio (OR): 1.163, 95%CI: 1.036-1.306, P=0.011] and the percentage of total lung volume receiving ≥20 Gy (tlV20) (OR: 1.171, 95%CI: 1.031-1.330, P=0.015), with chronic obstructive pulmonary disease (COPD) or not (OR: 0.158, 95%CI: 0.041-0.600, P=0.007), were independent predictors of symptomatic RP. Compared to patients with lower ilV30/tlV20 values (ilV30 and tlV20<cut-off point values) and without COPD, patients with higher ilV30/tlV20 values (ilV30 and tlV20>cut-off point values) and COPD had a significantly higher risk for developing symptomatic RP, with a hazard ratio (HR) of 1.350 (95%CI: 1.190-1.531, P<0.001).@*CONCLUSIONS@#Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy. The ilV30, tlV20, and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.

Gene-lifestyle interaction on coronary heart disease in adult twins of China / 中华流行病学杂志

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.

A descriptive analysis on coronary heart disease in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.

A descriptive analysis on type 2 diabetes in twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of type 2 diabetes in twins in Chinese National Twin Registry (CNTR), provide clues and evidence for revealing the influence of genetic and environmental factors for type 2 diabetes. Methods: Of all twins registered in the CNTR during 2010-2018, a total 18 855 twin pairs aged ≥30 years with complete registration information were included in the analysis. The random effect model was used to describe the population and area distribution characteristics and concordance of type 2 diabetes in twin pairs. Results: The mean age of the subjects was (42.8±10.2) years, the study subjects included 10 339 monozygotic (MZ) twin pairs and 8 516 dizygotic (DZ) twin pairs. The self-reported prevalence rate of type 2 diabetes was 2.2% in total population and there was no sighificant difference between MZ and DZ. Intra-twin pairs analysis showed that the concordance rate of type 2 diabetes was 38.2% in MZ twin pairs, and 16.0% in DZ twin pairs, the difference was statistically significant (P<0.001). The concordance rate of type 2 diabetes in MZ twin parts was higher than that in DZ twin pairs in both men and women, in different age groups and in different areas (P<0.05). Further stratified analysis showed that in northern China, only MZ twin pairs less than 60 years old were found to have a higher concordance rate of type 2 diabetes compared with DZ twin pairs (P<0.05). In southern China, the co-prevalence rate in male MZ twin pairs aged ≥60 years was still higher than that in DZ twin pairs (P<0.05). Conclusion: The twin pairs in this study had a lower self-reported prevalence of type 2 diabetes than the general population. The study results suggested that genetic factors play a role in type 2 diabetes prevalence in both men and women, in different age groups and in different areas, however, the effect might vary.

Effect of intermittent fasting on the cognitive dysfunction induced by irradiation / 中华放射医学与防护杂志

Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.

Trends in incidence and mortality of Alzheimer's disease in Zhejiang Province from 2003 to 2017 / 预防医学

Objective@#To analyze the trends in incidence and mortality of Alzheimer's disease (AD) in Zhejiang Province from 2003 to 2017, so as to provide the evidence for the development of AD prevention and control strategies. @* Methods@#The data pertaining to the incidence and mortality of AD in China from 2003 to 2017 were collected from the Global Burden Disease Study, and standardized to the data of the Sixth National Population Census in China in 2010. The trends in incidence and mortality of AD were analyzed using annual percent change (APC) and average annual percent change ( AAPC ) in Zhejiang Province from 2003 to 2017. @*Results@#The incidence of AD increased from 96.05/105 in 2003 to 140.96/105 in 2017 in Zhejiang Province, with AAPC of 2.776% ( P<0.05 ), and the greatest APC ( 3.419% ) was found during the period between 2003 and 2005 ( P<0.05 ). The standardized incidence of AD increased 102.06/105 in 2003 to 106.09/105 in 2017 in Zhejiang Province, with AAPC of 0.274% ( P<0.05 ), and the greatest APC ( 1.177% ) was measured during the period between 2003 and 2005 ( P<0.05). The mortality of AD increased from 24.60/105 in 2003 to 41.44/105 in 2017 in Zhejiang Province, with AAPC of 3.862% ( P<0.05 ), and the greatest APC (4.667%) was found during the period between 2005 and 2011 ( P<0.05 ). The standardized mortality of AD increased 26.83/105 in 2003 to 27.16/105 in 2017 in Zhejiang Province, with AAPC of 0.142% ( P>0.05 ), and the greatest APC ( 1.048% ) was measured during the period between 2005 and 2012 ( P<0.05 ).@*Conclusion@#Both the incidence and mortality of AD appeared a tendency towards a rise in Zhejiang Province from 2003 to 2017.

Chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar affect diversity of gut microbiota in rat model of malignant ascites induced by Walker-256 cells / 中国中药杂志

This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.

Virological response to direct-acting antiviral therapy and changes in liver fibrosis indices in chronic hepatitis C patients with different alanine aminotransferase and aspartate aminotransferase levels in a real-world setting / 临床肝胆病杂志

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Changes of brain functional network in neonates with different degrees of hypoxic-ischemic encephalopathy / 中华行为医学与脑科学杂志

Objective:To explore the changes of brain network functional connection in neonates with different degrees of hypoxic-ischemic encephalopathy(HIE), and to understand its influence on brain function.Methods:Clinical data of full-term HIE children hospitalized in Neonatology Department of Changzhou Children's Hospital from January 2017 to May 2020 were collected by convenient sampling method. A total of 44 cases were scanned by conventional and functional magnetic resonance image.Twenty-four of them met the inclusion criteria, including 11 mild patients (PT1 group) and 13 moderate and severe patients (PT2 group). The amplitude of low frequency fluctuation (ALFF) was used to compare the differences of ALFF values between PT1 group and PT2 group, and the differences of functional connectivity (FC) between PT1 group and PT2 group were compared by the method of brain network connectivity analysis.Results:In the edge analysis, compared with the PT1 group, the FC of the right supplementary motor area and the right precentral gyrus ( Z1=0.39, Z2 =-0.08), the right lingual gyrus and the right hippocampus ( Z1=0.61, Z2=0.20), the left calcarine cortex and the right amygdala ( Z1=0.30, Z2=-0.02), the right pallidus and the right posterior cingulate cortex ( Z1=0.33, Z2=0.05) were decreased in the PT2 group (all P<0.001, uncorrected). In ALFF analysis, there was no significant difference between PT1 group and PT2 group ( P>0.05, FDR adjusted). Conclusion:There are changes in functional connections in some brain regions in children with moderate and severe HIE.These functional connections are related to motor function, emotional processing, language development, cognitive function, learning and memory, etcetera.

Effects of fibrinogenase combined with aspirin on blood viscosity and clinical efficacy in patients with acute cerebral infarction / 中国医师进修杂志

Objective:To investigate the effect of fibrinogenase combined with aspirin on blood viscosity and clinical efficacy in patients with acute cerebral infarction.Methods:Senventy patients with mild to moderate acute cerebral infarction from October 2016 to June 2020 were collected from the Third People′s Hospital of Dalian. Patients were divided into control group and treatment group according to the random number table method, with 35 cases in each group. The control group was given oral aspirin plus an intravenous drip of normal saline equal to the treatment group, while the treatment group was given aspirin plus fibrinogenase by intravenous drip. Both groups were given symptomatic treatment such as management of blood glucose, blood pressure, arteriosclerosis plaque stabilization and improvement of circulation for 10 d. Blood viscosity and neurological deficit score were measured before and after treatment.Results:Compared with baseline values, WBV showed a slight decrease in all shear rates in the control group after treatment compared with that before treatment, but the difference was not statistically significant ( P>0.05). In the treatment group, all shear rates decreased compared with that before treatment ( P<0.05), and the effect of WBV was significant compared with that of the control group ( P<0.05). The improvement of neurological function in the treatment group was better than that in the control group. The significant efficiency and the total effective rate in the treatment group were significantly higher than those in the control group: 34.3% (12/35) vs. 25.7% (9/35), 88.6% (31/35) vs.71.4% (25/35). Conclusions:Fibrinogenase combined with aspirin in the treatment of acute cerebral infarction patients can safely and effectively reduce blood viscosity and improve clinical symptoms.

Current situation and influence factors of suicidal self-injurious behavior in teenagers in Guangdong / 上海预防医学

Objective:To investigate the current situation of suicidal self-injurious behavior in teenagers and analyze its influencing factors. Methods:From January to November 2020， a stratified sampling method was used to investigate 707 teenagers in Guangdong. The “questionnaire of health-related behaviors of Chinese teenagers” compiled by the Chinese Center for Disease Control and Prevention was used anonymously to investigate the current situation of suicidal self-injurious behavior of the teenagers. The chi-square test was used for univariate analysis， and logistic regression was used for multivariate analysis. Results:The incidence rate of suicidal self-injurious behavior was 14.57% （103/707）. It was 13.31% （45/338） in males， 15.72% （58/369） in females， 13.83% （48/347） in junior high school students and 15.28% （55/360） in senior high school students. There was no statistical significance in the incidence of suicidal self-injurious behavior of teenagers between different genders， different learning stages， smoking or not， asexual behavior or not， gambling or not， and fighting or not （all P>0.05）. The incidence of suicidal self-injurious behaviors in teenagers from single parent family， drunkenness， runaway， loneliness， under great study pressure， lovelorn， and mobile phone addiction was significantly higher （χ2=13.809， 10.852， 14.279， 11.451， 12.893， 22.905， 19.473， respectively. All P<0.001）. Logistic regression analysis showed that the following were main risk factors affecting the incidence of suicidal self-injurious behavior in teenagers： single parent family （OR=3.826， 95%CI： 1.402-7.501）， drunkenness （OR=3.903， 95%CI： 1.512-7.368）， runaway （OR=3.447， 95%CI： 1.669-7.715）， loneliness （OR=3.613， 95%CI： 1.504-7.697）， great study pressure （OR=3.712， 95%CI： 1.387-7.604）， lovelorn（OR=4.125， 95%CI： 1.516-8.117） and mobile phone addiction（OR=4.027， 95%CI： 1.499-7.984 （all P<0.001）. Conclusion:The incidence of suicidal self-injurious behavior in teenagers is not low in Guangdong， and targeted measures should be developed to screen and intervene based on the influencing factors.

Evodiamine inhibits high-fat diet-induced colitis-associated cancer in mice through regulating the gut microbiota / 中西医结合学报

OBJECTIVE@#High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention.@*METHODS@#Gut microbiota, serum d-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum d-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2'-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays.@*RESULTS@#In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of Bifidobacterium, Campylobacter and Lactobacillus were decreased. Serum endotoxin and d-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while Bifidobacterium, Campylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and d-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group.@*CONCLUSION@#EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

Recommendations from Experts in the Management of Adverse Reactions to ALK Inhibitors (2021 Version) / 中国肺癌杂志

Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions.
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A Case Report of Primary Pulmonary NUT Carcinoma and Literature Review / 中国肺癌杂志

NUT carcinoma is a rare, high lethal cancer which feature as the rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, and its pathogenesis and treatment is not yet clear, the prognosis is poor. Due to NUT carcinoma often occurred on the middle position of the body, such as eyes, nose and palate, mediastinum, so it is also called NUT midline carcinoma (NMC). In this case, we report a 70 years old man who was diagnosed as primary pulmonary NUT carcinoma in the Department of Thoracic Oncology, West China Hospital of Sichuan University. A tumor was found at the left hilus pulmonis when his physical examination without any symptom. Postoperative pathological showed poorly differentiated carcinoma, confirmed by fluorescence in situ hybridization technique for the NUT carcinoma. After operation, chemotherapy, antiangiogenesis therapy, and radiotherapy were given, and he got a long lifetime. Combined with the literature review, we report the clinical and pathological features, and treatment strategies of the rare pulmonary NUT carcinoma case.
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The role of neutrophils in asthma / 浙江大学学报·医学版

Bronchial asthma is a chronic respiratory disease，characterized by airway inflammation，airway hyperresponsiveness，reversible airway obstruction and airway remodeling，in which a variety of cells including airway inflammatory cells and structural cells are involved. Previous studies have shown that asthma is mainly driven by Th2 cytokines IL-4，IL-5，and IL-13，leading to airway eosinophil inflammation. With further research，however，it has been found that neutrophils are also closely related to asthma. Numbers of neutrophils are elevated in airway through increased chemotaxis and decreased apoptosis，which is earlier than eosinophils，leading to airway neutrophilic inflammation. Neutrophils can produce elastase，myeloperoxidase，neutrophil extra- cellular traps，chemokines and cytokines，participating in the occurrence and development of asthma. The antagonists against these molecules，such as anti-IL-8 receptor antibody，anti-IL-17 antibody，and DNase，have shown positive effects on neutrophilic asthma，but further studies are needed to support their clinical application. This article mainly reviews the role of neutrophils in asthma and related mechanisms.

A fetal electrocardiogram signal extraction method based on long short term memory network optimized by genetic algorithm / 生物医学工程学杂志

Fetal electrocardiogram signal extraction is of great significance for perinatal fetal monitoring. In order to improve the prediction accuracy of fetal electrocardiogram signal, this paper proposes a fetal electrocardiogram signal extraction method (GA-LSTM) based on genetic algorithm (GA) optimization with long and short term memory (LSTM) network. Firstly, according to the characteristics of the mixed electrocardiogram signal of the maternal abdominal wall, the global search ability of the GA is used to optimize the number of hidden layer neurons, learning rate and training times of the LSTM network, and the optimal combination of parameters is calculated to make the network topology and the mother body match the characteristics of the mixed signals of the abdominal wall. Then, the LSTM network model is constructed using the optimal network parameters obtained by the GA, and the nonlinear transformation of the maternal chest electrocardiogram signals to the abdominal wall is estimated by the GA-LSTM network. Finally, using the non-linear transformation obtained from the maternal chest electrocardiogram signal and the GA-LSTM network model, the maternal electrocardiogram signal contained in the abdominal wall signal is estimated, and the estimated maternal electrocardiogram signal is subtracted from the mixed abdominal wall signal to obtain a pure fetal electrocardiogram signal. This article uses clinical electrocardiogram signals from two databases for experimental analysis. The final results show that compared with the traditional normalized minimum mean square error (NLMS), genetic algorithm-support vector machine method (GA-SVM) and LSTM network methods, the method proposed in this paper can extract a clearer fetal electrocardiogram signal, and its accuracy, sensitivity, accuracy and overall probability have been better improved. Therefore, the method could extract relatively pure fetal electrocardiogram signals, which has certain application value for perinatal fetal health monitoring.

Effect of lncRNA MEG3 on radiosensitivity of nasopharyngeal carcinoma cells by down-regulating miR-7-5p expression / 中华放射肿瘤学杂志

Objective To investigate the effect and underlying mechanism of lncRNA MEG3 on the radiosensitivity of nasopharyngeal carcinoma cells.Methods this experiment,overexpression control group,MEG3 overexpression group,miR-NC inhibition group,miR-7-5p inhibition group,overexpression control+4 Gy group,MEG3 overexpression+4 Gygroup,miR-NC inhibition+4 Gy group,miR-7-5p inhibition+4 Gy group,MEG3 overexpression + miR-NC overexpression group,MEG3 overexpression + miR-7-Sp overexpression group were established.The expression of miR-7-5p and MEG3 was detected by qRT-PCR.The radiosensitivity of nasopharyngeal carcinoma cells was measured by clone formation assay.Cell apoptosis was assessed by flow cytometry.The fluorescence activity was evaluated by dual luciferase reporter assay.Results MEG3 was lowly expressed in nasopharyngeal carcinoma tissues and cells.Overexpression of MEG3 and inhibition of miR-7-5p expression increased the radiosensitivity of nasopharyngeal carcinoma cells and promoted radiation-induced cell apoptosis.MEG3 could targetedly regulate the miR-7-5p expression.Overexpression of miR-7-5p reversed the effect of overexpression of MEG3 on the sensitization of nasopharyngeal carcinoma cells and the promotion of apoptosis induced by radiation exposure.Conclusions Overexpression of MEG3 increases the radiosensitivity of nasopharyngeal carcinoma cells and promotes radiation-induced cell apoptosis.The mechanism may be related to the down-regulation of miR-7-5p expression.

Preliminary application of artificial intelligence-based image optimization in coronary CT angiography / 中华放射学杂志

Objective:To investigate the benefits of artificial intelligence (AI)-based image optimization technique on image quality of coronary CT angiography (CCTA).Methods:Sixty patients, who were referred for CCTA, were prospectively enrolled between May and June 2018 in Peking Union Medical College Hospital and were randomly divided into two groups. Group A was scanned with a low tube voltage of 80 kVp and a reduced contrast media volume of lopamiro at 0.7 ml /kg and group B was scanned with a standard 120 kVp tube voltage and an injection of 70 ml lopamiro. According to the different reconstruction methods, group A was divided into two subgroups. The images of group A1 were reconstructed with iterative reconstruction (IR). IR and further AI-based image optimization were used in group A2. Group B was also reconstructed by IR. To evaluate image quality objectively, the mean attenuation of contrast-enhancement values, background noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured and calculated in the region of interests (ROIs) of the aortic root (Ao), left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), respectively. In addition, the subjective evaluation was performed by two radiologists using Likert 4 scale (1 for excellent and 4 for poor) to evaluate the image quality of coronary artery branches and segments. The estimated radiation dose in terms of volume CT dose index (CTDI vol), dose length product (DLP) and effective dose (ED) was recorded and compared between group A and group B. Analyses of the differences between groups were compared with image quality, radiation dose by t test or Wilcoxon signed ranks test, and subjective assessments were compares with χ 2 test. Results:In terms of lumen enhancement, compared to group A2, there was no significant difference in CT value of each ROI ( P>0.05); CT value of group A1 and group A2 at Ao was significantly higher than that of group B ( P<0.01), but there was no significant difference in other ROI ( P>0.05). By comparing noise, SNR and CNR, it could be seen that compared to group B, A2 group optimized by AI had a significantly lower noise level at Ao than group B ( P<0.001), and there was no statistical difference in ROI for the rest (all P>0.05).SNR at Ao was significantly higher than that of group B ( P<0.001), and there was no statistical difference in ROI for the rest ( P>0.05).However, the CNR of group A2 was significantly higher than that of group B in all ROI ( P<0.001). Compared to the AI-optimized A2 group, the noise of A2 group was significantly lower than that of A1 group at all ROI, and SNR and CNR were significantly higher than that of A1 group ( P<0.001). The subjective evaluation results of coronary segments showed that image quality of group A2 and group B was significantly better than that of group A1 ( P=0.002,0.038). There was no significant difference between group A2 and group B ( P=0.543). The radiation dose indexes of CTDI vol, DLP and ED in group A were significantly lower than those in group B (all P<0.001). The ED was decreased by 70.4%. Meanwhile, the volume of contrast media in group A was reduced by 37.1% than that that in group B. Conclusion:Compared to conventional scanning, CCTA images optimized by AI technology improved subjective and objective image quality.