Reversible Switching Based on Truly Intramolecular Long-Range Proton Transfer─Turning the Theoretical Concept into Experimental Reality.

Herein, we demonstrate a working prototype of a conjugated proton crane, a reversible tautomeric switching molecule in which truly intramolecular long-range proton transfer occurs in solution at room temperature. The system consists of a benzothiazole rotor attached to a 7-hydroxy quinoline stator. According to the experimental and theoretical results, the OH proton is delivered under irradiation to the quinolyl nitrogen atom through a series of consecutive proton transfer and twisting steps. The use of a rigid rotor prevents undesired side processes that decrease the switching performance in previously described proton cranes and provides an unprecedented switching efficiency and fatigue resistance. The newly designed system confirms the theoretical concept for the application of proton transfer-initiated intramolecular twisting as the switching mechanism, developed more than 10 years ago, and provides unique insights for the further development of tautomeric molecular switches and motors, molecular logic gates, and new molecular-level energy storage systems.

Relationship between pericoronary fat-attenuation values quantified by coronary computed tomography angiography and coronary artery disease severity.

AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.

Correlation between left atrial appendage morphology based on fractal dimension quantification and its hemodynamic parameters in patients with atrial fibrillation.

AIMS: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. MATERIALS AND METHODS: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. RESULTS: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (ß = -11.755, P=0.001), LAA FV (ß = -17.364, P=0.004), LAA PEV (ß = -18.743, P<0.001), and LAA WMV (ß = -7.740, P=0.001) in multiple linear regression analysis. CONCLUSIONS: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.

[Role of liver sinusoidal endothelial cell damage in the developmental process of hepatic sinusoidal obstruction syndrome: a focus on the research progress of immune inflammatory mechanisms].

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Identification of vulnerable carotid plaque with CT-based radiomics nomogram.

AIM: To develop and validate a radiomics nomogram for identifying high-risk carotid plaques on computed tomography (CT) angiography (CTA). MATERIALS AND METHODS: A total of 280 patients with symptomatic (n=131) and asymptomatic (n=139) carotid plaques were divided into a training set (n=135), validation set (n=58), and external test set (n=87). Radiomic features were extracted from CTA images. A radiomics model was constructed based on selected features and a radiomics score (rad-score) was calculated. A clinical factor model was constructed by demographics and CT findings. A radiomics nomogram combining independent clinical factors and the rad-score was constructed. The diagnostic performance of three models was evaluated and validated by region of characteristic curves. RESULTS: Calcification and maximum plaque thickness were the independent clinical factors. Twenty-four features were used to build the radiomics signature. In the validation set, the nomogram (area under the curve [AUC], 0.977; 95% CI, 0.899-0.999) performed better (p=0.017 and p=0.031) than the clinical factor model (AUC, 0.862; 95% CI, 0.746-0.938) and radiomics signature (AUC, 0.944; 95% CI, 0.850-0.987). In external test set, the nomogram (AUC, 0.952; 95% CI, 0.884-0.987) and radiomics signature (AUC, 0.932; 95% CI, 0.857-0.975) showed better discrimination capability (p=0.002 and p=0.037) than clinical factor model (AUC, 0.818; 95% CI, 0.721-0.892). CONCLUSION: The CT-based nomogram showed satisfactory performance in identification of high-risk plaques in carotid arteries, and it may serve as a potential non-invasive tool to identify carotid plaque vulnerability and risk stratification.

[Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world].

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Value of pseudopod sign on high-frequency ultrasound in predicting the pathological invasion of extramammary Paget's disease lesions.

BACKGROUND: Vertical invasion of extramammary Paget's disease (EMPD) is associated with poor prognosis. The usual vertical invasion route is directly downward or along the skin appendages. High-frequency ultrasound (HFUS) can be used to measure the EMPD lesion thickness, and visualize the pseudopod extensions due to skin appendage involvement. It is a non-invasive method for evaluating the extent of vertical invasion in EMPD. OBJECTIVE: To investigate the value of HFUS in predicting the extent of vertical invasion in EMPD. METHODS: In this retrospective study, 85 patients with EMPD were divided into two groups based on the pathology: invasive EMPD (iEMPD) group (n = 13) and in situ EMPD group (n = 72). The clinical and HFUS features of both the groups were analysed. The different types of pseudopodia morphology on HFUS were as follows: no pseudopodia, irregular bottom, small sphere, short strip, long strip, vase shape and nodular convex. These were further stratified into low-risk and high-risk levels. RESULTS: The clinical features were comparable between the two groups (P > 0.05). There were significant differences between the two groups in the HFUS features (lesion thickness, lesion shape, bottom shape, layer involvement, pseudopodia morphology and colour Doppler blood flow signal; all P < 0.05). The distribution of the pseudopodia morphology types in the in situ EMPD and iEMPD groups was as follows: no pseudopodia, 30/72 and 0/13; irregular bottom, 5/72 and 0/13; small sphere, 5/72 and 0/13; short strip, 21/72 and 0/13; long strip, 8/72 and 3/13; vase shape, 3/72 and 3/13; and nodular convex, 0/72 and 7/13 (P < 0.05 for all). The sensitivity and specificity of high-risk pseudopodia in identifying iEMPD were 100% and 84.7%, respectively. CONCLUSIONS: High-frequency ultrasound provides morphological information regarding EMPD lesions. Risk stratification for pseudopodia can help to distinguish between iEMPD and in situ EMPD lesions.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats].

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.

Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

[Breast ultrasound optimization process analysis based on breast cancer screening for 1 501 753 rural women in China].

Objective: To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening. Methods: The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children's public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated. Results: A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area (P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area (P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area (P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area (P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area (P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area (P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions: The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

[The correlation between serum uric acid levels in the third trimester of pregnancy and adverse pregnancy outcomes].

Objective: To investigate the associations between serum uric acid levels during the third trimester of pregnancy and risks of adverse pregnancy outcomes. Methods: In this retrospective study, a cohort of 7 995 pregnant women who were hospitalized for childbirth from January 2014 to January 2019 were collected to compare pregnancy outcomes between subjects with or without hyperuricemia (HUA). A smooth curve analysis was used to evaluate the relationship between uric acid levels and preterm delivery, low birth weight and smaller than gestational age. Logistic regression analyses were performed to identify risk factors for adverse pregnancy outcomes, and the interaction of the factors. Results: During the third trimester of pregnancy, the uric acid levels of about 10% pregnant women were over 420 µmol/L. In those with HUA, the median neonatal birth weight was 2 590 (1 790, 3 410) g, the probability of premature birth was 49.81%, and the incidence of small than gestational age was 20.41%. These were significantly different from the women without HUA (the median neonatal birth weight: 3300 (2850, 3640) g; the probability of premature birth 23.09%; the incidence of small than gestational age 6.55%, respectively) (All P<0.001). Maternal uric acid levels were negatively correlated with neonatal birth weight, and positively correlated with the risk of smaller than gestational age. It has a U-shaped association with the probability of premature birth, and the lowest probability of premature birth was at 200-400 µmol/L of the uric acid. Risks of low birth weight (adjusted ß=-5.22, 95%CI-6.46--3.99) and smaller than gestational age (adjusted OR=1.03, 95%CI 1.02-1.04) were increased in the function of uric acid levels. High uric acid, hypertension, oligoamnios and preeclampsia were important risk factors for the adverse pregnancy outcomes. The risk of preterm delivery and low birth weight enhanced when hyperuricemia combined with hypertension and preeclampsia. Conclusions: Serum uric acid level can be used as one of reliable markers for predicting adverse pregnancy outcomes, which might provide theoretical basis for clinical intervention in practice.

[Accelerating the elimination of cervical cancer in China and building a paradigm for "Healthy China" cancer prevention].

Cervical cancer is a common malignant tumor that seriously threatens the health of Chinese women. The situation of prevention and control is still serious. In the past decade, the Chinese government has made great efforts to cervical cancer prevention and control and achieved remarkably in HPV vaccine development, sound health screening system, and treatment capacity of early cervical cancer and precancerous lesions. However, due to the large population base, unequal allocation of health resources, and uneven service quality across regions, there is still a significant gap to achieve the WHO's goal of eliminating cervical cancer by 2030. In order to fulfill the Global Strategy to accelerate the elimination of cervical cancer, China urgently needs to learn from the international experience, combined with the real situation of cervical cancer prevention and control and the latest research progress in China and to put forward appropriate action recommendations and implementation approaches, which will contribute to promote the cervical cancer elimination process and to build a paradigm for "Healthy China" cancer prevention.

[Global guidelines for cervical cancer screening: a systematic review].

Objective: To systematically summarize and evaluate the current cervical cancer screening guidelines worldwide. Methods: "Cervical cancer/cervical intraepithelial neoplasia", "screening", and "guidelines/recommendations" were searched as keywords in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data for cervical cancer screening guidelines. The language was limited to Chinese and English. A total of 29 guidelines were included before September 1, 2020. The basic information and recommendations of the guidelines issued were summarized. Results: Among the 29 cervical cancer screening guidelines, most guidelines targeted on the population aged 25-65 years. Cytology and human papillomavirus (HPV) testing are two commonly used methods for the cervical cancer screening, and HPV testing is increasingly recommended as the primary screening methods. Most guidelines recommended five years interval for the HPV testing-based screening or co-testing (HPV testing and cytology) based screening and three years for the cytology-based. For managing population with abnormal cervical cancer screening, triage or screening repeatedly to identify high-risk populations were more recommended. Direct colposcopy or treatment were allowed for women with higher risk of cervical intraepithelial neoplasia (CIN) during the screening procedure. Several guidelines involving HPV vaccination population recommended them the same strategy as the general population without vaccination. Conclusion: Currently, most of the cervical cancer screening guidelines applied to the population with the average risk of the CINs and were issued by the developed countries. Primary methods for the cervical cancer screening have gradually changed from the cytology to the HPV testing. There is a lack of recommendations targeting special population on cervical cancer screening in the current guidelines.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[Analysis of the reported data of National Cervical Cancer Screening Program in Rural Areas in China from 2009 to 2018].

Objective: To analyze the effectiveness of the National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in China. Methods: Data were collected in the form of quarterly statistical tables reported by NCCSPRA counties in 30 provinces (Hong Kong, Macao and Taiwan province of China were not included into the NCCSPRA, and Tibet Autonomous Region carried out the program but did not reported the data) from 2009 to 2018. The women aged 35-64 years with sexual behavior and the identity (Hukou) of rural area in these project counties were included into the NCCSPRA, and women receiving hysterectomy for non-cervical cancer or non-cervical lesions were excluded. The following indicators were analyzed: the positive rates of different screening methods, the abnormality rates of colposcopy and histopathology, the detection rate of precancerous lesions, the detection rate of cervical cancer and the rate of early diagnosis. Results: A total of 85 041 490 women aged 35-64 in rural areas received free cervical cancer screening and diagnosis if necessary. On the whole, the abnormality rate of cytology, HPV testing, VIA/VILI, colposcopy and histopathology was 3.71%(2 567 610), 9.91%(331 158), 10.10%(1 167 930), 28.85%(1 420 847), and 21.20%(303 068) respectively. The detection rate of cervical precancerous lesions was 153.88/100 000, and increased from 106.85/100 000 in 2012 to 223.89/100 000 in 2018 (P<0.001). Regionally, the east (207.37/100 000) reached higher rate than the middle (177.65/100 000), and the middle higher than the west (108.65/100 000) (P<0.001). The detection rate of invasive cervical cancer was 21.58/100 000, and increased from 18.02/100 000 in 2012 to 26.54/100 000 in 2018 (P<0.001). Regionally, the middle of China (25.46/100 000) reached the higher rate than the east (19.62/100 000) and the west (19.30/100 000) (P<0.001). The rate of early detection was 91.24%(136 140), which increased from 89.60% (11 883)in 2012 to 92.80%(26 962) in 2018 (P<0.001). Regionally, the east of China (94.02%, 37 600) reached the higher rate than the middle(91.06%, 56 488), and the middle higher than the west (89.12%, 42 052) (P<0.001). Conclusions: There are obvious difference in terms of the detection rate of cervical precancerous lesions and the rate of early diagnosis reflecting cervical cancer screening capacity among the eastern, middle and western regions,which showed service inequity among different areas indirectly. The middle and western regions, especially the western regions, are still the focus of future works.

[Research progress on non-alcoholic fatty liver disease animal models].

In recent years, with the changes in living standards and dietary structure, the incidence of non-alcoholic fatty liver disease has been increasing year by year in China, and the incidence rate in the general population is as high as 29.81%. An increasingly epidemiological evidence suggests that non-alcoholic fatty liver disease has become one of the causes of increasing liver cirrhosis and liver cancer. However, its etiology and pathogenesis are complex and have not yet been fully elucidated. Therefore, establishing an appropriate non-alcoholic fatty liver disease animal models for pre-clinical research is essential to elucidate its pathogenesis. This article summarizes the latest research progress of non-alcoholic fatty liver disease animal models, which are common at home and abroad in recent years.

[Study on serum metabolomics of combined injury induced by gas explosion in rats].

Objective: To analyze the changes of serum metabolomics in rats with combined injuries caused by gas explosion and explore its possible mechanism. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the gas explosion experiment. All 32 SD rats were randomly divided into four groups, control group (not involved in the explosion) , close range (40 m) group, medium range (160 m) group and long range (240 m) group, 8 in each group. The respiratory function at 2 hours and the neural behavior at 48 hours were detected after the explosion. The rats were anesthetized and sacrificed after 48 hours, and the serum, lung, liver and other tissues of the rats were isolated and histopathological changes of lung and liver tissues were observed by HE staining. Serum samples were detected by liquid chromatography-high resolution mass spectrometry (UPLC-Orbitrap Elite/MS) , and metabolic spectrum differences between groups were evaluated by principal component analysis. Differential metabolites were screened and identified, and metabolic pathways were analyzed. Results: Compared with control group, respiratory function indexes (respiratory frequency, minute ventilation, peak inspiratory flow rate, peak expiratory flow rate and 1/2 tidal volume expiratory flow) of rats in different explosion groups were significantly decreased (P<0.05) , but respiration pause, inspiratory time and 2/3 tidal volume required time were significantly increased (P<0.05) in 2 hours after the explosion. However, the residence times of the neurobehavioral indicators of the 40 m group and 160 m group were significantly increased (P<0.05) , and the movement distances were significantly decreased (P<0.05) in 48 hours after the explosion. HE staining results showed that the lung and liver tissues of the rats in the gas explosion group structurally damaged, and the cells were disordered, with inflammatory cell infiltration, bleeding and edema. Metabonomics analysis showed that there were significant differences in metabolic profiles between groups. A total of 18 differential metabolites were identified in serum samples, including aconitum acid, citric acid, niacinamide and pyruvate, which involved in 12 major metabolic pathways, including the glutamic acid and glutamine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, phenylalanine metabolism, nicotinic acid and nicotinamide metabolism, citric acid cycle (TCA cycle) . Conclusion: Gas explosion can cause multi-organ system damage in rats, the mechanism of which may be related to the biosynthesis of alanine, tyrosine and tryptophan, metabolism of niacin and niacinamide, metabolism of acetaldehyde and dicarboxylic acid, and TCA cycle, etc.

[Changes and significance of autophagy in rat lung injury induced by gas explosion].

Objective: To explore the changes and significance of autophagy in acute lung injury (ALI) induced by gas explosion in rats. Methods: In February 2018, the gas explosion in underground coal mine was simulated by large tunnel explosion experiment system, SD rats were randomly divided into control group and 6 distance groups (40 m, 80 m, 120 m, 160 m, 200 m, 240 m) with 18 rats in each group. The respiratory function of rats 24 h before and after explosion was detected. Post-explosion rats were anesthetized and sacrificed, histopathological changes of lung were observed by HE staining. Immunohistochemistry was performed to detect the in situ expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3B) . The expression levels of autophagy related gene 12 (Atg12) , LC3B, P62, lysosomal associated membrane protein 2 (Lamp2) , B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl2 interaction protein (Beclin-1) were detected by Western blot. Results: After gas explosion, the rats in 80 m distance point group had the hightest mortality (n=13, 72.22%) and the most severe lung injury degree, and the histopathological scores was (4.00±0.00) point. After gas explosion, the minute ventilation volume (MVb) , maximum inspiratory flow rate (PIFb) and maximum expiratory flow rate (PEFb) of rats were lower than before the gas explosion (P<0.05) . The respiratory frequency of rats in 80 m, 200 m, and 240 m distance point groups were significantly higher than that in the control group (P<0.05) . The expression levels of LC3B in 40 m, 80 m, 120 m, 160 m, and 200 m distance point groups were higher than that in the control group (P<0.05) . The relative expression levels of Atg12 and LC3BⅡ/Ⅰ in lung tissues of rats in different distance point groups were higher than those in the control group (P<0.05) . The relative expression levels of Beclin1 in 40 m, 80 m, 120 m, and 160 m distance point groups were significantly higher than that in the control group (P<0.05) . The relative expression levels of P62 in 80 m, 160 m and 200 m distance point groups were lower than that in the control group (P<0.05) . The relative expression levels of Lamp2 and Bcl-2 in lung tissues of rats in all distance groups except 240 m distance group were lower than those in the control group (P<0.05) . Conclusion: Gas explosion could induce increased autophagy in lung tissues of ALI rats. Autophagy-related signaling pathway could be involved in the pathophysiological process of ALI in rats caused by gas explosion, then the autophagy and the severity of the lesion showed a significant positive correlation.

[Influences of gas explosion on acute blast lung injury and time phase changes of pulmonary function in rats under real roadway environment].

Objective: The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed. Results: Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased (P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased (P<0.05) . After 72 h, MV in the long range group was significantly decreased (P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance (P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased (P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion: Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.