A comprehensive diversity analysis on the gut microbiomes of ASD patients: from alpha, beta to gamma diversities.

Autism spectrum disorder (ASD) is estimated to influence as many as 1% children worldwide, but its etiology is still unclear. It has been suggested that gut microbiomes play an important role in regulating abnormal behaviors associated with ASD. A de facto standard analysis on the microbiome-associated diseases has been diversity analysis, and nevertheless, existing studies on ASD-microbiome relationship have not produced a consensus. Here, we perform a comprehensive analysis of the diversity changes associated with ASD involving alpha-, beta-, and gamma-diversity metrics, based on 8 published data sets consisting of 898 ASD samples and 467 healthy controls (HC) from 16S-rRNA sequencing. Our findings include: (i) In terms of alpha-diversity, in approximately 1/3 of the studies cases, ASD patients exhibited significantly higher alpha-diversity than the HC, which seems to be consistent with the "1/3 conjecture" of diversity-disease relationship (DDR). (ii) In terms of beta-diversity, the AKP (Anna Karenina principle) that predict all healthy microbiomes should be similar, and every diseased microbiome should be dissimilar in its own way seems to be true in approximately 1/2 to 3/4 studies cases. (iii) In terms of gamma-diversity, the DAR (diversity-area relationship) modeling suggests that ASD patients seem to have large diversity-area scaling parameter than the HC, which is consistent with the AKP results. However, the MAD (maximum accrual diversity) and RIP (ratio of individual to population diversity) parameters did not suggest significant differences between ASD patients and HC. Throughout the study, we adopted Hill numbers to measure diversity, which stratified the diversity measures in terms of the rarity-commonness-dominance spectrum. It appears that the differences between ASD patients and HC are more propounding on rare-species side than on dominant-species side. Finally, we discuss the apparent inconsistent diversity-ASD relationships among different case studies and postulate that the relationships are not monotonic.

Deep skin diseases diagnostic system with Dual-channel Image and Extracted Text.

Background: Due to the lower reliability of laboratory tests, skin diseases are more suitable for diagnosis with AI models. There are limited AI dermatology diagnostic models combining images and text; few of these are for Asian populations, and few cover the most common types of diseases. Methods: Leveraging a dataset sourced from Asia comprising over 200,000 images and 220,000 medical records, we explored a deep learning-based system for Dual-channel images and extracted text for the diagnosis of skin diseases model DIET-AI to diagnose 31 skin diseases, which covers the majority of common skin diseases. From 1 September to 1 December 2021, we prospectively collected images from 6,043 cases and medical records from 15 hospitals in seven provinces in China. Then the performance of DIET-AI was compared with that of six doctors of different seniorities in the clinical dataset. Results: The average performance of DIET-AI in 31 diseases was not less than that of all the doctors of different seniorities. By comparing the area under the curve, sensitivity, and specificity, we demonstrate that the DIET-AI model is effective in clinical scenarios. In addition, medical records affect the performance of DIET-AI and physicians to varying degrees. Conclusion: This is the largest dermatological dataset for the Chinese demographic. For the first time, we built a Dual-channel image classification model on a non-cancer dermatitis dataset with both images and medical records and achieved comparable diagnostic performance to senior doctors about common skin diseases. It provides references for exploring the feasibility and performance evaluation of DIET-AI in clinical use afterward.

DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level.

BACKGROUND: The aim of this study was to illustrate the role of DERL3 in regulating the development of Colorectal cancer (CRC) and the underlying molecular mechanisms. METHODS: Relative levels of DERL3 in CRC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between DERL3 level and clinical indicators in CRC patients was analyzed by χ2 test. After intervening DERL3 level in HT29 and HCT-8 cells, phenotype changes were assessed by cell counting kit-8 (CCK-8) and Transwell assay. The interaction between DERL3 and its downstream target MYCN, and their involvement in the malignant development of CRC were explored. The influence of DERL3 on in-vivo growth of CRC was determined by establishing xenograft model in nude mice bearing CRC. RESULTS: DERL3 was lowly expressed in CRC tissues than adjacent normal ones. Compared with CRC patients expressing a high level of DERL3, those with a low level presented high rate of lymphatic metastasis or distant metastasis. Overexpression of DERL3 in HT29 cells suppressed proliferative, migratory, and invasive capacities, and knockdown of DERL3 in HCT-8 cells yielded the opposite results. MYCN was the downstream target binding DERL3, which was upregulated in CRC tissues and cell lines. MYCN could reverse the regulatory effects of DERL3 on proliferative, migratory, and invasive capacities in CRC cells. In-vivo overexpression of DERL3 in nude mice bearing CRC inhibited tumor growth by reducing the average tumor volume and tumor weight of CRC tissues. CONCLUSIONS: DERL3 is downregulated in CRC samples. Its level is closely linked to lymphatic metastasis or distant metastasis rate in CRC patients. Through negatively regulating MYCN level, DERL3 suppresses proliferative, migratory, and invasive capacities in CRC.

Effects of Konjaku Flour on the Gut Microbiota of Obese Patients.

Objective: Gut microbiota have been thought to play a role in the emergence of obesity and metabolic disorders, thus dietary fiber may be an effective strategy for the management of obesity by modulating the gut microbiota. The aim of the present study was to investigate the effects of konjaku flour (KF) supplementation on treating obesity and regulating intestinal microbiota in obese adults. Methods: In a 5-week, randomized, double-blind, place-controlled trial, sixty-nine obese volunteers aged 25 to 35 with body mass index ≥28 kg/m2 were randomly assigned to receive KF or placebo (lotus root starch). Obesity index, blood parameters, and gut microbiota were analyzed. Results: KF remarkably reduced the body mass index (BMI), fat mass, percentage body fat (PBF), serum triglyceride (TG), glycated hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in the patients (p <0.05 or p <0.01). Meanwhile, high-throughput sequencing and bioinformatics analysis showed that the konjac flour treatment notably increased the α-diversity and changed the ß-diversity of intestinal microflora in patients (p <0.01). Moreover, konjac flour could also evidently increase the abundance of some of the beneficial microorganisms related to obesity of patients, such as Lachnospiraceae, Roseburia, Solobacterium, R. inulinivorans, Clostridium perfringens, and Intestinimonas butyriciproducens, and reduce the abundance of the harmful microorganisms, such as Lactococcus, Bacteroides fragilis, Lactococcus garvieae, B. coprophilus, B. ovatus, and B. thetaiotaomicron (p <0.01). Specifically, C. perfringens was significantly negatively correlated with serum total cholesterol (TC) (p <0.01). Conclusion: These results suggested that KF can achieve positive effects on treating obesity, which manifest on reducing BMI, fat mass, blood glucose, and blood lipid, improving hepatic function, and also regulating intestinal microfloral structure. Therefore, changes in gut microbiota may explain in part the effects of KF.

Acute Urticaria in Inpatients Undergoing Non-emergent Coronary Angiography With Corticosteroid Prophylaxis: A Retrospective Study.

Background and Aims: Acute urticaria (AU) is the most frequently reported immediate hypersensitivity reaction in skin by administration of iodinated contrast media (ICM). We aimed to establish the pattern and identify the risk factors of AU among inpatients undergoing non-emergent coronary angiography (CAG) with prophylactic corticosteroids in China. Methods: Medical records of 19,326 adult inpatients undergoing non-emergent CAG with prophylactic methylprednisolone in 2013-2019 were retrospectively investigated. AU was identified within 1 h post-ICM administration, and diffuse involvement was defined when wheals occur in two or more body parts, including the back, abdomen, chest, and extremities. Age- and sex-matched inpatients (1:4) without AU were randomly selected for assessment of risk factors. Results: Approximately 0.8% of CAG inpatients had AU, including 101 diffuse and 64 limited form. The diffuse AU was more common in settings of non-diagnostic CAG, iohexol used, average ICM injection≥3 ml/min, recurrent CAG, and past history of immediate hypersensitivity to ICM. Inpatients with preexisting allergies, decreased evaluated glomerular filtration rate, and increased high sensitivity C reactive protein or neutrophil-to-lymphocyte ratio prior to CAG had a higher probability of AU (odds ratio >1, P < 0.05 for all variables). All AU inpatients complained of pruritus, and mild itching predominated. AU dissipated in several days under treatment of ebastine or levocetirizine 10 mg/daily, but ebastine showed superiority. Conclusions: ICM-induced AU is not uncommon in non-emergent CAG inpatients with prophylactic methylprednisolone. Preexisting allergies, renal dysfunction, and mild inflammation are high-risk factors, and antihistamine monotherapy is a favorable candidate for ICM-related AU.

Analysis of Intestinal Flora and Levels of Epidermal Growth Factor Receptor, Interleukin-32, and Gastrin 17 in Patients with Gastric Cancer via Carbon Nanoparticle Laparoscopy.

In order to explore the changes of intestinal flora and serum levels of relevant substances in patients with gastric cancer before and after surgery with carbon nanoparticle laparoscopy, a total of 180 patients with early distal gastric cancer who adopted laparoscopic radical gastrectomy for distal gastric cancer in the general surgery department of TCM Hospital of Shi Jia Zhuang City from January 2018 to January 2020 were selected and randomly divided into two groups: traditional laparoscopic operation (control group) and carbon nanoparticle laparoscopic operation (experimental group) were adopted for treatment for the two groups, respectively. Postoperative evaluation included the difference between the two groups in the operative time, the efficiency of intraoperative lymph node dissection, and the number of lymph node detection. The adverse reactions, changes of intestinal flora before and after surgery in the two groups, and the serum levels of epidermal growth factor receptor (EGFR), interleukin-32 (IL-32), and gastrin 17 were evaluated. In the experimental group, the success rate of carbon nanoparticle tracer black staining reached 100%, and the operation time of the experimental group was significantly shorter than that of the control group (P < 0.05). The lymph node detection rate of the experimental group was higher than that of the control group (P < 0.05), but there was no significant difference in the lymph node metastasis rate between the two groups (P > 0.05). The sentinel lymph node sensitivity of the experimental group reached 92.3%, and the specificity, accuracy, and positive and negative prediction rates reached 100%; the experimental group patients were with an obviously higher incidence of level I-II gastrointestinal reaction (P < 0.05). Postoperative increases in Bifidobacteria and Lactobacillus were observed in both groups, while decreases in Enterococcus and Escherichia coli were observed in both groups (P < 0.05). Moreover, the degree of increase and decrease in the experimental group was greater than that in the control group (P < 0.05). The serum levels of EGFR, IL-32, and gastrin 17 in the two groups were significantly lower than those in the control group on 3 d, 7 d, and 15 d after surgery (P < 0.05). In the radical gastrectomy for distal gastric cancer, carbon nanoparticle laparoscopy was not only helpful for the localization of small tumors but also for the thorough dissection of lymph nodes after the surgery, and the postoperative adverse reactions of carbon nanoparticle laparoscopy were also less, which was of great significance for the improvement of intestinal flora and the reduction of serum levels of EGFR, IL-32, and gastrin 17 in gastric cancer patients.

Prevalence and risk factors of severe postpartum hemorrhage: a retrospective cohort study.

BACKGROUND: Although maternal deaths are rare in developed regions, the morbidity associated with severe postpartum hemorrhage (SPPH) remains a major problem. To determine the prevalence and risk factors of SPPH, we analyzed data of women who gave birth in Guangzhou Medical Centre for Critical Pregnant Women, which received a large quantity of critically ill obstetric patients who were transferred from other hospitals in Southern China. METHODS: In this study, we conducted a retrospective case-control study to determine the prevalence and risk factors for SPPH among a cohort of women who gave birth after 28 weeks of gestation between January 2015 and August 2019. SPPH was defined as an estimated blood loss ≥1000 mL and total blood transfusion≥4 units. Logistic regression analysis was used to identify independent risk factors for SPPH. RESULTS: SPPH was observed in 532 mothers (1.56%) among the total population of 34,178 mothers. Placenta-related problems (55.83%) were the major identified causes of SPPH, while uterine atony without associated retention of placental tissues accounted for 38.91%. The risk factors for SPPH were maternal age < 18 years (adjusted OR [aOR] = 11.52, 95% CI: 1.51-87.62), previous cesarean section (aOR = 2.57, 95% CI: 1.90-3.47), history of postpartum hemorrhage (aOR = 4.94, 95% CI: 2.63-9.29), conception through in vitro fertilization (aOR = 1.78, 95% CI: 1.31-2.43), pre-delivery anemia (aOR = 2.37, 95% CI: 1.88-3.00), stillbirth (aOR = 2.61, 95% CI: 1.02-6.69), prolonged labor (aOR = 5.24, 95% CI: 3.10-8.86), placenta previa (aOR = 9.75, 95% CI: 7.45-12.75), placenta abruption (aOR = 3.85, 95% CI: 1.91-7.76), placenta accrete spectrum (aOR = 8.00, 95% CI: 6.20-10.33), and macrosomia (aOR = 2.30, 95% CI: 1.38-3.83). CONCLUSION: Maternal age < 18 years, previous cesarean section, history of PPH, conception through IVF, pre-delivery anemia, stillbirth, prolonged labor, placenta previa, placental abruption, PAS, and macrosomia were risk factors for SPPH. Extra vigilance during the antenatal and peripartum periods is needed to identify women who have risk factors and enable early intervention to prevent SPPH.

Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients. METHODS: DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform. RESULTS: According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection. CONCLUSIONS: GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.

DeepHPV: a deep learning model to predict human papillomavirus integration sites.

Human papillomavirus (HPV) integrating into human genome is the main cause of cervical carcinogenesis. HPV integration selection preference shows strong dependence on local genomic environment. Due to this theory, it is possible to predict HPV integration sites. However, a published bioinformatic tool is not available to date. Thus, we developed an attention-based deep learning model DeepHPV to predict HPV integration sites by learning environment features automatically. In total, 3608 known HPV integration sites were applied to train the model, and 584 reviewed HPV integration sites were used as the testing dataset. DeepHPV showed an area under the receiver-operating characteristic (AUROC) of 0.6336 and an area under the precision recall (AUPR) of 0.5670. Adding RepeatMasker and TCGA Pan Cancer peaks improved the model performance to 0.8464 and 0.8501 in AUROC and 0.7985 and 0.8106 in AUPR, respectively. Next, we tested these trained models on independent database VISDB and found the model adding TCGA Pan Cancer performed better (AUROC: 0.7175, AUPR: 0.6284) than the model adding RepeatMasker peaks (AUROC: 0.6102, AUPR: 0.5577). Moreover, we introduced attention mechanism in DeepHPV and enriched the transcription factor binding sites including BHLHA15, CHR, COUP-TFII, DMRTA2, E2A, HIC1, INR, NPAS, Nr5a2, RARa, SCL, Snail1, Sox10, Sox3, Sox4, Sox6, STAT6, Tbet, Tbx5, TEAD, Tgif2, ZNF189, ZNF416 near attention intensive sites. Together, DeepHPV is a robust and explainable deep learning model, providing new insights into HPV integration preference and mechanism. Availability: DeepHPV is available as an open-source software and can be downloaded from https://github.com/JiuxingLiang/DeepHPV.git, Contact: huzheng1998@163.com, liangjiuxing@m.scnu.edu.cn, lizheyzy@163.com.

Contact sensitization to cosmetic series of allergens in female patients with rosacea: A prospective controlled study in China.

BACKGROUND: Allergic contact dermatitis to cosmetics (ACDC) complicates the diagnosis and treatment of rosacea, and is increasingly observed in daily practice. AIMS: The present study aimed to identify the contact allergens responsible for ACDC in Chinese female rosacea patients with or without suspected ACDC (SACDC). METHODS: From a total of 1267 women with rosacea, 122 with SACDC, 145 without SACDC, and 100 age-matched healthy controls without rosacea or SACDC were examined on a voluntary basis. Skin patch tests with C-1000 cosmetic series (Chemotechnique Diagnostics, Malmo, Sweden) were conducted, including 20 selected allergens. RESULTS: Positive allergic reaction was found in 85.2% and 33.8% of SACDC and non-SACDC (P < .001), respectively, and 27.0% of healthy volunteers. Most reactions occurred at day 3, and the majority of all the examinees including normal controls reacted to more than 1 allergen. In SACDC patients, leading allergens were methylchloroisothiazolinone/methylisothiazolinone (28.7%), linalool hydroperoxide (27.1%), fragrance mix I (21.3%), methylisothiazolinone (17.2%), limonene hydroperoxides (16.4%), formaldehyde (14.8%), myroxylon pereirae (13.9%), and propolis (10.7%); the overall allergic reaction rate positively correlated with new onset of facial pruritus (P < .001). The occurrence of irritant contact reactions correlated with positive allergic reactions in rosacea patients with or without SACDC (P = .032 or P < .001, respectively). CONCLUSIONS: Preservatives and fragrances are primary culprits for ACDC in Chinese female rosacea patients. Patch testing should be considered in the suspected patients.

Genetic research and clinical analysis of deletional Chinese Gγ+(Aγδß)0 -thalassemia and Southeast Asian HPFH in South China.

Chinese Gγ+(Aγδß)0-thalassemia and SEA-HPFH are the most common types of ß-globin gene cluster deletion in Chinese population. The aim of the study was to analyze clinical features of deletional Chinese Gγ+(Aγδß)0-thalassemia and Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH) in South China. A total of 930 subjects with fetal hemoglobin (HbF) level ≥ 2% were selected on genetic research of Chinese Gγ+(Aγδß)0-thalassemia and SEA-HPFH. The gap polymerase chain reaction was performed to identify the deletions. One hundred cases of Chinese Gγ+(Aγδß)0-thalassemia were detected, including 90 cases of Chinese Gγ+(Aγδß)0/ßN-thalassemia, 7 cases of Chinese Gγ+(Aγδß)0 /ßN-thalassemia combined with α-thalassemia, 2 cases of Chinese Gγ+(Aγδß)0-thalassemia combined with ß-thalassemia, and 1 case of Chinese Gγ+(Aγδß)0-thalassemia combined with ß-gene mutation. One hundred nine cases of SEA-HPFH were detected, including 97 cases of SEA-HPFH/ßN, 9 cases of SEA-HPFH/ßN combined with α-thalassemia, 2 cases of SEA-HPFH combined with ß-thalassemia, and 1 case of SEA-HPFH combined with ß-gene mutation. Statistical analysis indicates significant differences in MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), and HbA2 and HbF levels between Chinese Gγ+(Aγδß)0-thalassemia heterozygotes and SEA-HPFH heterozygotes (P < 0.001). There are statistical differences in hematological parameters between them. Clinical phenotypic analysis can provide guidance for genetic counseling and prenatal diagnosis.

Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a pilot city in China.

BACKGROUND: Cell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China. METHODS: A total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed. RESULTS: Among 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives. CONCLUSIONS: This study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.

The Role of Cyclooxygenase-2 in Colorectal Cancer.

Colorectal cancer is the third common cancer in this world, accounting for more than 1 million cases each year. However, detailed etiology and mechanism of colorectal cancer have not been fully understood. For example, cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) have been closely linked to its occurrence, progression and prognosis. However, the mechanisms on how COX-2 and PGE2-mediate the pathogenesis of colorectal cancer are obscure. In this review, we have summarized recent advances in studies of pathogenesis and control in colorectal cancer to assist further advances in the research for the cure of the cancer. In addition, the knowledge gained may also guide the audiences for reduction of the risk and control of this deadly disease.

MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/ß-catenin signaling pathway and affects the biological functions of colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. AIM: To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms. METHODS: Sixty-two CRC patients admitted to the hospital were enrolled into the study group, and sixty healthy people from the same period were assigned to the control group. Elbow venous blood was sampled from the patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p mimics, miR-19a-3p inhibitor, miR-negative control, small interfering-FOXF2, and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and western blot (WB) analysis was conducted to evaluate the levels of FOXF2, glycogen synthase kinase 3 beta (GSK-3ß), phosphorylated GSK-3ß (p-GSK-3ß), ß-catenin, p-ß-catenin, α-catenin, N-cadherin, E-cadherin, and vimentin. The MTT, Transwell, and wound healing assays were applied to analyze cell proliferation, invasion, and migration, respectively, and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2. RESULTS: The patients showed high serum levels of miR-19a-3p and low levels of FOXF2, and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8. MiR-19a-3p and FOXF2 were related to sex, tumor size, age, tumor-node-metastasis staging, lymph node metastasis, and differentiation of CRC patients. Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelial-mesenchymal transition, invasion, migration, and proliferation of cells. WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3ß, ß-catenin, N-cadherin, and vimentin; and increased the levels of GSK-3ß, p-ß-catenin, α-catenin, and E-cadherin. The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2. In addition, a rescue experiment revealed that there were no differences in cell proliferation, invasion, and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group. CONCLUSION: Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/ß-catenin signaling pathway, thereby affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells. Thus, miR-19a-3p is likely to be a therapeutic target in CRC.

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis.

Chronic obstructive pulmonary disease (COPD) is a multifactorial and heterogeneous disease that creates public health challenges worldwide. The underlying molecular mechanisms of COPD are not entirely clear. In this study, we aimed to identify the critical genes and potential molecular mechanisms of COPD by bioinformatic analysis. The gene expression profiles of lung tissues of COPD cases and healthy control subjects were obtained from the Gene Expression Omnibus. Differentially expressed genes were analyzed by integration with annotations from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by construction of a protein-protein interaction network and weighted gene coexpression analysis. We identified 139 differentially expressed genes associated with the progression of COPD, among which 14 Hub genes were identified and found to be enriched in certain categories, including immune and inflammatory response, response to lipopolysaccharide and receptor for advanced glycation end products binding; in addition, these Hub genes are involved in multiple signaling pathways, particularly hematopoietic cell lineage and cytokine-cytokine receptor interaction. The 14 Hub genes were positively or negatively associated with COPD by wgcna analysis. The genes CX3CR1, PTGS2, FPR1, FPR2, S100A12, EGR1, CD163, S100A8 and S100A9 were identified to mediate inflammation and injury of the lung, and play critical roles in the pathogenesis of COPD. These findings improve our understanding of the underlying molecular mechanisms of COPD.