Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.

Updates on global epidemiology, risk and prognostic factors of gastric cancer.

Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China.

BACKGROUND: The gut microbiota (GM) has been proven to play a role in the regulation of host lipid metabolism, which provides a new theory about the pathogenesis of dyslipidemia. However, the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation. AIM: To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population. METHODS: This study ultimately recruited 142 participants (73 females and 69 males) at Honghui Hospital, Xi'an Jiaotong University. The anthropometric and blood metabolic parameters of all participants were measured. According to their serum lipid levels, female and male participants were classified into a high triglyceride (H_TG) group, a high total cholesterol (H_CHO) group, a low high-density lipoprotein cholesterol (L_HDL-C) group, and a control (CON) group with normal serum lipid levels. Fresh fecal samples were collected for 16S rRNA gene sequencing. UPARSE software, QIIME software, the RDP classifier and the FAPROTAX database were used for sequencing analyses. RESULTS: The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM. Different GM features were identified between females and males, and the associations between GM and serum lipid profiles were different in females and males. The GM features in different dyslipidemia subgroups changed in both female patients and male patients. Proteobacteria, Lactobacillaceae, Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females, while Coriobacteriia were enriched in L_HDL-C females. In the comparison among the three dyslipidemia subgroups in females, Lactobacillus_salivarius were enriched in H_CHO females, and Prevotellaceae were enriched in L_HDL-C females. Compared with CON or H_TG males, Prevotellaceae, unidentified_Ruminococcaceae, Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males (P value < 0.05), and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups. Additionally, Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels, and Roseburia were positively correlated with serum TG level. Furthermore, Proteobacteria (0.724, 95%CI: 0.567-0.849), Lactobacillaceae (0.703, 95%CI: 0.544-0.832), Lactobacillus (0.705, 95%CI: 0.547-0.834) and Lactobacillus_salivarius (0.706, 95%CI: 0.548-0.835) could distinguish H_CHO females from CON females, while Coriobacteriia (0.710, 95%CI: 0.547-0.841), Coriobacteriales (0.710, 95%CI: 0.547-0.841), Prevotellaceae (0.697, 95%CI: 0.534-0.830), Roseburia (0.697, 95%CI: 0.534-0.830) and Roseburia_inulinivorans (0.684, 95%CI: 0.520-0.820) could discriminate H_TG males from CON males. Based on the predictions of GM metabolic capabilities with the FAPROTAX database, a total of 51 functional assignments were obtained in females, while 38 were obtained in males. This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females, but decreased in L_HDL-C males compared with CON males. CONCLUSION: This study indicates associations of GM with serum lipid profiles, supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia, and sex differences should be considered.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori (H. pylori) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM: To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS: Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS: In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION: After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.

Ultrasound-Guided Percutaneous Needle Biopsy for Peripheral Pulmonary Lesions: Diagnostic Accuracy and Influencing Factors.

A retrospective study was carried out to evaluate the diagnostic accuracy and the factors influencing the diagnostic accuracy of 648 procedures of ultrasound-guided percutaneous needle biopsy (PNB) for peripheral pulmonary lesions (PPLs). We reviewed the histopathology results, the clinical records and the procedure reports of these 648 biopsies and the final diagnoses of 637 PPLs to determine the diagnostic accuracy of ultrasound-guided PNB. Factors that influenced the diagnostic accuracy were assessed by analysis of the biopsy procedures, which were classified as diagnostic cases (true-positive and true-negative) and non-diagnostic cases (false-positive, false-negative and indeterminate). Statistical analyses of factors that related to patient demographic characteristics, lesion characteristics and biopsy details were performed to determine possible effects on diagnostic accuracy. Biopsies were successfully performed in all cases, and 11 patients underwent second biopsies for the same lesions. Among the 637 PPLs, there were 326 (51.2%) malignant lesions, 272 (42.7%) benign lesions and 39 (6.1%) indeterminate lesions. Of the 272 benign lesions, 114 (41.9%) were found to be tuberculous. The overall diagnostic accuracy was 81.8%, and the rates of hemoptysis, symptomatic pneumothorax and chest-tube insertion were 8.0%, 1.7% and 0.9%, respectively. Lesions sizes were divided into 3 groups according to the measurement by ultrasound. For lesions that measured ≤20 mm, 21-49 mm and ≥50 mm, the diagnostic accuracy was 72.0%, 86.8% and 79.7%, while sensitivity and specificity were 54.3%-79.2%, 88.3%-90.7% and 79.4%-89.5% and 77.3%-100%, 96.8%-100% and 58.6%-100%, respectively. Diagnostic accuracy was significantly affected by lesion size when lesion size was measured by ultrasound (p = 0.006) and computed tomography (CT) (p = 0.001). In the 3 lesion groups of ≤20 mm, 21-49 mm or ≥50 mm, diagnostic accuracy among each group was significantly different (p <0.001). When lesion size was measured by ultrasound (p <0.001) and CT (p <0.001) and the 3 groups were analyzed (p <0.001), there was a statistically significant relationship between lesion size and the presence of necrosis. The rates of the presence of necrosis in lesions that measured ≤20 mm, 21-49 mm and ≥50 mm were 3.9%, 11.7% and 28.8%, respectively. No significance was found for age (p = 0.119), gender (p = 0.25), lesion location (p = 0.55), the presence of necrosis (p = 0.226), patient position (p = 0.25), needle size (p = 0.26), puncture angle (p = 0.34) and needle passes (p = 0.21). Ultrasound-guided PNB is an effective and safe diagnostic method for PPLs; the diagnostic accuracy is significantly affected by lesion size and decreases in smaller (≤20 mm) and larger (≥50 mm) lesions.

The characteristics of screening and confirmatory test results for HIV in Xi'an, China.

OBJECTIVES: Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an. METHODS: A 4th-generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB). The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates. RESULTS: In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai (9.88%), XinChuang (10.87%) and Livzon (8.93%), p<0.05. CONCLUSION: HIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.