[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies.

This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot meta-analysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, ß = -0.169, 95% CI = -0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal ∑DEHP exposure with z-SBP (ß = -0.109, 95% CI = -0.163 to -0.055) and z-diastolic BP (DBP, ß = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (ß = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal ∑DEHP exposure and triglycerides (ß = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to ∑DEHP throughout gestation was associated with a decrease in insulin (ß = -0.074, 95% CI = -0.144 to -0.004) and glucose (ß = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (ß = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal ∑DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.

Comparison of structures and emulsifying properties between water-extracted pectins from Fructus aurantii.

The structural characteristics of two water-extracted pectic polysaccharides from Fructus aurantii were investigated, and the impacts of their structures on the emulsifying stability were evaluated. FWP-60 (extracted by cold water and followed 60 % ethanol precipitation) and FHWP-50 (extracted by hot water and followed 50 % ethanol precipitation) were both high methyl-esterified pectins, which were composed of homogalacturonan (HG) and highly branched rhamnogalacturonan I (RG-I) regions. The weight-average molecular weight, methyl-esterification degree (DM) and HG/RG-I ratio of FWP-60 were 1200 kDa, 66.39 % and 4.45, respectively, which were 781 kDa, 79.10 % and 1.95 for FHWP-50. The methylation and NMR analysis of FWP-60 and FHWP-50 demonstrated that the main backbone consisted of different molar ratios of →4)-α-GalpA-(1 â†’ and →4)-α-GalpA-6-O-methyl-(1 →, and the side chains contained arabinan and galactan. Moreover, the emulsifying properties of FWP-60 and FHWP-50 were discussed. Compared with FHWP-50, FWP-60 had better emulsion stability. Overall, pectin had a linear HG domain and a small number of RG-I domain with short side chains to facilitate the stabilization of emulsions in Fructus aurantii. A comprehensive knowledge of the structure characteristic and emulsifying property would enable us to provide more information and theoretical guidance for the structure and emulsion preparation of Fructus aurantii pectic polysaccharides.

Bergamotane-type sesquiterpenes from the leaves and twigs of Illicium oligandrum and their anti-inflammatory activities.

Eight undescribed ß-bergamotene-type sesquiterpene oliganins A-H (1-8) and one known α-bergamotene-type sesquiterpene (9) were isolated from the leaves and twigs of Illicium oligandrum Merr. & Chun. The structures of compounds 1-8 were elucidated by extensive spectroscopic data, and the absolute configurations were determined by using a modified Mosher's method and electronic circular dichroism calculations. The isolates were further evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. Compounds 2 and 8 exhibited potent inhibitory effects on the production of NO with IC50 values ranging from 21.65 to 49.28 µM, which were greater than or comparable to those of dexamethasone (positive control).

Association of sodium-glucose cotransporter 2 inhibitors with cardiovascular outcome and safety events: A meta-analysis of randomized controlled clinical trials.

Background: The clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the effect of SGLT2 inhibitors on cardiovascular outcomes and safety events, giving particular attention to the benefits in subgroups of patients with different diseases. Method: Randomized controlled trials (RCTs) reporting cardiovascular outcomes following the administration of SGLT2 inhibitors and placebo were included in this study. Cardiovascular outcomes included all-cause death, major adverse cardiovascular events (MACEs), cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF). We also focused on the cardiovascular benefits of SGLT2 inhibitor application in subgroups of patients with different diseases, including type 2 diabetes (T2D), heart failure (HF), high risk of atherosclerotic cardiovascular disease (ACD), diagnosed ACD, and chronic kidney disease (CKD). Safety events associated with SGLT2 inhibitors, including acute kidney injury (AKI), diabetic ketoacidosis (DKA), hypoglycemia, urinary tract infection, thromboembolic event, bone fracture, volume depletion, and amputation, were also reported. Results: This meta-analysis included 15 RCTs with 78,212 participants. SGLT2 inhibitors reduced the risk of all-cause death (RR 0.89; 95% CI: 0.85-0.94; I2 = 32%; p < 0.01), CV death (RR 0.87; 95% CI: 0.82-0.93; I2 = 11%; p < 0.01), MACEs (RR 0.89; 95% CI: 0.84-0.94; I2 = 46%; p < 0.01), HHF (RR 0.70; 95% CI: 0.66-0.74; I2 = 0%; p < 0.01), and AKI (RR 0.81; 95% CI: 0.73-0.90; I2 = 0%; p < 0.01) but increased the risk of DKA (RR 2.56; 95% CI: 1.72-3.80; I2 = 0%; p < 0.01). However, no apparent benefit in MI and stroke was observed between the SGLT2 inhibitor and control groups. SGLT2 inhibitors reduced the risk of all-cause death, MACEs, CV death, and HHF in diabetic patients; reduced the risk of all-cause death, MACEs, CV death, MI, and HHF in primary prevention; reduced the risk of all-cause death, CV death, and HHF in patients with ACD and HF; and reduced the risk of MACEs, CV death, and HHF in patients with CKD. Conclusion: SGLT2 inhibitors have a positive effect in reducing the risk of all-cause death, CV death, MACE, HHF, and AKI and increasing the risk of DKA. The application of SGLT2 inhibitors in the primary prevention of ACD also has certain clinical benefits in reducing MI. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306490].

Identification of Tumor Antigens and Immune Subtypes of Esophageal Squamous Cell Carcinoma for mRNA Vaccine Development.

Purpose: The applicability of mRNA vaccines against esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we identified potential antigens for developing mRNA vaccines against ESCC and characterized immune subtypes to select appropriate patients for vaccination. Methods: RNA-seq, genetic alteration data, and corresponding clinical information of ESCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The RNA-seq data of normal esophageal tissue were obtained from the Genotype-Tissue Expression (GTEx) database. Potential tumor antigens were screened by analyzing differentially expressed and mutated genes and potential antigens with significant differences in prognosis were screened using the Kaplan-Meier method. The proportion of immune cell infiltration in the tumor microenvironment was estimated using CIBERSORT and MCPcounter, and the correlation of potential antigens with antigen-presenting cells and major histocompatibility complex class II was analyzed. Subsequently, immune subtypes were constructed using consensus clustering analysis and characterized by single-sample gene set enrichment analysis and weighted gene co-expression network analysis (WGCNA). The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to analyze the drug sensitivity of different immune subtypes. Results: Four overexpressed and mutated tumor antigens associated with antigen presentation and poor prognosis were identified in ESCC, including NLRC5, FCRL4, TMEM229B, and LCP2. By consensus clustering, we identified two immune-associated ESCC subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2); the prognosis of the two subtypes was statistically different. In addition, the two immune subtypes had distinctly different cellular, molecular, and clinical characteristics. IS1 patients have a distinct immune "hot" phenotype with strong immune tolerance, whereas patients with IS2 have an immune "cold" phenotype. Differential expression of immune checkpoints and immunogenic cell death modulators was observed between the different immune subtypes. Finally, we found that IS1 and IS2 patients showed different drug sensitivities to common anti-tumor drugs, possibly facilitating the development of individualized treatment regimens for patients. Conclusion: NLRC5, LCP2, TMEM229B, and FCRL4 are potential antigens for ESCC mRNA vaccines, and such vaccines may be more suitable for IS2 patients. This study provides a theoretical basis for mRNA vaccines against ESCC, by identifying the critical characteristics to predict ESCC prognosis and select suitable patients for vaccination.

Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats.

The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion (tMCAO) and reperfusion. Quercetin (10, 30, 50 mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats.

Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma.

We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.

A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism.

Emerging evidence suggests that cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in cancer and the development of PHGDH inhibitors in drug discovery.

Identification of novel STAT3 inhibitors bearing 2-acetyl-7-phenylamino benzofuran scaffold for antitumour study.

Signal transducer and activator of transcription 3 (STAT3) is identified as a promising target for multiple cancer therapy and attracts widespread concern. Herein, we reported the discovery of a series of 2-acetyl-7-phenylamino benzofuran derivatives as STAT3 inhibitors using scaffold fusion strategy. Further structure activity relationship study led to the discovery of compound C6, which displayed the most potent anti-proliferation activities against MDA-MB-468 cells (IC50 = 0.16 µM). Western blot assay demonstrated that C6 inhibited the activation of STAT3 (Tyr705) without influencing the phosphorylation of STAT1 (Tyr701). Further mechanistic studies indicated that C6 caused a notable G2/M cycle-arresting and early apoptosis in a concentration-dependent manner in MDA-MB-468 cells. Finally, molecular modelling study elucidated the binding mode of C6 in STAT3 SH2 domain.

Transanal minimally invasive surgery vs endoscopic mucosal resection for rectal benign tumors and rectal carcinoids: A retrospective analysis.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) is a good choice for resection of rectal neoplasms. Endoscopic mucosal resection (EMR) is also widely used in the treatment of benign rectal tumors such as rectal polyps and rectal adenomas. However, no studies have compared the outcome of TAMIS and EMR. AIM: To compare the short-term outcomes after TAMIS and EMR for rectal carcinoid and benign tumors (including rectal polyps and adenomas). METHODS: From January 2014 to January 2019, 44 patients who received TAMIS and 53 patients who received EMR at The Fifth People's Hospital of Shanghai were selected. Primary outcomes (surgical-related) were operating time, blood loss, length of postoperative hospital stay, rate of resection margin involvement and lesion fragmentation rate. The secondary outcomes were complications such as hemorrhage, urinary retention, postoperative infection and reoperation. RESULTS: No significant differences were observed in terms of blood loss (12.48 ± 8.00 mL for TAMIS vs 11.45 ± 7.82 mL for EMR, P = 0.527) and length of postoperative hospital stay (3.50 ± 1.87 d for TAMIS vs 2.72 ± 1.98 d for EMR, P = 0.065) between the two groups. Operating time was significantly shorter for EMR compared with TAMIS (21.19 ± 9.49 min vs 49.95 ± 15.28 min, P = 0.001). The lesion fragmentation rate in the EMR group was 22.6% (12/53) and was significantly higher than that (0%, 0/44) in the TAMIS group (P = 0.001). TAMIS was associated with a higher urinary retention rate (13.6%, 6/44 vs 1.9%, 1/53 P = 0.026) and lower hemorrhage rate (0%, 0/44 vs 18.9%, 10/53 P = 0.002). A significantly higher reoperation rate was observed in the EMR group (9.4%, 5/53 vs 0%, 0/44 P = 0.036). CONCLUSION: Compared with EMR, TAMIS can remove lesions more completely with effective hemostasis and lower postoperative hemorrhage and reoperation rates. TAMIS is a better choice for the treatment of rectal carcinoids.

Design, synthesis and biological evaluation of novel potent STAT3 inhibitors based on BBI608 for cancer therapy.

Persistently activated signal transducer and activator of transcription 3 (STAT3) plays an important role in the development of multiple cancers, and therefore is a potential therapeutic target for cancer prevention. Herein, we report the rational design, synthesis, and biological evaluation of novel potent STAT3 inhibitors based on BBI608. Among them, compound A11 exhibited the most potent in vitro tumor cell growth inhibitory activities toward MDA-MB-231, MDA-MB-468 and HepG2 cells with IC50 values as low as 0.67 ± 0.02 µM, 0.77 ± 0.01 µM and 1.24 ± 0.16 µM, respectively. Fluorescence polarization (FP) assay validated the binding of compound A11 in STAT3 SH2 domain with the IC50 value of 5.18 µM. Further mechanistic studies indicated that A11 inhibited the activation of STAT3 (Y705), and thus reduced the expression of STAT3 downstream genes CyclinD1 and C-Myc. Simultaneously, it induced cancer cell S phase arrest and apoptosis in a concentration-dependent manner. An additional in vivo study revealed that A11 suppressed the MDA-MB-231 xenograft tumor growth in mice at the dose of 10 mg/kg (i.p.) without obvious body-weight loss. Finally, molecular docking study further elucidated the binding mode of A11 in STAT3 SH2 domain.

Construction of a 26­feature gene support vector machine classifier for smoking and non­smoking lung adenocarcinoma sample classification.

The present study aimed to identify the feature genes associated with smoking in lung adenocarcinoma (LAC) samples and explore the underlying mechanism. Three gene expression datasets of LAC samples were downloaded from the Gene Expression Omnibus database through pre­set criteria and the expression data were processed using meta­analysis. Differentially expressed genes (DEGs) between LAC samples of smokers and non­smokers were identified using limma package in R. The classification accuracy of selected DEGs were visualized using hierarchical clustering analysis in R language. A protein­protein interaction (PPI) network was constructed using gene interaction data from the Human Protein Reference Database for the DEGs. Betweenness centrality was calculated for each node in the network and genes with the greatest BC values were utilized for the construction of the support vector machine (SVM) classifier. The dataset GSE43458 was used as the training dataset for the construction and the other datasets (GSE12667 and GSE10072) were used as the validation datasets. The classification accuracy of the classifier was tested using sensitivity, specificity, positive predictive value, negative predictive value and area under curve parameters with the pROC package in R language. The feature genes in the SVM classifier were subjected to pathway enrichment analysis using Fisher's exact test. A total of 347 genes were identified to be differentially expressed between samples of smokers and non­smokers. The PPI network of DEGs were comprised of 202 nodes and 300 edges. An SVM classifier comprised of 26 feature genes was constructed to distinguish between different LAC samples, with prediction accuracies for the GSE43458, GSE12667 and GSE10072 datasets of 100, 100 and 94.83%, respectively. Furthermore, the 26 feature genes that were significantly enriched in 9 overrepresented biological pathways, including extracellular matrix­receptor interaction, proteoglycans in cancer, cell adhesion molecules, p53 signaling pathway, microRNAs in cancer and apoptosis, were identified to be smoking­related genes in LAC. In conclusion, an SVM classifier with a high prediction accuracy for smoking and non­smoking samples was obtained. The genes in the classifier may likely be the potential feature genes associated with the development of patients with LAC who smoke.

Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo.

AIM: To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS). METHODS: Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 µg), and a model + high-dose toxin (ADHT; n = 20, 20 µg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa. RESULTS: Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05). CONCLUSION: Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Study on Adsorption and Desorption Characteristics of Cd2+ and Cu2+ on the Surface Sediments of Sanhuhekou of Yellow River by Using ICP-MS.

In order to study the interaction mechanism between Cd2+, Cu2+ and surface sediments in the upper reaches of the Yellow River, the surface sediment of Sanhuhekou (YRSSM) was chosen as research object with inductively coupled plasma mass spectrometry (ICP-MS) as analysis method. The adsorption reaction condition such as liquid-solid ratio, reaction time and pH were optimized, and the adsorption and desorption characteristics of Cd2+ and Cu2+ onto the surface sediments under the optimized experimental conditions were studied. The results showed that the adsorption capacity of Cu2+ was greater than that of Cd2+, the equilibrium absorption capacity were 0.88 and 0.13 mg·g-1 under each optimum experimental condition, respectively. The adsorptions of Cu2+ and Cd2+ were in accord with the pseudo-second-order kinetic, while adsorption rate of Cu2+ was also greater than that of Cd2+. The adsorption thermodynamics data were in accordance with the Freundlich model and the fitting. Results showed that the adsorption process of Cu2+ and Cd2+ belonged to the preferential adsorption, and were endothermic and spontaneous processes. The desorption process showed that the Elovich equation were suitable for Cd2+ and Cu2+ and belonged to the heterogeneous diffusion. Multi-ions competitive adsorption and desorption experiments indicated that Cu2+ was influenced more by co-existing ion. The study revealed not only the mechanism of adsorption and desorption between Cd2+, Cu2+ and surface sediment in Sanhuhekou, but also the influence of coexisting ions on the adsorption and desorption characteristics. The results demonstrated that the distribution mechanism of heavy metals between solid-liquid phases, and provided a theoretical basis for the migration ability of heavy metals. It also had a guiding significance for establishing heavy metals preventive and control measures of the study area.

Structural shift of gut microbiota during chemo-preventive effects of epigallocatechin gallate on colorectal carcinogenesis in mice.

AIM: To investigate the effect of epigallocatechin gallate (EGCG) on structural changes of gut microbiota in colorectal carcinogenesis. METHODS: An azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis mouse model was established. Forty-two female FVB/N mice were randomly divided into the following three groups: group 1 (10 mice, negative control) was treated with vehicle, group 2 (16 mice, positive control) was treated with AOM plus vehicle, and group 3 (16 mice, EG) was treated with AOM plus EGCG. For aberrant crypt foci (ACF) evaluation, the colons were rapidly took out after sacrifice, rinsed with saline, opened longitudinally, laid flat on a polystyrene board, and fixed with 10% buffered formaldehyde solution before being stained with 0.2% methylene blue in saline. For tumor evaluation, the colon was macroscopically inspected and photographed, then the total number of tumors was enumerated and tumor size measured. For histological examination, the fixed tissues were paraffin-embedded and sectioned at 5 mm thickness. Microbial genomic DNA was extracted from fecal and intestinal content samples using a commercial kit. The V4 hypervariable regions of 16S rRNA were PCR-amplified with the barcoded fusion primers. Using the best hit classification option, the sequences from each sample were aligned to the RDP 16S rRNA training set to classify the taxonomic abundance in QIIME. Statistical analyses were then performed. RESULTS: Treatment of mice with 1% EGCG caused a significant decrease in the mean number of ACF per mouse, when compared with the model mice treated with AOM/DSS (5.38 ± 4.24 vs 13.13 ± 3.02, P < 0.01). Compared with the positive control group, 1% EGCG treatment dependently decreased tumor load per mouse by 85% (33.96 ± 6.10 vs 2.96 ± 2.86, respectively, P < 0.01). All revealed that EGCG could inhibit colon carcinogenesis by decreasing the number of precancerous lesions as well as solid tumors, with reduced tumor load and delayed histological progression of CRC. During the cancerization, the diversity of gut microbiota increased, potential carcinogenic bacteria such as Bacteroides were enriched, and the abundance of butyrate-producing bacteria (Clostridiaceae, Ruminococcus, etc.) decreased continuously. In contrast, the structure of gut microbiota was relatively stable during the intervention of EGCG on colon carcinogenesis. Enrichment of probiotics (Bifidobacterium, Lactobacillu, etc.) might be a potential mechanism for EGCG's effects on tumor suppression. Via bioinformatics analysis, principal coordinate analysis and cluster analysis of the tumor formation process, we found that the diversity of gut microbiota increased in the tumor model group while that in the EGCG interfered group (EG) remained relatively stable. CONCLUSION: Gut microbiota imbalance might be a potential mechanism for the prevention of malignant transformation by EGCG, which is significant for diagnosis, treatment, prognosis evaluation, and prevention of colorectal cancer.

Five miRNAs Considered as Molecular Targets for Predicting Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is one of the most aggressive malignant gastrointestinal tumors; however the traditional therapies for EC are not effective enough. Great improvements are needed to explore new and valid treatments for EC. We aimed to screen the differentially expressed miRNAs (DEMs) in esophageal cancer and explore the pathogenesis of esophageal cancer along with functions and pathways of the target genes. MATERIAL AND METHODS: miRNA high-throughput sequencing data were downloaded from The Cancer Genome Atlas (TCGA), then the DEMs underwent principal component analysis (PCA) based on their expression value. Following that, TargetScan software was used to predict the target genes, and enrichment analysis and pathway annotation of these target genes were done by DAVID and KEGG, respectively. Finally, survival analysis between the DEMs and patient survival time was done, and the miRNAs with prediction potential were identified. RESULTS: A total of 140 DEMs were obtained, 113 miRNAs were up-regulated including hsa-mir-153-2, hsa-mir-92a-1 and hsa-mir-182; while 27 miRNAs were down-regulated including hsa-mir comprising 29a, hsa-mir-100 and hsa-mir-139 and so on. Five miRNAs (hsa-mir-103-1, hsa-mir-18a, hsa-mir-324, hsa-mir-369 and hsa-mir-320b-2) with diagnostic and preventive potential were significantly correlated with survival time. CONCLUSIONS: The crucial molecular targets such as p53 may provide great clinical value in treatment, as well to provide new ideas for esophageal cancer therapy. The target genes of miRNA were found to play key roles in protein phosphorylation, and the functions of the target genes during protein phosphorylation should be further studied to explore novel treatment of EC.

[Clinical application regularity of Fengfu (GV 16) acupoint: research on ancient Chinese medical literature].

OBJECTIVE: To sum up the application regularity of Fengfu (GV 16) acupoint in clinical practice through studying the ancient literature from the early stage of the Qin Dynasty to the Qing Dynasty. METHODS: Chinese ancient medical literature relevant to Fengfu (GV 16) was searched to establish a database containing information of clinical indications of GV 16, supplementary acupoints, relevant needling techniques, moxibustion methods, etc. RESULTS: A total of 277 articles about Fengfu (GV 16) for 61 types of clinical disorders or diseases involving internal medicine, surgery, paediatrics, five sense organs, etc. were obtained from 2,200 ancient Chinese medical books. Fengfu (GV 16) alone was most frequently used for treatment of disorders caused by exogenous factors, such as common cold, neck pain, headache, epilepsy, mania, dizziness, throat dumb, leg-foot problems, etc. , with the auxiliary acupoint being Fengchi (GB 20). In addition, 147 articles relevant to needling and moxibustion stimulation of GV 16 (7 types of methods) were found. CONCLUSION: Fengfu (GV 16) is mainly used for local problems in the human body, and also for problems occurred along the meridian trace, aiming at the pathogenesis. When employed, GV 16 is often stimulated by acupuncture needle.