ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

BACKGROUND: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. OBJECTIVE: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. SEARCH STRATEGY: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. DATA EXTRACTION AND ANALYSIS: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. RESULTS: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. CONCLUSION Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
Female ; Humans ; Dysmenorrhea/therapy* ; Acupuncture Therapy ; Pain Management ; Needles ; Placebo Effect

OBJECTIVE: The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. METHODS: First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. RESULTS: In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. CONCLUSION Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.
Humans ; Animals ; Mice ; Insulin-Like Growth Factor I/pharmacology* ; Cellular Senescence ; Aging ; Hippocampus ; DNA Polymerase III

Objective: To analyze the association between body mass index (BMI) and coronary heart disease. Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank (CKB) in Qingdao, a total of 33 355 participants aged 30-79 years were included in the study. Cox regression analyses were performed to evaluate the association between BMI and coronary heart disease. Results: During the follow-up for an average 9.2 years, a total of 2 712 cases of ischemic heart disease (IHD) and 420 cases of major coronary events (MCE) were found. Multivariate Cox regression analysis showed that, compared with participants with normal BMI, the participants who were overweight had a 41% and 87% higher risk of IHD and MCE, the adjusted HR were 1.41 (95%CI: 1.27-1.56) and 1.87 (95%CI: 1.43-2.44), respectively. The participants who were obesity had 91% and 143% higher risk of IHD and MCE, the adjusted HR were 1.91 (95%CI: 1.72-2.13) and 2.43 (95%CI: 1.82-3.24), respectively. Conclusion: Overweight and obesity might increase the risk for IHD and MCE.
Body Mass Index ; Coronary Disease/epidemiology* ; Humans ; Myocardial Ischemia/epidemiology* ; Obesity/epidemiology* ; Overweight/epidemiology* ; Prospective Studies

Objective The present study was conducted to identify the Vibrio cholera type and to analyze its antibiotic resistance in an epidemic of cholera in Haiyan County in 2018, which would provide the references for prevention and control of cholera. Methods Stool samples of the patient and his close contacts as well as the food and environmental samples were collected for identification of the type of Vibrio cholerae and the toxin gene. The resistance of identified Vibrio cholerae to 20 different common antibiotics were tested. Results A total of 176 samples were collected, including 101 stool samples from the case and his close contacts, 35 environmental samples and 40 food samples. Among those samples, only one strain of V. cholerae, O139, was isolated from the patient's first feces sample. It was detected as a toxin gene of ctxA positive by real-time fluorescence PCR. Antibiotic resistance test showed that the strain was sensitive to norfloxacin, levofloxacin, ciprofloxacin, cefotaxime, cephalothin, ampicillin, and amoxicillin. It was 100% resistant to tetracycline, doxycycline, neomycin, kanamycin, streptomycin, and rifampicin. Conclusion V. cholerae O139 strain with ctxA is detected in an epidemic of cholera. Norfloxacin, levofluoxacin and some other antibiotics could be used for clinical treatment and prevention. It should pay attention to this strain of V. cholera regarding the multiple drug resistance and the change of antibiotic resistance.

OBJECTIVE: To investigate the prognosis-related miRNA histological features and clinical significance of lung adenocarcinoma. METHODS: Using The Cancer Genome Atlas (TCGA) data, the miRNA expression profile data of human lung adenocarcinoma were searched for differential analysis, and the prognosis-related miRNAs were screened by Cox risk regression model. The targeted miRNAs were predicted by mirwalk analysis platform, KEGG functional enrichment analysis, and finally, predict the function of prognosis-related miRNAs. RESULTS: A total of 46 differential miRNAs in lung adenocarcinoma were screened, including 19 up-regulated and 27 down-regulated. Six prognostic-related miRNAs were screened by Cox survival analysis, namely hsa-mir-21, hsa-mir-142, hsa-mir-200a high expression, hsa-mir-101, hsa-let-7c, hsa-mir-378e low expression, hsa-mir-21 and hsa-mir-378e were associated with poor prognosis in patients with lung adenocarcinoma, and the survival time was shortened significantly (<0.05, AUC=0.618). KEGG analysis showed that the above prognosis-related miRNA targeting regulatory genes were related with immune response pathways, miRNA and cancer pathways, metabolic pathways and so on. CONCLUSIONS Hsa-mir-21 and hsa-mir-378e are associated with poor prognosis of lung adenocarcinoma, and may be used as a molecular marker for prognosis of lung adenocarcinoma after further clinical verification.
Adenocarcinoma of Lung ; Biomarkers, Tumor ; Computational Biology ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; MicroRNAs ; Prognosis

OBJECTIVE: To investigate the characterization of the salivary microbiome in people with obesity and the differences in microbial composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight controls. METHODS: The study was carried out in people with obesity and age- and sex-matched normal weight controls. None of these selected participants had the systemic disease, oral mucosal disease or periodontal disease. Unstimulated saliva samples were collected and oral examination was conducted. DNAs from saliva samples were extracted and sequenced in an Illumina NextSeq 500 platform. Community composition, linear discriminant analysis of taxonomic differences,gene prediction, gene set construction and annotation of gene function were performed. RESULTS: The classified bacterial reads of the samples were 2 630 428 for each sample. A total of 11 phyla, 19 classes, 26 orders, 41 families, 62 genera and 164 species were detected ultimately. All samples had the same predominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria). There were statistical differences between the groups at the class, order, family, genus and species levels. At the class level, Negativicutes and Erysipelotrichia were more abundant in the obesity group, while Flavobacteriia and Bateroidetes dominated in normal weight group (P<0.05). At the species level, 16 showed significant differences in relative abundance among the groups, in which Prevotella melaninogenica,Prevotella salivae,Solobacterium moorei and Atopobium parvulum ware more abundant in the obesity group, whereas Streptococcus sanguinis dominated in normal weight group (P<0.05). The people with obesity had a higher number of salivary microbial genes (P<0.05). We produced statistics on gene prediction and found salivary microbiome of obesity group had a higher number of genes (P < 0.05). Genes associated with the pathways of metabolism and environmental information processing and human diseases were significantly enriched in the saliva samples of people with obesity (P < 0.01). CONCLUSION Significant differences were seen in composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight people. We hope to go on further study with larger sample size in the near future.
Bacteria/isolation & purification* ; Female ; Humans ; Male ; Microbiota ; Obesity/microbiology* ; Pilot Projects ; RNA, Ribosomal, 16S ; Saliva/microbiology*

The sialyl Lewis X (SLex) antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin (E-selectin).The combination of SLex antigen and E-selectin represents an important way for malignant tumor metastasis.In the present study,the effect of the SLeX-binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated.Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels.The SLex expression in HepG2 cells treated with different concentrations of SLeX-binding DNA aptamer was detected by flow cytometry.Besides,the adhesion,migration,and invasion of HepG2 cells were measured by cell adhesion assay,and the Transwell migration and invasion assay.The results showed that the FUT7 expression was up-regulated at both mRNA and protein levels in HepG2 cells.SLeX-binding DNA aptamer could significantly decrease the expression of SLex in HepG2 cells.The cell adhesion assay revealed that the SLeX-binding DNA aptamer could effectively inhibit the interactions between E-selectin and SLex in the HepG2 cells.Additionally,SLeX-binding DNA aptamers at 20 nmol/L were found to have the similar effect to the monoclonal antibody CSLEX-1.The Transwell migration and invasion assay revealed that the number of penetrating cells on the down-side of Transwell membrane was significantly less in cells treated with 5,10,20 nmol/L SLeX-binding DNA aptamer than those in the negative control group (P＜0.01).Our study demonstrated that the SLeX-binding DNA aptamer could significantly inhibit the in vitro adhesion,migration,and invasion of HepG2 cells,suggesting that the SLeX-binding DNA aptamer may be used as a potential molecular targeted drug against metastatic hepatocellular carcinoma.

The Grainyhead-like 3 (GRHL3) is involved in epidermal barrier formation,neural tube closure and wound repair.Previous studies have suggested that GRHL3 has been linked to many different types of cancers.However,to date,its effects on human colorectal cancer (CRC) has not been clarified yet.Our microarray analysis has indicated predominant GRHL3 expression in CRC.The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues,as well as using distinct CRC cell lines (HT29 and DLD1).We observed increased GRHL3 expression at both mRNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.Moreover,silencing GRHL3 with siRNA could suppress CRC cell proliferation,viability and migration in vitro.We also found that knockdown of GRHL3 could promote cell cycle arrest at G0/G1 phase in HT29 cells and DLD1 cells,and induce cell apoptosis in HT29 cells.Together,our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G0/G1 phase and apoptosis.