ZNF26-Associated Genes as Prognostic Signatures in Colorectal Cancer with Broad Therapeutic Implications.

The identification of biomarkers correlated with colorectal cancer (CRC) prognosis holds substantial importance from both clinical and scientific perspectives. Zinc finger protein 26 (ZNF26) has not been previously investigated or documented in solid tumors; thus, further research is necessary to ascertain its prognostic value in CRC. Gene expression profiles and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) database. Subsequently, expression correlation was assessed utilizing the TCGA CRC cohort. The prognostic value of ZNF26 was evaluated through Kaplan-Meier (KM) and ROC curve analyses. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to perform enrichment analysis between high- and low-ZNF26 expression groups. The association between immune cells, immune checkpoint genes, and ZNF26 expression levels was examined. Lastly, the research findings were further validated using CRC tissue samples. The results revealed that, in comparison to healthy controls, CRC significantly reduced ZNF26 expression. Elevated ZNF26 expression was associated with poorer overall survival in CRC patients. Additionally, high ZNF26 expression exhibited an inverse relationship with the immunological score and immune checkpoint gene expression in CRC patients. The findings from the TCGA data analysis were corroborated by the PCR results obtained from CRC tissue samples. ZNF26 is markedly upregulated in colorectal cancer tissues, potentially serving as a biomarker for CRC.

Crosstalk between m6A modification and non-coding RNAs in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, with high morbidity and occurrence. Although various therapeutic approaches have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of HCC remain enigmatic. The N6-methyladenosine (m6A) RNA modification is believed to regulate RNA metabolism and further gene expression. This process is intricately regulated by multiple regulators, such as methylases and demethylases. Non-coding RNAs (ncRNAs) are involved in the regulation of the epigenetic modification, mRNA transcription and other biological processes, exhibiting crucial roles in tumor occurrence and development. The m6A-ncRNA interaction has been implicated in the malignant phenotypes of HCC and plays an important role in drug resistance. This review summarizes the effect of m6A-ncRNA crosstalk on HCC progression and their clinical implications as prognostic markers and therapeutic targets in this disease.

Bioinformatics Analysis Build Autophagy Prognosis Model of Cremastra Intervention Breast Cancer and Explore the Prognostic Markers.

Objective: Autophagy is the catabolic process where the components of eukaryotes experience damage, and the affected or superfluous components undergo self-degradation. However autophagy can promote cancer cell apoptosis or facilitate cell growth. This work aimed to investigat the significance of autophagy-related genes (ARGs) in predicting the prognosis of breast cancer (BC) intervened with Cremastra. Methods: Active ingredients and action targets were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. Then, the BC transcriptome and clinical data were downloaded in The Cancer Genome Atlas (TCGA), whereas ARGs were collected in the Human Autophagy Database (HADb). Meanwhile, Perl and R software were used for data processing and analysis. Firstly, the transcriptome data of BC were mapped to ARGs to screen the BC-ARGs. Secondly, the above genes were mapped to the action targets of Cremastra, ARGs of Cremastra-intervened BC were then screened out. Moreover, an enrichment analysis of biological function was carried out. Univariate Cox regression was carried out on ARGs of BC for preliminarily selecting the independent prognostic genes and constructing the autophagy prognosis model. These genes were mapped to ARGs involved in Cremastra-intervened BC. Finally, those mapped genes were optimized by multi-factor Cox regression, and the key ARGs and potential compounds were obtained. Finally, all cases were classified as low- or high-risk group based on the median risk score. Receiver operating characteristic (ROC) curve, Kaplan-Meier (K-M) survival, independent prognosis and clinical correlation analyses were conducted for model evaluation and identification of factors to independently predict prognosis. Results: Altogether, 66 active components and 38 targets of the Cremastra-intervened autophagy of BC were screened and the autophagy prognosis model demonstrate good predictive performance. As suggested by the survival curve, low-risk patients had a markedly increased survival rate compared with high-risk patients (P < .01). Besides, the gene expression levels of the high-risk group increased with the increases in patients' risk scores. Upon univariate regression, 34 differentially expressed ARGs related to BC treatment were screened. Multivariate regression identified 4 key ARGs, which were mainly derived from glycosides, lignans, flavonoids, and dibenzyl compounds. Thereafter, key genes were subjected to correlation analysis between clinicopathological features and prognosis, among which BCL2 and TP63, showed independent prognostic value. Conclusions: In this study, an autophagy prognosis model was established, and BCL2 and TP63 were predicted for the Cremastra intervention of BC by Bioinformatics, which will be applied to further work.

Traditional Chinese medicine as a novel therapy for colorectal cancer by modulating intestinal flora.

Colorectal cancer is a common clinical malignant tumor of the digestive tract, and intestinal flora has played an important role in the development of colorectal cancer. Bifidobacteria, as one of the main dominant florae in intestinal tract, can inhibit the occurrence and development of colorectal cancer through various mechanisms. Recent studies have shown that traditional Chinese medicine can regulate the abundance of bifidobacteria in intestinal tract and exhibit anti-tumor effects on colorectal cancer. Detailed investigations have revealed that the mechanisms of bifidobacteria in the treatment of colorectal cancer involve three aspects: the production of short-chain fatty acids, the regulation of the body's immunity, and the regulation of cell apoptosis and differentiation. In this review, we provide an updated summary of recent advances in our understanding of the mechanisms by which traditional Chinese medicine regulate intestinal flora to inhibit colorectal cancer development and metastasis.

Development of an immunogenic cell death prognostic signature for predicting clinical outcome and immune infiltration characterization in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remain unclear. The MSigDB database collecting ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients. Stomach adenocarcinoma (STAD) is a common gastric histological cancer type with a high mortality rate. Immunogenic cell death (ICD) plays a key factor during carcinogenesis progress, whereas the prognostic value and role of ICD-related genes (ICDRGs) in STAD remains unclear. The MSigDB database collected ICDRGs were selected by univariate Cox regression analysis and LASSO algorithm to establish a novel risk model. The Kaplan-Meier survival analysis indicated a significant difference of OS rate of patients by risk score stratification. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis (ssGSEA) algorithms were conducted to estimate the immune infiltration landscape by risk stratification. Subgroup analysis and tumor mutation burden analysis were also analyzed to identify characteristics between groups. Differences in therapeutic responsiveness to chemotherapeutic drugs and targeted drugs were also analyzed between high-risk group and low-risk group. The impact of one ICDRG, GPX1, on the proliferation, migration and invasiveness of was confirmed by in vitro experiments in GC cells to test the reliability of bioinformatics results. This study gives evidence of the involvement of ICD process in STAD and provides a new perspective for further accurate assessment of prognosis and therapeutic efficacy in STAD patients.

Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing.

Immune effector cells in the microenvironment tend to be depleted or remodeled, unable to perform normal functions, and even promote the malignant characterization of tumors, resulting in the formation of immunosuppressive microenvironments. The strategy of reversing immunosuppressive microenvironment has been widely used to enhance the tumor immunotherapy effect. Signal transducer and activator of transcription 3 (STAT3) was found to be a crucial regulator of immunosuppressive microenvironment formation and activation as well as a factor, stimulating tumor cell proliferation, survival, invasiveness and metastasis. Therefore, regulating the immune microenvironment by targeting the STAT3 oncogenic pathway might be a new cancer therapy strategy. This review discusses the pleiotropic effects of STAT3 on immune cell populations that are critical for tumorigenesis, and introduces the novel strategies targeting STAT3 oncogenic pathway for cancer immunotherapy. Lastly, we summarize the conventional drugs used in new STAT3-targeting anti-tumor applications.

Nodal properties of the resting-state brain functional network in childhood and adolescence.

BACKGROUND AND PURPOSE: Changes in the topological properties of brain functional network nodes during childhood and adolescence can provide more detailed and intuitive information on the rules of brain development. This study aims to explore the characteristics of nodal attributes in child and adolescent brain functional networks and analyze the correlation between nodal attributes in different brain regions and age. METHODS: Forty-two healthy volunteers aged 6-18 years who were right-handed primary and middle school students were recruited, and the subgroup analysis included children (6-12 years, n = 19) and adolescents (13-18 years, n = 23). Resting-state functional magnetic resonance imaging data were collected using a 3.0 Tesla MRI scanner. The topological properties of the functional brain network were analyzed using graph theory. RESULTS: Compared with the children group, the degree centrality and nodal efficiency of multiple brain regions in the adolescent group were significantly increased, and the nodal shortest path was reduced (q<0.05, false discovery rate corrected). These brain regions were widely distributed in the whole brain and significantly correlated with age. Compared with the children group, reduced degree centralities were observed in the left dorsolateral fusiform gyrus, left rostral cuneus gyrus, and right medial superior occipital gyrus. CONCLUSION: The transmission efficiency of the brain's core network gradually increased, and the subnetwork function gradually improved in children and adolescents with age. The functional development of each brain area in the occipital visual cortex was uneven and there was functional differentiation within the occipital visual cortex.

Astragaloside II enhanced sensitivity of ovarian cancer cells to cisplatin via triggering apoptosis and autophagy.

Cisplatin (DDP) based chemotherapy occurs a reduced therapeutic effect on the later treatment of ovarian cancer (OC) due to DDP resistance. Astragaloside II (ASII), a natural product extracted from Radix Astragali, has shown promising anticancer effects. However, the effects of ASII on OC have not been clarified. In this study, we found that ASII inhibited cell growth and promoted cell apoptosis of DDP-resistant OC cells in vitro and in vivo. Further study showed that ASII downregulated multidrug resistance-related protein MDR1 and cell cycle-related protein Cyclin D1 and PCNA, and also upregulated apoptosis-related protein leaved PRAP and cleaved caspase-3. In addition, ASII induced autophagy, characterized by upregulation of LC3II expression, downregulation of p62 expression, and elevation of LC3 punctuation, may be associated with inhibition of the AKT/mTOR signaling pathway. Moreover, the messenger RNA-sequencing was used to identify potential molecules regulated by ASII. In conclusion, these findings indicated that ASII increased sensitivity of DDP in the treatment of OC.

MEF2C-AS1 regulates its nearby gene MEF2C to mediate cervical cancer cell malignant phenotypes in vitro.

Cervical cancer (CC) is the second most common malignancy among women. GEPIA demonstrated that MEF2C-AS1 and its nearby gene MEF2C present downregulation in CC tissues. We attempted to clarify molecular mechanism between MEF2C-AS1 and MEF2C underlying CC progression. RT-qPCR was used to measure expression levels and subcellular distribution of MEF2C-AS1 and MEF2C in CC cell lines. Gain-of-function assays were conducted to reveal roles of MEF2C-AS1 and MEF2C in CC cell behaviors. Bioinformatics, RNA pull down, and RIP assays were performed to assess association of MEF2C-AS1 or MEF2C with miR-20 b-5p in CC cells. Rescue assays were done to assess regulatory function of the MEF2C-AS1-miR-20 b-5p-MEF2C axis in CC cellular processes. MEF2C-AS1 and its nearby gene MEF2C showed downregulation and had a positive expression correlation in CC tissues. MEF2C-AS1 and MEF2C presented downregulation in CC cells, and they majorly distributed in CC cell cytoplasm. MEF2C-AS1 and MEF2C upregulation repressed CC cell proliferative, migratory, and angiogenic abilities. MEF2C-AS1 competitively bound with miR-20 b-5p to upregulate MEF2C in CC cells. The impacts of MEF2C-AS1 elevation on CC cell proliferative, migratory, and angiogenic capabilities were countervailed by miR-20 b-5p overexpression. The impacts of miR-20 b-5p inhibitor on CC cell proliferative, migratory and angiogenic capabilities were countervailed by MEF2C depletion. To sum up, MEF2C-AS1 and its nearby gene MEF2C present downregulation and serve as tumor suppressors in CC cells. MEF2C-AS1 suppresses CC cell malignancy in vitro through sponging miR-20 b-5p to upregulate MEF2C, which may provide a potential new direction for seeking therapeutic plans of CC.

The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment.

Among all malignant tumors in the whole universe, the incidence and mortality of lung cancer disease rank first. Especially in the past few years, the occurrence of lung cancer in the urban population has continued to increase, which seriously threatens the lives and health of people. Among the many treatments for lung cancer, chemotherapy is the best one, but traditional chemotherapy has low specificity and drug resistance. To address the above issue, this study reviews the five biological pathways that common terpenoid compounds in medicinal plants interfere with the occurrence and development of lung cancer: cell proliferation, cell apoptosis, cell autophagy, cell invasion, metastasis, and immune mechanism regulation. In addition, the mechanism of the terpenoid natural traditional Chinese medicine monomer compound combined with Western medicine in the multipathway antilung cancer is summarized.

The Immune Infiltration in HNSCC and Its Clinical Value: A Comprehensive Study Based on the TCGA and GEO Databases.

BACKGROUND: Being potential field of research for tumor immunological therapy, the head and neck squamous cell carcinoma (HNSCC) is one of most discussed types of tumor. Recently, some clinical trials have also used immunological therapy and demonstrated a subset of HNSCC patients who have shown a clear longer survival time. OBJECTIVE: To conduct further studies and deeper research in the immunological oncology of HNSCC, a more detailed description and comprehending of the complicated landscape of immune infiltrative may be required. METHODS: Firstly, we have described the fraction of different infiltrating immune cells in the HNSCC tumor and then compared it to the normal tissue, and secondly, we have explored the clinical implications of various infiltrated immune cell fractions meticulously. The gene expression profiles of HNSCC tissue were obtained from databases of TCGA and GEO and utilized the deconvolution algorithm (CIBERSORT) to presume the fractions of 22 several immune sensitive cells. RESULTS: Our results indicated that the immune infiltrating cell fractions were considerably different between HNSCC tumor tissue and paired normal tissue, but at the same time, we found a potential internal correlation among the immune cells and also showed the association between immune infiltrating cells and their clinical characteristics. It is worth noting that the resting dendritic cells and M1 macrophages were linked with a favorable prognosis, while the CD4+ T cells with a poorer outcome. CONCLUSION: Fractions of immune cell percentage were also associated with tumors' pathological grade, age, and TNM stage.

Tumor suppressing role of serum-derived exosomal microRNA-15a in osteosarcoma cells through the GATA binding protein 2/murine double minute 2 axis and the p53 signaling pathway.

Exosomes are emerging tools for transporting lipids, proteins, microRNAs (miRNAs), or other biomarkers for clinical purposes. They have produced widespread concern in managing human diseases, including osteosarcoma (OS). This study focuses on the function of serum-derived exosomal miR-15a in the growth of OS cells and the mechanism of action. Differentially expressed genes between OS and normal samples were screened using two datasets GSE70367 and GSE65071. miR-15a was poorly expressed, whereas GATA-binding protein 2 (GATA2) and murine double minute 2 (MDM2) were abundantly expressed in OS samples. miR-15a and its target mRNAs, including GATA2, were enriched in the p53 signaling pathway. miR-15a directly targets GATA2 mRNA to inhibit its expression, whereas GATA2 activates the transcription of MDM2, a negative regulator of p53. Overexpression of GATA2 and MDM2 promoted proliferation and cell cycle progression of MG-63 cells, whereas miR-15a blocked this axis and suppressed cell growth. miR-15a was identified as a major cargo of serum-derived exosomes, and exosomes conveying miR-15a were internalized by OS cells. This study demonstrated that miR-15a suppresses the GATA2/MDM2 axis to inhibit the proliferation and invasiveness of OS cells in vitro through the p53 signaling pathway.

Analysis of the Significance of Immune Cell Infiltration and Prognosis of Non-Small-Cell Lung Cancer by Bioinformatics.

Objective: To perform gene set enrichment analysis (GSEA) and analysis of immune cell infiltration on non-small-cell lung cancer (NSCLC) expression profiling microarray data based on bioinformatics, construct TICS scoring model to distinguish prognosis time, screen key genes and cancer-related pathways for NSCLC treatment, explore differential genes in NSCLC patients, predict potential therapeutic targets for NSCLC, and provide new directions for the treatment of NSCLC. Methods: Transcriptome data of 81 NSCLC patients and the GEO database were used to download matching clinical data (access number: GSE120622). Form the expression of non-small cell lung cancer (NSCLC). TICS values were calculated and grouped according to TICS values, and we used mRNA expression profile data to perform GSEA in non-small-cell lung cancer patients. Biological process (GO) analysis and DAVID and KOBAS were used to undertake pathway enrichment (KEGG) analysis of differential genes. Use protein interaction (PPI) to analyze the database STRING, and construct a PPI network model of target interaction. Results: We obtained 6 significantly related immune cells including activated B cells through the above analysis (Figure 1(b), p < 0.001). Based on the TICS values of significantly correlated immune cells, 41 high-risk and 40 low-risk samples were obtained. TICS values and immune score values were subjected to Pearson correlation coefficient calculation, and TICS and IMS values were found to be significantly correlated (Cor = 0.7952). Based on non-small-cell lung cancer mRNA expression profile data, a substantial change in mRNA was found between both the high TICS group as well as the low TICS group (FDR 0.01, FC > 2). The researchers discovered 730 mRNAs that were considerably upregulated in the high TICS group and 121 mRNAs that were considerably downregulated in the low TICS group. High confidence edges (combined score >0.7) were selected using STRING data; then, 191 mRNAs were matched to the reciprocal edges; finally, an undirected network including 164 points and 777 edges was constructed. Important members of cellular chemokine-mediated signaling pathways, such as CCL19, affect patient survival time. Conclusion: (1) The longevity of patients with non-small-cell lung cancer was substantially connected with the presence of immature B cells, activated B cells, MDSC, effector memory CD4 T cells, eosinophils, and regulatory T cells. (2) Immune-related genes such as CX3CR1, CXCR4, CXCR5, and CCR7, which are associated with the survival of NSCLC, affect the prognosis of NSCLC patients by regulating the immune process.

Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: A Systematic Review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. As a widely used complementary and alternative therapy, acupuncture is increasingly used to treat PCOS. However, the effect of acupuncture in treating PCOS is uncertain, and the mechanisms are unclear. This systematic review aims to determine the efficacy of acupuncture on PCOS in animal preclinical models. METHODS: Experimental animal studies of acupuncture in PCOS animal models were searched in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Science and Technology Periodical Database from inception to December 2020. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. RESULTS: A total of 358 studies were screened based on the title and abstract, and 31 studies were included. A total of 722 animals were involved, and all studies used either Wistar rats or SD rats. Twenty-six studies used electroacupuncture, 9 studies used manual acupuncture, and 5 of them employed both electroacupuncture and manual acupuncture. A total of 22 acupoints were involved; 7 studies followed the modern acupuncture pattern, and the rest followed classic acupuncture theory. CONCLUSIONS: The present review summarizes the current evidence of the effects of acupuncture on PCOS in animal models. Unfortunately, we could not draw a definite conclusion due to the methodological weakness of the included studies and the high heterogeneity. Well-designed studies are needed in the future to fill this gap.

The Treatment of Complementary and Alternative Medicine on Premature Ovarian Failure.

It has been confirmed by growing evidence that common hormone replacement therapy is associated with an increasing risk of causing cardiovascular disease and cancer, while complementary and alternative medicine (CAM) is gaining popularity and application in more and more patients with premature ovarian failure (POF). Although there is little data concerning the clinical safety and efficacy of CAM, the literature includes application studies on the phytoestrogen-rich herbal, acupuncture treatment and intervention therapy. This article reviews recent literature on CAM therapy for POF, aiming to provide theoretical support for clinical application.

Gene Expression Profiling Studies Using Microarray in Osteoarthritis: Genes in Common and Different Conditions.

Osteoarthritis (OA), which is characterized mainly by cartilage degradation, is the most prevalent joint disorder worldwide. Although OA is identified as a major cause of joint pain, disability, and socioeconomic burden, the etiology of OA is still not clearly known. Recently, gene microarray analysis has become an efficient method for the research of complex diseases and has been employed to determine what genes and pathways are involved in the pathological process of OA. In this review, OA study results over the last decade are summarized for gene expression profiling of various tissues, such as cartilage, subchondral bone, and synovium in human OA and mouse OA models. Many differentially expressed genes, which mainly involve matrix metabolism, bone turnover, and inflammation pathways, were identified in diseased compared with "normal" tissues. Nevertheless, rare common genes were reported from studies using different tissue sources, microarray chips, and research designs. Thus, future novel and carefully designed microarray studies are required to elucidate underlying genetic mechanisms in the pathogenesis of OA as well as new directions for potential OA-targeted pharmaceutical therapies.

Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats.

Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance and a high risk of miscarriage during pregnancy. Similarly, in rats, maternal exposure to 5α-dihydrotestosterone (DHT) and insulin from gestational day 7.5 to 13.5 leads to hyperandrogenism and insulin resistance and subsequently increased fetal loss. A variety of hormonal and metabolic stimuli are able to trigger different types of regulated cell death under physiological and pathological conditions. These include ferroptosis, apoptosis and necroptosis. We hypothesized that, in rats, maternal hyperandrogenism and insulin-resistance-induced fetal loss is mediated, at least in part, by changes in the ferroptosis, apoptosis and necroptosis pathways in the gravid uterus and placenta. Compared with controls, we found that co-exposure to DHT and insulin led to decreased levels of glutathione peroxidase 4 (GPX4) and glutathione, increased glutathione + glutathione disulfide and malondialdehyde, aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition and activated ERK/p38/JNK phosphorylation in the gravid uterus. In addition, we observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction in the uteri of rats co-exposed to DHT and insulin. However, in the placenta, DHT and insulin exposure only partially altered the expression of ferroptosis-related markers (e.g. region-dependent GPX4, glutathione + glutathione disulfide, malondialdehyde, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). Moreover, we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA in placentas of rats co-exposed to DHT and insulin. Further, DHT + insulin-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal hyperandrogenism and insulin resistance causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Our data also suggest that apoptosis and necroptosis may play a role in coordinating or compensating for hyperandrogenism and insulin-resistance-induced ferroptosis when the gravid uterus and placenta are dysfunctional.

Acupuncture for cancer-related hiccups: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hiccups are involuntary contractions of the diaphragm and intercostal muscles, which lead to sudden contractions of the glottis. CAM, such as acupuncture is commonly used and stimulation of the vagus nerve and interference with phrenic nerve conduction are also used to treat hiccups. However, there is little evidence on the effectiveness of acupuncture for cancer-related hiccups. We will plan to conduct a systematic review and meta-analysis of RCTs to evaluate the current evidence on the effects of acupuncture for cancer-related hiccups. METHOD: The following databases will be searched: PubMed, the Cochrane Library, Wanfang Data, China National Knowledge Infrastructure (CNKI), SinoMed, VIP, Medline, Embase, and EI. Randomized controlled trials will be included to evaluate the effect and safety of acupuncture on cancer patients with hiccups. We will set standards for the curative effect on the basis of the standard of cure and improvement for clinical disease diagnoses. The risk of bias will be assessed by the Cochrane risk of bias tool. We will conduct a meta-analysis and sensitivity analysis, as well as a subgroup analysis if high heterogeneity is present, using Revman 5.3. We will use funnel plots to identify potential reporting biases. We will test asymmetry using Egger test. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to evaluate the quality of evidence. RESULTS: This study will be to assess the effect and safety of acupuncture for cancer-related hiccups. CONCLUSIONS: This study will assess the effect of acupuncture for cancer-related hiccups and provide reliable evidence for the choice of treatments.

miR-26a-5p Inhibit Gastric Cancer Cell Proliferation and Invasion Through Mediated Wnt5a.

PURPOSE: Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. PATIENTS AND METHODS: MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. RESULTS: The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ≥3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and ß-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. CONCLUSION: Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.

Auricular points acupressure for insulin resistance in overweight/obese women with polycystic ovary syndrome: protocol for a randomised controlled pilot trial.

INTRODUCTION: Approximately 5%-20% of reproductive women suffer from polycystic ovary syndrome (PCOS). Auricular points acupressure (AA) may serve as alternative management for PCOS for its benefits in both physical and psychological well-being. However, the effects of AA for insulin resistance (IR) in overweight/obese PCOS women have not been confirmed. METHODS AND ANALYSIS: The present study is designed as a randomised, placebo-controlled pilot trial to evaluate the effectiveness and safety of AA in treating IR in women with PCOS. A total of 60 eligible PCOS subjects will be randomised into an intervention group (AA group) and a control group (sham AA group) in a ratio of 1:1. Magnetic beads will be taped to the auricular points by the same senior acupuncture specialist from the First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The treatment will last for 12 weeks. Primary outcome measure will be changes in homeostasis model assessment of IR between baseline and after 3 months of AA/sham AA treatment. Secondary outcomes include hormonal profile, weight, waist/hip circumference, body mass index, blood pressure, Ferriman-Gallwey score, acne and the assessment of health-related quality of life. Outcome measures are collected at baseline and the end of treatment visit. ETHICS AND DISSEMINATION: The protocol has been approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (HZYLLKY201800301). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications. TRIAL REGISTRATION NUMBER: NCT03546595; Pre-results.