Nine dietary habits and risk of colorectal cancer: a Mendelian randomization study.

BACKGROUND: Epidemiological studies have provided evidence that there is an association between diet and colorectal cancer. However, the causal relationship between dietary habits and colorectal cancer remains unknown. METHODS: The UK Biobank provided summary-level genome-wide association study data for nine dietary habits, including alcohol consumption (n = 549,703), instant coffee consumption (n = 250,308), fruit consumption (n = 210,947), meat consumption (n = 210,947), full cream milk consumption (n = 41,306), sweets consumption (n = 25,521), tea consumption (n = 501,494), vegetable consumption (n = 210,947), and yogurt/ice cream consumption (n = 210,947). Additionally, data on colorectal cancer were collected, consisting of 5,567 cases and 372,016 controls. The MR analysis employed inverse variance weighted, weighted median, MR-Egger regression, and MR multivariate residuals tests. RESULTS: In the predominantly European population, a positive association was observed between vegetables (OR = 1.014, 95% CI = 1.000-1.029, p = 0.048) and an increased risk of colorectal cancer. The results for vegetable did not survive correction for multiple comparisons. However, no strong evidence was found for other dietary factors, such as alcohol (OR = 1.012, 95% CI = 0.974-1.051, p = 0.556), fruit (OR = 1.007, 95% CI = 0.986-1.029, p = 0.512), meat (OR = 1.000, 95% CI = 0.987-1.026, p = 0.968), full cream milk (OR = 1.019, 95% CI = 0.979-1.061, p = 0.357), sweets (OR = 0.998, 95% CI = 0.991-1.004, p = 0.524), and tea (OR = 1.002, 95% CI = 0.994-1.009, p = 0.672), with regards to colorectal cancer risk in the European population. CONCLUSIONS: Our study highlights the need for a more nuanced approach to dietary recommendations for CRC prevention, with greater emphasis adherence to the Mediterranean dietary pattern.

Association of sleep duration and risk of mental disorder: a systematic review and meta-analysis.

BACKGROUND: The effects of sleep duration on the development of mental illness remain controversial. Therefore, it is necessary to identify the effects of long or short sleep duration on psychological disorders, which could reveal new ways for preventing and treating mental health conditions cheaply. METHODS: Identifying published papers was accomplished by using the following five English databases on March 16, 2022: PubMed, MEDLINE, Embase, Web of Science databases, and Scopus. Cross-sectional and cohort studies were considered if they evaluated the association of sleep duration with all kinds of mental illness in adults. We excluded case reports, editorials, narrative reviews, and studies without detailed information on sleep duration. Summary effect-size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. Mantel-Haenszel's random-effects model was used to estimate the inconsistency index (I2) and Tau2 index (measurement of heterogeneity). RESULTS: A total of 52 studies were included in this analysis, consisting of 14 cohort studies and 38 cross-sectional studies. These studies involved a combined sample size of 1,407,891 participants who met the inclusion criteria. Cohort (adjusted RR = 1.42, 95% CI: 1.26-1.60, P < .001, I2 = 37.6%, Tau2 = 0.014) and cross-sectional studies (adjusted OR = 1.67, 95% CI: 1.57-1.77, P < .001, I2 = 79.7%, Tau2 = 0.060) concluded that short sleep duration increased mental disorder risks. The same conclusions were acquired in the subgroup analysis, especially for depression (adjusted RR = 1.43, 95% CI: 1.24-1.65, P < .001, I2 = 80.4%, Tau2 = 0.082), anxiety (adjusted RR = 1.30, 95% CI: 1.04-1.63, P = .002, I2 = 0.0%, Tau2 = 0.000), and PTSD (adjusted RR = 1.35, 95% CI: 1.04-1.76, P = .022, I2 = 24.1%, Tau2 = 0.013) in cohort studies. The results of subgroup analysis indicated that long sleep duration was not a risk factor for depression (adjusted RR = 1.15, 95% CI: 0.98-1.34, P = .088, I2 = 63.4%, Tau2 = 0.045) and anxiety (adjusted RR = 1.37, 95% CI: 0.93-2.03, P = .114, I2 = 0.0%, Tau2 = 0.000). CONCLUSIONS: Short sleep duration, not long sleep duration, is an independent predictor of developing mental disorders, particularly anxiety and depression.

[Preliminary Study on Microvasculature Normalization Induced by Peritumoral Electroacupuncture in Mice With Breast Cancer Xenografts].

Objective: To observe the effect of peritumoral electroacupuncture on the induction of vascular normalization in a mouse breast cancer model. Methods: A subcutaneous graft model of breast cancer was established with 4T1 breast cancer cell line in female BALB/c mice aged 6-8 weeks. The mice were randomly assigned to three groups, a tumor-bearing group (TG), peritumoral electroacupuncture tumor-bearing group (EATG), and bevacizumab tumor-bearing group (BTG), with 18 mice in each group. The TG mice did not receive any intervention, the EATG mice received peritumoral electroacupuncture for 30 minutes, and the BTG mice were intraperitoneally injected with bevacizumab at 10mg/kg. Immunofluorescence was performed to assess the expression of CD31/alpha smooth muscle actin (α-SMA) and hypoxia-inducible factor 1-alpha (HIF-1α) in the tumor tissue at various points of time, including before intervention and 3 days and 5 days after intervention. Then, 3 days after intervention, observation of morphological changes of the microvessels in the tumor tissue was performed through Hematoxylin and Eosin (HE) staining and scanning electron microscope. Results: There was no significant difference in the expression of CD31, α-SMA, and HIF-1α in the tumor tissues of all groups before experimental intervention ( P>0.05). On day 3 of the experimental interventions, the CD31 and HIF-1α expression levels in the tumor tissues of the EATG and BTG mice were significantly reduced ( P<0.01), while α-SMA expression levels were significantly increased ( P<0.01) in both groups. On day 5 of the experimental interventions, the CD31 and HIF-1α expression levels in the tumor tissues of the EATG and BTG mice were still significantly lower than those in the TG mice ( P<0.01), while the α-SMA expression level was significantly higher than that in the TG group ( P<0.05). On day 3 of the experimental interventions, H&E staining showed visible microvessels in the tumor tissues of all 3 groups. In addition, scanning electron microscopic observation showed that the tumor microvessel walls of the TG mice were rough and defective, and that obvious deformities appeared in the lumen. In contrast, the walls of the microvessels of the EATG and BTG mice were generally intact and there was no obvious deformities in the lumen. Conclusion: Peritumoral electroacupuncture may induce microvasculature normalization by decreasing microvascular density and increasing pericyte coverage of the neovasculature, thereby improving hypoxic microenvironment of breast cancer in mice.

[Exploration of the thinking and methods in treatment of cancer pain with acupuncture and moxibustion on the base of the fascia theory].

There is a commonality between jingjin (muscle region of meridian) and the fascial network for coordinating the balance in the body. The occurrence and the progression of tumor may disrupt the overall coordination between the fascial network and jingjin directly or indirectly, thereby, the impairment of this coordination may result in cancer pain. Rooted on the theory of overall balance of the fascial network, and combined with understanding of pain in jingjin theory, professor HUANG Jin-chang emphasizes the importance of "relaxing the knot" in treatment of cancer pain. It is recommended to select the fascia reaction point as the target point, in accordance with the principle of balance adjustment and apply various acupuncture and moxibustion therapies, such as Fu's subcutaneous needling, small-needle scalpel therapy, fire needling, and moxibustion.

Invasive acupuncture for gastroparesis after thoracic or abdominal surgery: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis aimed to systematically evaluate the efficacy of acupuncture in treating postsurgical gastroparesis syndrome (PGS) after thoracic or abdominal surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Twelve databases (PubMed, Embase, Cochrane Library Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) (from 1946), Web of Science, EBSCO, Scopus, Open Grey, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc (CBM)) and three registration websites (WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR)) were searched from the inception to September 2022, and citations of the included literature were screened. ELIGIBILITY CRITERIA: All randomised controlled trials addressing invasive acupuncture for PGS. DATA EXTRACTION AND SYNTHESIS: Key information on the included studies was extracted by two reviewers independently. Risk ratio (RR) with 95% CI was used for categorical data, and mean difference with 95% CI for continuous data. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Outcomes were conducted with trial sequential analysis (TSA). RESULTS: Fifteen studies with 759 patients met the inclusion criteria. Subgroup analyses revealed that compared with the drug group, the drug and acupuncture group had a greater positive effect on the total effective rate (TER) (nine trials, n=427; RR=1.20; 95% CI 1.08 to 1.32; P-heterogeneity=0.20, I2=28%, p=0.0004) and the recovery rate (RCR) (six trials, n = 294; RR = 1.61; 95% CI 1.30 to 1.98; P-heterogeneity=0.29, I2=19%, p<0.0001) of PGS after abdominal surgery. However, acupuncture showed no significant advantages in terms of the TER after thoracic surgery (one trial, p=0.13) or thoracic/abdominal surgery-related PGS (two trials, n = 115; RR=1.18; 95% CI 0.89 to 1.57; P-heterogeneity=0.08, I2=67%, p=0.24) and the RCR after thoracic/abdominal surgery (two trials, n=115; RR=1.40; 95% CI 0.97 to 2.01; P-heterogeneity=0.96, I2=0%, p=0.07). The quality of evidence for TER and RCR was moderate certainty. Only one study reported an acupuncture-related adverse event, in the form of mild local subcutaneous haemorrhage and pain that recovered spontaneously. TSA indicated that outcomes reached a necessary effect size except for clinical symptom score. CONCLUSION: Based on subgroup analysis, compared with the drug treatment, acupuncture combined drug has significant advantages in the treatment of PGS associated with abdominal surgery, but not with thoracic surgery. PROSPERO REGISTRATION NUMBER: CRD42022299189.

Tim-3, PD-1, CD244 and Foxp3 Positive T Cells' Relation to the Prognosis of Dermatomyositis and Polymyositis Patients.

OBJECTIVE: To explore the frequency of circulating CD4+ T cells expressing PD-1+, TIM-3+ in polymyositis (PM) and dermatomyositis (DM) patients and its correlation with inflammatory factors, CD244+ and FOXP3+ T cell subtypes and prognosis. STUDY DESIGN: Observational study. Place and Duration of the Study: Ganzhou people's Hospital, Ganzhou, Jiangxi, China, from July 2019 to June 2021. METHODOLOGY: PM and DM patients were treated according to the institution's guidelines and followed up for 2 years. Fifty healthy volunteers were enrolled as controls. Serum interleukin (IL)-6, C-reactive protein (CRP), IL-17, and tumour necrosis factor α (TNF-α) levels were detected by enzyme-linked immunosorbent assay (ELISA). TIM-3+, PD-1+, CD244+, and FOXP3+ expressions were measured using flow cytometry. Inability to live normally, recurrence or death was defined as poor prognosis. RESULTS: The ESR, ALT, AST, LDH and ferritin concentration in PM/DM patients were remarkably elevated than that in healthy volunteers. The frequencies of PD-1+, TIM-3+, CD244+, and FOXP3+ were all remarkably enhanced in PM/DM patients compared with the healthy volunteers. The frequencies of PD-1+, TIM-3+, FOXP3+, and TIM-3+/PD-1+ T cells were significantly elevated in the poor prognosis group compared with the good prognosis group. The frequency of CD4+TIM-3+PD-1+ had satisfactory diagnostic value for PM/DM patients with bad prognoses. IL-17, TIM-3+, PD-1+and TIM-3+ PD-1+ were the risk factors for PM/DM patients with bad outcomes. CONCLUSION: The frequency of circulating CD4+ T cells expressing TIM-3+PD-1+ could be used to predict the prognosis of PM/DM patients. KEY WORDS: Tim-3, PD-1, Dermatomyositis, Polymyositis, Inflammatory.

Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

Electroacupuncture promotes apoptosis and inhibits axonogenesis by activating p75 neurotrophin receptor for triple-negative breast xenograft in mice.

PURPOSE: The aim of this study was to investigate the anti-tumor effect of electroacupuncture (EA) on mice bearing breast tumors by regulating p75 neurotrophin receptor (p75NTR) and remodelling intratumoral innervation. METHODS: Female BALB/c mice were implanted with 4T1 breast tumor cells to establish a murine mammary cancer model. Tumor volume and weight were measured to evaluate tumor growth. Cell apoptosis was assessed by TUNEL assay. The relative expression of p75NTR, TrkA, TrkB, NGF and proNGF were detected by immunohistochemistry. Neurotransmitter and neurotrophin were detected by enzyme-linked immunosorbent assay. Intratumoral innervation was confirmed by ß3-tubulin and TH labeling immunohistochemistry. The antagonist TAT-Pep5 was employed to determine if the effects of EA on tumor growth and cell apoptosis were mediated by p75NTR. RESULTS: Peritumoral EA alleviated tumor growth especially after 14 days of intervention. Apoptosis index in the tumor tissue was obviously decreased after EA. Meanwhile, EA intervention significantly upregulated the expression of p75NTR and proNGF, along with a decline in the tumor growth and an increase in the cell apoptosis. Besides, EA reduced local sympathetic innervation and downregulated sympathetic neurotransmitter NE level in the local tumor. Furthermore, p75NTR antagonist alleviated EA-mediated cell apoptosis and intratumoral innervation. CONCLUSIONS: One mechanism of EA intervention for alleviating tumor progression is mediated by p75NTR to promote apoptosis and decrease intratumoral axonogenesis in the tumor microenvironment.

SARS-CoV-Related Pandemic Outbreaks and Mental Disorder Risk.

ABSTRACT: This study aimed to quantify the association between exposure to pandemic outbreaks and psychological health via a comprehensive meta-analysis. Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates were expressed as odds ratio (OR) with 95% confidence interval (CI). Data from 22 articles, involving 40,900 persons, were meta-analyzed. Overall analyses revealed a significant association of exposing to SARS-CoV-related pandemics with human mental health (OR, 1.32; 95% CI, 1.24-1.40; p < 0.001). Subgroup analyses showed that anxiety (OR, 1.37; 95% CI, 1.19-1.58; p < 0.001), depression (OR, 1.28; 95% CI, 1.15-1.42; p < 0.001), posttraumatic stress (OR, 1.36; 95% CI, 1.17-1.58; p < 0.001), and psychological distress (OR, 1.25; 95% CI, 1.11-1.40; p < 0.001) were all obviously related to pandemic diseases. In the context of infectious disease outbreaks, the mental health of general populations is clearly vulnerable. Therefore, all of us, especially health care workers, need special attention and psychological counseling to overcome pandemic together.

Association Between Recombinant Growth Hormone Therapy and All-Cause Mortality and Cancer Risk in Childhood: Systematic Review and Meta-Analysis.

Objectives: The safety of recombinant human growth hormone (rhGH) treatment in childhood and the role of rhGH therapy in promoting tumorigenesis and progression have been the subject of debate for decades. We aimed to systematically assess the relationship between rhGH therapy in children and adolescents and clinical outcomes, including all-cause mortality, cancer mortality, cancer incidence, and risk of the second neoplasm. Methods: Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as standardized mortality ratios (SMRs), standardized incidence ratio (SIR), and relative risk (RR) with a 95% CI. Results: Data from 24 articles, involving 254,776 persons, were meta-analyzed. Overall analyses revealed the association of rhGH therapy was not statistically significant with all-cause mortality (SMR = 1.28; 95% CI: 0.58-2.84; P = 0.547; I 2 = 99.2%; Tau2 = 2.154) and cancer mortality (SMR = 2.59; 95% CI: 0.55-12.09; P = 0.228; I 2 = 96.7%; Tau2 = 2.361) and also cancer incidence (SIR = 1.54; 95% CI: 0.68-3.47; P = 0.229; I 2 = 97.5%; Tau2 = 2.287), yet statistical significance was observed for second neoplasm (RR = 1.77; 95% CI: 1.33-2.35; P = 0.001; I 2 = 26.7%; Tau2 = 0.055). Differences in the geographic region, gender, treatment duration, mean rhGH dose, overall rhGH exposure dose, and initial disease accounted for heterogeneity in the subgroup analyses. Conclusion: Our findings indicate that the rhGH therapy is not related to all-cause mortality and cancer mortality and cancer incidence, yet it seems to trigger a second tumor risk. Future prospective studies are needed to confirm our findings and answer the more challenging question regarding the optimal dose of rhGH therapy in children and adolescents.

Pathology and ultrasound findings in diffuse sclerosing thyroid papillary carcinoma.

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Dimeric sesquiterpenoids and anti-inflammatory constituents of Sarcandra glabra.

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.

miR-125a attenuates the malignant biological behaviors of cervical squamous cell carcinoma cells through Rad51.

Cervical squamous cell carcinoma (CSCC), the most common cervical malignancy, is more likely to invade and metastasize than other cervical cancers. miR-125a, a tumor suppressor gene, has been confirmed to be associated with cancer metastasis. However, the role of miR-125a in CSCC and the underlying mechanism are unknown. miR-125a expression was confirmed by real-time quantitative PCR (RT-qPCR), and the Rad51 expression level was measured by western blotting analysis. CSCC cell proliferation, migration and invasion were assessed with functional assays, including CCK-8, colony formation, wound healing and Transwell assays. Our data confirmed that miR-125a is expressed at low levels in CSCC tissues and cells. Functionally, the overexpression of miR-125a greatly prevented the proliferation, migration and invasion of CSCC cells, and the inhibition of miR-125a expression strongly enhanced these behaviors in CSCC cells. Moreover, the expression of Rad51, a miR-125a target gene, greatly reversed the miR-125-mediated inhibition of CSCC cell proliferation, migration and invasion. In addition, we discovered that miR-125a downregulated the levels of phosphorylated PI3K, AKT and mTOR through Rad51 in CSCC cells. miR-125a, a tumor suppressor, can attenuate the malignant behaviors of CSCC cells by targeting Rad51. Therefore, the miR-125a/Rad51 axis might be a target for CSCC therapy.

[Research status and trends of acupuncture and moxibustion for cancer：a bibliometric analysis based on CiteSpace and VOSviewer].

To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methods，and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.

Acupuncture for cancer pain: an evidence-based clinical practice guideline.

BACKGROUND: This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. METHODS: The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. RESULTS: The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. CONCLUSION: This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Efficacy of acupuncture therapy for improving anorexia in tumor patients: a Meta-analysi.

OBJECTIVE: To use evidence-based medicine to systematically evaluate the effectiveness and safety of acupuncture therapy for improving anorexia in tumor patients. METHODS: We queried the China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, PubMed, Cochrane Library, and Embase databases to identify reports of randomized controlled trials (RCTs) that applied acupuncture therapy to improve anorexia in tumor patients, and used Rev Man 5.3 software to conduct a Meta-analysis of the effective rate, appetite score, Karnofsky Performance Status (KPS) score, Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale, and body weight in each study. Subgroup analysis was conducted based on whether radiotherapy or chemotherapy were also administered. RESULTS: A total of 10 RCTs were included with a total of 648 patients, including 343 patients in the treatment group and 305 patients in the control group. The Meta-analysis results showed that the clinical efficacy, appetite score, KPS score, and FAACT score of the treatment group (which received acupuncture to improve appetite) were better than those of the control group, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference in body weight between the treatment group and the control group (P > 0.05). The results of the subgroup analysis showed that the effective rate and appetite score for patients with long-term and chronic loss of appetite who underwent acupuncture were better than those of the control group, and the difference was statistically significant (P < 0.05). CONCLUSIONS: Acupuncture therapy has good efficacy and safety in the treatment of anorexia in tumor patients, and it also has good efficacy and safety for long-term and chronic loss of appetite. The reliability and stability of the above results need to be confirmed by high-quality RCTs with larger sample sizes.

Aralia armata (Wall.) Seem Improves Intimal Hyperplasia after Vascular Injury by Downregulating the Wnt3α/Dvl-1/ß-Catenin Pathway.

The aim of the study is to examine the mechanism of Aralia armata (Wall.) Seem (AAS) in improving intimal hyperplasia after vascular injury in rats. Rats with femoral artery injury were randomly divided into three groups: the model group, AAS low-dose group (40 mg/kg), and AAS high-dose group (80 mg/kg). The sham operation group was used as a control group. HE staining was used to observe the changes in femoral artery vessels. Immunohistochemistry was adopted to detect α-SMA, PCNA, GSK-3ß, and ß-catenin proteins in femoral artery tissue. The CCK-8 test and wound healing assay were employed to analyze the effect of AAS on proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in vitro. Western blotting (WB) and polymerase chain reaction (PCR) assays were used to evaluate the molecular mechanism. AAS reduced the stenosis of blood vessels and the protein expressions of α-SMA, PCNA, GSK-3ß, and ß-catenin compared to the model group. In addition, AAS (0-15 µg/mL) effectively inhibited the proliferation and migration of VSMCs. Moreover, the results of WB and PCR showed that AAS could inhibit the activation of ß-catenin induced by 15% FBS and significantly decrease the expression levels of Wnt3α, Dvl-1, GSK-3ß, ß-catenin, and cyclin D1 in the upstream and downstream of the pathway. AAS could effectively inhibit the proliferation and migration of neointima after vascular injury in rats by regulating the Wnt/ß-catenin signaling pathway.

Integrated analysis on the N6-methyladenosine-related long noncoding RNAs prognostic signature, immune checkpoints, and immune cell infiltration in clear cell renal cell carcinoma.

BACKGROUND: Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6-methyladenosine-related lncRNAs (m6A-related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear. METHODS: Gene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A-related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed. RESULTS: A total of 27 prognostic m6A-related lncRNAs were identified. These m6A-related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high-risk m6A-related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A-related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT were significantly increased in the high-risk patients, and there was a correlation between the risk score and immune cell infiltration. CONCLUSIONS: The seven m6A-related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A-related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.