Clinical outcomes of radiofrequency ablation using a radiofrequency needle device for varicose ulcer: A non-randomized controlled prospective study.

OBJECTIVE: To evaluate the short-term clinical outcomes of radiofrequency ablation (RFA) using a radiofrequency (RF) needle device for varicose ulcers. METHODS: From September 2020 to September 2021, a total of 80 patients with varicose ulcers were included in this study. Based on the different surgical methods, the patients were divided into RF group and control groups, with 40 cases in each group. In the RF group, RFA was performed using an RF needle device and foam sclerotherapy was used for superficial veins. The control group was treated with conventional high-ligation stripping. The surgical data, hospitalization data, clinical efficacy, and postoperative complications of two groups were compared. Meanwhile, the correlation between RBC, HB, HCT, and ulcer healing time was analyzed. RESULTS: Compared to the control group, RF group had shorter surgery time, duration in the hospital, and less intraoperative bleeding (p < .05). The VCSS and CIVIQ scores in RF group were significantly higher than that in control group (p < .05). The healing time of ulcers was shorter in the RF group (x2 = 19.766, p = .000). The RF group had fewer postoperative complications. There was a positive correlation between RBC, HB, and HCT, and ulcer healing time (p < .05). CONCLUSION: The use of the RF needle device for RFA to treat patients with varicose ulcers showed acceptable short-term clinical outcomes with less incidence of trauma, faster recovery, and fewer complications.

The effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment for hepatocellular carcinoma in China: a bayesian network meta-analysis.

PURPOSE: To investigate the effectiveness of problem-based learning (PBL) and case-based learning (CBL) teaching methods in clinical practical teaching in transarterial chemoembolization (TACE) treatment in China. MATERIALS AND METHODS: A comprehensive search of PubMed, the Chinese National Knowledge Infrastructure (CNKI) database, the Weipu database and the Wanfang database up to June 2023 was performed to collect studies that evaluate the effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment in China. Statistical analysis was performed by R software (4.2.1) calling JAGS software (4.3.1) in a Bayesian framework using the Markov chain-Monte Carlo method for direct and indirect comparisons. The R packages "gemtc", "rjags", "openxlsx", and "ggplot2" were used for statistical analysis and data output. RESULTS: Finally, 7 studies (five RCTs and two observational studies) were included in the meta-analysis. The combination of PBL and CBL showed more effectiveness in clinical thinking capacity, clinical practice capacity, knowledge understanding degree, literature reading ability, method satisfaction degree, learning efficiency, learning interest, practical skills examination scores and theoretical knowledge examination scores. CONCLUSIONS: Network meta-analysis revealed that the application of PBL combined with the CBL teaching mode in the teaching of liver cancer intervention therapy significantly improves the teaching effect and significantly improves the theoretical and surgical operations, meeting the requirements of clinical education.

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression. METHODS: A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting. RESULTS: The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030). CONCLUSIONS: A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions. TRIAL REGISTRATION: Registration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.

Unravelling the complex causal effects of substance use behaviours on common diseases.

BACKGROUND: Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake. METHODS: In this study, we assess 11 commonly used Mendelian Randomization (MR) methods by simulation and apply them to investigate the causal relationship between 7 SUB traits and health outcomes. We also combine stratified regression, genetic correlation, and MR analyses to investigate the dosage-dependent effects. RESULTS: We show that smoking initiation has widespread risk effects on common diseases such as asthma, type 2 diabetes, and peripheral vascular disease. Alcohol consumption shows risk effects specifically on cardiovascular diseases, dyslipidemia, and hypertensive diseases. We find evidence of dosage-dependent effects of coffee and tea intake on common diseases (e.g., cardiovascular disease and osteoarthritis). We observe that the minor allele effect of rs4410790 (the top signal for tea intake level) is negative on heavy tea intake ( b ̂ G W A S = - 0.091 , s . e . = 0.007 , P = 4.90 × 10 - 35 ) but positive on moderate tea intake ( b ̂ G W A S = 0.034 , s . e . = 0.006 , P = 3.40 × 10 - 8 ) , compared to the non-tea-drinkers. CONCLUSION: Our study reveals the complexity of the health effects of SUB and informs design for future studies aiming to dissect the causal relationships between behavioural traits and complex diseases.

Many people smoke or consume alcohol, coffee and tea. The relationship between using these types of substance and the development of different diseases is not well understood. Previous studies have suggested that differences in genetics, i.e. inherited characteristics, could have an impact on how each substance impacts a particular person's health. We used a method called Mendelian Randomization to look at the impact of consuming tobacco, alcohol, coffee and tea on the development of various common diseases using genetic information. We found that relationships were complicated and many were dosage-dependent, but that consumption of a large amount of all substances tended to have negative health impacts regardless of lifestyle, behavioural or inherited characteristics.

The use of Esketamine in CT-guided percutaneous liver tumor ablation reduces the consumption of remifentanil: a randomized, controlled, double-blind trial.

Background: In the anesthesia management of percutaneous liver tumor ablation, the requirement of analgesia is very strict. Currently, intravenous anesthesia is commonly used, such as remifentanil combined with sedative drugs. However, the pain relief is not instantaneous after increasing the dosage of remifentanil. Esketamine, a medium- or long-term analgesic drug, does not inhibit respiration to maintain patient comfort during the ablation and reduces the consumption of remifentanil. Therefore, this experiment was designed to investigate the potential of combinational therapy and the most appropriate dose of esketamine. Methods: A total of 120 patients were randomly divided into three groups by SPSS. The regular anesthesia model included dexmedetomidine 0.5 µg/kg, intravenous glucose tolerance test, remifentanil continuous infusion, flurbiprofen 50 mg, i.v., palonosetron 0.225 mg, i.v., and 1% lidocaine for local anesthesia. Group A was the regular control group, only using the regular model; Group B also received with 0.1 mg/kg esketamine, i.v.; and Group C also received 0.2 mg/kg esketamine, i.v.. The whole experiment was double-blind. Results: From December 2020 to March 2021, 120 patients were randomized in total, and 108 were included in the analysis: 36, 37, 35 were allocated to Group A, Group B, and Group C, respectively. The total dosage of remifentanil in Group A, Group B, Group C was 179.38±123.37, 120.31±57.96 and 115.91±62.42 µg, respectively. We found the total dosage of remifentanil in Group B and Group C were significantly decreased in comparison to that of Group A (P=0.004, P=0.003, respectively). The maximum dosage of remifentanil in Group A, Group B, and Group C was 1.76±0.62, 1.37±0.47, and 1.33±0.56 ng/mL, respectively. The maximum dosage of remifentanil in Group B and Group C were significantly decreased in comparison to that of Group A (P=0.003, P=0.001, respectively). The incidence of severe pain during the ablation in Group B was significantly lower than that in Group A (3 vs. 12, P<0.05). Conclusions: The use of esketamine can reduce the dosage of opioids for liver tumor ablation and reduce the occurrence of severe pain. We found that 0.1 mg/kg esketamine, i.v. is the most suitable dose for liver tumor ablation. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049152.

Promoter-anchored chromatin interactions predicted from genetic analysis of epigenomic data.

Promoter-anchored chromatin interactions (PAIs) play a pivotal role in transcriptional regulation. Current high-throughput technologies for detecting PAIs, such as promoter capture Hi-C, are not scalable to large cohorts. Here, we present an analytical approach that uses summary-level data from cohort-based DNA methylation (DNAm) quantitative trait locus (mQTL) studies to predict PAIs. Using mQTL data from human peripheral blood ([Formula: see text]), we predict 34,797 PAIs which show strong overlap with the chromatin contacts identified by previous experimental assays. The promoter-interacting DNAm sites are enriched in enhancers or near expression QTLs. Genes whose promoters are involved in PAIs are more actively expressed, and gene pairs with promoter-promoter interactions are enriched for co-expression. Integration of the predicted PAIs with GWAS data highlight interactions among 601 DNAm sites associated with 15 complex traits. This study demonstrates the use of mQTL data to predict PAIs and provides insights into the role of PAIs in complex trait variation.

Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia.

The AML1/ETO fusion protein is essential to the development of t(8;21) acute myeloid leukemia (AML) and is well recognized for its dominant-negative effect on the coexisting wild-type protein AML1. However, the genome-wide interplay between AML1/ETO and wild-type AML1 remains elusive in the leukemogenesis of t(8;21) AML. Through chromatin immunoprecipitation sequencing and computational analysis, followed by a series of experimental validations, we report here that wild-type AML1 is able to orchestrate the expression of AML1/ETO targets regardless of being activated or repressed; this is achieved via forming a complex with AML1/ETO and via recruiting the cofactor AP-1 on chromatin. On chromatin occupancy, AML1/ETO and wild-type AML1 largely overlap and preferentially bind to adjacent and distinct short and long AML1 motifs on the colocalized regions, respectively. On physical interaction, AML1/ETO can form a complex with wild-type AML1 on chromatin, and the runt homology domain of both proteins are responsible for their interactions. More importantly, the relative binding signals of AML1 and AML1/ETO on chromatin determine which genes are repressed or activated by AML1/ETO. Further analysis of coregulators indicates that AML1/ETO transactivates gene expression through recruiting AP-1 to the AML1/ETO-AML1 complex. These findings enrich our knowledge of understanding the significance of the interplay between the wild-type protein and the oncogenic fusion protein in the development of leukemia.

Preferential eradication of acute myelogenous leukemia stem cells by fenretinide.

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34(+) cells, especially the LSC-enriched CD34(+)CD38(-) subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34(+) cells but not those from normal CD34(+) cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-κB and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide-down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.