miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Prediction and analysis of albumin-bilirubin score combined with liver function index and carcinoembryonic antigen on liver metastasis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor, and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients' survival rate and quality of life. Indicators such as albumin bilirubin (ALBI) score, liver function index, and carcinoembryonic antigen (CEA) have shown some potential in the prediction of liver metastasis but have not been fully explored. AIM: To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI, liver function index, and CEA, and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance. METHODS: This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1. The risk factors for liver metastasis in patients with CRC were analyzed, a prediction model was constructed by least absolute shrinkage and selection operator (LASSO) logistic regression, internal validation was performed by the bootstrap method, the reliability of the prediction model was evaluated by subject-work characteristic curves, calibration curves, and clinical decision curves, and a column graph was drawn to show the prediction results. RESULTS: Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria. Through LASSO regression variable screening and logistic regression analysis. The ALBI score, alanine aminotransferase (ALT), and CEA were found to be independent predictors of liver metastases in CRC patients [odds ratio (OR) = 8.062, 95% confidence interval (CI): 2.545-25.540], (OR = 1.037, 95%CI: 1.004-1.071) and (OR = 1.025, 95%CI: 1.008-1.043). The area under the receiver operating characteristic curve (AUC) for the combined prediction of CRLM in the modeling group was 0.921, with a sensitivity of 78.0% and a specificity of 95.0%. The H-index was 0.921, and the H-L fit curve had χ2 = 0.851, a P value of 0.654, and a slope of the calibration curve approaching 1. This indicates that the model is extremely accurate, and the clinical decision curve demonstrates that it can be applied effectively in the real world. We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method. The AUC was 0.913, while the accuracy was 0.869 and the kappa consistency was 0.709. The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918, sensitivity of 85.0%, specificity of 95.6%, C-index of 0.918, and an H-L fitting curve with χ 2 = 0.586, P = 0.746. CONCLUSION: The ALBI score, ALT level, and CEA level have a certain value in predicting liver metastasis in patients with CRC. These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC. The risk prediction model developed in this work shows great potential for practical application.

Evaluating new biomarkers for diabetic nephropathy: Role of α2-macroglobulin, podocalyxin, α-L-fucosidase, retinol-binding protein-4, and cystatin C.

BACKGROUND: The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis. AIM: To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN. METHODS: From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility. RESULTS: After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97. CONCLUSION: This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.

Ultrasound-guided serratus anterior plane block enhances postoperative analgesia and recovery in thoracoscopic surgery.

BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.

Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke.

BACKGROUND: Eighty percent of stroke patients develop upper limb dysfunction, especially hand dysfunction, which has a very slow recovery, resulting in economic burden to families and society. AIM: To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke. METHODS: Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group, each with 50 cases. The control group underwent head acupuncture plus routine upper limb rehabilitation training (acupuncture therapy). In addition to acupuncture and rehabilitation, the observation group underwent upper limb task-oriented training (30 min). Each group underwent treatment 5 d/wk for 4 wk. Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Wolf Motor Function Rating Scale (WMFT), modified Barthel Index (MBI), and Canadian Occupational Performance Measure (COPM). Quality of life was evaluated using the Short-Form 36-Item Health Survey (SF-36). Clinical efficacy of the interventions was also evaluated. RESULTS: Before intervention, no significant differences were observed in the FMA-UE, MBI, and WMFT scores between the two groups (P > 0.05). After intervention, the FMA-UE, WMFT, MBI, COPM-Functional Mobility and Satisfaction, and SF-36 scores increased in both groups (P < 0.05), with even higher scores in the observation group (P < 0.05). The observation group also obtained a higher total effective rate than the control group (P < 0.05). CONCLUSION: Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility, quality of life, and clinical efficacy in patients with early stroke.

Avoiding misdiagnosis of multilocular thymic cysts as malignant tumors on computer tomography.

This editorial provides insights from a case report by Sun et al published in the World Journal of Clinical Cases. The case report focuses on a case where a multilocular thymic cyst (MTC) was misdiagnosed as a thymic tumor, resulting in an unnecessary surgical procedure. Both MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate diagnosis. However, the similarity in their imaging presentations can lead to misinterpretation, resulting in unnecessary surgical procedures. Due to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors, we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of misdiagnosis. When computer tomography (CT) values surpass 20 Hounsfield units and display comparable morphology, there is a risk of misdiagnosing MTCs as thymic tumors. Employing various differential diagnostic methods like biopsy, molecular biology, multi-slice CT, CT functional imaging, positron emission tomography/CT molecular functional imaging, magnetic resonance imaging and radiomics, proves advantageous in reducing clinical misdiagnosis. A deeper understanding of these conditions requires increased attention and exploration by healthcare providers. Moreover, the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses, provide appropriate treatment options, and improve the quality of life for patients with thymic tumors and MTCs in the future.

Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions.

BACKGROUND: The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years. AIM: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions. METHODS: We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups. RESULTS: Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05). CONCLUSION: CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

Research on acupuncture and glial cells: A bibliometric analysis.

BACKGROUND: There are a growing number of studies on the effect of acupuncture on glial cells in the central nervous system; however, there are few related bibliometric analyses in this area. Therefore, the purpose of this bibliometric study was to visualize the literature on acupuncture-regulated glial cells. METHODS: On November 23, 2022, regular and review articles on acupuncture and glial cell-related research were retrieved from the Web of Science Core Collection database. The R package "bibliometrix" was used to summarize the main findings, count the occurrences of the top keywords, visualize the international collaboration network, and generate a 3-field plot. The VOSviewer software was used to conduct both co-authorship and co-occurrence analyses. CiteSpace was used to identify the best references and keywords with the highest citation rates. RESULTS: Overall, 348 publications on acupuncture and glial cells were included. The publications were primarily from China, Korea, and the United States of America. The majority of publications were found in relevant journals. Apart from "acupuncture" and "glial cells," the most frequently used keywords were "neuroinflammation," "hyperalgesia," and "pain." CONCLUSION: This bibliometric study mapped a fundamental knowledge structure comprising countries, institutions, authors, journals, and articles in the research fields of acupuncture and glial cells over the last 3 decades. These results provide a comprehensive perspective on the wider landscape of this research area.

Combined traditional Chinese medicine therapy for the treatment of infertility with polycystic ovary syndrome: A network meta-analysis of randomized controlled trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.

[Imaging findings in 12 cases of Warthin-like mucoepidermoid carcinoma].

PURPOSE: To summarize the ultrasound, CT and MRI manifestations of Warthin-like mucoepidermoid carcinoma (WT-MEC), and to explore its imaging characteristics, so as to provide reference for clinical and preoperative diagnosis. METHODS: The clinical information and imaging data of ultrasound, CT and MRI of 12 patients with WT-MEC diagnosed by pathology in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were collected, and their specific characteristics were retrospectively summarized. RESULTS: Among the 12 WT-MEC patients, there were 7 males and 5 females, with an average age of (42.7±16) years. Seven cases underwent ultrasound examination, 6 cases underwent CT examination, and 2 cases underwent MRI examination. Radiologically, all the lesions presented as a solitary mass. 11/12 lesions(91.7%) were identified as well-defined margins, and 10/12(83.3%) as solid-cystic masses. All solid-cystic lesions contained multiple cystic areas with variable sizes. On US images, most lesions showed mixed-echoic echogenicity(5/7, 71.4%), poor vascularization (6/7, 85.7%) and acoustic enhancement (6/7, 85.7%). CT revealed all the lesions (6/6, 100%) as a soft-tissue mass with heterogeneous enhancement (5/6, 83.3%). MRI imaging demonstrated the neoplasm with low or iso-signal intensity on plain T1WI and hyperintensity on T2WI. The heterogeneous enhancement was shown on contrast-enhanced T1WI. CONCLUSIONS: Most WT-MECs represent as a solitary, well-defined, solid-cystic mass in the parotid gland. The neoplasm may be characterized by the multiple and variable-sized cystic components within the tumor.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Fatigue and physical activity in post-CABG patients: the parallel mediation model of kinesiophobia and self-efficacy : a prospective multicentre and cross-sectional study in China.

OBJECTIVES: The objective of this study was to investigate how kinesiophobia and self-efficacy explain the relationship between fatigue and physical activity (PA) in post-coronary artery bypass grafting (post-CABG) patients over the age of 45. DESIGN: A prospective multicentre and cross-sectional study. SETTING: The study was conducted in four public tertiary hospitals in China. PARTICIPANTS: A total of 1278 patients who underwent CABG surgery were selected from the case pool, with their surgeries occurring between 3 and 19 months prior to selection. Out of 1038 patients who met the inclusion criteria and were invited to participate in the study, 759 patients agreed to participate and complete the questionnaire. Ultimately, 376 questionnaires were deemed eligible and included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The questionnaire included the following scales: the Chinese version of the Multidimensional Fatigue Inventory (MFI-20), the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart), the Cardiac Exercise Self-Efficacy Instrument (CESEI) and the International Physical Activity Questionnaire-Long (IPAQ-L). A serial mediation model was used to test whether the association between fatigue and PA was mediated by kinesiophobia and self-efficacy, in the overall sample and subsamples defined by age. RESULTS: The results confirmed that fatigue was directly (95% CI (-5.73 to -3.02)) associated with PA. Higher kinesiophobia (95% CI (-0.16 to -0.05)) or lower PA self-efficacy (95% CI (-0.11 to -0.02)) were parallel pathways through which higher fatigue impediment reduced PA levels. In both subgroups, the street pathways of kinesiophobia and self-efficacy were altered. In the age, 45-60 years group, kinesiophobia (Boot 95% CI (-0.19 to-0.05)) was a mediator of fatigue on PA levels, while in the 61-75 years age group, self-efficacy (Boot 95% CI (-0.17 to -0.04)) was a mediator of fatigue on PA levels. CONCLUSIONS: A clear relationship between fatigue and PA was mediated by both kinesiophobia and self-efficacy. Furthermore, our findings highlight the importance of adapting the intervention according to the age of the patients, mainly by reducing patients' kinesiophobia in patients aged 45-60 years and increasing patients' self-efficacy in patients aged 61-75 years. It may be possible to improve PA levels in post-CABG patients over 45 years of age by eliminating kinesiophobia and increasing self-efficacy.

Three Undescribed Protoilludane-type Sesquiterpene Aryl Esters from Armillaria gallica.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ2(3) and Δ12(13)-protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC50 value of 4.525 µM.

Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1.

Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate ß-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/ß-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.

Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. METHODS: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. RESULTS: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). CONCLUSIONS: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. TRIAL REGISTRATION: Prospero Registration Number CRD42021243185.

Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus).

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1ß (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 µg mL-1; superoxide dismutase: 0.589 µg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 µg mL-1). CONCLUSION: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

Cold sub-mucosal injection versus traditional cold snare polypectomy for diminutive and small colorectal polyps: A systematic review and meta-analysis.

BACKGROUND: The guidelines recommend conventional cold snare polypectomy (C-CSP) for diminutive and small colorectal polyps (≤ 10 mm). However, it remains unclear whether CSP with sub-mucosal injection (SI-CSP) achieves comparable efficacy to C-CSP for managing these lesions. This study compares SI-CSP with C-CSP for patients with diminutive and small colorectal polyps. METHODS: An electronic literature search was conducted to retrieve articles comparing resection outcomes between SI-CSP and C-CSP in diminutive and small colorectal polyps (registration number INPLASY2023100096). Our primary outcomes of interest were the complete resection rate (CRR), complications (namely immediate bleeding, delayed bleeding and perforation) and polypectomy time. Mean differences with 95% confidence intervals (CI) were employed for continuous variables, while odds ratios (OR) with 95% CI were calculated for categorical variables. Data was analyzed using a random effects model and the I2 test was utilized to assess heterogeneity. RESULTS: Eight studies involving 1470 patients with 2223 polyps were included in our analysis. The CRR was not significantly higher in the SI-CSP group, with an OR of 95% CI 0.50 (0.22, 1.15). The incidences of immediate bleeding (OR 95% CI 0.60 [0.26-1.40]) and delayed bleeding (OR 95% CI 0.88 [0.32-2.42]) did not differ significantly between the two groups. On average, the mean polypectomy time was 64.75 seconds shorter in the C-CSP group (95% CI, - 102.96 to - 26.53). Notably, no perforation events were reported in the included studies. CONCLUSIONS: The use of SI-CSP was not superior to C-CSP in managing diminutive and small colorectal polyps and the procedure required significantly more time.

Spatiotemporally Controllable Covalent Bonding of RNA for Multi-Protein Interference.

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.