Protective Effect of Long Noncoding RNA OXCT1-AS1 on Doxorubicin-Induced Apoptosis of Human Myocardial Cells by the Competitive Endogenous RNA Pattern. / Efeito Protetor do RNA Não Codificante Longo OXCT1-AS1 na Apoptose de Células Miocárdicas Humanas Induzida pela Doxorrubicina pelo Padrão Competitivo de RNA Endógeno.

BACKGROUND: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. OBJECTIVE: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. METHODS: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. RESULTS: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. CONCLUSION: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis.

FUNDAMENTO: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. OBJETIVO: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. MÉTODOS: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. RESULTADOS: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. CONCLUSÃO: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1.

Preparation and characterization of metal-polyphenol networks encapsulated in sodium alginate microbead hydrogels for catechin and vitamin C delivery.

A novel encapsulation system was designed, utilizing sodium alginate (SA) polysaccharide as the matrix and easily absorbed Fe2+ as the metal-organic framework, to construct microbead scaffolds with both high catechins (CA) and vitamin C (Vc) loading and antioxidant properties. The structure of microbead hydrocolloids was investigated using SEM, XPS, FTIR, XRD and thermogravimetry, and the antioxidant activity, in vitro digestion and the release of CA and Vc were evaluated. These results revealed that the microbead hydrocolloids SA-CA-Fe and SA-CA-Vc-Fe exhibited denser and stronger cross-linking structures, and the formation of inter- and intramolecular hydrogen and coordination bonds improved thermal stability. Moreover, SA-CA-Fe (44.9 % DPPH and 47.8 % ABTS) and SA-CA-Vc-Fe (89.9 % DPPH and 89.3 % ABTS) displayed strong antioxidant activity. Importantly, they were non-toxic in Caco2 cells. The SA-CA-Fe and SA-CA-Vc-Fe achieved significantly higher CA (56.9 and 62.7 %, respectively) and Vc (42.2 %) encapsulation efficiency while maintaining higher CA and Vc release in small intestinal environment. These results suggested that SA polysaccharide-based encapsulation system using Fe2+ framework as scaffold had greater potential for delivery and controlled release of CA and Vc than conventional hydrocolloids, which could provide new insights into the construction of high loading, safe, targeted polyphenol delivery system.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Micro-Milling of Additively Manufactured Al-Si-Mg Aluminum Alloys.

Additively manufactured aluminum alloy parts attract extensive applications in various felids. To study the machinability of additively manufactured aluminum alloys, micro-milling experiments were conducted on the additively manufactured AlSi7Mg and AlSi10Mg. By comparing the machinability of Al-Si-Mg aluminum alloys with different Si content, the results show that due to the higher hardness of the AlSi10Mg, the cutting forces are higher than the AlSi7Mg by about 11.8% on average. Due to the increased Si content in additively manufactured Al-Si-Mg aluminum alloys, the surface roughness of AlSi10Mg is 26.9% higher than AlSi7Mg on average. The burr morphology of additively manufactured aluminum alloys in micro-milling can be divided into fence shape and branch shape, which are, respectively, formed by the plastic lateral flow and unseparated chips. The up-milling edge exhibits a greater burr width than the down-milling edge. Due to the better plasticity of AlSi7Mg, the burr width of the down-milling edge is 28.1% larger, and the burr width of the up-milling edge is 10.1% larger than the AlSi10Mg. This research can provide a guideline for the post-machining of additively manufactured aluminum alloys.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Clinical values of serum C5a in Alzheimer's disease patients with different dementia stages.

Alzheimer's disease (AD) is characterized by abnormal inflammatory responses, and complement C5a (C5a) is known to initiate inflammation. This study aimed to investigate the associations between serum C5a, inflammatory responses, and cognitive function in AD patients. A total of 242 AD patients and 132 age-matched controls were included. Enzyme-linked immunosorbent assay revealed increased levels of C5a, interleukin (IL)-4, IL-6, IL-10, IL-1ß, and tumor necrosis factor (TNF)-α with advancing stages of AD. Pearson correlation coefficient and receiver operating characteristic curve revealed positive correlations between serum C5a levels, inflammatory cytokine levels, Neuropsychiatric Inventory (NPI) and Activities of Daily Living (ADL) scores, and negative correlations with Mini-mental State Examination (MMSE) and Montreal cognitive assessment (MoCA) scores. Serum C5a above 68.68 pg/mL could aid in the diagnosis of AD. Multivariable logistic analysis revealed that serum C5a was an independent risk factor for IL-1ß/IL-6/IL-10/TNF-α and an independent protective factor for IL-4. Higher serum C5a levels were associated with lower MMSE and MoCA scores. In conclusion, elevated serum C5a levels were beneficial for AD diagnosis and predictive of inflammation and cognitive dysfunction.

Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.

Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group ( P >0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P <0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P <0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P <0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P <0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P <0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P <0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P <0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis. / 艾灸对ApoE-/-åŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å°é¼ SIRT1/FOXO3a信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM: To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS: The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS: The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION: The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

Peptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment.

Microvascular disease, modifiable risk factor profiles and incident arrhythmias in type 2 diabetes.

BACKGROUND: To assess the roles of diabetic microvascular disease and modifiable risk factors and their combination in the development of arrhythmias. METHODS: We included participants with type 2 diabetes (T2D) who were free of arrhythmias during recruitment in the UK Biobank study. The associations of microvascular disease states (defined by the presence of retinopathy, peripheral neuropathy or chronic kidney disease), four modifiable arrhythmic risk factors (body mass index, smoking, systolic blood pressure and glycosylated haemoglobin) and their joint associations with incident arrhythmias were examined. RESULTS: Among the 25 632 participants with T2D, 1705 (20.1%) of the 8482 with microvascular disease and 2017 (11.8%) of the 17 150 without microvascular disease developed arrhythmias during a median follow-up of 12.3 years. Having any of the three microvascular diseases was associated with a 48% increase in the hazard of developing arrhythmias. Incorporating microvascular disease states into a model alongside 11 traditional risk factors significantly enhanced arrhythmia prediction. Furthermore, individuals with microvascular disease who had optimal levels of zero to one, two, three or four arrhythmic risk factors showed an HR of 2.05 (95% CI 1.85, 2.27), 1.67 (95% CI 1.53, 1.83), 1.35 (95% CI 1.22, 1.50) and 0.91 (95% CI 0.73, 1.13), respectively, compared with those without microvascular disease. CONCLUSIONS: Although microvascular disease, a non-traditional risk factor, was associated with incident arrhythmias in individuals with T2D, having optimal levels of risk factors may mitigate this risk.

Transvaginal natural orifice transluminal endoscopic surgery for myomectomy: A more suitable surgical approach for enhanced recovery after surgery.

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is widely recognized for its potential benefits, including reducing post-surgical pain and leaving no discernible scarring. However, the anatomical specificity of the vNOTES approach may elevate the risk of nearby organ damage, such as the rectum and bladder. Thus, this study aims to demonstrate the safety and relative merits of vNOTES over transumbilical laparoendoscopic single-site surgery (LESS). METHODS: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 110 patients who underwent myomectomy in vNOTES or LESS from January 2021 to December 2022. This study prospectively collected and compared perioperative and follow-up data of the two groups. RESULTS: In the vNOTES group, patients had shorter postoperative anal exhaust time, lower pain medications use rate, shorter hospital stay but higher intraoperative conversion rate, and higher postoperative fever rate. vNOTES decreased the anal exhaust time by approximately 8.7 h (95 %CI: -16.182, -1.262, p = 0.007). Moreover, vNOTES reduces pain medication use risk by 73.1 % (OR: 0.269, 95 %CI: 0.172, 0.318, p = 0.016). CONCLUSION: Relative to LESS, vNOTES can make patients mitigate postoperative discomfort, accelerate the recovery of gastrointestinal function, curtail hospitalization duration, and enable a more rapid return to daily activities in myomectomy. However, vNOTES has a higher risk of surgical conversion and adjacent organ injury. Therefore, larger scale prospective studies are needed to prove its security and promote the widespread application of vNOTES in myomectomy.

Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study.

CONTEXT: The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated. OBJECTIVE: To investigate the role of MVD and CVHMs in the development of CHD among T2DM. DESIGN: We included 19,664 participants with T2DM from the UK Biobank who had data on CVH metrics (CVHMs) and were free of CHD during recruitment. CVHMs were defined based on five behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and three biological factors (glycemic control, hyperlipidemia, and hypertension). MVD was defined as the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. HR and 95% CI of CHD were estimated by multivariable Cox regression models. RESULTS: There were 3,252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each of the unfavorable CVHMs was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR=4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs. CONCLUSIONS: Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such an association may be amplified by unfavorable CVHMs.

Transvaginal natural orifice endoscopic surgery for tubal ectopic pregnancy: A more suitable surgical approach for enhanced recovery after surgery.

Objective: We aimed to determine the safety of Vaginal natural orifice transluminal endoscopic surgery (vNOTES) in terms of the Enhanced Recovery after Surgery (ERAS) concept for tubal pregnancy surgery and provide a detailed process of vNOTES for tubal pregnancy surgery, including experience and key points for surgeons performing this procedure. Methods: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 219 patients who underwent tubal ectopic pregnancy surgery between September 2021 and March 2022. The patients underwent salpingectomy or salpingostomy using transumbilical laparoendoscopic single-site surgery (LESS) or vNOTES, according to their preferences. This study prospectively collected perioperative and one-year follow-up data on tubal pregnancy outcomes after vNOTES and compared them with those after LESS. Results: The vNOTES group showed a shorter surgical duration, hospitalization duration, and postoperative exhaust time and a lower analgesic medication usage rate, but it showed a higher surgical conversion rate. The vNOTES approach reduced the postoperative exhaust time by approximately 9 h (95% confidence interval [CI]: -11.93, -5.57 h, p < .001) and the risk of postoperative analgesic drug use by 77% (odds ratio, 0.23; 95% CI: 0.10, 0.61, p = .023). Conclusion: vNOTES can shorten the exhaust time and duration of hospitalization, reduce postoperative pain, and avoid surface surgical scars in tubal pregnancy surgeries, consistent with the ERAS concept. However, more comprehensive preoperative evaluation of patients who choose vNOTES is required to reduce the occurrence of intraoperative conversion.Trial registration: ChiCTR2100053483.

Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION: Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

[Effect of Microplastics and Phenanthrene on Soil Chemical Properties, Enzymatic Activities, and Microbial Communities].

Microplastic and polycyclic aromatic hydrocarbon (PAHs) pollution have received increasing attention due to their ubiquitous distribution and potential risks in soils. However, the effects of microplastics-PAHs combined pollution on soil ecosystems remain unclear. Polyethylene (PE)/polypropylene (PP) and phenanthrene (PHE) were selected as the representatives of microplastics and PAHs, respectively. A 300-day soil microcosm experiment was conducted to study the single and combined effects of PE/PP and PHE on soil chemical properties, enzymatic activities, and bacterial communities (i.e., quantity, composition, and function), using the soil agricultural chemical analysis method and 16S amplicon sequencing technology. The interactions of soil properties, enzyme activities, and flora in the presence of PE/PP and PHE were analyzed. The results showed that the addition of PE/PP and PHE slightly changed the pH, available phosphorus (AP), and microbial quantity (i.e., bacteria, actinomycetes, and mold) but considerably increased the fluorescein diacetate hydrolase (FDAse) activity. There was a significant enhancement of soil organic matter (SOM) and urease activity in PE, PP, PHE-PE, and PHE-PP amended systems. PHE, PHE-PE, and PHE-PP obviously increased the dehydrogenase/neutral phosphatase activities and available nitrogen (AN) content. PHE had little effect on the microbial community. The PE, PP, PHE-PE, and PHE-PP addition influenced the microbial community to some extent. PE/PP and PHE showed positive effects on the energy production, growth, and reproduction of soil microorganisms and then accelerated the metabolism/degradation of pollutants and membrane transport. The changes in AN and SOM induced by PE/PP and PHE were the key factors affecting soil enzyme activities. Alterations in AN, AP, and pH were mainly responsible for the increase in microbial population. The changes in the microbial community were related to soil chemical properties and enzyme activities, and SOM had a significant effect on the microbial community. The presence of different carbon sources (PE/PP and PHE) in the soil and the microbial interaction also affected the microbiota. In conclusion, the addition of single or combined pollutants of PE/PP and PHE influenced the soil chemical properties, enzymatic activities, bacterial communities, and their interaction processes, thus facilitating the adaptation of the microbial community to pollutant stress.

Crocin alleviates neurotoxicity induced by bupivacaine in SH-SY5Y cells with inhibition of PI3K/AKT signaling.

BACKGROUND: Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. OBJECTIVE: The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. METHOD: Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. RESULT: Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3ß. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. CONCLUSION: These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.

Phellinus linteus polysaccharides: A review on their preparation, structure-activity relationships, and drug delivery systems.

Phellinus linteus polysaccharides exhibit antitumor, immunomodulatory, anti-inflammatory, and antioxidant properties, mitigate insulin resistance, and enhance the diversity and abundance of gut microbiota. However, the bioactivities of P. linteus polysaccharides vary owing to the complex structure, thereby, limiting their application. Various processing strategies have been employed to modify them for improving the functional properties and yield. Herein, we compare the primary modes of extraction and purification employed to improve the yield and purity, review the structure-activity relationships, and discuss the application of P. linteus polysaccharides using nano-carriers for the encapsulation and delivery of various drugs to improve bioactivity. The limitations and future perspectives are also discussed. Exploring the bioactivity, structure-activity relationship, processing methods, and delivery routes of P. linteus polysaccharides will facilitate the development of functional foods and dietary supplements rich in P. linteus polysaccharides.

Pantoea jilinensis D25 enhances tomato salt tolerance via altering antioxidant responses and soil microbial community structure.

As a major challenge to global food security, soil salinity is an important abiotic stress factor that seriously affects the crop growth and yield. In this study, the mechanism of salt resistance of Pantoea jilinensis D25 and its improving effect on salt tolerance of tomato were explored with salt resistance-related genes identified in strain D25 by genomic sequencing. The results showed that in comparison with the treatment of NaCl, strain D25 significantly increased the fresh weight, shoot length, root length, and chlorophyll content of tomato under salt stress by 46.7%, 20%, 42.4%, and 44.2%, respectively, with increased absorptions of various macronutrients and micronutrients and decreased accumulation of Na+. The activities of defense enzymes (peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, and polyphenol oxidase) were enhanced, while the content of malondialdehyde was decreased. The results of quantitative real-time PCR analysis showed that the expressions of genes (SlSOS1, SlNHX1, SlHKT1.1, SlSOD1, SlAPX2, SlAOS, SlPin II, Solyc08g066270.1, Solyc03g083420.2 and SlGA20ox1) related to ion transporters, antioxidant machinery, key defense, serine/threonine protein kinase synthesis, and gibberellin (GA) signal protein were up-regulated and were the highest in the treatment of both NaCl and strain D25. The activities of enzymes (dehydrogenase, urease, invertase, and catalase activities) related to soil fertility were enhanced. The results of 16S rRNA sequencing showed that soil microbial diversity and the abundance of probiotics (e.g., Acidibacter, Limnobacter, and Romboutsia) were significantly increased. Our study provided strong experimental evidence to support the agricultural application of strain D25 in the promotion of growth in crops.