Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Neuroimaging of motor recovery after ischemic stroke - functional reorganization of motor network.

The long-term motor outcome of acute stroke patients may be correlated to the reorganization of brain motor network. Abundant neuroimaging studies contribute to understand the pathological changes and recovery of motor networks after stroke. In this review, we summarized how current neuroimaging studies have increased understanding of reorganization and plasticity in post stroke motor recovery. Firstly, we discussed the changes in the motor network over time during the motor-activation and resting states, as well as the overall functional integration trend of the motor network. These studies indicate that the motor network undergoes dynamic bilateral hemispheric functional reorganization, as well as a trend towards network randomization. In the second part, we summarized the current study progress in the application of neuroimaging technology to early predict the post-stroke motor outcome. In the third part, we discuss the neuroimaging techniques commonly used in the post-stroke recovery. These methods provide direct or indirect visualization patterns to understand the neural mechanisms of post-stroke motor recovery, opening up new avenues for studying spontaneous and treatment-induced recovery and plasticity after stroke.

Short-term ozone exposure and cancer mortality in Brazil: A nationwide case-crossover study.

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short-term O3 exposure and site-specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time-stratified case-crossover design was applied to assess the O3-cancer mortality association. Subgroup analyses by age, sex, season, time-period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non-threshold exposure-response relationship was observed for short-term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%-1.20%) increase in all-cancer mortality risks for each 10-µg/m3 increment of three-day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000-2019, a total of 147,074 (116,690-177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014-28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations.

Type 2 diabetes increase the risk of arteriovenous fistula non-maturation, mediated by postoperative vascular hemodynamics.

BACKGROUND: The progression of atherosclerosis in small and medium-sized vessels has been associated with Type 2 diabetes (T2D). However, the influence of T2D on postoperative vascular remodeling and arteriovenous fistula (AVF) maturation is inconclusive. Besides, hemodynamic changes of postoperative vessel are also associated with AVF maturation. This study is intended to investigate the link between T2D and the occurrence of AVF non-maturation, as well as to delve into the impact of postoperative vascular hemodynamic parameters in this process. METHODS: A total of 477 hemodialysis patients, with or without type 2 diabetes, underwent AVF creation at Beijing Haidian Hospital (Haidian Section of Pecking University Third Hospital) from August 2018 to March 2022 were collected, and were followed for 1-5 years. Logistic regression was applied to analyze the association of T2D, postoperative vascular hemodynamic parameters with the risk of AVF non-maturation. To verify the stability of the results, the sensitivity analyses were performed using propensity scores to match patients. We further investigated the regulatory role of the postoperative vascular hemodynamics. RESULTS: There were 173 patients with T2D and 304 patients without T2D in this study. The maturation rate in T2D and non-T2D group was 47.977% and 63.816%, respectively. The findings of logistic regression analysis suggested that T2D significantly increased the risk of AVF immaturity [OR 1.716 (1.019-2.890), P = 0.042]. Besides, T2D was associated with the restriction of postoperative vascular hemodynamic parameters changes, including with decreased diameter of forearm cephalic radial artery and dilation rate of radial artery. The result of logistic regression analysis indicated that cephalic vein diameter at 1-month [0.402 (0.237-0.681), P = 0.001] and cephalic vein diameter at 2-month [0.501 (0.355-0.708), P < 0.001] were independently correlated with AVF maturation. Besides, the results of sensitivity analysis were consistent with that of logistic regression analysis. Moreover, the mediating effects of cephalic vein diameter were significant. CONCLUSION: Our findings discovered that T2D significantly increased the risk of arteriovenous fistula non-maturation, which was mainly mediated by the changes of cephalic vein diameter.

The association between air pollution and obesity: an umbrella review of meta-analyses and systematic reviews.

The objective of this umbrella review was to investigate comprehensive and synthesized evidence of the association between ambient air pollution and obesity based on the current systematic reviews and meta-analyses. Related studies from databases including PubMed, EMBASE, Web of Science, and the Cochrane Library, published before July 16, 2023, were considered in the analysis. All selected systematic reviews and meta-analyses were included in accordance with PRISMA guidelines. The risk of bias and the methodological quality were evaluated using the AMSTAR 2 tool. The protocol for this umbrella review was documented in PROSPERO with the registration number: CRD42023450191. This umbrella review identified 7 studies, including 5 meta-analyses and 2 systematic reviews, to assess the impacts of air pollutants on obesity. Commonly examined air pollutants included PM1, PM2.5, PM10, NO2, SO2, O3. Most of the included studies presented that air pollution exposure was positively associated with the increased risk of obesity. The impact of air pollution on obesity varied by different ambient air pollutants. This study provided compelling evidence that exposure to air pollution had a positive association with the risk of obesity. These findings further indicate the importance of strengthening air pollution prevention and control. Future studies should elucidate the possible mechanisms and pathways linking air pollution to obesity.

Short-Term Exposure to Wildfire-Specific PM2.5 and Hospitalization for Diabetes Morbidity: A Study in Multiple Countries and Territories.

OBJECTIVE: To evaluate associations of wildfire fine particulate matter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS: We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000-2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS: Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011-1.022), 1.023 (1.011-1.035), 1.023 (1.015-1.032), 0.962 (0.823-1.032), 1.033 (1.001-1.066), and 1.013 (1.004-1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. Relative risks (95% CI) of 0.67% (0.16-1.18%) and 1.02% (0.20-1.81%) for all cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS: We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury.

Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.

Prevalence of skin diseases among elderly prisoners in Taiwan: an examination of skin health in prison.

BACKGROUND: Although prisoner health is a topic of significant importance, it has received limited attention in epidemiological studies, likely due to challenges in obtaining data. Therefore, this study aimed to investigate the prevalence of skin diseases among elderly prisoners in Taiwan. METHODS: We examined the presence of skin diseases in 2215 elderly prisoners based on the International Classification of Diseases, 9th revision Clinical Modification (ICD-9-CM). Additionally, the most common types of skin diseases among elderly prisoners in Taiwan were identified. RESULTS: The prevalence of skin diseases among prisoners was estimated to be 55.03%. Elderly men prisoners exhibited a higher prevalence of skin diseases than the women prisoners. The most common skin diseases observed were as follows: contact dermatitis and other forms of eczema; pruritus and related conditions; cellulitis and abscesses; and urticaria. CONCLUSION: Skin diseases were identified in more than half of the elderly prisoners. The overall quality of life of elderly prisoners can be improved by addressing their skin health, which would contribute to the fulfilment of their basic human rights. CLINICAL TRIALS NUMBER: NA.

Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect.

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects, substantial tumor recurrence, and long-lasting bone reconstruction post tumor resection. Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices. Here, by deposition of calcium-based bilayer coating on the surface, a Mg-based composite implant platform is developed with tailored degradation characteristics, simultaneously integrated with chemotherapeutic (Taxol) loading capacity. The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles, not only in eliciting desirable osteoinductivity, but allows for modification of tumor microenvironment (TME) owing to the continuous release of degradation products. Specifically, the sustainable H2 evolution and Ca2+ from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction, which in turn leads to significant tumor-growth inhibition in vivo. In addition, the local chemotherapeutic delivery of the implant minimizes toxicity and side effects, but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model. Taken together, a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

Association of remnant cholesterol with renal function and its progression in patients with type 2 diabetes related chronic kidney disease.

Background: The association of Remnant cholesterol (RC) with renal function and its progression in patients with Type 2 diabetes (T2DM) related chronic kidney disease (CKD) remains unclear. Methods: 8,678 patients with T2DM-related CKD were included in cross-sectional analysis, and 6,165 patients were enrolled in longitudinal analysis and followed up for a median of 36.0 months. The outcomes were renal composite endpoint event and rapid progression of renal function. Results: 24.54% developed a renal composite endpoint event, and 27.64% rapid progression of renal function. RC levels above 0.56 mmol/L independently increased the risk of both renal composite endpoint (HR, 1.17; 95% CIs, 1.03-1.33) and rapid progression of renal function (OR, 1.17; 95% CIs, 1.01- 1.37). TG levels above 1.65 mmol/L only increased the risk of renal composite endpoint (HR, 1.16; 95% CIs, 1.02 -1.32). TC levels above 5.21 mmol/L increased the risk of renal composite endpoint (HR, 1.14; 95% CIs, 1.01-1.29) only in patients with proteinuria≥0.5g/d. Conversely, HDL-C levels below 1.20 mmol/L or above 1.84 mmol/L increased the risk of rapid progression of renal function (OR, 0.88; 95% CIs, 0.70 -0.99) in patients with proteinuria<0.5g/d (all P<0.05). Conclusion: In patients with T2DM-related CKD, RC was an independent risk factor for progression of renal function, and maintaining it below 0.56 mmol/L could reduce the risk of renal function progression.

Portable Near-Infrared to Near-Infrared Platform for Homogeneous Quantification of Biomarkers in Complex Biological Samples.

Förster resonance energy transfer (FRET)-based homogeneous immunoassay obviates tedious washing steps and thus is a promising approach for immunoassays. However, a conventional FRET-based homogeneous immunoassay operating in the visible region is not able to overcome the interference of complex biological samples, thus resulting in insufficient detection sensitivity and poor accuracy. Here, we develop a near-infrared (NIR)-to-NIR FRET platform (Ex = 808 nm, Em = 980 nm) that enables background-free high-throughput homogeneous quantification of various biomarkers in complex biological samples. This NIR-to-NIR FRET platform is portable and easy to operate and is mainly composed of a high-performance NIR-to-NIR FRET pair based on lanthanide-doped nanoparticles (LnNPs) and a custom-made microplate reader for readout of NIR luminescence signals. We demonstrate that this NIR-to-NIR FRET platform is versatile and robust, capable of realizing highly sensitive and accurate detection of various critical biomarkers, including small molecules (morphine and 1,25-dihydroxyvitamin D), proteins (human chorionic gonadotropin), and viral particles (adenovirus) in unprocessed complex biological samples (urine, whole blood, and feces) within 5-10 min. We expect this NIR-to-NIR FRET platform to provide low-cost healthcare for populations living in resource-limited areas and be widely used in many other fields, such as food safety and environmental monitoring.

Exploring the microRNA-mRNA regulatory network associated with solasonine in bladder cancer.

Background: Solasonine has been demonstrated to exert an inhibitory effect on bladder cancer (BC), but the potential mechanisms remain unclear. Therefore, the aim of this study is to explore the association between microRNAs (miRNAs)-mediated regulation and the anti-tumor activities of solasonine in BC. Methods: MiRNA sequencing was performed to identify the differentially expressed microRNAs (DE-miRNAs) associated with solasonine in BC cells. Functional enrichment analyses of the DE-miRNAs activated and inhibited by solasonine were then conducted. The DE-miRNAs with prognostic value for BC and those differentially expressed in the BC samples were subsequently identified as the hub DE-miRNAs. After identifying the messenger RNAs (mRNAs) that were targeted by the hub DE-miRNAs and those differentially expressed in the BC samples, a protein-protein interaction analysis was performed to identify the core downstream genes, which were then used to construct a solasonine-miRNA-mRNA regulatory network. Results: A total of 27 activated and 19 inhibited solasonine-mediated DE-miRNAs were identified that were found to be associated with several tumor-related biological functions and pathways. After integrating the results of the survival analysis and expression assessment, the following nine hub DE-miRNAs were identified: hsa-miR-127-3p, hsa-miR-450b-5p, hsa-miR-99a-5p, hsa-miR-197-3p, hsa-miR-423-3p, hsa-miR-4326, hsa-miR-625-3p, hsa-miR-625-5p, and hsa-miR-92a-3p. The DE-mRNAs targeted by the hub DE-miRNAs were predicted, and 30 core downstream genes were used to construct the solasonine-miRNA-mRNA regulatory network. miR-450b-5p was shown to be associated with the most mRNAs in this network, which suggests that it plays a crucial role in the solasonine-mediated anti-BC effect. Conclusions: A regulatory network, including solasonine, miRNAs, and mRNAs related to BC, was constructed. This network provides extensive insights into the molecular regulatory mechanisms that underlie the anti-cancer efficacy of solasonine in BC.

Self-perceived knowledge, attitude, and practice of evidence-based medicine before and after training among healthcare workers in Taizhou, China.

BACKGROUND: Evidence-based medicine (EBM) is the combination of the best research evidence with our clinical expertise, specific situations, and the unique values of our patients. It is essential to evaluate the effectiveness of EBM training for healthcare workers (HCWs). OBJECTIVES: This study aims to assess the impact of EBM training on HCWs' knowledge, attitude, and practice (KAP) related to EBM. METHODS: A self-reported online survey was carried out to investigate KAP related to EBM among HCWs at a tertiary hospital in Taizhou, China. HCWs participated in EBM training on 9 and 10 September 2023. The questionnaire survey was conducted to understand KAP related to EBM before and after the training, and to compare and analyze the results before and after the training. The R software (version 4.1.0) was used to analyze data. RESULTS: Sixty-four HCWs completed the survey with a response rate of 52.5% (64/122). The overall average scores of KAP related to EBM before training were 55.3, 63.0, and 34.5, respectively, and 56.9, 66.5, and 34.7 were the scores of KAP after training. HCWs' scores of knowledge (P = 0.033) and attitude (P < 0.001) related to EBM improved significantly after the training. CONCLUSION: This study implied that EBM training may improve the knowledge and attitude of HCWs, and its teaching effect is considerable.

Heterogeneous core-shell Co2(PS3)@Co2P nanowires with accelerated surface reconstruction for efficient electrocatalytic seawater oxidation.

The design of pre-catalysts and the rational manipulation of corresponding electrochemical reconstruction are vitally important to construct the highly durable and active catalysts for seawater oxidation, but rather challenging. Herein, a novel core-shell catalyst of Co2(PS3)@Co2P (labeled as CoPS) by epitaxial growth of amorphous cobalt phosphide (Co2P) on crystalline cobalt phosphorous trichalcogenide (Co2(PS3)) is firstly designed as a pre-catalyst for alkaline seawater oxidation. Various characterization techniques are employed to demonstrate that the unique amorphous-crystalline nanowire structure (CoPS) achieves the rapid surface reconstruction into active CoOOH and diversiform oxyanions species (labeled as CoPS-R). Theoretical simulations uncover that the in situ derived oxyanions (PO42-, SO32- and SO42-) on the surface of CoOOH can tune the electron distribution of Co site, thereby optimizing the chemisorption of oxygen evolution reaction (OER) intermediates on CoOOH and reducing the energy barrier of determining step. Consequently, in an alkaline natural seawater solution, the reconstructed CoPS-R catalyst exhibits small overpotentials of 357 and 402 mV for OER at 200 and 500 mA cm-2, respectively, together with an impressive durability over 500 h at a large current density of 500 mA cm-2 benefiting from the strong repulsive effect of the derived PO42-, SO32- and SO42- oxyanions. This work offers a new insight for comprehending the relationship of structure-composition-activity and develops a new approach toward the construction of efficient and robust OER catalysts for seawater electrolysis.

Enhancing efficacy and reducing toxicity: Therapeutic optimization in locoregionally advanced nasopharyngeal carcinoma.

When applied as the standard therapeutic modality, intensity-modulated radiotherapy (IMRT) improves local control and survival rates in patients with nasopharyngeal carcinoma (NPC). However, distant metastasis continues to be the leading cause of treatment failure. Here, we review the most recent optimization strategies for combining chemotherapy with IMRT in high-risk patients with locoregionally advanced NPC. We focus on major clinical trials on induction chemotherapy and metronomic adjuvant chemotherapy, emphasizing their efficacy in mitigating distant metastasis and prognosis. We also highlight innovations in reducing toxicity in low-risk patients, particularly through approaches of excluding chemotherapy, adopting equivalent low-toxicity drugs, or selectively exempting lymph nodes with low metastatic risk from irradiation. These approaches have provided positive treatment outcomes and significantly enhanced patients' quality of life. Finally, we provide an overview of the evolving immunotherapy landscape, with a focus on the ongoing trials and future potential of immune checkpoint inhibitors in advanced NPC treatment.

Comparison of the Ability of Gadobenate Dimeglumine and Gadolinium Ethoxybenzyl Dimeglumine to Display the major Features for Noninvasively Diagnosing Hepatocellular Carcinoma According to the LI-RADS 2018v.

OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines.

OBJECTIVE: Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer (NSCLC) and elucidates the underlying molecular mechanisms. METHODS: The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays. Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots. Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology, were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model. RESULTS: Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5'-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer. Please cite this article as follows: Zhu LH, Liang YP, Yang L, Zhu F, Jia LJ, Li HG. Cycloastragenolinduces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small celllung cancer cell lines. J Integr Med. 2024: Epub ahead of print.

Comparative analysis of the performance of hepatobiliary agents in depicting MRI features of microvascular infiltration in hepatocellular carcinoma.

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

Epitranscriptomic cytidine methylation of the hepatitis B viral RNA is essential for viral reverse transcription and particle production.

Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of viral RNAs. One prominent modification, the cytidine methylation 5-methylcytidine (m5C), is found on the RNA of HIV-1, where m5C enhances the translation of HIV-1 RNA. However, whether m5C functionally enhances the RNA of other pathogenic viruses remains elusive. Here, we surveyed a panel of commonly found RNA modifications on the RNA of hepatitis B virus (HBV) and found that HBV RNA is enriched with m5C as well as ten other modifications, at stoichiometries much higher than host messenger RNA (mRNA). Intriguingly, m5C is mostly found on the epsilon hairpin, an RNA element required for viral RNA encapsidation and reverse transcription, with these m5C mainly deposited by the cellular methyltransferase NSUN2. Loss of m5C from HBV RNA due to NSUN2 depletion resulted in a partial decrease in viral core protein (HBc) production, accompanied by a near-complete loss of the reverse transcribed viral DNA. Similarly, mutations introduced to remove the methylated cytidines resulted in a loss of HBc production and reverse transcription. Furthermore, pharmacological disruption of m5C deposition led to a significant decrease in HBV replication. Thus, our data indicate m5C methylations as a critical mediator of the epsilon elements' function in HBV virion production and reverse transcription, suggesting the therapeutic potential of targeting the m5C methyltransfer process on HBV epsilon as an antiviral strategy.