Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

Molluscan pleiotropic FADD involved in innate immune signaling and induces apoptosis.

Fas-associated protein with death domain (FADD) was initially identified as a crucial adaptor protein in the apoptotic pathway mediated by death receptor (DR). Subsequently, many studies have confirmed that FADD plays a vital role in innate immunity and inflammatory responses in animals. However, the function of this pleiotropic molecule in mollusk species has not been well explored. In this study, we successfully verified the gene sequence of FADD in the Zhikong scallop (Chlamys farreri) and designated it as CfFADD. The CfFADD protein contains a conserved death effector and death domains. Phylogenetic analysis showed that CfFADD is a novel addition to the molluscan FADD family with a close evolutionary relationship with molluscan FADD subfamily proteins. CfFADD mRNA expression in various scallop tissues was significantly induced by challenge with pathogen-associated molecular patterns (lipopolysaccharide, peptidoglycan, and poly(I:C)), suggesting its role in innate immunity in scallops. Co-immunoprecipitation showed that CfFADD interacted with the scallop DR (tumor necrosis factor receptor) and a signaling molecule involved in the Toll-like receptor pathway (interleukin-1 receptor-associated kinase), confirming that CfFADD may be involved in DR-mediated apoptosis and innate immune signaling pathways. Further studies showed that CfFADD interacted with CfCaspase-8 and activated caspase-3. HEK293T cells exhibited distinct apoptotic features after transfection with a CfFADD-expression plasmid, suggesting a functional DR-FADD-caspase apoptotic pathway in scallops. Overexpression of CfFADD led to a significant dose-dependent activation of interferon ß and nuclear factor-κB reporter genes, demonstrating the key role of CfFADD in innate immunity. In summary, our research has confirmed the critical roles of CfFADD in innate immunity and apoptosis and provides valuable information for developing comparative immunology theories.

Development and validation of a simultaneous quantitative analytical method for two Alternaria toxins and their metabolites in plasma and urine using ultra-high-performance liquid chromatography-tandem mass spectrometry.

Much more attention has been paid to the contamination of Alternaria toxins because of food contamination and the threat to human health. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous detection of the prototypical alternariol, alternariol monomethylether, and the metabolites 4-oxhydryl alternariol, and alternariol monomethylether 3-sulfate ammonium salt of Alternaria toxins. The positive samples were used as matrix samples to optimize the different experimental conditions. 0.01% formic acid solution and acetonitrile were used as the mobile phase, and analytes were scanned in negative electron spray ionization under multiple reaction monitoring, and quantitative determination by isotope internal standard method. Application of this method to samples of human plasma and urine showed the detection of the above analytes. The results showed that the recoveries were from 80.40% to 116.4%, intra-day accuracy was between 0.6% and 8.0%, and inter-day accuracy was between 1.1% and 12.1%. The limit of detection of the four analytes ranged from 0.02 to 0.6 µg/L in urine, and 0.02 to 0.5 µg/L in plasma, respectively. Thus, the developed method was rapid and accurate for the simultaneous detection of analytes and provided a theoretical basis for the risk assessment of Alternaria toxins for human exposure.

Mechanistic insight into near-infrared light-driven Cu2O/WO2 Ohmic contact photothermal catalysts for high-efficiency antibiotic wastewater purification.

Near-infrared (NIR) light-induced photothermal effect is beneficial for accelerating catalytic processes; thus, it is imperative to develop novel photothermal catalysts for promoting practical application. Herein, we synthesized NIR-responsive Cu2O/WO2 Ohmic contact photothermal catalysts through a facile ethylene glycol-assisted liquid-phase reduction method. In this photothermal catalyst, a new-type NIR-responsive Cu2O semiconductor is integrated with an NIR-responsive WO2 semimetal component to form an Ohmic contact, which is more beneficial for simultaneously promoting photocharge separation and enhancing NIR light absorption for a high-efficiency photothermal effect. As expected, the Cu2O/WO2 composite displays higher NIR light-driven photothermal catalytic performance for tetracycline removal from wastewater. Various characterization methods and density functional theory calculations were performed to obtain in-depth mechanistic insights into the NIR light-driven Cu2O/WO2 Ohmic contact photothermal catalysts. Hopefully, this research could provide a useful guideline for researchers focusing on the photothermal engineering of new composite photocatalysts.

Molecular cloning and functional study of a Rel homologous gene in sea urchin Strongylocentrotus intermedius.

NF-κB (Nuclear factor-kappa B) family proteins are versatile transcription factors that play crucial regulatory roles in cell development, growth, apoptosis, inflammation, and immune response. However, there is limited research on the function of these key genes in echinoderms. In this study, an NF-κB family gene (SiRel) was identified in sea urchin Strongylocentrotus intermedius. The gene has an open reading frame length of 1809 bp and encodes for 602 amino acids. Domain prediction results revealed that the N-terminal of SiRel protein encodes a conserved Rel homology domain (RHD), including the RHD-DNA binding domain and the RHD-dimerization domain. Multiple sequence comparison results showed that the protein sequences of these two domains were conserved. Phylogenetic analysis indicated that SiRel clustered with Strongylocentrotus purpuratus p65 protein and Rel protein of other echinoderms. Results from quantitative real-time PCR demonstrated detectable SiRel mRNA expression in all tested sea urchin tissues, with the highest expression level found in the gills. And SiRel mRNA expression levels were significantly induced after LPS (Lipopolysaccharide) and poly(I:C) (Polyinosinic:polycytidylic acid) stimulation. In addition, SiRel protein expression can be found in cytoplasm and nucleus of HEK293T cells. Co-immunoprecipitation results showed that SiRel could interact with sea urchin IκB (Inhibitor of NF-κB) protein. Western blotting and dual-luciferase reporter gene assay results indicated that overexpression of SiRel in HEK293T cells could impact the phosphorylation levels of JNK (c-Jun N-terminal kinase) and Erk1/2 (Extracellular signal-regulated kinases1/2) and activate interleukin-6 (IL-6), activating protein 1 (AP-1), interferon (IFN)α/ß/γ, and signal transducer and activator of transcription 3 (STAT3) reporter genes in HEK293T cells. In conclusion, this study reveals that SiRel plays an important role in the innate immune response of sea urchins and enriches our understanding of comparative immunology theory.

Surgical Correction of Orbital Hypertelorism With Absorbable Plate Instead of Frontal and Orbital Bar and Inverted U-Shaped Osteotomy.

OBJECTIVE: The aim of the study is to investigate the effect and feasibility of using absorbable plate instead of frontal and orbital bar and inverted U-shaped osteotomy to correct the widening of orbital distance. METHODS: The surgical effect and feasibility of using absorbable plate instead of frontal and orbital bridge plus inverted U-osteotomy for orbital widening syndrome in seven cases between January 2019 and February 2022 were retrospectively analyzed. First, the surgical procedure for orbital hypertelorism was inverted U-shaped orbital osteotomy, and a frontal bone flap was removed, exposing the superior orbital margin and the orbital circumference, and the orbital bone was directly cut off by inverted U-shaped osteotomy. The widened bone in the middle of the orbit was removed, and a long absorbable plate was used to replace the orbitofrontal bridge. The two sides of the orbit were fixed on the absorbable plate, and the absorbable plate was fixed on the rear skull. The clinical effect of treatment, complications (such as cerebrospinal fluid leakage and infection), safety, and feasibility of surgery were evaluated. RESULTS: Using absorbable plate instead of fronto-orbital bridge achieved the effect of orbitofrontal bridge, without orbital distance widening, cerebrospinal fluid leakage, and intracranial infection. Operating time was reduced. There was no metal fixation, and there was no risk of a second operation. CONCLUSIONS: The effect of replacing the frontal-orbital bridge with an absorbable plate and inverted U-shaped osteotomy is positive, the operation time is short, and the orbital distance is clearly improved. This approach can replace the traditional orbital-distance operation, and the incidence of postoperative cerebrospinal fluid leakage and infection is low. Long-term follow-up results are stable.

[Research advances in the development and function of macrophages and classical dendritic cells during resting and infection].

Macrophages (MACs) and classical dendritic cells (cDCs) represent the front line of immune defense, playing crucial roles in both innate and adaptive immunity due to their remarkable tissue specificity and precise adaptation to environmental cues. MACs contribute to maintaining tissue homeostasis and immune surveillance, while cDCs function as the most efficient antigen-presenting cells, playing a critical role in immune responses. These two cell types share similarities and interconnections. Both MACs and cDCs are capable of recognizing pathogens and tissue damage, secreting cytokines to activate other innate immune cells, and initiating or modulating adaptive immunity through interactions with T cells. In this review, we provide a comprehensive analysis of the research advances in the development and functions of MACs and cDCs during resting and infection processes, elucidate their interrelationships and interactions within the immune system, and offer a theoretical basis for in-depth studies of diseases.

Assessing the feasibility of digital keypress statistics to detect seizures and capture cognitive impairment in patients with epilepsy: A pilot study.

BACKGROUND: Efficient, non-invasive monitoring may provide a more accurate and comprehensive understanding of seizure frequency and the development of some comorbidities in people with epilepsy. Novel keyboard technology measuring digital keypress statistics has demonstrated its practical value for neurodegenerative diseases including Parkinson's Disease and Dementia. Smartphones integrated into daily life may serve as a low-burden longitudinal monitoring system for patients with epilepsy. OBJECTIVE: This study aimed to assess the feasibility of keyboard statistics as an objective measure of seizure frequency for patients with epilepsy, in addition to tracking differences between cognitively normal and cognitively impaired patients. METHODS: Six adult patients admitted to the Epilepsy Monitoring Unit (EMU) at Mayo Clinic in Rochester, Minnesota were studied. The keyboard was installed on the patient's smartphone. In the EMU, typing statistics were correlated to electroencephalogram (EEG) confirmed seizures. After discharge, participants continued using their keyboards and kept a seizure log. We also analyzed the key press/release times and usage of participants' keyboards for adherence. RESULTS: Keyboard sessions during and after seizures assessed for key press/release differences versus baseline showed no statistically significant difference (p = 0.44). Using one-way ANOVA, cognitive impairment's potential impact on keyboard statistics was explored in patients who had neuropsychological testing (N = 3). Significant differences were found between patients with and without cognitive impairment (p < 0.001). No significant difference was noted between patients with mild intellectual disability and normal cognitive function (p = 0.55).

Diagnostic and Management Value of Multi-Slice Computed Tomography in Esophageal Jujube Pit Impaction.

Objective: The diagnostic value of multi-slice computed tomography (MSCT) in esophageal jujube pit impaction was explored in this study. Methods: A retrospective analysis was performed on MSCT data obtained from a cohort of 40 patients experiencing esophageal jujube pit impaction. The study period encompassed the interval from December 2018 to November 2019. The analysis involved examining the age distribution of the patients, the location of the jujube pit impaction, its connection to the esophagus, associated complications, and the methods used for treatment. All imaging results were compared with the outcomes of surgical or endoscopic interventions. Results: (1) Out of 40 patients, 30 individuals were 58 years old or above, constituting 75% of the study sample. (2) In 80% of the instances (32 cases), the jujube pit was located in the initial segment of the esophagus, exhibiting a spindle shape with varying levels of central low density. (3) We examined the correlation between the angle of the impacted jujube pit and the esophageal longitudinal axis, categorizing 2 cases as longitudinal impaction, 16 as oblique impaction, and 22 as transverse impaction. Among the 40 cases, 28 displayed only slight thickening of the esophageal wall at the impaction site, while 9 cases exhibited heightened periesophageal fat density, and 3 showed small periesophageal air bubbles. (4) Endoscopic evaluation identified damage to the esophageal mucosa in 35 instances and the formation of esophageal perforation in 5 cases. Among patients with perforation, one or both ends of the jujube pit had penetrated the esophageal wall, accompanied by different levels of surrounding inflammatory encapsulation. Conclusion: MSCT is crucial for pinpointing jujube pit impaction and its relation to the esophageal wall and nearby structures, aiding in preoperative and postoperative complications. It is highly feasible for endoscopic cases but limited in complex ones needing thoracoscopy or open-heart surgery.

Preliminary study on AI-assisted diagnosis of bone remodeling in chronic maxillary sinusitis.

OBJECTIVE: To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. METHODS: Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. RESULTS: Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. CONCLUSION: It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

A newly identified scallop MyD88 interacts with TLR and functions in innate immunity.

Myeloid differentiation factor-88 (MyD88) is a key adaptor of the toll-like receptor (TLR) signaling pathway and plays a crucial role in innate immune signal transduction in animals. However, the MyD88-mediated signal transduction mechanism in shellfish has not been well studied. In this study, a new MyD88 gene, CfMyD88-2, was identified in the Zhikong scallop, Chlamys farreri. The 1779 bp long open reading frame encodes 592 amino acids. The N-terminus of CfMyD88-2 contains a conserved death domain (DD), followed by a TIR (TLR/Interleukin-1 Receptor) domain. The results of the multi-sequence comparison showed that the TIR domain sequences were highly conserved. Phylogenetic analysis revealed that CfMyD88-2 was first associated with Mizuhopecten yessoensis MyD88-4 and Argopecten irradians MyD88-4. CfMyD88-2 mRNA was expressed in all scallop tissues, as detected by qRT-PCR, and the expression level was the highest in the mantle and hepatopancreas. In addition, CfMyD88-2 mRNA expression significantly increased after pathogen-associated molecular patterns (PAMPs, such as lipopolysaccharide, peptidoglycan, or polyinosinic-polycytidylic acid) stimulation. The results of the co-immunoprecipitation experiments in HEK293T cells showed that both CfMyD88-1 and CfMyD88-2 interacted with the TLR protein of scallops, suggesting the existence of more than one functional TLR-MyD88 signaling axis in scallops. Dual luciferase reporter gene assays indicated that the overexpressed CfMyD88-2 in HEK293T cells activated interferon (IFN) α, IFN-ß, IFN-γ, and NF-κB reporter genes, indicating that the protein has multiple functions. The results of the subcellular localization experiment uncovered that CfMyD88-2 was mainly localized in the cytoplasm of human cells. In summary, the novel identified CfMyD88-2 can respond to the challenge of PAMPs, participate in TLR immune signaling, and may activate downstream effector genes such as NF-κB gene. These research results will be useful in advancing the theory of innate immunity in invertebrates and provide a reference for the selection of disease-resistant scallops in the future.

Cavitation erosion-corrosion properties of as-cast TC4 and LPBF TC4 in 0.6 mol/L NaCl solution: A comparison investigation.

In this work study, a comparative analysis was undertaken to investigate investigation into the cavitation erosion (CE) and corrosion behavior of laser powder bed fusion (LPBF) TC4 and as-cast TC4 in 0.6 mol/L NaCl solution. Relevant results indicated that LPBF TC4 revealed a rectangular checkerboard-like pattern with a more refined grain size compared to as-cast TC4. Meanwhile, LPBF TC4 surpassed its as-cast counterpart in CE resistance, demonstrating approximately 2.25 times lower cumulative mass loss after 8 h CE. The corrosion potential under alternating CE and quiescence conditions demonstrated that both LPBF TC4 and as-cast TC4 underwent a rapid potential decrease at the initial stages of CE, while a consistent negative shift in corrosion potential was observed with the continuously increasing CE time, indicative of a gradual decline in repassivation ability. The initial surge in corrosion potential during the early CE stages was primarily attributed to accelerated oxygen transfer. As CE progressed, the significant reduction in corrosion potential for both LPBF TC4 and as-cast TC4 was attributed to the breakdown of the passive film. The refined and uniform microstructure in LPBF TC4 effectively suppresses both crack formation and propagation, underscoring the potential of LPBF technology in enhancing the CE resistance of titanium alloys. This work can provide important insights into developing high-quality, reliable, and sustainable CE-resistant materials via LPBF technology.

The Microbiome Protocols eBook initiative: Building a bridge to microbiome research.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

Efficacy and safety of immune checkpoint inhibitors in solid tumor patients combined with chronic coronary syndromes or its risk factor: a nationwide multicenter cohort study.

BACKGROUND: Although, immune checkpoint inhibitors (ICIs) have been widely applied in the therapy of malignant tumors, the efficacy and safety of ICIs in patients with tumors and pre-existing CAD, especially chronic coronary syndromes (CCS) or their risk factors (CRF), is not well identified. METHODS: This was a nationwide multicenter observational study that enrolled participants who diagnosed with solid tumors and received ICIs therapy. The main efficacy indicators were progression-free survival (PFS) and overall survival (OS), followed by objective response rate (ORR) and disease control rate (DCR). Safety was assessed by describing treatment-related adverse events (TRAEs) during ICIs therapy evaluated by the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). RESULTS: In the current research, we retrospectively analyzed the data of 551 patients diagnosed with solid tumors and received ICIs therapy, and these patients were divided into CCS/CRF group and non-CCS/CRF group. Patients with CCS/CRF had more favorable PFS and OS than patients without CCS/CRF (P < 0.001) and the pre-existing CCS/CRF was a protective factor for survival. The ORR (51.8% vs. 39.1%) and DCR (95.8% vs. 89.2%) were higher in CCS/CRF group than in non-CCS/CRF group (P = 0.003, P = 0.006). In this study, there was no significant difference in treatment-related adverse events (TRAEs), including immune-related adverse events (irAEs), between the two groups. CONCLUSIONS: We concluded that ICIs appear to have better efficacy in malignant solid tumor patients with pre-existing CCS/CRF and are not accompanied by more serious irAEs.

High-security multidimensional data protection system based on the Hartley algorithm-driven chaotic scheme.

This paper proposes a high-security multidimensional data protection system based on the Hartley algorithm-driven chaotic scheme. We utilize the fast Hartley algorithm instead of the fast fourier computation, and we employ chaotic sequences generated by the multi-winged chaotic system to achieve chaos-driven 3D constellation mapping, effectively integrating the chaotic system with the stochastic amplitude modulator. We reduce the signal's peak-to-average power ratio (PAPR) by deploying a random amplitude modulator. Simultaneously, this approach enhances the security of the physical layer of the signal. The PAPR reduction can reach up to 2.6 dB, while the most robust and stable modulator scheme can gain 2 dB. Finally, in the Hartley frequency domain, the signal's frequency is disrupted, providing the entire system with a key space of 10131 to resist violent cracking and thus improving the system's overall security. To validate the feasibility of our scheme in comparison to conventional IFFT-based encrypted 3D orthogonal frequency division multiplexing, We achieved a transmission rate of 27.94 Gb/s over a 2 km multicore fiber. Experimental results show that since the random amplitude generator effectively reduces PAPR, our proposed encryption scheme increases the forward error correction threshold range by 1.1 dB, verifying that our proposed scheme has highly reliable security performance.

Association of screen-based sedentary behavior with executive function in school-aged children: A functional near-infrared spectroscopy study.

Screen-based sedentary behavior (SSB) is a significant risk factor for the health of school-aged children, and guidelines recommend limiting SSB to 2 hr per day. This study aimed to examine association and potential mechanisms between SSB and executive function (EF) by comparing Stroop performance and frontal hemodynamic responses between children with and without excessive SSB. A total of 70 children aged 10 to 15 years were recruited and divided into two groups: excessive screen time (≥2 hr/day; n = 35; ES group) and normal screen time (<2 hr/day; n = 35; NS group). The Chinese version of the Adolescent Sedentary Activities Questionnaire was used to assess SSB, whereas EF was evaluated using the Stroop task. The frontal hemodynamic responses during the Stroop task were measured using functional near-infrared spectroscopy. The results indicated that the ES group had lower accuracy, longer reaction times, and greater activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and left pre-supplementary motor area (Pre-SMA) compared with the NS group. Furthermore, significant correlations were observed between Stroop performance and cortical activation in the left DLPFC and Pre-SMA. These findings demonstrate that excessive SSB is associated with poor EF, which may be explained by a decrease in neural efficiency of the left DLPFC and Pre-SMA.

Major depression disorder and heart failure: A two-sample bidirectional Mendelian randomization study.

OBJECTIVE: To determine whether a bidirectional causal relationship exists between major depressive disorder (MDD) and heart failure (HF). METHODS: Our two-sample bidirectional Mendelian randomization (MR) study consisted of two parts. In the first part, we conducted a forward MR analysis where MDD was considered as the exposure and HF as the outcome. In the second part, a reverse MR analysis was performed, treating HF as the exposure and MDD as the outcome. Summary data on MDD and HF were obtained from the IEU Open GWAS database. RESULTS: Based on the results of the MR-Egger regression intercept test, there was no evidence of horizontal pleiotropy in this study. Furthermore, the IVW results consistently suggested estimates of causal effect values. The findings revealed that individuals with MDD had a 16.9% increased risk of HF compared to those without MDD (OR = 1.169, 95%CI: 1.044-1.308, P = 0.007). However, there was no evidence to support that HF would increase the risk of MDD (OR = 1.012, 95%CI: 0.932-1.099, P = 0.773). Heterogeneity in SNPs of MDD and HF was observed through the heterogeneity test and funnel plot. Additionally, the leave-one-out method did not identify any instances where a single SNP was biased toward or dependent on causation. CONCLUSION: Our study provides evidence supporting a one-way causal relationship between MDD and HF. Specifically, MDD increases the risk of developing HF. However, our findings did not provide any evidence suggesting that HF increases the risk of developing MDD.

Untargeted Metabolomics Based on Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Differential Metabolite Analysis of Pinelliae Rhizoma and Its Adulterants.

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis.

Objectives: The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness. Methods: We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311). Results: From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events. Conclusions: Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.