[Mechanism of Huachansu Injection against colorectal cancer based on network pharmacology and cellular experimental].

This study aimed to elucidate the mechanism of Huachansu Injection(HCSI) against colorectal cancer(CRC) using network pharmacology, molecular docking technology, and cellular experimental. This research group initially used LC-MS/MS to detect the content of 16 bufadienolides in HCSI. Ten bufadienolide components were selected based on a content threshold of greater than 10 ng·mL~(-1). Their potential targets were further predicted using the SwissTargetPrediction database. CRC-related targets were obtained through GeneCards, OMIM, TTD, and PharmGKB databases. The intersection targets of HCSI in the treatment of CRC were obtained through Venny. The "active component-target-disease" network and target protein-protein interaction(PPI) network were constructed via Cytoscape software. Core targets were screened based on the degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on these key targets. Molecular docking was conducted using AutoDock software on major bufadienolide active components and key targets. Different concentrations of HCSI, psi-bufarenogin(BUF), and bufotalin(BFT) were tested for their effects on cell viability, migration, and apoptosis rates in CRC HCT116 cells. Western blot was conducted to detect the expression of proteins related to the PI3K/Akt/mTOR signaling pathway in HCT116 cells. Eight main active components of HCSI, including arenobufagin, BUF, and BFT, as well as 20 key targets of HCSI in combating CRC, such as EGFR, IL6, and mTOR, were identified. Based on KEGG pathway enrichment and molecular docking results, the PI3K/Akt/mTOR signaling pathway was selected for further verification. Cellular experimental demonstrated that HCSI, BUF, and BFT significantly inhibited the proliferation and migration abilities of HCT116 cells, induced apoptosis in these cells, and downregulated the expression of PI3K/Akt/mTOR pathway-related proteins. This result suggests that HCSI, BUF, and BFT may exert their anti-CRC effects by regulating the PI3K/Akt/mTOR signaling pathway through targets such as mTOR and PIK3CA. This study provides theoretical evidence for exploring the active ingredients and mechanism of HCSI against CRC.

Factors influencing secondary overtriage in trauma patients undergoing interhospital transfer: A 10-year multi-center study in Hong Kong.

BACKGROUND: With the development of regionalised trauma networks, interhospital transfer of trauma patients is an inevitable component of the trauma system. However, unnecessary transfer is a common phenomenon, and it is not without risk and cost. A better understanding of secondary overtriage would enable emergency physicians to make better decisions about trauma transfers and allow guidelines to be developed to support this decision making. This study aimed to describe the pattern of secondary overtriage in Hong Kong and identify its associated factors. METHODS: This was a retrospective review of 10-years of prospectively collected multi-center data from two trauma registries in the New Territories of Hong Kong (2013-2022). The primary outcome is secondary overtriage, which was defined as early discharge alive within 48 h, Injury Severity Score (ISS) <15, and no surgical operation done. Patient characteristics, physiology, anatomy and investigation variables were compared against secondary overtriage using univariate and multivariable analyses. RESULTS: During the study period, 3852 patients underwent interhospital transfer from a non-trauma center to a trauma center, and 809 (21 %) of the transfers were considered secondary overtriage. The secondary overtriage rate was higher in pediatric age groups at 34.8 % (97/279). Logistic regression analysis showed secondary overtriage to be associated with blunt trauma and an Abbreviated Injury Scale (AIS) score of <3 for head or neck, thorax, abdomen and extremities. CONCLUSION: Interhospital transfer is an essential component of the trauma system. However, over one-fifth of the transfers were considered unnecessary in Hong Kong, and this could be considered to be an inefficient use of resources as well as cause inconvenience to patients and their families. We have identified related factors including blunt trauma, AIS <3 scores for head or neck, thorax, abdomen and extremities, and opportunities to establish and improve on transfer protocols. Further research should be aimed to safely reduce interhospital transfers in the future to improve the efficiency of the Hong Kong trauma system.

The Effect of Cosmetic Makeup on Body Imagery and Anxiety and Depression in Patients Undergoing Postoperative Chemotherapy for Breast Cancer: A Randomized Controlled Study.

Purpose: The objective was to compare the body images of breast cancer patients undergoing postoperative chemotherapy and the varying degrees of their anxiety and depression. The comparison involved those who received four consecutive cycles of cosmetic makeup and those who did not. Patients and Methods: Seventy-four breast cancer patients receiving postoperative chemotherapy were randomly assigned to either the control group or the intervention group. The control group received usual care, while the intervention group received four consecutive cycles of chemotherapy along with cosmetic makeup intervention on top of usual care. The intervention was carried out on the first day after the completion of each chemotherapy cycle. Assessments were made before the first intervention and 1 month after the fourth intervention using the Hospital Anxiety and Depression Scale and the Scale of Body Imagery. Results: After four cycles of intervention, significant differences emerged between the intervention and control groups regarding anxiety, depression, and body imagery. Additionally, within the intervention group, notable changes in these aspects were observed over time. Conclusion: The results showed that cosmetic interventions can effectively reduce the level of anxiety and depression of breast cancer patients receiving postoperative chemotherapy and effectively improve the body imagery of patients.

Inheritance of chlorantraniliprole resistance and fitness costs in a field population of Cnaphalocrocis medinalis (Lepidoptera: Pyralidae) in China.

BACKGROUND: Cnaphalocrocis medinalis is one of the major rice insect pests in Asia. Chlorantraniliprole is one of the most important insecticides for the control of C. medinalis. In this study, a field-resistant population and a susceptible strain of C. medinalis were used to evaluate the inheritance of chlorantraniliprole resistance and fitness costs in the field. RESULTS: The field-resistant population (Cm-RR) showed 128.4-fold resistance to chlorantraniliprole compared with the susceptible strain (Cm-SS). The dose-response of reciprocal cross progeny (F1 and F1') showed no significant difference, which indicated the inheritance of resistance to chlorantraniliprole in C. medinalis was autosomal. The degrees of dominance (D) of resistance for F1 and F1' were -0.19 and -0.05, respectively, indicating that the chlorantraniliprole resistance of C. medinalis was incompletely recessive inheritance. At the same time, significant differences between observed and expected mortalities of self-cross (F2 and F2') and backcross (BC and BC') progenies suggested chlorantraniliprole resistance is controlled by multiple genes. Furthermore, the Cm-RR population had a relative fitness of 0.32 with a substantially decreased pupation rate, emergence rate, fecundity, and substantially increased developmental time of larval and pupa stages. CONCLUSION: Current research showed that the inheritance of chlorantraniliprole resistance to C. medinalis was autosomal, incompletely recessive and multigene. The field-resistant population had a relative fitness of 0.32 when compared with the susceptible strain. This study provided valuable information for facilitating the development of chlorantraniliprole resistance management strategies. © 2024 Society of Chemical Industry.

Microsphere-Composite Hydrogel for Recruiting Stem Cells and Promoting Osteogenic Differentiation.

By recruiting stem cells into scaffolds and differentiating them into osteoblasts, stem cells can be mobilized to directly repair bone defects, which avoids a series of disadvantages of exogenous stem cell implantation. In this study, a microsphere-composite hydrogel for the recruitment and osteogenic differentiation of stem cells was constructed. Methacrylic anhydride modified gelatin (GelMA) and heparin (HepMA), as well as nanohydroxyapatite (nHAP), were used to prepare microspheres followed by adsorbing platelet-derived growth factor BB (PDGF-BB) whose loading efficiency was 53.7 ± 2.2%. Then the microspheres were compounded to the GelMA hydrogel encapsulated with simvastatin (SIM) to obtain microsphere-composite hydrogel GHnH-P@GS. GHnH-P@GS hydrogel could slowly release SIM and PDGF-BB, and the extents of release within 7 days were 44.1 ± 2.0% and 32.8 ± 1.1%. The synergistic effect of small molecule drugs and growth factors not only induced the recruitment of rabbit bone marrow-derived mesenchymal stem cells, but also promoted the osteogenic differentiation of stem cells, which was confirmed by experiments of cell migration, alkaline phosphatase, and alizarin red staining. Collectively, the microsphere-composite hydrogel GHnH-P@GS has a certain reference significance for the design of scaffolds for alveolar bone repair and regeneration.

Au/Ag@polyoxometalate core-shell structures: from nanoparticles to atomically precise nanoclusters.

This review summarizes the progress in the research on polyoxometalate (POM)-decorated gold (Au) and silver (Ag) core-shell structures (Au/Ag@POMs), emphasizing their substantial application potential in catalysis, medicine, and biology. It outlines the central strategies for fabricating Au/Ag@POMs with diverse morphologies and dimensions, leveraging POMs as protective ligands and reducing agents as well as for ligand exchange. Of particular note is the focus on the analysis of the nanoparticle size, shape, and intricate architecture of POM shells using cryo-electron microscopy techniques. By integrating recent findings on atomically precise POM-stabilized nanoclusters, this review delves deeper into understanding surface interface structures, intrinsic atomic architectures, and electronic interactions between POM shells and metallic cores. Collectively, advancements in this field underscore significant strides in the controllable synthesis and precise structural manipulation of Au/Ag@POM architectures, thus paving the way for engineering high-performance metal catalysts.

Metagenomic next-generation sequencing assisted in the successful treatment of pneumonia caused by Talaromyces marneffei in an immunocompetent patient.

INTRODUCTION: Talaromyces marneffei (T. marneffei), a kind of endemic opportunistic pathogen, was previously thought to occur in HIV-positive individuals and non-HIV hosts with impaired immune function. However, the infection of T. marneffei in patient with normal immune function was rarely reported. CASE PRESENTATION: We report a case of severe pneumonia caused by T. marneffei in an immunocompetent and HIV-negative patient, which was rapidly confirmed by metagenomics next-generation sequencing (mNGS) and treated successfully. The patient was a previously healthy 63-year-old male, who was admitted to hospital with fever for 11 days, cough and sputum for 1 week, and chest distress for 4 days. The infection of T. marneffei was quickly determined by alveolar lavage under bedside bronchoscope and mNGS test. RESULTS: Patient's condition improved rapidly after voriconazole treatment, and he was evaluated as a HIV-negative case of T. marneffei infection with normal immune function. This is a sporadic case of T. marneffei in non-endemic areas, and mNGS played a very important role in the treatment of the disease. The patient's immune function was relatively normal which was rare in clinical practice.

Exploring cross-modal plasticity in the auditory-visual cortex post cochlear implantation: implications for auditory and speech function recovery and mechanisms.

Objective: The aim of this is to explore changes in cross-modal reorganization within the auditory-visual cortex after cochlear implantation, examining their influence on auditory and speech functions along with their underlying mechanisms. Methods: Twenty prelingually deaf children who received cochlear implantation and rehabilitation training at our hospital between February 2022 and February 2023 comprised the prelingual deaf group. Simultaneously, 20 healthy children served as the control group. The prelingual deaf group underwent brain cortical activity assessment and evaluation of auditory-speech recovery pre-surgery, at postoperative weeks 1 and 2, and at months 1, 3, 6, 9, and 12. The control group underwent parallel assessments and evaluations. We analyzed the correlation between cortical activity in the auditory-visual cortex of patients and their auditory-speech functional recovery. Results: The group with prelingual deafness displayed elevated levels of auditory and visual cortical electromagnetic intensity compared to the control group, both prior to and 9 months after surgery. However, by the 12-month mark post-surgery, there was no discernible distinction between the two groups. Following surgery, the prelingually deaf group exhibited a progressive improvement in both Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR), initially lagging behind the control group. Notably, a negative correlation emerged between auditory and visual cortical electromagnetic intensity values and CAP/SIR scores at the 12-month post-surgery assessment. Conclusion: Cochlear implantation in prelingually deaf children results in elevated activity within the auditory and visual cortices, demonstrated by heightened electromagnetic intensity readings. Cross-modal reorganization is observed temporarily at 3 months post-surgery, which resolves to baseline levels by 12 months post-surgery. This phenomenon of reversal correlates with the restoration of auditory and speech functions in these children.

Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.

BACKGROUND: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized. METHODS: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development. RESULTS: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups. CONCLUSION: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology.

Clinical Predictors of Medication Compliance in Patients With Acute Herpetic Neuralgia.

PURPOSE: Pain is one of the most common and harmful symptoms experienced by individuals with acute herpetic neuralgia (AHN). In this population, studies to determine the causes that affect patients taking medications compliance are rare. This study aimed to construct a predictive model for medication compliance of patients with AHN and to verify its performance. DESIGN AND METHODS: In this prospective study of 398 patients with AHN who were discharged from a tertiary hospital with medications from July 2020 to October 2022, we used logistic regression analysis to explore the predictive factors of medication compliance of patients with AHN and to construct a nomogram. The area under the curve was used to evaluate the predictive effect of the model. RESULTS: A predictive model of drug compliance of patients with AHN was constructed based on the following four factors: disease duration, pain severity before treatment, medication beliefs, and comorbidity of chronic diseases. The area under the curve of the model was 0.766 (95% confidence interval [0.713, 0.819]), with a maximum Youden's index of 0.431, sensitivity of 0.776, and specificity of 0.655. A linear calibration curve was found with a slope close to 1. CONCLUSIONS: The prediction model constructed in this study had good predictive performance and provided a reference for early clinical screening of independent factors that affected the medication compliance of patients with AHN.

Expression of Iron Metabolism Genes Is Potentially Regulated by DOF Transcription Factors in Dendrocalamus latiflorus Leaves.

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus.

Icariin protects testicular damage in streptozotocin-induced diabetic rats through regulation of glycolysis pathway.

OBJECTIVE: This study aims to investigate potential beneficial actions of icariin (ICA) on testicular spermatogenic function in male rats with streptozotocin (STZ)-induced diabetes and to explore the underlying mechanisms. Background: ICA was found to reduce blood glucose, regulate the endocrine function of the reproductive system, and improve testicular spermatogenic function. METHODS: Adult rats were intraperitoneally injected with STZ (65 mg/kg) to induce type 1 diabetes mellitus (T1DM). Diabetic rats were randomly classified intoT1DM (n = 6) and T1DM + ICA (n = 6) groups. Rats without STZ and ICA treatment were assigned as control group (n = 6). The morphology of testicular tissues was examined by histological staining. The mRNA and protein expression levels were determined by quantitative real-time PCR, Western blot and immunostaining, respectively. RESULTS: Rats from T1DM group showed a reduction in epididymis and testis weight, and a decrease in sperm count when compared to control group (p < 0.01), which was attenuated by ICA treatment (p < 0.05) Diabetic rats from T1DM group also exhibited reduced diameter and area of seminiferous tubules, along with decreased spermatogonia and primary spermatocytes number when compared to control group (p < 0.01), which was partially reversed by ICA treatment (p < 0.05) Rats from T1DM group exhibited down-regulation of PCNA mRNA and protein in the testis when compared to control group (p < 0.01); while ICA treatment up-regulated PCNA expression in the testis of diabetic rats compared to T1DM group (p < 0.05). Rats from T1DM group showed up-regulation of Bax and capase-3 and down-regulation of Bcl-2, PKM2, HK2 and lactate dehydrogenase A in the testes when compared to control group (p < 0.05), which was reversed by ICA treatment (p < 0.05). CONCLUSION: These findings suggest that ICA may exert its protective effects on testicular damage in diabetic rats through modulation of glycolysis pathway and suppression of apoptosis.

Swimming training attenuates doxorubicin induced cardiomyopathy by targeting the mir-17-3p/KEAP1/NRF2 axis.

Doxorubicin (DOX), as a first-line anticancer drug, is widely used in the treatment of various cancers. However, its clinical application is restricted due to its severe cardiac toxicity. Previous studies have indicated exercise training can alleviate the DOX-induced cardiotoxicity (DIC), but the underlying mechanism remains unclear. Our research has discovered, post-exercise, an elevated expression level of mir-17-3p, but in DIC its level decreases. Therefore, we further studied the effect of exercise mir-17-3p axis on DIC. In vivo, we simulated DIC mouse model, followed by an intervention using swimming and adenovirus to inhibit mir-17-3p. We found that inhibition of mir-17-3p can weaken the protection of exercise against DIC, presenting as weakened heart function. Besides, the levels of Malondialdehyde and Fe2+ in the cardiac tissue increased, along with diminished glutathione peroxidase 4 and Solute Carrier Family 7 Member 11 levels, and a decline in the concentration of glutathione, causing an increase in ferroptosis. Moreover, in vitro, we used dual-luciferase assay to confirm that Kelch Like ECH Associated Protein 1 (KEAP1) can be a target gene of mir-17-3p. We used Keap1/NFE2 Like BZIP Transcription Factor 2 (NRF2) inhibitor brusatol and Stimulator of Interferon Response CGAMP Interactor 1 (STING) agonist SR-717 to verify the mir-17-3p/KEAP1 axis can affect the Cyclic GMP-AMP Synthase (CGAS)/STING pathway, leading to further ferroptosis in DIC. This manifested as a reduction in ferroptosis. In summary, our research suggests swimming training enhances the levels of mir-17-3p, thereby activating the KEAP1/NRF2 pathway, and weakening the CGAS/STING pathway, improving ferroptosis in DIC.

Emerging Microglial Therapies and Targets in Clinical Trial.

Modulation of microglia function for treatment of neurodegenerative and neuropsychiatric disorders is an emerging field of neuroscience drug development. This is largely attributed to human genetic association studies combined with biological evidence indicating that the innate immune system acts as a causal contributor superimposed on the reactive component of neuronal loss in neurological dysfunction. The identification of disease risk gene variants that encode immune-modulatory proteins in microglia provides tools to evaluate how microglia cellular function or dysfunction affect neuronal health. The development of clinical stage therapeutic compounds that modify myeloid cell function enables us to investigate how modulating microglia function could become a transformational approach to mitigate neurological disorders. Improving our ability to boost microglia-promoting homeostatic and reparative functions hopefully will translate into achieving a better outcome for patients affected by neurological diseases. In this chapter, we aim to provide an overview of the microglial emerging therapies and targets being studied in current clinical trials.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Comprehensive biochemical analysis and nutritional evaluation of fatty acid and amino acid profiles in eight seahorse species (Hippocampus spp.).

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa.

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

Door-to-antibiotic time and mortality in patients with sepsis: Systematic review and meta-analysis.

OBJECTIVES: To evaluate whether the timing of initial antibiotic administration in patients with sepsis in hospital affects mortality. METHODS: This systematic review and meta-analysis included studies from inception up to 19 May 2022. Interventional and observational studies including adult human patients with suspected or confirmed sepsis and reported time of antibiotic administration with mortality were included. Data were extracted by two independent reviewers. Summary estimates were calculated by using random-effects model. The primary outcome was mortality. RESULTS: We included 42 studies comprising 190,896 patients with sepsis. Pooled data showed that the OR for patient mortality who received antibiotics ≤1 hr was 0.83 (95 %CI: 0.67 to 1.04) when compared with patients who received antibiotics >1hr. Significant reductions in the risk of death in patients with earlier antibiotic administration were observed in patients ≤3 hrs versus >3 hrs (OR: 0.80, 95 %CI: 0.68 to 0.94) and ≤6 hrs vs 6 hrs (OR: 0.57, 95 %CI: 0.39 to 0.82). CONCLUSIONS: Our findings show an improvement in mortality in sepsis patients with early administration of antibiotics at <3 and <6 hrs. Thus, these results suggest that antibiotics should be administered within 3 hrs of sepsis recognition or ED arrival regardless of the presence or absence of shock.

Gender and tumor size-specific calcitonin cutoff value for diagnosing MTC in 10,618 patients with thyroid nodule surgery.

BACKGROUND: Calcitonin is a sensitive marker for medullary thyroid carcinoma (MTC) diagnosis and postsurgical follow-up. This study aimed to define the gender and tumor size-specific calcitonin cutoff values for diagnosing MTC. METHODS: This retrospective study recruited 95 MTC patients and 10,523 non-MTC patients who underwent thyroid nodule surgery at Zhongshan Hospital between January 2015 and June 2023. Receiver operating characteristic (ROC) curves were used to assess calcitonin cutoff values for diagnosing MTC. RESULTS: Calcitonin levels in non-MTC patients were influenced by gender, CKD stage and age, with gender being the highest ranked predictor. In MTC patients, calcitonin levels were associated with tumor diameter, lymph node metastasis, and TNM stage. In the entire study population, calcitonin cutoff values to diagnose MTC were 17.75 pg/mL for males (sensitivity: 97.60%, specificity: 99.40%) and 7.15 pg/mL for females (sensitivity: 94.34%, specificity: 99.22%). In patients with a thyroid nodule diameter ≤10 mm, the calcitonin cutoff values to diagnose MTC were 17.50 pg/mL for males (sensitivity: 95.00%, specificity: 99.27%) and 7.15 pg/mL for females (sensitivity: 90.91%, specificity: 99.04%). In patients with a thyroid nodule diameter >10 mm, the calcitonin cutoff values to diagnose MTC were 104.80 pg/mL for males (sensitivity: 100.00%, specificity: 100.00%) and 32.60 pg/mL for females (sensitivity: 96.77%, specificity: 100.00%). CONCLUSION: We have identified the gender and tumor size-specific cutoff values for the diagnosis of MTC. Cutoff values based on gender and tumor diameter may help to improve the accuracy of preoperative diagnosis of MTC, which is worth to be verified by future studies.

Meta-analysis of the accuracy for RASSF1A methylation in bronchial aspirates for the diagnosis of lung cancer.

OBJECTIVE: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis. METHODS: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias. RESULTS: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance. CONCLUSIONS: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer.