Gelsemium elegans Benth (G. elegans) is a traditional medicinal plant; however, it is highly toxic, and toxicity varies significantly between species. The cause of this difference has not been clarified. Humantenirine is an important toxic alkaloid in G. elegans, and its metabolism has been poorly studied. This study aimed to compare the different metabolites formed by human liver microsomes, pig liver microsomes, and goat liver microsomes.

High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to study the metabolism of humantenirine in human liver microsomes, pig liver microsomes, and goat liver microsomes.

A total of eight metabolites (M1-M8) were identified, and three major metabolic pathways were found: demethylation (M1), dehydrogenation (M2, M3, M7), and oxidation (M4, M5, M6, M8).

Based on these results, it is hypothesized that demethylation is the major detoxification pathway for humantenirine, providing important information to better understand the metabolism and toxicity differences between species of G. elegans.

The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched targeted therapies have experienced significantly improved survival rates. Modern molecular laboratories, equipped with advanced technologies such as next-generation sequencing, can simultaneously test hundreds of genes and thousands of hotspots in a single run with multiple samples analyzed side by side. Bioinformatics tools provide seamless, evidence-based information to determine whether the detected mutations are benign or pathogenic, somatic or germline, druggable or diagnostic. This review is divided into five sections, each aiming to provide a comprehensive overview of the genetic landscape of myeloid and lymphocytic neoplasms. It highlights the challenges and proposes potential solutions to facilitate interpretation and maximize the clinical utility of molecular profiling results.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor that can affect cell proliferation, migration, invasion, apoptosis, and other cellular processes. The study aimed to clarify the effect of ELK3 in the biological activity and ferroptosis phenotype of RA fibroblast-like synoviocytes (FLS), and to reveal its molecular mechanism in regulating ferroptosis in RA FLS.

We investigated the impact of ELK3 on the biological activity and ferroptosis phenotype of RA FLS using real-time quantitative polymerase chain reaction, immunohistochemistry, Transwell assay, CCK-8 assay, and ferroptosis-related indicator kit. The molecular mechanism of ELK3 in RA FLS was further explored using Western blot, chromatin immunoprecipitation polymerase chain reaction, and other experiments.

ELK3 was highly expressed in RA. Silencing ELK3 inhibited the invasion and proliferation of RA FLS (both p < 0.05). After silencing ELK3 in imidazole ketone erastin-induced RA FLS, intracellular reactive oxygen species, lipid peroxidation levels, ferrous ion content, 4-Hydroxynonenal levels, and Malondialdehyde concentrations all increased. Additionally, ELK3 affects ferroptosis in RA FLS by regulating kelch-like ECH-associated protein 1 (p < 0.05).

Silencing ELK3 leads to decreased invasion and proliferation of RA FLS, affecting their biological activity. ELK3 inhibits ferroptosis by suppressing its transcriptional activity through binding to the kelch-like ECH-associated protein 1 promoter. This suggests that ELK3 may be a potential target for RA therapy.

Nail psoriasis is common in patients with plaque psoriasis and is associated with morbidity, including onychomycosis, which can complicate psoriasis treatments and be difficult to differentiate. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a fast and simple technique for identifying microorganisms through protein analysis. This study aimed to determine the sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with nail psoriasis, by using conventional mycological and histological methods as the reference standard.

A prospective study was conducted on 88 patients with clinically and histopathologically confirmed nail psoriasis. One hundred nail samples were obtained for direct examination, fungal culture, and mass spectrometry. None of the patients were receiving antifungal or systemic immunosuppressive therapy at the time of sampling.

Potassium hydroxide preparation and fungal culture were positive in 58 out of 100 nail samples from patients with psoriasis. MALDI-TOF identified onychomycosis in 68 out of 100 samples, distinguishing these cases from nail psoriasis without onychomycosis (32 out of 100). An excellent correlation (0.95) was found between MALDI-TOF and conventional onychomycosis diagnostic methods. The sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with psoriatic nails were 95.4% and 97.5%, respectively.

MALDI-TOF can be used to accurately differentiate cases of nail psoriasis without infection from those with onychomycosis.

Helicobacter pylori (H. pylori) infection can cause multiple secondary digestive disorders. Some studies have found that polymorphisms in Toll-like receptor (TLR) genes, including TLR10 rs10004195, may be associated with increased susceptibility to H. pylori infection. Despite conflicting reports, we conducted a meta-analysis to clarify the relationship between these factors.

We conducted an exhaustive review, encompassing all relevant literature up to February 2024, using databases such as PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure. We screened studies based on specific criteria and evaluated their quality using the Newcastle-Ottawa scale. Heterogeneity testing and meta-analysis were performed using Stata 17.0 software, and SPSSAU was used for publication bias evaluation and sensitivity analysis.

Eight of the 487 identified studies met the inclusion criteria, comprising 3,004 and 2,140 individuals in the H. pylori-positive and negative control groups, respectively. Our results demonstrated that individuals carrying the AA genotype at the TLR10 rs10004195 locus had a significantly increased likelihood of H. pylori infection when analyzed using the recessive genetic model (OR: 1.64, CI: 1.04–2.58, p = 0.034). No statistically significant associations were found in the other four genetic models.

Our findings suggest that carrying the TLR10 rs10004195 AA genotype is associated with a significantly elevated risk of H. pylori infection. This information could be used to assess future risk of H. pylori infection in healthy individuals and provide personalized health guidance based on individual genetic polymorphisms.

Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.

This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.

In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.

MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.