Clinical outcomes among patients with concurrent blunt cerebrovascular injury and traumatic intracranial hemorrhage.

BACKGROUND: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage. MATERIALS AND METHODS: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke. RESULTS: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction. CONCLUSIONS: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively.

Cpd861 Targeting BCL2 to Alleviate Hepatic Fibrosis: Network Pharmacology, Mendelian Randomization, and Molecular Docking Mechanisms.

BACKGROUND: Compound 861 (Cpd861) is a traditional Chinese herbal compound for the treatment of hepatic fibrosis (HF). In the current investigation, Cpd861 has been demonstrated to have an underlying molecular mechanism and material foundation for the treatment of HF through network pharmacology, Mendelian randomization (MR), and molecular docking. METHODS: Public databases were consulted for Cpd861 constituents and HF targets. Protein-protein interactions (PPIs) were established using STRING software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To elucidate the causal relationship between potential targets and liver injury, MR was used as a methodological tool. Finally, a molecular docking analysis was conducted between the active compound and the key target. RESULTS: We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2. CONCLUSION: This study made predictions regarding the efficacious components, as well as potential targets and pathways of Cpd861 in the therapy of HF. This will open up a new perspective for further investigation of the molecular mechanism of Cpd861 in the treatment of HF.

Impact of shared decision-making in Taiwanese patients with atrial fibrillation eligible for novel oral anticoagulant therapy.

BACKGROUND/PURPOSE: Shared decision-making (SDM) promotes patient awareness about medical conditions and treatments, facilitating patient involvement in care decisions. This two-stage multicenter study evaluated impacts of SDM in Taiwanese adults with atrial fibrillation (AF) eligible for novel oral anticoagulant (NOAC) therapy. METHODS: Participants were NOAC-naïve (part I) or dabigatran-experienced (part II). During Stage I, part I participants (n = 124) completed a semi-structured survey (understanding evaluation sections only) before and after viewing SDM materials on stroke prevention for AF. Surveys collected data on anxiety about AF, confidence in healthcare professionals, usefulness of the SDM materials, and perception of different NOACs. During Stage II, part I participants after being prescribed NOACs, and part II participants completed another survey to compare impacts of SDM. RESULTS: During Stage I, dabigatran was the preferred NOAC after viewing the SDM materials among 90% of part I participants. During Stage II, both part I (n = 87) and part II participants (n = 104) completed another survey. Fewer part I participants were anxious about AF (p < 0.01), and more had confidence in healthcare professionals (p < 0.01) after viewing SDM materials than before. Most part I participants (≥90%) rated the SDM materials as "very helpful". In Stage II, participants viewing SDM before initiating dabigatran had lower anxiety (part I, 43%; part II, 53%; p < 0.01) and a higher trust (part I, 92%; part II, 84%; p < 0.01). CONCLUSION: In conclusion, SDM reduced anxiety and improved trust in healthcare professionals among NOAC-naïve participants with AF.

Therapeutic Potential of Salvia miltiorrhiza Root Extract in Alleviating Cold-Induced Immunosuppression.

The interaction between environmental stressors, such as cold exposure, and immune function significantly impacts human health. Research on effective therapeutic strategies to combat cold-induced immunosuppression is limited, despite its importance. In this study, we aim to investigate whether traditional herbal medicine can counteract cold-induced immunosuppression. We previously demonstrated that cold exposure elevated immunoglobulin G (IgG) levels in mice, similar to the effects of intravenous immunoglobulin (IVIg) treatments. This cold-induced rise in circulating IgG was mediated by the renin-angiotensin-aldosterone system and linked to vascular constriction. In our mouse model, the cold-exposed groups (4 °C) showed significantly elevated plasma IgG levels and reduced bacterial clearance compared with the control groups maintained at room temperature (25 °C), both indicative of immunosuppression. Using this model, with 234 mice divided into groups of 6, we investigated the potential of tanshinone IIA, an active compound in Salvia miltiorrhiza ethanolic root extract (SMERE), in alleviating cold-induced immunosuppression. Tanshinone IIA and SMERE treatments effectively normalized elevated plasma IgG levels and significantly improved bacterial clearance impaired by cold exposure compared with control groups injected with a vehicle control, dimethyl sulfoxide. Notably, bacterial clearance, which was impaired by cold exposure, showed an approximately 50% improvement following treatment, restoring immune function to levels comparable to those observed under normal temperature conditions (25 °C, p < 0.05). These findings highlight the therapeutic potential of traditional herbal medicine in counteracting cold-induced immune dysregulation, offering valuable insights for future strategies aimed at modulating immune function in cold environments. Further research could focus on isolating tanshinone IIA and compounds present in SMERE to evaluate their specific roles in mitigating cold-induced immunosuppression.

The impact of tumor resection on survival and functional outcomes for patients with primary central nervous system lymphoma.

PURPOSE: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection. METHODS: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection. RESULTS: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3 cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective. CONCLUSIONS: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3 cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes.

Early peripheral perfusion index predicts 28-day outcome in patients with septic shock.

BACKGROUND: To investigate the prognostic value of the peripheral perfusion index (PPI) in patients with septic shock. METHODS: This prospective cohort study, conducted at the emergency intensive care unit of Peking University People's Hospital, recruited 200 patients with septic shock between January 2023 and August 2023. These patients were divided into survival (n=84) and death (n=116) groups based on 28-day outcomes. Clinical evaluations included laboratory tests and clinical scores, with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission. Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses. Receiver operator characteristic (ROC) curve was used to assess predictive performance. Mortality rates were compared, and Kaplan-Meier survival plots were created. RESULTS: Compared to the survival group, patients in the death group were older and had more severe liver damage and coagulation dysfunction, necessitating higher norepinephrine doses and increased fluid replacement. Higher lactate levels and lower PPI levels at 0 h, 6 h, and 12 h were observed in the death group. Multivariate Cox regression identified prolonged prothrombin time (PT), decreased 6-h PPI and 12-h PPI as independent risk factors for death. The area under the curves for 6-h PPI and 12-h PPI were 0.802 (95% CI 0.742-0.863, P<0.001) and 0.945 (95% CI 0.915-0.974, P<0.001), respectively, which were superior to Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) scores (0.864 and 0.928). Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups (6-h PPI: 77.52% vs. 22.54%; 12-h PPI: 92.04% vs. 13.79%, P<0.001). CONCLUSION: PPI may have value in predicting 28-day mortality in patients with septic shock.

MicroRNA-376a-3p sensitizes CPT-11-resistant colorectal cancer by enhancing apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) through the IGF1R/PI3K/AKT pathway.

Colorectal cancer (CRC) remains the third most prevalent type of cancer worldwide contributing to an estimated 10 % of all cancer cases. CPT-11 is one of the first-line drugs for CRC treatment. Unfortunately, the development of drug resistance significantly exacerbates the adverse impact of CRC. Consequent tumor recurrences and metastasis, years after treatment are the frequently reported incidences. MicroRNAs (miRNA) are short non-coding RNA with the functionality of gene suppression. The insulin-like growth factor type 1 receptor (IGF1R) is a tyrosine kinase receptor frequently upregulated in cancers and is associated with cell survival and drug resistance. MiRNAs are frequently reported to be dysregulated in cancers including CRC. Evidence suggests that dysregulated miRNAs have direct consequences on the biological processes of their target genes. We previously demonstrated that miRNA-376a-3p is upregulated in CPT-11responsive, CRC cells upon treatment with CPT-11. We therefore aimed to investigate the involvement of miRNA-376a-3p in CPT-11 resistance and its probable association with IGF1R-mediated cancer cell survival. Our experimental approach used knockdown and overexpression experiments supplemented with western blot, RT-qPCR, flow cytometry, MTT, and migration assays to achieve our aim. Our data reveals the mechanism through which IGF1R and miRNA-376a-3p perpetrate and attenuate CPT-11 resistance respectively. MiRNA-376a-3p overexpression negatively regulated the IGF1R-induced cell survival, PI3K/AKT pathway, and reversed the epithelial-mesenchymal transition, hence sensitizing resistant cells to CPT-11. Our findings suggests that the miRNA-376a-3p/IGF1R axis holds promise as a potential target to sensitize CRC to CPT-11 in cases of drug resistance.

Light-induced remodeling of phytochrome B enables signal transduction by phytochrome-interacting factor.

Phytochrome B (phyB) and phytochrome-interacting factors (PIFs) constitute a well-established signaling module critical for plants adapting to ambient light. However, mechanisms underlying phyB photoactivation and PIF binding for signal transduction remain elusive. Here, we report the cryo-electron microscopy (cryo-EM) structures of the photoactivated phyB or the constitutively active phyBY276H mutant in complex with PIF6, revealing a similar trimer. The light-induced configuration switch of the chromophore drives a conformational transition of the nearby tongue signature within the phytochrome-specific (PHY) domain of phyB. The resulting α-helical PHY tongue further disrupts the head-to-tail dimer of phyB in the dark-adapted state. These structural remodelings of phyB facilitate the induced-fit recognition of PIF6, consequently stabilizing the N-terminal extension domain and a head-to-head dimer of activated phyB. Interestingly, the phyB dimer exhibits slight asymmetry, resulting in the binding of only one PIF6 molecule. Overall, our findings solve a key question with respect to how light-induced remodeling of phyB enables PIF signaling in phytochrome research.

Serum Klotho Is Elevated in Patients with Acute Myocardial Infarction and Could Predict Poor In-Hospital Prognosis.

INTRODUCTION: Klotho has emerged as a potential protective factor for cardiovascular diseases recently. Nevertheless, the levels of serum Klotho in acute coronary syndrome (ACS) have not been reported. Hence, we undertook a study to investigate the potential correlation between serum Klotho and ACS patients. METHOD: This observational cohort study was conducted at Peking University People's Hospital between May 2016 and April 2020. Upon admission, we collected the patients' clinical data and conducted ELISA tests to measure their serum Klotho levels. RESULT: A total of 349 patients were enrolled in this study, including 14 patients with UA and 335 patients with AMI. We observed that serum Klotho levels were obviously higher in the AMI group compared to the UA group (median 479.8 vs. 233.8 pg/mL, p = 0.035). In addition, serum Klotho levels were positively correlated with cardiac function and more pronounced in patients who died in the hospital (median 721.1 vs. 468.3 pg/mL, p < 0.001). A logistic regression analysis indicated that age ≥ 78 years old, HR ≥ 90 bpm, Killip classification ≥ 3 grade, and serum Klotho > 645.0 pg/mL were risk factors for poor prognosis. CONCLUSIONS: Serum Klotho is obviously increased in patients with AMI and with a positive correlation with cardiac function, and its elevation could serve as a predictor of poor prognosis in ACS patients.

The RNA N6-methyladenosine demethylase FTO regulates ATG5 to inhibit malignant progression of uveal melanoma.

PURPOSE: This research aimed to identify the function of fat mass- and obesity-associated protein (FTO), an eraser of N6-methyladenosine (m6A), and explore its possible mechanisms in uveal melanoma (UVM). METHODS: We performed quantitative real-time PCR (qPCR), Western blotting and gene correlation analysis with GEPIA2 to assess FTO expression and identify its potential targets in UVM. CCK-8, colony formation, cell cycle, cell apoptosis, wound healing and Transwell invasion assays were utilized to assess cell viability, cell cycle distribution, apoptosis, migration and invasion. Western blotting, qPCR and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were carried out to explore the underlying mechanism of FTO in 2 UVM cell lines. RESULTS: FTO, a key m6A demethylase, was found to be upregulated in human UVM tissues compared with normal choroid tissues. Knockdown of FTO in Mel270 and OMM2.3 cells significantly promoted proliferation and migration and suppressed apoptosis. Mechanistically, knockdown of FTO decreased the expression of ATG5, an autophagy-related gene, leading to attenuation of autophagosome formation, thereby inhibiting autophagy. Upon FTO knockdown, increased levels of methylated ATG5 and decreased ATG5 stability were detected. Furthermore, ATG5 dramatically alleviated FTO downregulation-induced tumor growth and metastasis. CONCLUSIONS: Our research highlights the importance of the m6A demethylase FTO in UVM by demonstrating that it direct regulates ATG5-induced autophagy in an m6A-dependent manner. These findings suggest that FTO may serve as a potential therapeutic target for UVM.

High-Performance Semiconducting Carbon Nanotube Transistors Using Naphthalene Diimide-Based Polymers with Biaxially Extended Conjugated Side Chains.

Polymer-wrapped single-walled carbon nanotubes (SWNTs) are a potential method for obtaining high-purity semiconducting (sc) SWNT solutions. Conjugated polymers (CPs) can selectively sort sc-SWNTs with different chiralities, and the structure of the polymer side chains influences this sorting capability. While extensive research has been conducted on modifying the physical, optical, and electrical properties of CPs through side-chain modifications, the impact of these modifications on the sorting efficiency of sc-SWNTs remains underexplored. This study investigates the introduction of various conjugated side chains into naphthalene diimide-based CPs to create a biaxially extended conjugation pattern. The CP with a branched conjugated side chain (P3) exhibits reduced aggregation, resulting in improved wrapping ability and the formation of larger bundles of high-purity sc-SWNTs. Grazing incidence X-ray diffraction analysis confirms that the potential interaction between sc-SWNTs and CPs occurs through π-π stacking. The field-effect transistor device fabricated with P3/sc-SWNTs demonstrates exceptional performance, with a significantly enhanced hole mobility of 4.72 cm2 V-1 s-1 and high endurance/bias stability. These findings suggest that biaxially extended side-chain modification is a promising strategy for improving the sorting efficiency and performance of sc-SWNTs by using CPs. This achievement can facilitate the development of more efficient and stable electronic devices.

Mediation of radiation-induced bystander effect and epigenetic modification: The role of exosomes in cancer radioresistance.

Exosomes are nano-sized extracellular vesicles produced by almost all mammalian cells. They play an important role in cell-to-cell communication by transferring biologically active molecules from the cell of origin to the recipient cells. Ionizing radiation influences exosome production and molecular cargo loading. In cancer management, ionizing radiation is a form of treatment that exerts its cancer cytotoxicity by induction of DNA damage and other alterations to the targeted tissue cells. However, normal bystander non-targeted cells may exhibit the effects of ionizing radiation, a phenomenon called radiation-induced bystander effect (RIBE). The mutual communication between the two groups of cells (targeted and non-targeted) via radiation-influenced exosomes enables the exchange of radiosensitive molecules. This facilitates indirect radiation exposure, leading, among other effects, to epigenetic remodeling and subsequent adaptation to radiation. This review discusses the role exosomes play in epigenetically induced radiotherapy resistance through the mediation of RIBE.

Estimating the risk of major adverse cardiac events following radiotherapy for left breast cancer using a modified generalized Lyman normal-tissue complication probability model.

BACKGROUND: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT). MATERIALS AND METHODS: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups. RESULTS: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D50 = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D50 = 30 Gy) compared to the low-comorbidity group (D50 = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively. CONCLUSION: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT.

Factor structure of the Chinese version of Emotion Regulation Goals Scale.

Recent studies in Western cultures suggested emotion regulation goals have important implications for mental health. This study aimed to test the factor structure of Emotion Regulation Goals Scale (ERGS) in a Chinese cultural context. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were first used to examine the factor structure of the ERGS, and then reliability and validity tests were conducted to examine the psychometric properties of the ERGS. Results showed that the original five-factor model demonstrated fit during both EFA and CFA, and was thus adopted for further psychometric analyses. Most of the five factors were significantly associated with emotion regulation tendencies and negative emotional outcomes (e.g., depression), except for the non-significant associations between pro-hedonic goals and expressive suppression, and pro-social and impression management goals with depression. The ERGS also showed good internal consistency and split-half reliability. However, the test-retest reliabilities varied substantially across the five factors. The pro-hedonic goal had a higher test-retest reliability, whereas the contra-hedonic, performance, pro-social, and impression management goals showed lower values, especially the latter two. In brief, the ERGS showed a promising five-factor structure in assessing emotion regulation goals in Chinese cultural context.

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR-342-5p/CFL1.

BACKGROUND: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. METHODS: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. RESULTS: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. CONCLUSION: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

Strigolactones positively regulate HY5-dependent autophagy and the degradation of ubiquitinated proteins in response to cold stress in tomato.

Autophagy, involved in protein degradation and amino acid recycling, plays a key role in plant development and stress responses. However, the relationship between autophagy and phytohormones remains unclear. We used diverse methods, including CRISPR/Cas9, ultra-performance liquid chromatography coupled with tandem mass spectrometry, chromatin immunoprecipitation, electrophoretic mobility shift assays, and dual-luciferase assays to explore the molecular mechanism of strigolactones in regulating autophagy and the degradation of ubiquitinated proteins under cold stress in tomato (Solanum lycopersicum). We show that cold stress induced the accumulation of ubiquitinated proteins. Mutants deficient in strigolactone biosynthesis were more sensitive to cold stress with increased accumulation of ubiquitinated proteins. Conversely, treatment with the synthetic strigolactone analog GR245DS enhanced cold tolerance in tomato, with elevated levels of accumulation of autophagosomes and transcripts of autophagy-related genes (ATGs), and reduced accumulation of ubiquitinated proteins. Meanwhile, cold stress induced the accumulation of ELONGATED HYPOCOTYL 5 (HY5), which was triggered by strigolactones. HY5 further trans-activated ATG18a transcription, resulting in autophagy formation. Mutation of ATG18a compromised strigolactone-induced cold tolerance, leading to decreased formation of autophagosomes and increased accumulation of ubiquitinated proteins. These findings reveal that strigolactones positively regulate autophagy in an HY5-dependent manner and facilitate the degradation of ubiquitinated proteins under cold conditions in tomato.

Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population.

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies. METHODS: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated. RESULTS: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy. CONCLUSION: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting.

Hub metastatic gene signature and risk score of breast cancer patients with small tumor sizes using WGCNA.

BACKGROUND: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices. METHODS: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression. RESULTS: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3. CONCLUSION: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms.

A preliminary investigation of dissociation between subjective cognitive complaints and objective cognitive impairments in female patients with fibromyalgia: a role of information processing speed.

OBJECTIVES: Fibromyalgia (FM) is a chronic condition characterised by widespread pain, and cognitive difficulties represent one of the most common symptoms of FM. However, subjective cognitive complaints (SCC) may not necessarily indicate significant abnormalities in objective cognitive performances, and there is limited research investigating the relationship between these two aspects. This study thus aims to analyse the differences between SCC and objective cognitive performance in FM patients and to explore their associations. METHODS: A total of 32 FM female patients (age: 50.91±7.06; years since diagnosis: 4.34±4.53) recruited in this study underwent a comprehensive assessment covering four domains: pain, depression, trait anxiety, SCC, and objective cognitive functions (memory, executive function, and information processing speed). RESULTS: Eighty-seven percent of patients experienced significant negative impacts from pain; meanwhile, 91% and 62% showed marked tendencies towards trait anxiety and depression, respectively. Additionally, 56% of patients reported significantly higher levels of SCC. However, less than one-third of patients demonstrated impairments in various cognitive functions. SCC significantly correlated with pain intensity, depression, information processing speed, and trait anxiety, with pain intensity being a significant predictor (R2=.30). Furthermore, patients with significant SCC exhibited more abnormalities in pain, information processing speed, and trait anxiety compared to those without significant SCC. CONCLUSIONS: SCC may not necessarily correlate with objective cognitive impairments and might be specifically linked to defective information processing speed. It thus merits that clinical assessments for FM patients should incorporate measurements of information processing speed to gain a comprehensive understanding of SCC in FM patients.