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Abstract Background In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. Methods This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. Results A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 – 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44–13.61), 7.5 months (95% CI 7.33–8.17), and 4.01 months (95% CI 3.94–4.08), respectively, with a log-rank test p-value

ObjectiveTo assess the impact of the COVID-19 pandemic on the presentation, treatment, and survival of patients with early breast cancer (Stage I–III).MethodsThis study utilized data from the Surveillance, Epidemiology, and End Results database from January 1, 2018, to December 31, 2020. Patients diagnosed with primary breast cancer in 2020 were compared to those diagnosed in 2018 or 2019. The primary outcomes were stage distribution and changes in the treatment modalities for early breast cancer. The secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS).ResultsWe analyzed 142,038 patients. There has been a decrease in breast cancer diagnoses in 2020, as well as the smaller number of surgeries. The distribution of breast cancer stages among patients exhibited a notable shift in 2020, with a decrease in the proportion of Stage 0-I and an increase in advanced-stage. Additionally, there was a significant decrease in the proportion of breast-conserving surgery (BCS) performed in 2020. The proportion of patients undergoing radiation decreased, while that of chemotherapy cases increased significantly in 2020. Patients showed a shorter treatment delay in 2020 than in 2018 or 2019 (2018: hazard ratio [HR] = 0.969, 95% confidence interval [CI] = 0.956–0.982, p < 0.001; 2019: HR=0.959, 95% CI = 0.946–0.972, p < 0.001). Diagnosis in 2020 showed a significant correlation with worse OS than diagnosis in 2018 (HR = 0.861, 95% CI = 0.743-0.996, p = 0.045).ConclusionWe observed a shift to advanced-stage and a change of treatment modalities of early breast cancer in 2020. The OS of patients with breast cancer was worse during the pandemic than before the pandemic. The findings could provide empirical basis for optimizing cancer prevention and control strategies in future public health emergencies.

Based on the complexity and metrological requirements of temperature calibration within the rotor of a medical low-temperature centrifuge, a wireless temperature calibration device for medical centrifuges has been designed and developed. The temperature probe is integrated into the centrifuge tube, and the entire device can be placed inside the rotor of the centrifuge, allowing for the measurement and analysis of the actual temperature of the test solution inside the centrifuge tube under dynamic rotation conditions. Furthermore, the force situation during dynamic calibration is analyzed and performance tested. The calibration device can consistently and dependably achieve dynamic temperature data acquisition under high-speed conditions of medical low-temperature centrifuges, facilitating dynamic temperature calibration within the centrifuge rotor and offering support for centrifuge temperature control processes.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Abstract Background Thalidomide‐containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose‐dependent, identifying the most appropriate dose for each patient is essential. Aims This study aimed to investigate the effects of a thalidomide dose step‐up strategy on treatment response and progression‐free survival (PFS). Methods and Results This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide‐related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p

Purpose: Although the medical decision-making process can be overwhelming for some surrogates, there is a lack of understanding regarding their experiences. The objectives of this study were to examine the decision self-efficacy and decisional conflict experienced by surrogates in intensive care units (ICUs) when faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation. In addition, predictors and mediators influencing these decision-making processes were identified. Methods: This study utilized a cross-sectional design to investigate the decision-making processes of 174 surrogates who were faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation in the internal ICU of a medical center between August 2021 and February 2022. Structured questionnaires were administered to collect data on the surrogates' background information, decision self-efficacy, decisional conflict, and positive and negative affect. The patients’ background information was also collected. Univariate and multivariate analyses were performed to model the data. Results: The mean decision self-efficacy score of the surrogates was 82.41 points, and 20.7% surrogates had decisional conflict scores exceeding 37.5 points, suggesting that they faced challenges in the decision-making process. Surrogates' employment status and negative affect significantly predicted their decision self-efficacy. In addition, patients' activities of daily living prior to hospitalization and the decision self-efficacy of the surrogate significantly predicted surrogate decisional conflict. The impact of surrogates’ negative affect on decisional conflict was fully mediated by decision self-efficacy. Conclusions: Surrogate decision self-efficacy mediates the relationship between negative affect and decisional conflict. Providing clinical care interventions that focus on enhancing surrogate self-efficacy and reducing negative affect can help alleviate decisional conflict in this population.

Abstract The initiation, development and resolution of hepatic fibrosis are influenced by various cytokines, chemokines, damage-associated molecular patterns (DAMPs) and signaling pathways. A significant number of studies in recent years have indicated that the progression of hepatic fibrosis is closely linked to programmed cell death processes such as apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis, and PANoptosis. Inducement of hepatic stellate cells (HSCs) death or preventing death in other liver cells can delay or even reverse hepatic fibrosis. Nevertheless, the roles of programmed cell death in hepatic fibrosis have not been reviewed. Therefore, this review summarizes the characteristics of various of hepatic fibrosis and programmed cell death, focuses on the latest progress of programmed cell death in the promotion and regression of hepatic fibrosis, and highlights the different roles of the programmed cell death of HSCs and other liver cells in hepatic fibrosis. In the end, the possible therapeutic approaches targeting programmed cell death for treating hepatic fibrosis are discussed and prospected.

AIM: To investigate the effect of orbital decompression on the central macular choroidal thickness(CMCT)in patients with thyroid-associated ophthalmopathy(TAO).METHOD: Prospective clinical studies. A total of 29 TAO patients(42 eyes)treated in our department from January 2021 to January 2022 were analyzed, and they were divided into 20 cases(30 eyes)in the moderate and severe group and 9 cases(12 eyes)in the extremely severe group. Both groups of patients received orbital decompression, and the changes of CMCT, visual acuity, intraocular pressure, exophthalmos, and clinical activity score(CAS)at 3 and 6mo before and after surgery were compared between the two groups.RESULTS: All patients completed follow-up. The CMCT, exophthalmos, intraocular pressure, and CAS of the extremely severe group at 3 and 6mo were 355.13±15.59 and 339.61±13.17μm, 19.33±2.23 and 17.83±1.70mm, 18.86±3.05 and 18.09±1.37mmHg, 3.75±0.87 and 2.42±1.00 points, respectively. The moderate and severe group was 325.00±10.48 and 321.04±11.34μm, 16.07±1.74 and 15.6±1.98mm, 16.65±2.04 and 16.03±2.3mmHg, 1.50±0.51 and 1.43±0.50 points, and there was differences with those before operation(extremely severe group: 396.46±17.61μm, 22.00±2.3mm, 21.85±2.82mmHg, 5.33±1.44 points; moderate and severe group: 335.77±11.60μm, 19.07±1.84mm, 18.89±3.06mmHg, 1.63±0.49 points; all P

Motor learning is crucial for the survival of many animals. Acquiring a new motor skill involves complex alterations in both local neural circuits in many brain regions and long-range connections between them. Such changes can be observed anatomically and functionally. The primary motor cortex (M1) integrates information from diverse brain regions and plays a pivotal role in the acquisition and refinement of new motor skills. In this review, we discuss how motor learning affects the M1 at synaptic, cellular, and circuit levels. Wherever applicable, we attempt to relate and compare findings in humans, non-human primates, and rodents. Understanding the underlying principles shared by different species will deepen our understanding of the neurobiological and computational basis of motor learning.

By An amphibious bionic robot has good movement ability under several working conditions, so as to better perform tasks in complex terrain environments. In this study, the development background, research status and main applications of amphibious bionic robots are summarized. According to the degree of bionic reference, amphibious bionic robots are divided into two categories: imitating motion mode and imitating motion structure. The relevant research is introduced and the characteristics of different robot types are analyzed. Furthermore, the technical advantages and typical application scenarios of amphibious bionic robots are described.

ObjectiveTo study the value of Onodera’s prognostic nutrition index (PNI) in patients with gastric neuroendocrine cancer (G-NEC).MethodsThe clinical data on 148 cases of G-NEC presented between March 2010 and April 2022 were retrospectively analyzed. The relationship between the clinical characteristics of the patients and PNI was analyzed. Optimal PNI cutoff values for G-NEC prognosis prediction were calculated using the X-tile software. The survival curves were created using the Kaplan–Meier method. A Cox proportional hazards model was also established to identify independent prognostic factors that impact the prognosis of patients with G-NEC.ResultsThe median overall survival (OS) rate was 30 months (range 6–127 months), and the OS rates at 1, 3 and 5 years were 89.2, 71.6 and 68.2%, respectively. The mean PNI of the 148 patients before the operation was 49.5 ± 8.0. The mean PNI of patients with anemia (p

Six benzophenone derivatives, carneusones A-F (1–6), along with seven known compounds (7–13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 μM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 μM.

Abstract Objective/hypothesis This study correlated audiological results with magnetic resonance (MR) images to predict positive cochlear endolymphatic hydrops (EH) on MR images in patients with Meniere's disease (MD). Study design Retrospective study. Methods Twenty definite MD patients with positive cochlear EH on MR images were assigned to Group A. Another 20 definite MD patients with negative cochlear EH on MR images were assigned to Group B. All patients underwent an inner ear test battery followed by MR imaging using HRDROPS‐Mi2 technique. Results The mean hearing levels (MHLs) at frequencies of 125, 250, 500 and 1000 Hz revealed significantly worse in Group A than Group B. Significantly deteriorated MHLs were noted from Grades 0 to II at low frequency (125, 250, and 500 Hz), but not at mid‐frequency and high frequency. The respective cutoff hearing thresholds at frequencies of 125, 250, and 500 Hz were 27.5, 32.5, and 40 dBHL, which help predict positive cochlear EH on MR images. By using the sum (27.5 + 32.5 + 40 = 100 dBHL) of cutoff thresholds from three low frequencies as a cutoff value, Group A (80%) showed significantly more ears with sum of low‐frequency hearing threshold >100 dBHL than Group B (30%). Conclusion When sum of three low‐frequency (125, 250, and 500 Hz) hearing levels is >100 dBHL, positive cochlear EH may be shown on MR images in definite MD patients. In contrast, those MD patients with sum of three low‐frequency hearing levels

Background/Purpose: This study utilized the recently advanced technique in MR imaging to establish its role on diagnosing all types of endolymphatic hydrops (EH). Methods: Twenty-two patients (26 ears) with clinical EH were admitted due to acute hearing loss and/or vertiginous attack. Each patient underwent an inner ear test battery comprising audiometry, cervical and ocular vestibular-evoked myogenic potential tests, and caloric test, followed by MR imaging for confirmation. Results: Of the 22 clinical EH patients, 12 patients were referred to primary EH (Meniere's disease), 8 patients were secondary EH (including delayed EH in 5), and 2 patients were EH of embryopathic origin. MR imaging of 26 affected ears demonstrated EH in the cochlea only for 14 ears, in the utricle and saccule only for 1 ear, and in all three endorgans for 3 ears, accounting for a sensitivity of 69% (18/26). The 8 affected ears showing negative MR images were EH patients with hearing recovery 1, just after vertiginous attack 3, and chronic low-tone hearing loss 4. In contrast, 3 out of 18 unaffected ears demonstrated asymptomatic EH in the cochlea, representing a specificity of 83% (15/18). Conclusion: The sensitivity and specificity of MR imaging for confirming all types of EH were 69% and 83%, respectively. Although diagnostic criteria can identify primary and delayed EH, MR imaging may provide a supplementary tool for diagnosing secondary, embryopathic, or asymptomatic EH, if patients are not with hearing recovery, chronic low-tone hearing loss, or just after vertiginous attack.

Abstract Background COVID-19 affects healthcare resource allocation, which could lead to treatment delay and poor outcomes in patients with acute myocardial infarction (AMI). We assessed the impact of the COVID-19 pandemic on AMI outcomes. Methods We compared outcomes of patients admitted for acute ST-elevation MI (STEMI) and non-STEMI (NSTEMI) during a non-COVID-19 pandemic period (January–February 2019; Group 1, n = 254) and a COVID-19 pandemic period (January–February 2020; Group 2, n = 124). Results For STEMI patients, the median of first medical contact (FMC) time, door-to-balloon time, and total myocardial ischemia time were significantly longer in Group 2 patients (all p 0.05). For NSTEMI patients, Group 2 patients had a higher rate of conservative therapy, a lower rate of reperfusion therapy, and longer FMC times (all p

Sorghum mosaic virus (SrMV, the genus Potyvirus of the family Potyviridae) is a causal agent of common mosaic in sugarcane and poses a threat to the global sugar industry. In this study, a total of 901 sugarcane leaf samples with mosaic symptom were collected from eight provinces in China and were detected via RT-PCR using a primer pair specific to the SrMV coat protein (CP). These leaf samples included 839 samples from modern cultivars (Saccharum spp. hybrids) and 62 samples from chewing cane (S. officinarum). Among these, 632 out of 901 (70.1%) samples were tested positive for SrMV. The incidences of SrMV infection were 72.3% and 40.3% in modern cultivars and chewing cane, respectively. Phylogenetic analysis showed that all tested SrMV isolates were clustered into three clades consisting of six phylogenetic groups based on 306 CP sequences (this study = 265 and GenBank database = 41). A total of 10 SrMV isolates from South America (the United States and Argentina) along with 106 isolates from China were clustered in group D, while the remaining 190 SrMV isolates from Asia (China and Vietnam) were dispersed in five groups. The SrMV isolates in group F were limited to Yunnan province in China, and those in group A were spread over eight provinces. A significant genetic heterogeneity was elucidated in the nucleotide sequence identities of all SrMV CPs, ranging from 69.0% to 100%. A potential recombination event was postulated among SrMV isolates based on CP sequences. All tested SrMV CPs underwent dominant negative selection. Geographical isolation (South America vs. Asia) and host types (modern cultivars vs. chewing cane) are important factors promoting the genetic differentiation of SrMV populations. Overall, this study contributes to the global understanding of the genetic evolution of SrMV and provides a valuable resource for the epidemiology and management of the mosaic in sugarcane.

Background: Endovascular thrombectomy (EVT) for acute ischemic stroke associated with tandem lesion is challenging. Achieving rapid intracranial revascularization and managing the extracranial lesion without complications are the main challenges. Materials and Methods: The balloon angioplasty followed by aspiration of large-vessel occlusion (BAFALO) technique was used to address this clinical issue. A review of a prospectively maintained stroke registry from January 2015 to April 2020 was performed. Patients had stroke with TO and treated with the BAFALO technique were included. Results: Twelve patients were enrolled: 11 had anterior circulation stroke, and 1 had posterior circulation stroke. There were 10 ipsilateral internal carotid artery stenosis/occlusion, one left common carotid artery to subclavian artery bypass stenosis, and 1 vertebral artery orifice stenosis. The median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 14–16). Revascularization with a Modified Thrombolysis in Cerebral Infarction score of 2b or more was achieved in 11 (92%) patients. The median puncture-to-revascularization time was 25 min (IQR: 19.5–31). Emergent stent implantation was performed in five (42%) patients. Three had distal protection devices (DPDs) with no distal embolization. Two patients did not use a DPD, and one had intracranial reocclusion. Eight (67%) proximal stenotic vessels remained patent. No symptomatic intracranial hemorrhage occurred. Eight (67%) patients had favorable clinical outcomes (modified Rankin Score 0–2 at 90 days). Conclusion: While managing TO, the BAFALO technique could achieve rapid intracranial revascularization and treat extracranial lesions under embolic protection. These merits translate into favorable clinical outcomes.

Fragile X Syndrome (FXS) is the best-known form of inherited intellectual disability caused by the loss-of-function mutation in a single gene. The FMR1 gene mutation abolishes the expression of Fragile X Messenger Ribonucleoprotein (FMRP), which regulates the expression of many synaptic proteins. Cortical pyramidal neurons in postmortem FXS patient brains show abnormally high density and immature morphology of dendritic spines; this phenotype is replicated in the Fmr1 knockout (KO) mouse. While FMRP is well-positioned in the dendrite to regulate synaptic plasticity, intriguing in vitro and in vivo data show that wild type neurons embedded in a network of Fmr1 KO neurons or glia exhibit spine abnormalities just as neurons in Fmr1 global KO mice. This raises the question: does FMRP regulate synaptic morphology and dynamics in a cell-autonomous manner, or do the synaptic phenotypes arise from abnormal pre-synaptic inputs? To address this question, we combined viral and mouse genetic approaches to delete FMRP from a very sparse subset of cortical layer 5 pyramidal neurons (L5 PyrNs) either during early postnatal development or in adulthood. We then followed the structural dynamics of dendritic spines on these Fmr1 KO neurons by in vivo two-photon microscopy. We found that, while L5 PyrNs in adult Fmr1 global KO mice have abnormally high density of thin spines, single-cell Fmr1 KO in adulthood does not affect spine density, morphology, or dynamics. On the contrary, neurons with neonatal FMRP deletion have normal spine density but elevated spine formation at 1 month of age, replicating the phenotype in Fmr1 global KO mice. Interestingly, these neurons exhibit elevated thin spine density, but normal total spine density, by adulthood. Together, our data reveal cell-autonomous FMRP regulation of cortical synaptic dynamics during adolescence, but spine defects in adulthood also implicate non-cell-autonomous factors.