Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Lower Limb Proprioception in Low Back Pain and Its Relationship With Voluntary Postural Control.

This study aimed to investigate whether patients with low back pain (LBP) had impaired lower limb proprioception and its association with somatosensory acuity. Thirty patients with LBP and 30 asymptomatic people volunteered, using Sway Discrimination Apparatus tests to assess somatosensory acuity during voluntary anteroposterior and mediolateral postural sway. Results showed significantly reduced somatosensory acuity in mediolateral sway in LBP patients (p = 0.005) with ankle, knee, and hip proprioception showing significantly impairment compared to asymptomatic controls (all p ≤ 0.012). Regression analysis showed that ankle and hip proprioception were significantly associated with somatosensory perception (0.001 ≤ p ≤ 0.026, 0.067 ≤ R2≤ 0.235). Overall, findings suggested a global deterioration of lower limb proprioception in LBP patients, with ankle and hip proprioception playing crucial role in somatosensory perception.

Preparation of a Polymeric Phosphoramide Flame-Retardant and Its Effect on the Flame-Retardant Properties of Epoxy Resin.

The flammability of epoxy resins and knowing how to achieve curing are particularly important factors during use. A novel approach for enhancing the fire resistance and reducing the smoke emission of epoxy resin during the curing process is suggested, which involves the utilization of a three-source integrated polymerization intumescent flame-retardant. In this study, the synthesis of poly 4,4-diaminodiphenylsulfone spirocyclic pentaerythritol bisphosphonate (PCS) is achieved through using solution polymerization, utilizing 4,4'-diaminodiphenylsulfone (DDS) and spirocyclic pentaerythritol bisphosphorate disphosphoryl chloride (SPDPC) as initial components. Following that, the EP underwent the inclusion of PCS to examine its resistance to heat, its ability to prevent flames, its effectiveness in reducing smoke and its curing effect. Compared to the unmodified epoxy resin, the addition of PCS can not only cure the epoxy resin, but also decompose before the epoxy resin and has a good carbonization effect. With the addition of 7 wt.% PCS, the LOI value can achieve 31.2% and successfully pass the UL-94 test with a V-0 rating. Moreover, the cone calorimeter experiment demonstrated a noteworthy decline of 59.7% in the maximum heat release rate (pHRR), 63.7% in overall heat release (THR), and 42.3% in total smoke generation (TSP). Based on the examination of TG-FTIR and SEM findings, there is ample evidence to suggest that PCS, functioning as a phosphorus-nitrogen intumescent flame-retardant that combines three origins, has the potential to exhibit a favorable flame-retardant impact in both its gas and condensed phases.

Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

Carbonization of quercetin into nanogels: a leap in anticoagulant development.

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGsQur) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGsQur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo. Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGsQur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGsQur synthesized at 270 °C (CNGsQur270) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGsQur310) and 290 °C (CNGsQur290) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGsQur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGsQur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGsQur270 effectively delays and even prevents FeCl3-induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.

Knee osteoarthritis patients assessed during walking for ankle inversion movement discrimination sensitivity.

Background: Knee osteoarthritis (KOA) is a common musculoskeletal condition that affects dynamic balance control and increases the risk of falling during walking. However, the mechanisms underlying this are still unclear. Diminished ankle proprioception during walking has been found to be related to fear of falling in older adults, with a gender difference in incidence of falling. This study aimed to determine 1) whether ankle inversion proprioceptive acuity during walking is impaired in patients with KOA; and 2) whether there is any difference between genders. Methods: Thirty-two patients with KOA (F:M = 17:15, Median age = 52.5, BMI = 22.3 ± 3.0) and 34 healthy controls without KOA (HC) (F:M = 17:17; median age = 49.0, BMI = 22.5 ± 2.7) were recruited. In patients with KOA, ankle inversion proprioceptive acuity was measured on the affected side using the ankle inversion discrimination apparatus for walking (AIDAW), whilst HC were assessed on a randomly selected side. Two-way (2*2) analysis of variance (ANOVA) was performed to determine the main effects and interaction between gender and KOA condition. Results: Two-way ANOVA showed a significant KOA main effect (F = 26.6, p < 0.001, ƞp 2 = 0.3) whereby AIDAW scores during walking for individuals with KOA were significantly lower than those without KOA (KOA vs. HC: 0.746 ± 0.057 vs. 0.807 ± 0.035). There was neither a gender main effect nor interaction (both p > 0.05). Conclusion: Individuals with KOA demonstrated lower ankle proprioception scores during walking compared to their healthy counterparts, with a similar level of impairment in ankle proprioceptive acuity between male and female patients. A low score may contribute to an increased risk of falling in the KOA population. The current findings suggest the need for global concern about lower limb proprioception in the clinical management of KOA.

Modulation of Heart Rate Variability and Brain Excitability through Acute Whole-Body Vibration: The Role of Frequency.

This cross-over study aimed to explore effects of acute whole-body vibration (WBV) at frequencies of 5-35 Hz on heart rate variability and brain excitability. Thirteen healthy physically active college students randomly completed eight interventions under the following conditions: static upright standing without vibration (CON), static squat exercise (knee flexion 150°) on the vibration platform (SSE), and static squat exercise (knee flexion 150°) combined with WBV at vibration frequency of 5, 9, 13, 20, 25, and 35 Hz. Five bouts × 30 s with a 30-s rest interval were performed for all interventions. The brain's direct current potentials (DCPs), frequency domain variables (FDV) including normalized low frequency power (nLF), normalized high frequency power (nHF) and the ratio of LF to HF (LF/HF), along with the mean heart rate (MHR) were collected and calculated before and after the WBV intervention. Results suggested that WBV frequency at 5 Hz had a substantial effect on decreasing DCPs [-2.13 µV, t(84) = -3.82, p < 0.05, g = -1.03, large] and nLF [-13%, t(84) = -2.31, p = 0.04, g = -0.62, medium]. By contrast, 20-35 Hz of acute WBV intervention considerably improved DCPs [7.58 µV, t(84) = 4.31, p < 0.05, g = 1.16, large], nLF [17%, t(84) = 2.92, p < 0.05, g = 0.79, large] and the LF/HF [0.51, t(84) = 2.86, p < 0.05, g = 0.77, large]. A strong (r = 0.7, p < 0.01) correlation between DCPs and nLF was found at 5 Hz. In summary, acute WBV at 20-35 Hz principally activated the sympathetic nervous system and increased brain excitability, while 5-Hz WBV activated the parasympathetic nervous system and reduced brain excitability. The frequency spectrum of WBV might be manipulated according to the intervention target on heart rate variability and brain excitability.

Ankle inversion proprioception measured during stair descent can identify chronic ankle instability.

BACKGROUND: Individuals with chronic ankle instability (CAI) may experience recurrent ankle sprains and symptoms during daily activities such as stair descent, where the associated proprioceptive deficit is largely unevaluated. OBJECTIVES: To evaluate the reliability and validity of an ankle inversion discrimination apparatus for stair descent, and examine whether proprioceptive scores from this apparatus are associated with patient-reported symptoms. DESIGN: Cross-sectional study. METHOD: Sixty-six participants volunteered in this study. The ankle inversion discrimination apparatus was purpose-built to assess ankle proprioception across four positions of ankle inversion (10°, 12°, 14°, and 16°) during stair descent. The Area Under the Receiver Operating Curve (AUC) was employed as the ankle proprioceptive discrimination score. RESULTS: Test-retest reliability ICC (3,1) for the whole group was 0.825, with 0.747 for the non-CAI group (95%CI = 0.331-0.920) and 0.701 for CAI (95%CI = 0.242-0.904). The CAI group performed at a significantly lower level than non-CAI on the ankle inversion discrimination apparatus for stair descent assessment (0.769 ± 0.034 vs. 0.830 ± 0.035, F = 33.786, p < 0.001). CAIT scores were strongly and significantly correlated with scores from this apparatus (Spearman's rho = 0.730, p < 0.001). CONCLUSIONS: The ankle inversion discrimination apparatus for stair descent is reliable and valid for assessing task-specific ankle proprioceptive impairments in CAI. The strong and significant relationship found between ankle proprioception during stair descent and the severity of CAI suggests that rehabilitation programs focusing on deficits in ankle inversion proprioception during stair descent may improve self-reported instability in CAI.

A Unique Surgical Case of Mixed Metaplastic Breast Carcinoma With Heterologous Mesenchymal Differentiation and Conventional Adenocarcinomatous Elements.

Metaplastic breast carcinoma (MBC) is very rare among all invasive breast carcinomas, accounting for less than 1.0% of them. MBCs are classified into five subtypes, including mixed MBC - where the mix might be multiple metaplastic elements or a mixture of epithelial and mesenchymal elements. Overall survival for mixed MBC tends to correlate with a significantly worse outcome. Therefore, an early accurate diagnosis and surgical treatment for mixed MBCs must allow for an improved quality of life and better prognosis. However, there have not been many recently published papers describing the detailed cytological features of mixed MBCs on fine-needle aspiration (FNA) specimens. A 60-year-old female presented with a history of a hard breast mass on the left lateral side, showing an ill-defined and marginally enhanced tumor nodule on magnetic resonance imaging. The cytologic specimens of FNA contained a large number of three-dimensional, cohesive and sheet-like clusters, or non-cohesive single cells, of highly atypical spindled sarcomatoid to oval epithelioid cells having hyperchromatic pleomorphic nuclei and mitotic figures, in a necrotic and hemorrhagic background. A small amount of osteoid matrix-like substance was rarely seen, associated with a very small number of osteoclast-like giant cells. We first interpreted it as an invasive breast carcinoma of high grade. A mastectomy was performed, and a gross examination of the neoplasm revealed a hemorrhagic solid tumor lesion with a gray-whitish cut surface, measuring approximately 35 × 24 × 21 mm in diameter. On a microscopic examination, the tumor was predominantly composed of the proliferation of highly atypical oval to spindled cells predominantly in a sarcomatous growth fashion with focal production of chondroid and osteoid matrix, peripherally coexisted with a smaller volume of conventional invasive breast carcinoma. Immunohistochemistry showed that the sarcomatous tumor cells were specifically positive for vimentin, α-smooth muscle actin, or epithelial membrane antigen. Therefore, we finally made a diagnosis of invasive mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements. To the best of our knowledge, this would most recently be the first case report of mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements, with a focus on its FNA cytomorphologic findings. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of MBC, based on multiple and adequate samplings.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

An RRM domain protein SOE suppresses transgene silencing in rice.

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum.

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

Improvement of idiopathic pulmonary fibrosis through a combination of Astragalus radix and Angelica sinensis radix via mammalian target of rapamycin signaling pathway-induced autophagy in rat.

Background: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF) in clinic. Astragalus radix (AR; Huangqi) and Angelica sinensis radix (AS; Danggui) have been frequently used in the treatment of IPF. This study aimed to reveal the pharmacological effects and the mechanisms of the action of an AR-AS combination in treating IPF. Methods: Sprague-Dawley rats were randomly divided into six groups (n=5): control, bleomycin (BLM) model, AR, AS, AR + AS, and prednisone (PDN) groups. A transforming growth factor-ß1 (TGF-ß1)-induced MRC-5 cell model were also used. Pulmonary fibrosis, inflammation, oxidative stress, and autophagy were evaluated by performing hematoxylin and eosin (H&E) staining, Masson staining, immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and hydroxyproline assay following the treatment of AR, AS, and the AR-AS herb pair. Results: Rats administered the AR-AS herb pair had lower α-smooth muscle actin (α-SMA), collagen I, fibronectin, and vimentin levels in lung tissues, and lower inflammatory cytokine levels in rat serum. In addition, the AR-AS herb pair induced mammalian target of rapamycin (mTOR)-mediated autophagy and reduced oxidative stress in BLM-induced rats. The effects of the AR and AS combination were confirmed in MRC-5 cells treated with TGF-ß1. Specifically, the combination of AR and AS attenuated MRC-5 cell fibrosis, inflammation, and oxidative stress while inducing autophagy. Conclusions: The combination of AR and AS protects against IPF by inducing autophagy via inhibiting the mTOR signaling pathway. The synergistic action of AR and AS is superior to that of either AR or AS alone.

Density Functional Theory Calculations on Fluorescence-Enhanced Mechanisms of the Optical Sensor for Zinc Ions, ADPA.

N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) as a specific ion sensor for Zn2+ has been widely applied. Although the photo-induced electron transfer (PET) mechanism was proposed previously, its fluorescence-enhanced effect still remains somewhat ambiguous, according to unknown influences of non-radiative energy decay pathways, such as intersystem crossing and internal conversion. Herein, a thorough study using density functional theory has been performed for low-lying electronic states of the ADPA monomer and hydrated ADPA-Zn2+ complex. Based on interfragment charge transfer analyses, we quantitatively calculated the amount of transferred electrons in the monomer and complex, providing solid evidences for the PET mechanism and in line with the conclusion of frontier molecular orbital analyses. Moreover, the ISC process of S1→T2 was confirmed to play a considerable role in the excitation energy relaxation process of the ADPA monomer, but this influence was significantly suppressed in the hydrated ADPA-Zn2+ complex. These results provide additional clues for the design of new metal ion-specific fluorescence probes.

Angelicin: A leading culprit involved in fructus Psoraleae liver injury via inhibition of VKORC1.

ETHNOPHARMACOLOGICAL RELEVANCE: The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years. AIM OF THE STUDY: To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments. MATERIALS AND METHODS: Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components. RESULTS: Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role. CONCLUSION: The results indicate that six targets, especially VKORC1, are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1.

The Effectiveness of Low-dose Esmketamine Versus Remifentanil Adjunct to Propofol for Sedation in Patients Undergoing Radiofrequency Thermocoagulation for Trigeminal Neuralgia.

Objectives: To access the effectiveness of propofol-esketamine versus propofol-remifentanyl in patients undergoing radiofrequency Thermocoagulation for Trigeminal Neuralgia of gasserian ganglion. Methods: In this clinical trial, 80 patients were candidates for RFT were randomly divided into two groups (n= 40). These patients aged from 21 to 81 years old. Before the start of the procedure, both groups received propofol TCI with a target level of 1.5 µgml-1. The intervention group (group E) received esketamine 0.15 mgkg-1, and the control group (group R) received remifentanyl 1.0 µgkg-1. The patients, the anesthetists and the surgeons were unaware of the medication regimen. Sedation level (based on a MOAA/S), blood pressure, oxygen saturation, the dosage of propofol, recovery time (based on Aldrete scores), postoperation pain (based on NRS), surgeons and patient satisfaction, and Pittsburgh Sleep Quality Index (PQSI) were recorded. Results: Data from 80 patients were analyzed. The sedative effects were equal in the two groups (P = .680) and the MOAA/s scores of both groups were basically maintained at or below 2 points, however, the dosage of propofol in group E was significantly less than that in group R [5.3mgkg-1h-1 (5.0 to 5.7) vs 5.8 mgkg-1h-1 ( 5.3 to 6.3), P = .000]. The group E had higher blood pressure levels during the procedure (PSBP = .002, PDBP = .023). Surgeons and patient satisfaction (Ps = .164, Pp = .580), recovery time (P = .228),The NRS values after 24hrs (P = .777)and PQSI showed no significant differences between the two groups (P = .133). Conclusions: Low-dose esketamine reduces the total amount of propofol necessary for sedation and incidence of respiratory depression during RFT of gasserian ganglion in American Society of Anesthesiologists I to III patients without affecting recovery time, satisfaction of surgeons and patients, cardiovascular adverse events, when compared with remifentanil.

Factors influencing the implementation of early discharge hospital at home and admission avoidance hospital at home: a qualitative evidence synthesis.

BACKGROUND: Worldwide there is an increasing demand for Hospital at Home as an alternative to hospital admission. Although there is a growing evidence base on the effectiveness and cost-effectiveness of Hospital at Home, health service managers, health professionals and policy makers require evidence on how to implement and sustain these services on a wider scale. OBJECTIVES: (1) To identify, appraise and synthesise qualitative research evidence on the factors that influence the implementation of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home, from the perspective of multiple stakeholders, including policy makers, health service managers, health professionals, patients and patients' caregivers. (2) To explore how our synthesis findings relate to, and help to explain, the findings of the Cochrane intervention reviews of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home services. SEARCH METHODS: We searched MEDLINE, CINAHL, Global Index Medicus and Scopus until 17 November 2022. We also applied reference checking and citation searching to identify additional studies. We searched for studies in any language. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with qualitative data collection and analysis methods examining the implementation of new or existing Hospital at Home services from the perspective of different stakeholders. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, extracted study characteristics and intervention components, assessed the methodological limitations using the Critical Appraisal Skills Checklist (CASP) and assessed the confidence in the findings using GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research). We applied thematic synthesis to synthesise the data across studies and identify factors that may influence the implementation of Hospital at Home. MAIN RESULTS: From 7535 records identified from database searches and one identified from citation tracking, we included 52 qualitative studies exploring the implementation of Hospital at Home services (31 Early Discharge, 16 Admission Avoidance, 5 combined services), across 13 countries and from the perspectives of 662 service-level staff (clinicians, managers), eight systems-level staff (commissioners, insurers), 900 patients and 417 caregivers. Overall, we judged 40 studies as having minor methodological concerns and we judged 12 studies as having major concerns. Main concerns included data collection methods (e.g. not reporting a topic guide), data analysis methods (e.g. insufficient data to support findings) and not reporting ethical approval. Following synthesis, we identified 12 findings graded as high (n = 10) and moderate (n = 2) confidence and classified them into four themes: (1) development of stakeholder relationships and systems prior to implementation, (2) processes, resources and skills required for safe and effective implementation, (3) acceptability and caregiver impacts, and (4) sustainability of services. AUTHORS' CONCLUSIONS: Implementing Admission Avoidance and Early Discharge Hospital at Home services requires early development of policies, stakeholder engagement, efficient admission processes, effective communication and a skilled workforce to safely and effectively implement person-centred Hospital at Home, achieve acceptance by staff who refer patients to these services and ensure sustainability. Future research should focus on lower-income country and rural settings, and the perspectives of systems-level stakeholders, and explore the potential negative impact on caregivers, especially for Admission Avoidance Hospital at Home, as this service may become increasingly utilised to manage rising visits to emergency departments.

The Progress and Prospects of Immune Cell Therapy for the Treatment of Cancer.

Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body's natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.