Post-marketing safety concerns with palbociclib: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVES: To explore the association between palbociclib and related adverse events (AEs) in the real world through U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: The signal strength of palbociclib-related AEs was done by disproportionality analysis. Clinical priority of palbociclib-related AEs was scored and ranked by assessing five different features. Outcome analysis, time to onset analysis, dose-report /AEs number analysis, and stratification analysis were all performed. RESULTS: There were 61,821 'primary suspected (PS)' reports of palbociclib and 195,616 AEs associated with palbociclib. The four algorithms simultaneously detected 18 positive signals at the SOC level, and 65 positive signals at the PT level. Bone marrow failure, neuropathy, peripheral, pleural effusion, myelosuppression, pulmonary edema, and pulmonary thrombosis were also found to have positive signals. Gender (female vs male, χ2 = 5.287, p = 0.022) and age showed significant differences in serious and non-serious reports. Palbociclib-related AEs had a median onset time of 79 days (interquartile range [IQR] 20-264 days). CONCLUSIONS: The study identified potential Palbociclib-related AEs and offered warnings for special AEs, providing further data for palbociclib safety studies in breast cancer patients. Nonetheless, prospective clinical trials are needed to validate these results and explain their relationship.

An ionic liquid-modified PEDOT/Ti3C2TX based molecularly imprinted electrochemical sensor for pico-molar sensitive detection of L-Tryptophan in milk.

L-Tryptophan (L-Trp) is essential for the human body and can only be obtained externally. It is important to develop a method to efficiently detect L-Trp in food. In this work, ionic liquid (IL) modified poly(3,4-ethylendioxythiophene)/ Titanium carbide (PEDOT/Ti3C2TX) was used as a substrate material to improve detection sensitivity. Molecular imprinted polymers (MIP) film for specific recognition of L-Trp was fabricated on the surface of modified electrodes using electrochemical polymerization. The monitoring results showed that the molecularly imprinted electrochemical sensors (MIECS) exhibited good linearity ranges (10-6 - 0.1 µM and 0.1-100 µM) with a low detection limit (LOD) of 2.09 × 10-7 µM. In addition, the MIECS exhibited remarkable stability, reproducibility, and immunity to interference. A good recovery (93.54-99.59%) was demonstrated in the detection of milk. The sensor was expected to be developed as a highly selective and sensitive portable assay, and applied to the detection of L-Trp in food.

Defective state regulation of Ru-doped Nb2O5 boosts fast lithium storage.

Breaking through the limitations of lithium-ion transmission is imperative for high-power rechargeable batteries. As a promising anode material for fast-charging lithium-ion batteries (LIBs), niobium pentoxide (Nb2O5) has garnered considerable research attention due to its exceptional rate performance, stable lithium storage performance and high safety attributes. Nevertheless, the limited intrinsic conductivity of Nb2O5, coupled with its structural degradation during the cycling process, imposes constraints on its viability as a commercially viable electrode material. Herein, a ruthenium (Ru) doping method is employed to regulate the oxygen defects and the interlayer spacing of the tetragonal Nb2O5 (M-Nb2O5), offering superior reaction kinetics, higher stability for lithium storage sites and more unobstructed lithium-ion transport channels. Ru-doped Nb2O5 (RNO) manifests excellent electrochemical properties, including remarkable rate capacity (166 mAh/g at 80C), reversible capacity (246.98 mAh/g at 0.5C), improved initial Coulombic efficiency (95.77 % compared to 81.44 % of the pure sample) and cycling stability (maintaining a capacity of 113.5 mAh/g at 10C for 2,000 cycles). The enhancement mechanism of Ru doping on the structural stability and ion transport kinetics in tetragonal Nb2O5 is comprehensively elucidated through diverse electrochemical analyses and in-situ techniques.

Carbon Fiber Reinforced Recycled Polypropylene/Polyolefin Elastomer Composites with High Mechanical Properties.

The treatment of waste plastics has gradually become a hot topic in the current scientific community. In response to the needs for high-impact performance R-PP-based composites, carbon fiber (CF)-reinforced polyolefin elastomer (POE)/recycled polypropylene (R-PP) composite (CF/POE/R-PP) was prepared by the mechanical blending method, and its mechanical and thermal properties were systematically studied. It was found that the CF could effectively improve the bending and notch impact strength as well as enhance the thermal stability of POE/R-PP. Furthermore, a stable and dispersed composite interface formed by the combination of maleic anhydride-grafted polypropylene (PP-g-MAH) with the surface of CF and the fusion alkyl chains in R-PP and POE further enhanced the CF's reinforcing effect. As a result, the addition of 9 wt.% CF successfully improved the heat resistance of the composite material, and the residual carbon content increased by 97.84% after sintering. The composite toughening of POE and CF effectively improved the impact strength of the composite material, with a maximum increase of over 1000%. This study ultimately resulted in a high-impact-resistant composite material.

A novel molecularly imprinted electrochemical sensor from poly (3, 4-ethylenedioxythiophene)/chitosan for selective and sensitive detection of levofloxacin.

The improper usage of levofloxacin (LEV) endangers both environmental safety and human public health. Therefore, trace analysis and detection of LEV have extraordinary significance. In this paper, a novel molecularly imprinted polymer (MIP) electrochemical sensor was developed for the specific determination of LEV by electrochemical polymerization of o-phenylenediamine (o-PD) using poly(3,4-ethylenedioxythiophene)/chitosan (PEDOT/CS) with a porous structure and rich functional groups as a carrier and LEV as a template molecule. The morphology, structure and properties of the modified materials were analyzed and studied. The result showed that the electron transfer rate and the electroactive strength of the electrode surface are greatly improved by the interconnection of PEDOT and CS. Meanwhile, PEDOT/CS was assembled by imprinting with o-PD through non-covalent bonding, which offered more specific recognition sites and a larger surface area for the detection of LEV and effectively attracted LEV through intermolecular association. Under the optimized conditions, MIP/PEDOT/CS/GCE showed good detection performance for LEV in a wide linear range of 0.0019- 1000 µM, with a limit of detection (LOD, S/N = 3) of 0.4 nM. Furthermore, the sensor has good stability and selectivity, and exhibits excellent capabilities in the microanalysis of various real samples.

Single Crystal Seed Induced Epitaxial Growth Stabilizes α-FAPbI3 in Perovskite Solar Cells.

FAPbI3 stands out as an ideal candidate for the photoabsorbing layer of perovskite solar cells (PSCs), showcasing outstanding photovoltaic properties. Nonetheless, stabilizing photoactive α-FAPbI3 remains a challenge due to the lower formation energy of the competitive photoinactive δ-phase. In this study, we employ tetraethylphosphonium lead tribromide (TEPPbBr3) single crystals as templates for the epitaxial growth of PbI2. The strategic use of TEPPbBr3 optimizes the evolution of intermediates and the crystallization kinetics of perovskites, leading to high-quality and phase-stable α-FAPbI3 films. The TEPPbBr3-modified perovskite exhibits optimized carrier dynamics, yielding a champion efficiency of 25.13% with a small voltage loss of 0.34 V. Furthermore, the target device maintains 90% of its initial PCE under maximum power point (MPP) tracking over 1000 h. This work establishes a promising pathway through single crystal seed based epitaxial growth for achieving satisfactory crystallization regulation and phase stabilization of α-FAPbI3 perovskites toward high-efficiency and stable PSCs.

ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition.

The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-µM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.

Theoretical and experimental study of attenuation in cancellous bone.

Significance: Photoacoustic (PA) technology shows great potential for bone assessment. However, the PA signals in cancellous bone are complex due to its complex composition and porous structure, making such signals challenging to apply directly in bone analysis. Aim: We introduce a photoacoustic differential attenuation spectrum (PA-DAS) method to separate the contribution of the acoustic propagation path to the PA signal from that of the source, and theoretically and experimentally investigate the propagation attenuation characteristics of cancellous bone. Approach: We modified Biot's theory by accounting for the high frequency and viscosity. In parallel with the rabbit osteoporosis model, we build an experimental PA-DAS system featuring an eccentric excitation differential detection mechanism. Moreover, we extract a PA-DAS quantization parameter-slope-to quantify the attenuation of high- and low-frequency components. Results: The results show that the porosity of cancellous bone can be evaluated by fast longitude wave attenuation at different frequencies and the PA-DAS slope of the osteoporotic group is significantly lower compared with the normal group (**p<0.01). Conclusions: Findings demonstrate that PA-DAS effectively differentiates osteoporotic bone from healthy bone, facilitating quantitative assessment of bone mineral density, and osteoporosis diagnosis.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons.

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

Tumor Microenvironment-Activatable Nanosystem Capable of Overcoming Multiple Therapeutic Obstacles for Augmenting Immuno/Metal-Ion Therapy.

Abnormal tumor microenvironment (TME) imposes barriers to nanomedicine penetration into tumors and evolves tumor-supportive nature to provide tumor cell protection, seriously weakening the action of antitumor nanomedicines and posing significant challenges to their development. Here, we engineer a TME-activatable size-switchable core-satellite nanosystem (Mn-TI-Ag@HA) capable of increasing the effective dose of therapeutic agents in deep-seated tumors while reversing tumor-supportive microenvironment for augmenting immuno/metal-ion therapy. When activated by TME, the nanosystem disintegrates, allowing ultrasmall-sized Ag nanoparticles to become unbound and penetrate deep into solid tumors. Simultaneously, the nanosystem produces O2 and releases TGF-ß inhibitors in situ to drive macrophage M2-to-M1 polarization, increasing intratumoral H2O2 concentration, and ultimately augmenting metal-ion therapy by accelerating hypertoxic Ag+ production. The nanosystem can overcome multiple obstacles that aid in tumor resistance to nanomedicine, demonstrating effective tumor penetration, TME regulation, and tumor inhibition effects. It can provoke long-term immunological memory effects against tumor rechallenge when combined with immune checkpoint inhibitor anti-PD-1. This work provides a paradigm for designing efficient antitumor nanomedicines.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 µmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.

[Yeast extract improves the inflammatory response of HepG2 cells induced by ethyl alcohol and lipopolysaccharide].

OBJECTIVE: To explore the ameliorative effect of yeast extract(YE) on the inflammatory response of human hepatoma cells(HepG2) induced by ethyl alcohol(EtOH) and lipopolysaccharide(LPS), and further explore the potential molecular mechanism based on Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) signaling pathway. METHODS: HepG2 cells were induced by 50 mmol/L EtOH and 1 µg/mL LPS combined with YE intervention. The expression level of inflammatory cytokines was detected by ELISA. The expression level of TLR4 and the nuclear translocation of NF-κB were detected by immunofluorescence staining. The expression levels of TLR4, NF-κB, phospho-NF-κB-P65(P-NF-κB-p65), nucleus-phospho-NF-κB-p65(N-P-NF-κB-p65), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) were detected by Western blot. RESULTS: Compared with the control group, the cells in EtOH+LPS group produced a large number of inflammatory factors and had a significant inflammatory response. YE intervention significantly alleviated EtOH+LPS induced hepatocyte inflammatory response. Further molecular mechanism studies showed that YE significantly reduced TLR4 expression level and inhibited NF-κB nuclear translocation in hepatocytes. CONCLUSION: YE can effectively inhibit the inflammatory response of HepG2 cells induced by EtOH and LPS, and its molecular mechanism may be related to the down-regulation of TLR4/NF-κB pathway.

Capacitive Bionic Magnetic Sensors Based on One-Step Biointerface Preparation.

Magnetic biomolecule-based bionic magnetic field sensors are anticipated to open up novel pathways for magnetic field detection. The detection range and accuracy of current bionic magnetic field sensors are limited, and little work is based on the capacitive response principle. We successfully developed a biochemical interface with an extralarge target-receptor size ratio, which can be manufactured in a single step for weak magnetic field detection across a wide frequency range, and we used electrochemical capacitance as a magnetic field change conduction strategy. The thickness-controllable nanoscale bovine serum albumin/graphene layer on an indium tin oxide working electrode combines with the one-step preparation method to immobilize the MagR/Cry4 complex. This capacitive bionic magnetic sensor can achieve the detection range of 0-120 mT. This biointerface design strategy obtains the further improvement of the performance of this bionic magnetic field sensor. Furthermore, the biointerface construction and optimization methodology in this proposal has potential applications in the design of other medical biosensors.

Anion-Involved Solvation Structure of Lithium Polysulfides in Lithium-Sulfur Batteries.

Lithium polysulfides (LiPSs) are pivotal intermediates involved in all the cathodic reactions in lithium-sulfur (Li-S) batteries. Elucidating the solvation structure of LiPSs is the first step for rational design of electrolyte and improving Li-S battery performances. Herein, we investigate the solvation structure of LiPSs and find that Li salt anions tend to enter the first solvation sheath of LiPSs and form contact ion pairs in electrolyte. The anion-involved solvation structure of LiPSs significantly influences the intrinsic kinetics of the sulfur redox reactions. In particular, the LiPS solvation structure modified by lithium bis(fluorosulfonyl)imide endows Li-S batteries with reduced polarization and enhanced rate performances under high sulfur areal loading and lean electrolyte volume conditions. This work updates the fundamental understanding of the solvation chemistry of LiPSs and highlights electrolyte engineering for promoting the performances of Li-S batteries.

All-Year High IAA and ABA Contents in Rhizome Buds May Contribute to Natural Four-Season Shooting in Woody Bamboo Cephalostachyum pingbianense.

To explore the regulation mechanism of endogenous phytohormones on rhizome bud germination in Cephalostachyum pingbianense, the contents of IAA, ABA, GA, and CTK in seven above- and under-ground bamboo structure components were determined using enzyme-linked immunosorbent assays (ELISA). The results showed that a higher content of IAA, GA, and CTK all year was found in above-ground components and dormant rhizome buds. Meanwhile, a higher ABA content in young shoots and a lower ABA content in the culm base and dormant rhizome buds were detected during the peak period of shooting. The amounts of emerging shoots and the grown bamboo culms were positively correlated with the content of IAA and the ratio of IAA/ABA and (IAA + CTK + GA)/ABA, while they were negatively correlated with the ratio of CTK/IAA in dormant rhizome buds. The all-year high contents of IAA (19-31 ng/g) and ABA (114-144 ng/g) in rhizome buds, as well as interactions among four hormones, may be the key physiological mechanisms to maintain rhizome bud germination throughout the year in C. pingbianense. As C. pingbianense is a special bamboo species of multi-season shoot sprouting, the above results may supplement scientific data for a comprehensive understanding of physiological mechanisms within the bamboo subfamily.

Identification and Validation of a Hypoxia and Glycolysis Prognostic Signatures in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) represents a prevalent subtype of non-small cell lung cancer with a complex molecular landscape. Dysregulated cellular energetics, notably the interplay between hypoxia and glycolysis, has emerged as a hallmark feature of LUAD tumorigenesis and progression. In this study, we aimed to identify hypoxia and glycolysis related gene signatures and construct a prognostic model to enhance the clinical management of LUAD. Methods: A gene signature associated with hypoxia and glycolysis was established within the The Cancer Genome Atlas (TCGA) cohort and subsequently validated in the GSE31210 cohort. Additionally, a nomogram was formulated to aid in predictive modeling. Subsequently, an evaluation of the tumor microenvironment and immune checkpoints expression levels was conducted to discern disparities between low risk and high risk groups. Lastly, an exploration for drugs with potential effectiveness was carried out. Results: Our analyses revealed a distinct hypoxia and glycolysis related gene signature consisting of 6 genes significantly associated with LUAD patient survival. Integration of these genes into the prognostic model demonstrated superior predictive accuracy for patient outcomes. Furthermore, we developed a user-friendly nomogram that effectively translates the model's prognostic information into a practical tool for clinical decision-making. Conclusion: This study elucidates the critical role of hypoxia and glycolysis related genes in LUAD and offers a novel prognostic model with promising clinical utility. This model has the potential to refine risk stratification and guide personalized therapeutic interventions, ultimately improving the prognosis of LUAD patients.

Herb-drug interactions of silybinin and cilofexor in beagle dogs based on pharmacokinetics by UPLC-MS/MS.

Objective: A remarkably sensitive, accurate, and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed as a facile and expeditious method for measuring cilofexor concentration in beagle dogs, the herb-drug interactions between silybinin and cilofexor was explored based on pharmacokinetics. Methods: The plasma sample protein of the beagles were rapidly sedimented with acetonitrile, and cilofexor and tropifexor (internal standard, ISTD) were separated by gradient elution using a 0.1% formic acid aqueous solution and acetonitrile as the mobile phase. The concentrations were detected using positive ion multiple reaction monitoring (MRM) mode. Mass transfer pairs were m/z 587.91→267.91 for cilofexor and m/z 604.08→228.03 for ISTD, respectively. A two-period self-controlled experimental design was adopted for the HDIs experiment. In the first period (Group A), six beagle dogs were orally administered cilofexor at a dose of 1 mg/kg. In the second period (Group B), silybinin (3 mg/kg) was orally administered to the six beagle dogs twice a day for seven consecutive days, after which cilofexor was orally administered. The cilofexor concentration in beagle dogs was determined, and HDIs were evaluated based on their pharmacokinetics. Results: The accuracy and precision of cilofexor were both less than 15%, and the recoveries, matrix effects, and stability met the relevant requirements. The Cmax of cilofexor in group B was 49.62% higher than that in group A, whereas the AUC(0-t) and AUC(0-∞) of cilofexor in group B were 47.85% and 48.52% higher, respectively, than those in group A. Meanwhile, the t1/2 extended from 7.84 h to 9.45 h, CL and Vz decreased in Group B. Conclusion: A novel UPLC-MS/MS approach was successfully applied for the measurement of cilofexor in beagle dog plasma. Silybinin can alter the pharmacokinetics of cilofexor in beagle dogs, thereby increasing plasma exposure to cilofexor.

Efficacy and Safety in Early application of Ruxolinitib for high-risk: Acute lymphoblastic leukemia to prevent GVHD and recurrence after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been identified as the potentially curative treatment for high-risk acute lymphoblastic leukemia (ALL) in adult patients. However, relapse of the disease and/or development of graft-versus-host disease (GVHD) remain to be the most common barriers for successful allo-HSCT. Preclinical studies showed that ruxolitinib, a Janus tyrosine kinase (Jak)1 and Jak2 inhibitor, has a selective anti-GVHD effects while preserving a potent graft-versus-leukemia (GVL) effect. Our study aimed to investigate the efficacy and safety in early application of ruxolitinib for the high-risk ALL patients to prevent GVHD. METHODS: There were eight patients undergoing allo-HSCT at the Bone Marrow Transplantation Center of the Third Xiangya Hospital of Central South University between April 2020 and April 2021. Ruxolitinib (5-10 mg twice daily) was administered early (median time: 45 days) after stem cell infusion. RESULTS: After a median follow-up of 14 months (range from 8 to 18 months), the ALL disease relapse occurred in two cases. Among all eight patients, two of them developed grade I/II acute (a) GVHD, while no patient developed grade III/IV aGVHD, and one patient developed chronic (c) GVHD. As for the virus activation, no patient developed EBV activation or EBV related lymphoproliferative disease, and three patients developed CMV activation. Our results suggest that the early application of ruxolitinib could safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, it may have a limited effect on preventing the recurrence of high-risk ALL and thus may require additional therapy with other anti-relapse drugs. CONCLUSIONS: Our preliminary observations suggest that an early application of ruxolitinib can safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, ruxolitinib may have a limited effect on preventing the ALL recurrence of high-risk patients.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.