Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Low Gilbert damping in Bi/In-doped YIG thin films with giant Faraday effect

Magnetic films with low Gilbert damping are crucial for magnonic devices,which provide a promising platform forrealizing ultralow-energy devices.In this study,low Gilbert damping and coercive field were observed in Bi/In-dopedyttrium iron garnet(BiIn:YIG)thin films.The BiIn:YIG(444)films were deposited onto different substrates using pulsedlaser deposition.Low coercivity(<1 Oe)with saturation magnetization of 125.09 emu/cc was achieved along the in-planedirection of BiIn:YIG film.The values of Gilbert damping and inhomogeneous broadening of ferromagnetic resonance inBiIn:YIG films were obtained to be as low as 4.05×10^(-4)and 5.62 Oe,respectively.In addition to low damping,the giantFaraday rotation angles(up to 2.9×10^(4)deg/cm)were also observed in the BiIn:YIG film.By modifying the magneticstructure and coupling effect between Bi^(3+)and Fe^(3+)of Bi:YIG,doped In^(3+)plays a key role on variation of the magneticproperties.The low damping and giant Faraday effect made the BiIn:YIG film an appealing candidate for magnonic andmagneto-optical devices.

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation

A distinct population of skeletal stem/progenitor cells(SSPCs)has been identified that is indispensable for the maintenance and remodeling of the adult skeleton.However,the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined.Here,we established models of premature aging by conditional depletion of Zmpste24(Z24)in mice and found that Prx1-dependent Z24 deletion,but not Osx-dependent Z24 deletion,caused significant bone loss.However,Acan-associated Z24 depletion caused only trabecular bone loss.Single-cell RNA sequencing(sc RNA-seq)revealed that two populations of SSPCs,one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells,were significantly decreased in Prx1-Cre;Z24^(f/f)mice.Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation.Physical exercise reversed the effects of Z24depletion on cellular apoptosis,extracellular matrix expression and bone mass.This study identified two populations of SSPCs that are responsible for premature aging-related bone loss.The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.

SA-Model:Multi-Feature Fusion Poetic Sentiment Analysis Based on a Hybrid Word Vector Model

Sentiment analysis in Chinese classical poetry has become a prominent topic in historical and cultural tracing,ancient literature research,etc.However,the existing research on sentiment analysis is relatively small.It does not effectively solve the problems such as the weak feature extraction ability of poetry text,which leads to the low performance of the model on sentiment analysis for Chinese classical poetry.In this research,we offer the SA-Model,a poetic sentiment analysis model.SA-Model firstly extracts text vector information and fuses it through Bidirectional encoder representation from transformers-Whole word masking-extension(BERT-wwmext)and Enhanced representation through knowledge integration(ERNIE)to enrich text vector information;Secondly,it incorporates numerous encoders to remove text features at multiple levels,thereby increasing text feature information,improving text semantics accuracy,and enhancing the model’s learning and generalization capabilities;finally,multi-feature fusion poetry sentiment analysis model is constructed.The feasibility and accuracy of the model are validated through the ancient poetry sentiment corpus.Compared with other baseline models,the experimental findings indicate that SA-Model may increase the accuracy of text semantics and hence improve the capability of poetry sentiment analysis.

Mechanical regulation of bone remodeling

Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis;skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.

The RNA-binding protein Musashi2 governs osteoblast-adipocyte lineage commitment by suppressing PPARγsignaling

Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.

Motivating in the Production-Oriented Approach:From Theory to Practice

Motivating is the most creative phase of the Production-Oriented Approach(POA),making it different from other teaching approaches from the outset.This study aims to introduce the theory of motivating and its application to College English teaching practice by adopting dialectal research(DR).First,it gives an overall introduction to motivating,including its function,steps,and categories.Then it demonstrates two rounds of motivating practice in teaching College English by using the POA-based textbook iEnglish.The first round of motivating practice mainly focuses on how to follow the three steps of motivating in a specific case,namely,the teacher providing scenarios,the students trying out the productive activity,and the teacher explaining the productive objectives.The second round attempts to apply the criteria of motivating effectiveness to practice,namely,authentic communication,cognitive challenges and appropriate productive objectives.Furthermore,the teaching effectiveness of the motivating practice is appraised by both the teacher’s and students’retrospective evaluations.Finally,some suggestions for motivating design and future research are proposed.

Stem cell properties and neural differentiation of sheep amniotic epithelial cells

This study was designed to verify the stem cell properties of sheep amniotic epithelial cells and their capacity for neural differentiation. Immunofluorescence microscopy and reverse transcription-PCR revealed that the sheep amniotic epithelial cells were positive for the embryonic stem cell marker proteins SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, and the totipotency-associated genes Oct-4, Sox-2 and Rex-1, but negative for Nanog. Amniotic epithelial cells expressed β-Ⅲ-tubulin, glial fibrillary acidic protein, nestin and microtubule-associated protein-2 at 28 days after induction with serum-free neurobasal-A medium containing B-27. Thus, sheep amniotic epithelial cells could differentiate into neurons expressing β-Ⅲ-tubulin and microtubule-associated protein-2, and glial-like cells expressing glial fibrillary acidic protein, under specific conditions.

Changes in motor function in the unaffected hand of stroke patients should not be ignored

Motor function changes in the unaffected hand of stroke patients with hemiplegia. These changes are often ignored by clinicians owing to the extent of motor disability of the affected hand. Finger tapping frequency and Lind-mark hand function score showed that the motor function of unaffected hands in stroke patients was poorer than that of a healthy control hand. After 2 weeks of rehabilitation treatment, motor function of the unaffected hand of stroke patients was obviously improved. Therefore, attention should also be paid to motor function in the unaffected hand of stroke patients with hemiplegia during rehabilitation.

SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

Engineering miniature gold nanorods with tailorable plasmonic wavelength in NIR region via ternary surfactants mediated growth

Plasmonic nanoparticles are endowed profound capability for sensing,biomedicine,and cancer therapy.However,the inaccessibly adjustable wavelength in near infrared(NIR)region window and size limit for the particles penetration in tumor strongly hinder their developments.Miniature gold nanorods(mini-Au NRs)with diameter less than 12 nm can effectively address this challenge due to the tiny size and tailorable NIR absorption.Herein,we adopt ternary surfactants(hexadecyl trimethyl ammonium bromide(CTAB),sodium oleate(NaOL),and sodium salicylate(NaSal))mediated growth strategy to precisely synthesize miniature Au NRs under micelle space-confinement.Importantly,the selectively dense accumulation of ternary surfactants can efficiently improve the micellar stacking parameters(p)and lower micellar free energy(F),further tends to achieve the formation of Au NRs with tiny diameter and high purity.Compared with that of conventional methods,the purity of mini-Au NRs up to 100%can be dramatically improved via varying the relative concentration of ternary surfactants.The diameter of Au NRs can be dynamically controlled to 6,8,and 11 nm through regulating the concentration of silver nitrate and the mole ratio of ternary surfactants.Such ternary surfactants system is favorable for the aging of tiny Au NRs,and further enables the aspect ratio-tunable in the region from 2.70 to 7.32,as well as tailorable plasmonic wavelength in wide NIR window from 700 to 1,147 nm.Therefore,our findings shed a light on the precise preparation of small sized plasmonic nanoparticles and pave the way to applications in biomedicine,imaging,and cancer therapy.

Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health.With the passing of time,the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumulates.To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China,the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission.This recommendations includes the epidemiology,diagnosis,management,maternal care,medication treatment,care of birth and newborns,and psychological support associated with maternal SARS-CoV-2 infection.It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Improved symptoms following bumetanide treatment in children aged 3-6 years with autism spectrum disorder:a randomized,double-blind,placebo-controlled trial

With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.

In situ carbon nanotube clusters grown from three- dimensional porous graphene networks as efficient sulfur hosts for high-rate ultra-stable Li-S batteries

Carbon nanotube （CNT） clusters grown in situ in three-dimensional （3D） porous graphene networks （3DG-CNTs）, with integrated structure and remarkable electronic conductivity, are desirable S host materials for Li-S batteries. 3DG-CNT exhibits a high surface area （1,645 m^2·g^-1）, superior electronic conductivity of 1,055 S·m^-1, and a 3D porous networked structure. Large clusters of CNTs anchored on the inner walls of 3D graphene networks act as capillaries, benefitting restriction of agglomeration by high contents of immersed S. Moreover, the capillary-like CNT clusters grown in situ in the pores efficiently form restricted spaces for Li polysulfides, significantly reducing the shuttling effect and promoting S utilization throughout the charge/discharge process. With an areal S mass loading of 81.6 wt.%, the 3DG-CNT/S electrode exhibits an initial specific capacity reaching 1,229 mA·h·g^-1 at 0.5 C and capacity decays of 0.044% and 0.059% per cycle at 0.5 and 1 C, respectively, over 500 cycles. The electrode material also reveals a remarkable rate performance and the large capacity of 812 mA·h·g^-1 at 3 C.

Co-regulation of circadian clock genes and microRNAs in bone metabolism

Mammalian bone is constantly metabolized from the embryonic stage,and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation,mediated by osteoclasts and osteoblasts.It is widely recognized that circadian clock genes can regulate bone metabolism.In recent years,the regulation of bone metabolism by non-coding RNAs has become a hotspot of research.MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism,including circadian clock genes.However,research in this field has been conducted only in recent years and the mechanisms involved are not yet well established.Recent studies have focused on how to target circadian clock genes to treat some diseases,such as autoimmune diseases,but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases.Therefore,in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs,aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data

The genetically engineered pig is regarded as an optimal source of organ transplantation for humans and an excellent model for human disease research,given its comparable physiology to human beings.A myriad of single-cell RNA sequencing(sc RNA-seq)data on humans has been reported,but such data on pigs are scarce.Here,we apply sc RNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs,generating the single-cell atlas of 13,580 cells covering 16 major cell types.Based on these data,we systematically characterize the similarities and differences in the cellular cross-talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared with human lungs.Furthermore,we analyze pig lung xenotransplantation barriers and reported the cell-type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation.We also investigate the conserved transcription factors(TFs)and their candidate target genes and constructed five conserved TF regulatory networks in the main cell types shared by pig and human lungs.Finally,we present a comprehensive and openly accessible online platform,Scdb Lung.Our sc RNA-seq atlas of the domestic pig lung and Scdb Lung database can guide pig lung research and clinical applicability.

Shanghai Autism Early Development:An Integrative Chinese ASD Cohort

Why Was the Cohort Set Up?Autism spectrum disorder(ASD)is a child neurodevelopmental disorder,the onset of which is generally within 3 years of age,and often leads to lifelong impaired social and cognitive functions,which impose significant mental pressure and economic burdens on the family and society.