Cognitive impairment is one of the manifestations of nervous system injury,which is mainly closely related to neurodegeneration,and the incidence rate is increasing year by year,which has seriously affected the health level of the population.The gut microbiota plays an important role in the health of the body and participates in the regulation of the cognitive behavior of body.The microbiome-gut-brain axis acts as a bridge connecting gut microbiota and the nervous system,and plays a regulatory role between gut microbiota and the nervous system.Therefore,this review summarizes the latest progress in the effects of gut microbiota and nervous system on the cognitive ability of body through the bidirectional regulation of neurotransmitters,gut microbiota derivatives,neuroinflammation,oxidative stress,autophagy and their crosstalk through the microbial-intestinal-brain axis,and providing a reference for the clinical research of targeted transplantation of gut microbiota for preventing and treating cognitive disorders.

Bone tissue engineering(BTE)is expected to be used as an autologous bone graft substitute for bone defects,and in the se-lection of BTE scaffold materials,collagen(Col)and hydroxyapatite(HA)have attracted attention due to their unique biomimetic ad-vantages.Collagen/hydroxyapatite(CHA)composite scaffolds made by combining the two have been shown to have excellent biocompat-ibility and bone-enhancing potential in various in vitro,in vivo,and clinical studies.With the development of three-dimensional(3D)printing technology in the field of tissue engineering,bone scaffolds constructed using 3D printing methods have been shown to possess superior clinical potential.This review describes new advances in 3D printed CHA composite scaffolds and introduces the application of 3D printed CHA scaffolds in oral and maxillofacial bone regenerative repair.

Cognitive impairment is one of the manifestations of nervous system injury,which is mainly closely related to neurodegeneration,and the incidence rate is increasing year by year,which has seriously affected the health level of the population.The gut microbiota plays an important role in the health of the body and participates in the regulation of the cognitive behavior of body.The microbiome-gut-brain axis acts as a bridge connecting gut microbiota and the nervous system,and plays a regulatory role between gut microbiota and the nervous system.Therefore,this review summarizes the latest progress in the effects of gut microbiota and nervous system on the cognitive ability of body through the bidirectional regulation of neurotransmitters,gut microbiota derivatives,neuroinflammation,oxidative stress,autophagy and their crosstalk through the microbial-intestinal-brain axis,and providing a reference for the clinical research of targeted transplantation of gut microbiota for preventing and treating cognitive disorders.

Objective To assess the therapeutic efficacy of low-intensity focused ultrasound(LIFU)on knee arthrofibrosis in rats and explore its underlying mechanisms.Methods Fifteen male SD rats(8 weeks old,weighing 250～300 g)were randomly divided into a blank control group,a model group,and an ultrasound treatment group,with 5 animals in each group.Rat model of knee joint stiffness was established in the model and ultrasound treatment group.The rats in the ultrasound group received LIFU intervention(frequency:1 MHz,power:1.5 W,20 min per session,5 times/week)for 4 weeks.The knee ranges of motion(ROM,flexion and extension)were measured in all 3 groups at 0,14 and 28 d after intervention.Histological analysis was conducted for the morphological changes in the posterior capsular area of the knee.After the synovial fibroblasts were primary isolated from rat knee joints,the cells were divided into blank control,LIFU,TGF-β(10 ng/mL),and TGF-β+LIFU groups.Changes in fibrosis-related indicators and the TGF-β/Smad signaling pathway were assessed in each group.Results In the animal experiments,LIFU intervention for 14 d resulted in significantly improved flexion-extension ROM in knee joints when compared with the rats in the model group(P<0.05),and the improvement was more obvious at 28 d after intervention(P<0.05).After 28 d of LIFU intervention,the fibrosis of the posterior capsule of the knee joint was notably improved in the ultrasound group than the model group,and the expression levels of fibrosis-related indicators(α-SMA,TGF-β)were decreased(P<0.05).In the cellular experiments,the TGF-β group exhibited remarkable up-regulation of fibrosis-related molecules(α-SMA,COL1A1,COL3A1)at both protein and mRNA levels(P<0.05),and activation of the TGF-β/Smad signaling pathway when compared to the blank control group.While LIFU intervention inhibited the expression of TGF-β-induced upregulation of fibrotic indicators(α-SMA,COL1A1,COL3A1)and the activation of TGF-β/Smad signaling pathway(P<0.05).Conclusion LIFU can effectively improve knee arthrofibrosis in rats,which potentially through the inhibition of fibroblast activation and modulation of the TGF-β/Smad signaling pathway.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Bone tissue engineering(BTE)is expected to be used as an autologous bone graft substitute for bone defects,and in the se-lection of BTE scaffold materials,collagen(Col)and hydroxyapatite(HA)have attracted attention due to their unique biomimetic ad-vantages.Collagen/hydroxyapatite(CHA)composite scaffolds made by combining the two have been shown to have excellent biocompat-ibility and bone-enhancing potential in various in vitro,in vivo,and clinical studies.With the development of three-dimensional(3D)printing technology in the field of tissue engineering,bone scaffolds constructed using 3D printing methods have been shown to possess superior clinical potential.This review describes new advances in 3D printed CHA composite scaffolds and introduces the application of 3D printed CHA scaffolds in oral and maxillofacial bone regenerative repair.

Objective To introduces drug treatment and individualized pharmaceutical care for a patient with dilated cardiomyopathy digoxin poisoning and provides ideas for pharmaceutical care.Methods The pharmacist used therapeutic drug management to analyze the course of drug treatment before and after hospitalization,combined with therapeutic drug monitoring and drug-gene detection,to analyze the causes of poisoning in digoxin from the perspectives of underlying diseases,polymor-phism,drug dosage,combination of drugs,physiological and other pathological factors,and to assist in clinical drug reformula-tion and optimization of drug treatment regimens.Results The clinician accepted the clinical pharmacist's suggestion.The pa-tient had a good prognosis,and digoxin poisoning did not occur in the later period.Conclusion This case provides a feasible treatment for dilated cardiomyopathy and other patients with digoxin intoxication;it can be used as a reference for the prevention and treatment of digoxin poisoning and provide a new direction for the development of hospital pharmaceutical care and pharma-ceutical professionals.

Background::Studies that comprehensively address the characteristics of centenarian deaths are rare. The present study aimed to depict the characteristics of centenarian deaths in China and their changing trends.Methods::Data on centenarian deaths between 2013 and 2020 were obtained from the national mortality surveillance system of China, including date, place of death (PoD), and underlying cause of death (CoD). Descriptive analyses were performed to understand the epidemiological characteristics, and a joinpoint regression model was adopted to examine the changing trends in the proportions of different PoDs, CoDs among centenarians, and centenarian deaths accounting for all deaths and deaths among people aged 65 years and older.Results::There were 46,938 registered centenarian deaths between 2013 and 2020 that included 34,311 females (73.10%) and 12,627 males (26.90%). January (12.05%), February (9.99%), and December (9.74%) were the top three months with the highest number of deaths. The proportions of deaths that occurred in homes, hospitals, and nursing homes were 81.71%, 13.63%, and 2.68%, respectively. The proportion of deaths in nursing homes increased by 9.60% (95% confidence intervals [CIs], 6.4-12.9%) from 2014 to 2020. Heart disease (35.72%) was the leading cause of death, followed by respiratory diseases (17.63%), cerebrovascular disease (15.60%), and old age (11.22%). The proportion of respiratory diseases decreased by 4.8% (95% CI, -8.8 to -0.7%), and the proportion of deaths from old age decreased by 2.3 % (95% CI, -4.4 to -0.1%) per year. Shanghai had the highest proportions of deaths in hospitals (39.38%) and nursing homes (14.68%). Sichuan had the highest proportion of deaths attributed to respiratory diseases (32.30%), while Jiangsu (26.58%) and Zhejiang (23.61%) had the highest proportions of deaths from old age.Conclusion::Unlike other countries, centenarian deaths in China are characterized by a higher proportion of home and heart disease deaths, and this death pattern differs across provinces.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.