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Background: Thrombolytic therapy is essential for acute ischemic stroke (AIS) management but poses a risk of hemorrhagic transformation (HT), necessitating accurate prediction to optimize patient care. Methods: A comprehensive search was conducted across PubMed, Web of Science, Scopus, Embase, and Google Scholar, covering studies from inception until July 10, 2024. Studies were included if they used machine learning (ML) or deep learning algorithms to predict HT in AIS patients treated with thrombolysis. Exclusion criteria included studies involving endovascular treatments and those not evaluating model effectiveness. Data extraction and quality assessment were performed following PRISMA guidelines and using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST) tools. Results: Out of 1943 identified records, 12 studies were included in the final analysis, encompassing 18 007 AIS patients who received thrombolytic therapy. The ML models demonstrated high predictive performance, with pooled area under the curve (AUC) values ranging from 0.79 to 0.95. Specifically, XGBoost models achieved AUCs of up to 0.953 and Artificial Neural Network (ANN) models reached up to 0.942. Sensitivity and specificity varied significantly, with the highest sensitivity at 0.90 and specificity at 0.99. Significant predictors of HT included age, glucose levels, NIH Stroke Scale (NIHSS) score, systolic and diastolic blood pressure, and radiomic features. Despite these promising results, methodological disparities and limited external validation highlighted the need for standardized reporting and further rigorous testing. Conclusion: ML techniques, especially XGBoost and ANN, show great promise in predicting HT following thrombolysis in AIS patients, enhancing risk stratification and clinical decision-making. Future research should focus on prospective study designs, standardized reporting, and integrating ML assessments into clinical workflows to improve AIS management and patient outcomes.

Cardiovascular disease (CVD) is a leading cause of human mortality worldwide, with patients often at high risk of heart failure (HF) in myocardial infarction (MI), a common form of CVD that results in cardiomyocyte death and myocardial necrosis due to inadequate myocardial perfusion. As terminally differentiated cells, cardiomyocytes possess a severely limited capacity for regeneration, and an excess of dead cardiomyocytes will further stress surviving cells, potentially exacerbating to more extensive heart disease. The article focuses on the relationship between programmed cell death (PCD) of cardiomyocytes, including different forms of apoptosis, necrosis, and autophagy, and MI, as well as the potential application of these mechanisms in the treatment of MI. By gaining a deeper understanding of the mechanisms of cardiomyocyte death, it aims to provide new insights into the prevention and treatment of MI., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Macrophages - one of the crucial immune cells, are recruited to the cardiac tissue by chemokines, cytokines and upregulated endothelial adhesion molecules after myocardial infarction (MI). During the course of inflammation in the cardiac tissue, necrotic cells and matrix debris is phagocytosed by M1 macrophages. During the resolution phase of cardiac inflammation, M2 macrophages promote cardiac recovery. Suppression or over expression of both the M1 and M2 macrophage subtypes significantly affect the reparation of infarction. Stem cells therapy, cytokine regulation and immune cells therapy are considered as effective interventions to regulate the phenotypic transformation of cardiac macrophages after MI. Intervention with macrophages in the myocardium has shown unique advantages. In this review, the mechanisms and role of macrophages in the development of MI are elaborated in detail, the promising therapeutic methods for regulating macrophage phenotypes, their limitations and possible future research directions are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cognitive impairment, a major determinant of poor functioning in schizophrenia, had limited responses to existing antipsychotic drugs. The limited efficacy could be due to regional differences in the dysregulation of the dopamine system. This study investigated striatal and peripheral dopaminergic makers in schizophrenia and their relationship with cognitive impairment., Methods: Thirty-three patients with schizophrenia and 36 age- and sex-matched healthy controls (HC) participated. We evaluated their cognitive performance, examined the availability of striatal dopamine transporter (DAT) using single-photon emission computed tomography with 99mTc-TRODAT, and measured plasma levels of dopaminergic precursors (phenylalanine and tyrosine) and three branched-chain amino acids (BCAA) that compete with precursors for brain uptake via ultra-performance liquid chromatography., Results: Schizophrenia patients exhibited lower cognitive performance, decreased striatal DAT availability, and reduced levels of phenylalanine, tyrosine, leucine, and isoleucine, and the ratio of phenylalanine plus tyrosine to BCAA. Within the patient group, lower DAT availability in the left caudate nucleus (CN) or putamen was positively associated with attention deficits. Meanwhile, lower tyrosine levels and the ratio of phenylalanine plus tyrosine to BCAA were positively related to executive dysfunction. Among all participants, DAT availability in the right CN or putamen was positively related to memory function, and plasma phenylalanine level was positively associated with executive function., Conclusions: This study supports the role of dopamine system abnormalities in cognitive impairment in schizophrenia. The distinct associations between different dopaminergic alterations and specific cognitive domain impairments suggest the potential need for multifaceted treatment approaches to target these impairments.

The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs., Competing Interests: Declarations Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical Approval Not applicable. Consent to Participate None. Consent for Publication All the authors have read and approved the final version of the manuscript and gave their consent for publication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research., Competing Interests: Declaration of competing interest All authors of this manuscript have directly participated inplanning, execution, and/or analysis of this study. The contents of this manuscript have not been copyrighted or published previously. The contents of this manuscript are not now under consideration for publication elsewhere. The contents of this manuscript will not be copyrighted, submitted, or published elsewhere. There are no directly related manuscripts or abstracts, published or unpublished, by any authors of this manuscript. No financial support or incentive has been provided for this manuscript. I am one author signing on behalf of all co-authors of this manuscript, and attesting to the above., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases., (© 2024. The Author(s).)

Objectives: The quality of care for patients may be partly determined by the time they are admitted to the hospital. This study was conducted to explore the effect of admission time and describe the pattern and magnitude of weekly variation in the quality of patient care., Study Design: A retrospective observational study., Methods: Data were collected from the Medical Care Quality Management and Control System for Specific (Single) Diseases in China. A total of 238,122 patients treated for acute ischemic stroke between January 2015 and December 2017 were included. The primary outcomes were completion of the ten process indicators and in-hospital death., Results: The quality of in-hospital care varied according to hospital arrival time. We identified several patterns of variation across the days of the week. In the first pattern, the quality of four indicators, such as stroke physicians within 15 min, was lowest for arrivals between 08:00 and 11:59, increased throughout the day, and peaked for arrivals between 20:00 and 23:59 or 00:00 and 03:59. In the second pattern, the quality of four indicators, such as the application of antiplatelet therapy within 48 h, was not significantly different between days and weeks. There was no difference in in-hospital mortality between the different admission times., Conclusions: The effect of admission time on the quality of in-hospital care of patients with acute ischemic stroke showed several diurnal patterns. Detecting the times when quality is relatively low may lead to quality improvements in health care. Quality improvement should also focus on reducing diurnal temporal variation., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.

Ferroptosis is a novel type of iron-dependent programmed cell death characterised by intracellular iron overload, increased lipid peroxidation and abnormal accumulation of reactive oxygen species.It has been implicated in the progression of several diseases including cancer, ischaemia-reperfusion injury, neurodegenerative diseases and liver disease. The etiology of endometriosis (EMS) is still unclear and is associated with multiple factors, often accompanied by various forms of cell death and a complex microenvironment. In recent decades, the role of non-traditional forms of cell death, represented by ferroptosis, in endometriosis has come to the attention of researchers. This article reviews the transitional role of iron homeostasis in the development of ferroptosis, the characteristics and regulatory mechanisms of ferroptosis, and focuses on summarising the links between iron death and various pathogenic mechanisms of EMS, including oxidative stress, dysregulation of lipid metabolism, inflammation, autophagy and epithelial-mesenchymal transition. The possible applications of ferroptosis in the treatment of EMS, future research directions and current issues are discussed with the aim of providing new ideas for further understanding of EMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aging causes degenerative changes in organs, leading to a decline in physical function. Over the past two decades, researchers have made significant progress in understanding the rejuvenating effects of young blood on aging organs, benefiting from heterochronic parabiosis models that connect the blood circulation of aged and young rodents. It has been discovered that young blood can partially rejuvenate organs in old animals by regulating important aging-related signaling pathways. Clinical trials have also shown the effectiveness of young blood in treating aging-related diseases. However, the limited availability of young blood poses a challenge to implementing anti-aging therapies on a large scale for older individuals. As a promising alternative, scientists have identified some specific anti-aging circulating factors in young blood that have been shown to promote organ regeneration, reduce inflammation, and alleviate fibrosis associated with aging in animal experiments. While previous reviews have focused primarily on the effects and mechanisms of circulating factors on aging, it is important to acknowledge that studying the rejuvenating effects and mechanisms of young blood has been a significant source of inspiration in this field, and it will continue to be in the future. In recent years, new findings have emerged, further expanding our knowledge in this area. This review aims to summarize the rejuvenating effects and mechanisms of young blood and circulating factors, discussing their similarities and connections, addressing discrepancies in previous studies, outlining future research directions, and highlighting the potential for clinical translation in anti-aging interventions., Competing Interests: All authors disclosed no relevant relationships., (© 2024 The Author(s).)

Background: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments., Aims: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions., Methods: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT., Results: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function., Conclusions: This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Current evidence of volume changes in hippocampal subdivisions in schizophrenia remains inconsistent, and few studies have investigated the relationship between regional hippocampal volumes and symptom remission., Methods: In this cross-sectional study, we recruited 31 patients with schizophrenia and 31 healthy controls (HCs). Symptomatic remission in schizophrenia was determined according to Remission in Schizophrenia Working Group criteria. The volumes of hippocampal longitudinal subregions and transverse subfields were measured using manual and automatic techniques, respectively. Between-group regional hippocampal volume differences were analyzed using multivariate analysis of covariance followed by univariate analysis of covariance., Results: Compared with the HCs, the patients with schizophrenia had smaller bilateral heads and tails along the longitudinal axis; they also had reduced volumes of the bilateral CA1, CA3, CA4, GC-ML-DG, molecular layer, tail, left subiculum, left HATA, and right parasubiculum along the transverse axis in the hippocampus (all corrected p < 0.05). Furthermore, compared with the HCs and patients with remitted schizophrenia, the patients with nonremitted schizophrenia had smaller bilateral hippocampal tail subfields (corrected p < 0.05)., Conclusion: Our results indicated that the pathophysiology and symptomatic remission of schizophrenia are related to changes in the volumes of hippocampal subdivisions. These volume changes might be clinically relevant as biomarkers for schizophrenia identification and treatment., Competing Interests: Conflicts of interest: The authors declare that there are no conflicts of interest related to the subject matter or materials discussed in the article., (Copyright © 2024, the Chinese Medical Association.)

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Liu, Wang, Wu, Wei, Xue, Zou, Zhou, Chen and Li.)

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI., Method: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions., Results: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT., Conclusion: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI., Trial Registration: This trial was registered at http://www., Clinicaltrials: in.th/ (TCTR 20,220,328,009)., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases., Aim of the Study: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms., Materials and Methods: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E 2 (PGE 2 ) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein., Results: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE 2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein., Conclusion: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 Elsevier B.V. All rights reserved.)

(1) Background: The hippocampus (HP) and amygdala are essential structures in obsessive-compulsive behavior (OCB); however, the specific role of the HP in patients with behavioral variant frontotemporal dementia (bvFTD) and OCB remains unclear. (2) Objective: We investigated the alterations of hippocampal and amygdalar volumes in patients with bvFTD and OCB and assessed the correlations of clinical severity with hippocampal subfield and amygdalar nuclei volumes in bvFTD patients with OCB. (3) Materials and methods: Eight bvFTD patients with OCB were recruited and compared with eight age- and sex-matched healthy controls (HCs). Hippocampal subfield and amygdalar nuclei volumes were analyzed automatically using a 3T magnetic resonance image and FreeSurfer v7.1.1. All participants completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI). (4) Results: We observed remarkable reductions in bilateral total hippocampal volumes. Compared with the HCs, reductions in the left hippocampal subfield volume over the cornu ammonis (CA)1 body, CA2/3 body, CA4 body, granule cell layer, and molecular layer of the dentate gyrus (GC-ML-DG) body, molecular layer of the HP body, and hippocampal tail were more obvious in patients with bvFTD and OCB. Right subfield volumes over the CA1 body and molecular layer of the HP body were more significantly reduced in bvFTD patients with OCB than in those in HCs. We observed no significant difference in amygdalar nuclei volume between the groups. Among patients with bvFTD and OCB, Y-BOCS score was negatively correlated with left CA2/3 body volume ( τ b = -0.729, p < 0.001); total NPI score was negatively correlated with left GC-ML-DG body ( τ b = -0.648, p = 0.001) and total bilateral hippocampal volumes (left, τ b = -0.629, p = 0.002; right, τ b = -0.455, p = 0.023); and FBI score was negatively correlated with the left molecular layer of the HP body ( τ b = -0.668, p = 0.001), CA4 body ( τ b = -0.610, p = 0.002), and hippocampal tail volumes ( τ b = -0.552, p < 0.006). Mediation analysis confirmed these subfield volumes as direct biomarkers for clinical severity, independent of medial and lateral orbitofrontal volumes. (5) Conclusions: Alterations in hippocampal subfield volumes appear to be crucial in the pathophysiology of OCB development in patients with bvFTD.

Posttraumatic stress disorder (PTSD) is a neuropsychiatric disease closely related to life-threatening events and psychological stress. Re-experiencing, hyperarousal, avoidance, and numbness are the hallmark symptoms of PTSD, but their underlying neurological processes have not been clearly elucidated. Therefore, the identification and development of drugs for PTSD that targets brain neuronal activities have stalled. Considering that the persistent fear memory induced by traumatic stimulation causes high alertness, high arousal, and cognitive impairment of PTSD symptoms. While the midbrain dopamine system can affect physiological processes such as aversive fear memory learning, consolidation, persistence, and extinction, by altering the functions of the dopaminergic neurons, our viewpoint is that the dopamine system plays a considerable role in the PTSD occurrence and acts as a potential therapeutic target of the disorder. This paper reviews recent findings on the structural and functional connections between ventral tegmental area neurons and the core synaptic circuits involved in PTSD, gene polymorphisms related to the dopamine system that confer susceptibility to clinical PTSD. Moreover, the progress of research on medications that target the dopamine system as PTSD therapies is also discussed. Our goal is to offer some hints for early detection and assist in identifying novel, efficient approaches for treating PTSD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the initial safety and efficacy of femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) for advanced keratoconus. Methods: It was a case series study. Patients with advanced keratoconus who underwent FL-MILK between August 2017 and April 2020 at Shandong Eye Hospital were prospectively included. The femtosecond laser was used to create an intrastromal pocket in the recipient cornea and a lamellar cornea in the donor. The lamellar cornea was then gently inserted into the intrastromal pocket through the incision and flattened. Clinical measurements included best-corrected visual acuity, 3-mm anterior corneal mean keratometry, anterior and posterior central corneal elevation, central corneal thickness, corneal biomechanics, and endothelial cell density. The follow-up was conducted at 1 month, 12 months, and 24 months after the operation. Results: There were 33 patients (35 eyes) in the study. Twenty-six patients were male and 7 patients were female. The mean age was (20.34±5.24) years old. All patients completed 12 months of follow-up, and 25 patients (27 eyes) completed 24 months of follow-up. No epithelial ingrowth, infection, or allogeneic rejection was observed. Compared with the preoperative data, the anterior central corneal elevation significantly decreased ( P <0.001), the mean keratometry significantly decreased ( P <0.05), and the central corneal thickness significantly increased ( P <0.001). The corneal biomechanical strength was significantly improved, with the deformation amplitude ratio at 2.0 mm decreasing from 1.39±0.14 preoperatively to 1.21±0.10 at 24 months postoperatively ( P <0.001) and the stiffness parameter at the first applanation increasing from 41.49±11.47 preoperatively to 88.41±18.17 at 24 months postoperatively ( P <0.001). There were no significant changes in the mean best-corrected visual acuity, posterior corneal elevation, mean spherical equivalent, and endothelial cell density (all P >0.05). Conclusions: FL-MILK may be a feasible option for advanced keratoconus. This procedure may provide a new resolution for keratoconus.

Introduction: Amygdala and serotonergic system abnormalities have been documented in major depressive disorder (MDD). However, most studies have been conducted on recurrent MDD, and only a few have assessed their interaction. This study aimed to concurrently examine both the amygdala and serotonergic systems and their clinical relevance in first-episode, drug-naïve MDD., Methods: This study included 27 patients with first-episode, drug-naïve MDD and 27 age- and gender-matched healthy controls (HCs). The amygdala substructure volumes were performed with Freesurfer from a 1.5 T magnetic resonance image. Serotonin transporter (SERT) availability was detected by single-photon emission computed tomography with 123 I-ADAM. The Benjamini-Hochberg method was applied to adjust for multiple comparisons., Results: No significant difference was found in the amygdala substructure volume and SERT availability between the two groups, respectively. Within MDD patients, the right medial, cortical nucleus, and centromedial volumes were positively associated with caudate SERT availability, respectively. Moreover, the right lateral nucleus volume in the amygdala was positively correlated with depression severity. However, these significances did not survive correction for multiple testing., Conclusions: There were no significant abnormalities in the amygdala substructure volumes and SERT availability in patients with first-episode, drug-naïve MDD. We did not observe an association between amygdala substructure volume and serotonergic dysregulation and their correlations with depression severity in patients with MDD. A larger sample size is warranted to elucidate the actual correlation., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Co-occurring depressive disorder (DD) in patients of methamphetamine use disorder (MAUD) impacts the diagnosis, treatment, and prognosis of the disease. Although FKBP5 has been associated with a variety of psychiatric disorders, whether FKBP5 influences depression susceptibility in MAUD is unknown so far., Methods: Here, we sequenced six FKBP5 single-nucleotide polymorphism (SNP) sites (rs4713916, rs6926133, rs9470080, rs737054, rs4713902, and rs9470079) in 282 methamphetamine users. MAUD and DD were evaluated by clinical questionnaires. SPSS was used to analyze the relationship between FKBP5 SNPs and DD in individuals with MAUD., Results: Of the 282 methamphetamine users, 161 individuals met the MAUD criteria, and among them, 50 patients (31.1%) had DD co-occurring. Importantly, the incidence of DD in individuals with MAUD was 3.314 times greater than that of the methamphetamine users who did not meet the MAUD criteria ( p < 0.001). Although none of the six SNPs of FKBP5 were correlated with the co-occurrence of DD in the population with MAUD, two FKBP5 alleles (rs4713916A and rs6926133A) were substantially associated with the higher DD scores in patients with MAUD ( p < 0.05). Moreover, those with the two risk alleles do not have much higher scores than those with a single risk allele, and the strong linkage disequilibrium of the two SNPs may be the underlying cause of this result. Despite having weak linkage disequilibrium with either rs4713916 or rs6926133, FKBP5 rs9470079 became risky when paired with either., Conclusion: The results of this study revealed that the FKBP5 risk alleles (rs4713916A and rs6926133A) were associated with a greater probability of severe DD in patients with MAUD. These findings here would help with the development of biological early warning markers and the creation of personalized treatment strategies for MAUD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fang, Liu, Tian, Lu, Li, Zhang, Liu, Hao, Wu, Li and Li.)

Background: Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated., Purpose: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM., Methods: Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs)., Results: The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG . For the characteristic Aβ and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1 , RAB14 , ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases., Conclusion: The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ye, Liu, Wang, Cheng, Li, Bai, Yang, Wang, Wen, Xu, Zhang, Xu and Li.)

We studied the effect of fibroblast growth factor receptor 3 (FGFR3) inhibitor BGJ-398 on the differentiation of bone marrow mesenchymal stem cells (BM MSC) into osteoblasts in wild type (wt) mice and in animals with mutation in TBXT gene (mt) and possible differences in the pluripotency of these cells. Cytology tests showed that the cultured BM MSC could differentiate into osteoblasts and adipocytes. The effect of different BGJ-398 concentrations on the expression of FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 were studied by quantitative reverse transcription PCR. The expression of RUNX2 protein was evaluated by Western blotting. BM MSC of mt and wt mice did not differ in pluripotency and expressed the same membrane marker antigens. BGJ-398 inhibitor reduced the expression of FGFR3 and RUNX2. In BM MSC from mt and wt mice have similar gene expression (and its changing) in FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 genes. Thus, our experiments confirmed the effect of decreased expression of FGFR3 on osteogenic differentiation of BM MSC from wt and mt mice. However, BM MSC from mt and wt mice did not differ in pluripotency and are an adequate model for laboratory research., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Treatment refractory depression (TRD) in the elderly is a common psychiatric disorder with high comorbidity and mortality. Older adults with TRD often have complicated comorbidities and several predisposing risk factors, which may lead to neuropsychiatric dysfunction and poor response to treatment. Several hypotheses suggest the underlying mechanisms, including vascular, immunological, senescence, or abnormal protein deposition. Treatment strategies for TRD include optimization of current medication dose, augmentation, switching to an alternative agent or class, and combination of different antidepressant classes, as well as nonpharmacological adjuvant interventions such as biophysical stimulation and psychotherapy. In summary, treatment recommendations for TRD in the elderly favor a multimodal approach, combining pharmacological and nonpharmacological treatments., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The amyloid framework forms the central medical theory related to Alzheimer disease (AD), and the in vivo demonstration of amyloid positivity is essential for diagnosing AD. On the basis of a longitudinal cohort design, the study investigated clinical progressive patterns by obtaining cognitive and structural measurements from a group of patients with amnestic mild cognitive impairment (MCI); the measurements were classified by the positivity (Aβ+) or absence (Aβ-) of the amyloid biomarker. We enrolled 185 patients (64 controls, 121 patients with MCI). The patients with MCI were classified into two groups on the basis of their [ 18 F]flubetaben or [ 18 F]florbetapir amyloid positron-emission tomography scan (Aβ+ vs. Aβ-, 67 vs. 54 patients) results. Data from annual cognitive measurements and three-dimensional T1 magnetic resonance imaging scans were used for between-group comparisons. To obtain longitudinal cognitive test scores, generalized estimating equations were applied. A linear mixed effects model was used to compare the time effect of cortical thickness degeneration. The cognitive decline trajectory of the Aβ+ group was obvious, whereas the Aβ- and control groups did not exhibit a noticeable decline over time. The group effects of cortical thickness indicated decreased entorhinal cortex in the Aβ+ group and supramarginal gyrus in the Aβ- group. The topology of neurodegeneration in the Aβ- group was emphasized in posterior cortical regions. A comparison of the changes in the Aβ+ and Aβ- groups over time revealed a higher rate of cortical thickness decline in the Aβ+ group than in the Aβ- group in the default mode network. The Aβ+ and Aβ- groups experienced different APOE ε4 effects. For cortical-cognitive correlations, the regions associated with cognitive decline in the Aβ+ group were mainly localized in the perisylvian and anterior cingulate regions. By contrast, the degenerative topography of Aβ- MCI was scattered. The memory learning curves, cognitive decline patterns, and cortical degeneration topographies of the two MCI groups were revealed to be different, suggesting a difference in pathophysiology. Longitudinal analysis may help to differentiate between these two MCI groups if biomarker access is unavailable in clinical settings.

Background: Cognitive impairments, the main determinants of functional outcomes in schizophrenia, had limited treatment responses and need a better understanding of the mechanisms. Dysfunctions of the dopamine system and N-methyl-d-aspartate receptor (NMDAR), the primary pathophysiologies of schizophrenia, may impair cognition. This study explored the effects and interactions of striatal dopamine transporter (DAT) and plasma NMDAR-related amino acids on cognitive impairments in schizophrenia., Methods: We recruited 36 schizophrenia patients and 36 age- and sex-matched healthy controls (HC). All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT and ultra-performance liquid chromatography were applied to determine DAT availability and plasma concentrations of eight amino acids, respectively., Results: Compared with HC, schizophrenia patients had lower cognitive performance, higher methionine concentrations, decreased concentrations of glutamic acid, cysteine, aspartic acid, arginine, the ratio of glutamic acid to gamma-aminobutyric acid (Glu/GABA), and DAT availability in the left caudate nucleus (CN) and putamen. Regarding memory scores, Glu/GABA and the DAT availability in left CN and putamen exhibited positive relationships, while methionine concentrations showed negative associations in all participants. The DAT availability in left CN mediated the methionine-memory relationship. An exploratory backward stepwise regression analysis for the four biological markers associated with memory indicated that DAT availability in left CN and Glu/GABA remained in the final model., Conclusions: This study demonstrated the interactions of striatal DAT and NMDAR-related amino acids on cognitive impairments in schizophrenia. Future studies to comprehensively evaluate their complex interactions and treatment implications are warranted., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objective: The purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs., Methods: Three datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer., Results: The present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05)., Conclusion: The ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Serum chloride (Cl - ), which is an important analyte that reflects the electrolyte and acid-base balance in humans, is affected by several specific agents or substances. It has been reported that the abuse of bromine-containing drugs, such as bromvalerylurea may lead to pseudohyperchloremia, which is very rare yet, caused by the treatment dose of bromine-containing drugs. In this case report, we describe an epilepsy patient whose serum Cl - was falsely elevated due to the long-term use of phenobarbital and sodium bromide compound tablets. We also discuss the anti-interference capacity of different analyzers and the disturbance of bromide-containing drugs in Cl - determination., Case Description: A 34-year-old woman diagnosed with epilepsy for 11 years was admitted to our hospital for further treatment. She had increasingly frequent loss of consciousness and seizures. Her medication history included carbamazepine, levetiracetam, phenobarbital and sodium bromide compound tablets. The video electroencephalogram (VEEG) was moderately abnormal. No obvious abnormality was found in blood routine test, liver and kidney function, except an aberrantly elevated serum Cl - level of 130 mmol/L; however, the patient did not present with the relevant signs and symptoms of hyperchloremia, such as thirst, fatigue, nausea and vomiting. Subsequently, we used three different analyzers to determine her Cl - level and obtained the following results: an arterial blood Cl - level of 107 mmol/L; a serum Cl - level of 112 mmol/L; and no result. Reviewing her medical history, we discovered that the patient had been taking phenobarbital and sodium bromide compound tablets for 6 months to treat her seizures. Her serum bromide was 4.89 mmol/L, which may cause pseudohyperchloremia. After changing her treatment to phenobarbital tablets, her serum Cl - returned to the normal range (106 mmol/L)., Conclusions: Bromide-containing drugs can cause a falsely elevated Cl - level. When pseudohyperchloremia is suspected, different methods or instruments should be used to measure Cl - levels., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3419/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: Cortisol is associated with cognition in both healthy individuals and patients with neuropsychiatric disorders. Regarding the effects of cortisol on the dopamine system and the association between dopamine transporter (DAT) and cognition, DAT might be a central target linking cortisol and cognition. This study explored the role of striatal DAT in the cortisol-cognition relationship., Methods: We recruited 33 patients with carbon monoxide poisoning and 33 age- and sex-matched healthy controls. All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT was used to determine striatal DAT availability. Plasma cortisol, tumor necrosis factor α, and interleukin-10 levels were measured using enzyme-linked immunosorbent assays., Results: Compared with healthy controls, patients with carbon monoxide poisoning had lower cognitive performance, bilateral striatal DAT availability, and plasma tumor necrosis factor-α levels and higher cortisol and interleukin-10 levels. In all participants, plasma cortisol level and bilateral striatal DAT availability were negatively and positively related to cognition, respectively, including memory and executive function with β from -0.361 (95% confidence interval [CI] = -0.633 to -0.090) to 0.588 (95% CI = 0.319 to 0.858). Moreover, bilateral striatal DAT mediated the cortisol-cognition relationship with indirect effects from -0.067 (95% CI = -0.179 to -0.001) to -0.135 (95% CI = -0.295 to -0.024). The cytokine levels did not influence the mediation effects., Conclusions: This is the first study to demonstrate that striatal DAT mediates the cortisol-cognition relationship. Future studies are needed to comprehensively evaluate the role of the dopamine system in cortisol-cognition associations and treatment implications., (Copyright © 2022 by the American Psychosomatic Society.)

To develop an efficient solid acid catalysts for the Friedel-Crafts alkylation reaction, especially for involving bulky molecules, the direct synthesis of hierarchical nanocrystalline β zeolites were achieved by using amphiphilic organosilane ([(CH 3 O) 3 SiC 3 H 6 N(CH 3 ) 2 C 18 H 37 ]Cl, TPOAC) as collaborative structure-directing agent (SDA). The growth evolution of β crystals and the influence of TPOAC/SiO 2 molar ratio on the mesoporous structure, crystal size, and acidic properties of β zeolites were investigated and discussed in detail. The characterization results reveal that intracrystalline mesopores and intercrystalline mesopores/macropores via the stacking of β nanocrystals were generated over the hierarchical β zeolites. Moreover, most of the strong acid sites were well remained compared with the conventional microporous β zeolite. Consequently, the hierarchical nanocrystalline β zeolite synthesized under the optimized synthesis conditions shows improved specific catalytic activity of acid sites (turnover number, TON) in alkylation of benzene with benzyl alcohol, which can be attributed to the integrated balance of considerable mesoporosity, accessibility of the acid sites, and well-remained strong acid sites in the hierarchical β zeolite., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the molecular pathogenesis and clinical features of unrelated 12 patients with inherited coagulation protein C (PC) deficiency in Chinese population. Methods: The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and enzyme linked immunosorbent assay, respectively. The nine exons and flanking sequences of the protein C (PROC) gene were amplified by polymerase chain reaction with direct sequencing, and the suspected mutations were validated by reverse sequencing (clone sequencing for deletion mutations) . Results: The PC:A of the 12 probands decreased significantly, ranging from 18% to 55%, and the PC:Ag of the 10 probands decreased significantly. Eleven mutations were found, out of which four mutations [c.383G>A (p.Gly128Asp) , c.997G>A (p.Ala291Thr) , c.1318C>T (p.Arg398Cys) , and c.532G>C (p.Leu278Pro) ] were discovered for the first time. Six mutations were in the serine protease domain, four mutations were located in epidermal growth factor (EGF) -like domains, and one mutation was located in activation peptide. There were two deletion mutations (p.Met364Trp fsX15 and p.Lys192del) , and the rest were missense mutations. Mutations p.Phe181Val and p.Arg189Trp were identified in three unrelated families. All mutations may be inherited, and consanguineous marriages were reported in two families. Among the probands, nine cases had venous thrombosis, two cases had poor pregnancy manifestations, and one case had purpura. Conclusion: Patients with PC deficiency caused by PROC gene defects are prone to venous thrombosis, especially when there are other thrombotic factors present at the same time.

Objectives: To present the history and potential for development of evidence-based (EB) social work in China., Study Design and Setting: The conception and methodology of EB social work is a potential strategy to support high quality development of social work in China. This article documents and analyzes the progress of EB social work in China. We focus on current research, reasons, challenges, and strategies., Results: EB social work started late in China. The number of EB social work literature and systematic reviews has increased since 2004. The development of EB social work has been uneven nationally with few practitioners and decision makers involved. However, more and more social work researchers received training in evidence-based practice through national workshops and conferences., Conclusion: EB social work faced various challenges, but there are now more opportunities for EB social work development in China. Researchers, practitioners, managers and decision makers are encouraged to work together to establish a thorough methodological system and use existing evidence as much as possible when carrying out social work programs and services., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Engaging in a secondary task while walking increases motor-cognitive interference and exacerbates fall risk in older adults with mild cognitive impairment (MCI). Previous studies have demonstrated that Tai Chi (TC) may improve cognitive function and dual-task gait performance. Intriguingly, with emerging studies also indicating the potential of transcranial direct current stimulation (tDCS) in enhancing such motor-cognitive performance, whether combining tDCS with TC might be superior to TC alone is still unclear. The purpose of this study was to investigate the effects of combining tDCS with TC on dual-task gait in patients with MCI. Materials and Methods: Twenty patients with MCI were randomly assigned to receive either anodal or sham tDCS, both combined with TC, for 36 sessions over 12 weeks. Subjects received 40 min of TC training in each session. During the first 20 min, they simultaneously received either anodal or sham tDCS over the left dorsolateral prefrontal cortex. Outcome measures included dual-task gait performance and other cognitive functions. Results: There were significant interaction effects between groups on the cognitive dual task walking. Compared to sham, the anodal tDCS group demonstrated a greater improvement on cadence and dual task cost of speed. Conclusion: Combining tDCS with TC may offer additional benefits over TC alone in enhancing dual-task gait performance in patients with MCI. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [TCTR20201201007]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liao, Liu, Wang, Walsh and Lau.)

Endocrine and paracrine signals can be key regulators of ovarian physiology. The oocyte secretes growth factors which directly induce follicular development by a complex paracrine signalling process, and the transforming growth factorβ (TGF-β) superfamily has a pivotal role in this process. The bone morphogenetic protein 15 ( BMP15 ) and growth differentiation factor 9 ( GDF9 ) genes are relevant members of the TGF-β superfamily that encode proteins secreted by the oocytes into the ovarian follicles, where they contribute to creating an environment supporting follicle selection and growth. Their main functions include regulating cellular proliferation/differentiation, follicular survival/atresia, and oocyte maturation. Recent functional studies have validated genetic factors (Progesterone receptor membrane component 1 ( PGRMC1 )), Fragile X mental retardation 1 ( FMR1 , GDF9 and BMP15 ) as being causative of primary ovarian insufficiency (POI), BMP15/GDF9 gene variants were found to have a high incidence on the POI phenotype. This review considers the most recent research regarding the role of BMP15 and GDF9 in the genetic control of follicular development, paying special attention to the pathogenesis of POI.

Background: The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin., Methods: Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ 2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT)., Results: From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P = .438), and significantly longer than the rate of group R1/0 (P = .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P = .023) and R1/0 (P = .001). Cox multivariate analysis identified the radiologic feature (P = .012) and PORT (P = .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P = .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P = .002) but not distant metastases (P > .999)., Conclusions: PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Hippocampal volume reduction was reported to underlie depressive symptomatology, however, the evidence to date remains inconsistent. For the complex intrinsic organization of hippocampus, the hippocampal volumes can be further divided into subfields or axial parts. The current study aimed to explore the alterations of hippocampal sub-regional volumes in first episode drug-naïve major depressive disorder (MDD) by two segmentation methods. Thirty-five first-episode drug-naïve MDD and 35 age- and gender-matched healthy controls (HC) were recruited. Volumes of three sub-regions of hippocampus along the longitudinal axis (head, body and tail) were analyzed manually and eight transverse subfields were automatically determined using FreeSurfer. An asymmetric index (AI) of volumes was defined as (∣Left - Right∣/∣Left + Right∣) * 100. There were significant reductions in the volumes of bilateral hippocampal head in MDD compared to HC. The volumes of eight subfields were not different between groups. MDD patients had higher AI values in the subfield of cornu ammonis 4/dentate gyrus than HC. The change in hippocampal sub-regional volumes might be an imaging biomarker in the first-episode, drug-naïve patients with MDD. Current findings may contribute to developing new diagnostic and therapeutic strategies for major depression., (Copyright © 2021. Published by Elsevier B.V.)

Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naïve MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naïve MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD., (Copyright © 2021. Published by Elsevier B.V.)

Macrophages are heterogeneous cells that have different physiological functions, such as chemotaxis, phagocytosis, endocytosis, and secretion of various factors. All physiological functions of macrophages are integral to homeostasis, immune defense and tissue repair. However, in several diseases, macrophages are recruited from the blood towards inflammatory sites. This process is called macrophage migration, which promotes deleterious disease progression. Macrophage migration is a key player in many inflammatory diseases, autoimmune diseases and cancers because it contributes to the accumulation of proinflammatory factors, the destruction of tissues and the development of tumors. Therefore, macrophage migration is proposed to be a potential therapeutic target. Macrophages migrate between two-dimensional (2D) and three-dimensional (3D) environments, implying that distinct migratory features and mechanisms are involved. Compared with the 2D migration of macrophages, 3D migration involves more complex variations in cellular morphology and dynamics. The structure of the extracellular matrix, a key factor, is modified in diseases that influence macrophage 3D migration. Macrophage 3D migration relates to disease pathology. Research that focuses on macrophage 3D migration is an emerging field and was reviewed in this article to indicate the molecular and cellular mechanisms of macrophage migration in 3D environments and to provide potential targets for controlling disease progression associated with this migration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Y-chromosome haplotypes of 527 non-related males (176 Han, 186 Tibetan, and 165 Yi) in the Tibetan-Yi corridor were analyzed using SureID® PathFinder Plus. In the populations of Han, Tibetans, and Yi, the haplotype diversity was 0.9989, 0.9981, and 0.9993, respectively, and the discrimination capacity was 0.9148, 0.8925, and 0.9576, respectively. Phylogenetic relationships among 12 studied ethnic groups and 7 other ethnic groups in the Tibetan-Yi corridor were investigated. Both multi-dimensional scaling analysis and phylogenetic reconstructions indicated that Tibetans appeared separated from the Han and Yi ethnic groups in the Tibetan-Yi corridor. Their genetic homogeneity or heterogeneity has not entirely been affected by their geographical distance and linguistic origin.

Ginseng has been widely applied in clinical practice, but the cultivation age cannot be ignored as it influences the quality of ginseng and its products. In this work, different cultivation ages of fresh ginseng (FG) from four to seven years were analysed by UPLC-Q-TOF-MS/MS. Principal component analysis and supervised orthogonal partial least squared discrimination analysis, which belong to the normal method of multivariate statistical analysis, were applied to discover the characteristic components of FG at different cultivation ages. The components of new type of red ginseng (NRG) derived from FG at different cultivation ages were compared by HPLC analysis. The pharmacological anti-inflammatory activity was evaluated by ELISA and qPCR. The result showed that the characteristic components of both 6- and 7-year-old ginseng were ginsenoside Rb1, mal-ginsenoside Rb1, ginsenoside Rc, mal-ginsenoside Rc, mal-ginsenoside Rb1 isomer, and mal-ginsenoside Rb2. Moreover, the characteristic components of both 4- and 5-year-old ginseng were ADP-glucose and 3-hydroxyhexanoyl CoA. In addition, 6-year-old NRG has higher rare ginsenosides than 4-year-old NRG, which possesses great anti-inflammatory activity in vitro. The results reveal the ginsenoside transformation law of NRG processing and suggest that the cultivation age of FG influences the content of ginsenosides in NRG. Therefore, 6-year-old ginseng is more suitable for red ginseng processing and clinical use., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cardiovascular disease (CVD), including heart failure, myocardial fibrosis and myocardial infarction, etc, remains one of the leading causes of mortality worldwide. Evidence shows that miRNA plays an important role in the pathogenesis of CVD. miR-29 family is one of miRNA, and over the past decades, many studies have demonstrated that miR-29 is involved in maintaining the integrity of arteries and in the regulation of atherosclerosis, especially in the process of myocardial fibrosis. Besides, heart failure, myocardial fibrosis and myocardial infarction are inseparable from the regulatory role of miR-29. Here, we comprehensively review recent studies regarding miR-29 and CVD, illustrate the possibility of miR-29 as a potential marker for prevention, treatment and prognostic observation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abnormalities of neuroinflammatory process and serotonergic system have been reported in major depressive disorder (MDD). However, most previous studies were performed in recurrent MDD and only a few studies explored the interaction of the two systems. This study examined both systems concurrently and their clinical relevance in first-episode drug-naive MDD. Thirty-four MDD patients and 34 age and gender matched healthy controls (HC) were recruited. Plasma concentrations of the cytokines of interleukin-1 (IL-1) family, including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2) were measured using enzyme-linked immune-sorbent assays. The serotonin transporter (SERT) availability in midbrain, thalamus, caudate, and putamen was examined by single-photon emission computed tomography with 123 I-ADAM. There were significantly lower concentrations of pro-inflammatory IL-1β and its inhibitor, IL-1R2 in MDD than HC. The SERT availability was at the same level between groups. A negative association between IL-1Ra concentration and the SERT availability in midbrain was observed in MDD but not in HC. Both IL-1β concentration and the SERT availability in caudate negatively correlated with depression severity and the effect of IL-1β was not moderated or mediated by the SERT. In conclusion, this study demonstrated the involvement of IL-1 family in the early stage of MDD, especially for IL-1β. SERT was not the main central target of altered IL-1β and these two systems might contribute to MDD by different mechanisms. The pathophysiology might be varied between early and recurrent MDD and tuning treatment strategies at different clinical stages might be needed., (Copyright © 2021. Published by Elsevier Ltd.)