The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells.

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.

[Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm]. / 脑功能连接及非线性动力学分析在发作控制的婴儿痉挛症患儿脑功能评估中的应用.

OBJECTIVES: To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS). METHODS: A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity. RESULTS: Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05). CONCLUSIONS: Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

A Bibliometric and Visualized Analysis of Uremic Cardiomyopathy From 1990 to 2021.

Background: Uremic cardiomyopathy is commonly presented in chronic kidney disease (CKD), and it severely affects the prognosis of patients with CKD. In the past few decades, the investigation of uremic cardiomyopathy has developed rapidly. However, no report has summarized the situation of uremic cardiomyopathy research to date. This study aimed to evaluate the state of uremic cardiomyopathy research in the last 30 years and identify important topics and achievements, as well as emerging trends through bibliometric analysis. Materials and Methods: Publications related to uremic cardiomyopathy were collected from Science Citation Index Expanded. HistCite, VOSviewer, CiteSpace, and the Bibliometrix Package were used for bibliometric analysis and visualization, including the analysis of the overall distribution of the annual publication, leading countries, and active institutions and authors, core journals, co-cited references, and keywords. Results: A total of 2,403 studies related to uremic cardiomyopathy were obtained, and progress related to uremic cardiomyopathy was slower in past 3 years. A total of 10,077 authors from 2,697 institutions in 89 countries or regions reported investigations on uremic cardiomyopathy. The United States of America was the most productive and the most cited country. Myles Wolf, Joseph I Shapiro, and Carmine Zoccali published most articles in uremic cardiomyopathy, and journals in nephrology possessed core status in the field. Phosphate metabolism was the hotspot in uremic cardiomyopathy research in recent years, and future progress may concentrate on phosphate metabolism, endogenous natriuretic factors, and novel biomarkers. Conclusion: The United States of America and European countries played central roles in uremic cardiomyopathy research, while Chinese scholars should be more involved in this field. Global publications on uremic cardiomyopathy have entered platform stage, and the fibroblast growth factor-23-klotho axis remained a hotspot in this field. Endogenous natriuretic factors and novel biomarkers may be potential directions in future investigations.

Irisin, a fascinating field in our times.

Irisin is a muscle-secreted hormone that is generated by cleavage of membrane protein FNDC-5 (fibronectin type III domain-containing protein 5). Irisin is considered to be a mediator of exercise-induced metabolic improvements, such as browning of white adipose tissue, and is known to alleviate several chronic non-metabolic diseases. Thus, irisin may be an ideal therapeutic target for metabolic and non-metabolic diseases. However, several controversies regarding irisin have hindered its clinical translation. We review the generation, regulation (especially in exercise), and metabolic as well as therapeutic effects of irisin on metabolic and non-metabolic diseases. Furthermore, we discuss controversies regarding irisin and highlight potential future research directions.

Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease.

Regular exercise has been shown to reduce the risk of Alzheimer's disease (AD). Our previous study showed that the protein aquaporin 4 (AQP4), which is specifically expressed on the paravascular processes of astrocytes, is necessary for glymphatic clearance of extracellular amyloid beta (Aß) from the brain, which can delay the progression of Alzheimer's disease. However, it is not known whether AQP4-regulated glymphatic clearance of extracellular Aß is involved in beneficial effects of exercise in AD patients. Our results showed that after 2 months of voluntary wheel exercise, APP/PS1 mice that were 3 months old at the start of the intervention exhibited a decrease in Aß burden, glial activation, perivascular AQP4 mislocalization, impaired glymphatic transport, synapse protein loss, and learning and memory defects compared with mice not subjected to the exercise intervention. In contrast, APP/PS1 mice that were 7 months old at the start of the intervention exhibited impaired AQP4 polarity and reduced glymphatic clearance of extracellular Aß, and the above-mentioned impairments were not alleviated after the 2-month exercise intervention. Compared with age-matched APP/PS1 mice, AQP4 knockout APP/PS1 mice had more serious defects in glymphatic function, Aß plaque deposition, and cognitive impairment, which could not be alleviated after the exercise intervention. These findings suggest that AQP4-dependent glymphatic transport is the neurobiological basis for the beneficial effects of voluntary exercises that protect against the onset of AD.

Diagnosis and treatment of Rosai-Dorfman disease of the spine: a systematic literature review.

PURPOSE: To review and summarize the clinical features, diagnosis, treatment strategies, and prognosis of spinal Rosai-Dorfman disease (RDD). METHODS: RDD is also termed as sinus histiocytosis with massive lymphadenopathy. We searched the databases of PubMed, Elsevier ScienceDirect, SpringerLink, and OVID. The keywords were Rosai-Dorfman disease and spine/central nervous system. Research articles and case reports with accessibility to full texts regarding spinal RDD were eligible for the inclusion. A total of 62 articles were included, and they contained 69 cases. We extracted the information of interest and analyzed them using SPSS statistics package. RESULTS: The average age was 33.1 ± 18.3 years. The ratio of males to females was 1.9/1. Overall, 63 cases presented with spine-related symptoms. A total of 27 cases (39.1%) had multi-organ lesions, and 12 cases had records of massive lymphadenopathy. Among 47 cases who first manifested spine-related symptoms, 93.6% were preoperatively misdiagnosed. The disease had a predilection for cervical spine (38.8%) and thoracic spine (40.3%). 62.9% of lesions were dura-based. Surgery remained the mainstream treatment option (78.8%), with or without adjuvant therapies. Total lesion resection was achieved in 34.8% of cases. The rate of lesion recurrence/progression was 19.5%, which was marginally lower for total resection than for non-total resection. CONCLUSION: Spinal RDD has no pathognomonic clinical and imaging features. Most cases first present with spine-relevant symptoms. Massive lymphadenopathy is not common, but a tendency for multi-organ involvement should be considered. Spinal RDD has a high recurrence rate; thus, total resection is the treatment of choice. Adjuvant therapies are indicated for multi-organ lesions and residual lesions. A wait and watch strategy is recommended for asymptomatic patients. Herein, a workflow of diagnosis and treatment of the spinal RDD is established.

Roles for fibroblast growth factor-23 and α-Klotho in acute kidney injury.

Acute kidney injury is a global disease with high morbidity and mortality. Recent studies have revealed that the fibroblast growth factor-23-α-Klotho axis is closely related to chronic kidney disease, and has multiple biological functions beyond bone-mineral metabolism. However, although dysregulation of fibroblast growth factor-23-α-Klotho has been observed in acute kidney injury, the role of fibroblast growth factor-23-α-Klotho in the pathophysiology of acute kidney injury remains largely unknown. In this review, we describe recent findings regarding fibroblast growth factor-23-α-Klotho, which is mainly involved in inflammation, oxidative stress, and hemodynamic disorders. Further, based on these recent results, we put forth novel insights regarding the relationship between the fibroblast growth factor-23-α-Klotho axis and acute kidney injury, which may provide new therapeutic targets for treating acute kidney injury.

A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac Hypertrophy.

Cardiac hypertrophy is a common feature in patients with CKD. Recent studies revealed that two phosphate regulators, fibroblast growth factor-23 and α-Klotho, are highly involved in the pathophysiologic process of CKD-induced cardiac hypertrophy. With decreasing renal function, elevated fibroblast growth factor-23 and decreased α-Klotho may contribute to cardiac hypertrophy by targeting the heart directly or by inducing systemic changes, such as vascular injury, hemodynamic disorders, and inflammation. However, several studies have demonstrated that disturbances in the fibroblast growth factor-23/α-Klotho axis do not lead to cardiac hypertrophy. In this review, we describe the cardiac effects of the fibroblast growth factor-23/α-Klotho axis and summarize recent progress in this field. In addition, we present not only the main controversies in this field but also provide possible directions to resolve these disputes.

How does the sagittal spinal balance of the scoliotic population deviate from the asymptomatic population?

BACKGROUND: Previously, the sagittal spinal balance in both asymptomatic and scoliotic Caucasian people has been characterized and compared. Very recently, the sagittal spino-pelvic parameters among asymptomatic Chinese adults have been studied, and the results were compared with Caucasian adults, indicating that a difference did exist. Unfortunately, the distribution of sagittal standing posture patterns among the Chinese population has not been characterized in either asymptomatic or scoliotic groups. METHODS: We conducted a radiographic comparison study to define the deviation of sagittal balance in scoliotic patients from that of an asymptomatic population. A total of 126 asymptomatic and 117 idiopathic scoliotic (IS) young adults were recruited. Radiographic data from each subject were reviewed, and sagittal spinopelvic parameters were measured. The Roussouly type was then determined, as well as the relative position of the C7 plumbline with respect to the sacrum and hip axis. Comparison analyses were undertaken between the two different groups. RESULTS: The IS group had a larger pelvic incidence, pelvic tilt and sacral slope, but a smaller spinal tilt than the asymptomatic group (P < 0.05), while other sagittal parameters were similar. The distribution of Roussouly types was similar between the asymptomatic and IS groups, of which 49.2% and 45.3% belonged to Roussouly Type 3, respectively. Asymptomatic males and females had a similar distribution, which was different between the two genders in the IS group (P < 0.05), with more females possessing a neutral sagittal standing posture. In addition, more IS subjects had forward displacement of the C7 plumbline than asymptomatic ones (P < 0.05), while there was no difference between the two genders in either group. CONCLUSIONS: Although sagittal pelvic parameters were greater in the IS population, their sagittal spinal balance was maintained and there was no sagittal standing posture pattern correlated with IS. The occurrence of anterior displacement of the C7 plumbline was more common in IS patients than asymptomatic adults, but did not appear to be correlated with gender in both populations.

Enriched physical environment reverses spatial cognitive impairment of socially isolated APPswe/PS1dE9 transgenic mice before amyloidosis onset.

AIMS: Social isolation increases the onset of Alzheimer's disease (AD). Environmental enrichment, a complicated social and physical construct, plays beneficial effects on brain plasticity and function. This study was designed to determine whether physical enrichment can reduce the deleterious consequences of social isolation on the onset of AD. METHODS: One-month-old APPswe/PS1dE9 transgenic AD model mice were singly housed in the enriched physical environment for 8 weeks and then received behavioral tests, neuropathological analyses, and Western blot of the hippocampus. RESULTS: The enriched physical environment reversed spatial cognitive decline of socially isolated APPswe/PS1dE9 mice. The functional reversal was associated with decreases in cellular apoptosis, synaptic protein loss, inflammation, and glial activation in the hippocampus, without changes in amyloid ß neuropathology. CONCLUSION: These results suggest that the enriched physical environment may serve as a nonpharmacological intervention for delaying the onset of AD accompanied with social isolation.

Surgeries for Patients with Tandem Spinal Stenosis in Cervical and Thoracic Spine: Combined or Staged Surgeries?

BACKGROUND: Cervical and thoracic tandem spinal stenosis (ct-TSS) is a rare yet challenging degenerative disease. When the diagnosis is made, surgical decompression is indicated for both lesions. However, literature about the surgical approaches and prognosis of this disease is lacking. METHODS: From March 2005 to April 2013, 30 patients with ct-TSS and a mean age of 49.8 years were recruited. We outlined 2 types of ct-TSS lesions-adjacent and skip lesions. The surgical approach for ct-TSS with adjacent lesions was combined cervical and thoracic decompression via a single posterior incision; the approach for skip lesions was 2-stage sequential cervical and thoracic decompressions. Neurologic status was evaluated with the Japanese Orthopaedic Association scale for cervical myelopathy. RESULTS: Seventeen patients underwent 1-stage surgery, and 13 patients underwent the 2-stage procedure. After surgery, 27 patients (90%) experienced improvement. Main complications included transient neurologic deterioration in 7 patients, dural tears in 14 patients, and new radiculopathy in 4 patients. Combined and staged groups were comparable in terms of total length of decompression, occurrence of perioperative complications, and recovery rate (P > 0.05). The average Japanese Orthopaedic Association score increased significantly from 9.8 ± 1.9 to 13.7 ± 3.0 (P < 0.05), and the average recovery rate was 54.4%. CONCLUSIONS: The types of stenotic lesions should be considered when planning surgery for patients with ct-TSS. One-stage decompression is suitable for patients with adjacent stenotic lesions; staged procedures should be considered for other patients.

Decision-making Impairments in Primary Angle-closure Glaucoma Patients.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a common eye disease and a common cause of blindness. Inappropriate medical decisions severely affect the prognosis. This study investigated decision-making under risk in PACG patients. METHODS: Thirty patients with first acute attack of PACG before surgery and thirty healthy controls were included in the study. Decision-making under risk was evaluated with the game of dice task (GDT). The results of Eysenck Personality Questionnaire (EPQ) and GDT between PACG patients and healthy controls were compared. RESULTS: Risky decisions in PACG patients were more than those in healthy controls as measured by mean score of GDT (12.47 ± 5.72 vs. 4.33 ± 3.30, P< 0.001). Higher neuroticism score in EPQ was found in PACG patients compared to healthy controls (14.97 ± 3.93 vs. 9.90 ± 4.49, P< 0.001). Neuroticism scores in EPQ were associated with decision-making performance (r = 0.417, P = 0.001). CONCLUSIONS: Neuroticism positively correlated with risky decisions. Decision-making might be influenced by neuroticism. Future studies will show whether therapy compliance will be improved by emotional management and psychological intervention in PACG patients.

Clinical variations in Parkinson's disease patients with or without REM sleep behaviour disorder: a meta-analysis.

This study aimed to evaluate the clinical variations in patients with Parkinson's disease (PD) with (PDRBD) or without REM sleep behaviour disorder (RBD) (Non-RBD), and PDRBD patients were classified into Confirmed-RBD (definite diagnosis with polysomnography, PSG) and Probable-RBD (without PSG re-confirmation). The clinical difference between the groups of patients was measured as an odds ratio (OR) or standardized mean difference (SMD, Cohen d). A total of 31 articles with data from 5,785 participants were obtained for our analysis. Overall, the occurrence of Confirmed-RBD was more frequent in male patients (OR = 1.25; p = 0.038), elderly patients (SMD = 0.25; p = 0.000), and patients with longer disease duration (SMD = 0.30; p = 0.000), increased Hoehn-Yahr scale (SMD = 0.30; p = 0.000), and higher UPDRS-III score (SMD = 0.38; p = 0.002). On the other hand, the frequency of Probable-RBD was increased with disease duration (SMD = 0.29; p = 0.000), Hoehn-Yahr scale (SMD = 0.30; p = 0.000), and UPDRS-III score (SMD = 0.26; p = 0.001). Our study indicate that PDRBD patients may have different clinical features compared to patients with Non-RBD.

Cerebrospinal Fluid Leakage after Thoracic Decompression.

OBJECTIVE: The objective of this study is to review cerebrospinal fluid leakage (CSFL) after thoracic decompression and describe its regular and special features. DATA SOURCES: Literature cited in this review was retrieved from PubMed and Medline and was primarily published during the last 10 years. "Cerebrospinal fluid", "leakage", "dural tears", and "thoracic decompression" were the indexed terms. Relevant citations in the retrieved articles were also screened to include more data. STUDY SELECTION: All retrieved literature was scrutinized, and four categories were recorded: incidence and risk factors, complications, treatment modalities, and prognosis. RESULTS: CSFL is much more frequent after thoracic decompression than after cervical and lumbar spinal surgeries. Its occurrence is related to many clinical factors, especially the presence of ossified ligaments and the adhesion of the dural sac. While its impact on the late neurological recovery is currently controversial, CSFL increases the risk of other perioperative complications, such as low intracranial pressure symptoms, infection, and vascular events. The combined use of primary repairs during the operation and conservative treatment postoperatively is generally effective for most CSFL cases, whereas lumbar drains and reoperations should be implemented as rescue options for refractory cases only. CONCLUSIONS: CSFL after thoracic decompression has not been specifically investigated, so the present study provides a systematic and comprehensive review of the issue. CSFL is a multi-factor-related complication, and pathological factors play a decisive role. The importance of CSFL is in its impact on the increased risk of other complications during the postoperative period. Methods to prevent these complications are in need. In addition, though the required treatment resources are not special for CSFL after thoracic decompression, most CSFL cases are conservatively curable, and surgeons should be aware of it.

Gender differences associated with orienting attentional networks in healthy subjects.

BACKGROUND: Selective attention is considered one of the main components of cognitive functioning. A number of studies have demonstrated gender differences in cognition. This study aimed to investigate the gender differences in selective attention in healthy subjects. METHODS: The present experiment examined the gender differences associated with the efficiency of three attentional networks: alerting, orienting, and executive control attention in 73 healthy subjects (38 males). All participants performed a modified version of the Attention Network Test (ANT). RESULTS: Females had higher orienting scores than males (t = 2.172, P < 0.05). Specifically, females were faster at covert orienting of attention to a spatially cued location. There were no gender differences between males and females in alerting (t = 0.813, P > 0.05) and executive control (t = 0.945, P > 0.05) attention networks. CONCLUSIONS: There was a significant gender difference between males and females associated with the orienting network. Enhanced orienting attention in females may function to motivate females to direct their attention to a spatially cued location.

Effects of painful stimulation and acupuncture on attention networks in healthy subjects.

Pain is a subjective sensory and emotional experience, and it has been reported that many different brain regions are regulated by pain, and that pain can impact attention. Acupuncture is an important treatment component of Chinese traditional medicine, and has been used for thousands of years to treat a wide variety of conditions. Although several studies have shown that acupuncture improves consciousness, the precise impact of both acupuncture and painful stimulation on attention is unclear. Are all of the attention networks modulated, or do these stimuli act on a specific network? Is the effect of painful stimulation similar to that of acupuncture? We administered the attention network test to 30 participants (15 males) to investigate the relative efficiencies of three independent attention networks (alerting, orienting, and executive control networks) under three conditions: baseline, after painful stimulation, and after acupuncture. The degree of pain experienced was assessed on a horizontally oriented visual analogue scale. The results showed that painful stimulation and acupuncture had similar effects on the orienting and executive control networks; however, there was a significantly different effect between the three conditions on the alerting network. In conclusion, (1) painful stimulation can selectively impact attention; (2) acupuncture can also selectively impact attention; i.e., both have selective influences on the alerting and executive control networks, but not on the orienting network; (3) the effects of acupuncture and painful stimulation are not identical. The mechanisms by which painful stimulation and acupuncture influence attention warrant further research.

Design and synthesis of hydroxypyridinone-L-phenylalanine conjugates as potential tyrosinase inhibitors.

A range of hydroxypyridinone-L-phenylalanine conjugates were synthesized starting from kojic acid. Their tyrosinase activity was determined, and it was found that one of the compounds ((S)-(5-(benzyloxy)-1-octyl-4-oxo-1,4-dihydropyridin-2-yl)methyl 2-amino-3-phenylpropanoate, 5e) showed potent inhibitory effect against mushroom tyrosinase, the IC50 values for monophenolase and diphenolase activities being 12.6 and 4.0 µM, respectively. It was also demonstrated that these conjugates are mixed-type inhibitors, suggesting they could bind to both the free enzyme and the enzyme-substrate complexes. MTT assay indicated that 5e was nontoxic to three cell lines. This compound may find applications in food preservation and cosmetics.

3,3'-Dihy-droxy-6,6'-bis-(hy-droxy-meth-yl)-2,2'-(pentane-1,1-di-yl)di-4H-pyran-4-one.

In the title mol-ecule, C(17)H(20)O(8), the two pyran rings form a dihedral angle of 61.2 (2)°. The two hy-droxy-methyl groups are each disordered over two sets of sites in a 0.764 (3):0.236 (3) ratio. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the ac plane.

[Mechanism of impaired attention network in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To explore the influences of stable chronic obstructive pulmonary disease (COPD) on attention functions. METHODS: The research objects came from the Hospital Affiliated to Anhui Medical University from February to September in 2011. Attention network test (ANT) was employed to compare stable COPD patients (n = 38) with healthy controls (n = 36) in the efficiencies of anatomically defined attentional networks: alertness, orientation and executive attention. RESULTS: Significant group differences were found in orientation ((27 ± 8) ms vs (57 ± 4) ms, P = 0.001), but not in alertness ((19 ± 7) ms vs (32 ± 4) ms, P = 0.115) or executive attention network ((94 ± 15) ms vs (119 ± 11) ms, P = 0.196). The accuracy of attention network test was significantly slower in the COPD group than in the healthy controls (90.2% ± 1.6% vs 96.3% ± 1.7%, P = 0.011). The score of verbal fluency test was significantly lower in COPD patients than in healthy controls (18.2 ± 0.5 vs 21.4 ± 0.6, P = 0.000). CONCLUSIONS: The attention functions of COPD patients are impaired, especially oriental network efficiency. It is probably due to chronic hypoxia, hypoxia-related low blood flow of temporal or parietal lobe or long-term anticholinergic drug use.