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Abstract Traumatic encephalopathy syndrome (TES) is used to describe the clinical manifestations of chronic traumatic encephalopathy (CTE). However, effective treatment and prevention strategies are lacking. Increasing evidence has shown that rehabilitation training could prevent cognitive decline, enhance brain plasticity, and effectively improve neurological function in neurodegenerative diseases. Therefore, the mechanisms involved in the effects of rehabilitation exercise therapy on the prognosis of CTE are worth exploring. The aim of this article is to review the pathogenesis of CTE and provide a potential clinical intervention strategy for CTE.

Abstract Background Scientific research ability (SRA) is very important for clinical postgraduates. However, the factors affecting students' SRA are constantly changing with the development of medicine. The aim of this study was to investigate the current situation of SRA in clinical postgraduates and exploring the potential factors and the corresponding countermeasures under the background of new medical science. Methods A total of 133 postgraduates (first- or second-year) were investigated by questionnaire in the Second Affiliated Hospital of Fujian Medical University. All results were analyzed by R software. Results In terms of the SRA, academic-degree postgraduate students (ADPSs) were significantly better than professional-degree postgraduate students (PDPSs) (P = 0.001), the students with scientific research interest were remarkably better than those without scientific research interest (P = 0.004), the students who mastered statistical analysis methods were more prominent than those who did not (P = 0.007), the students with paper-writing skills were obviously superior to those without it (P = 0.003), and the second-year students were notably better than the first-year students (P = 0.003). Stratified analysis by the above factors except the degree type showed no significant difference in the first-year postgraduates. In the second-year postgraduates, the ADPSs were remarkably superior to the PDPSs (P = 0.002), the students with scientific research interest were obviously better than those without scientific research interest (P = 0.014), the students with more time investment in scientific research were more prominent than those with less time investment in scientific research (P = 0.025), the students with paper-writing skills were notably superior to those without it (P = 0.031), and the students with plotting ability were better than those without it (P = 0.013). Conclusion The important factors affecting the SRA of clinical postgraduates include the degree type, the grade of student, scientific research interest, time investment in scientific research, statistical analysis methods, paper-writing skills, plotting ability. In short, earlier systematic SRA training contributes to the improvement of SRA in clinical postgraduates, especially in PDPSs.

Abstract To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1–3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

BackgroundObesity has been reported to lead to increased incidence of depression. Glycerol-3-phosphate acyltransferases 4 (GPAT4) is involved in triacylglycerol synthesis and plays an important role in the occurrence of obesity. GPAT4 is the only one of GPAT family expressed in the brain. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism.ResultsA high-fat diet resulted in increased body weight and blood lipid. HFD induced depression like behavior in the force swimming test, tail suspension test and sucrose preference test. HFD significantly up-regulated the expression of GPAT4 in hippocampus, IL-1β, IL-6, TNF-α and NF-κB, accompanied with down-regulation of BDNF expression in hippocampus and ventromedical hypothalamus, which was attributed to AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB).ConclusionOur findings suggest that hippocampal GPAT4 may participate in HFD induced depression through AMPK/CREB/BDNF pathway, which provides insights into a clinical target for obesity-associated depression intervention.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening. [ABSTRACT FROM AUTHOR]

Panax ginseng is widely used in Asian countries and its active constituents—ginsenosides—need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD. Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale. Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity. Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD. [ABSTRACT FROM AUTHOR]

AbstractIn our study, a method based on affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was established to select Glucagon-like peptide-1 receptor (GLP-1R) agonists from natural products, and as an example, the GLP-1R agonists from Panax ginseng was selected using our established method. As a result, total five GLP-1R agonists were selected from Panax ginseng for the first time. Our results indicated that activating GLP-1R to promote insulin secretion probably was another important hypoglycemia mechanism for ginsenosides in Panax ginseng, which had great influence on the study of the anti-diabetes effect of ginsenosides. [ABSTRACT FROM AUTHOR]

Background: Obesity has been reported to lead to increased incidence of depression. Glycerol-3-phosphate acyltransferases 4 (GPAT4) is involved in triacylglycerol synthesis and plays an important role in the occurrence of obesity. GPAT4 is the only one of GPAT family expressed in the brain. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism. Results: A high-fat diet resulted in increased body weight and blood lipid. HFD induced depression like behavior in the force swimming test, tail suspension test and sucrose preference test. HFD significantly up-regulated the expression of GPAT4 in hippocampus, IL-1β, IL-6, TNF-α and NF-κB, accompanied with down-regulation of BDNF expression in hippocampus and ventromedical hypothalamus, which was attributed to AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB). Conclusion: Our findings suggest that hippocampal GPAT4 may participate in HFD induced depression through AMPK/CREB/BDNF pathway, which provides insights into a clinical target for obesity-associated depression intervention. [ABSTRACT FROM AUTHOR]

Background. Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary head and neck movements and postures. Reports on microstructural and functional abnormalities in multiple brain regions not limited to the basal ganglia have been increasing in patients with CD. However, the neural bases of CD are unclear. This study is aimed at identifying cerebral functional abnormalities in CD by using resting-state functional magnetic resonance imaging (rs-fMRI). Methods. Using rs-fMRI data, voxel-mirrored homotopic connectivity (VMHC) and degree centrality were used to compare the alterations of the rs-functional connectivity (FC) between 19 patients with CD and 21 healthy controls. Regions showing abnormal FCs from two measurements were the regions of interest for correlation analyses. Results. Compared with healthy controls, patients with CD exhibited significantly decreased VMHC in the supplementary motor area (SMA), precuneus (PCu)/postcentral gyrus, and superior medial prefrontal cortex (MPFC). Significantly increased degree centrality in the right PCu and decreased degree centrality in the right lentiform nucleus and left ventral MPFC were observed in the patient group compared with the control group. Further correlation analyses showed that the VMHC values in the SMA were negatively correlated with dystonia severity. Conclusion. Local abnormalities and interhemispheric interaction deficits in the sensorimotor network (SMA, postcentral gyrus, and PCu), default mode network (MPFC and PCu), and basal ganglia may be the key characteristics in the pathogenesis mechanism of CD. [ABSTRACT FROM AUTHOR]

Objectives: Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever, which is the most severe spotted fever group (SFG) rickettsiosis. Developing a simple and reliable detection method is required. Methods: A detection method for R. rickettsii was established based on a recombinase polymerase amplification (RPA) assay and the lateral flow (LF) test. A specific target sequence was screened, and corresponding primers and probes were designed, synthesized, and screened for establishing an RPA assay with high amplification efficiency. Reagent concentrations, amplification time, and loading volume for strip development were optimized. The detection limit, analytic sensitivity and specificity were evaluated. Results: A rapid, visual, sensitive and specific method for the detection of R. rickettsii based on RPA and the LF test was successfully established. The novel method had a limit of detection of 10 to 50 copies/reaction without recognizing other organisms. Analytical sensitivity and specificity were ≥90% and 100%, respectively, as evaluated by animal and simulative human samples. Conclusions: Using the established method, detection could be completed in 30 min with visually detectable results by the naked eye, without requirement of any instrument except a constant temperature equipment. The technique shows superior detection performance and is promising for wide use in the field as well as resource-limited areas for R. rickettsii detection. [ABSTRACT FROM AUTHOR]

Objective: Several networks in human brain are involved in the development of blepharospasm. However, the underlying mechanisms for this disease are poorly understood. A voxel-mirrored homotopic connectivity (VMHC) method was used to quantify the changes in functional connectivity between two hemispheres of the brain in patients with blepharospasm. Methods: Twenty-four patients with blepharospasm and 24 healthy controls matched by age, sex, and education were recruited. The VMHC method was employed to analyze the fMRI data. The support vector machine (SVM) method was utilized to examine whether these abnormalities could be applied to distinguish the patients from the controls. Results: Compared with healthy controls, patients with blepharospasm showed significantly high VMHC in the inferior temporal gyrus, interior frontal gyrus, posterior cingulate cortex, and postcentral gyrus. No significant correlation was found between abnormal VMHC values and clinical variables. SVM analysis showed a combination of increased VMHC values in two brain areas with high sensitivities and specificities (83.33 and 91.67% in the combined inferior frontal gyrus and posterior cingulate cortex; and 83.33 and 87.50% in the combined inferior temporal gyrus and postcentral gyrus). Conclusion: Enhanced homotopic coordination in the brain regions associated with sensory integration networks and default-mode network may be underlying the pathophysiology of blepharospasm. This phenomenon may serve as potential image markers to distinguish patients with blepharospasm from healthy controls. [ABSTRACT FROM AUTHOR]

Coxiella burnetii, a global-distributed biological warfare agent, is the causative agent of Q fever. Correct diagnosis of Q fever is challenging and developing a fast, simple, and reliable detection method is necessary. In this study, recombinase polymerase amplification (RPA) assay combined with lateral flow (LF) test was developed targeting 23S rRNA gene of C. burnetii Xinqiao strain. Primers and probe were designed and synthesized, with one set with high amplification efficiency screened for establishment of the method. Reaction conditions were optimized. Sensitivity, specificity, and accuracy were evaluated. The established RPA-LF reaction could be completed in 30 minutes by combining RPA at 37°C with LF at room temperature, with visually judged results. The method showed good specificity without recognizing other bacteria evaluated. It detected positive plasmid and genomic DNA at levels of 10 copies/reaction and 7 copies/reaction, respectively, levels comparable to that of real-time quantitative PCR (RT-qPCR) targeting 23S rRNA gene established previously. Both RPA-LF and RT-qPCR were used to detect C. burnetii-infected mouse samples and the results were fully consistent. The method showed superior detection performance and will provide technical support against C. burnetii in resources-limited areas. [ABSTRACT FROM AUTHOR]

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects. [ABSTRACT FROM AUTHOR]

AbstractAstragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Oral Mucositis (OM) is a common and highly symptomatic complication of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet (JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism remains unclear., Objectives: This study validated the efficacy and explored the potential mechanisms of JNT in the treatment of OM by integrating network pharmacological analyses and experimental verification., Methods: Network pharmacology and molecular docking techniques were used to predict the active components, key targets, and potential mechanisms of action of JNT against OM. The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the anti-NFκB activity of JNT., Results: A total of 236 Chinese herbal components and 201 corresponding targets were predicted for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be the major targets. Molecular docking revealed that these active compounds exhibited strong binding interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological processes, such as inflammatory response and oxidative stress., Conclusion: Network pharmacological and experimental evidence indicates that JNT has a potential therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments., Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL., Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1β (IL1β), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1β and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/β (IKKα/β), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells., Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL., Competing Interests: Authors QY, QH, HZ, XZ, and HW were employed by Scientific Research Institute of Beijing Tongrentang Co., Ltd. Author CF was employed by Beijing Zhongyan Tongrentang Medicine Research and Development Co., Ltd., (Copyright © 2024 Yin, Huang, Zhang, Zhang, Fan and Wang.)

Our study aimed to investigate the diagnostic value of long non-coding RNA (lncRNA) GAS5 for coronary artery disease (CAD) and to explore the mechanism of the role of GAS5 in CAD. A total of 30 patients with CAD were selected from January 2015 to January 2017 in The First Hospital of Tianmen. In addition, 30 healthy individuals were selected as a control group, and patients with various other types of cardiovascular diseases were also selected. Expression of GAS5 in plasma of all participants was detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to investigate the diagnostic value of GAS5 for CAD. Levels of mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR) in human primary coronary artery endothelial cells (HCAECs) were detected by western blotting. Compared with normal healthy people, expression level of lncRNA Novlnc6 was significantly reduced in patients with CAD and diabetes mellitus, but not in patients with other types of cardiovascular diseases, such as hypertension, abnormal aortic aneurysm, viral myocarditis. In addition, the expression level of GAS5 was significantly lower in patients with CAD compared to patients with diabetes mellitus. ROC curve analysis showed that GAS5 may serve as a promising biomarker for CAD. GAS5 knockdown and overexpression showed no significant effect on the level of mTOR) in HCAECs. However, GAS5 knockdown significantly increased the level of phospho-mTOR (p-mTOR), and GAS5 overexpression significantly decreased the level of p-mTOR. Treatment with mTOR inhibitor and activator showed no significant effect on expression of GAS5 in HCAECs. GAS5 plays a role as upstream regulator of the mTOR pathway to participate in the development of CAD. GAS5 was specifically downregulated in patients with CAD, and it may serve as a promising biomarker for CAD.