Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery.

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment.

Level and influencing factors of transition shock among new nurses in China: A multicenter cross-sectional study.

Background and Aims: New nurses are an important part of nursing teams. The failure of new nurses to successfully transition seriously affects personal career development and nursing work quality, and important influencing factors deserve the attention of nursing managers. At present, multicenter, large-sample investigations of transition shock among new nurses are lacking in China. This study aims to investigate the current level and influencing factors of transition shock among new nurses in China. Methods: We conducted a multicenter, cross-sectional study with 3414 new nurses from 16 provinces in 7 regions in China from October 22, 2021, to November 8, 2021. We used the snowball sampling method and an online questionnaire produced by the researchers to collect data; the questionnaire included questions on demographic information, a transition shock scale for new nurses and open-ended questions. Data were analyzed using SPSS version 24. Results: The effective response rate of this study was 97.89%, with 3342 effective participants from 189 hospitals in China, most of whom were female (94.88%). The study showed that the transition shock of new nurses in China was at a moderate level, with pre-job anxiety, unsatisfactory welfare treatment, resignation intention, adverse events, poor sleep quality, 1 or fewer exercise sessions per week, inability to balance work and life, and gluttony negatively affecting the transition shock of new nurses in China. Psychological shock was the strongest among the four dimensions of transition shock. Conclusions: The transition shock of new nurses, especially their psychological shock, deserves more attention from international society. Nursing managers should continue to take supportive measures to intervene in the factors influencing transition shock, with the aim of reducing the level of transition for new nurses, promoting their personal thriving, improving the quality of nursing work and increasing the retention rate of nurses.

A Combination of EGFR Inhibitors and AE-PDT Could Synergistically Suppress Breast Cancer Progression.

BACKGROUND: Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancerrelated deaths in women. Activation of EGFR by EC-secreted EGFR ligands promotes breast cancer progression. Current treatments provide limited benefits in triple-negative breast cancer (TNBC). Photodynamic therapy (PDT) has been proven effective for the treatment of TNBC through the EGFR pathway, but the underlying mechanism is still unclear. PURPOSE: The purpose of this study was to determine the role of the EGFR pathway in the treatment of PDT on TNBC in a co-culture system. METHODS: MB-231 and HUVEC were co-cultured for experiments (HU-231). Cell viability and ROS production were detected after AE-PDT, a combination of EGFR inhibitors (AEE788)with PDT to test angiogenesis, apoptosis, and pyroptosis. WB detects expression of EGFR. EGFR, P-EGFR, VEGF, caspase-1, capase-3, and GSDMD . RESULTS: AE-PDT inhibited HU-231 cell proliferation and tumor angiogenesis, and induced cell apoptosis and pyroptosis by promoting ROS production. AEE788, an inhibitor of the EGFR, enhanced HU-231 cell killing after AE-PDT. CONCLUSION: Our study suggested that the combination of EGFR inhibitors and AE-PDT could synergistically suppress breast cancer progression, providing a new treatment strategy.

C-Reactive Protein Levels and Cognitive Decline following Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.

The effectiveness and safety of blood flow restriction training for the post-operation treatment of distal radius fracture.

INTRODUCTION: Distal radius fracture (DRF) is a common injury in the upper extremities. Blood flow restriction (BFR) has been proven to be effective in improving function in low-load training, which is suitable for post-op rehabilitation. We explored the effectiveness and safety of BFR therapy in DRF patients who underwent surgery. MATERIALS AND METHODS: Thirty-five patients were randomly assigned to either the BFR or the regular training (RT; no BFR therapy) groups. All patients completed the same 4-week postoperative rehabilitation program, including anti-inflammatory treatments, strengthening and range of motion (ROM) training. In the BFR group, the pressure was 120 mmHg in strengthening training course. Pain, circumferences of wrists and forearms, ROM, muscle strength, and D-dimer levels were evaluated at weeks 0, 2, and 4. Radius union scoring system (RUSS) was measured at weeks 4 and 12. Finally, wrist functionality (Cooney modification) was evaluated at week 12. RESULTS: The BFR group had significantly decreased pain levels compared with the RT group (p < 0.01, effect size= 2.33, -2.44 at weeks 2 and 4). Swelling was effectively relieved in both groups. The wrist swelling was less in the BFR group (p < 0.01, effect size = -2.17 at week 4). The isometric strength of wrist extension (p < 0.01, effect size = 1.5, 3.02 at weeks 2 and 4), flexion (p < 0.01, effect size = 1.33, 2.53 at weeks 2 and 4), and functionality significantly increased in the BFR group (p < 0.01, effect size = 2.80 at week 12). No risk of VT in the BFR group was found. BFR did not threaten bone healing. CONCLUSIONS: In patients with DRF who underwent corrective surgery, BFR therapy effectively relieved pain and swelling, increased muscle strength and wrist function, and had no additional risks for bone healing and VT.

BFR therapy can significantly reduce pain, strengthen muscles, and improve function.BFR therapy did not significantly improve passive ROM, and further research is needed to determine its ability to reduce swelling.BFR therapy is safe and effective for DRF patients after ORIF, but requires individualized protocols and frequent assessments. Further research is needed for other orthopedic surgeries.

Residents of Mountainous Areas Have a Higher Low Back Pain Prevalence Than Flat Areas of Chongqing, China: A Cross-Sectional Study.

Background and Purpose: Epidemiological studies on low back pain in residents living in mountainous areas are scarce. The study was aimed at investigating the prevalence and associated factors of low back pain in Chongqing, relatively impoverished mountainous areas of China. Materials and Methods: This was a cross-sectional study conducted at selected community or village health service centers in Chongqing over a 2-month period (May 2021 to June 2021), which included adults of Chongqing aged >18 years with or without low back pain (N=1820) chosen by stratified, cluster-sampling. Associated factors of low back pain including sociodemographic characteristics, lifestyle, and occupational features were collected, along with medical history, Oswestry Disability Questionnaire (ODI), and Numerical Rating Scale (NRS) of patients with low back pain, and carried out for at least 20 minutes per respondent. Univariate and multivariate logistic regression models were utilized for statistical analysis. Results: Overall, 30.5% of 1704 respondents presented with low back pain, with 26.3% living in flat areas and 35.6% in mountainous areas. The associated factors of low back pain were mountainous area residence (OR 1.4, 95% CI 1.1-1.8), advanced age (OR 1.8, 95% CI 1.3-2.5 for those aged 45-59 years, OR 2.3, 95% CI 1.6-3.4 for those aged 60-74 years, and OR 2.1, 95% CI 1.2-3.6 for those aged ≥75 years), married or remarried (OR 1.9, 95% CI 1.1-3.2), divorced or widowed (OR 2.7, 95% CI 14-5.4), moderate labor intensity (OR 1.4, 95% CI 1.1-1.8), frequent stoop (OR 1.6, 95% CI 1.1-2.4), and depressed mood (OR 1.6, 95% CI 1.2-2.1). Residents in the mountainous areas had a higher score on Oswestry Disability Questionnaire (8.3 [SD 6.3] vs 6.2 [SD 4.3]) than those in flat areas. Conclusion: Mountainous areas in Chongqing had higher prevalence of low back pain as 35.6%, compared with 26.3% in flat areas, with more severe dysfunction in low back pain patients. Multifactorial analysis found that the factors associated with low back pain in Chongqing residents included mountain residence, labor intensity, stoop, psychological factors and frequency of exercise.

Transcranial direct current stimulation alleviated ischemic stroke induced injury involving the BDNF-TrkB signaling axis in rats.

Ischemic stroke causes a complicated sequence of apoptotic cascades leading to neuronal damage and functional impairments. Transcranial direct current stimulation (tDCS) is a non-invasive treatment technique that uses electrodes to deliver weak current to the head. It could influence brain activity and has a crucial role in neuronal survival and plasticity. The current study investigated the neuroprotective effects and potential mechanisms of tDCS by brain-derived neurotrophic factor (BDNF) and its related receptor tropomyosin-receptor kinase B (TrkB) against apoptosis following ischemic injury in vivo. The effect of consecutive treatment with tDCS for seven days on rats after Middle cerebral artery occlusion/reperfusion (MCAO/R) surgery was studied. Western blotting, immunofluorescent staining, TUNEL assay, and electron microscope were conducted seven days after tDCS treatment, and the motor function was assessed at 1, 3, and 7 days. Activities of BDNF-TrkB signaling axis and apoptosis-related proteins were determined in the cerebral cortex. At seven days after tDCS treatment, it increased BDNF levels and promoted the regeneration of axons compared with the MCAO/R group. There was also a reduction in neuronal apoptosis and improved functional deficits. Whereafter, a TrkB receptor inhibitor K252a was administrated to clarify whether the neuroprotection of tDCS is exerted via BDNF-TrkB signaling. The results depicted that K252a application significantly inhibited the neuroprotection impact of tDCS treatment. It was accompanied by a significant downregulation of phosphorylation of TrkB, PI3K, and Akt. Our study investigated the neuroprotective effects of tDCS against ischemic injury. The results indicate that upregulation of BDNF and its critical receptor TrkB, as well as its downstream PI3K/Akt pathway, were involved in the protective effects exerted by tDCS.

Real-life experience of accepting assistive device services for Tibetans with dysfunction: A qualitative study.

Objective: This study aimed to understand the real-life experiences of Tibetans in China with dysfunction in the process of accepting assistive device services and to provide a reference for service quality improvement and policy formulation. Methods: Semi-structured personal interviews were used to collect data. Ten Tibetans with dysfunction representing three categories of different economic level areas in Lhasa, Tibet were selected to participate in the study by purposive sampling method from September to December 2021. The data were analyzed using Colaizzi's seven-step method. Results: The results present three themes and seven sub-themes: identification of tangible benefits from assistive devices (enhancing self-care ability for persons with dysfunction, assisting family members with caregiving and promoting harmonious family relationships), problems and burdens (difficulty in accessing professional services and cumbersome processes, not knowing how to use it correctly, psychological burden: fear of falling and stigmatization), and needs and expectations (providing social support to reduce the cost of use, enhancing the accessibility of barrier-free facilities at the grassroots level and improving the environment for the use of assistive devices). Conclusion: A proper understanding of the problems and challenges faced by Tibetans with dysfunction in the process of accepting assistive device services, focusing on the real-life experiences of people with functional impairment, and proposing targeted suggestions for improving and optimizing the user experience can provide reference and basis for future intervention studies and related policy formulation.

The ALK1­Smad1/5­ID1 pathway participates in tumour angiogenesis induced by low­dose photodynamic therapy.

Photodynamic therapy (PDT) is an effective and low­invasive tumour therapy. However, it can induce tumour angiogenesis, which is a main factor leading to tumour recurrence and metastasis. Activin receptor­like kinase­1 (ALK1) is a key factor regulating angiogenesis. However, it remains unclear whether ALK1 plays an unusual role in low­dose PDT­induced tumour angiogenesis. In the present study, human umbilical vein endothelial cells (HUVECs) co­cultured with breast cancer MDA­MB­231 cells (termed HU­231 cells) were used to construct an experimental model of tumour angiogenesis induced by low­dose PDT. The viability, and the proliferative, invasive, migratory, as well as the tube­forming ability of the HU­231 cells were evaluated following low­dose PDT. In particular, ALK1 inhibitor and and an adenovirus against ALK1 were used to further verify the role of ALK1 in low­dose PDT­induced tumour angiogenesis. Moreover, the expression of ALK1, inhibitor of DNA binding 1 (ID1), Smad 1, p­Smad1/5, AKT and PI3K were detected in order to verify the underlying mechanisms. The findings indicated that low­dose PDT enhanced the proliferative ability of the HU­231 cells and reinforced their migratory, invasive and tube formation capacity. However, these effects were reversed with the addition of an ALK1 inhibitor or by the knockdown of ALK1 using adenovirus. These results indicated that ALK1 was involved and played a critical role in tumour angiogenesis induced by low­dose PDT. Furthermore, ALK1 was found to participate in PDT­induced tumour angiogenesis by activating the Smad1/5­ID1 pathway, as opposed to the PI3K/AKT pathway. On the whole, the present study, for the first time, to the best of our knowledge, demonstrates that ALK1 is involved in PDT­induced tumour angiogenesis. The inhibition of ALK1 can suppress PDT­induced tumour angiogenesis, which can enhance the effects of PDT and may thus provide a novel treatment strategy for PDT.

Non-invasive brain stimulation for limb motor function and daily living activity improvement in acute stroke: A meta-analysis.

OBJECTIVE: To evaluate the effect of non-invasive brain stimulation (NIBS) in improving limb motor dysfunction and daily living activity during at the phase of acute stroke. MATERIALS AND METHODS: Randomized controlled trials about the effect of NIBS on hemiparesis in acute stroke were retrieved from databases of China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, CBM, PubMed, Embase, Cochrane Library, and Web of Science from inception until January 3rd 2022. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using Review Manager 5.3 and STATA 14. The effect size was evaluated by using the weighed mean difference (WMD) and a 95% confidence interval (CI). The stability and sensitivity of the results and sources of heterogeneity were also analyzed. RESULTS: 12 studies involving 639 patients were included. Our meta-analysis showed that NIBS could improve the Fugl-Meyer Assessment (weighed mean difference = 3.96, 95% confidence interval = 3.45 to 4.48) and Barthel Index (weighed mean difference = 12.29, 95% confidence interval = 4.93 to 19.66), while reducing the National Institutes of Health Stroke Scale (weighed mean difference = -2.37, 95% confidence interval = -3.43 to -1.31). CONCLUSION: NIBS is effective in improving paretic limb motor function and activities of daily living in patients during at the phase of acute stroke.

Factors Influencing Utilization of Assistive Devices by Tibetan Seniors on the Qinghai-Tibet Plateau: Based on Research Strategy of Triangulation.

Purpose: To investigate the current situation of assistive device (AD) usage among seniors in Tibet, China, and explore its influencing factors. Methods: A mixed-methods design was used. Cognition, attitude, behavior, and preference toward ADs were assessed by a self-designed questionnaire. Additionally, participants responded to the open-ended questions. Anderson's behavior model analyzed the impacts of the prerequisite factors, enabling factors, and demand factors influencing the utilization of ADs by Tibetan seniors. Results: Of the 211 Tibetan seniors, 149 (70.6%) Tibetan seniors expressed the willingness to utilize ADs. Binary Logistic regression analysis showed that one prerequisite factor: age; one enabling factor: care situation, and one demand factor: dysfunctional condition were factors influencing the utilization of ADs. Qualitative comments described: psychological, physical environment, and social support factors were the main influencing factors. Conclusion: This study presents the current situation to utilize ADs by Tibetan seniors on the Qinghai-Tibet Plateau, incorporates Anderson's behavioral model for quantitative analysis, and combines qualitative research to explore the facilitating and hindering factors, to provide reference and basis for the development of ADs for seniors and policy formulation. The sample size of this study is relatively small and limited to ethnic groups, and we plan to increase the sample size and include more ethnic groups in the future study.

Ultrasonic-controlled "explosive" hydrogels to precisely regulate spatiotemporal osteoimmune disturbance.

Spatiotemporal Immune disorder is a key factor leading to the failure of bone tissue healing. It is of vital importance to accurately suppress excessive peak immune response within 24-48 h of the injury and so regulate the spatiotemporal osteoimmune disturbance of bones. In this study, Ultrasound Controlled "Explosive" (UCE) hydrogels were prepared from gelatin-hyaluronic acid methacrylate hydrogels loaded with resveratrol nanobubbles produced by double emulsification through a condensation reaction. Such materials innovatively enable ultrasound-controlled RES release for precise regulation of spatiotemporal osteoimmune disorders. Under an ultrasonic power level of 1.5 W/cm2, the rate of effectively released RES through the blast of UCE hydrogels reached 38.14 %. And compared with the control group, the in vivo inhibition of inflammation and osteogenesis effects of UCE hydrogels were more effective, respectively. As suggested by the results, the excessive local inflammatory response was inhibited by the release of resveratrol, the temporospatial disorder of bone immune was precisely regulated, and as a result, the process of bone repair was accelerated. Altogether, this study confirms that the newly created UCE Hydrogels effectively promote bone repair by intervening peak inflammation during the early phase of fracture healing.

Effect of Manual Lymphatic Drainage on Breast Cancer-Related Postmastectomy Lymphedema: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Manual lymphatic drainage (MLD) is widely used in the treatment of breast cancer-related postmastectomy lymphedema (BCRL). However, the therapeutic benefit of MLD on BCRL remains controversial. OBJECTIVE: The aim of this study was to analyze the efficacy of MLD for BCRL. METHOD: Four electronic databases were systematically searched for trials comparing MLD and no MLD treatment as options for BCRL. Comparative treatment results included reduction of upper extremity limb volume with subgroup analysis by the number and duration of treatments. RESULTS: A total of 457 patients were included in the analysis. There was no significant difference in the amount of upper extremity edema between the MLD treatment and control or no MLD groups ( P = .11). However, when the treatment course was ≥20 sessions, there was a significant reduction in the upper extremity volume ( P = .03). There was also a significant reduction in the upper extremity volume when treatment duration was >2 weeks ( P = .03). CONCLUSION: Manual lymphatic drainage treatment statistically did not reduce the upper extremity limb volume of BCRL, but upper extremity volume was reduced at statistically significant levels when treatment number were ≥20 sessions or the duration of treatment was >2 weeks. IMPLICATION FOR PRACTICE: Reduction in upper limb volume is dependent on the number and duration of treatments. When treatment number were ≥20 sessions, or the duration of treatment was >2 weeks, reduction of upper limb volume was statistically achieved. Manual lymphatic drainage treatment can be clinically recommended to treat BCRL according to these parameters.

Nutrition and sarcopenia: Current knowledge domain and emerging trends.

Objective: Non-pharmacological management like nutrient supplements has shown positive impacts on muscle mass and strength, which has burgeoned clinical and research interest internationally. The aim of this study was to analyze the current knowledge domain and emerging trends of nutrition-related research in sarcopenia and provide implications for future research and strategies to prevent or manage sarcopenia in the context of aging societies. Materials and methods: Nutrition- and sarcopenia-related research were obtained from the Web of Science Core Collection (WoSCC) database from its inception to April 1, 2022. Performance analysis, science mapping, and thematic clustering were performed by using the software VOSviewer and R package "bibliometrix." Bibliometric analysis (BA) guideline was applied in this study. Results: A total of 8,110 publications were extracted and only 7,510 (92.60%) were selected for final analysis. The production trend in nutrition and sarcopenia research was promising, and 1,357 journals, 107 countries, 6,668 institutions, and 31,289 authors were identified in this field till 2021. Stable cooperation networks have formed in the field, but they are mostly divided by region and research topics. Health and sarcopenia, metabolism and nutrition, nutrition and exercise, body compositions, and physical performance were the main search themes. Conclusions: This study provides health providers and scholars mapped out a comprehensive basic knowledge structure in the research in the field of nutrition and sarcopenia over the past 30 years. This study could help them quickly grasp research hotspots and choose future research projects.

A photochemical-responsive nanoparticle boosts doxorubicin uptake to suppress breast cancer cell proliferation by apoptosis.

In the course of chemotherapy for breast cancer, doxorubicin (DOX) is one of the most commonly prescribed agents. However, it has been recognized as clinically circumscribed on account of its poor selectivity and toxic reactions to normal tissues. Fortunately, the distinct merit of photochemical-responsive nanoparticle delivery systems to enhance cellular drugs uptake through localized concentration, adequate selective and minimizing systemic toxicity has aroused substantial interest recently. In this study, we synthesized photochemical-responsive nanoparticle by incorporating DOX, curcumin (CUR), and perfluorooctyl bromide (PFOB) into poly(lactic-co-glycolic acid) (PLGA) via double emulsification (DOX-CUR-PFOB-PLGA). The synthesized composite nanoparticles, which featured good ultrasound imaging, engendered photochemical activation for drug release when given laser irradiation. Cumulative release rates for DOX were 76.34%, and for CUR were 83.64%, respectively. Also, MCF-7 cells displayed significant intracellular DOX uptake and reactive oxygen species (ROS) levels, degraded cytoskeleton, and decreased cell growth and migration capacity. At the molecular level, cellular pAKT levels decreased, which resulted in downregulated HIF-1α and BAX/BCl-2 levels, leading to Caspase-3 activation and thus induction of apoptosis. Therefore, the photochemical-responsive nanoparticles possess the potential to elicit apoptosis in MCF-7 cells via enhanced DOX uptake.

Effects of Curcumin-mediated photodynamic therapy on autophagy and epithelial-mesenchymal transition of lung cancer cells.

BACKGROUND: This study aimed to investigated whether Curcumin-mediated PDT can suppress EMT in lung cancer cells, and explore the roles of autophagy in the process of regulating EMT. METHODS: Lung cancer cell viability was assessed by CCK-8 assay. The expression of epithelial marker and mesenchymal markers, the conversion of LC3-I to LC3-II and the levels of p62 and beclin1 in A549 and SPCA1 cells were measured by Western blotting assay. The Wound healing and Transwell assays were used to detect the migration and invasion abilities of the A549 and SPCA1 cells. Autophagosome formation was detected via observing the colocalization of Lamp-2 with LC3 in A549 cells, and the autophagy ultrastructure was observed by TEM. RESULTS: Curcumin-PDT inhibited EMT, migration and invasion and induced autophagy in lung cancer cells. Curcumin-PDT induced autophagy was involved in the process of PDT inhibiting EMT, but it presented a promoting effect of EMT in lung cancer cells. Curcumin-PDT combined with CQ further inhibited EMT, invasion and migration of lung cancer cells. CONCLUSIONS: The role of PDT-induced autophagy in the regulation of EMT was determined to be a promoting effect in lung cancer. Therefore, Curcumin-mediated PDT combined with autophagy inhibitor further suppressed EMT of lung cancer cells, and may represent a potential strategy against invasion and migration of lung cancer.

Peripheral blood and urine metabolites and biological functions in post-stroke depression.

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral blood and urine metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral blood and urine of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was "phenylalanine metabolism" and the pathway containing the most associated metabolites was "aminoacyl-tRNA biosynthesis", which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral blood and urine are associated with PSD, especially the disruption of "phenylalanine metabolism" and "aminoacyl-tRNA biosynthesis" pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD.

7,8-Dihydroxyflavone protects neurons against oxygen-glucose deprivation induced apoptosis and activates the TrkB/Akt pathway.

BACKGROUND: 7,8-dihydroxyflavone (7,8-DHF), a selective agonist of tropomyosin related kinase receptor B (TrkB), is known to exert protective effects in neurodegenerative diseases. However, the role of 7,8-DHF in TrkB signaling after ischemic stroke has remained elusive. METHODS: In the vitro model of ischemic stroke, we investigated the neuroprotective effect of 7,8-DHF through activation of TrkB signaling. Neurons subjected to oxygen and glucose deprivation/reperfusion were treated with the protein kinase inhibitor K252a and a knockdown of TrkB. Cell counting kit-8 (CCK-8) assay, Flow Cytometric Analysis (FACS), TdT-mediated dUTP nick end labeling (TUNEL) assay were conducted for measuring cell viability and numbers of apoptotic cells. And apoptosis-associated proteins were analyzed by Western blotting. RESULTS: Compared with the Control group, OGD/R group revealed lower cell viability by CCK-8 assay FACS and TUNEL assay showed increased rates of neuronal apoptosis. However, 7,8-DHF treatment increased cell viability and reduced neuronal apoptosis. Western blotting indicated upregulated Bax and cleaved caspase-3 and but downregulated Bcl-2 following OGD/R. Whereas 7,8-DHF treatment downregulated Bax and cleaved caspase-3 but upregulated Bcl-2. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt following 7,8-DHF administration. However, the administration of K252a and knockdown of TrkB could alleviate those effects. CONCLUSION: Our study demonstrates that activation of TrkB signaling by 7,8-DHF protects neurons against OGD/R injury via the TrkB/Akt pathway, which provides the evidence for the role of TrkB signaling in OGD-induced neuronal damage and may become a potential therapeutic target for ischemic stroke.