Parkinson's disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins.

OBJECTIVE: This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson's disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. METHODS: A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. RESULTS: The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aß1-42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum. CONCLUSIONS: The frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

Purinergic Astrocyte Signaling Driven by TNF-α After Cannabidiol Administration Restores Normal Synaptic Remodeling Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis.

BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.

Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.

OBJECTIVES: Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction. METHODS: A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively. RESULTS: Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024). CONCLUSIONS: In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score. CLINICAL RELEVANCE STATEMENT: The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients. KEY POINTS: • In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

MDMA targets miR-124/MEKK3 via MALAT1 to promote Parkinson's disease progression.

BACKGROUND: Parkinson's disease (PD) is a well-known neurodegenerative disease that is usually caused by the progressive loss of dopamine neurons and the formation of Lewy vesicles. 3,4-Methylenedioxymethamphetamine (MDMA) has been reported to cause damage to human substantia nigra neurons and an increased risk of PD, but the exact molecular mechanisms need further investigation. METHODS: MPTP- and MPP+-induced PD cells and animal models were treated with Nissl staining to assess neuronal damage in the substantia nigra (SN) area; immunohistochemistry to detect TH expression in the SN; TUNEL staining to detect apoptosis in the SN area; Western blotting to detect the inflammatory factors NF-κB, TNF-α, IL-6 and mitogen-activated protein kinase kinase kinase 3 (MEKK3); Griess assay for NO; RT‒qPCR for metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-124 expression; Cell proliferation was assessed by CCK-8. Dual luciferase reporter genes were used to verify targeting relationships. RESULTS: MDMA promoted MALAT1 expression, and knockdown of MALAT1 alleviated the MDMA-induced inhibition of SH-SY5Y cell proliferation, inflammation, NO release, SN neuronal injury, and TH expression inhibition. Both inhibition of miR-124 and overexpression of MEKK3 reversed the neuroprotective effects exhibited by knockdown of MALAT1. CONCLUSION: MDMA promotes MALAT1 expression and inhibits the targeted downregulation of MEKK3 by miR-124, resulting in upregulation of the expression of MEKK3 and finally jointly promoting PD progression.

High-Throughput Phytochemical Unscrambling of Flowers Originating from Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao and Astragalus membranaceus (Fisch.) Bug. by Applying the Intagretive Plant Metabolomics Method Using UHPLC-Q-TOF-MS/MS.

Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao (MO) and Astragalus membranaceus (Fisch.) Bug. (ME) are two primary sources of the Astragalus herb, also known as "Huangqi" in China, which is widely applied to treat hypertension, glomerulonephritis, ischemic heart disease, and diabetes mellitus. As two different sources of the Astragalus herb, the chemical profiles of MO and ME may be different. Previous studies showed abundant differences in chemical composition between MO and ME. Therefore, the by-products of MO and ME, such as Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao flower (MOF) and Astragalus membranaceus (Fisch.) Bug. flower (MEF), may have different phytochemical profiles. In this paper, a metabolomics method combined with ultra-high-performance liquid chromatography and electrospray ionization/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze the components of MOF and MEF. Consequently, the results of principal component analysis (PCA) showed that MOF and MEF could be separated clearly. In total, 31 chemical markers differentiating MOF and MEF were successfully identified, including 22 flavonoids, 8 isoflavones and 1 benzopyran. Among them, the contents of 18 components, including Calycosin, Cyanidin-3-O-glucoside, Quercetin, Rutin, Kaempferol, Formononetin, Isomucronulatol and Prim-O-glucosylcimifugin in MEF, were significantly higher than in MOF. In turn, the contents of another 13 components, covering Biochanin A, Tectoridin, Isomucronulatol-7-O-glucoside, Liquiritin, Rhamnetin, etc., were lower in the MEF group than that in the MOF group. It is worth noting that flavonoids, especially flavonoid glycosides, were the primary active chemical ingredients in MOF and MEF. The 18 ingredients in MEF with a higher level carried out diverse activities, like anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor activities, which led us to speculate that MEF may have greater pharmacological effects and potential development prospects than MOF. The present results displayed that the contents of ingredients in the two different species of plants were radically different, and there was significant uniqueness to the components of MOF and MEF. Our study not only provides helpful chemical information for further quality assessment and active mechanism research of MOF and MEF but also offers scientific support for the resource utilization of MOF and MEF.

Mesenchymal stem cell exosomes rich in miR-23b-3p affect the Wnt signaling pathway and promote neuronal autophagy to alleviate PD symptoms.

This study aims to elucidate the role of miR-23b-3p in mesenchymal stem cell exosomes in regulating the Wnt signaling pathway to promote autophagy of neurons and alleviate Parkinson's disease (PD) symptoms. We generated rat and cellular PD models with 6-OHDA, treated them with mesenchymal stem cell exosomes rich in miR-23b-3p and determined the expression of α-syn and Wnt/ß-catenin pathway and autophagy-related genes. In the plasma of PD patients, the levels of miR-23b-3p and the Wnt/ß-catenin pathway-related genes ß-catenin and DAT were low, while α-syn expression was high. In the PD cell model, miR-23b-3p was downregulated, the Wnt pathway was inhibited, α-syn was upregulated, neuron autophagy was inhibited, and the revitalization of the Wnt/ß-catenin pathway could promote the autophagy of neurons. Coculture of miR-23b-3p-enriched exosomes with MN9D cells confirmed that miR-23b-3p-enriched exosomes could promote autophagy in MN9D cells in a PD cell model. Moreover, animal experiments confirmed the results of the cell experiments. Therefore, miR-23b-3p-enriched mesenchymal stem cell exosomes promote neuronal autophagy by regulating the Wnt signaling pathway, thus alleviating PD progression and providing an important basis for the clinical treatment of PD.

BDNF alleviates Parkinson's disease by promoting STAT3 phosphorylation and regulating neuronal autophagy.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual death of dopaminergic neurons. Brain-derived neurotrophic factor (BDNF) and its receptors are widely distributed throughout the central nervous system, which can promote the survival and growth of neurons and protect neurons. This study revealed that BDNF promotes STAT3 phosphorylation and regulates autophagy in neurons. The PD mouse model was established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, SH-SY5Y cells were treated with 1-methyl-4-phenyl-pyridinium (MPP+) to establish a PD cell model. The level of BDNF was low in PD model mice and SH-SY5Y cells treated with MPP+. BDNF enhanced the levels of p-TrkB, P-STAT3, PINK1, and DJ-1. BDNF promoted autophagy, inhibited the level of p-α-syn (Ser129) and enhanced cell proliferation. The autophagy inhibitor 3-Methyladenine (3-methyladenine, 3-MA) reversed the protective effects of BDNF on neurons. BiFC assay results showed that there was a direct physical interaction between BDNF and STAT3, and coimmunoprecipitation experiments indicated an interaction between STAT3 and PI3K. The PI3K agonist Recilisib activated the PI3K/AKT/mTOR pathway, promoted autophagy, and alleviated neuronal cell damage. BDNF alleviates PD pathology by promoting STAT3 phosphorylation and regulating neuronal autophagy in SH-SY5Y cells and cultured primary neurons. Finally, BDNF has neuroprotective effects on PD model mice.

Efficacy and safety of apatinib combined with radiotherapy in the treatment of advanced pancreatic cancer: a meta-analysis.

OBJECTIVE: At present, pancreatic cancer (PC) has a high morbidity and mortality rate and a poor prognosis. The aim of this article was to study the efficacy and safety of apatinib combined with radiotherapy in the treatment of advanced PC. METHODS: The PubMed, Cochrane Library, Embase, Wanfang, CNKI, VIP, and CBM databases were searched by computer to identify studies on the application of apatinib in patients with advanced PC. The patients in the included study were divided into an observation group (apatinib combined with radiotherapy) and a control group (radiotherapy only), and meta-analysis was performed for each outcome with Revman 5.4 software. This study was successfully registered on the PROSPERO website, and the registration number is CRD: 42,022,384,056 (available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384056 ). RESULTS: A total of 7 randomized controlled trials (RCTs) with 428 patients were included, including 215 in the observation group and 213 in the control group. Compared with the control group, the observation group showed a greater objective response rate [OR = 3.26, 95% CI (2.18, 4.87), P < 0.0001], disease control rate [OR = 5.04, 95% CI (3.12, 8.12), P < 0.0001], complete response rate [OR = 3.87, 95% CI (1.51, 9.88), P = 0.005], and partial response rate [OR = 2.43, 95% CI (1.63, 3.61), P < 0.001], The 1-year survival rate [OR = 2.39, 95% CI (1.15, 4.96), P < 0.05], 2-year survival rate [OR = 2.41, 95% CI (1.03, 5.61), P < 0.05], progression-free survival time [MD = 1.17, 95% CI (0.37, 1.96), P < 0.05], overall survival time [MD = 1.47, 95% CI (0.13, 2.80), P < 0.05], while the stability rate [OR = 1.14, 95% CI (0.72, 1.81), P = 0.58] and various complications were not significantly different between the two groups. CONCLUSION: Apatinib combined with radiotherapy was more effective than radiotherapy alone in the treatment of advanced pancreatic cancer (PC), and apatinib had acceptable safety. However, since our study was limited by the quantity and quality of the included studies, we look forward to more large-sample, multicentre, and high-quality RCTs in the future to verify the conclusions.

Outcomes after the watch-and-wait strategy and local excision treatment for rectal cancer: a meta-analysis.

BACKGROUND: The watch-and-wait (W&W) strategy and local excision (LE) have been used in patients with clinical complete response (cCR) for rectal cancer, but the comparative outcomes of the two strategies are controversial. We compared the efficacy of the W&W strategy with LE for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) or total neoadjuvant therapy (TNT). RESEARCH DESIGN AND METHODS: Several domestic and foreign databases were searched for the relevant literature on comparative trials of the W&W strategy and LE surgery for rectal cancer after neoadjuvant therapy with the following outcomes; differences in local recurrence (LR), distant metastasis (DM/DM+LR), 3-year disease-free survival (DFS), 3-year local recurrence-free survival (LRFS) and 3-year overall survival (OS). RESULTS: Nine articles, were analyzed. Overall, 442 patients were included, with 267 and 175 patients in the W&W and LE groups, respectively. Meta-analysis results showed no significant differences the between W&W and LE groups with respect to LR, DM/DM+LR, 3-year DFS, 3-year LRFS, and 3-year OS. This study has been registered in PROSPERO (registration number: CRD42022331208). CONCLUSION: The W&W strategy may be preferred for some rectal cancer patients who select LE and reach cCR or near cCR after nCRT or TNT.

HOXA10 Expressing UCMSCs Transplantation Improved Endometrial Receptivity on Endometrial Injury.

BACKGROUND: Endometrial injury is considered the major cause of female infertility. Traditional therapies such as estrogen substitution therapy are not satisfactory due to individual variation in response to treatment, thereby warranting the use of alternative strategies such as stem cell therapy. Transplantation of stem cells, such as umbilical cord mesenchymal stem cells (UCMSCs), has been shown to improve endometrial healing. However, due to the effect of the intrauterine environment, the therapeutic effect of UCMSCs is limited, and its efficacy is unstable. HOXA10, encoded by the HOXA10 gene, plays an important role in endometrium morphology maintenance, proliferation, differentiation, and embryo implantation. Moreover, UCMSCs do not show HOXA10 expression. OBJECTIVE: Our study aimed to evaluate the therapeutic effects of HOXA10-transfected UCMSCs on endometrial injury repair in vivo. METHODS: First, we established T10-UCMSCs (UCMSCs transfected with HOXA10) for transplantation. To establish the endometrial injury model, we injected 95% ethanol into the uterine cavity and transplanted T10-UCMSCs into the uterine cavity from the cornua uteri. Fourteen days later, uteri were collected for histological and biochemical analysis of endometrial growth and receptivity. RESULTS: Our results showed the endometrial receptivity was better in T10-UCMSCs group than in UCMSCs group, suggesting that HOXA10 could enhance the repairing ability of UCMSCs in the endometrium injury repair. More importantly, the fertility test showed that more embryos were implanted in the T10- UCMSCs group. CONCLUSION: Our results suggest that UCMSCs with HOXA10 expression could improve the therapeutic effects on endometrial injury repairing.

Ninety-seven cases of experiences with the left thoracotomy approach for off-pump conventional revascularization: a retrospective cohort study.

Background: Minimally invasive coronary surgery-coronary artery bypass grafting (MICS CABG) is well adopted in clinical practice. However, this procedure did not really achieve conventional complete revascularization. The present study aimed to explore the feasibility and safety of conventional revascularization via the left thoracotomy (8-10 cm) approach. Methods: From January 2020 to March 2022, a total of 97 consecutive patients who needed coronary artery revascularization were operated on using this technique. The patients' preoperative, intraoperative, postoperative, and follow-up data were collected. Perioperative variables were compared between the single graft and non-single graft groups. All patients received dual-source computerized tomographic angiography at 1-week postoperatively to evaluate the graft patency and detect pulmonary embolism and aortic dissection. The patients were followed up for 3-27 months. Results: The mean age of the entire cohort was 61.5±8.8 years, there were 16 (16.5%) female patients, and 1-4 grafts were performed per patient. There were no conversions to median sternotomy or on-pump CABG. The average number of grafts was 1.9±0.9, and that of the non-single graft group was 2.5±0.6. Among the 97 included patients, one patient in the single graft group suffered from aspiration pneumonia after a stroke and died. The 30-day mortality was 1.0% (one patient), one patient required re-exploration for bleeding (1.1%), and a total of 191 grafts were performed. All grafts were unobstructed except for one graft to the obtuse marginal branch (OM) (0.5%). Follow-up was performed by phone or via outpatient visits and was available for 92 patients (95%). During the follow-up period, 1 (1.1%) patient suffered an acute myocardial infarction and received percutaneous coronary intervention with no redo-surgery. All patients are alive and angina-free. Conclusions: Left thoracotomy for conventional revascularization is a safe procedure for appropriately selected patients, with few early complications and good early and mid-term results. More cases are ongoing and long-term results are in observation.

Preparation of gastrodin-modified dendrimer-entrapped gold nanoparticles as a drug delivery system for cerebral ischemia-reperfusion injury.

OBJECTIVE: This study sought to evaluate the feasibility of multifunctional gastrodin (GAS)-containing nano-drug carrier system against cerebral ischemia-reperfusion injury (CIRI). METHODS: The drug-loaded nanocomposite (Au-G5.NHAc-PS/GAS) with certain encapsulation efficiency (EE) was prepared by physical adsorption method using different proportions of GAS and drug-carrying system (Au-G5.NHAc-PS). High-performance liquid chromatography was used to determine the drug loading and EE. Cultured rat astrocytes and hypothalamic neurons were assigned into four groups: PBS, Au-G5.NHAc-PS, Au-G5.NHAc-PS/GAS, and GAS. CCK-8 assay, flow cytometry, and quantitative real-time PCR were performed to examine the cell viability, apoptosis, and the expression of tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 in the astrocytes and hypothalamic neurons, respectively. Cellular uptake of GAS and Au-G5.NHAc-PS/GAS was analyzed by using Hoechst 33342 staining. The animal model with focal cerebral ischemia was generated by middle cerebral artery occlusion (MCAO) in healthy male Sprague Dawley (SD) rats, and pathological changes of brain tissue and major organs in the rats were identified by hematoxylin and eosin (HE) staining. Apoptosis in rat astrocytes and hypothalamic neurons was detected by TUNEL staining and flow cytometry. RESULTS: Au-G5.NHAc-PS had a spherical shape with a uniform size of 157.3 nm. Among the nanoparticles, Au-G5.NHAc-PS/GAS with an EE of 70.3% displayed the best release delay effect. Moreover, we observed that in vitro cytotoxicity and cellular uptake of Au-G5.NHAc-PS/GAS were higher than those of GAS, whereas the expression of TNF-α, IL-1ß, and IL-6 was significantly downregulated in Au-G5.NHAc-PS/GAS group as compared to G5.NHAc-PS group. Notably, HE staining revealed that although Au-G5.NHAc-PS/GAS had no toxic and side effects on the main organs of rats, it alleviated the damage of brain tissue in the MCAO rats. Besides, Au-G5.NHAc/GAS markedly reduced MCAO-induced apoptosis. CONCLUSION: Au-G5.NHAc-PS showed favorable surface morphology, sustained drug release ability, no measurable toxicity, and good biocompatibility, indicating that GAS exerts anti-inflammatory and antiapoptotic effects on CIRI.

The Reactive Astrocytes After Surgical Brain Injury Potentiates the Migration, Invasion, and Angiogenesis of C6 Glioma.

BACKGROUND: Surgical resection is a key method for glioma treatment. This inherently invasive procedure alters the tumor microenvironment of glioma cells that cannot be removed by surgery. However, few studies have focused on the impact of this microenvironment change on the growth of glioma cells. METHODS: The authors preconstructed a surgical brain injury model, and then C6 glioma cells were transplanted. HE staining was used to observe the general morphology of tumor cells, and immunohistochemistry of MMP-2, MMP-9, GFAP, and CD31 was used to evaluate the invasiveness of glioma cells and activation of astrocytes and calculate microvessel density. In vitro, primary rat astrocytes were exposed to different temperature gradients. The supernatant was made into conditioned medium for culturing C6 glioma cells. The scratch test and transwell test were used to evaluate the migration and invasion of tumor cells. RESULTS: GFAP expression was stronger in surgical brain injury rats, C6 cells implanted in these rats showed stronger expression of MMP-2 and MMP-9, and CD31 was expressed in more microvessels. Astrocytes exposed to high temperatures of 40°C and 43°C expressed stronger GFAP, and C6 cells cultured in their supernatants had stronger scratch healing ability and the ability to cross transwell chambers. CONCLUSIONS: The microenvironment changes caused by surgical brain injury will enhance the migration and invasion of glioma cells and increase the microvessel density in the tumor. This effect may be related to the activation of astrocytes caused by the thermal injury of bipolar coagulation during surgery.

Analysis of Clinical Characteristics and Risk Factors of Postoperative Recurrence and Malignant Transformation of Low-Grade Glioma.

This research was developed to explore the clinical characteristics and related risk factors of postoperative recurrence and malignant transformation of low-grade glioma (LGG). The subjects were rolled into observation group (19 cases) and control group (51 cases) according to recurrence and malignant transformation during the follow-up period. The clinical data of the two groups were compared, and the risk factors of recurrence and malignant transformation were analyzed with the time of recurrence and malignant transformation as independent variables. The experimental results showed that the proportion of patients aged over 45 years in the observation group (63.16%) was higher than that in the control group (50.98%). The proportion of preoperative functional status score (KPS) ≥80 in the observation group (68.42%) was lower than that in the control group (78.43%). The proportion of patients with tumor over 5 cm in the control group (27.45%) was lower than that in the observation group (52.63%), and the proportion of total resection of tumor in the control group (47.06%) was higher than that in the observation group (21.05%). Furthermore, the multivariate analysis showed that preoperative KPS score, preoperative duration of disease, resection scope, postoperative treatment, oncotesticular antigen (OY-TES-1) mRNA, P53, mouse double microbody amplification gene (MDM2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) were independent risk factors (all P < 0.05). In summary, patients with postoperative recurrence and malignant transformation had poorer physical condition and higher degree of malignancy before surgery. Preoperative KPS score, duration of disease, surgical resection scope, postoperative treatment, OY-TES-1 mRNA, P53, MDM2, VEGF, and EGFR were the risk factors.

WASH regulates the oxidative stress Nrf2/ARE pathway to inhibit proliferation and promote apoptosis of HeLa cells under the action of Jolkinolide B.

Jolkinolide B (JB), a diterpenoid compound isolated from the roots of Euphorbia fischeriana, has gained research attention for its antitumor effects. In recent years, JB reportedly displayed anti-tumor activity in solid tumors, such as breast, ovarian, and prostate cancer, and leukemia. In this study, we evaluated the effect of JB on HeLa cells with a focus on cell growth inhibition and related mechanisms. HeLa cells were cultured in vitro and divided into a blank control group, HeLa-Scramble (0, 0.25, 0.5 mM), and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) protein silenced group, HeLa-shWASH (0, 0.25, 0.5 mM). Morphological changes were observed using an inverted microscope. The inhibition rate of cell proliferation was detected using the WST-1 method. Flow cytometry Brdu+PI double standard method was used to detect cell replication ability and FITC+PI double standard method was used to detect cell apoptosis rate. Western blot was used to verify the expression of Nrf2, HO-1, WASH, Bax, Bcl-2, and PCNA. The mRNA expression of cytokines (IL-1α, IL-6, and IL-8) was detected using RT-qPCR. The results showed that JB induced cell apoptosis and arrested cells at the G2/M phase in HeLa-shWASH cells compared with HeLa-Scramble cells (P < 0.05, P < 0.01, respectively). In addition, JB upregulated IL-1α, IL-6, and IL-8 in HeLa-shWASH cells. We conclude that WASH protein participates in JB-induced regulation of the Nrf2/ARE pathway, aggravates inflammatory responses, and promotes cancer cell apoptosis, thus inhibiting the proliferation and invasion abilities of HeLa cells. JB may have anti-tumor effects and potential clinical value for the treatment of cervical cancer.