Reorganization of motor network in patients with Parkinson's disease after deep brain stimulation.

AIMS: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis. METHODS: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated. RESULTS: The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. CONCLUSION: The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.

The severity assessment of Parkinson's disease based on plasma inflammatory factors and third ventricle width by transcranial sonography.

BACKGROUND: Predicting Parkinson's disease (PD) can provide patients with targeted therapies. However, disease severity can be roughly evaluated in clinical practice based on the patient's symptoms and signs. OBJECTIVE: The current study attempted to explore the factors linked with PD severity and construct a predictive model. METHOD: The PD patients and healthy controls were recruited from our study center while recording their basic demographic information. The serum inflammatory markers levels, such as Cystatin C (Cys C), C-reactive protein (CRP), RANTES (regulated on activation, normal T cell expressed and secreted), Interleukin-10 (IL-10), and Interleukin-6 (IL-6) were determined for all the participants. PD patients were categorized into early and mid-advanced groups based on the Hoehn and Yahr (H-Y) scale and evaluated using PD-related scales. LASSO logistic regression analysis (Model C) helped select variables based on clinical scale evaluations, serum inflammatory factor levels, and transcranial sonography measurements. The optimal harmonious model coefficient λ was determined via 10-fold cross-validation. Moreover, Model C was compared with multivariate (Model A) and stepwise (Model B) logistic regression. The area under the curve (AUC) of a receiver operator characteristic (ROC), brier score, calibration curve, and decision curve analysis (DCA) helped determine the discrimination and calibration of the predictive model, followed by configuring a forest plot and column chart. RESULTS: The study included 113 healthy individuals and 102 PD patients, with 26 early and 76 mid-advanced patients. Univariate analysis of variance screened out statistically significant differences among inflammatory markers Cys C and RANTES. The average Cys C level in the mid-advanced stage was significantly higher than in the early stage (p < 0.001) but not for RANTES (p = 0.740). The LASSO logistic regression model (λ.1se = 0.061) associated with UPDRS-I, UPDRS-II, UPDRS-III, HAMA, PDQ-39, and Cys C as the included independent variables revealed that the Model C discrimination and calibration (AUC = 0.968, Brier = 0.049) were superior to Model A (AUC = 0.926, Brier = 0.079) and Model B (AUC = 0.929, Brier = 0.071) models. CONCLUSION: The study results show multiple factors are linked with PD assessment. Moreover, the inflammatory marker Cys C and transcranial sonography measurement could objectively predict PD symptom severity, helping doctors monitor PD evolution in patients while targeting interventions.

The guiding effect of local field potential during deep brain stimulation surgery for programming in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. METHODS: Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker-guided programming groups and compared the outcomes. RESULTS: In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio-guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS-III. There were no significant differences in the IR of UPDRS-III, post-LED, IR-PDQ39, number of programmings, and the contact change rate between the gamma oscillations-guided programming and empirical programming groups. CONCLUSION: Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement.

Bilateral globus pallidus interna deep brain stimulation in the treatment of mixed cerebral palsy in ataxia with dyskinesia: a case report.

Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time.

Deep brain stimulation improves central nervous system inflammation in Parkinson's disease: Evidence and perspectives.

BACKGROUND: In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD. METHODS: We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed. RESULTS: RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs  = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1  = 0.644, p = 0.033 and rs2  = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels. CONCLUSION: The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

Effect of deep brain stimulation compared with drug therapy alone on the progression of Parkinson's disease.

Background: Parkinson's disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD. Objective: The aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD. Methods: A total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient's annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage. Results: The UPDRS-III score of the patients in the "off" state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients' psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G. Conclusion: PD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient's motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.

Altered brain network centrality in Parkinson's disease patients after deep brain stimulation: a functional MRI study using a voxel-wise degree centrality approach.

OBJECTIVE: After deep brain stimulation (DBS), patients with Parkinson's disease (PD) show improved motor symptoms and decreased verbal fluency, an effect that occurs before the initiation of DBS in the subthalamic nucleus. However, the underlying mechanism remains unclear. This study aimed to evaluate the effects of DBS on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients. METHODS: The authors obtained resting-state functional MRI data of 28 PD patients before and after DBS surgery. All patients underwent MRI scans in the off-stimulation state. The DC method was used to evaluate the effects of DBS on whole-brain FC at the voxel level. Seed-based FC analysis was used to examine network function changes after DBS. RESULTS: After DBS surgery, PD patients showed significantly weaker DC values in the left middle temporal gyrus, left supramarginal gyrus, and left middle frontal gyrus, but significantly stronger DC values in the midbrain, left precuneus, and right precentral gyrus. FC analysis revealed decreased FC values within the default mode network (DMN). CONCLUSIONS: This study demonstrated that the DC of DMN-related brain regions decreased in PD patients after DBS surgery, whereas the DC of the motor cortex increased. These findings provide new evidence for the neural effects of DBS on voxel-based whole-brain networks in PD patients.

Mouse Bone Marrow Mesenchymal Stem Cells Inhibit Sepsis-Induced Lung Injury in Mice via Exosomal SAA1.

Sepsis is a global disease burden, and approximately 40% of cases develop acute lung injury (ALI). Bone marrow mesenchymal stromal cells (BMSCs) and their exosomes are widely used in treating a variety of diseases including sepsis. As an acute phase protein, serum amyloid A1 (SAA1) regulates inflammation and immunity. However, the role of SAA1 in BMSCs-exosomes in septic lung injury remains to be elucidated. Exosomes derived from serum and BMSCs were isolated by ultracentrifugation. SAA1 was silenced or overexpressed in mouse BMSCs using lentiviral plasmids, containing either SAA1-targeting short interfering RNAs or SAA1 cDNA. Sepsis was induced by cecal ligation and puncture (CLP). LPS was used to induce ALI in mice. Mouse alveolar macrophages were isolated by flow cytometry. Levels of SAA1, endotoxin, TNF-α, and IL-6 were measured using commercial kits. LPS internalization was monitored by immunostaining. RT-qPCR or immunoblots were performed to test gene and protein expressions. Serum exosomes of patients with sepsis-induced lung injury had significantly higher levels of SAA1, endotoxin, TNF-α, and IL-6. Overexpression of SAA1 in BMSCs inhibited CLP- or LPS-induced lung injury and decreased CLP- or LPS-induced endotoxin, TNF-α, and IL-6 levels. Administration of the SAA1 blocking peptide was found to partially inhibit SAA1-induced LPS internalization by mouse alveolar macrophages and reverse the protective effect of SAA1. In conclusion, BMSCs inhibit sepsis-induced lung injury through exosomal SAA1. These results highlight the importance of BMSCs, exosomes, and SAA1, which may provide novel directions for the treatment of septic lung injury.

Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice.

Excessive iron released by hemoglobin and necrotic tissues is the predominant factor that aggravates the outcome of traumatic brain injury (TBI). Regulating the levels of iron and its metabolism is a feasible way to alleviate damage due to TBI. However, the spatial-temporal iron metabolism and iron deposition in neurons and glial cells after TBI remains unclear. In our study, male C57BL/6 mice (8-12 weeks old, weighing 20-26 g) were conducted using controlled cortical impact (CCI) models, combined with treatment of iron chelator deferoxamine (DFO), followed by systematical evaluation on iron deposition, cell-specific expression of iron metabolic proteins and ferroptosis in ipsilateral cortex. Herein, ferroptosis manifest by iron overload and lipid peroxidation was noticed in ipsilateral cortex. Furthermore, iron deposition and cell-specific expression of iron metabolic proteins were observed in the ipsilateral cortical neurons at 1-3 days post-injury. However, iron overload was absent in astrocytes, even though they had intense TBI-induced oxidative stress. In addition, iron accumulation in oligodendrocytes was only observed at 7-14 days post-injury, which was in accordance with the corresponding interval of cellular repair. Microglia play significant roles in iron engulfment and metabolism after TBI, and excessive affects the transformation of M1 and M2 subtypes and activation of microglial cells. Our study revealed that TBI led to ferroptosis in ipsilateral cortex, iron deposition and metabolism exhibited cell-type-specific spatial-temporal changes in neurons and glial cells after TBI. The different effects and dynamic changes in iron deposition and iron metabolism in neurons and glial cells are conducive to providing new insights into the iron-metabolic mechanism and strategies for improving the treatment of TBI.

The Effects of Different Anesthesia Methods on the Treatment of Parkinson's Disease by Bilateral Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) surgery for Parkinson's disease (PD) is routinely performed at medical centers worldwide. However, it is debated whether general anesthesia (GA) or traditional local anesthetic (LA) is superior. Purpose: This study aims to compare the effects of LA and GA operation methods on clinical improvement in patients with PD, such as motor and non-motor symptoms, after STN-DBS surgery at our center. Method: A total of 157 patients with PD were retrospectively identified as having undergone surgery under LA (n = 81) or GA (n = 76) states. In this study, the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III) in three states, levodopa-equivalent-daily-dose (LEDD), surgical duration, intraoperative microelectrode recording (iMER) signal length, postoperative intracranial volume, electrode implantation error, neuropsychological function, quality of life scores, and complication rates were collected and compared. All patients with PD were routinely followed up at 6, 12, 18, and 24 months postoperatively. Result: Overall improvement in UPDRS-III was demonstrated at postoperative follow-up, and there was no significant difference between the two groups in medication-off, stimulation-off state and medication-off, stimulation-on state. However, UPDRS-III scores in medication-on, stimulation-on state under GA was significantly lower than that in the LA group. During postoperative follow-up, LEDD in the LA group (6, 12, 18, and 24 months, postoperatively) was significantly lower than in the GA group. However, there were no significant differences at baseline or 1-month between the two groups. The GA group had a shorter surgical duration, lower intracranial volume, and longer iMER signal length than the LA group. However, there was no significant group difference in electrode implantation accuracy and complication rates. Additionally, the Hamilton Anxiety Scale (HAMA) was significantly lower in the GA group than the LA group at 1-month follow-up, but this difference disappeared at longer follow-up. Besides, there was no significant group difference in the 39-item Parkinson's Disease Questionnaire (PDQ-39) scale scores. Conclusion: Although both groups showed overall motor function improvement without a significant postoperative difference, the GA group seemed superior in surgical duration, intracranial volume, and iMER signal length. As the accuracy of electrode implantation can be ensured by iMER monitoring, DBS with GA will become more widely accepted.

Rapid fingerprint analysis based on supercritical fluid chromatography for quality evaluation of Hedyotis diffusa.

In this study, quality evaluations of Hedyotis diffusa (H. diffusa) batches by rapid fingerprint analysis based on supercritical fluid chromatography (SFC) were accomplished. Abundant chemical components of H. diffusa were effectively extracted by optimal supercritical fluid extraction conditions (20 % MeOH as modifier, 45 °C, 300 bar and 60 min). Then, the extract was separated by SFC on a Torus 1-AA column (100 × 3.0 mm i.d., 1.7 µm) within 10 min by gradient elution increasing from 5 % to 45 % modifier (MeOH containing 0.05 % TFA) at 1.2 mL/min, 30 °C and 2000 psi. The SFC approach exhibited short analysis time, while maintaining good peak shape and resolution. Seven major compounds were further identified by SFC coupled with tandem mass spectrometer to be phenylpropanoid, iridoids and anthraquinones. Finally, fingerprint analysis of 10 batches of H. diffusa by the developed SFC method was accomplished. The similarity values were between 0.894 and 0.968, indicating quality differences of H. diffusa from depending on origin and harvest year exist. The result demonstrates the feasibility of the SFC in batch quality evaluation of H. diffusa.

Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report.

Background and Importance: Deep brain stimulation (DBS) has been approved to treat a variety of movement disorders, including Parkinson's disease (PD), essential tremor, and dystonia. Following the DBS surgery, some perioperative and even delayed complications due to intracranial and hardware-related events could occur, which may be life-threatening and require immediate remedial measures. Clinical Presentation: We report a case of an older woman with advanced PD who developed the unique complication of unilateral cyst formation at the tip of the DBS electrode after undergoing bilateral placement of subthalamic nucleus DBS. After a period of controlled motor symptoms, the patient showed new neurological deficits related to right peri-lead edema. However, the new neurological symptoms regressed quickly over several days with stereotactic implantation of a puncture needle to drain the cyst fluid without removing the affected lead. Conclusion: The occurrence of an intraparenchymal cyst following DBS surgery is a rare but life-threatening complication that could relate to edema around the electrodes or cerebrospinal fluid tracking. Stereotactic aspiration makes the intracranial cyst regress safely and effectively and ensures that the electrode is in the optimal position of the target nucleus to achieve an effective DBS surgery.

LncRNA SCIRT is downregulated in atherosclerosis and suppresses the proliferation of human aortic smooth muscle cells (HAOSMCs) by sponging miR-146a in cytoplasm.

BACKGROUND: SCIRT has been characterized as a key player in cancer biology, while its role in other human diseases is unclear. This study explored its role in atherosclerosis, with a specific focus on its interaction with SCIRT and miR-146a. METHODS: The expression of SCIRT and miR-146a in atherosclerosis-affected tissues and healthy tissues from 56 atherosclerosis patients were analyzed by RT-qPCR. The expression of SCIRT in nuclear and cytoplasm samples was detected by RNA fractionation assay. The direct interaction between SCIRT and miR-146a was detected by RNA pull-down assay. SCIRT and miR-146a were overexpressed in human aortic smooth muscle cells (HAOSMCs) to study the crosstalk between them. The role of SCIRT and miR-146a in the proliferation of HAOSMCs was analyzed with BrdU assay. RESULTS: SCIRT was downregulated by atherosclerosis, while miR-146a was upregulated by atherosclerosis. SCIRT was detected in both cytoplasm and nuclear samples, and it directly interacted with miR-146a. In HAOSMCs, overexpression of SCIRT and miR-146a did not affect the expression of each other. Interestingly, SCIRT suppressed the proliferation of HAOSMCs and reduced the enhancing effects of miR-146a on cell proliferation. CONCLUSION: Therefore, SCIRT is downregulated in atherosclerosis and it suppresses the proliferation of HAOSMCs by sponging miR-146a in cytoplasm.

Altered Spontaneous Neural Activity and Functional Connectivity in Parkinson's Disease With Subthalamic Microlesion.

BACKGROUND: Transient improvement in motor symptoms are immediately observed in patients with Parkinson's disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood. PURPOSE: We utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS. METHOD: Overall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients. RESULT: Relative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN). CONCLUSION: The subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.

Evaluation of efficacy and safety of PARP inhibitors in breast cancer: A systematic review and meta-analysis.

BACKGROUND: Many breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy. METHODS: A comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients. RESULTS: Six RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56-0.74), OS (HR, 0.86; 95% CI, 0.73-1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05-1.82). PARPi, however, significantly increased risk of grade 3-4 thrombocytopenia (RR, 1.63; 95% CI, 1.06-2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52-0.79). CONCLUSIONS: PARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3-4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment.

Heat stress decreases egg production of laying hens by inducing apoptosis of follicular cells via activating the FasL/Fas and TNF-α systems.

Heat stress (HS) causes significant economic losses in the poultry industry every year. However, the mechanisms for the adverse effects of HS on avian follicular development are largely unknown. The aim of this study was to test whether HS induces apoptosis of follicular cells and impairs egg production by activating the FasL/Fas and tumor necrosis factor (TNF)-α systems. To this end, Hy-Line Brown laying hens, at 32 wk of age, were either exposed to HS of 35°C to 37°C or maintained at 24°C to 26°C (control) for 5 D. At the end of the HS period, follicle numbers, apoptosis, FasL/Fas and TNF-α activation, oxidative stress, and hormone secretion were examined in ovarian follicles. Egg production was observed daily during both the stressed (day S1-S5) and the poststress recovery (day R1-R15) periods. The results demonstrated that HS on hens significantly 1) decreased laying rates from day S3 to R6; 2) reduced numbers of large yellow and hierarchical follicles; 3) triggered apoptosis while increasing the expression of FasL, Fas, TNF-α, and TNF-receptor 1 in small and large yellow follicles; and 4) increased levels of oxidative stress, corticotrophin-releasing hormone, and corticosterone while decreasing the estradiol/progesterone ratio in follicular fluid in small and large yellow follicles. Taken together, the results suggested that hen HS impaired egg production by reducing the number of follicles through inducing apoptosis and that it triggered apoptosis in follicular cells by activating the FasL/Fas and TNF-α systems.

TRIM3 attenuates apoptosis in Parkinson's disease via activating PI3K/AKT signal pathway.

This article aims to study tripartite motif-containing protein 3 (TRIM3) effects on Parkinson's disease (PD). TRIM3 expression in venous blood of PD patients was detected by qRT-PCR. PD mouse model and PD SH-SY5Y cell model were constructed. PD cells were treated by LY294002 (a PI3K inhibitor). The apoptosis of PD mouse midbrain was detected. Glutathione (GSH) and superoxide dismutase (SOD) level in PD cells and mice midbrain was analyzed. Intracellular reactive oxygen species (ROS) and MMP were detected. The effect of TRIM3 on cell viability, apoptosis and PI3K/AKT signal pathway were analyzed. As a result, TRIM3 expression in venous blood of PD patients was decreased. TRIM3 up-regulation in PD mouse decreased midbrain tissues apoptosis. TRIM3 up-regulation increased GSH and SOD levels in PD mice midbrain tissues and PD cells. TRIM3 up-regulation in PD cells prominently reduced ROS and MMP. TRIM3 up-regulation increased PD cells viability and decreased apoptosis. TRIM3 up-regulation in PD cells elevated Bcl-2 protein expression and weakened Bax, Cleaved-caspase 3 and Cleaved-caspase 9 proteins expression. TRIM3 up-regulation increased p-PI3K/PI3K and p-AKT/AKT ratio. PI3K inhibitor treatment reversed the inhibitory effect of TRIM3 up-regulation on PD cells apoptosis. Thus, TRIM3 might attenuate apoptosis in PD via activating PI3K/AKT signal pathway.

Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide­induced acute lung injury.

Mechanical ventilation (MV) and lipopolysaccharide (LPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (LPS)­induced acute lung injury (ALI). Gene expression data of adult C57BL/6 mice with ALI induced by inhaling LPS, MV and LPS + MV were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) associated with MV, LPS and LPS + MV were screened, followed by functional enrichment analysis, protein­protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription­quantitative PCR. A total of 63, 538 and 1,635 DEGs were associated with MV, LPS and LPS + MV, respectively. MV­associated genes were significantly enriched in the 'purine ribonucleotide metabolic process'. LPS and LPS + MV­associated genes were significantly enriched in 'cellular response to cytokine stimulus' and 'cell chemotaxis'. All three conditions were enriched in 'TNF signaling pathway' and 'IL­17 signaling pathway'. Expression levels of C­X­C motif chemokine ligand (CXCL)2, CXCL3 and CXCL10 were upregulated in the LPS and LPS + MV groups. Adenosine A2b receptor, zinc finger and BTB domain­containing 16 and hydroxycarboxylic acid receptor 2 were identified as DEGs in the MV group. Compared with the control group, Early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV­ and LPS­induced ALI, and MV may enhance the effects of LPS on gene expression. MV may affect urine ribonucleotide metabolic­related processes, whereas LPS may cause cell chemotaxis and cytokine stimulus responses in ALI progression. The inflammatory response was shared by MV and LPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ALI.

Can the Executive Control Network be Used to Diagnose Parkinson's Disease and as an Efficacy Indicator of Deep Brain Stimulation?

OBJECTIVE: The aim of this work was to investigate whether there are differences in the executive control network (ECN) between patients with Parkinson's disease (PD) before and after deep brain stimulation (DBS) surgery and to explore how deep brain stimulation (DBS) surgery affects ECN connectivity in patients with PD. METHODS: Resting-state magnetic resonance imaging (MRI) data were obtained from 23 patients with Parkinson's disease preoperatively (pre-PD) and postoperatively (post-PD) and 14 normal controls (CN). The right dorsolateral prefrontal cortex (DLPFC) was used as the seed region of interest (ROI) to study the characteristics of the functional connectivity of the ECN in these subjects. RESULTS: There were differences in the ECN among PD patients before and after surgery and between the CN. Compared with the CN group, the pre-PD patients showed significantly reduced functional connectivity (FC) between the DLPFC and the left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior parietal gyrus, right posterior central gyrus, right precuneus, and right inferior frontal gyrus. Compared to the CN group, the post-PD patients showed significantly reduced FC between the DLPFC and left inferior frontal gyrus, left precuneus, left cerebellum posterior lobe, right middle frontal gyrus, right inferior frontal gyrus, and right parietal lobule. There is no difference in the ECN between the pre-PD patients and the post-PD patients. CONCLUSIONS: The FC of ECN in PD patients was different from that in normal controls, but the FC of the ECN in patients with PD may not be altered by DBS. This suggests that the ECN may be considered an imaging biomarker for the identification of PD but may not be a good imaging biomarker for the evaluation of DBS efficacy.

Proteomics and bioinformatics approaches for the identification of plasma biomarkers to detect Parkinson's disease.

The aim of the present study was to screen for biomarkers of Parkinson's disease (PD) using proteomics and bioinformatics approaches. PD patients were divided into three groups: Those without surgery (PD1 group); those who had undergone deep brain stimulation (DBS) surgery without electrode stimulation (PD2 group); and those who had undergone DBS surgery with 1 month of electrode stimulation (PD3 group). The non-Parkinson control group (CK group) was also involved. Quantitative proteomic analysis of human sera was performed through the use of tandem mass tag markers and liquid chromatography-mass spectrometry (LC-MS)-based techniques. For the proteins with quantitative information, a systematic bioinformatics analysis was then performed, including protein annotation, functional classification, functional enrichment and cluster analysis based on functional enrichment. Of the 739 proteins identified, quantitative information was available for 644. With regard to differential expression, 18 upregulated and 21 downregulated proteins were screened in the PD1/CK comparison group; 12 upregulated and 12 downregulated proteins in the PD2/PD1 comparison group; and 16 upregulated and 19 downregulated proteins in the PD3/PD2 comparison group. Coiled-coil domain-containing protein 154 (CCDC154) and tripartite motif-containing protein 3 (TRIM3) were key proteins involved in the molecular mechanisms of PD, participating in intracellular vesicle, ubiquitin protein ligase and transition metal ion-binding activities. After DBS surgery, desert hedgehog protein (DHH) was downregulated, whereas neuropilin-2 (NRP2) was upregulated; these participated in the ensheathment of neurons and the semaphorin receptor complex, respectively. The expression level of chloride intracellular channel protein 1 (CLIC1) was increased after 1 month of electrode stimulation following DBS. By combining proteomic approaches and LC-MS methods, significant proteins including CCDC154, TRIM3, DHH, NRP2 and CLIC1 were detected with high specificity and sensitivity. These may be used as novel biomarkers for early diagnosis of PD and the future development of treatments.