Safety and efficiency of deep brain stimulation in the elderly patients with Parkinson's disease.

AIMS: Deep brain stimulation (DBS) is not routinely performed in elderly patients (≥75 years old) to date because of concerns about complications and decreased benefit. This study aimed to evaluate the safety and efficacy of DBS in elderly patients with Parkinson's disease. METHODS: A retrospective analysis was performed using data from 40 elderly patients from four centers who were treated with neurosurgical robot-assisted DBS between September 2016 and December 2021. These patients were followed up for a minimum period of 2 years, with a subgroup of nine patients followed up for 5-7 years. Patient demographic characteristics, surgical information, pre- and postoperative motor scores, non-motor scores, activities of daily living, and complications were retrospectively analyzed. RESULTS: The mean surgical procedure duration was 1.65 ± 0.24 h, with a mean electrode implantation duration of 1.10 ± 0.23 h and a mean pulse generator implantation duration of 0.55 ± 0.07 h. The mean pneumocephalus volume, electrode fusion error, and Tao's DBS surgery scale were 16.23 ± 12.81 cm3, 0.81 ± 0.23 mm, and 77.63 ± 8.08, respectively. One patient developed a skin infection, and the device was removed. The Unified Parkinson's disease rating scale, Unified Parkinson's disease rating scale of Part III, tremor, rigidity, bradykinesia, axial, and Barthel index for activities of daily living (ADL-Barthel) scores significantly improved at the 2-year follow-up (p < 0.05). The levodopa equivalent daily dose (LEDD) was significantly reduced at the 2-year follow-up (p < 0.05). However, the Montreal cognitive assessment, Hamilton depression scale, and Hamilton anxiety scale scores did not significantly change during the 2-year follow-up (p > 0.05). Additionally, in the subgroup with a 5-year follow-up, the motor symptoms, ADL-Barthel score, and cognitive function worsened over time compared to baseline. However, there was still an improvement in motor symptoms and ADL with DBS on-stimulation compared with the off-stimulation state. The LEDD increased 5 years after surgery compared to that at baseline. Eleven patients had passed away during follow-up, the mean survival time was 38.3 ± 17.3 months after surgery, and the mean age at the time of death was 81.2 (range 75-87) years. CONCLUSION: Robot-assisted DBS surgery for the elderly patients with Parkinson's disease is accurate and safe. Motor symptoms and ADL significantly improve and patients can benefit from long-term neuromodulation, which may decrease the risk of death.

DDB2 and MDM2 genes are promising markers for radiation diagnosis and estimation of radiation dose independent of trauma and burns.

In the field of biodosimetry, the current accepted method for evaluating radiation dose fails to meet the need of rapid, large-scale screening, and most RNA marker-related studies of biodosimetry are concentrating on a single type of ray, while some other potential factors, such as trauma and burns, have not been covered. Microarray datasets that contain the data of human peripheral blood samples exposed to X-ray, neutron, and γ-ray radiation were obtained from the GEO database. Totally, 33 multi-type ray co-induced genes were obtained at first from the differentially expressed genes (DEGs) and key genes identified by weighted gene co-expression network analysis (WGCNA), and these genes were mainly enriched in DNA damage, cellular apoptosis, and p53 signaling pathway. Following transcriptome sequencing of blood samples from 11 healthy volunteers, 13 patients with severe burns, and 37 patients with severe trauma, 6635 trauma-related DEGs and 7703 burn-related DEGs were obtained. Through the exclusion method, a total of 12 radiation-specific genes independent of trauma and burns were identified. ROC curve analysis revealed that the DDB2 gene performed the best in diagnosis of all three types of ray radiation, while correlation analysis showed that the MDM2 gene was the best in assessment of radiation dose. The results of multiple-linear regression analysis indicated that such analysis could improve the accuracy in assessment of radiation dose. Moreover, the DDB2 and MDM2 genes remained effective in radiation diagnosis and assessment of radiation dose in an external dataset. In general, the study brings new insights into radiation biodosimetry.

Shikonin inhibits immune checkpoint PD-L1 expression on macrophage in sepsis by modulating PKM2.

Sepsis, a life-threatening condition whereby immune dysregulation develops, is one of the major causes of death worldwide. To date, there is still no clinically effective therapeutic method for sepsis. As a natural product from traditional Chinese medicine, Shikonin has been demonstrated to have pleiotropic medical effects, including anti-tumor, anti-inflammation, and relieving sepsis. PD-L1, as the receptor of PD-1, was also involved in exacerbating sepsis by inducing immunosuppression, but the relationship between them is still unclear. In this study, we aimed to evaluate the effect of Shikonin on modulating PD-L1 expression and its contact with PKM2. The results showed that Shikonin significantly decreased the levels of sepsis mice serum inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß) and maintain the percentage of T cells from the spleen and significantly reduce the apoptosis of splenocytes in LPS-induced sepsis mice. Our data also demonstrated that Shikonin significantly decreased PD-L1 expression on macrophages, not PD-1 expression on T cells in vivo and in vitro. Additionally, we revealed that Shikonin attenuated PD-L1 expression on macrophages and was associated with downregulating phosphorylation and nuclear import of PKM2, which could bind to the HRE-1 and HRE-4 sites of the PD-L1 promoter. As the present research was conducted in sepsis mice model and macrophage cell line, further study is required to evaluate Shikonin to regulate PD-L1 by targeting PKM2 in clinical samples.

A Modified Power-on Programming Method after Deep Brain Stimulation for Parkinson Disease.

OBJECTIVE: To explore the feasibility of using a modified power-on programming method in deep brain stimulation (DBS) for Parkinson disease (PD). METHODS: We conducted a retrospective cohort study including 151 PD patients with bilateral robot-assisted DBS surgery from July 2017 to June 2020. Ninety-seven patients were adopted to the modified power-on programming method (Group I) and 54 patients were adopted to the traditional power-on programming method (Group II). In one-year follow-up, power-on programming duration, stimulation parameters, scores of Unified PD Rating Scale (UPDRS) and UPDRS-III of the 2 groups were recorded and compared. RESULTS: There were no significant differences in the postoperative UPDRS, UPDRS-III improvement rate, and stimulation parameters between the 2 groups. The duration of power-on programming of Group I (1.7 ± 1.1 hours) was significantly less than that of Group II (3.5 ± 1.8 hours, P < 0.0001). CONCLUSIONS: The modified power-on programming method can achieve a similar clinical effect to the traditional method, with the advantage of more efficiency.

A comparative study of asleep and awake deep brain stimulation robot-assisted surgery for Parkinson's disease.

To compare the differences between asleep and awake robot-assisted deep brain stimulation (DBS) surgery for Parkinson's Disease (PD), we conducted this retrospective cohort study included 153 PD patients undergoing bilateral robot-assisted DBS from June 2017 to August 2019, of which 58 cases were performed under general anesthesia (GA) and 95 cases under local anesthesia (LA). Procedure duration, stimulation parameters, electrode implantation accuracy, intracranial air, intraoperative electrophysiological signal length, complications, and Unified PD Rating Scale (UPDRS) measurements were recorded and compared. The clinical evaluation was conducted by two raters who were blinded to the choice of anesthesia. Procedure duration was significantly shorter in the GA group, while on stimulation off medication motor scores (UPDRS-III) were significantly improved in both the GA and LA group. ANCOVA covariated for the baseline UPDRS-III and levodopa challenge exhibited no significant differences. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS power-on were similar. There were no significant differences in electrode implantation accuracy, intraoperative electrophysiological signal length, or intracerebral hemorrhage (no occurrences in either group). The pneumocephalus volume was significantly smaller in the GA group. Six patients exhibited transient throat discomfort associated with tracheal intubation in the GA group. The occurrence of surgical incision infection was similar in both groups. Compared with the awake group, the asleep group exhibited a shorter procedure duration with a similar electrode implantation accuracy and short-term motor improvement. Robot-assisted asleep DBS surgery is a promising surgical method for PD.

Sunflower seed oil combined with ginseng stem-leaf saponins as an adjuvant to enhance the immune response elicited by Newcastle disease vaccine in chickens.

The present study was to evaluate the adjuvant effect of sunflower seed oil containing saponins extracted from the stem and leaf of Panax ginseng C.A. Meyer (E515-D) on the immune response induced by an inactivated Newcastle disease virus (NDV) in chickens. The results showed that E515-D promoted significantly higher serum NDV-specific HI and neutralizing antibody responses, IFN-γ and IL-4 levels, and lymphocyte proliferative responses to Con A, LPS, and NDV antigen than the conventional adjuvant Marcol 52. Different adjuvant effect between E515-D and Marcol 52 may be attributed to different genes expressed in two groups. Transcriptome analysis of splenocytes showed that there were 1198 differentially expressed genes (DEGs) with 539 up and 659 down regulated in E515-D group while 1395 DEGs with 697 up and 698 down regulated in Marcol 52 group in comparison with the control group. Analysis of gene ontology (GO) term and kyoto encyclopedia of Genes and Genomes (KEGG) pathways showed that the predominant immune related pathways included "Toll-like receptor signaling pathway", "NOD-like receptor signaling pathway", "C-type lectin receptor signaling pathway", and "Phosphatidylinositol signaling system" in E515-D group while Marcol 52 were "NOD-like receptor signaling pathway", "Phagosome", and "Lysosome", and the most relevant DEGs in E515-D group were STAT1, STAT2, PI3K, and IL-6. Considering the excellent adjuvant activity and vegetable origin, E515-D deserves further study as an adjuvant for vaccines used in food animals.

Enhanced Immune Responses with Serum Proteomic Analysis of Hu Sheep to Foot-and-Mouth Disease Vaccine Emulsified in a Vegetable Oil Adjuvant.

Our previous study demonstrated that a vegetable oil consisting of soybean oil, vitamin E, and ginseng saponins (SO-VE-GS) had an adjuvant effect on a foot-and-mouth disease (FMD) vaccine in a mouse model. The present study was to compare the adjuvant effects of SO-VE-GS and the conventional ISA 206 on an FMD vaccine in Hu sheep. Animals were intramuscularly (i.m.) immunized twice at a 3-week interval with 1 mL of an FMD vaccine adjuvanted with SO-VE-GS (n = 10) or ISA 206 (n = 9). Animals without immunization served as control (n = 10). Blood was sampled prior to vaccination and at 2, 4, 6, and 8 weeks post the booster immunization to detect FMD virus (FMDV)-specific IgG. Blood collected at 8 weeks after the booster was used for the analyses of IgG1 and IgG2, serum neutralizing (SN) antibody, IL-4 and IFN-γ production, and proteomic profiles. The results showed that IgG titers rose above the protection level (1:128) in SO-VE-GS and ISA 206 groups after 2 and 4 weeks post the booster immunization. At 6 weeks post the booster, the ISA 206 group had 1 animal with IgG titer less than 1:128 while all the animals in the SO-VE-GS group retained IgG titers of more than 1:128. At 8 weeks post the booster, 6 of 9 animals had IgG titers less than 1:128 with a protective rate of 33.3% in the ISA 206 group, while only 1 of 10 animals had IgG titer less than 1:128 with a protective rate of 90% in the SO-VE-GS group, with statistical significance. In addition, IgG1, IgG2, SN antibodies, IL-4, and IFN-γ in the SO-VE-GS group were significantly higher than those of the ISA 206 group. Different adjuvant effects of SO-VE-GS and ISA 206 may be explained by the different proteomic profiles in the two groups. There were 39 and 47 differentially expressed proteins (DEPs) identified in SO-VE-GS compared to the control or ISA 206 groups, respectively. In SO-VE-GS vs. control, 3 immune related gene ontology (GO) terms and 8 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were detected, while 2 immune related GO terms and 5 KEGG pathways were found in ISA 206 vs. control. GO and KEGG analyses indicated that 'positive regulation of cytokine secretion', 'Th1/Th2 cell differentiation', and 'Toll-like receptor signaling pathways', were obviously enriched in the SO-VE-GS group compared to the other groups. Coupled with protein-protein interaction (PPI) analysis, we found that B7TJ15 (MAPK14) was a key DEP for SO-VE-GS to activate the immune responses in Hu sheep. Therefore, SO-VE-GS might be a promising adjuvant for an FMD vaccine in Hu sheep.

Comparison of Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation Surgery on Parkinson Disease-Related Pain.

OBJECTIVE: To analyze and compare the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) and globus pallidus internus (GPi)-DBS on Parkinson disease (PD)-related pain. METHODS: A retrospective study was performed of 64 patients (28 who underwent GPi-DBS and 36 who underwent STN-DBS) with PD-related pain in our hospital between January 2017 and July 2019. A numerical rating scale (NRS) was used to evaluate the degree of pain preoperatively and 4 months after operation, and the unified PD scale III (UPDRS-III) was completed simultaneously to assess motor symptoms. RESULTS: The average NRS score of all 64 patients after surgery was 1.09 ± 1.39, which was significantly lower than that before operation (4.44 ± 1.67; P < 0.0001). The improvement rate of NRS was 75 ± 27% in the 28 GPi-DBS patients and 79 ± 27% in the 36 STN-DBS patients, with no significant difference (P = 0.577). The improvements in NRS and UPDRS-III were significantly correlated in the STN-DBS group (r = 0.3707, P = 0.026) but not significantly correlated in the GPi-DBS group (P = 0.516). CONCLUSIONS: Both GPi-DBS and STN-DBS were effective for analyzing PD-related pain and seemed to have similar efficacy. This study provides an important first-step toward determining different DBS targets for controlling PD-related pain. Follow-up prospective research is an appropriate next step on the path to multicenter clinical trials.

Assessment of Deep Brain Stimulation Implantation Surgery: A Practical Scale.

BACKGROUND: Patients requiring deep brain stimulation (DBS) will undergo extensive preoperative and postoperative evaluations. However, the field lacks a robust scoring system for quantifying the outcomes of DBS surgery. We sought to determine whether a practical scale could assess the outcomes of DBS surgery and the clinical significance. METHODS: A retrospective study was performed of the data from 150 patients who had undergone DBS from February 2017 to February 2019. An independence analysis and multivariate testing were used to identify significant independent predictors. The scale scores were computed by summing across the weighted predictors. The correlation between the scale scores and the intraoperative electrophysiological signal length (IESL), DBS power-on voltage, improvement rate in the unified Parkinson disease rating scale (UPDRS) and UPDRS part III (UPDRS III) scores was analyzed. Receiver operating characteristics curve analysis was used to quantify the discriminative capacity of the scale for predicting the prognosis. RESULTS: Listwise exclusion of patients with incomplete data sets yielded a final sample of 130 patients with Parkinson disease who had undergone bilateral DBS. Multivariate testing identified 3 independent predictors of the prognosis, including electrode implantation duration, postoperative pneumocephalus volume, and electrode fusion error. The scale scores correlated significantly with the subthalamic nucleus DBS power-on voltage (r = -0.4063; P < 0.0001), globus pallidus internus DBS power-on voltage (r = -0.4723; P = 0.0014), and improvement rate of the UPDRS (r = 0.3490; P < 0.0001) and UPDRS III (r = 0.6623; P < 0.0001) scores. However, the scale scores did not significantly correlate with the subthalamic nucleus IESL and globus pallidus internus IESL. Receiver operating characteristics curve analysis revealed impressive outcome discrimination for the UPDRS and UPDRS III scores (UPDRS: area under the curve, 0.62, P = 0.0219; UPDRS III: area under the curve, 0.85, P < 0.0001). CONCLUSIONS: We have introduced a novel practical scale capable of assessing the outcomes of DBS surgery and predicting the prognosis of patients after DBS surgery.

Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant.

The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-ß1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.

The polysaccharide from the roots of Actinidia eriantha activates RAW264.7 macrophages via regulating microRNA expression.

The polysaccharide from the roots of Actinidia eriantha (AEPS), a potent antitumor agent and immunological adjuvant, has been previously reported to activate RAW264.7 macrophages via TLRs/NF-κB signaling. The objective of this study was to investigate microRNA (miRNA) expression profiles and explore the role of miRNAs in AEPS-activated RAW264.7 cells using microarray assay and specific inhibitor. AEPS induced 82 differentially expressed miRNAs including 43 up-regulated and 39 down-regulated in RAW264.7 cells. A set of 11 differentially expressed miRNAs and their 62 target mRNAs were predicted to involve in activation of RAW264.7 cell induced by AEPS based on computational databases and validated reports. miR-155 inhibitor significantly down-regulated the mRNA expression of proinflammatory factors (IL-1ß, IL-6, COX-2 and NOS2), and blocked the production of NO in RAW264.7 cell induced by AEPS. The expression of accessory and costimulatory molecules (CD80, CD86, MHC I and MHC II) in AEPS-activated RAW264.7 cells was also remarkably reduced by miR-155 inhibitor. These results suggested that AEPS may induce macrophage activation through regulating miRNAs expression such as miR-155. This study further expanded current knowledge on the mechanisms of plant polysaccharides.

Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease is a major health problem worldwide. Resveratrol is a natural polyphenol found in edible plants that has a variety of biochemical and physiological effects. AIMS: To evaluate the effect of resveratrol on insulin resistance, glucose and lipid metabolism in non-alcoholic fatty liver disease. METHODS: Double-blind, randomized, placebo-controlled trial: 60 subjects with non-alcoholic fatty liver disease were given 2 placebo capsules (placebo group) or 2 150mg resveratrol capsules (resveratrol group) twice daily for three months. Liver ultrasound imaging, anthropometric profile, serum liver enzymes, insulin, glucose, C-peptide, lipid profile, and inflammation-related cytokines were compared pre and post-treatment. RESULTS: Compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol [-6.00 (-9.00, -3.00) IU/L, -0.64±0.31mmol/L, and -0.41±0.35mmol/L, respectively, P≤0.001] alanine aminotransferase, total cholesterol [-7.00 (-11.0, -2.50) IU/L and -0.67±0.50mmol/L, respectively, P=0.002], and homeostasis model assessment insulin resistance index (-0.60±1.15, P=0.016). In the resveratrol group significant reductions of the levels of tumour necrosis factor-alpha, cytokeratin 18 fragment, and fibroblast growth factor 21 [-0.53±1.30pg/mL, -26.9 (-70.3, 5.12) IU/L and -23.3 (-43.0, 0.31) pg/mL, respectively, P<0.05] and elevation of adiponectin level [1.22 (-0.37, 1.60) ng/mL, P=0.025] were observed. CONCLUSION: Resveratrol supplementation may benefit patients with non-alcoholic fatty liver disease.