Background: DBS has been shown to significantly affect motor symptoms in Parkinson's disease (PD). However, some studies have suggested that it may have adverse effects on patients' neurocognitive function. To clarify this operation's effect on neurocognitive function, we collected studies containing neurocognitive function evaluation for qualitative and quantitative analysis.Methods: We searched relevant clinical studies through Pubmed and Embase databases and extracted and sorted out information such as sample size, post-operative scores, pre-operative and post-operative evaluation interval, PD course, and exclusion criteria, from articles meeting the standards. The magnitude and variance of the DBS group's combined effects and the drug therapy group in each neurocognitive domain were calculated and analyzed by the random-effects model.Results: Compared with the drug treatment group, the verbal fluency of patients in the experimental group was significantly decreased at least moderately (ES = −0.553), in which the phonemic fluency declines greatly (ES = −0.842), learning and memory ability was slightly decreased (ES = −0.305), and other neurocognitive functions were not significantly decreased.Conclusion: STN-DBS can affect verbal fluency and damage learning and memory. There was no significant correlation between the above effects and disease progression itself, and it was more likely to be associated with STN-DBS. It is suggested that post-operative patients should be trained and evaluated regularly for their verbal fluency and learning and memory ability. The safety of STN-DBS is acceptable for the majority of patients with motor symptoms.

Previous investigations have demonstrated FN400 and LPC, 2 event-related potential old/new effects that respectively reflect familiarity- and recollection-based processes in memory. However, it is unclear whether these effects are susceptible to processing fluency, particularly different types of processing fluency. To address this issue, applying a masked priming paradigm, we conducted an event-related potential experiment by manipulating semantic relations between the prime and the target as identical (reflecting perceptual fluency), thematically and taxonomically related (referring to conceptual fluency), and unrelated. A remember/know (R/K) judgment task in the test phase was used to distinguish familiarity- and recollection-based processes. Behaviorally, both task performance and response speed were modulated by the variables of priming condition, item type, and response type. All 4 priming conditions elicited significant FN400 and LPC. Compared with the K response, the R response was more relevant to the recollection-based processes reflected by LPC. Both FN400 and LPC were modulated by whether there was a response of R, K, or new. The former was susceptible only to conceptual fluency, and the latter was sensitive to both perceptual fluency and conceptual fluency, which offered telling evidence for the dual process model. Considerations for future investigations are proposed. See supplemental materials here: https://www.press.uillinois.edu/journals/ajp/media/evidence_in_remember_know_paradigm/

Background Cervical cancer is the fourth most commonly diagnosed malignant neoplasm among women worldwide. Despite improvements in treatment, the rate of postoperative metastasis remains a problem. Nomograms have been used to predict risk of tumor metastasis. We designed a nomogram to predict postoperative distant metastasis among cervical cancer patients, based on the SEER database, and estimated the performance of the nomogram by internal and external validations. Material/Methods We included 6421 participants and divided them into training (n=4495) and testing (n=1926) sets. Multivariate logistic regression was used to explore predictors. The nomogram’s predictive value was assessed by internal (testing set) and external (561 Chinese patients) validations. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) value was calculated to evaluate the nomogram’s discrimination. The nomogram’s calibration was assessed via the Hosmer-Lemeshow test and calibration curve. Results Histologic type, T stage, treatment, tumor size, and positive lymph node were identified as independent predictors of postoperative distant metastasis in surgical patients ( P <0.05). The developed nomogram had an AUC of 0.866 (95% CI: 0.844 to 0.888). The AUC and the chi-square for the Hosmer-Lemeshow test of the nomogram were 0.847 (95% CI: 0.807 to 0.888) and 11.292, respectively, ( P >0.05) in the internal validation, and were 0.626 (95% CI: 0.548 to 0.704) and 316.53, respectively, ( P <0.05) in the external validation. Conclusions Our nomogram showed a good predictive performance for postoperative distant metastasis in cervical cancer patients based on the SEER database. It remains to be determined if it is applicable to other populations.

Purpose: Chordoma is a rare malignant bone tumor transformed from the remnants of notochord. It is characterized as highly aggressive and locally invasive, difficult to be completely removed by surgery, and has a poor clinical prognosis. Glycogen synthase kinase 3 beta (GSK-3β) is involved in many cellular processes. GSK-3β overexpression has been shown to promote the development of many cancers, according to previous studies. However, the role of GSK-3β in chordoma remains unclear. Methods: Immunohistochemistry (IHC) and Western blotting (WB) were performed on clinical specimens to measure GSK-3β expression in chordoma, and immunofluorescence and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to examine the expression of GSK-3β and P21 in cell lines. Cell proliferation was detected by the CCK-8 assay and colony formation analysis, cell migration and invasion checked by Transwell experiments, and cell apoptosis was determined by Annexin V/propidium iodide staining. P21 was predicted as a downstream target gene of GSK-3β using STRING and UNIHI databases. Moreover, we used immunoprecipitation to confirm that GSK-3β and P21 interacted with each other. The double luciferase reporter gene assay showed that GSK-3β could regulate the promoter activity of P21. Finally, the role of the GSK-3β -P21 pathway in chordoma tumorigenesis was analyzed in vivo in nude mice. Results: Our study showed that GSK-3β was significantly higher in chordoma tissues than in paracancer tissues, and siRNA knockdown of GSK-3β inhibited chordoma cell proliferation and promoted cell apoptosis. Additionally, our research found that GSK-3β bound and downregulated the expression of the P21 gene, and the expression of silencing P21 partially reversed the inhibitory effect of knockdown GSK-3β on chordoma. Furthermore, xenografts showed that knockdown GSK-3β inhibited the formation of chordomas in vivo. Conclusion:Our results indicated that the GSK-3β-P21 axis may be an important signaling pathway for the occurrence and development of chordoma, providing a new therapeutic target for the clinical treatment of this disorder.

BackgroundObservation studies have confirmed the association between the gut microbiome and reproductive endocrine diseases (REDs), namely, polycystic ovary syndrome (PCOS), endometriosis, and female infertility. However, their association has never been confirmed by a two-sample Mendelian randomization (MR) analysis.MethodsWe conducted a two-sample MR analysis to evaluate the relationship between the gut microbiome and the three aforementioned REDs. In order to get more comprehensive results, two different thresholds were adopted to select instrumental variables (IVs): one was a locus-wide significance threshold (P &lt;1.0×10–5) and the other was a genome-wide significance level (P&lt; 5×10-8). Summary-level statistics for the gut microbiome and REDs were collected from public databases. Inverse-variance weighted (IVW) was the main method used to estimate causality, and sensitivity analyses were conducted to validate the MR results.ResultsAt the locus-wide significance level, we identified that the genera Streptococcus (OR=1.52, 95%CI: 1.13-2.06, P=0.006) and RuminococcaceaeUCG005 (OR=1.39, 95%CI: 1.04-1.86, P=0.028) were associated with a high risk of PCOS, while Sellimonas (OR= 0.69, 95%CI: 0.58-0.83, P=0.0001) and RuminococcaceaeUCG011(OR=0.76, 95%CI: 0.60-0.95, P=0.017) were linked to a low PCOS risk. The genus Coprococcus2 (OR=1.20, 95%CI: 1.01-1.43, P=0.039) was correlated with an increased risk of female infertility, while Ruminococcus torques (OR=0.69, 95%CI: 0.54-0.88, P=0.002) were negatively associated with the risk of female infertility. The genera Olsenella (OR= 1.11, 95%CI: 1.01-1.22, P=0.036), Anaerotruncus (OR= 1.25, 95%CI: 1.03-1.53, P=0.025), and Oscillospira (OR= 1.21, 95%CI: 1.01-1.46, P=0.035) were linked to a high risk of endometriosis. However, the results showed that the gut microbiome did not possess a causal link with REDs risk based on the genome-wide significance level. Sensitivity analyses further confirmed the robustness of the MR results.ConclusionOur study provides evidence that gut microbiome is closely related with REDs. Subsequent studies should be conducted to promote microbiome-orientated therapeutic strategies for managing REDs.