[Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation].

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer, by X. Yu, Z.-L. Wang, C.-L. Han, M.-W. Wang, Y. Jin, X.-B. Jin, Q.-H. Xia, published in Eur Rev Med Pharmacol Sci 2019; 23 (22): 9814-9820-DOI: 10.26355/eurrev_201911_19544-PMID 31799648" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19544.

LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.

OBJECTIVE: Recent studies have revealed that long noncoding RNAs (lncRNAs) are dysregulated in malignant tumors and participates in carcinogenesis. The purpose of our study was to uncover the mechanisms underlying lncRNA CASC15 in bladder cancer (BLCA). PATIENTS AND METHODS: In this research, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect cancer susceptibility candidate 15 (CASC15) expression in BLCA samples and cells. Besides, the wound healing assay and transwell assay were performed in BLCA cells after CASC15 was knocked down. Furthermore, the bioinformatics analysis and dual-luciferase reporter assay were conducted to explore the target miRNA of CASC15, which was further verified through rescue experiments in BLCA cells. RESULTS: CASC15 expression was upregulated in BLCA tissue samples. Moreover, CASC15 downregulated the miR-130b-3p expression and promoted cell migration and invasion in BLCA in vitro. The rescue experiments also revealed that the inhibitory effects by the silence of CASC15 could be reversed through the inhibition of miR-130b-3p. CONCLUSIONS: Our study suggested a vital regulatory mechanism of CASC15 in BLCA, and the CASC15/miR-130b-3p axis might serve as a new therapeutic interventional target for BLCA patients.

[Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease with mild cognitive impairment].

Objective: To investigate the characteristics of cerebral metabolism associated with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal PD and normal control to find a PET biomarker for the diagnose and estimate of PD-MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild cognitive impairment) and 20 control subjects were enrolled. All the subjects were evaluated with FDG-PET and clinical scale. The statistical parametric mapping (SPM) were analyzed to determine metabolic patterns that may be useful in differentiating between the three groups. Results: SPM analysis showed that significant hypometabolism were observed in both side of front lobe, parietal lobe, left temporal lobe and left occipital lobe; in the contrast, the relative hypermetabolism had been observed in the cerebellum, vermis, hippocampus and supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that the significant hypermetabolism were in the insular and cerebellum while hypometabolism were in the both side of occipital compared to PD without MCI. Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is an effective way to analysis the FDG uptake pattern of PD patients. The hypermetabolism in the insula and cerebellum and hypometabolism in the both side of occipital may be a biomarker for make a diagnosis of PD-MCI.

Association of betel nut chewing with exercise performance in a military male cohort: the CHIEF study.

INTRODUCTION: Betel nut chewing may cause obesity, neurohormonal activation and inflammation, possibly impairing exercise performances. METHODS: We examined the cross-sectional association in 4388 military male adults aged 18-50 years from the cardiorespiratory fitness in armed forces study in Taiwan between 2013 and 2014. The status of betel nut chewing was classified as current and former/never based on each participant's response to a questionnaire. Physical fitness was evaluated by three basic exercise tests including 3000 m running, 2 min sit-ups and 2 min push-ups. Multiple logistic regression for the best 10% and the worst 10% performers in each exercise, and linear regression were used to determine the relationship. RESULTS: There were 564 current chewers and 3824 non-current chewers for the analysis. The linear regression shows that current betel nut chewing was positively correlated with 3000 m running duration (r=0.37, p=0.042) after adjusting for age, service specialty, body mass index, exercise frequency and alcohol intake. In addition, the logistic regression shows that as compared with non-current chewers, current chewers had lower odds of being the top 10% performers in 2 min push-ups and higher odds of being the bottom 10% performers in 2 min sit-ups (ORs and 95% CIs: 0.71 (0.50 to 0.99) and 1.32 (1.00 to 1.75), respectively). However, the associations between betel nut chewing and physical fitness were all insignificant after further adjusting for current smoking. CONCLUSIONS: Our findings suggest that the impairment of physical fitness associated with betel nut chewing of military young men might be mainly mediated or moderated by the coexisted cigarette smoking.

Age-, sex- and glucose-dependent correlation of plasma soluble vascular adhesion protein-1 concentration with cardiovascular risk factors and subclinical atherosclerosis.

OBJECTIVE: Soluble vascular adhesion protein-1 (sVAP-1) may act as a biomarker for atherosclerosis and cardiovascular diseases. The associations of sVAP-1 concentration with cardiovascular risk factors and subclinical atherosclerosis at the population level have not been reported. PATIENTS AND METHODS: This cross-sectional study included 834 asymptomatic subjects (49.1 ± 9.3 years). sVAP-1 was measured by enzyme-linked immunosorbent assay. Subclinical atherosclerosis was assessed by brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (CIMT). RESULTS: sVAP-1 increased with age. Women had a higher concentration than men in age > 40 years. In women, sVAP-1 was negatively associated with estradiol (p < 0.01) and body mass index (BMI) (p < 0.05). In men, sVAP-1 was negatively associated with apolipoprotein A (ApoA) (p < 0.01), alcohol intake (p < 0.01) and uric acid (p < 0.05), but positively associated with ApoB/ApoA (p < 0.05). In hyperglycemia subjects, sVAP-1 positively correlated with fasting plasma glucose (p < 0.05) and hemoglobin A1c (p < 0.05), but in normoglycemic subjects, sVAP-1 negatively correlated with BMI (p < 0.01), triglyceride (p < 0.05), alcohol intake (p < 0.05). sVAP-1 independently influenced CIMT (ß = 0.001, p = 0.040) and carotid plaques [odds ratio 1.380 (95% confidence interval 1.051-1.813, p = 0.021)] in hyperglycemia, and baPWV (ß = 31.605, p = 0.014) in age > 55 years. CONCLUSIONS: sVAP-1 concentration correlates with cardiovascular risk factors and subclinical atherosclerosis in an age-, sex- and glucose-dependent manner.

Clinical, demographic and histopathological features of symmetrical acral keratoderma.

BACKGROUND: A series of cases of symmetrical acral keratoderma have been described recently in China. However, no studies about its demographic information and epidermal barrier function have been documented. OBJECTIVES: To describe the clinical manifestation, demographic information and clinicopathological features of 71 cases with symmetrical acral keratoderma. PATIENTS AND METHODS: Seventy-one cases with symmetrical acral keratoderma were retrospectively reviewed. Their demographic information, clinical manifestations, histopathology and epidermal barrier function were analysed. RESULTS: Among these patients, there were 64 males and seven females, ranging in age from 4 to 53 years with an average age at onset of 27 ± 8·9 years. Clinical manifestation was characterized by brown hyperkeratotic patches over the dorsum of the hands, palms and feet, dorsal digits and wrists, elbows, knees and ankles. The lesions became dramatically whitish with mild swelling immediately after soaking in water and resolved spontaneously in winter. In patients, a moderate increase of transepidermal water loss (TEWL) from 16·16 ± 6·15 to 9·9 ± 4·21 g m(-2)  h(-1) (P = 0·0054) and a moderate decrease of skin hydration from 65·9 ± 5·06 to 42·58 ± 10·73 (P < 0·01) in comparison with the control group were observed. Histopathological examination revealed epidermal hyperkeratosis, acanthosis and papillomatous hyperplasia as well as dermal infiltration with a few lymphocytes. CONCLUSIONS: Symmetrical acral keratoderma is characterized by symmetry, acra, keratinization and marked seasonal changes. The epidermal barrier function of the skin was negatively affected.

Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol.

BACKGROUND AND PURPOSE: Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol. EXPERIMENTAL APPROACH: Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg(-1) ·day(-1), i.p.) and metoprolol (20 mg·kg(-1) ·day(-1), p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling-related proteins were evaluated. KEY RESULTS: Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-κB-light-chain-enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth-associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol. CONCLUSIONS AND IMPLICATIONS: Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy.

Neointimal formation by circulating bone marrow cells.

The origin of smooth muscle cells involved in vascular healing was examined. Eighteen C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 106 bone nucleated marrow cells from congenic (Ly 5.1) male donors. Successful repopulation by donor marrow was demonstrated after 4 weeks by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal antibody. The iliac artery of six of the chimeric mice was scratch-injured by five passes of a probe, causing severe medial damage. After 4 weeks the arterial lumen was obliterated by a cell-rich neointima, with alpha-smooth muscle actin-containing cells present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y chromosome-specific probe. An organized arterial thrombus was formed in the remaining 12 chimeric mice by inserting an 8-0 silk suture into the left common carotid artery. Donor cells staining with alpha-smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage. Our results suggest that bone marrow-derived cells are recruited in vascular healing as a complementary source of smooth muscle-like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair.

Blood vessels from bone marrow.

Lengths of silastic tubing were inserted into the peritoneal cavity of rats or rabbits. By two weeks the free-floating implants had become covered by a capsule consisting of several layers of "macrophage"-derived myofibroblasts and collagen matrix overlaid by a single layer of mesothelial cells. The tubing was removed from the harvested implant and the tissue everted. This now resembled an artery with an inner lining of mesothelial cells (the "intima"), a "media" of myofibroblasts, and an outer collagenous "adventitia." The tube of living tissue was grafted by end-to-end anastomoses into the transected carotid artery or abdominal aorta of the same animal in which the tissue had been grown, where it remained patent for four months and developed structures resembling elastic lamellae. The myofibroblasts developed a high volume fraction of myofilaments and became responsive to contractile and relaxing agents similar to smooth muscle cells of the adjacent artery wall.

Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family--implications for etiology of fetal alcohol syndrome and alcohol-related diseases.

The alcohol dehydrogenase (ADH) family is involved in the metabolism of both ethanol and retinoids. To quantitatively assess the potential contributions to first-pass metabolism of ethanol and the ethanol interference with retinoid homeostasis, saturation kinetics for ethanol oxidation as well as inhibition kinetics by ethanol for all-trans-retinol oxidation of human class I alpha alpha, beta1beta1, beta2beta2, gamma1gamma1, class II pi pi, class III chi chi, and class IV mu mu were evaluated and compared. Class I and class II ADHs exhibited substrate inhibition with inhibition constants ranging over 250-720 mM (except gamma1gamma1) ethanol. Class IV ADH displayed no appreciable inhibition up to 1 M ethanol. Activity of the class III enzyme (190 nM subunit) was undetectable at 250 mM ethanol. The kinetic simulations indicate that the hepatic pi pi and the gastric mu mu can most effectively contribute to first-pass metabolism of alcohol. The Michaelis constant (Km), turnover number (k(cat)), and catalytic efficiency (k(cat)/Km) for retinol oxidation relative to that for ethanol oxidation in class I, class II, and class IV ADHs ranged over 0.00022-1.3, 0.071-0.48, and 0.24-650, respectively. Ethanol was a competitive inhibitor against retinol for class I, II, and IV ADHs with apparent inhibition constants ranging over 0.037-11 mM, indicating that retinoic acid synthesis through the ADH pathways can be tremendously blocked during social/heavy drinking. These findings support the notion that first-pass metabolism of alcohol may occur mainly in the liver through class II pi pi and that cellular retinoid signaling may be perturbed by ethanol via ADH pathways.

Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: results from a seroepidemiological case-control study.

OBJECTIVE: To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas. METHODS: We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression. RESULTS: Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stronger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95% CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive tumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76, 18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.35, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-16. The risk associated with HPV-16 seropositivity was higher among smokers (OR 8.5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13). CONCLUSION: Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of some vulvar tumors and that smoking may be an important cofactor involved in the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the role of smoking and other cofactors in this disease process are warranted.

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Effects of the calcium antagonist isradipine on 24-hour ambulatory blood pressure, platelet aggregation, and neutrophil oxygen free radicals in hypertension.

The effects of isradipine on ambulatory blood pressure, platelet aggregation, and oxygen free radicals were assessed in 30 patients with hypertension in a non-comparative 16-week study. After 4 weeks of placebo run-in, patients received isradipine at 2.5 mg twice daily for 12 weeks. The average supine systolic/diastolic blood pressure (155 +/- 17/101 +/- 11 mm Hg) was significantly reduced at the end of treatment (144 +/- 13/95 +/- 9 mm Hg; p less than 0.01). The heart rate was not significantly altered. Isradipine had no adverse effects on red or white blood cells or on plasma viscosity. The thromboxane B2 level and epinephrine-induced platelet aggregation were significantly (p less than 0.05) reduced. High-density lipoprotein cholesterol was significantly (p less than 0.01) increased after vs. before treatment; total cholesterol was significantly (p less than 0.05) increased at midstudy, but this was not significant at the end of the study. Other biochemical parameters were unchanged. Studies of neutrophil oxygen free radicals by serum opsonized zymosan and phorbol myristate acetate were not affected by isradipine. In conclusion, isradipine is an effective antihypertensive agent that also has beneficial effects on platelet aggregation and lipids while having no effects on neutrophil oxygen free radicals or most of the biochemical variables tested, making it an ideal agent for hypertension.