Comprehensive methylation profile of CSF cfDNA revealed pathogenesis and diagnostic markers for early-onset PD

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.

Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer

Background. The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis. Methods. A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients. Results. The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB. Conclusion. GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

Investigation on the current situation of stroke patients in northernern Henan Province of China

Objectives: To analyze the basic situations and clinical characteristics of stroke patients in our hospital from May 2018 to April 2021, lay a foundation for the prevention and reasonable treatment of stroke patients in northern Henan Province. Methods: The basic information of 835 stroke patients in our hospital was collected and classified according to age, gender, bad habits, accompanied diseases and drug use before admission to hospital, and severity of the stroke patients were also evaluated according to mRS scoring standard. Results: A total of 835 stroke patients were collected from May 2018 to April 2021 in our hospital. The age range of stroke patients was 28-95 years old, 96.29% stroke patients was above 40 years old; there were 202 stroke patients with smoking history and 225 stroke patients with drinking history; Among the 835 stroke patients, hypertension, cerebral infarction and diabetes mellitus were the main accompanied diseases. Antihypertensive drugs (506 cases), antiplatelet drugs (208 cases), statins (173 cases) and antidiabetic drugs (143 cases) were the main therapeutic drugs in stroke patients before admission in the northern Henan Province; the results of mRS scoring standard showed that among 835 stroke patients, there were 609 cases with milder symptoms, accounting for 82.84% (there were 330 stroke patients with 1 points, 279 stroke patients with 2 points, and 83 stroke patients with 3 points), and 120 cases with severe symptoms, accounting for 14.37% (55 cases with 4 points, 65 cases with 5 points). Conclusion: The age of stroke patients in northern Henan Province was mainly over 40 years old, most of stroke patients were in the early stage of stroke; smoking, drinking, hypertension and diabetes mellitus were main risk factors of stroke. And there was a sex difference between male stroke patients and female stroke patients in stroke risk factors smoking and hypertension. those data may help us for active prevention and rational drug use for stroke in clinic.

The influence of negative mood on solitary drinking preference: An experiment with young adult solitary drinkers

Solitary drinking is a risk marker for alcohol use disorder; thus, it is important to identify why individuals drink alone and for whom this association is particularly relevant. Evidence suggests the desire to ameliorate negative affect (NA) motivates solitary drinking, with some individuals particularly likely to drink alone to cope, but all past studies are cross-sectional. The present study therefore aimed to determine whether 1) experimentally induced NA increased preferences to drink alcohol alone, and 2) whether the relationship between NA and choosing to drink alcohol alone was moderated by neuroticism, drinking to cope motives, and social anxiety. Current drinkers (ages 21-29) with a solitary drinking history (N=126) were randomly assigned to either NA, positive affect [PA], or no affect change (control) conditions via differing cognitive task feedback. After the mood manipulation, participants chose between drinking alcoholic or nonalcoholic beverages in one of two contexts: alone or socially. Evidence regarding effectiveness of the mood manipulation was mixed, and few chose non-alcoholic beverages in either context. Condition did not influence outcome choice. Across conditions, increases in NA and the importance placed on receiving one’s context choice were associated with solitary (versus social) alcohol preference. Neuroticism and its interaction with NA change also influenced choice; individuals high in neuroticism chose more solitary (versus social) drinking contexts while the opposite was true for those low in neuroticism, and among the latter, the preference difference was more pronounced with relatively smaller NA increases. Findings are discussed based on the existing solitary drinking literature.

Alcohol Quantity and Type on Risk of Gouty tophi

Objective: The aim of this study was to explore the impact of drinking alcohol on tophi and its surrounding inflammation in the joints by ultrasound. Methods: We conducted a cross-sectional study on 356 gout patients and collected their information of drinking history, clinical biochemical parameters and ultrasound results. Multiple regression analyses including several variables and potential confounders were then performed. Results: Relative to no drinking, more alcohol intake (>200 g/week), longer drinking time (>20 years) and higher frequency of drinking (>2 times/week) had significant positive effects on the size of tophus after controlling for potential confounders (P=0.024; P=0.002; P=0.040). Further subgroup analysis of different ages illustrated that more alcohol consumption had positive effects on the size of tophi only in the younger gout patients (≤50 years old), rather than in older ones (>50 years old). However, alcohol consumption had no significant association with the formation and number of tophus, and the associations between type of drinking and tophi was not observed in the current study. Moreover, except for tophi, there was no relationship between alcohol consumption and other ultrasound signs including double-contour sign (DCS), bone erosion, effusion and synovial hypertrophy.Conclusion: Alcohol consumption is closely associated with ultrasound-detected tophi in gout patients. More alcohol intake, longer drinking time and higher frequency of drinking are crucial factors that positively affect the size of tophus, especially in younger gout patients. However, significant association between type of alcohol and tophi was not observed in the current study.

Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment

(1) Background: Alcohol use disorder (AUD) is associated with poor medical, psychological, and psychosocial outcomes and approximately 60% of individuals with AUD relapse six months after treatment. Craving is a core aspect of AUD and associated with high risk of relapse. One promising avenue to improve outcomes may be in understanding the relationship between COMT genotype, craving, and treatment outcomes. (2) Methods: To this end, we assessed craving, recent drinking history, and impulsivity in 70 individuals with AUD undergoing a standard course of treatment at a regional Veteran Affairs (VA) medical center. Saliva samples were collected to determine COMT genotype. In this prospective observational study, participants were followed for six months to determine who went on to relapse after treatment. (3) Results: Results revealed a significant interaction between craving and catechol-O-methyltransferse (COMT) genotype in predicting relapse. Post hoc exploratory analyses indicated that Met/Met homozygotes reported the highest levels of craving, and craving was associated with recent drinking history. Among Val/Val homozygotes, who had higher rates of relapse, craving was associated with impulsivity. (4) Conclusions: These associations highlight that specific profiles of psychological and biological factors may be important in understanding which individuals are at highest risk of relapse following treatment. Future studies that build on these findings are warranted.

Evaluating Incidence, Location, and Predictors of Positive Surgical Margin Among Chinese Men Undergoing Robot-Assisted Radical Prostatectomy

Purpose To evaluate the incidence and locations of positive surgical margin (PSM) among Chinese men undergoing RARP and identify the preoperative predictors for PSM. Methods We retrospectively identified 393 patients who underwent RARP according to inclusion criteria by single surgeon in our hospital. PSM was defined as the presence of cancer adjacent to inked surface of the specimen and categorized into four groups based on locations: apex, posterolateral, base, and multifocal. Logistic regression analysis was performed to identify the predictors of overall and location-specific PSM. Results The overall PSM rate was 133/393 (34%). The PSM rates for pT2, pT3, and pT4 stage were 63/278 (23%), 50/89 (56%), and 20/26 (77%), respectively. The estimated rates for apical, posterolateral, basal, and multifocal PSM were 8%, 4%, 7%, and 14%, respectively. In univariate analysis, overall PSM related to tPSA, f/tPSA, percentage of positive needles, and Gleason score. Multifocal PSM correlated with smoking history, drinking history, tPSA, f/tPSA, percentage of positive needles, and Gleason score. In multivariate analysis, percentage of positive needles reminded the only independent predictor for overall (OR = 10.5, 95% CI: 2.58–44.4) and basal PSM (OR = 24.0, 95% CI: 3.22–179.4). The f/tPSA (OR = 2.59, 95% CI: 2.18–5.71) and percentage of positive needles (OR = 31.0, 95% CI: 3.17–303) were independent risk factors for multifocal PSM. Conclusion The multifocal sites were the most common location of positive surgical margin, followed by apical and basal sites among Chinese patients undergoing RARP. The percentage of positive needles was an independent predictor for overall, basal, and multifocal PSM.

An Evaluation of Potential Unintended Consequences of a Nicotine Product Standard: A Focus on Drinking History and Outcomes

Background A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced-nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking. Methods Adults who smoke daily (n=752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes. Results Higher baseline alcohol use (versus no-use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps<.05). No additional moderation was supported (ps>.05). In the subsample who drank (n=415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Week 17-20 and odds of binge drinking were significantly reduced from Week 9-17. By Week 7 in the VLNC cigarette condition (n=272), smoking no longer predicted alcohol use but remained associated with binge drinking. Conclusions We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally impacted smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior. Implications There was no evidence that a very low nicotine content product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking very low nicotine content cigarettes may result in a decoupling of the daily associations between smoking and drinking.

Transitions in alcohol use over time: a survival analysis

Background The current study examined the predictors of the onset of alcohol use as well as predictors of remission and relapse, both from heavy drinking and from alcohol dependence. Similarities and differences in both clinical and psychosocial predictors across the transitions were examined. Methods A sample of men from the Vietnam Era Twin Registry (N = 1769) completed an assessment of lifetime drinking history, which allowed age markers for starting and stopping different drinking patterns. The men also completed various assessments regarding personality, alcohol motives, and psychiatric diagnoses. Survival analyses were used to examine the predictors of the three transitions of onset, remission, and relapse for the phenotypes of heavy drinking and of alcohol dependence, censoring the individuals who had not yet experienced an event. Results As expected, predictors of onset for drinking, heavy drinking, and alcohol dependence were largely consistent and included externalizing symptomology, nicotine dependence, and cotwin history of drinking as risk factors. Predictors of remission from heavy drinking, somewhat similarly to remission from alcohol dependence, included the risk factor of externalizing disorders but also, as predicted, included more risk and protective factors in the psychosocial realm that were not predictors of onset. Contrary to our prediction, relapse to heavy drinking and alcohol dependence were predicted largely by unique psychosocial risk and protective factors including social and coping motives. Conclusion Current findings extend the findings of past research to remission and relapse in the later decades of life and have implications for treatment of alcohol use problems.

Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma

Objective To investigate the risk factors of early postoperative recurrence in patients with single and small (≤3 cm) hepatitis B virus-associated primary hepatocellular carcinoma (HBV-HCC). Methods This retrospective study analyzed patients with single and small HBV-HCC. All patients were followed up for 1 year after surgery. Results Among 182 patients, 54 patients had early recurrence within 1 year. The recurrence group had higher proportions of men, drinking history, Child–Turcotte–Pugh (CTP) class C, patients who underwent transarterial chemoembolization (TACE), and serum alpha-fetoprotein (AFP) >10 ng/mL as well as higher gamma-glutamyl transpeptidase (GGT) levels and lower total protein (TP) and CD8+ T lymphocyte levels than the no recurrence group. Cox multivariate regression analysis demonstrated that drinking history (HR, 1.312; 95% CI, 1.042–1.652), CTP class C (HR, 1.236; 95% CI, 1.037–1.473), TACE treatment (HR, 1.241; 95% CI, 1.026–1.501), GGT (HR, 1.138; 95% CI, 1.042–1.243), TP (HR, 0.729; 95% CI, 0.555–0.957), and AFP (HR, 2.519; 95% CI, 1.343–4.726) were independently associated with early postoperative recurrence. Conclusion Drinking history, CTP class C, TACE, serum AFP, GGT, and TP levels were independently associated with early postoperative recurrence in patients with single and small HBV-HCC.