A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve

OBJECTIVE: To establish a model of long-term free drinking mouse by feeding mice with alcohol to simulate the state of human voluntary long-term drinking, and on this basis, to further discuss the evaluation criteria of long-term free drinking mice model in sports, anxiety and cognitive behavior. METHODS: Forty six-week-old SPF C57BL/6 male mouse were randomly divided into two groups: Long-term free drinking group (n=20) and normal control group (n=20). The two groups were given solid feed normally. The long-term free drinking group was free to take 10% alcohol and water every day, while the normal drinking group only took water every day. The mice were fed for 7 months, and were evaluated by a series of behavioral methods, including Rota-rod test, balance beam test, open filed test, the elevated plus maze, two-box social behavior, new object recognition, Y maze and water maze. RESULTS: With the increase of drinking days, the mice showed significant alcohol addiction in the alcohol preference test. With the increase of alcohol intake, the mice in the long-term free choice drinking group had slightly shiny fur and reduced diet. Compared with the control group, the weight gain began to slow down from the third month, and the weight decreased significantly by the sixth and seventh months (P=0.006, P < 0.001). The mice showed reduced balance locomotion ability (P=0.003, P=0.001) in the rotary bar and balance beam test. In the open field and elevated cross test, the mice had obvious anxiety-like behavior (P < 0.001). The mice showed decreased social ability in the two boxes of social behavior (P < 0.016). In the experiment of new object recognition and Y maze, the exploration of new object decreased (P=0.018, P=0.040). In the water maze, cognitive functions, such as learning and spatial memory were reduced (P < 0.001). CONCLUSION The successful establishment of the long-term free drinking mouse model is more convenient for us to carry out further research on the neural mechanism of alcohol addiction, and lays an experimental foundation for exploring the neural mechanism of alcohol addiction and related new targets.
Mice ; Male ; Humans ; Animals ; Alcoholism ; Mice, Inbred C57BL ; Alcohol Drinking/psychology* ; Anxiety ; Disease Models, Animal ; Ethanol

INTRODUCTION: Few studies have examined the changes in the prevalence of comorbidity of mental and physical disorders in recent years. The present study sought to examine whether the prevalence of comorbidity of mental and physical disorders in Singapore showed any changes between 2010 and 2016. METHODS: We extracted data from two repeated nationally representative cross-sectional surveys conducted among resident adults aged ≥ 18 years in Singapore. Significant changes were tested using pooled multinomial logistic regression analyses. RESULTS: The prevalence of comorbid mental and physical disorders increased significantly from 5.8% in 2010 to 6.7% in 2016. Among those with physical disorders, there were significant increases over time in the prevalence of comorbid generalised anxiety disorder (GAD) (0.1% vs. 0.4%) and obsessive-compulsive disorder (OCD) (1.4% vs. 3.9%) in diabetes mellitus, and alcohol dependence in cardiovascular disorders (0.1% vs. 1.3%). Among those with mental disorders, there were significant increases over time in the prevalence of comorbid diabetes mellitus in OCD (4.1% vs. 10.9%), cancer in major depressive disorder (0.4% vs. 2.4%), and cardiovascular disorders in GAD (0.4% vs. 6.7%) and alcohol dependence (0.9% vs. 11.8%). Significant changes in the overall prevalence of comorbid mental and physical disorders were also observed across age group, education and employment status. CONCLUSION The prevalence of comorbid mental and physical disorders increased significantly over time. This finding supports the need for more appropriate clinical management with better integration between mental health and general medical care professionals across all aspects of the healthcare system to treat this comorbidity in Singapore.
Adult ; Alcoholism/epidemiology* ; Comorbidity ; Cross-Sectional Studies ; Depressive Disorder, Major/epidemiology* ; Humans ; Mental Disorders/epidemiology* ; Prevalence ; Singapore/epidemiology*

The purpose of this study was to investigate the effects of α₂ adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α₂ adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α₂ adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use* ; Alcoholism/drug therapy* ; Animals ; Dexmedetomidine/therapeutic use* ; Hippocampus/metabolism* ; Male ; Norepinephrine ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2/metabolism* ; Substance Withdrawal Syndrome/drug therapy* ; Yohimbine/pharmacology*

OBJECTIVES: To investigate the epidemiological characteristics of antisocial personality disorder (ASPD) in young men in Chengdu and explore the characteristics and risks of violence. METHODS: Stratified random sampling was used to conduct a self-assessment questionnaire survey in 4 108 males aged from 18 to 34 in Chengdu, including general demographic characteristics, structured clinical interview for the diagnostic and statistical manual of mental disorders-Ⅳ axis Ⅱ disorders (SCID-Ⅱ) personality disorder screen questionnaire, violence questionnaire, psychosis screening questionnaire (PSQ), Alcohol Use Disorders Identification Test (AUDIT) and drug use. χ² test, univariate and multivariate logistic regression were used for analysis and odds ratio (OR) was calculated. RESULTS: The positive rate of ASPD was 5.91%, which was associated with young age, unmarried, unemployment state, low educational level, violent behavior, psychotic symptoms, alcohol and drug use (P<0.05). Young men with ASPD also had a risk (P<0.05) of violence (OR was 8.51), multiple violence (OR was 16.57), injury (OR was 6.68), intentional violence (OR was 11.41), etc., the risk decreased after controlling for psychotic symptoms and substance abuse, but was still statistically significant. CONCLUSIONS The risk of violence, severe violence and intentional violence in young men in Chengdu is high, and psychotic symptoms and substance abuse increase the risk of ASPD violence and relate characteristics.
Alcoholism/epidemiology* ; Antisocial Personality Disorder/epidemiology* ; Comorbidity ; Humans ; Male ; Substance-Related Disorders/epidemiology* ; Surveys and Questionnaires

BACKGROUND/AIMS: Refeeding syndrome (RFS) is a fatal clinical complication that can occur as a result of fluid and electrolyte shifts during early nutritional rehabilitation for malnourished patients. This study was conducted to determine the clinical implications of RFS in patients with acute pancreatitis (AP). METHODS: Between 2006 and 2016, AP patients with very early mortality were retrospectively enrolled from three university hospitals. RESULTS: Among 3,206 patients with AP, 44 patients died within 3 days after diagnosis. The median age was 52.5 years (range, 27 to 92 years), male-to-female ratio was 3:1, and median duration from admission to death was 33 hours (range, 5 to 72 hours). The etiology of AP was alcohol abuse in 32 patients, gallstones in five patients, and hypertriglyceridemia in two patients. Ranson score, bedside index for severity of AP, and acute physiology and chronic health evaluation-II were valuable for predicting very early mortality (median, [range]; 5 [1 to 8], 3 [0 to 5], and 19 [4 to 45]). RFS was diagnosed in nine patients who died of septic shock (n=5), cardiogenic shock (n=2), or cardiac arrhythmia (n=2). In addition, patients with RFS had significant hypophosphatemia compared to non-RFS patients (2.6 mg/dL [1.3 to 5.1] vs 5.8 mg/dL [0.8 to 15.5]; p=0.001). The early AP-related mortality rate within 3 days was approximately 1.4%, and RFS occurred in 20.5% of these patients following sudden nutritional support. CONCLUSIONS: The findings of current study emphasize that clinicians should be aware of the possibility of RFS in malnourished AP patients with electrolyte imbalances.
Alcoholism ; Arrhythmias, Cardiac ; Diagnosis ; Gallstones ; Hospitals, University ; Humans ; Hypertriglyceridemia ; Hypophosphatemia ; Mortality ; Nutritional Support ; Pancreatitis ; Physiology ; Prognosis ; Refeeding Syndrome ; Rehabilitation ; Retrospective Studies ; Shock, Cardiogenic ; Shock, Septic

BACKGROUND AND OBJECTIVES: To investigate the relationship between hearing impairment and alcohol drinking patterns in South Korean adults. SUBJECTS AND METHODS: Data collection was performed by Korean National Health and Nutrition Survey from January 1 to December 31, 2012. Data analyses were performed from February 20 to March 3, 2018. Data from 3,860 adults 20 years of age or older without a history of malignancy or chronic otitis media in the Korean National Health and Nutrition Survey 2012 database who participated in the health questionnaires, and who had available results from otologic examinations that included pure tone audiogram, were included. Pure-tone average hearing thresholds were calculated at 500, 1,000, 2,000, and 4,000 Hz. Hearing loss was defined as a pure-tone average >40 dB in one or both ears. The Alcohol Use Disorder Identification Test was used to evaluate drinking statuses of subjects. Data were analyzed using the complex-sample χ²-test of independence and a complex-sample logistic regression analysis. RESULTS: Of the 29,954,319 individuals in the weighted cross-sectional study population, 15,106,040 (50.4%) were men and 14,848,098 (49.6%) were women. A total of 8.1% of men and 7% of women had hearing impairment. The degrees of drinking with appropriate, risky, and hazardous drinking habits were 58.2, 32.1, and 9.7% among men; and 76.4, 12.5, and 11.1% among women, respectively. Among men, the odds ratio of hearing loss increased by 2.506 times when comparing hazardous and appropriate drinking (confidence interval, 1.083 to 5.800, p=0.002). Moderate alcohol consumption (≤2 drinks per day) was not protective for hearing in either group. CONCLUSIONS: As hazardous drinking tends to coexist with hearing impairment in men, appropriate prevention and intervention strategies should be emphasized. A longitudinal study to investigate harmful drinking and the mechanism of hearing loss should be performed.
Adult ; Alcohol Drinking ; Alcoholism ; Cross-Sectional Studies ; Data Collection ; Deafness ; Drinking ; Ear ; Female ; Hearing Loss ; Hearing ; Humans ; Logistic Models ; Longitudinal Studies ; Male ; Nutrition Surveys ; Odds Ratio ; Otitis Media ; Prevalence ; Retrospective Studies ; Risk Factors ; Statistics as Topic

This study investigated advantages and potential risks associated with drinking alcohol in Koreans based on the alcohol flush reaction. Our investigation reviewed published studies and examined moderate-drinking levels for Koreans based on modified National Institute on Alcohol Abuse and Alcoholism guidelines. Fourteen articles out of a total 198 publications were searched using PubMed, EMBASE, KoreaMed, and RISS (Research Information Sharing Service) databases and selected for review. Individuals without alcohol flush reaction (non-flushers) exhibited lower risks associated with insulin resistance, metabolic syndrome, and hyperhomocysteinemia and their 10-year cardiovascular disease risk when alcohol consumption was ≤8 drinks/wk. Conversely, risks associated with insulin resistance, metabolic syndrome, high blood pressure, prediabetes or type-2 diabetes, and high intraocular pressure and increases in carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels were present when >8 drinks were consumed. For individuals with flushing reaction (flushers), advantages were reported in relation to risks of hyperhomocysteinemia when alcohol consumption was ≤4 drinks/wk, whereas consumption of >4 drinks/wk increased the risk of insulin resistance, metabolic syndrome, high blood pressure, pre-diabetes or type-2 diabetes, high-risk colorectal adenoma, and high intraocular pressure and increased carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels. The moderate drinking level for Koreans is ≤8 drinks/wk for men aged ≤65 years and ≤4 drinks/wk for men aged over 65. For women, these limits should be half of those for men. Furthermore, individuals with flushing reaction should maintain an alcohol consumption level half of that for non-flushers.
Adenoma ; Alcohol Drinking ; Blood Glucose ; Cardiovascular Diseases ; Drinking ; Female ; Flushing ; Humans ; Hyperhomocysteinemia ; Hypertension ; Information Dissemination ; Insulin Resistance ; Intraocular Pressure ; Male ; National Institute on Alcohol Abuse and Alcoholism (U.S.) ; Prediabetic State ; Transferases ; Transferrin

Disulfiram has been used for the treatment of alcohol dependence for nearly 65 years and is approved by the Food and Drug Administration. It causes negative reinforcement by accumulating toxic acetaldehyde due to irreversible inhibition of aldehyde dehydrogenase. Disulfiram has very few side effects when taken without alcohol. Epileptic seizure induction is a rare side effect in therapeutic doses, and its mechanism is unknown. We present a patient with a single epileptic seizure which was thought to be due to disulfiram used in the treatment of alcohol dependence. We did not find it ethical to administer disulfiram again because the patient discontinued alcohol use and was afraid of epileptic seizures.
Acetaldehyde ; Alcoholism ; Aldehyde Dehydrogenase ; Disulfiram ; Epilepsy ; Humans ; Reinforcement (Psychology) ; United States Food and Drug Administration