The use of premixed drugs in commodity packets in the population: prevalence and correlates revealed by the 2018 National Survey of Substance Use in Taiwan.

BACKGROUND: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug packet users. METHODS: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs and other psychoactive substances, among others. RESULTS: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had a lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were similar to those of the exclusive use of other drugs except that there was a lack of gender differences in the use of drugs in commodity packets but not in the exclusive use of other drugs. CONCLUSION: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug packet use.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

Survey of substance use among adolescent drug offenders referred from juvenile courts in Taiwan: Clinical epidemiology of single versus multiple illicit substance use.

BACKGROUND: Substance use during adolescence might cause substantial health burden. Little is known regarding profiles of multiple illicit substance users compared to single illicit substance users in adolescent population in Taiwan. METHODS: We enrolled 106 adolescent illicit drug users who received addiction treatment referred by juvenile courts in Taiwan between September, 2016 and September, 2021. We divided them into two groups: single versus multiple illicit drug users, and further compared their socio-demographic characteristics, psychiatric and substance comorbidities. The independent t test or Mann-Whitney U test was used for continuous variables and Pearson's chi-square test for nominal variables. Multivariate logistic regression was used to examine the suicide and violence risk among adolescents. RESULTS: 71.7% of participants were multiple illicit drug users while 28.3% of them were single drug users. Multiple illicit substance users were more likely to use methamphetamine (p = 0.005), ketamine (p < 0.001), new psychoactive substance (NPS) (p < 0.001), MDMA (p = 0.003), and nitrous oxide (p < 0.001) compared to single illicit substance users. In addition, multiple illicit drug users were more likely to have ADHD (p = 0.030), major depressive disorder (p = 0.050), and lifetime suicidal attempts (p = 0.048) compared to single illicit drug users. In further analysis (NPS vs. traditional drugs), we found NPS users tended to use larger numbers of illicit drugs (p < 0.001) and were more likely to have substance-induced psychotic disorder (p = 0.008), ADHD (p = 0.011), suicidal attempts (p = 0.020). CONCLUSION: Our findings highlight the distinct profiles of multiple illicit drug users compared to single illicit drug users among adolescent population. High suicidality and high psychiatric comorbidities in multiple illicit drug users call for special need for suicide screening and a more integrated care incorporating psychiatric and substance treatment.

Gender differences in clinical characteristics of emergency department patients involving illicit drugs use with analytical confirmation.

BACKGROUND: To compare gender differences in socio-demographics, clinical manifestations, and laboratory test results of individuals who visited emergency departments (EDs) involving drug use. METHODS: We retrospectively collected the data from 10 hospitals in Taiwan on drug-related ED visits from May 2017 to December 2020. We then examined the gender differences in their socio-demographics, clinical manifestations, urine toxicological results, and other laboratory tests results using chi-square or multivariable logistic regression. RESULTS: Among individuals with drug-related ED visits, there were 546 (73.7%) men and 195 (26.3%) women. The most commonly used drugs were meth/amphetamine, followed by synthetic cathinones, and ketamine and its analogs. Compared to men, women were younger (32.03 ± 10.86 vs. 36.51 ± 10.84 years, p < 0.001) and more likely to use new psychoactive substances (NPS) (p = 0.011). Men were more likely to have human immunodeficiency virus infection (p < 0.001), whereas women were more likely to report psychiatric comorbidities (p = 0.003). Women were less likely to have aggressive behaviors (odds ratio (OR): 0.59, 95% CI: 0.39-0.88). After adjusting for socio-demographics and drug types, women were still less likely to have aggressive behaviors than men (adjusted OR: 0.59, 95% CI: 0.38-0.93). The likelihood of rhabdomyolysis and intensive care unit admission was higher in men (p < 0.001). CONCLUSION: We found considerable gender differences in clinical characteristics among ED-visiting drug users, which could offer valuable information for the future development of more tailored gender-specific drug prevention and treatment strategies.

Characteristics of patients with analytically confirmed γ-hydroxybutyric acid/γ-butyrolactone (GHB/GBL)-related emergency department visits in Taiwan.

The recreational drug γ-hydroxybutyric acid (GHB) is a central nervous system depressant, and can produce euphoria at low doses. GHB is a controlled substance in Taiwan. However, the organic solvents γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are unregulated, may be used as an alternative source of GHB. There is no clinical report of analytically confirmed GHB use in Taiwan. We retrospective reviewed the clinical characteristics from the medical charts between May 2017 and April 2020. The urine samples of patients presented to the emergency departments with drug-related complaints were sent for toxicological analysis. Patients with urine samples detected GHB >10 µg/mL by liquid chromatography/tandem mass spectrometry were included. Overall, 11 men and one woman with an average age of 35.3 ± 8.7 years were included. Most patients co-ingested amphetamine (n = 6) and initially presented with depressed consciousness levels (n = 7). One patient presented with out-of-hospital cardiac arrest and one with respiratory depression. All patients regained consciousness within 6 h of admission. All patients used GBL to evade conviction. Although patients recovered with supportive care, respiratory failure and cardiac arrest occurred after GHB/GBL use. It is important to legislate GBL and BD as controlled chemical substances in Taiwan.

Albumin-to-alkaline phosphatase ratio serves as a prognostic indicator in unresectable pancreatic ductal adenocarcinoma: a propensity score matching analysis.

BACKGROUND: Recent evidence suggests that albumin-to-Alkaline Phosphatase Ratio (AAPR) functions as a novel prognostic marker in several malignancies. However, whether it can predict the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) remains unclear. Herein, we seek to investigate this possibility by a propensity score matching (PSM) analysis. METHODS: This was a retrospective cohort study in which 419 patients diagnosed with unresectable PDAC and receiving chemotherapy were recruited. Patients were stratified based on the cutoff value of AAPR. The PSM analysis was performed to identify 156 well-balanced patients in each group for overall survival (OS) comparison and subgroup analysis. Univariate and multivariate analyses were carried out to examine the potential of AAPR to indicate the prognosis of unresectable PDAC. The prediction performance of conventional model and combined model including AAPR was compared using the Akaike Information Criterion (AIC) and concordance index (C-index). RESULTS: We identified an AAPR of 0.4 to be the optimal cutoff for OS prediction. Patients with AAPR≤0.4 had significantly shorter OS compared with patients with AAPR> 0.4 (6.4 versus 9.3 months; P < 0.001). Based on the PSM cohort and entire cohort, multivariate Cox analysis revealed that high pretreatment for AAPR was an independent marker predicting favorable survival in unresectable PDAC (hazard ratio, 0.556; 95% confidence interval, 0.408 to 0.757; P < 0.001). Significant differences in OS were observed in all subgroups except for the group of patients age ≤ 60. Combined prognostic model including AAPR had lower AIC and higher C-index than conventional prognostic model. CONCLUSIONS: Pretreatment AAPR servers as an independent prognostic indicator for patients with unresectable PDAC. Inclusion of AAPR improved the prediction performance of conventional prognostic model, potentially helping clinicians to identify patients at high risk and guide individualized treatment.

Psychiatric and Other Medical Manifestations of Nitrous Oxide Abuse: Implications From Case Series.

BACKGROUND: Nitrous oxide (N2O), a commonly used anesthetic agent in dentistry, has emerged as a global public health threat in young population. Although N2O-related neurological sequelae such as spinal cord degeneration and sensorimotor peripheral neuropathy are well known, psychiatric manifestations of heavy N2O use remain unclear. Here, we presented 7 treatment-seeking patients with severe N2O use disorder to delineate the psychiatric profiles of N2O users in Asia. METHODS: Seven patients with severe N2O use disorder who sought treatment in Taipei City Psychiatric Center between 2017 and 2018 were enrolled. We used chart review method to retrospectively collect their clinical information including sociodemographics, psychiatric and substance history, urine toxicology findings, and treatment course. RESULTS: These N2O users all had diagnoses of severe N2O use disorder. They usually initiated N2O use in late adolescence and early adulthood. Six of them had histories of mood disorders; all of them reported other illicit substance use before using N2O. The main reasons for treatment seeking were irritability, psychotic symptoms, self-harm, or violent behaviors as four of them were given a diagnosis of substance-induced psychotic disorder. Urine drug screen showed negative for other illicit drug use except for 1 positive case for cannabis and 1 for amphetamine. Three of 7 cases were hospitalized because of the severity of their psychiatric symptoms and suicidal risk. CONCLUSIONS: These cases with severe N2O use disorder showed high prevalence of psychotic symptoms and dangerous behaviors such as suicide or violence. This study highlights the addiction potential of N2O and its related adverse consequences in the psychiatric aspect.

Association of Craving and Depressive Symptoms in Ketamine-Dependent Patients Undergoing Withdrawal Treatment.

BACKGROUND AND OBJECTIVES: Ketamine has emerged as one of the major illicit substances worldwide. Craving, a primary symptom for addiction, is a key challenge for ketamine abusers attempting abstinence. A link between craving and negative affect has been suggested previously for other substances. We examined the relationship between craving and negative effect (depression and anxiety) in patients with ketamine dependence (KD) undergoing withdrawal treatment. METHODS: We included 104 patients with KD (76 males and 28 females) who received inpatient treatment for ketamine withdrawal and assessed them by using Beck Depression Inventory (BDI), Beck Anxiety Inventory, and a visual analog scale (VAS; 0-100 mm) for ketamine craving on day 2 to 3 of admission. RESULTS: Fifty-nine (59%) and 38 (38.7%) of our patients reported moderate-to-severe depression and anxiety symptoms, respectively. Patients with greater cravings (ie, greater than the median VAS) reported spending more days on ketamine in the preceding month and displayed severer depressive symptoms than did those with lower cravings. VAS was significantly correlated with BDI scores after adjustment. Patients who stayed in the treatment longer (more than 2 weeks) experienced more cravings and depressive symptoms than those who did not. DISCUSSION AND CONCLUSIONS: We observed a high prevalence of depression in patients with KD, particularly those with higher cravings. Patients with greater cravings and severer depression might require a longer duration of withdrawal treatment. SCIENTIFIC SIGNIFICANCE: This research provides intimal evidence for an association between depression and craving in patients with KD. Screening and management of depression are recommended for this population. (Am J Addict 2019;00:00-00).

Characteristics of analytically confirmed illicit substance-using patients in the Emergency Department.

BACKGROUND/PURPOSE: Although illicit substance use-induced toxicity or complication is a frequent cause of visit to the emergency department (ED), there are limited data on cases confirmed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. This study aimed to describe clinical presentations of patients who visited the ED because of acute illicit substance-related complications. METHODS: We performed a retrospective study between May 2017 and August 2018 on patients presenting to the ED with positive urine illicit substance analysis by LC-MS/MS. RESULTS: Of 203 patients with at least one illicit substance detected in their urine, 162 (79.8%) showed traditional illicit substances, and 56 (32.0%) showed new psychoactive substances (NPS). Methamphetamine was the most common illicit substance (67.9%). The most common NPS was ketamine (21.7%), followed by synthetic cathinones (14.8%). We divided patients into traditional, NPS and combined (both traditional illicit substance and NPS) groups. Polysubstance use was more common in the NPS group than in the traditional group (P < 0.001). Most patients were men (78.3%), and the average age was lower in the NPS group compared to the traditional group (P < 0.001). Although the chemical structures of cathinones are similar to that of amphetamine, 92.0% of the cathinone use cases without combination with methamphetamine use showed negative immunoassay results. CONCLUSION: Our study provided the acute illicit substance complications at ED by LC-MS/MS analysis in Taiwan. Our study showed that more than one-third cases studied were NPS users. Young adults and polysubstance users were more common among NPS users.

Overexpressed N-fucosylation on the cell surface driven by FUT3, 5, and 6 promotes cell motilities in metastatic pancreatic cancer cell lines.

Pancreatic cancer is a highly malignant tumor of the digestive system. Previous studies have shown that abnormal cell surface glycosylation is associated with cancer metastasis, which suggests that glycosylation changes may open a new window for discovering metastasis-related pathways. In this study, we used a microarray with 55 lectins to screen for altered glycosylation between two metastatic pancreatic cancer lines (Capan-1 and Su.86.86) and two nonmetastatic pancreatic cancer lines (Panc-1 and MIA PaCa-2), and we further analyzed three lectins with high-binding activities (AAL, UEA-I, and PHA-E) in cell motility assays using these pancreatic cancer cells to detect whether blocking certain forms of cell surface glycosylation affects any processes associated with metastasis. As a result, we found that AAL, a fucose-specific lectin, has different binding patterns between metastatic pancreatic cancer and nonmetastatic pancreatic cancer lines and inhibits cell motility in metastatic pancreatic cancer cells. Furthermore, the N-fucosylation-related genes FUT3, 5, and 6 were found to be responsible for the elevated fucosylation in metastatic pancreatic cells through real-time PCR screening. In summary, our findings that the specific bindings of AAL on cell surfaces and highly expressed FUT3, 5, and 6 in metastatic pancreatic cancer cells, although preliminary, are encouraging, and our established combined method is also suitable for discovering metastasis-related mechanisms in other cancers.

Systemic immune-inflammation index predicts prognosis of patients with advanced pancreatic cancer.

BACKGROUND: Systemic inflammation and immune dysfunction have been proved to be associated with cancer progression and metastasis in various malignancies. The aim of this retrospective study was to evaluate the prognostic significance of pre-treatment systemic immune-inflammation index (SII) in patients with advanced pancreatic cancer. METHODS: In total, 419 patients diagnosed with advanced pancreatic cancer, between January 2011 and December 2015, were retrospectively enrolled. The SII was developed based on a training set of 197 patients from 2011 to 2013 and validated in an independent cohort of 222 patients from 2014 to 2015. Data on baseline clinicopathologic characteristics; pre-treatment laboratory variables such as absolute neutrophil, lymphocyte, and platelet counts; and carbohydrate antigen 19-9 (CA19-9), total bilirubin (TBIL), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) levels were collected. The association between clinicopathologic characteristics and SII was assessed. The overall survival was calculated using the Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic value of the SII. RESULT: An optimal cutoff point for the SII of 440 stratified the patients with advanced pancreatic cancer into high (> 440) and low (≤ 440) SII groups in the training cohort. Univariate and multivariate analyses revealed that the SII was an independent predictor for overall survival. The prognostic significance of the SII was confirmed in both normal and elevated CA19-9 levels. CONCLUSION: The baseline SII serves as an independent prognostic marker for patients with advanced pancreatic cancer and can be used in patients with both normal and elevated CA19-9 levels.

Antipsychotic Polypharmacy in Older Adult Asian Patients With Schizophrenia: Research on Asian Psychotropic Prescription Pattern.

BACKGROUND AND OBJECTIVE: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors. METHODS: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form. RESULTS: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses (P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness (P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics (P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics (P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics (P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP. CONCLUSION: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.

CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer.

More and more evidence has demonstrated that Chromobox protein homolog 3(CBX3) has an important role in carcinogenesis by regulating several mechanisms, such as heterochromatin formation, gene silencing, DNA replication and repair. However, its role in pancreatic cancer has seldom been discussed. In the present study, we silenced CBX3 expression in pancreatic cancer cell lines and identified the positive roles of CBX3 in cancer cell proliferation. Furthermore, we demonstrated that silencing CBX3 in pancreatic cancer cells inhibited aerobic glycolysis, the basis for providing cancer cells with building blocks for macromolecule synthesis and ATP that required. To search for the underlying molecular mechanism, we turned to examine the impact of CBX3 on the expression of FBP1, a negative regulator of aerobic glycolysis in pancreatic cancer and indicated that CBX3 negatively regulated FBP1 expression. Silencing FBP1 expression attenuated the decrease in glycolytic capacity that caused by CBX3 knockdown in pancreatic cancer cells. Taken together, these data reveal that CBX3 serves as a positive regulator of aerobic glycolysis via suppressing of the FBP1 in pancreatic cancer cells. Disrupting the CBX3-FBP1 signaling axis would be effective to treat pancreatic cancer and prevent aerobic glycolysis.

Trends of Polypharmacy and Prescription Patterns of Antidepressants in Asia.

PURPOSE: Little is known regarding the trend of polypharmacy in Asia. We used data from 5 Asian countries to examine the patterns of antidepressant (AD) prescription and trends of psychotropic polypharmacy over time. METHODS: We used the cross-sectional, pharmacoepidemiological data from 2004 and 2013 REAP-AD (Research on Asian Psychotropic Prescription Patterns for Antidepressants) to examine the patterns of AD prescriptions in clinical settings in China, Japan, Korea, Singapore, and Taiwan. We compared the trend in polypharmacy (ie, concomitant use of ≥2 classes of psychotropic) among individuals receiving AD prescriptions in 2004 and 2013 using multivariable logistic regression models in different diagnostic categories. RESULTS: The proportion of patients with psychotropic polypharmacy decreased from 2004 to 2013 in all 3 diagnostic categories, including mood disorders (adjusted odds ratio [aOR], 0.44 [0.35-0.56]; P < 0.001), anxiety disorders (aOR, 0.58 [0.36-0.94]; P = 0.028), and psychotic disorders (aOR, 0.18 [0.05-0.60]; P = 0.006). Among individuals with AD prescriptions, concomitant use of anxiolytics (including sedative-hypnotics) decreased in patients with mood disorders (aOR, 0.34 [0.27-0.42]; P < 0.001) and anxiety disorders (aOR, 0.43 [0.27-0.67]; P < 0.001). In contrast, concomitant use of antipsychotics in patients with mood disorders increased (aOR, 1.43 [1.15-1.77]; P = 0.001), and concomitant use of mood stabilizers in patients with psychotic disorders also increased (aOR, 3.49 [1.50-8.14]; P = 0.004). CONCLUSIONS: This is the first study examining trends in psychotropic polypharmacy in East Asia. We found a generally decreasing trend of psychotropic polypharmacy in contrast to the increasing trend reported from Western countries. These findings could offer significant implications for health system reform or policy making.

Polypharmacy and psychotropic drug loading in patients with schizophrenia in Asian countries: Fourth survey of Research on Asian Prescription Patterns on antipsychotics.

AIM: The aim of the present study was to survey the prevalence of antipsychotic polypharmacy and combined medication use across 15 Asian countries and areas in 2016. METHODS: By using the results from the fourth survey of Research on Asian Prescription Patterns on antipsychotics, the rates of polypharmacy and combined medication use in each country were analyzed. Daily medications prescribed for the treatment of inpatients or outpatients with schizophrenia, including antipsychotics, mood stabilizers, anxiolytics, hypnotics, and antiparkinson agents, were collected. Fifteen countries from Asia participated in this study. RESULTS: A total of 3744 patients' prescription forms were examined. The prescription patterns differed across these Asian countries, with the highest rate of polypharmacy noted in Vietnam (59.1%) and the lowest in Myanmar (22.0%). Furthermore, the combined use of other medications, expressed as highest and lowest rate, respectively, was as follows: mood stabilizers, China (35.0%) and Bangladesh (1.0%); antidepressants, South Korea (36.6%) and Bangladesh (0%); anxiolytics, Pakistan (55.7%) and Myanmar (8.5%); hypnotics, Japan (61.1%) and, equally, Myanmar (0%) and Sri Lanka (0%); and antiparkinson agents, Bangladesh (87.9%) and Vietnam (10.9%). The average psychotropic drug loading of all patients was 2.01 ± 1.64, with the highest and lowest loadings noted in Japan (4.13 ± 3.13) and Indonesia (1.16 ± 0.68), respectively. CONCLUSION: Differences in psychiatrist training as well as the civil culture and health insurance system of each country may have contributed to the differences in these rates. The concept of drug loading can be applied to other medical fields.

Clinical management of gamma-hydroxybutyrate (GHB) withdrawal delirium with CIWA-Ar protocol.

Gamma-hydroxybutyrate (GHB) is a synthetic drug used mainly for recreational purpose. Although the prevalence of GHB abuse is low in Taiwan, GHB has become increasingly popular in certain subpopulations such as clubbers and men who have sex with men (MSM). GHB dependence could be associated with severe withdrawal syndrome including hallucinations and delirium. Despite systematic studies on detoxification and management of GHB withdrawal have been performed, no validated measurement for severity of GHB withdrawal syndrome is available. Here we present a case of GHB withdrawal delirium that was treated successfully with fixed and symptom-triggered benzodiazepine dosing regimen based on Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. The utilization of CIWA-Ar in such cases could offer useful guidance for benzodiazepine dosing. To the best of our knowledge, this is the first case report of GHB withdrawal delirium in Taiwan.

Overexpression of CBX3 in Pancreatic Adenocarcinoma Promotes Cell Cycle Transition-Associated Tumor Progression.

BACKGROUND: Previous studies showed that Chromobox protein homolog 3 (CBX3) was overexpressed in several types of human cancers, however its pattern and role in pancreatic adenocarcinoma (PAAD) has not yet been understood. The aim of this study was to identify the expression and function of CBX3 in PAAD. METHODS: Data of transcriptomic and protein expression of CBX3 in PAAD were collected from different databases and analyzed. The in vitro and in vivo role of CBX3 in PAAD was examined. RESULTS: CBX3 was overexpressed in human PAAD tissues, which was associated with poor prognosis of overall and disease-free survival of the patients. Overexpression of CBX3 induced the in vitro proliferation, anchorage-free growth, migration and invasion of the PAAD cells, and led to in vivo growth of orthotoptic PAAD tumors in mice. GO and KEGG pathway analysis, as well as experimental observation showed that CBX3 may be associated with cell cycle transition of PAAD cells, and cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen (PCNA) may mediate the tumor-promoting action of CBX3. CDK1 knockdown attenuated the cell cycle transition, proliferation and invasion of CBX3-overexpressing PAAD cells. CONCLUSION: Our findings suggest the tumor-promoting role of CBX3 in PAAD to be targeted by novel therapeutic strategies.

Sex and age differences in risk factors of marijuana involvement during adolescence.

OBJECTIVES: We aimed to examine whether there are sex and age differences in psychosocial risk factors of marijuana use during adolescence. METHODS: Data were drawn from 57,767 adolescents (8th and 10th graders) from the 2012-2013 Monitoring the Future study. We examined the association between socio-demographic and behavioral correlates with different frequencies of past-year marijuana use (non-use, occasional use: <10 time, frequent use: 10-39 times, and regular use: 40+ times). We further investigated whether these associations were similar for boys and girls of different ages. RESULTS: Overall, 20.6% of the adolescents reported past-year marijuana use: 12.1% occasional use, 4.3% frequent use, and 3.8% regular use. Girls were less likely to be frequent and regular marijuana users (frequent use: OR=0.83 [0.75, 0.93]; regular use: OR=0.41 [0.36, 0.48]) while no sex difference was noted for occasional use. Also, the odds of deviant behaviors were higher as the frequencies of marijuana use were higher. Compared to younger girls, older boys and girls had higher association between all levels of marijuana use and low self-esteem, low perceived harm, peer influence and perceived easy access. Besides, younger boys were more likely than younger girls to report an association between regular marijuana use with low self-esteem, peer influence, and perceived easy access but not with perceived low harm. CONCLUSIONS/IMPORTANCE: Findings suggest the relationship between these psychosocial correlates and frequency of marijuana involvement varies across sex and age groups. These variations ask for a nuanced approach to prevention of marijuana involvement in different groups of youth.

Acupuncture for cancer-related fatigue in lung cancer patients: a randomized, double blind, placebo-controlled pilot trial.

BACKGROUND: Cancer-related fatigue (CRF) is a distressing symptom that is the most common unpleasant side effect experienced by lung cancer patients and is challenging for clinical care workers to manage. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial to evaluate the clinical effect of acupuncture on CRF in lung cancer patients. Twenty-eight patients presenting with CRF were randomly assigned to active acupuncture or placebo acupuncture groups to receive acupoint stimulation (LI-4, Ren-6, St-36, KI-3, and Sp-6) twice per week for 4 weeks, followed by 2 weeks of follow-up. The primary outcome was the change in intensity of CFR based on the Chinese version of the Brief Fatigue Inventory (BFI-C). As the secondary endpoint, the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) was adopted to assess the influence of acupuncture on patients' quality of life (QOL). Adverse events and safety of treatments were monitored throughout the trial. RESULTS: Our pilot study demonstrated feasibility among patients with appropriate inclusion criteria and good compliance with acupuncture treatment. A significant reduction in the BFI-C score was observed at 2 weeks in the 14 participants who received active acupuncture compared with those receiving the placebo (P < 0.01). At week 6, symptoms further improved according to the BFI-C (P < 0.001) and the FACT-LCS (P = 0.002). There were no significant differences in the incidence of adverse events in either group (P > 0.05). CONCLUSION: Fatigue is a common symptom experienced by lung cancer patients. Acupuncture may be a safe and feasible optional method for adjunctive treatment in cancer palliative care, and appropriately powered trials are warranted to evaluate the effects of acupuncture.