Novel silicene-mesoporous silica nanoparticles conjugated gemcitabine induced cellular apoptosis via upregulating NF-κB p65 nuclear translocation suppresses pancreatic cancer growthin vitroandin vivo.

Pancreatic cancer's high fatality rates stem from its resistance to systemic drug delivery and aggressive metastasis, limiting the efficacy of conventional treatments. In this study, two-dimensional ultrathin silicene nanosheets were initially synthesized and near-infrared-responsive two-dimensional silicene-mesoporous silica nanoparticles (SMSNs) were successfully constructed to load the clinically-approved conventional pancreatic cancer chemotherapeutic drug gemcitabine. Experiments on nanoparticle characterization show that they have excellent photothermal conversion ability and stability. Then silicene-mesoporous silica nanoparticles loaded with gemcitabine nanoparticles (SMSN@G NPs) were employed in localized photothermal therapy to control pancreatic tumor growth and achieve therapeutic effects. Our research confirmed the functionality of SMSN@G NPs through immunoblotting and apoptotic assays, demonstrating its capacity to enhance the nuclear translocation of the NF-κB p65, further affect the protein levels of apoptosis-related genes, induce the apoptosis of tumor cells, and ultimately inhibit the growth of the tumor. Additionally, the study assessed the inhibitory role of SMSN@G NPs on pancreatic neoplasm growthin vivo, revealing its excellent biocompatibility. SMSN@G NPs have a nice application prospect for anti-pancreatic tumors.

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).

Long-term cardiovascular disease mortality among 160 834 5-year survivors of adolescent and young adult cancer: an American population-based cohort study.

AIMS: Our aim was to assess the risk of cardiovascular disease (CVD) mortality in US 5-year survivors of adolescent and young adult (AYA) cancer compared with those of the general population and contemporaneous 5-year survivors of childhood cancer. METHODS AND RESULTS: A total of 160 834 5-year AYA cancer survivors (aged 15-39 years at diagnosis) were included, representing 2 239 390 person-years of follow-up. Overall, 2910 CVD deaths occurred, which was 1.4-fold [95% confidence interval (CI) 1.3-1.4] that expected in the general population, corresponding to 3.6 (95% CI 3.2-3.9) excess CVD deaths per 10 000 person-years. The highest risk of cardiac mortality was experienced after Hodgkin's lymphoma (HL), and the highest risk of cerebrovascular mortality was observed with central nervous system (CNS) tumours. Even survivors in their 6th and 7th decades of life, the risk of CVD mortality remained markedly higher than that of the matched general population. Competing risk analysis showed that the cumulative mortality of CVD was elevated among AYA cancer survivors compared with childhood cancer survivors during the whole study period. CONCLUSION: Long-term AYA cancer survivors have a greater risk of CVD mortality than the US general population and childhood cancer survivors. Vulnerable subgroups, especially survivors of HL and CNS tumours, require continued close follow-up care for cardiovascular conditions throughout survivorship.

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.

Multiple Perspectives Reveal the Role of DNA Damage Repair Genes in the Molecular Classification and Prognosis of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly heterogeneous and immunosuppressive cancer. This study investigated the diversity of DNA damage repair (DDR) and immune microenvironment in PAAD by transcriptomic and genomic analysis. Patients with PAAD were divided into two DDR-based subtypes with distinct prognosis and molecular characteristics. The differential expression genes were mostly enriched in DDR and immune-related pathways. In order to distinguish high- and low-risk groups clinically, a DDR- and immune-based 5-gene prognostic signature (termed DPRS) was established. Patients in the high-risk group had inferior prognosis, a low level of immune checkpoint gene expression and low sensitivity to DDR-associated inhibitors. Furthermore, single-cell sequencing was used to observe the performance of the DDR-based signature in a high dimension, and immunohistochemistry was used to verify the relationship between the genes we identified and the prognosis of patients with PAAD. In conclusion, the DDR heterogeneity of PAAD was demonstrated, and a novel DDR- and immune-based risk-scoring model was constructed, which indicated the feasibility of DPRS in predicting prognosis and drug response in PAAD patients.

Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling.

BACKGROUND: Kaempferol, a natural flavonoid, exhibits anticancer properties by scavenging reactive oxygen species (ROS). However, increasing evidence has demonstrated that, under certain conditions, kaempferol can inhibit tumor growth by upregulating ROS levels. In this study, we aimed to investigate whether kaempferol effectively suppresses pancreatic cancer through upregulation of ROS, and to explore the underlying molecular mechanism. METHODS: PANC-1 and Mia PaCa-2 cells were exposed to different concentrations of kaempferol. Cell proliferation and colony formation were evaluated by CCK-8 and colony formation assays. Flow cytometry was performed to assess the ROS levels and cell apoptosis. The mRNA sequencing and KEGG enrichment analysis were performed to identify differentially expressed genes and to reveal significantly enriched signaling pathways in response to kaempferol treatment. Based on biological analysis, we hypothesized that tissue transglutaminase (TGM2) gene was an essential target for kaempferol to induce ROS-related apoptosis in pancreatic cancer. TGM2 was overexpressed by lentivirus vector to verify the effect of TGM2 on the ROS-associated apoptotic signaling pathway. Western blot and qRT-PCR were used to determine the protein and mRNA levels, respectively. The prognostic value of TGM2 was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) tools based on public data from the TCGA database. RESULTS: Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway. CONCLUSIONS: Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling, and TGM2 may represent a promising prognostic biomarker for pancreatic cancer.

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.

Design and development of spirulina polysaccharide-loaded nanoemulsions with improved the antitumor effects of paclitaxel.

Aims: In this study, we prepared spirulina polysaccharides into spirulina polysaccharide-loaded nanoemulsions (SPS-NEs), and determined the antitumor effect of SPS-NEs, when combined with paclitaxel (PTX).Methods: SPS-NEs were prepared by a phase transformation method. The Characterisation and stability of SPS-NEs was measured. The antitumor effect of SPS-NEs combined with PTX was determined by S180 cells or RAW 264.7 macrophages and S180 tumour-bearing mice.Results: SPS-NEs were spherical and stable, the particle size of SPS-NEs was 84.6 ± 3.31 nm, PDI = 0.235 ± 0.02. PTX + SPS-NEs exhibited a much greater toxicity against RAW 264.7 cells than PTX. PTX + SPS-NEs increased the release of NO, IL-6 and TNF-α, and the expression of p-p65 NF-κB, p-I-κB, TLR4. In addition, PTX + SPS-NEs significantly inhibited tumour growth by 72.82% and increased the secretion of serum IL-2, TNF-α and IFN-γ.Conclusions: SPS-NEs can regulate immunity through TLR4/NF-κB signalling pathways, which enhances the anti-tumour effect of PTX.

Investigation of Early Warning Indexes in a Three-Dimensional Chaotic System with Zero Eigenvalues.

A rare three-dimensional chaotic system with all eigenvalues equal to zero is proposed, and its dynamical properties are investigated. The chaotic system has one equilibrium point at the origin. Numerical analysis shows that the equilibrium point is unstable. Bifurcation analysis of the system shows various dynamics in a period-doubling route to chaos. We highlight that from the evaluation of the entropy, bifurcation points can be predicted by identifying early warning signals. In this manner, bifurcation points of the system are analyzed using Shannon and Kolmogorov-Sinai entropy. The results are compared with Lyapunov exponents.

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.

New therapeutic aspects of steroidal cardiac glycosides: the anticancer properties of Huachansu and its main active constituent Bufalin.

AIM OF THE REVIEW: In the past decade, increasing research attention investigated the novel therapeutic potential of steroidal cardiac glycosides in cancer treatment. Huachansu and its main active constituent Bufalin have been studied in vitro, in vivo and clinical studies. This review aims to summarize the multi-target and multi-pathway pharmacological effects of Bufalin and Huachansu in the last decade, with the aim of providing a more comprehensive view and highlighting the recently discovered molecular mechanisms. RESULTS: Huachansu and its major derivative, Bufalin, had been found to possess anti-cancer effects in a variety of cancer cell lines both in vitro and in vivo. The underlying anti-cancer molecular mechanisms mainly involved anti-proliferation, apoptosis induction, anti-metastasis, anti-angiogenesis, epithelial-mesenchymal transition inhibition, anti-inflammation, Na+/K+-ATPase activity targeting, the steroid receptor coactivator family inhibitions, etc. Moreover, the potential side-effects and toxicities of the toad extract, Huachansu, and Bufalin, including hematological, gastrointestinal, mucocutaneous and cardiovascular adverse reactions, were reported in animal studies and clinic trails. CONCLUSIONS: Further research is needed to elucidate the potential drug-drug interactions and multi-target interaction of Bufalin and Huachansu. Large-scale clinical trials are warranted to translate the knowledge of the anticancer actions of Bufalin and Huachansu into clinical applications as effective and safe treatment options for cancer patients in the future.

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.

Do Patients Diagnosed with Metastatic Pancreatic Cancer Benefit from Primary Tumor Surgery? A Propensity-Adjusted, Population-Based Surveillance, Epidemiology and End Results (SEER) Analysis.

BACKGROUND With the progress in surgical techniques and management of complications, pancreatic resection can be safely performed in experienced hospitals. Pancreatic resection enables surgeons to assess the effect of surgery for metastatic cases, even when there is limited information. In the present study we evaluated the role of primary tumor resection for metastatic pancreatic cancer (mPC) by using the Surveillance, Epidemiology and End Results (SEER) database. MATERIAL AND METHODS Metastatic pancreatic cancer patients treated at our hospital from 2004 to 2015 were identified. The effect of surgery on cancer-specific survival was assessed by restricted mean survival time (RMST) and stabilized inverse probability of treatment weight-adjusted analysis after propensity score matching (PSM). RESULTS A total of 2694 mPC patients were included. Of this population, 365 adults underwent primary tumor resection. After propensity matching, postsurgical patients had longer RMST than non-surgery patients (1: 1 PSM 11.60 months vs. 8.98 months; 1: 2 PSM 11.61 months vs. 9.10 months; p<0.01). Stabilized inverse probability of treatment weight-adjusted analysis yielded similar results (p<0.01). CONCLUSIONS Our study supports the hypothesis that patients with mPC can benefit from primary tumor surgery. However, the surgical inclusion criteria and the appropriate role of surgery, such as its effect on symptom control, quality of life, and the extent to which it prolongs survival for metastatic pancreatic cancer, remain to be completely assessed by well-designed, prospective, randomized clinical trials.