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Cynanchum paniculatum (Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(−) PR(−)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(−)) in a 24 h scratch assay. Our data suggested that ER(−) PR(−) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(−) cells, and this correlated with MMP-2 regulation. The migration of ER(−) PR(−) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis.

Aim Depressive disorders are common in old age. Antipsychotics (APs) are often used as an adjunctive treatment with antidepressants (ADs) in this population but its patterns of use in Asia are not known. This study explored the rate of combination of APs and ADs in older adult psychiatric patients in Asia. Methods This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses. Results A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs. Conclusion Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.

Background: Although disorganized speech is seen as one of the nuclear features of schizophrenia, there have been few reports of disorganized speech-associated psychotropic drug-prescribing patterns in large samples of schizophrenia patients. Objective: We aimed to examine the prevalence of disorganized speech and its correlates in terms of psychotropic drug prescribing, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. Method: A total of 3744 patients with the ICD-10 diagnosis of schizophrenia were enrolled from 71 survey centers in 15 Asian countries/areas. An essential criterion of disorganized speech was that it was “severe enough to impair substantially effective communication” as defined in the DSM-5. A binary logistic model was fitted to identify the psychotropic drug-prescribing correlates of disorganized speech. Results: After adjusting for the potential effects of confounding variables, the binary logistic regression model showed that the presence of disorganized speech was directly associated with adjunctive use of mood stabilizers (P

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). The participants were 1,478 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. The factor analysis identified three factors: F1 (sialorrhea, akathisia, dystonia, and dyskinesia), F2 (gait and bradykinesia), and F3 (muscle rigidity and tremor). The present results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: central dopaminergic mechanisms with the pathophysiology other than acute parkinsonism (F1), acute parkinsonism observed during action (F2), and acute parkinsonism observed at rest (F3).

Work-related musculoskeletal disorders (WMSD) refer to musculoskeletal injuries caused by the occupation. Physical therapists (PTs) suffer from a high risk of WMSD despite their extensive knowledge in ergometrics and injury prevention. This study aims to discover the incidence and prevalence of WMSD among PTs using Taiwan's nationwide claims database. The trend of annual patients seeking rehabilitation and the prevalence of WMSD among PTs were presented. The age- and gender-specific incidence of WMSD were also calculated. The prevalence of WMSD in PTs varied from 6.1% to 75.2%, and the incidence ranged from 6.1 to 29.1 per 100 person-years during 1997 and 2012. For those aged ≤30 years, the incidence was higher in females than males (incidence rate ratio = 1.08, 95% confidence interval [CI]: 1.02-1.14, P = .011), whereas for those aged from 31 to40 years, females had lower incidence of WMSD than males (incidence rate ratio = 0.88, 95% CI: 0.80-0.96, P = .007). The patients/PTs ratio was higher (270.56-337.74) in 1998 and 2004 to 2007 and became stable (245.93-252.82) in 2008 to 2012, correlating with a rise in the WMSD prevalence in 1999 to 2007 and a steady prevalence after 2008 (63.5%-66.3%) in PTs. In conclusion, the risk of WMSD among PTs was positively correlated to the frequency of patients seeking rehabilitation service. In addition, age and gender were important risk factors for developing WMSD among PTs.

Kaempferitrin is extracted in significantly high quantities from the leaves of Cinnamomum osmophloeum, which belongs to a group of plant species that comes under the genus Cinnamomum, well-known for its established anti-diabetic property in Chinese medicine. Oral administration of kaempferitrin and Cinnamomum osmophloeum extract reduced blood sugar in alloxan-induced diabetic rats and improved the lipid profile in hamsters respectively. In this paper we studied the differential protein expression profile using mass spectrometry approach in the kaempferitrin-treated conditioned medium of liver cancer cell line HepG2. We discovered that 33 genes were up/down-regulated consistently between two biological samples. A slightly different version of the analysis software selected 28 genes, and the final 18 genes that appeared in both lists were selected. Interestingly, 5 proteins out of 18 were either exosomal markers or reported in high frequency of occurrence in exosome/secreted vesicles. We also examined the extracellular particles with atomic force microscopy (AFM), which showed that the conditioned medium of kaempferitrin treated had larger vesicles and fewer small vesicles. Expression of some lipid-regulating genes were also altered. Our data suggested that extracellular vesicle secretions may be regulated by kaempferitrin, and regulation of lipid profile by kampeferitrin involves multiple mechanisms.

Cynanchum paniculatum (Bge.) Kitag. (CP) is an important medicinal herb used in Chinese herbal medicine, with a variety of biological activities including anticancer property. In this study, we explored the water extract of CP, for its anticancer effects against breast cancer cells with different mutation types. Cells were grouped as untreated (Control); CP direct treatment (dir-CP); Conditioned medium from CP treated (sup-CP), and untreated cells (sup-Control). Effects of dir-CP and sup-CP were compared to corresponding untreated cells on cytotoxicity, cell migration, and protein expression (cleaved caspase-3, caspase-9, and MMP-2 and 9). CP treatment showed time-dependent decrease in cell number of MDA-MB-231 and SK-Br-3 (both ER(−) PR(−)), while the decrease in cell number was not as significant in MCF-7 and ZR-75-1 cells (both ER(+) PR(+)). sup-CP treatment inhibited the cell migration of MDA-MB-231 and MCF-7 (Her2(−)) in a 24 h scratch assay. Our data suggested that ER(−) PR(−) cells are more sensitive to the CP in terms of direct cytotoxicity, which is not regulated by caspase-3. CP inhibited the migration of the two Her2(−) cells, and this correlated with MMP-2 regulation. The migration of ER(−) PR(−) cells was more sensitive to conditioned medium with CP treatment than to direct CP, and this is not regulated by MMP-2. Our data suggested that CP has anticancer potential on various breast cancer cells through different mechanisms and is specifically effective in inhibiting the migration of the triple negative MDA-MB-231. Our data provide insight into the mechanism of CP against breast cancer progression and would benefit the medical practitioners in better management with CP usage.

Background Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. Subjects and methods Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight pre-obese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. Results In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. Conclusion Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

Background: Recent years have witnessed wide applications of exergames to balance training among the older adults. However, research concerning balance training with the use of Kinect for Xbox has remained scarce. While previous studies have shown the positive effects of exergames on improving balance and preventing falling among the older adults, there has been a paucity of empirical evidence supporting the superiority of Kinect exercise to conventional exercise over balance training among the older adults. Therefore, this study aimed to compare the feasibility, safety, and effectiveness of Kinect exercise against conventional exercise over balance training among the community older adults. Method: A total of 20 participants were randomly assigned to the Kinect Exercise Group (N = 10) or the Conventional Exercise Group (N = 10) for a 5-week balance training (45 minutes a time, 2 times a week). Assessor blinding was employed to assess the participants’ performance before and after the treatment, including 30-Second Chair Stand Test (30-sec CST), Timed Up and Go (TUG), Functional Reach Test (FRT), and One-Leg Stance Test (OLST) respectively with eyes open and closed. Subjective feeling of the intensity of pain and side effects were recorded throughout the investigation period. Nonparametric statistics was used for data analysis. Results: Within-group comparison between the pre-test and post-test indicated that significant differences existed in all of the 5 tests (30-sec CST, TUG, FRT, OLST with eyes open, and OLST with eyes closed) in the Kinect exercise group. To the Conventional exercise group, however, significant differences were only observed in 30-sec CST, FRT and OLST with eyes open. With regard to between-group comparison, significant differences were only found in FRT. Conclusion: Such results indicated that both treatments were helpful in improving the participants’ balance performance, that Kinect exercise was more effective in terms of overall balance ability, and that Kinect exercise was particularly beneficial to functional reach enhancement in comparison with traditional exercise. Kinect exercise could be a feasible, safe, and effective alternative for dynamic balance training among older adults.

Background: PIM-Taiwan criteria were first established in 2010 for potentially inappropriate medications (PIMs). Currently, updating of PIM criteria is mandatory because of newly established evidence and newly developed medications. This study aims to evaluate the prevalence of PIM based on country-specific PIM criteria and factors associated with PIM use by applying 2010 version and newly updating PIM-Taiwan criteria in a cohort with polypharmacy. Methods: The baseline data of Medication Safety Review Clinic Taiwan (MSRC–Taiwan) study were used to investigate the prevalence of PIMs. Older patients (aged ⩾65 years) who were either having polypharmacy or visited ⩾3 different physicians were enrolled between August and October 2007. Bivariate analysis and multivariate logistic regressions were used to evaluate the factors associated with PIM use. Results: The prevalence of having at least one PIM was 46.1% for 2010 version and increased to 74.6% for 2018 version. The average number of PIMs generally to be avoided per patient also increased for 2018 version (0.2 versus 1.2, p < 0.0001). In contrast, the average number of PIMs considering chronic conditions per patient decreased (0.6 versus 0.3, p < 0.001). The associated chronic conditions of PIM users were distinct between 2010 and 2018 version. The major leading PIMs were benzodiazepines (BZDs) in both versions of criteria. Conclusions: As there were significant differences in medication lists between PIM-Taiwan version 2010 and 2018, the prevalence of PIM and factors associated with PIM users varied accordingly. Physicians should pay special attention before prescribing BZDs which keep being the major leading PIM.

Potentially inappropriate medication (PIM) was associated with adverse clinical outcomes and higher healthcare resource utilization among older patients. In order to investigate the prevalence of PIM use based on three different sets of criteria and their associated factors among older patients in the emergency department (ED) in Taiwan. The National Health Insurance Research Database was used for this cross-sectional study. Older patients who visited the ED at least once in 2009 were enrolled. PIMs were identified based on the Beers Criteria, PIM-Taiwan criteria, and PRISCUS criteria. Average patient age was 76.7 ± 7.4 years and patients visited the ED 1.8 ± 2.1 times in 2009. The prevalence and frequency of being prescribed at least one PIM at each visit were high according to all three sets of criteria. Performance of the PIM-Taiwan criteria was only inferior to that of the Beers Criteria. The most important factor associated with PIM was the number of medications prescribed in the ED, and PIM use was associated with higher annual health resource utilization in the ED. PIM use was a significant issue and was associated with higher annual emergency care resource utilization in the ED.

BACKGROUND The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia. METHODS Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data. RESULTS Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P

Background Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. Methods Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression. Loss- and gain-of function assays were performed to investigate the role of Chibby in NPC cells. Western blot, cell proliferation, Glucose uptake, Lactate release, ATP level, and O2 consumption assays were used to determine the mechanism of Chibby regulation of underlying targets. Finally, immunohistochemistry assay of fresh NPC and nasopharyngeal normal tissue sample were used to detect the expression of Chibby, β-Catenin, and PDK1 by immunostaining. Results We observed that Chibby, a β-catenin-associated antagonist, is down-regulated in nasopharyngeal carcinoma cell lines and inhibits Wnt/β-Catenin signaling induced Warburg effect. Mechanism study revealed that Chibby regulates aerobic glycolysis in NPC cells through pyruvate dehydrogenase kinase 1(PDK1), an important enzyme involved in glucose metabolism. Moreover, Chibby suppresses aerobic glycolysis of NPC via Wnt/β-Catenin-Lin28/let7-PDK1 cascade. Chibby and PDK1 are critical for Wnt/β-Catenin signaling induced NPC cell proliferation both in vitro and in vivo. Finally, immunostaining assay of tissue samples provides an important clinical relevance among Chibby, Wnt/β-Catenin signaling and PDK1. Conclusions Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/β-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0769-4) contains supplementary material, which is available to authorized users.

AIM The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long-term prognoses. In this study, we used a nationwide population-based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders. METHODS In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed. RESULTS In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7-year follow-up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%. CONCLUSION Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future.

Aim Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. Methods In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. Results The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. Conclusion We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

Objective: Little is known about the prescription pattern of psychotropic drugs for patients with schizophrenia in Pakistan. The purpose of this study was to evaluate the characteristic features of psychotropic drug prescriptions for patients with schizophrenia in Pakistan. Methods: Three centers in Pakistan participated in a large scale collaborative study known as Research on Asian Prescription Pattern (REAP). The 2016 REAP survey included centers from 15 countries in Asia and used a unified research protocol. The design of the study was quantitative and of descriptive epidemiology. Analysis was made on the data collected from three centers i.e., Lahore, Karachi and Islamabad. The data collected in Pakistan were compared with those from other Asian countries. The details of REAP were presented on the homepage of REAP (http://www.REAP.Asia). Results: From Pakistan, 298 patients were included. Patients with schizophrenia in Pakistan received higher rate of antipsychotic polypharmacy and a higher rate of co-prescription of mood stabilizers and anxiolytics when compared with participants from other South Asian countries (India and Bangladesh). Conclusion: The main findings of the study were that a majority of the patients were prescribed antipsychotic polypharmacy drugs in Pakistan. Insufficient training on the use of psychotropic drugs and a lack of treatment guideline are considered to be the major contributing factors. Further education and training on the proper use of psychotropic drugs are recommended to psychiatrists in Pakistan. The guidelines on pharmacotherapy for patients with schizophrenia should also be developed and promoted in Pakistan.

Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis. Conversely, AR knockdown suppressed lactate formation and inflammation. Using cultured liver cancer cells, we also demonstrated that AKT1 was essential for AR-induced dysregulation of AKT/mTOR signaling, metabolic reprogramming, antioxidant defense, and inflammatory responses. These findings suggest that aberrantly overexpressed/over-activated hepatic AR promotes HCC development at least in part by interacting with oncogenic AKT1 to augment AKT/mTOR signaling. Inhibition of AR and/or AKT1 might serve as an effective strategy for the prevention and therapy of liver cancer.

Air Engines (AE) are commonly designed to work in combination with internal combustion engines (ICE) due to low energy density. The emission of heat from ICE boosts the efficiency of Air Engines, whereas the high-pressure gas from AE serves as a form of turbo charging for ICE, increasing its efficiency. Unlike batteries, the air tank that AE requires is not limited by certain restrictions in order to prolong its lifetime, therefore, the Air Hybrid System is believed to have great potential. There has already been quite some research on power management strategy of electric hybrid systems, however, little is done on Air hybrid systems. A numerical models of Air Hybrid Systems is established using MATLAB in this study, the characteristics of the model, such as the efficiency map and driving cycles are further analyzed to obtain the optimal energy management strategy for Air Hybrid Systems. These findings are expected to help the realization of physical models and the establishment of controller design. Through genetic algorithms, the optimal system structures, operation modes and power management strategies are found to ensure that both engines are operating within the most efficient range. Simulation results suggest that the efficiency of the Air Hybrid System is 26.13% higher comparing to a lone Air Engine.

Aim This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. Methods In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Results Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. Conclusion Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

Aim We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. Methods Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. Results Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. Conclusion Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

Auditory neuropathy is an important entity in childhood sensorineural hearing loss. Due to diverse etiologies and clinical features, the management is often challenging. This study used an integrative patient-history, audiologic, genetic, and imaging-based approach to investigate the etiologies and audiologic features of 101 children with auditory neuropathy. Etiologically, 48 (47.5%), 16 (15.8%), 11 (10.9%), and 26 (25.7%) children were categorized as having acquired, genetic, cochlear nerve deficiency-related, and indefinite auditory neuropathy, respectively. The most common causes of acquired and genetic auditory neuropathy were prematurity and OTOF mutations, respectively. Patients with acquired auditory neuropathy presented hearing loss earlier (odds ratio, 10.2; 95% confidence interval, 2.2–47.4), whereas patients with genetic auditory neuropathy had higher presence rate of distortion product otoacoustic emissions (odds ratio, 10.7; 95% confidence interval, 1.3–85.4). In patients with different etiologies or pathological sites, moderate to strong correlations (Pearson’s r = 0.51–0.83) were observed between behavioral thresholds and auditory steady-state response thresholds. In conclusion, comprehensive assessments can provide etiological clues in ~75% of the children with auditory neuropathy. Different etiologies are associated with different audiologic features, and auditory steady-state responses might serve as an objective measure for estimating behavioral thresholds.

The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia.Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug.Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015).Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

// Jie Jiang 1 , Guojun Geng 1 , Xiuyi Yu 1 , Hongming Liu 1 , Jing Gao 1 , Hanxiang An 2 , Chengfu Cai 1 , Ning Li 1 , Dongyan Shen 3 , Xiaoqiang Wu 3 , Lisheng Zheng 4 , Yanjun Mi 1, 2 , Shuyu Yang 5 1 Department of Thoracic Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 3 Biobank, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 5 Xiamen Diabetes Institution, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Correspondence to: Shuyu Yang, email: yangshuyu2016@126.com Yanjun Mi, email: Myjgj_77@163.com Keywords: dihydroartemisinin, non-small-cell lung cancer, Warburg effect, metastasis, NF-κB Received: April 06, 2016 Accepted: November 02, 2016 Published: November 24, 2016 ABSTRACT Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-κB signaling to inhibit the GLUT1 translocation. Blocking the NF-κB signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-κB signaling pathway and DHA may deserve further investigation in NSCLC treatment.

Capturing hand motions for hand function evaluations is essential in the medical field. Various data gloves have been developed for rehabilitation and manual dexterity assessments. This study proposed a modular data glove with 9-axis inertial measurement units (IMUs) to obtain static and dynamic parameters during hand function evaluation. A sensor fusion algorithm is used to calculate the range of motion of joints. The data glove is designed to have low cost, easy wearability, and high reliability. Owing to the modular design, the IMU board is independent and extensible and can be used with various microcontrollers to realize more medical applications. This design greatly enhances the stability and maintainability of the glove.

Aim Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy. Methods Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk-set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity-scoring method in sensitivity analyses to validate any associations. Results Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose-dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044). Conclusion This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

Aims Little is known about electroconvulsive therapy (ECT) use in Asian inpatients with schizophrenia. This study examined trends of ECT use for schizophrenia patients in Asia between 2001 and 2009 and its independent demographic and clinical correlates. Methods Data on 6761 hospitalized schizophrenia patients (2001 = 2399, 2004 = 2136, and 2009 = 2226) in nine Asian countries and territories were collected by either chart review or interviews during a 1-month period. Patients’ sociodemographic and clinical characteristics, prescriptions of psychotropic drugs and ECT use were recorded using a standardized protocol and data-collection procedure. Results The frequency of ECT was 3.3% in the whole sample; rising from 1.8% in 2001 to 3.3% in 2004 and 4.9% in 2009 (P

Insulin is associated with the progression of numerous different types of cancer. However, the association between insulin and non-small cell lung carcinoma (NSCLC) remains unknown. The aim of the present study was to evaluate the role of insulin in the proliferation, migration and drug resistance of NSCLC cells, and to determine whether the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway was involved. NSCLC cells were treated with insulin in the absence or presence of LY294002, an inhibitor of the PI3K/Akt pathway. Following co-incubation with insulin, cell proliferation and drug resistance were measured by MTT; cell migration was examined by wound healing and Transwell assays; and the expression of cyclin A, proliferating cell nuclear antigen (PCNA), p27, matrix metalloproteinase 3 (MMP3), P-gp and proteins involved in the PI3K/Akt pathway were assessed via western blotting. The results of the current study demonstrated that insulin enhanced the proliferation, migration and drug resistance of NSCLC cells. Correspondingly, insulin upregulated the expression of cyclin A, PCNA, MMP3, P-gp and downregulated p27 expression in NSCLC cells. Following treatment with insulin, it was demonstrated that phospho-Akt expression increased in a dose-dependent manner. However, the effects of insulin on NSCLC cells was inhibited by the PI3K/Akt pathway inhibitor LY294002. Therefore, the results of the current study indicate that insulin is associated with the development of NSCLC by activating the PI3K/Akt pathway. This may improve understanding of the mechanism of action of insulin in NSCLC in the future.

The aberrant expression of retinoic acid receptor-α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells. The expression of RARα was significantly elevated in LSCC tissues compared with adjacent noncancerous tissues (78.1 vs. 6.3%, P

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.

Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD.In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs.The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence.We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.