Medication non-adherence and self-inflicted violence behaviors among 185,800 patients with schizophrenia in the community: a 12-year cohort study.

BACKGROUND: Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose-response relationship existed (hypothesis 2). METHODS: This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of "regular adherence" by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses. RESULTS: One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM < 0.8) had a lower risk of suicide (HR, 0.527, 95% CI, 0.447-0.620), an increased risk of NSSI (HR, 1.229, 95% CI, 1.088-1.388), and non-significant risk of attempted suicide compared with adherence group (PRM ≥ 0.8). For hypothesis 2, the lowest medication adherence (PRM < 0.2) was associated with increased risks of suicide attempt (HR, 1.614, 95% CI, 1.412-1.845), NSSI (HR, 1.873, 95% CI, 1.649-2.126), and a decreased risk of suicide (HR, 0.593, 95% CI, 0.490-0.719). The other non-adherence groups had lower risks for all three self-inflicted violence behaviors. The associations between medication adherence in continuous-variable and three outcomes were consistent with the categorical medication adherence results. CONCLUSIONS: Almost no medication taken as prescribed was associated with an increased risk of suicide attempt and NSSI. However, medication adherence did not appear to prevent completed suicide. Besides, patients with moderate adherence had a lower incidence of suicide attempt and NSSI. These findings highlight the need for a more detailed portrayal of medication adherence and the need to be vigilant for suicide intent in schizophrenics with good medication adherence who may be overlooked previously.

Adverse childhood experiences in offspring living with parental mental illness: a controlled study from China.

BACKGROUND: Adverse childhood experiences (ACEs) affect children's development, and their harm to health is pervasive throughout the life course. AIMS: To identify ACEs and their risk factors in Chinese household with or without parental mental illness. METHODS: A controlled study was conducted among 181 young adults with parental mental illness (positive group) and 201 demographically matched individuals without parental mental illness (negative group). Univariate and multivariate analyses were performed to study the correlation between ACEs and their risk factors. RESULTS: The positive group suffered emotional abuse, domestic violence, bullying, and cumulative ACEs more frequently than the negative group. In the positive group, living in rural areas and having a low household economic status during childhood were identified as risk factors for cumulative ACEs, whereas a higher education level of the mother was a protective factor for cumulative ACEs in univariate analyses. Low household economic status remained an independent risk factor for cumulative ACEs in the positive group in multivariate analyses. CONCLUSIONS: Children living with parental mental illness are more vulnerable to ACEs, and our findings highlight the importance of socioeconomic factors in increasing the risk of ACEs. To alleviate the deleterious impact of parental mental illness on offspring, multidimensional supports are needed.

[Association Between Medication Compliance and Various Risky Behaviors in Patients With Schizophrenia]. / ç²¾ç¥žåˆ†è£‚ç—‡æ‚£è€ æœè¯ä¾ä»Žæ€§ä¸Žä¸åŒç±»åž‹å±é™©è¡Œä¸ºçš„å ³è”ç ”ç©¶.

Objective: To investigate the status of medication adherence and various types of risky behaviors of schizophrenia patients in a certain area of western China and to explore accordingly the correlation between the two. Methods: A total of 292 667 patients with schizophrenia were enrolled in a follow-up survey between 2006 and 2018. In addition, based on the outcome-wide analysis strategy, a multivariate Cox proportional risk regression model was used to estimate and compare the impact of medication adherence on different types of risky behaviors in schizophrenia patients. Results: In this 13-year prospective cohort, 65 175 patients (31.4%) showed good medication adherence, while 142 394 patients (68.6%) showed poor medication adherence. The incidence rates of various risky behaviors during the follow-up period were as follows, minor nuisances, 12.25%, violation of the Law of the People's Republic of China on Penalties for Administration of Public Security (APS law), 3.82%, violation of criminal law, 0.94%, suicide completed, 0.28%, self-harm, 1.42%, and attempted suicide, 0.82%. Schizophrenia patients who had poor medication adherence had higher risks of committing violence against others and self-inflicted injury compared to patients with good medication adherence did, with the associated effects being minor nuisances (hazard ratio [HR]=1.31, 95% confidence interval [CI]: 1.27-1.35), violation of APS law (HR=1.47, 95% CI: 1.38-1.56), violation of criminal law (HR=1.17, 95% CI: 1.05-1.31), and self-harm (HR=1.43, 95% CI: 1.32-1.56), respectively, while the risk of suicide completed is lower in schizophrenia patients with poor medication adherence than that in patients with good medication adherence (HR=0.56, 95% CI: 0.47-0.66). There was no statistically significant association between attempted suicide and medication adherence. Conclusion: There are variations in the direction and strength of the association between medication adherence and different types of risky behaviors and further research is needed to elucidate the mechanisms of the association.

[Factors Influencing Suicide Deaths in Patients With Schizophrenia Based on Cohort Data: An Empirical Study of a Sample of 170006 Patients in Sichuan Province].

Objective: To prospectively explore the risk factors of suicide in patients with schizophrenia. Methods: Data on schizophrenia patients in Sichuan Province between 2006 and 2018 were obtained from the National Severe Mental Disorders Information System, and the Cox proportional hazards regression model was used to explore for risk factors for suicide in schizophrenia patients. Result: A total of 170006 patients with schizophrenia were included in the study. At the end of the follow-up period, 160570 patients were alive and 9436 died from various causes, 929 of which being suicide deaths, resulting in a suicide rate of 223.61/100, 000 person-years. The Cox proportional hazards regression model suggested that risk factors for suicide in patients with schizophrenia included poverty ( HR=1.20, 95% CI: 1.02-1.41), higher education level (primary school [ HR=1.32, 95% CI: 1.09-1.60], middle school [ HR=1.40, 95% CI: 1.14-1.73], high school and above [ HR=1.93, 95% CI: 1.49-2.52]) in comparison with illiteracy and semi-literacy, suicide attempts ( HR=2.70, 95% CI: 1.70-4.29), strict medication compliance ( HR=1.91, 95% CI: 1.66-2.20), history of antipsychotic drug therapy ( HR=1.42, 95% CI: 1.06-1.90), younger age group of patients of 46-60 ( HR=1.95, 95% CI: 1.60-2.39), 31-45 ( HR=3.61, 95% CI: 2.92-4.47), and 15-30 ( HR=12.37, 95% CI: 9.69-15.78) compared with the 61-90 age group, and doing agriculture jobs ( HR=1.36, 95% CI: 1.13-1.65). Conclusion: Young and middle-aged schizophrenia patients with higher education levels, especially those with a history of suicide attempts, are at high risk for suicide. Focused interventions should be directed at high-risk groups to reduce suicide deaths in patients with schizophrenia.

[Quality of Life and Its Influencing Factors Among Schizophrenia Patients Living in Urban and Rural Areas].

Objective: To investigate the status quo of the quality of life of schizophrenia patients in a city in Sichuan Province and to explore, thereof, the urban-rural differences in the factors influencing their quality of life. Methods: A total of 824 schizophrenia patients were selected for the study through multistage stratified cluster random sampling method. All the subjects were selected from a pool of patients covered by the Sichuan Provincial Information System for the Comprehensive Management of Severe Mental Disorders. Questionnaire surveys were conducted with the Schizophrenia Quality of Life Scale (SQLS), the Social Support Rating Scale (SSRS), the general circumstance questionnaire, and the lifestyle questionnaire. In addition, univariate and multiple linear regression models were used to analyze the influencing factors of quality of life among schizophrenia patients living in urban areas and those in rural areas. Results: Rural patients had poorer quality of life than urban patients did in all measurement domains ( P<0.05). Marital status, vocational skills, physical exercise, and social support were influencing factors of the quality of life among urban patients ( P<0.05). Age, marital status, annual household income, vocational skills, participation in community rehabilitation activities, and the time required to walk to the nearest medical institution were influencing factors of the quality of life among rural patients ( P<0.05). Conclusion: Targeted measures for the enhancement of the quality of life of schizophrenia patients should be formulated on the basis of urban and rural characteristics in terms of economic support, vocational skills training, input in mental health services, community rehabilitation services, and social support.

Quality of life and its influencing factors in patients with schizophrenia. / ç²¾ç¥žåˆ†è£‚ç—‡æ‚£è€ ç”Ÿæ´»è´¨é‡åŠå ¶å½±å“å› ç´ .

Schizophrenia is a chronic mental disease. With the change of medical model, quality of life has gradually become an important prognostic indicator for patients with schizophrenia. People with schizophrenia have a lower quality of life than the general population or people with other chronic diseases, Sociodemographic factors such as age, gender, employment, education level, income and living situation; clinical factors such as psychiatric symptoms, medication compliance and insight; and psychosocial factors such as social support, cognition, stigma, self-esteem and needs are the main influencing factors for schizophrenia patients. Medication and psychological interventions such as social skills training, family intervention, cognitive correction and cognitive behavioral therapy can be used to improve the quality of life of patients with schizophrenia. Understanding the factors affecting the quality of life of schizophrenia patients and the improvement measures helps to provide reference for improving their quality of life.

Investigation of the In Vivo, In Vitro, and In Silico Wound Healing Potential of Pinctada martensii Purified Peptides.

Previous studies found that both oral and topical administration of enzymatic digestion products < 3 K Da ultrafiltration fractions of Pinctada martensii mantle (PMPs) had pro-healing effects. Thus, we further purified them by Sephadex-G25 and screened them by cellular assays to obtain Pinctada martensii purified peptides (PMPPs). In this study, we explored the mechanism of PMPPs on wound healing by in vivo, in vitro, and in silico experiments. LC-MS/MS results showed that PMPPs consisted of 33 peptides with molecular weights ranging from 758.43 to 2014.04 Da, and the characteristic peptide was Leu-Asp. The results of cellular assays showed that PMPPs promoted the proliferation of human skin fibroblasts (HSF) (135%) and human immortalized keratinocyte (HaCaT) cells (125%) very significantly at 12.5 µg/mL. The in vivo results showed that PMPPs could achieve scarless healing by inhibiting the inflammatory response, accelerating the epithelialization process, and regulating collagen I/III ratio. The optimal peptide sequence FAFQAEIAQLMS of PMPPs was screened for key protein receptors in wound healing (EGFR1, FGFR1, and MMP-1) with the help of molecular docking technique, which also showed to be the key pro-healing active peptide sequence. Therefore, it may provide a therapeutic strategy with great potential for wound healing.

Can scope-of-practice transfer psychiatrists be up for their job? A cross-sectional study of clinical competence status and related factors.

BACKGROUND: The great economic and social changes have resulted in the prevalence of mental disorder increasing year by year in China. Mental health medical service resources of China are significantly insufficient. The program of Transfer Training for psychiatrist was launched in China in October 2015. Thousands of physicians completed the transfer training and obtained certificates. To date, there is little evidence to identify the status and related factors of clinical competence among scope-of-practice transfer psychiatrists in China. PURPOSE: This study aimed to investigate the status and related factors of clinical competence among scope-of-practice transfer psychiatrists of Sichuan Province, China. PATIENTS AND METHODS: The sample was composed of 291 physicians who certificated the transfer training. Data were collected between September and November 2021, using self-made questionnaire with a total of 22 items to record demographic characteristics, practice status and workplace of participants. Descriptive statistics analysis, independent sample T-test, one-way ANOVA, Spearman rank correlation, and multiple regression analysis were used to analyze the data. RESULTS: The clinical competence of participants score was (8.02 ± 1.48). Significant differences were found in clinical competence scores among: the subgroups of practice category, reasons for attending in the transfer training for psychiatrists, whether transfer to/ add mental health practice registration, whether engage in mental / psychological work after training, whether the level of transfer training meeting participants' job needs, whether the level of transfer training meeting their theoretical learning needs, whether the level of transfer training meeting their clinical practice needs, salary change compared with pre-training, whether join in continuing education after training, whether wanted to join in continuing education after training, whether the workplace before training has mental / psychological department, whether the workplace after training has mental / psychological department, institutional nature, institutional level and institutional affiliation. Multiple regression analysis identified that level of transfer training meeting participants' job needs, level of transfer training meeting their clinical practice needs, Whether the workplace before training has mental / psychological department, whether wanted to join in continuing education after training, institutional nature were the contributors of clinical competence. CONCLUSION: The study demonstrated that clinical competence of scope-of-practice transfer psychiatrists needed to be improved. Whether workplace has mental/psychological departments was an important factor of clinical competence. Besides, interest of physicians is another crucial factor for their clinical competence. The continuing education of those psychiatrists may be one effective measure considering their factual working conditions.

A longitudinal study on emotional distress among local government staff seven years after the 2008 Wenchuan earthquake in China.

BACKGROUND: The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality of life (ProQOL) on emotional distress. METHODS: This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL. RESULTS: The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress. CONCLUSIONS: Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.

Effects of camptothecin on histological structures and gene expression profiles of fat bodies in Spodoptera frugiperda.

Spodoptera frugiperda is a serious threat to global food production. Our previous study demonstrated that Camptothecin (CPT), a bioactive secondary metabolite from Camptotheca acuminata (Decne: Nyssaceae), exhibits adverse impact on the larval midgut of S. frugiperda and inhibits insect growth. However, effects of CPT on fat bodies of S. frugiperda larvae have not been examined yet. In the present study, we found that histological structures of fat bodies of S. frugiperda larvae were damaged in insects treated with CPT. Comparative transcriptomic analyses among different fat body samples from controls and insects treated with 1.0 and 5.0 µg/g CPT were performed. A total of 4212 and 5044 differentially expressed genes (DEGs) were identified in the samples treated with 1.0 and 5.0 µg/g CPT, respectively. Our data indicated that the pathways of detoxification, immune response, fatty acids, chitin, and hormone biosynthesis in fat bodies were affected by CPT treatments based on DEGs. These results provided a comprehensive view of the damage and gene expression changes in fat bodies of S. frugiperda after CPT exposure, which shall be useful to reveal the mechanism of CPT toxicity against S. frugiperda in future.

Risk behavior in patients with severe mental disorders: a prospective study of 121,830 patients managed in rural households of western China.

BACKGROUND: The management of severe mental disorder (SMD) patients in communities is an important initiative of healthcare reform in China. Yet the effects in terms of risk behavior of patients are unclear, particularly in rural areas. This study aims to examine high risk behaviors, changing trends, and possible associated factors among SMD patients in the rural areas of western China. METHODS: This analysis examined incidence rate (IR) of high risk behavior of 121,830 managed SMD patients in rural area of Sichuan province, based on data from the national system from 2006 to 2013. Register rate, high risk behavior IR, and time distribution and area distribution of high risk behavior were described. Two-level Poisson regression model was used to analyze associates of high risk behavior of patients, which include demographic characteristics at individual level, socio-economic condition and health system indicators at region level. RESULTS: It was revealed that 6804 (5.58%) of managed patients were involved in 17,220 high risk behavior events, which gave an overall IR of 0.0998 (per person year) on the basis of 172,564 person years of follow-up. The IR varied widely across municipalities, in the range of 0.0305-0.3397. The IR of high risk behavior in the cohort had increased since 2006, and peaked by 2011, at 0.2392. At the individual level, males aged 25 to 44, who were unmarried and in poverty, illiterate or semiliterate, had a family history of mental disorders and antipsychotic treatments, longer duration illnesses, were associated with an increased IR risk. At the regional level, higher psychiatric practitioner visits and the lower annual net income of rural residents per capita, were associated with an increased IR risk. CONCLUSIONS: This is the first large prospective study that revealed the current situation of the register rate, high risk behavior incidence rate in SMD patients in rural area of western China, and examined associates and the differences of high risk behavior of patients among municipalities. The findings may provide evidences that lead to guide prevention and control for risk behavior in SMD patients in rural areas of China, as well as to improve mental health services for this population. It could provide some reference for other developing countries too.

A new small-molecule Aurora B inhibitor shows antitumor activity in human cancer cell lines.

The Aurora kinase family, as a group of serine/threonine kinases regulating cell cycles, are frequently overexpressed or amplified in human tumors. Here, we showed that the small molecule S4 could inhibit Aurora kinase in both of biochemincal and cell-based levels. The Aurora B inhibition of S4 treatment inhibited the phosphorylation of Histone H3 at serine 10 in HeLa and SMMC7721 cells. Cell proliferation assay showed that inhibition of Aurora kinase led to reduced cancer cell growth. As assessed in colony formation experiment, S4 blocked the capability of the HeLa cells to develop colonies. Subsequently, S4 treatment blocked the mitotic G2/M-G1 phase progression which is characterized by the accumulations of cells with 4 N DNA content, induced a cell cycle arrest in a pseudo G1 phase and resulted in apoptotic cell death in a dose- and time-dependent manners. Taken together, this Aurora kinase inhibitor S4 induces growth inhibition of cancer cell line.

Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages.

BACKGROUND: The molecular history of animal evolution from single-celled ancestors remains a major question in biology, and little is known regarding the evolution of cell cycle regulation during animal emergence. In this study, we conducted a comprehensive evolutionary analysis of CDK and cyclin proteins in metazoans and their unicellular relatives. RESULTS: Our analysis divided the CDK family into eight subfamilies. Seven subfamilies (CDK1/2/3, CDK5, CDK7, CDK 20, CDK8/19, CDK9, and CDK10/11) are conserved in metazoans and fungi, with the remaining subfamily, CDK4/6, found only in eumetazoans. With respect to cyclins, cyclin C, H, L, Y subfamilies, and cyclin K and T as a whole subfamily, are generally conserved in animal, fungi, and amoeba Dictyostelium discoideum. In contrast, cyclin subfamilies B, A, E, and D, which are cell cycle-related, have distinct evolutionary histories. The cyclin B subfamily is generally conserved in D. discoideum, fungi, and animals, whereas cyclin A and E subfamilies are both present in animals and their unicellular relatives such as choanoflagellate Monosiga brevicollis and filasterean Capsaspora owczarzaki, but are absent in fungi and D. discoideum. Although absent in fungi and D. discoideum, cyclin D subfamily orthologs can be found in the early-emerging, non-opisthokont apusozoan Thecamonas trahens. Within opisthokonta, the cyclin D subfamily is conserved only in eumetazoans, and is absent in fungi, choanoflagellates, and the basal metazoan Amphimedon queenslandica. CONCLUSIONS: Our data indicate that the CDK4/6 subfamily and eumetazoans emerged simultaneously, with the evolutionary conservation of the cyclin D subfamily also tightly linked with eumetazoan appearance. Establishment of the CDK4/6-cyclin D complex may have been the key step in the evolution of cell cycle control during eumetazoan emergence.

Glyoxalase 1 is up-regulated in hepatocellular carcinoma and is essential for HCC cell proliferation.

Glyoxalase 1 (Glo1), belonging to the glyoxalase system, participates in the detoxification of methylglyoxal (MG), a byproduct of glycolysis. Glo1 is associated with the progression of many human malignancies. However, the role of Glo1 in hepatocellular carcinoma (HCC) is unclear. We have discovered that the expression of Glo1 is up-regulated in HCC tissues compared with adjacent non-tumorous tissues, and knockdown of Glo1 expression by RNA interference significantly inhibited the proliferation of human HCC cell lines. Glo1 knockdown resulted in the accumulation of its cytotoxic substrate, MG. Overall, thus Glo1 might be essential for HCC progression and can be designated as a potential therapeutic target for HCC in the future.

Zinc finger transcription factor 191, directly binding to ß-catenin promoter, promotes cell proliferation of hepatocellular carcinoma.

UNLABELLED: Activation of ß-catenin, the central effector of the canonical wingless-type (Wnt) pathway, has been implicated in hepatocellular carcinoma (HCC). However, the transcription regulation mechanism of the ß-catenin gene in HCC remains unknown. Here we report that human zinc finger protein 191 (ZNF191) is a potential regulator of ß-catenin transcription. ZNF191, a Krüppel-like protein, specifically interacts with the TCAT motif, which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase (TH) gene ex vivo. We demonstrate that ZNF191 is significantly overexpressed in human HCC specimens and is associated with growth of human HCC cells. Global profiling of gene expression in ZNF191 knockdown human hepatic L02 cells revealed that the important Wnt signal pathway genes ß-catenin and cyclin D1 messenger RNAs (mRNAs) are significantly down-regulated. In agreement with transcription level, ß-catenin and cyclin D1 proteins are also down-regulated in transient and stable ZNF191 knockdown L02 and hepatoma Hep3B cell lines. Moreover, significant correlation between ZNF191 and ß-catenin mRNA expression was detected in human HCCs. Promoter luciferase assay indicated that ZNF191 can increase transcription activity of the full-length ß-catenin (CTNNB1) promoter, and nucleotide (nt)-1407/-907 of the CTNNB1 promoter exhibited the maximum transcriptional activity. Electrophoretic mobility shift assay showed that purified ZNF191 protein can directly bind to the CTNNB1 promoter, and the binding region is located at nt-1254/-1224. Finally, we demonstrate that the key binding sequence of ZNF191 in vivo is ATTAATT. CONCLUSION: ZNF191 can directly bind to the CTNNB1 promoter and activate the expression of ß-catenin and its downstream target genes such as cyclin D1 in hepatoma cell lines. This study uncovers a new molecular mechanism of transcription regulation of the ß-catenin gene in HCC.

Effects of azadirachtin on detoxification-related gene expression in the fat bodies of the fall armyworm, Spodoptera frugiperda.

The fall armyworm, Spodoptera frugiperda, has become a worldwide pest and threatens world food production. A previous study indicated that azadirachtin, the most effective botanical insecticide for S. frugiperda, inhibits larval growth of the insect. The effect of azadirachtin on the tissues of the larvae, however, remains to be determined. In this study, the effects of azadirachtin on the structure of fat bodies were analyzed. Comparative transcriptomic analysis was conducted between controls and samples treated with 0.1 µg/g azadirachtin for 7 days to explore potential relevant mechanisms. The expression of 5356 genes was significantly affected after azadirachtin treatment, with 3020 up-regulated and 2336 down-regulated. Among them, 137 encode detoxification enzymes, including 53 P450s, 20 GSTs, 27 CarEs, 16 UGTs, and 12 ABC transporters. Our results indicated that azadirachtin could destroy fat body structure and change the mRNA levels of detoxification-related genes. The up-regulated genes encoding detoxification enzymes might be related to detoxifying azadirachtin. Our results elucidate a preliminary mechanism of azadirachtin detoxification in the fat bodies of S. frugiperda larvae.

Risk factors for mortality due to natural causes and suicide among people with severe mental illness in western China.

Excess mortality in people with severe mental illness (SMI) has been extensively reported. However, little is known about mortality due to natural causes and suicide and their risk factors among people with SMI in western China. The study was conducted to determine the risk factors of natural death and suicide among people with SMI in western China. A totoal of 20,195 SMI patients in western China derived from severe mental illness information system in Sichuan province (January 1, 2006, through July 31, 2018) were included in the cohort study. Mortality rates per 10,000 person-years of natural causes and suicide for patients were calculated with different characteristics. Fine-Gray competing risk model was used to identify risk factors of natural death and suicide. The mortality was 132.8 per 10,000 person-years for natural death and 13.6 per 10,000 person-years for suicide. Males, older age, divorced/widowed, poverty and no anti-psychotic treatment were significantly associated with natural death. Higher education and suicide attempt were strong risk factors of suicide. Risk factors were not shared across natural death and suicide among people with SMI in western China. Risk management and interventions for people with SMI should be tailored for specific causes of death.

Medication Nonadherence and Risk of Violence to Others Among Patients With Schizophrenia in Western China.

Importance: Reducing violence to others in community-based patients with schizophrenia has important implications for public health. Increasing medication adherence is often used to reduce the risk of violence, yet little is known about the association between medication nonadherence and violence to others in this population. Objective: To examine the association between medication nonadherence and violence to others among community-based patients with schizophrenia. Design, Setting, and Participants: This large, naturalistic, prospective cohort study was performed in western China from May 1, 2006, to December 31, 2018. The data set was from the integrated management information platform for severe mental disorders. As of December 31, 2018, 292 667 patients with schizophrenia were registered in the platform. During follow-up, patients could enter or leave the cohort at any time. Maximum follow-up was 12.8 years, with a mean (SD) of 4.2 (2.3) years. Data analysis was conducted from July 1, 2021, to September 30, 2022. Exposures: Medication nonadherence. Main Outcomes and Measures: Violence to others throughout the follow-up period was the outcome, including minor nuisances, violating the Law of the People's Republic of China on Penalties for Administration of Public Security (APS law), and violating criminal law. Information about these behaviors was provided by the public security department. Directed acyclic graphs were used to identify and control confounders. Propensity score matching and generalized linear mixed-effects models were used for analysis. Results: The final study sample included 207 569 patients with schizophrenia. The mean (SD) age was 51.3 (14.5) years, and 107 271 (51.7%) were women; 27 698 (13.3%) perpetrated violence to others, including 22 312 of 142 394 with medication nonadherence (15.7%) and 5386 of 65 175 with adherence (8.3%). In 112 710 propensity score-matched cases, risks of minor nuisances (odds ratio [OR], 1.82 [95% CI, 1.75-1.90]; P < .001), violating APS law (OR, 1.91 [95% CI, 1.78-2.05]; P < .001), and violating criminal law (OR, 1.50 [95% CI, 1.33-1.71]; P < .001) were higher in patients with nonadherence. However, the risk did not increase with higher medication nonadherence. There were differences in risk of violating APS law between urban and rural areas. Conclusions and Relevance: Medication nonadherence was associated with a higher risk of violence to others among community-based patients with schizophrenia, but the risk did not increase as medication nonadherence increased.

Childhood experiences and needs of offspring living with paternal and maternal severe mental illness: A retrospective study in China.

OBJECTIVE: Parental mental illness is considered one of the strongest risk factors for the development of children. This study aimed to describe the adverse childhood experiences and needs of offspring living with parental severe mental illness (SMI) in China and to compare the differences in needs between offspring living with maternal SMI and those living with paternal SMI. METHOD: Overall, 381 participants, including 76 living with paternal SMI, 104 living with maternal SMI, and 201 living without parental mental illness, were enrolled. Data were collected using questionnaires from five sites in China. Differences among the three groups were compared using analysis of variance and chi-square test. Factors were extracted using exploratory factor analysis, and differences in factor scores between the paternal and maternal SMI groups were compared using the rank sum test. RESULTS: The percentages of poverty, family care, and housework were significantly higher in the paternal SMI group and maternal SMI group, compared with the control group, and those of school dropout and relationship with friends were significantly higher in the maternal SMI group (p < 0.0167). The need for stigma reduction in the maternal SMI group was significantly higher than that in the paternal SMI group (p = 0.015). CONCLUSION: Our findings highlight the importance of considering the impact of maternal and paternal SMI on child development. There is an urgent need to develop a national program to assist families with mentally ill parents to provide services for children living with parental SMI.

Caenorhabditis elegans UCP4 protein controls complex II-mediated oxidative phosphorylation through succinate transport.

The novel uncoupling proteins (UCP2-5) are implicated in the mitochondrial control of oxidant production, insulin signaling, and aging. Attempts to understand their functions have been complicated by overlapping expression patterns in most organisms. Caenorhabditis elegans nematodes are unique because they express only one UCP ortholog, ceUCP4 (ucp4). Here, we performed detailed metabolic analyzes in genetically modified nematodes to define the function of the ceUCP4. The knock-out mutant ucp4 (ok195) exhibited sharply decreased mitochondrial succinate-driven (complex II) respiration. However, respiratory coupling and electron transport chain function were normal in ucp4 mitochondria. Surprisingly, isolated ucp4 mitochondria showed markedly decreased succinate uptake. Similarly, ceUCP4 inhibition blocked succinate respiration and import in wild type mitochondria. Genetic and pharmacologic inhibition of complex I function was selectively lethal to ucp4 worms, arguing that ceUCP4-regulated succinate transport is required for optimal complex II function in vivo. Additionally, ceUCP4 deficiency prolonged lifespan in the short-lived mev1 mutant that exhibits complex II-generated oxidant production. These results identify a novel function for ceUCP4 in the regulation of complex II-based metabolism through an unexpected mechanism involving succinate transport.