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To comprehensively investigate the risk factors associated with depression, traditional Chinese medicine constitution (TCMC) has been found to be related to depression. However, the underlying mechanism remains unclear. This study examined the association between the concept of unbalanced TCMCs and major depressive disorder (MDD), investigated the overlapping polygenic risks between unbalanced TCMC and MDD, and performed a mediation test to establish potential pathways. In total, 11,030 individuals were recruited from the Taiwan Biobank, and the polygenic risk score (PRS) for MDD for each participant was calculated using the data from the Psychiatric Genomics Consortium. Unbalanced TCMC were classified as yang-deficiency, yin-deficiency, and stasis. The MDD PRS was associated with yang-deficiency odds ratio [OR] per standard deviation increase in standardized (PRS = 1.07, p = 0.0080), yin-deficiency (OR = 1.07, p = 0.0030), and stasis constitution (OR = 1.06, p = 0.0331). Yang-deficiency (OR = 2.07, p < 0.0001) and stasis constitutions (OR = 1.65, p = 0.0015) were associated with an increased risk of MDD. A higher number of unbalanced constitutions was associated with MDD (p < 0.0001). The effect of MDD PRS on MDD was partly mediated by yang-deficiency (10.21%) and stasis (8.41%) constitutions. This study provides evidence for the shared polygenic risk mechanism underlying depression and TCMC and the potential mediating role of TCMC in the polygenic liability for MDD., (© 2024 Wiley Periodicals LLC.)

The genus Camellia is widely distributed, primarily in East Asia. Camellia japonica is located at the northern limit of this genus distribution, and understanding changes in its distribution is crucial for understanding the evolution of plants in this region, as well as their relationship with geological history and climate change. Moreover, the classification of sect. Camellia in Japan has not been clarified. Therefore, this study aims to understand the evolutionary history of the Japanese sect. Camellia . The genetic population structure was analysed using SNP data and MIG-seq. The relationship between the Japanese sect. Camellia , including the related species in China, was further inferred from the phylogeny generated by RA x ML, SplitsTree and PCA. Population genetic structure was inferred using a Bayesian clustering method (ADMIXTURE). We subsequently employed approximate Bayesian computation, which was further supported by the coalescent simulations (DIYABC, fastsimcoal and Bayesian Skyline Plots) to explore the changes in population, determining which events appropriately explain the phylogeographical signature. Ecological niche modelling was combined with genetic analyses to compare current and past distributions. The analyses consistently showed that C. japonica and C. rusticana are distinct, having diverged from each other during the Middle to Late Miocene period. Furthermore, C. japonica differentiated into four major populations (North, South, Ryukyu-Taiwan and Continent). The Japanese sect. Camellia underwent speciation during archipelago formation, reflecting its ancient evolutionary history compared with other native Japanese plants. C. rusticana did not diverge from C. japonica in snow-rich environments during the Quaternary period. Our results suggest that both species have been independent since ancient times and that ancestral populations of C. japonica have persisted in northern regions. Furthermore, the C. japonica population on the continent is hypothesised to have experienced a reverse-colonisation event from southern Japan during the late Pleistocene glaciation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis. We also additionally describe two longitudinal cohorts - the Brisbane Longitudinal Twin Study in Australia and the Lifelines Cohort Study in the Netherlands. By applying the methodological framework to these two unique datasets, our future research will explore the complex interplay between genetic factors, gene expression, and environmental influences on substance use behaviors and disorders across different life stages and populations.

To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRS SCZ ) and BPD (PRS BPD ), shared PRS between SCZ and BPD (PRS SCZ+BPD ), and SCZ-specific PRS (PRS SCZvsBPD ). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRS SCZ was split into PRS SCZ&#95;concordant /PRS SCZ&#95;discordant , and PRS BPD was split into PRS BPD&#95;concordant /PRS BPD&#95;discordant . Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRS SCZ, PRS BPD , and PRS SCZ+BPD were positively associated with educational attainment, whereas PRS SCZvsBPD was negatively associated with educational attainment. PRS SCZ was negatively associated with MMSE, while PRS BPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRS SCZ&#95;concordant and PRS BPD&#95;concordant mainly determined these effects mentioned above . PRS SCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous., Competing Interests: Competing interests CYC is an employee of Biogen. The remaining authors declare no conflict of interest., (© 2024. The Author(s).)

The mechanism underlying the co-occurrence of major depressive disorder (MDD) and gynecological diseases remains unclear. This study aimed to investigate the familial co-aggregation and shared genetic loading between MDD and gynecological diseases, namely dysmenorrhea, endometriosis, uterine leiomyomas (UL), and polycystic ovary syndrome (PCOS). Overall, 2,121,632 females born 1970-1999 with parental information were enrolled from the Taiwan National Health Insurance Research Database (NHIRD); 25,142 same-sex twins and 951,779 persons with full-sibling(s) were selected. Genome-wide genotyping data were available for 67,882 unrelated female participants from the Taiwan Biobank linked to the NHIRD. A generalized linear model with a logistic link function was used to examine the associations of individual history, family history in parents/full-siblings/same-sex twins, and polygenic risk scores (PRS) for MDD with the risk of gynecological diseases; generalized estimating equations were used to consider the non-independence of data. Both parents affected with MDD was associated with four gynecological diseases, and its magnitude of association was higher than either affected parent; maternal MDD showed a higher magnitude of association than paternal MDD. Full-siblings of patients with MDD had a higher risk of four gynecological diseases; same-sex twins of patients with MDD had a greater association with dysmenorrhea and PCOS. PRS for MDD was associated with dysmenorrhea and endometriosis. Familial co-aggregation was observed in the co-occurrence of MDD and four gynecological diseases. There exists a shared polygenic liability between MDD and dysmenorrhea and endometriosis. Individuals with MDD-affected relatives or a higher PRS for MDD should be monitored for gynecological diseases., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or nonfinancial interests to disclose., (© 2024. Springer Nature B.V.)

Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.

Background: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear., Methods: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa., Results: Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively., Conclusions: There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa., (© 2024. The Author(s).)

In recent years, embedded system technologies and products for sensor networks and wearable devices used for monitoring people's activities and health have become the focus of the global IT industry. In order to enhance the speech recognition capabilities of wearable devices, this article discusses the implementation of audio positioning and enhancement in embedded systems using embedded algorithms for direction detection and mixed source separation. The two algorithms are implemented using different embedded systems: direction detection developed using TI TMS320C6713 DSK and mixed source separation developed using Raspberry Pi 2. For mixed source separation, in the first experiment, the average signal-to-interference ratio (SIR) at 1 m and 2 m distances was 16.72 and 15.76, respectively. In the second experiment, when evaluated using speech recognition, the algorithm improved speech recognition accuracy to 95%.

Objectives  This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods  This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results  We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p  = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions  Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: This study explored the phenotypic association of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BPD), with a range of substance involvement, including lifetime experience and age at initiation of tobacco, alcohol, and betel nut use. Additionally, we elucidated polygenic risk score (PRS) association., Methods: In total, 132,615 community participants were recruited from the Taiwan Biobank. Genome-wide genotyping data were available for 106,806 unrelated individuals, and the PRS for MDD and BPD was calculated. The significance of mood disorders and PRSs associated with substance involvement were evaluated using a linear/logistic regression model with adjustment for potential confounders. Sex differences were assessed., Results: MDD and BPD were associated with regular alcohol consumption, drinking cessation, tobacco smoking, smoking cessation, betel nut chewing, and earlier onset of drinking. BPD was associated with an earlier onset of smoking. MDD PRS was associated with regular alcohol use (odds ratio [OR] per standard deviation increase in PRS = 1.03, p = 0.018), alcohol cessation (OR = 1.05, p = 0.03), regular tobacco use (OR = 1.08, p < 0.0001), and betel nut chewing (OR = 1.06, p < 0.0001), whereas BPD PRS was not associated with substance use. Phenotypic association strengths between MDD/BPD and regular drinking/smoking and the polygenic association between MDD PRS and regular smoking were larger in females than in males., Limitations: Retrospective self-reported MDD/BPD diagnoses and substance involvement., Conclusions: Mood disorders were associated with a range of substance involvement. Shared genetic architecture contributed to the co-occurrence of MDD and substance involvement. These findings may help design prevention and cessation strategies for substance use., Competing Interests: Declaration of competing interest Chia-Yen Chen is an employee of Biogen. The remaining authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neuroimaging studies have demonstrated the association of the cognitive control network (CCN) with the maintenance of chronic pain. However, whether and how dorsolateral prefrontal cortex (DLPFC), a key region within the CCN, is altered in menstrual pain is unclear. In this study, we aimed to investigate alterations in the DLPFC functional connectivity network in patients with primary dysmenorrhea (PDM). The study comprised 41 PDM patients and 39 matched healthy controls (HCs), all of whom underwent a resting-state functional MRI scan during the menstrual stage. All participants were instructed to complete the clinical assessment before the MRI scan. We used the DLPFC as the seed in resting-state functional connectivity (rsFC) analysis to investigate the difference between PDM patients and HCs. Compared to HCs, PDM patients showed increased right DLPFC rsFC at the bilateral lingual gyrus, dorsal anterior cingulate cortex (dACC), and middle cingulate cortex, and decreased left DLPFC rsFC at the right orbital frontal cortex. In addition, increased right DLPFC-bilateral dACC connectivity mediated the association between disease duration and the self-rating anxiety scale (SAS) scores in PDM patients. We confirmed that the DLPFC-dACC rsFC was associated with higher SAS scores, which could mediate the association between disease duration and anxiety symptoms in patients with PDM. Our findings provide central pathological evidence for an abnormal rsFC of the CCN in PDM patients, which may contribute to a better understanding of the neuropathophysiological mechanisms underlying PDM., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea., Objective: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval., Design, Setting, Participants and Interventions: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval., Main Outcome Measures: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms., Results: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05)., Conclusion: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the causal influence of sleep and circadian traits on coronary artery disease and sudden cardiac arrest with adjustment for obesity through a two-sample Mendelian randomization study., Methods: We used summary statistics of 5 sleep and circadian traits for genome-wide association studies, including chronotype, sleep duration, long sleep (≥9 h a day), short sleep (<7 h a day), and insomnia (sample size range: 237,622-651,295). Coronary artery disease genome-wide association studies with 60,801 cases and 123,504 controls, sudden cardiac arrest genome-wide association studies with 3939 cases and 25,989 controls, and obesity genome-wide association studies with 806,834 individuals were also used. Multivariable Mendelian randomization was performed to estimate the causality., Results: After adjusting for obesity, genetically predicted short sleep (odds ratio = 1.87 and p = .02), and genetically predicted insomnia (odds ratio = 1.17 and p = .001) were causally associated with increased odds of coronary artery disease. Genetically predicted long sleep (odds ratio = 0.06 and p = .02) and genetically predicted longer sleep duration (odds ratio = 0.36 for per-hour increase in sleep duration and p = .0006) were causally associated with decreased odds of sudden cardiac arrest., Conclusions: The findings of this Mendelian randomization study indicate that insomnia and short sleep contribute to the development of coronary artery disease, whereas a longer sleep duration protects from sudden cardiac arrest, independent of the influence of obesity. The mechanisms underlying these associations warrant further investigation., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) is associated with high heterogeneity in clinical presentation. In addition, response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably among patients. Therefore, identifying genetic variants that may contribute to SSRI treatment responses in MDD is essential. In this study, we analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. Treatment response was defined for all syndromal factors and total scores. In addition, a genome-wide association study was performed to investigate the treatment outcomes at week 4 and repeatedly assess all visits during follow-up by using mixed models adjusted for age, gender, and population substructure. Moreover, the role of genetic variants in suicidal and sexual side effects was explored, and five syndromal factors for depression were derived: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. Subsequently, several known genes were mapped to suggestive signals for treatment outcomes, including single-nucleotide polymorphisms (SNPs) in PRF1, UTP20, MGAM, and ENSG00000286536 for psychomotor-insight and in C4orf51 for anorexia. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (β = -0.638, p = 1.8 × 10 -4 ) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (β = 0.089, p = 2.0 × 10 -6 ) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10 -8 ). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, we identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The comorbidity of obesity and major depressive disorder (MDD) may be attributable to a bidirectional relationship and shared genetic influence. We aimed to examine the polygenic associations between obesity and MDD and to characterize their corresponding impacts on the obesity mechanism., Methods: Genome-wide genotyping was available in 106,604 unrelated individuals from Taiwan Biobank. Polygenic risk score (PRS) for body mass index (BMI) and MDD was derived to evaluate their effects on obesity-related traits. Stratified analyses were performed for the modified effect of depression on the polygenic associations., Results: The MDD PRS was positively associated with waistline (beta in per SD increase in PRS = 0.12), hipline (beta = 0.08), waist-hip ratio (WHR) (beta = 0.05), body fat rate (beta = 0.08), BMI (beta = 0.05), overweight (OR = 1.02 for BMI ≥ 25), and obesity (OR = 1.05 for BMI ≥ 30). For the synergism between depression and BMI PRS, the presence of active depression symptoms defined by the PHQ-4 (p for interaction < 0.05 for waistline, WHR, and BMI) was more salient than lifetime MDD., Limitations: Limitations include recall bias for MDD due to a retrospective self-reporting questionnaire, a low response rate of the PHQ-4 for evaluating active psychological symptoms, and limited generalizability to non-Taiwanese ancestries., Conclusions: The shared genetic etiology of obesity and depression was demonstrated. The amplified effect of BMI polygenic effect on obesity for individuals with active depressive symptoms was also characterized. The study may be helpful for designing public health interventions to reduce the disease burden caused by obesity and depression., Competing Interests: Conflict of interest Chia-Yen Chen is an employee of Biogen. The remaining authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The clinical characteristics and prognosis of intracranial hemorrhage (ICH) in patients with hematological diseases remain controversial. This study aimed to describe the clinical characteristics and explore the prognostic factors in such patients. A total of 238 ICH patients with a hematological disease were recruited from the Institute of Hematology and Blood Diseases Hospital, China, from January 2015 to April 2020. The Cox proportional hazards model was used to identify the prognostic factors for 30-day mortality in ICH patients with a hematological disease. There were 123 cases of acute leukemia (AL), 20 of myelodysplasia/myeloproliferative neoplasm, 35 of aplastic anemia (AA), 29 of immune thrombocytopenia (ITP), 19 of congenital/acquired coagulation factor deficiency, and 12 of other hematological diseases. Furthermore, 121 patients presented with a multi-site hemorrhage (MSH), 58 with a single-site hemorrhage in the brain parenchyma (PCH), 23 with a subarachnoid hemorrhage, 33 with a subdural hemorrhage (SH), and three with an epidural hemorrhage. The Cox proportional hazards model indicated association of SH (vs PCH, hazard ratio [HR]: 0.230; 95% confidence interval [CI]: 0.053-0.996; P = 0.049), low white blood cells (≤ 100 × 10 9 /L vs > 100 × 10 9 /L, HR: 0.56; 95% CI: 0.348-0.910; P = 0.019), AA (vs AL, HR: 0.408; 95% CI: 0.203-0.821; P = 0.012), and ITP (vs AL, HR: 0.197; 95% CI: 0.061-0.640; P = 0.007) with improved 30-day mortality. However, increased age (HR: 1.012; 95% CI: 1.001-1.022; P = 0.034), MSH (vs PCH, HR: 1.891; 95% CI: 1.147-3.117; P = 0.012), and a disturbance of consciousness (HR: 1.989; 95% CI: 1.269-3.117; P = 0.003) were associated with increased risk of 30-day mortality. In conclusion, in this study, we revealed the clinical characteristics of Chinese ICH patients with a hematological disease. Moreover, we identified risk factors (age, white blood cells, AA, ITP, SH, MSH, and a disturbance of consciousness) that may influence 30-day mortality., (© 2022. The Author(s).)

Some personality traits, especially neuroticism, has been found to be associated with suicide attempt (SA) in mood disorder patients. The present study explored the association between personality traits and SA using polygenic risk scores (PRS) for personality among patients with mood disorders. We also investigated the effects of a variety of psychosocial variables on SA. Patients with bipolar disorder (BPD, N = 841) and major depressive disorder (MDD, N = 710) were recruited from hospitals in Taiwan. Lifetime SA and information on psychosocial factors was collected. We calculated the PRS of neuroticism and extraversion. A trend test for SA was performed across quartiles of the PRS for neuroticism and extraversion, and logistic regression analyses were performed to examine the associations between psychosocial factors and SA, accounting for the PRS of personality traits. The prevalence of SA was higher in MDD than in BPD patients. The risk of SA was elevated in MDD patients with a higher quintile of PRS in neuroticism and a lower quintile of PRS in extraversion. The multiple regression analysis results demonstrated that later age of onset, higher family support and resilience, and lower overall social support were protective factors against SA. From the perspective of suicide prevention efforts, strengthening family support and conducting resilience training for patients with mood disorders may be beneficial interventions in clinical settings., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89-18.01, P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91-1.01, P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations., (© 2022. The Author(s).)

Background: The study aimed to investigate how acupuncture modulates brain activities across multiple frequency bands to achieve therapeutic effects in PDM., Methods: A total of 47 patients with PDM were randomly assigned to the verum acupuncture group and sham acupuncture group with three menstrual cycles of the acupuncture course. The fMRI scans, visual analog scale (VAS) scores, and other clinical evaluations were assessed at baseline and after three menstrual-cycles treatments. The global functional connectivity density (gFCD) analyses were performed between the pre-and post-acupuncture course of two groups at full-low frequency band, Slow-3 band, Slow-4 band, and Slow-5 band., Results: After the acupuncture treatments, the patients with PDM in the verum acupuncture group showed significantly decreased VAS scores ( p < 0.05). The frequency-dependent gFCD alternations were found in the verum acupuncture group, altered regions including DLPFC, somatosensory cortex, anterior cingulate cortex (ACC), middle cingulate cortex (MCC), precuneus, hippocampus, and insula. The sham acupuncture modulated regions including angular gyrus, inferior frontal gyrus, and hippocampus. The gFCD alternation in DLPFC at the Slow-5 band was negatively in the patients with PDM following verum acupuncture, and S2 at the Slow-4 band was positively correlated with VAS scores., Conclusion: These findings supported that verum acupuncture could effectively modulate frequency-dependent gFCD in PDM by influencing abnormal DLPFC at Slow-5 band and hippocampus at the Slow-3 band. The outcome of this study may shed light on enhancing the potency of acupuncture in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Li, Tian, Zhang, Shen, Wei, Guo, Chen, Su, Yang, Yu and Yang.)

Background: Obesity has been associated with cognition in observational studies; however, whether its effect is confounding or a reverse causality remains inconclusive. This study aimed to investigate the causal relationships of overall obesity, measured by body mass index (BMI), and abdominal adiposity, measured by waist-hip ratio adjusted for BMI (WHRadjBMI), and cognition across European and Asian populations using Mendelian randomization (MR) analysis., Methods: We used publicly available genome-wide association study (GWAS) summary data of European ancestry, including BMI (n = 322,154) and WHRadjBMI (n = 210,088) from the GIANT consortium, and cognition performance (n = 257,828) from the UK Biobank and COGENT consortium. Data for individuals of Asian ancestry were retrieved from Taiwan Biobank to perform GWAS for BMI (n = 65,689), WHRadjBMI (n = 65,683), and Mini-Mental State Examination (MMSE, n = 21,273). MR analysis was carried out using the inverse-variance weighted method for the main results. Further, we examined the overall pleiotropy by MR-Egger intercept, and detected and adjusted for possible outliers using MR PRESSO., Results: No causal effect of BMI on cognition performance (beta [95% CI] = 0.00 [-0.07, 0.07], p value = 0.91) was found for Europeans; however, a 1-SD increase in WHRadjBMI was associated with a 0.07 standardized score decrease in cognition performance (beta [95% CI] = -0.07 [-0.12, -0.02], p value = 0.006). Further, no causal effect of BMI on MMSE (beta [95% CI] = 0.01 [-0.08, 0.10], p = 0.91) was found for Asians; however, a 1-SD increase in WHRadjBMI was associated with a 0.17 standardized score decrease in MMSE (beta [95% CI] = -0.17 [-0.30, -0.03], p = 0.02). In both populations, overall pleiotropy was not detected, and outliers did not affect the robustness of the main findings., Conclusions: This trans-ethnic MR study reveals that abdominal adiposity, as measured by WHR adjusted for BMI, impairs cognition, whereas weak evidence suggests that BMI impairs cognition., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Understanding public discourse about a COVID-19 vaccine in the early phase of the COVID-19 pandemic may provide key insights concerning vaccine hesitancy. However, few studies have investigated the communicative patterns in which Twitter users participate discursively in vaccine discussions., Objectives: This study aims to investigate 1) the major topics that emerged from public conversation on Twitter concerning vaccines for COVID-19, 2) the topics that were emphasized in tweets with either positive or negative sentiment toward a COVID-19 vaccine, and 3) the type of online accounts in which tweets with either positive or negative sentiment were more likely to circulate., Methods: We randomly extracted a total of 349,979 COVID-19 vaccine-related tweets from the initial period of the pandemic. Out of 64,216 unique tweets, a total of 23,133 (36.03%) tweets were classified as positive and 14,051 (21.88%) as negative toward a COVID-19 vaccine. We conducted Structural Topic Modeling and Network Analysis to reveal the distinct topical structure and connection patterns that characterize positive and negative discourse toward a COVID-19 vaccine., Results: Our STM analysis revealed the most prominent topic emerged on Twitter of a COVID-19 vaccine was "other infectious diseases", followed by "vaccine safety concerns", and "conspiracy theory." While the positive discourse demonstrated a broad range of topics such as "vaccine development", "vaccine effectiveness", and "safety test", negative discourse was more narrowly focused on topics such as "conspiracy theory" and "safety concerns." Beyond topical differences, positive discourse was more likely to interact with verified sources such as scientists/medical sources and the media/journalists, whereas negative discourse tended to interact with politicians and online influencers., Conclusions: Positive and negative discourse was not only structured around distinct topics but also circulated within different networks. Public health communicators need to address specific topics of public concern in varying information hubs based on audience segmentation, potentially increasing COVID-19 vaccine uptake., Competing Interests: The authors have declared that no competing interests

Functional nucleic acids (FNAs), such as aptamers, nucleic acid enzymes and riboswitches play essential roles in various fields of life sciences. Tailoring of ingenious chemical moieties toward FNAs can enhance their biomedical properties and/or confer them with exogenic biological functions that, in turn, can considerably expand their biomedical applications, or even improve their clinical translations. Herein, we report the first example of a general chemical tailoring strategy that enables the divergent ligation of DNA sequences. By applying this technology, different types of aptamers and single-stranded nucleic acids of various lengths could be efficiently tailored to deliver the designed circular bivalent aptamers (CBApts) and cyclized DNA sequences with high yields. It is worth noting that CBApts exhibited significantly enhanced nuclease resistance, as well as considerably improved binding, targeting and tumor tissue enrichment abilities, which may pave the way for different investigations for biomedical purposes., (© The Author(s) 2022. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Widespread COVID-19 vaccination is critical to slow the spread of the illness. This study investigates how political ideology is associated with COVID-19 vaccine intention via perceived effectiveness of the vaccine, perceived side effects, and perceived severity of the illness, three key aspects of the Health Belief Model (HBM). This study also examines how partisan information flow moderates the effects of ideology on these three HBM components. Using survey data collected from two battleground states in the 2020 election (N = 1849), regression, mediation and moderation analyses revealed that conservatives were less likely to intend to get vaccinated against COVID-19, and this association was significantly mediated by perceived effectiveness and perceived side effects of vaccination, as well as perceived severity of COVID-19. In addition, partisanship of news sources and discussion partners were significant moderators of ideology's association with perceived vaccine effectiveness, with conservatives viewing COVID-19 vaccination as less effective if they were frequently exposed to liberal news, and if they had frequent conversations with fellow conservatives. This suggests boomerang effects for cross-cutting mass media exposure, and reinforcement effect for interpersonal communication. Implications for efforts to promote COVID-19 vaccine uptake are discussed, including tailored and targeted campaign strategies.

Aims/hypothesis: Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association., Methods: A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes., Results: A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes., Conclusions/interpretation: The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Human cardiac fibroblasts (HCFs) play key roles in normal physiological functions and pathological processes in the heart. Our recent study has found that, in HCFs, sphingosine 1-phosphate (S1P) can upregulate the expression of cyclooxygenase-2 (COX-2) leading to prostaglandin E 2 (PGE 2 ) generation mediated by S1P receptors/PKC α /MAPKs cascade-dependent activation of NF- κ B. Alternatively, G protein-coupled receptor- (GPCR-) mediated transactivation of receptor tyrosine kinases (RTKs) has been proved to induce inflammatory responses. However, whether GPCR-mediated transactivation of RTKs participated in the COX-2/PGE 2 system induced by S1P is still unclear in HCFs. We hypothesize that GPCR-mediated transactivation of RTKs-dependent signaling cascade is involved in S1P-induced responses. This study is aimed at exploring the comprehensive mechanisms of S1P-promoted COX-2/PGE 2 expression and apoptotic effects on HCFs. Here, we used pharmacological inhibitors and transfection with siRNA to evaluate whether matrix metalloprotease (MMP)2/9, heparin-binding- (HB-) epidermal growth factor (EGF), EGF receptor (EGFR), PI3K/Akt, MAPKs, and transcription factor AP-1 participated in the S1P-induced COX-2/PGE 2 system determined by Western blotting, real-time polymerase chain reaction (RT-PCR), chromatin immunoprecipitation (ChIP), and promoter-reporter assays in HCFs. Our results showed that S1PR1/3 activated by S1P coupled to G q - and G i -mediated MMP9 activity to stimulate EGFR/PI3K/Akt/MAPKs/AP-1-dependent activity of transcription to upregulate COX-2 accompanied with PGE 2 production, leading to stimulation of caspase-3 activity and apoptosis. Moreover, S1P-enhanced c-Jun bound to COX-2 promoters on its corresponding binding sites, which was attenuated by these inhibitors of protein kinases, determined by a ChIP assay. These results concluded that transactivation of MMP9/EGFR-mediated PI3K/Akt/MAPKs-dependent AP-1 activity was involved in the upregulation of the COX-2/PGE 2 system induced by S1P, in turn leading to apoptosis in HCFs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Chien-Chung Yang et al.)

Background: Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients., Methods: We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded., Results: A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model., Conclusion: In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease., Competing Interests: Conflicts of interest: Dr. Peng-Hui Wang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders., Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors., Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged., Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine. In this report, four dogs presented with fracture of sacrum vertebrae or fracture of seventh lumbar and lumbosacral displacement after road traffic accidents. The clinical signs include lumbosacral pain (4/4), paraparesis (3/4), paraplegia (1/4), and urinary incontinence (4/4). All dogs were treated by surgical decompression with or without stabilization 1 to 7 weeks after trauma. Allogeneic canine Ad-MSCs (cAd-MSCs) were injected locally on nerve roots through the surgical region in all dogs. One dose of intravenous transplantation and 4 doses of local transplantation were also performed within 8 weeks after the surgery separately. All dogs showed significant neurological improvements with normal ambulatory ability (4/4) and urinary control (3/4) 3 months after the surgery and the first cAd-MSCs transplantation. No side effect was related to multiple cAd-MSCs transplantations during 6 months monitoring in all dogs. In conclusion, multiple cAd-MSCs transplantations could be a recommended treatment combined with surgery in dogs with lumbosacral SCI.

There is little literature on the impact of donation on individual wellbeing in China. This study examines individual donations in China to answer the question of whether helping others makes us happier and to provide policy implications for in Chinese context. Based on the 2012 Chinese General Social Survey (CGSS) data and using ordered logit and OLS as benchmark models, this study finds that donation can significantly increase individual happiness. After using propensity score matching (PSM) to eliminate the possible impact of self-selection, the above conclusion remains robust. After a sub-sample discussion, it is found that this effect is more pronounced under completely voluntary donation behavior, and is not affected by economic factors, indicating that the happiness effect of donation does not vary significantly depending on the individual's economic status. This study contributes to the literature on donation behavior by examining the impact of donation behavior on donors' subjective happiness in China, and further identifies subjective happiness differences, as between voluntary and involuntary donations, thereby providing theoretical and empirical support for the formulation of policies for the development of donation institutions in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Yu, Yao, Su, Zhang, Ti, Lin, Zhang, Zhang and Yang.)

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations., Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression., Design, Setting, and Participants: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021., Exposures: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts., Main Outcomes and Measures: Depression status was defined based on health records and self-report questionnaires., Results: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = -0.003, SE = 0.005, P = .53 for rs4656484 and β = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent., Conclusions and Relevance: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.

Poria cocos , called fuling, is a famous tonic in traditional Chinese medicine that reportedly possesses various pharmacological properties, including anti-inflammation and immunomodulation. However, few studies have investigated the effects of P. cocos on allergic diseases, such as allergic asthma. Allergic asthma is caused primarily by Th2 immune response and characterized by airway inflammation. This study first demonstrated the anti-allergic and anti-asthmatic effects of P. cocos extract (Lipucan ® ). P. cocos extract distinctly exhibited reduced inflammatory cell infiltration in the peribronchial and peribronchiolar regions compared to the asthma group in the histological analysis of pulmonary tissue sections. Prolonged P. cocos extract administration significantly reduced eosinophil infiltration, PGE2 levels, total IgE, and OVA-specific IgE. Moreover, P. cocos extract markedly suppressed Th2 cytokines, IL-4, IL-5, and IL-10. On the other hand, P. cocos extract significantly elevated IL-2 secretion by Th1 immune response. In addition, P. cocos extract elevated the IFN-γ level at a lower dose. We also observed that P. cocos extract increased the activity of NK cells. Our results suggest that P. cocos extract remodels the intrinsic Th1/Th2 response to prevent or alleviate allergy-induced asthma or symptoms.

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos ) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan ® ) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity.

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs . 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Background: Poor ovarian response (POR) is a high-incidence disease of women, which cause in vitro fertilization failure. Various treatment options have been proposed for women with POR to improve their ovarian response, but with little effect. In recent years, there is a wide range of applications of acupuncture in the process of in vitro fertilization. The meta-analysis and systematic review are designed to analyze whether acupuncture is effective for patients with POR., Methods: The following databases will be searched from inception to March 2020: Electronic databases consist of MEDLINE, EMBASE, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and Wanfang Database. Other literature resources will also be searched including clinical trial registries, key journals, and meeting records. The results of randomized controlled trials of acupuncture therapy on POR, which are published in Chinese or English, will be embedded. The primary outcome is the clinical pregnancy rate. Data identification, data selection, data extraction, and assessment of bias risk will be completed independently by 2 or more reviewers. STATA/IC 16 will be used to perform the meta-analysis. We will use the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the quality of our evidence. A systematic narrative synthesis will be provided if the quantitative analysis is not available., Discussion: This study will provide the first meta-analysis and systematic review to evaluate the efficacy of acupuncture in treating POR. This protocol provides details to guide this study., Conclusions: From this review may benefit POR patients or clinical decision-makers., Prospero Registration Number: PROSPERO CRD42020169560.

In the regions of tissue injuries and inflammatory diseases, sphingosine 1-phosphate (S1P), a proinflammatory mediator, is increased. S1P may induce the upregulation of cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 ) system in various types of cells to exacerbate heart inflammation. However, the detailed molecular mechanisms by which S1P induces COX-2 expression in human cardiac fibroblasts (HCFs) remain unknown. HCFs were incubated with S1P and analyzed by Western blotting, real time-Polymerase chain reaction (RT-PCR), and immunofluorescent staining. Our results indicated that S1P activated S1PR 1/3 -dependent transcriptional activity to induce COX-2 expression and PGE 2 production. S1P recruited and activated PTX-sensitive G i or -insensitive G q protein-coupled S1PR and then stimulated PKCα-dependent phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, leading to activating transcription factor NF-κB. Moreover, S1P-activated NF-κB was translocated into the nucleus and bound to its corresponding binding sites on COX-2 promoters determined by chromatin immunoprecipitation (ChIP) and promoter-reporter assays, thereby turning on COX-2 gene transcription associated with PGE 2 production in HCFs. These results concluded that in HCFs, activation of NF-κB by PKCα-mediated MAPK cascades was essential for S1P-induced up-regulation of the COX-2/PGE 2 system. Understanding the mechanisms of COX-2 expression and PGE 2 production regulated by the S1P/S1PRs system on cardiac fibroblasts may provide rationally therapeutic interventions for heart injury or inflammatory diseases., (Copyright © 2020 Yang, Hsiao, Su and Yang.)

Background: MiRNAs play essential roles in plant development and response to biotic and abiotic stresses through interaction with their target genes. The expression level of miRNAs shows great variations among different plant accessions, developmental stages, and tissues. Little is known about the content within the plant genome contributing to the variations in plants. This study aims to identify miRNA expression-related quantitative trait loci (miR-QTLs) in the maize genome., Results: The miRNA expression level from next generation sequencing (NGS) small RNA libraries derived from mature leaf samples of the maize panel (200 maize lines) was estimated as phenotypes, and maize Hapmap v3.2.1 was chosen as the genotype for the genome-wide association study (GWAS). A total of four significant miR-eQTLs were identified contributing to miR156k-5p, miR159a-3p, miR390a-5p and miR396e-5p, and all of them are trans-eQTLs. In addition, a strong positive coexpression of miRNA was found among five miRNA families. Investigation of the effects of these miRNAs on the expression levels and target genes provided evidence that miRNAs control the expression of their targets by suppression and enhancement., Conclusions: These identified significant miR-eQTLs contribute to the diversity of miRNA expression in the maize penal at the developmental stages of mature leaves in maize, and the positive and negative regulation between miRNA and its target genes has also been uncovered.

This study examined an aquaponic approach of circulating water containing ammonia excretions from African catfish grown in an aquaculture tank for bacterial conversion into nitrates, which then acted as a nutrient substance to cultivate lettuce in hydroponic tank. We found that microwave pyrolysis biochar (450 g) having microporous (1.803 nm) and high BET surface area (419 m 2 /g) was suitable for use as biological carrier to grow nitrifying bacteria (63 g of biofilm mass) that treated the water quality through removing the ammonia (67%) and total suspended solids (68%), resulting in low concentration of remaining ammonia (0.42 mg/L) and total suspended solid (59.40 mg/L). It also increased the pH (6.8), converted the ammonia into nitrate (29.7 mg/L), and increased the nitrogen uptake by the lettuce (110 mg of nitrogen per plant), resulting in higher growth in lettuce (0.0562 %/day) while maintaining BOD 5 level (3.94 mg/L) at acceptable level and 100% of catfish survival rate. Our results demonstrated that microwave pyrolysis biochar can be a promising solution for growing nitrifying bacteria in aquaponic system for simultaneous toxic ammonia remediation and generation of nitrate for growing vegetable in aquaculture industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Schizophrenia and substance involvement frequently co-occur in individuals, and a bidirectional relationship between the two has been proposed; shared underlying genetic factors could be an alternative explanation. This study investigated the genetic overlap between schizophrenia and substance involvement, including tobacco, alcohol and betel nut use. The study subjects were recruited from the Taiwan Biobank, and genome-wide genotyping data was available for 18 327 participants without schizophrenia. We calculated the Psychiatric Genomics Consortium-derived polygenic risk score (PRS) for schizophrenia in each participant. The significance of the schizophrenia PRS associated with substance involvement was evaluated using a regression model with adjustments for gender, age and population stratification components. The modified effect of gender or birth decade was also explored. The schizophrenia PRS was positively associated with lifetime tobacco smoking in women (OR in per SD increase in PRS = 1.12 with 95% CI 1.04-1.20, P = .002), but not in men (OR = 0.99 with 95% CI 0.95-1.04, P = .74), and the gender-PRS interaction reached significance (P = .006). The OR between PRS and lifetime tobacco smoking increased with the birth decade (P of birth decade-PRS interaction = .0002). In women, OR increased from 0.97 (P = .85) for subjects with a birth decade before 1950 to 1.21 (P = .04) for subjects with a birth decade after 1980; in men, the corresponding OR increased from 0.88 (P = .04) to 1.13 (P = .11). There was no association between schizophrenia PRS and alcohol/betel nut use phenotypes. This study provides evidence for the genetic overlap between schizophrenia and tobacco use in women, and this overlap was stronger in the younger population., (© 2020 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

In early stages, patients with bipolar disorder are often diagnosed as having unipolar depression in mood disorder diagnosis. Because the long-term monitoring is limited by the delayed detection of mood disorder, an accurate and one-time diagnosis is desirable to avoid delay in appropriate treatment due to misdiagnosis. In this paper, an elicitation-based approach is proposed for realizing a one-time diagnosis by using responses elicited from patients by having them watch six emotion-eliciting videos. After watching each video clip, the conversations, including patient facial expressions and speech responses, between the participant and the clinician conducting the interview were recorded. Next, the hierarchical spectral clustering algorithm was employed to adapt the facial expression and speech response features by using the extended Cohn-Kanade and eNTERFACE databases. A denoizing autoencoder was further applied to extract the bottleneck features of the adapted data. Then, the facial and speech bottleneck features were input into support vector machines to obtain speech emotion profiles (EPs) and the modulation spectrum (MS) of the facial action unit sequence for each elicited response. Finally, a cell-coupled long short-term memory (LSTM) network with an L -skip fusion mechanism was proposed to model the temporal information of all elicited responses and to loosely fuse the EPs and the MS for conducting mood disorder detection. The experimental results revealed that the cell-coupled LSTM with the L -skip fusion mechanism has promising advantages and efficacy for mood disorder detection.

Objective: Dermatological problems after chemotherapy are often neglected with gynecological oncologists. Since paclitaxel is one of most popular agents for gynecology organ-related cancers, dermatologic change after paclitaxel treatment is seldom reported before., Case Report: Two patients with gynecological organ malignancy who underwent the postoperative dose-dense weekly schedule of paclitaxel 80 mg/m 2 plus carboplatin (area of curve 5) every three weeks had repeat dermatological problems (skull, facial and upper trunk areas) during the treatment. They included dermatitis, eczema, and folliculitis. Topical use of anti-fungal cream and oral anti-histamine agents stopped the disease progression and all had completed their chemotherapy without interruption., Conclusion: Clinicians should be aware of paclitaxel-induced skin toxicities, especially on the skull, face and upper trunk areas to minimize the occurrence of severe morbidity and to provide the better quality of life when cure is our primary priority in the management of gynecological organs-related malignancies., (Copyright © 2019. Published by Elsevier B.V.)

In 2008, we published a review article entitled "Differential diagnosis of gynecologic organ-related diseases in women presenting with ascites" in the Taiwanese Journal of Obstetrics and Gynecololgy. Ascites might be the results of the physiological or pathological status, and the underlying mechanisms varied greatly in the different genders. The diagnostic challenge is frequently found in clinical practice. This review summarizes the recent knowledge and clinical practice for women presenting with ascites. Approach includes history, physical examination, laboratory examination, ultrasound, paracentesis and possible laparoscopy. Accurate and prompt diagnosis not only provides the better care and management but also diminishes the unnecessary psychological stress in women presenting with ascites., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To explore the methods of establishing and maintaining community injecting drug user (IDU) cohort. Methods: From June 2014 to June 2017, a community survey was conducted on basis of local needle and syringe exchange site to recruit 200 HIV sero-negative IDU for a prospective cohort study in Longyang district of Baoshan city, Yunan province. Follow-up was carried out every six month to investigate high risk drug use behavior and sexual behavior, and blood samples were collected from them for the tests of HIV and HCV serum antibodies. The cohort would be opened every 12 months to replenish the cohort to 200 subjects. Results: The follow up was conducted for 3 years in 229 IDUs. Cohort follow-up rate was 93.0 % (213/229) for 6 months, 92.1 % (211/229) for 12 months, 91.7 % (200/218) for 18 months, 87.2 % (190/218) for 24 months, 86.0 % (172/200) for 30 months and 86.0 % (172/200) for 36 months. Conclusion: The community IDU cohort has a high follow-up rate.

A mild amination protocol of N-heteroaryl alkyl ethers with various amines is described. This transformation is achieved by utilizing simple and readily available base as promoter via C-O bond cleavage, offering a new amination strategy to access several anticancer-active compounds. This work is highlighted by the excellent functional group compatibility, scalability, wide substrate scope, and easy derivatization of a variety of drugs.

Suicide is a major threat to adolescent health. Sleep problems increase the risk of adolescent suicidal behavior, but the role of sleep-disordered breathing (e.g., sleep apnea) is unclear. We investigated whether sleep apnea had an effect on suicidal ideation that was independent of depression and perceived stress. We examined a series of sleep variables with suicidal ideation in 746 fifth and seventh graders using self-reported questionnaires to assess time in bed, sleep quality, insomnia, and sleep apnea while controlling depression and perceived stress. Overall, 8.8% of students aged 10-14 years reported having recent suicidal ideation, and 33% or 3.8%, depending on the screening criteria, reported having suspected sleep apnea. The sleep variables were all associated with an increased risk of suicidal ideation, but the magnitude of effects was largely attenuated when depression and perceived stress were included in the models. Suspected sleep apnea using daytime sleepiness as a screening criterion was independently associated with suicidal ideation (odds ratio = 2.25, p < 0.05). Suspected sleep apnea was associated with suicidal ideation that was partly independent of depression and stress, which reveals the pertinence of screening for sleep apnea among school students and designing proper prevention strategies for reducing youth suicidal behavior.