Assessing causal associations of blood counts and biochemical indicators with pulmonary arterial hypertension: a Mendelian randomization study and results from national health and nutrition examination survey 2003-2018.

Background: Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH). Methods: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship. Results: The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH. Conclusion: Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.

Combined effect of compassionate and uncompassionate self-responding on Chinese college students' mental health during the initial wave of the COVID-19 pandemic: a response surface analysis.

Background: The initial wave of the COVID-19 pandemic significantly deteriorated mental health, especially among college students. Self-compassion has demonstrated benefits for psychological outcomes such as depressive symptoms, life satisfaction, posttraumatic stress symptoms (PTSS), and posttraumatic growth (PTG). Notably, existing literature suggests that the protective and vulnerable aspects within the Self-Compassion Scale, namely, compassionate and uncompassionate self-responding (CSR and USR), can coexist within individuals and influence their mental health through various coexisting patterns. However, this process has not been sufficiently explored.Objective: This study aimed to explore the combined effects of CSR and USR on college students' depressive symptoms, life satisfaction, PTSS, and PTG during the initial wave of the pandemic.Method: In this cross-sectional study, 4450 Chinese college students (51.9% females, Mage = 20.58 years, SD = 1.49) completed self-report measures amid the COVID-19 pandemic's initial wave in 2020. Response surface analyses were utilised to investigate the combined effects of CSR and USR.Results: Simultaneously increased CSR and USR were associated with a slight increase in depressive symptoms, PTSS, and life satisfaction, but a substantial increase in PTG. Conversely, increased CSR and decreased USR were associated with a considerable decrease in depressive symptoms and PTSS, a significant increase in life satisfaction, and a moderate increase in PTG.Conclusions: CSR and USR demonstrated protective and vulnerable impacts, respectively. It is imperative to analyse their combined effects as an interactive system and consider the specific characteristics of different psychological responses.

Increased CSR and decreased USR were associated with less depressive symptoms and PTSS as well as more life satisfaction.CSR mitigated the negative effects of USR on depressive symptoms, life satisfaction, and PTSS.Simultaneously increased CSR and USR were associated with a substantial increase in PTG.

Predictors, clinical impact, and management strategies for conduction abnormalities after transcatheter aortic valve replacement: an updated review.

Transcatheter aortic valve replacement (TAVR) has increasingly become a safe, feasible, and widely accepted alternative surgical treatment for patients with severe symptomatic aortic stenosis. However, the incidence of conduction abnormalities associated with TAVR, including left bundle branch block (LBBB) and high-degree atrioventricular block (HAVB), remains high and is often correlated with risk factors such as the severity of valvular calcification, preexisting conditions in patients, and procedural factors. The existing research results on the impact of post-TAVR conduction abnormalities and permanent pacemaker (PPM) requirements on prognosis, including all-cause mortality and rehospitalization, remain contradictory, with varied management strategies for post-TAVR conduction system diseases across different institutions. This review integrates the latest research in the field, offering a comprehensive discussion of the mechanisms, risk factors, consequences, and management of post-TAVR conduction abnormalities. This study provides insights into optimizing patient prognosis and explores the potential of novel strategies, such as conduction system pacing, to minimize the risk of adverse clinical outcomes.

Causal effect of gallstone disease on the risk of coronary heart disease or acute myocardial infarction: a Mendelian randomization study.

Gallstone disease (GSD) is thought to be associated with the risk of coronary heart disease (CHD) or acute myocardial infarction (AMI), which may be due to abnormal cholesterol metabolism. We used multiple Mendelian randomization (MR) methods based on publicly available genome-wide association study data to assess whether this association is genetically causal and to search for loci driving causality. Pooled data for GSD were obtained from FinnGen Biobank and Biobank Japan, while CHD and AMI were obtained as pooled data from the CARDIoGRAMplusC4D consortium. In this MR study, we found a significant negative causal effect of genetic susceptibility to GSD on AMI in the Finnish population, but no causal effect was found on CHD. This causal effect was not confounded by reverse causality and the same findings were obtained in the Japanese population. Furthermore, the negative causal effect of GSD on AMI risk may be driven by the rs4245791-regulated ABCG5/8 protein. In conclusion, the results of this MR study support a negative causal effect of GSD on AMI and suggest that rs4245791 is the causal driver locus of this effect, which provides new ideas and evidence for the prevention and etiologic study of AMI in patients with GSD.

A robust optimal scheduling system based on multi-performance driving for complex manufacturing systems.

A robust optimal scheduling method driven by multi-objects is proposed for the collaborative optimization problem between dynamic scheduling, preventive maintenance of equipment, and robustness of scheduling schemes in a complex manufacturing system. Firstly, the equipment maintenance task is mapped to the process level, and composite dispatching rules with weight parameters are designed, which flexibly consider equipment maintenance and system processing status. Secondly, the performance-driven ideology is analyzed through two models based on the IWOA-MLP algorithm. Thirdly, the feedback mechanism ideology facilitates adaptive closed-loop optimizations. Finally, a series of experiments were carried out on the simulation platform of a semiconductor manufacturing enterprise in Shanghai. The experimental results show that the proposed robust optimal scheduling system can effectively deal with mixed uncertainty, improve production performances, and maintain highly robust measures.

Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Clinical features and power spectral entropy of electroencephalography in Wilson's disease with dystonia.

OBJECTIVE: To study the clinical features and power spectral entropy (PSE) of electroencephalography signals in Wilson's disease (WD) patients with dystonia. METHODS: Several scale evaluations were performed to assess the clinical features of WD patients. Demographic information and electroencephalography signals were obtained in all subjects. RESULTS: 34 WD patients with dystonia were recruited in the case group and 24 patients without dystonia were recruited in the control group. 20 healthy individuals were included in the healthy control group. The mean body mass index (BMI) in the case group was significantly lower than that in the controls (p < .05). The case group had significantly higher SAS, SDS, and Bucco-Facial-Apraxia Assessment scores (p < .05). Total BADS scores in the case group were lower than those in the control group (p < .01). Note that 94.11% of the case group presented with dysarthria and 70.59% of them suffered from dysphagia. Dysphagia was mainly related to the oral preparatory stage and oral stage. Mean power spectral entropy (PSE) values in the case group were significantly different (p < .05) from those in the control group and the healthy group across the different tasks. CONCLUSIONS: The patients with dystonia were usually accompanied with low BMI, anxiety, depression, apraxia, executive dysfunction, dysarthria and dysphagia. The cortical activities of the WD patients with dystonia seemed to be more chaotic during the eyes-closed and reading tasks but lower during the swallowing stages than those in the control group.

A patient with hereditary transthyretin amyloidosis involving multiple cranial nerves due to a rare p.(Phe84Ser) variant.

We report a 30-year-old man involving gastrointestinal symptoms, vitreous opacity, and multiple cranial neuropathies. Transthyretin-related hereditary amyloidosis genetic testing revealed a rare c.251T > C variant p.(Phe84Ser). Only four cases with this variant have been reported before.

Exposure to BDE-47 and BDE-209 impaired antioxidative defense mechanisms in Brachionus plicatilis.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P < 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P < 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis, our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution.

Segmentation of Laser Marks of Diabetic Retinopathy in the Fundus Photographs Using Lightweight U-Net.

Diabetic retinopathy (DR) is a prevalent vision-threatening disease worldwide. Laser marks are the scars left after panretinal photocoagulation, a treatment to prevent patients with severe DR from losing vision. In this study, we develop a deep learning algorithm based on the lightweight U-Net to segment laser marks from the color fundus photos, which could help indicate a stage or providing valuable auxiliary information for the care of DR patients. We prepared our training and testing data, manually annotated by trained and experienced graders from Image Reading Center, Zhongshan Ophthalmic Center, publicly available to fill the vacancy of public image datasets dedicated to the segmentation of laser marks. The lightweight U-Net, along with two postprocessing procedures, achieved an AUC of 0.9824, an optimal sensitivity of 94.16%, and an optimal specificity of 92.82% on the segmentation of laser marks in fundus photographs. With accurate segmentation and high numeric metrics, the lightweight U-Net method showed its reliable performance in automatically segmenting laser marks in fundus photographs, which could help the AI assist the diagnosis of DR in the severe stage.

Persistence with medical treatment for Wilson disease in China based on a single center's survey research.

BACKGROUND: Wilson's disease (WD) is one of the few hereditary diseases that can be successfully treated with medicines. We conduct this survey research to assess treatment persistence among patients with WD and try to identify what factors affect the treatment persistence. METHODS: We employed WeChat which is the most popular social software in China to carry out this anonymous questionnaire research. The questionnaire included medication adherence scale. We also collected available medical records related to demographic and clinical characteristics. All the patients were divided into group of persistence with drug treatment (PDT) and nonpersistence with drug treatment (n-PDT). RESULTS: We collected 242 qualified questionnaires. Only 66.5% of patients were PDT during the mean 12.6 years of follow-up. In PDT group, better outcomes were observed: improvement (78.3%) and no change (16.1%) versus those in n-PDT (55.6%; and 28.4%, respectively). In PDT group, only nine patients deteriorated (6.8%) in comparison with 13 patients in n-PDT (16.0%). The adverse events (AEs) in PDT group were significantly less than those in n-PDT group. There were no significant differences in clinical type, gender, age, education level, and family knowledge about WD between the two groups. There were significant differences in AEs and family position toward treatment. CONCLUSION: Medication Adherence of Chinese WD patients was low. One third of the patients (33.5%) were unable to PDT, and it had an important negative effect on clinical outcome. AEs and family support had an important impact on treatment persistence.

Giant "heart appearance-like sign" on MRI in bilateral ponto-medullary junction infraction: case report.

BACKGROUND: Bilateral medial medullary infarction (MMI) is uncommon and bilateral medial pons infarction (MPI) is even rarer. "Heart appearance" on magnetic resonance imaging (MRI) is a characteristic presentation of bilateral medial medullary infarction (MMI). CASE PRESENTATION: We present 67-year-old Chinese diabetic and hypertensive female patient affected with "heart appearance-like" infarction in bilateral ponto-medullary junction on MRI. Abnormal signal was observed in the bilateral ponto-medullary junction on T1, T2, fluid-attenuated inversion recovery and apparent diffusion coefficient (ADC). The whole brain digital subtraction angiography (DSA) showed the basilar artery and vertebral artery remained intact. Therefore, we speculated that the bilateral ponto-medullary junction infarction might be caused by the deep perforating branch of the basilar artery. CONCLUSIONS: As far as we know, the "heart appearance-like" infraction in bilateral ponto-medullary junction was not reported. Our case also suggests that bilateral ischemic infraction involvement of the medulla and pon is possible even in the context of an intact basilar artery.

Complex posttraumatic stress disorder in Chinese young adults using the International Trauma Questionnaire (ITQ): A latent profile analysis.

BACKGROUND: The ICD-11 includes posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as two distinct disorders. Several empirical studies have supported the distinction between PTSD and CPTSD in various trauma population and different culture backgrounds. However, research documenting qualitatively distinction between PTSD and CPTSD using the International Trauma Questionnaire (ITQ) in a large general population from non-English-speaking countries is limited. METHODS: Self-report measures were used to assess CPTSD, dissociation, depression, and posttraumatic growth in a sample of 1,760 Chinese college students who had experienced at least one traumatic event. Latent profile analysis was utilized to identify the number of classes based on the 18-item version of ITQ. RESULTS: A four-class solution (low symptoms, disturbance of self-organization, PTSD, CPTSD) was the most appropriate one in our study. Compared to the PTSD class, the CPTSD class was associated with more serious psychopathology symptoms. LIMITATIONS: Sample characteristics in this study limit its generalizability to other population (e.g., low educational level, clinical sample). The type of traumatic event in predicting distinct classes should also be investigated in future studies. CONCLUSIONS: Distinction between PTSD and CPTSD as ICD-11 proposed was supported in a Chinese young adult sample. DSO symptoms might inhibit healing and recovery process, and subsequent intervention could consider treat CPTSD based on addressing DSO symptoms.

COVID-19 Infection Risk and Depressive Symptoms Among Young Adults During Quarantine: The Moderating Role of Grit and Social Support.

Prior research has demonstrated that the adverse consequences of the coronavirus disease 2019 (COVID-19) pandemic may go beyond its economic hardships and physical health concerns, having a significant influence on psychological distress for individuals under quarantine. Nevertheless, relatively little attention has been paid to exploring the risk and protective factors in the link between COVID-19 infection risk and psychological distress among young adults. Following a socioecological framework, the current study examines the moderating role of grit (perseverance and consistency) and social support in the association between COVID-19 infection risk and depressive symptoms. A sample of 1,251 young adults under home quarantine (62.6% female; M age = 20.92 years, SD = 1.47; age ranged from 18 to 25 years) was involved in this study, and they were asked to complete a set of self-reported questionnaires online. Results of a linear regression analysis exhibited that COVID-19 infection risk was positively associated with depressive symptoms in young adults in quarantine. Moreover, moderation analyses showed that this association was moderated by perseverance and social support. To be specific, for those reporting higher levels of social support, this linkage was not significantly positive; in contrast, for those reporting lower levels of social support, perseverance was a significant protective factor for depressive symptoms when young adults were exposed to a high infection risk of COVID-19. The current study suggests that greater social support is essential to helping young adults deal with possible negative emotions in the context of the COVID-19 pandemic. Moreover, university-based counseling services should pay specific attention to those young adults with relatively insufficient social support resources and low levels of perseverance.

Supercurrent switch in π topological junctions based upon a narrow quantum spin Hall insulator.

The narrow quantum spin Hall (QSH) insulator is characterized by interedge coupling, which could feature exotic transport phenomena, and thus serves as the key element for topological superconducting electronic devices. Herein, we theoretically explore possible Josephson π states in a QSH insulator strip touching on two s-wave superconductors in the presence of the interedge coupling. It is shown that the interedge coupling could give rise to a 0 - π transition modulated by the gate voltage, originating from an additional π phase difference caused by the interedge backscattering. The 0 - π transition in turn can manifest the helical spin texture of the edge states. A considerable residual value of the supercurrent at the 0 - π transition point is always exhibited, suggesting a very efficient performance of the device as a supercurrent switch. Moreover, the region of coexisting 0 and π states is found fairly large, which can be used to improve accuracy in the design of a π superconducting quantum interference device.

miR-200b inhibits CD133+ glioma cells by targeting the AKT pathway.

MicroRNA-200b (miR-200b) is a tumor suppressor in multiple tumor types, including gastric cancer, breast cancer, ovarian cancer and glioma. The biological significance of a known normal and cancer stem cell marker, CD133, remains elusive. The aim of the present study was to identify the function and mechinism of miR-200b in suppressing CD133+ glioma cells. CD133+ glioma cells were sorted by flow cytometry. The expression of miR-200b, Ki67, GAP43, GFAP and CD133 were tested by reverse transcription-quantitative polymerase chain reaction. The binding of miR-200b to prominin 1 (PROM1) was certificated by luciferase reporter assay. Cell proliferation was analyzed by bromodeoxyuridine staining. The protein level of CD133, p-AKT, AKT and Notch1 was detected by western blot analysis. Analysis of glioma samples revealed that CD133 expression is negatively associated with miR-200b. PROM1, which is the gene that codes CD133, was certified to be a target of miR-200b. miR-200b expression inhibited the stemness properties and division of the CD133+ glioma cells. Our results identified a miR-200b/CD133/PI3K/Akt signaling axis, exploring the fundamental role of miR-200b and CD133 in glioma stem cell behavior.

Role of sestrin2 in H2O2-induced PC12 apoptosis.

Sestrin2 is involved in different kind of cellular response to stress conditions. However, the function of Sestrin2 in oxidative stress related neurological diseases remains unknown. In this study, we tested whether Sestrin2 has a beneficial effect on PC12 cell apoptosis induced by H2O2. We found that H2O2 induces expression of Sestrin2 in PC12 cells in a time-dependent and dose-dependent manner. We also found that Knockdown of Sestrin2 using small RNA interference promotes cell apoptosis induced by H2O2. In addition, our results show that the c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway is activated by H2O2. Inhibiting the activity of the JNK pathway and JNK siRNA transfection abolishes the increase of Sestrin2 induced by H2O2. These findings suggest that the inductive effect of Sestrin2 is mediated by the JNK/c-Jun pathway. In this study, we investigated the role of Sestrin2 in oxidative stress-induced cell apoptosis using PC12 cells as the model, implying that stimulating expression of Sestrin2 might be considered as a neuroprotective target against H2O2-induced oxidative stress.

Icariin exerts estrogen-like activity in ameliorating EAE via mediating estrogen receptor ß, modulating HPA function and glucocorticoid receptor expression.

BACKGROUND: Estrogen exerts neuroprotective and anti-inflammatory effects in EAE and multiple sclerosis (MS), but its clinical application is hindered due to side effects and risk of tumor. Phytoestrogen structurally or functionally mimics estrogen with fewer side effects than endogenous estrogen. Icariin (ICA), an active component of Epimedium extracts, demonstrates estrogen-like neuroprotective effects. However, it is unclear whether ICA is effective in EAE and what are the underlying mechanisms. OBJECTIVE: To determine the therapeutic effects of ICA in EAE and explore the possible mechanisms. METHODS: C57BL/6 EAE mice were treated with Diethylstilbestrol, different dose of ICA and mid-dose ICA combined with ICI 182780. The clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT) concentrations were then analyzed. Western blot were performed to investigate the expressions of glucocorticoid receptor (GR), estrogen receptor alpha (ERα) and ERß in the cerebral white matter of EAE mice. RESULTS: High dose ICA is equally effective in ameliorating neurological signs of EAE as estrogen. Estrogen and ICA has no effects on serum concentrations of IL-17 in EAE. While the CORT levels were decreased by ICA at mid or high doses, the expressions of GR, ERα and ERß were up-regulated by estrogen or different doses of ICA in a dosedependent manner. Estrogen induced the elevation of ERα more markedly than ICA. In contrast, ICA at mid and high doses promoted ERß more significantly than estrogen. CONCLUSION: ICA exerts estrogen-like activity in ameliorating EAE via mediating ERß, modulating HPA function and up-regulating the expression of GR in cerebral white matter. ICA may be a promising therapeutic option for MS.