Search

Abstract The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson’s disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Abstract Background Overdose-related suicide attempts represent a significant portion of self-harm presentations in the psychiatric emergency department (ED). Identifying specific patient characteristics associated with these attempts holds promise for pinpointing drug classes with elevated risk and paving the way for tailored suicide prevention interventions. This study aims to examine the demographic profiles of ED patients who had experienced overdose-related suicide attempts. Methods This retrospective study was conducted at Beijing Anding Hospital, Capital Medical University, from January 2020 to December 2021. Patients with psychiatric drug overdose suicide attempts presenting to the psychiatric ED were included. Sociodemographic characteristics and the specific classes of drugs involved were collected, and analysed descriptively. Results This study examined 252 overdose patients, excluding 51 patients treated with alcohol or nonpsychiatric drugs, and a total 201 cases were included. The mean age of the patients was 28 ± 16 years (median 23, range 12–78), and 82% (n = 165) of the sample were females. Notably, nearly half (45%) of the patients were aged ≤ 20 years. While the number of cases decreased with increasing age, a significant increase was observed in 2021 compared to 2020. Benzodiazepines (BZDs) were the most frequently implicated substance class (n = 126, 63%), followed by antidepressants (n = 96, 48%), antipsychotics (n = 44, 22%), Z-drugs (n = 43, 21%), and mood stabilizers (n = 36, 18%). For adolescents, antidepressants (n = 52, 71%) overtook BZDs (n = 38, 52%) as the most common drug. The monthly distribution of cases revealed peaks in April and November. Furthermore, 21% (n = 42) of patients ingested more than two psychotropic medications concurrently. Finally, approximately half (n = 92) of the patients required inpatient admission for further treatment. Comparisons between hospitalized and nonhospitalized patients did not reveal any significant differences. Conclusions The present study revealed a greater prevalence of suicide overdose attempts among young females receiving prescriptions for antidepressants and/or BZDs. This finding suggests a potential need for enhanced monitoring of suicidal behaviour in this specific population when prescribing psychotropic medications. These findings contribute to the growing body of knowledge regarding drug overdose suicide attempts in psychiatric emergency settings and underscore the importance of further research to develop targeted prevention interventions.

Abstract Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%–38.7%), level III aggression was 29.5% (95%CI = 26.3%–32.6%), and level VI aggression was 7.0% (95%CI = 5.4%–8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, “Increased motor activity-energy” emerged as the central symptom, with the highest centrality expected influence, followed by “Emotional Instability” and “Disruptive/aggression behavior”. Notably, “Emotional Instability” appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, “Speech rate and amount” exhibited the strongest positive correlation with testosterone levels, followed closely by “Disruptive/aggression behavior”. The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, “Increased motor activity-energy” stood out as the most influential symptom, and “Speech rate and amount” acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.

ObjectiveThe clinical management of catatonia has always been a focus of psychiatric nursing. Unfortunately, there is still limited research on the risk factors and nursing methods for patients with catatonia and bacterial pneumonia. Few studies have identified and analyzed the clinical risk factors for catatonia patients with bacterial pneumonia. This study aims to explore the risk factors and preventive nursing measures for pneumonia in patients with catatonia.MethodsA total of 88 patients with catatonia treated in the emergency department of a psychiatric hospital from January 2019 to October 2021 were selected. They were divided into bacterial pneumonia group (n=17) and non-pneumonia group (n=71) based on whether they had pneumonia. The demographic data and clinical characteristics of the two groups were compared. Logistic regression analysis and point-biserial correlation were used to analyze the risk factors for developing pneumonia in patients with catatonia.ResultsThe incidence of pneumonia in patients with catatonia was 19.32%. Correlation analysis showed that age (r=0.216, p=0.043), The Activities of Daily Living Scale (ADL) score (r=0.265, p=0.013), cell count of white blood (r=0.591, p

BackgroundChronic subdural hematoma (CSDH) represents a prevalent medical condition, posing substantial challenges in postoperative management due to risks of recurrence. Such recurrences not only cause physical suffering to the patient but also add to the financial burden on the family and the health care system. Currently, prognosis determination largely depends on clinician expertise, revealing a dearth of precise prediction models in clinical settings. ObjectiveThis study aims to use machine learning (ML) techniques for the construction of predictive models to assess the likelihood of CSDH recurrence after surgery, which leads to greater benefits for patients and the health care system. MethodsData from 133 patients were amassed and partitioned into a training set (n=93) and a test set (n=40). Radiomics features were extracted from preoperative cranial computed tomography scans using 3D Slicer software. These features, in conjunction with clinical data and composite clinical-radiomics features, served as input variables for model development. Four distinct ML algorithms were used to build predictive models, and their performance was rigorously evaluated via accuracy, area under the curve (AUC), and recall metrics. The optimal model was identified, followed by recursive feature elimination for feature selection, leading to enhanced predictive efficacy. External validation was conducted using data sets from additional health care facilities. ResultsFollowing rigorous experimental analysis, the support vector machine model, predicated on clinical-radiomics features, emerged as the most efficacious for predicting postoperative recurrence in patients with CSDH. Subsequent to feature selection, key variables exerting significant impact on the model were incorporated as the input set, thereby augmenting its predictive accuracy. The model demonstrated robust performance, with metrics including accuracy of 92.72%, AUC of 91.34%, and recall of 93.16%. External validation further substantiated its effectiveness, yielding an accuracy of 90.32%, AUC of 91.32%, and recall of 88.37%, affirming its clinical applicability. ConclusionsThis study substantiates the feasibility and clinical relevance of an ML-based predictive model, using clinical-radiomics features, for relatively accurate prognostication of postoperative recurrence in patients with CSDH. If the model is integrated into clinical practice, it will be of great significance in enhancing the quality and efficiency of clinical decision-making processes, which can improve the accuracy of diagnosis and treatment, reduce unnecessary tests and surgeries, and reduce the waste of medical resources.

Highlights Critical solvation structure changes the hydrogen bond network through “catchers”. Catcher further arrests the active molecules to promote Zn2+ deposition. The Zn||Zn symmetric battery can stably cycle for 2250 h. Zn||V6O13 full battery achieved a capacity retention rate of 99.2% after 10,000 cycles.

C21H19ClO3, orthorhombic, P212121 (no. 19), a = 6.0384(3) Å, b = 11.5696(7) Å, c = 24.6624(14) Å, V = 1722.96(17) Å3, Z = 4, Rgt(F) = 0.0253, wRref(F2) = 0.0637, T = 100(2) K.

BackgroundSpondylitis caused by Brucella infection is a rare but challenging condition, and its successful management depends on timely diagnosis and appropriate treatment. This study reports two typical cases of thoracic and lumbar brucellosis spondylitis, highlighting the pivotal roles of real-time polymerase chain reaction (real-time PCR) detection and surgical intervention.Case presentationCase 1 involved a 49-year-old male shepherd who presented with a 6-month history of fever (40°C), severe chest and back pain, and 2-week limited lower limb movement with night-time exacerbation. Physical examination revealed tenderness and percussion pain over the T9 and T10 spinous processes, with grade 2 muscle strength in the lower limbs. CT showed bone destruction of the T9 and T10 vertebrae with narrowing of the intervertebral space, whereas MRI demonstrated abnormal signals in the T9–T10 vertebrae, a spinal canal abscess, and spinal cord compression. The Rose Bengal plate agglutination test was positive. Case 2 was a 59-year-old man who complained of severe thoracolumbar back pain with fever (39.0°C) and limited walking for 2 months. He had a 2.5 kg weight loss and a history of close contact with sheep. The Rose Bengal test was positive, and the MRI showed inflammatory changes in the L1 and L2 vertebrae. Diagnosis and treatment: real-time PCR confirmed Brucella infection in both cases. Preoperative antimicrobial therapy with doxycycline, rifampicin, and ceftazidime-sulbactam was administered for at least 2 weeks. Surgical management involved intervertebral foraminotomy-assisted debridement, decompression, internal fixation, and bone grafting under general anesthesia. Postoperative histopathological examination with HE and Gram staining further substantiated the diagnosis. Outcomes: both patients experienced significant pain relief and restored normal lower limb movement at the last follow-up (4–12 weeks) after the intervention.ConclusionReal-time PCR detection offers valuable diagnostic insights for suspected cases of brucellosis spondylitis. Surgical treatment helps in infection control, decompression of the spinal cord, and restoration of stability, constituting a necessary and effective therapeutic approach. Prompt diagnosis and comprehensive management are crucial for favorable outcomes in such cases.

The reserve of glycogen is essential for embryonic development. In oviparous fish, egg is an isolated system after egg laying with all the required energy deposits by their mothers. However, the key regulated factor mediates the storage of maternal glycogen reserve which support for embryogenesis in the offspring is largely unknown. Glycogen synthase (GYS) is a central enzyme for glycogen synthesis. In our previous study, we generated a gys1 knockout zebrafish line, showed an embryonic developmental defect in F3 generation. In this study, firstly we determined that the gys1 was maternal origin by backcrossing the F2 mutant with wildtype lines. PAS staining and glycogen content measurement showed that glycogen reserve was reduced both in ovaries and embryos in the mutant group compared to wildtypes. Free glucose measurement analysis showed a 50 % of reduction in gys1 mutant embryos compared to wildtype embryos at 24 hpf; showed an approximal 50 % of reduction in gys1 mutant adults compared to wildtypes. Microinjection of 2-NBDG in embryos and comparison of fluorescent signal demonstrated that glucose uptake ability was decreased in the mutant embryos, indicating an impaired glucose metabolism. Untargeted metabolomics analysis then was employed and revealed that key modified metabolites enriched into vitamin B pathway, carbohydrate and unsaturated fatty acid pathways. These results demonstrated that gys1 played a role on glycogen metabolism, involved into the maternal glycogen reserve which essentially contribute to embryonic development.

Abstract Suicidality in mood disorder patients is common, especially in emergency department (ED), but the patterns and associated factors of suicidality are not clear. This study compared biomarkers and mental health symptoms (i.e., depression, anxiety, and psychiatric symptoms) between mood disorder patients with and without the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), and suicide attempt (SA). This cross-sectional, comparative, convenient-sampling study was conducted between January 2021 and March 2022, in emergency department of Beijing Anding Hospital, China. Patients with mood disorders at a psychiatric emergency department were assessed, with measurements of suicidality, biomarkers, depressive, anxiety, and psychiatric symptoms were assessed using the 24 items-Hamilton Depression Rating Scale (HAMD-24), Hamilton Anxiety Rating Scale (HAMA), Young Manic Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), respectively. The propensity score matching (PSM) method was used to identify patients in mood disorder with and without SI, SP, and SA. A generalized linear model (GLM) was used to assess the differences in biomarkers, depressive, anxiety, and psychiatric symptoms between patients in mood disorder with and without SI, SP, and SA. In total, 898 participated in this survey and completed the assessment. Illness duration was significantly negatively associated with SA (OR = 0.969, 95%CI = 0.939–0.999, P = 0.046). HAMD-24 total score was significantly positively associated with the SI (OR = 1.167, 95%CI = 1.134–1.201, p

This study presents a novel real-time prediction technique for multi-degree-of-freedom ship motion and resting periods utilizing Long Short-Term Memory (LSTM) networks. The primary objective is to enhance the safety and efficiency of shipborne helicopter landings by accurately predicting heave, pitch, and roll data over an 8 s forecast horizon. The proposed method utilizes the LSTM network’s capability to model complex nonlinear time series while employing the User Datagram Protocol (UDP) to ensure efficient data transmission. The model’s performance was validated using real-world ship motion data collected across various sea states, achieving a maximum prediction error of less than 15%. The findings indicate that the LSTM-based model provides reliable predictions of ship resting periods, which are crucial for safe helicopter operations in adverse sea conditions. This method’s capability to provide real-time predictions with minimal computational overhead highlights its potential for broader applications in marine engineering. Future research should explore integrating multi-model fusion techniques to enhance the model’s adaptability to rapidly changing sea conditions and improve the prediction accuracy.

Cholangiocarcinoma (CCA) is a highly heterogeneous tumor that occurs in the bile duct epithelium; adenosquamous carcinoma is a rare pathological subtype of CCA. The clinical treatment of patients with metastatic distal CCA poses significant challenges. We report a 53-year-old female diagnosed with a stage III adenosquamous carcinomas of distal CCA. Metastasis occurred 4 months postoperatively and she was diagnosed with stage IV disease. The patient was treated with Gemcitabine + Oxaliplatin (GEMOX) and Capecitabine + Oxaliplatin (CAPEOX), followed by sintilimab monotherapy. After two cycles of treatment, the patient achieved partial response (PR) and the lesion continued to shrink. After 37 months of follow-up, the patient’s liver metastasis had almost completely disappeared, and complete response (CR) was achieved. Moreover, she had more than 46 months of disease progression-free survival (PFS). Immunohistochemical testing showed high expression of PD-L1, and next-generation sequencing revealed the presence of mutations in DNA damage repair (DDR) pathway genes. To the best of our knowledge, this is the first reported case of the successful treatment of metastatic distal adenosquamous CCA with sintilimab alone. Remarkably, patients of CCA with high PD-L1 expression and DDR pathway gene mutations may benefit from sintilimab treatment.

Pholis fangi is a small, bottom-dwelling fish species endemic to the Yellow Sea and Bohai Sea in China. While previous research has focused on its population biology and molecular structure, little is known about the early developmental stages of this species. In this study, larval and juvenile P. fangi specimens were collected from the Sheyang Sea Area, Jiangsu Province, in 2017. Morphological features were examined using microscopy, and DNA barcoding was conducted to confirm species identification. The research documented detailed changes in yolk sac, fin development, and melanophore distribution patterns across larval and juvenile stages of P. fangi. Comparative analysis with other Pholis species revealed that melanophore distribution is a key distinguishing characteristic, allowing effective differentiation between larval and juvenile stages, as well as between Pholis species. This study provides valuable insights into the early life history of P. fangi, contributing to a better understanding of the genus Pholis. The findings demonstrate the utility of combining traditional morphological observation and molecular techniques for accurate species identification, particularly during the critical larval and juvenile developmental phases.

Abstract Rapid assessment and intervention of suicide risk are common and challenging in psychiatric emergency departments (PED). It is unclear whether distinct pathophysiological processes exist among depressive patients with suicidality. This study examined the network structures of biomarkers on Hypothalamic-Pituitary-Adrenal (HPA) axis, such as Adrenocorticotropic hormone (ACTH) and Corticosterone (Cort), as well as suicidality and depressive symptoms in mood disorder patients in PED. Mood disorder patients in PED were assessed with the measurements of suicidality and depressive symptoms, respectively. A network analysis was performed to identify central symptoms and bridge symptoms of this network and their links to ACTH and Cort. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. A total of 1815 mood disorder patients were recruited. The prevalence of SI was 31.2% (95% CI: 28.15–34.21%), SP was 30.4% (95% CI: 27.39–33.41%), SA was 30.62% (95% CI: 27.61–33.64%) among psychiatric outpatients. The mean score of HAMD-24 was 13.87 ± 8.02. Network analysis revealed that ‘Somatic anxiety’ had the highest expected centrality, followed by ‘Hopelessness’ and ‘Suicide attempt’. ‘Corticosterone’ and ‘Retardation’ may be the main bridge symptoms between depressive symptoms and the suicidality community. The network model showed a high degree of stability. Gender did not significantly influence the network structure. The central symptoms and key bridge symptoms identified could be potential targets for interventions of the HPA axis, which is designed for regular screening of a range of suicidal activity. In the light of this, timely treatment should be provided for psychiatric emergency care.

Angiopoietin-1 (ANG1) is a pro-angiogenic regulator that contributes to the progression of solid tumors by stimulating the proliferation, migration and tube formation of vascular endothelial cells, as well as the renewal and stability of blood vessels. However, the functions and mechanisms of ANG1 in triple-negative breast cancer (TNBC) are unclear. The clinical sample database shows that a higher level of ANG1 in TNBC is associated with poor prognosis compared to non-TNBC. In addition, knockdown of ANG1 inhibits TNBC cell proliferation and induces cell cycle G1 phase arrest and apoptosis. Overexpression of ANG1 promotes tumor growth in nude mice. Mechanistically, ANG1 promotes TNBC by upregulating carboxypeptidase A4 (CPA4) expression. Overall, the ANG1-CPA4 axis can be a therapeutic target for TNBC.

AbstractBackground Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis.Methods Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)’s risk of bias tools.Results Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p

Metabolite-specific echo-planar imaging (EPI) sequences with spectral–spatial (spsp) excitation are commonly used in clinical hyperpolarized [1-13C]pyruvate studies because of their speed, efficiency, and flexibility. In contrast, preclinical systems typically rely on slower spectroscopic methods, such as chemical shift imaging (CSI). In this study, a 2D spspEPI sequence was developed for use on a preclinical 3T Bruker system and tested on in vivo mice experiments with patient-derived xenograft renal cell carcinoma (RCC) or prostate cancer tissues implanted in the kidney or liver. Compared to spspEPI sequences, CSI were found to have a broader point spread function via simulations and exhibited signal bleeding between vasculature and tumors in vivo. Parameters for the spspEPI sequence were optimized using simulations and verified with in vivo data. The expected lactate SNR and pharmacokinetic modeling accuracy increased with lower pyruvate flip angles (less than 15°), intermediate lactate flip angles (25° to 40°), and temporal resolution of 3 s. Overall SNR was also higher with coarser spatial resolution (4 mm isotropic vs. 2 mm isotropic). Pharmacokinetic modelling used to fit kPL maps showed results consistent with the previous literature and across different sequences and tumor xenografts. This work describes and justifies the pulse design and parameter choices for preclinical spspEPI hyperpolarized 13C-pyruvate studies and shows superior image quality to CSI.

The implementation of Li metal anode with high-voltage Ni/Co rich cathode is plagued by low coulombic efficiency and inferior cycling stability. Here authors propose an anion-enriched interface to facilitate the columnar-structure of Li deposits to solve this issue.

ObjectiveThe aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade.MethodsWe retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020–2029 by developing the Bayesian age-period-cohort model.ResultsThe global number of deaths from AFF increased from 117,038.00 in 1990 to 315,336.80 in 2019. This number is projected to reach 404,593.40 by 2029. The age-standardized mortality rates (ASMRs) of AFF have increased significantly in low- to middle-sociodemographic index (SDI) regions, which will surpass that in high SDI regions and reach above 4.60 per 100,000 by 2029. Globally, women have a higher ASMR than men, which is largely attributed to disproportionately higher mortality in women than men in lower SDI regions. Notably, AFF-related premature mortality continues to worsen worldwide. A pandemic of high systolic blood pressure and high body mass index (BMI) largely contributes to AFF-associated death. In particular, low- to middle-SDI regions and younger populations are increasingly affected by the rapidly growing current and future risk of high BMI.ConclusionThe global death burden of AFF in low-income countries and younger generations have not been sufficiently controlled in the past and will continue growing in the future, which is largely attributed to metabolic risks, particularly for high BMI. There is an urgent need to implement effective measures to control AFF-related mortality.