Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis.

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation-Reprotonation Process.

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and - according to a structural model - active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation-reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site-directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.

Learn to optimize-a brief overview.

Most optimization problems of practical significance are typically solved by highly configurable parameterized algorithms. To achieve the best performance on a problem instance, a trial-and-error configuration process is required, which is very costly and even prohibitive for problems that are already computationally intensive, e.g. optimization problems associated with machine learning tasks. In the past decades, many studies have been conducted to accelerate the tedious configuration process by learning from a set of training instances. This article refers to these studies as learn to optimize and reviews the progress achieved.

Computed tomography radiomics study of invasion and instability of lung adenocarcinoma manifesting as ground glass nodule.

Background: Ground-glass nodule (GGN) is the most common manifestation of lung adenocarcinoma on computed tomography (CT). Clinically, the success rate of preoperative diagnosis of GGN by puncture biopsy and other means is still low. The aim of this study is to investigate the clinical and radiomics characteristics of lung adenocarcinoma presenting as GGN on CT images using radiomics analysis methods, establish a radiomics model, and predict the classification of pathological tissue and instability of GGN type lung adenocarcinoma. Methods: This study retrospectively collected 249 patients with 298 GGN lesions who were pathologically confirmed of having lung adenocarcinoma. The images were imported into the Siemens scientific research prototype software to outline the region of interest and extract the radiomics features. Logistic model A (a radiomics model to identify the infiltration of lung adenocarcinoma manifesting as GGNs) was established using features after the dimensionality reduction process. The receiver operating characteristic (ROC) curve of the model on training set and the verification set was drawn, and the area under the curve (AUC) was calculated. Second, a total of 112 lesions were selected from 298 lesions originating from CT images of at least two occasions, and the time between the first CT and the preoperative CT was defined as not less than 90 days. The mass doubling time (MDT) of all lesions was calculated. According to the different MDT diagnostic thresholds instability was predicted. Finally, their AUCs were calculated and compared. Results: There were statistically significant differences in age and lesion location distribution between the "noninvasive" lesion group and the invasive lesion group (P<0.05), but there were no statistically significant differences in sex (P>0.05). Model A had an AUC of 0.89, sensitivity of 0.75, and specificity of 0.86 in the training set and an AUC of 0.87, sensitivity of 0.63, and specificity of 0.90 in the validation set. There was no significant difference statistically in MDT between "noninvasive" lesions and invasive lesions (P>0.05). The AUCs of radiomics models B1, B2 and B3 were 0.89, 0.80, and 0.81, respectively; the sensitivities were 0.71, 0.54, and 0.76, respectively; the specificities were 0.83, 0.77, and 0.60, respectively; and the accuracies were 0.78, 0.65, and 0.69, respectively. Conclusions: There were statistically significant differences in age and location of lesions between the "noninvasive" lesion group and the invasive lesion group. The radiomics model can predict the invasiveness of lung adenocarcinoma manifesting as GGNs. There was no significant difference in MDT between "noninvasive" lesions and invasive lesions. The radiomics model can predict the instability of lung adenocarcinoma manifesting as GGN. When the threshold of MDT was set at 813 days, the model had higher specificity, accuracy, and diagnostic efficiency.

Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

A novel strategy with in vivo characterization, extraction, isolation and activity evaluation for discovery of absorbed anti-inflammatory oligosaccharides from Zhu-Ling decoction.

Zhu-Ling decoction (ZLD), a classical traditional Chinese medicine (TCM) formula, is used for the treatment of chronic kidney diseases. However, the structure and activity of absorbed oligosaccharides (OSs) in ZLD are not clear. In this study, a novel strategy with in vivo characterization, extraction, isolation, activity evaluation was established and applied to identify absorbed anti-inflammatory OSs in ZLD. The results revealed that 30 OSs (22 reducing and 8 non-reducing OSs) and 11 OSs (7 reducing and 4 non-reducing OS) were characterized from ZLD in vitro and in vivo by using UPLC/Q-TOF-MS with PMP derivatization, respectively. Among them, a series of -1 â†’ 3-ß-D-Glcp-OSs were isolated and identified by HPLC-HILIC-UVD-ELSD, SPHPLC-HILIC-RID, monosaccharide composition, MS and 1D/2D-NMR spectroscopy, including laminaritriose, laminaritetraose, laminaripentaose, laminarihexaose, laminariheptaose, laminarioctaose and laminarinonaose. Moreover, the 4 non-reducing absorbed OSs were identified by comparison with reference standards, including sucrose, trehalose, raffinose and stachyose. Among them, laminaritriose, laminaritetraose and laminaripentaose significantly inhibited TNF-α and IL-6 levels in LPS-induced HK-2 cell and exerted significant anti-inflammatory effects via the NF-κB and Akt/mTOR signaling pathways. Together, our work provides a novel strategy for discovery of absorbed anti-inflammatory OSs and broadens new horizons for the discovery of in vivo pharmacodynamic substances in TCM formulas.

Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Exploring the mechanism of Si-Miao-Yong-An decoction on heart failure based on molecular docking and network pharmacology.

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.

Development of gelatin-methacryloyl composite carriers for bone morphogenetic Protein-2 delivery: A potential strategy for spinal fusion.

To reduce the risk of nonunion after spinal fusion surgery, the in situ transplantation of bone marrow mesenchymal stem cells (BMSCs) induced toward osteogenic differentiation by bone morphogenetic protein-2 (BMP2) has been proven effective. However, the current biological agents used for transplantation have limitations, such as a short half-life and low bioavailability. To address this, our study utilized a safe and effective gelatin-methacryloyl (GelMA) as a carrier for BMP2. In vitro, experiments were conducted to observe the ability of this composite vehicle to induce osteogenic differentiation of BMSCs. The results showed that the GelMA hydrogel, with its critical properties and controlled release performance of BMP2, exhibited a slow release of BMP2 over 30 days. Moreover, the GelMA hydrogel not only enhanced the proliferation activity of BMSCs but also significantly promoted their osteogenic differentiation ability, surpassing the BMP2 effects. To investigate the potential of the GelMA-BMP2 composite vehicle, a rabbit model was employed to explore its ability to induce in situ intervertebral fusion by BMSCs. Transplantation experiments in rabbits demonstrated the effective induction of intervertebral bone fusion by the GelMA-BMP2-BMSC composite vehicle. In conclusion, the GelMA-BMP2-BMSC composite vehicle shows promising prospects in preclinical translational therapy for spinal intervertebral fusion. It addresses the limitations of current biological agents and offers a controlled release of BMP2, enhancing the proliferation and osteogenic differentiation of BMSCs.

Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Create artilysins from a recombinant library to serve as bactericidal and antibiofilm agents targeting Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a critical pathogen and novel treatments are urgently needed. The out membrane of P. aeruginosa facilitates biofilm formation and antibiotic resistance, and hinders the exogenous application against Gram-negative bacteria of endolysins. Engineered endolysins are investigated for enhancing antimicrobial activity, exemplified by artilysins. Nevertheless, existing research predominantly relies on laborious and time-consuming approaches of individually artilysin identification. This study proposes a novel strategy for expedited artilysin discovery using a recombinant artilysin library comprising proteins derived from 38 antimicrobial peptides and 8 endolysins. In this library, 19 colonies exhibited growth inhibition against P. aeruginosa exceeding 50 %, and three colonies were designated as dutarlysin-1, dutarlysin-2 and dutarlysin-3. Remarkably, dutarlysin-1, dutarlysin-2 and dutarlysin-3 demonstrated rapid and enhanced antibacterial activity, even minimum inhibitory concentration of them killed approximately 4.93 lg units, 6.75 lg units and 5.36 lg units P. aeruginosa, respectively. Dutarlysins were highly refractory to P. aeruginosa resistance development. Furthermore, 2 µmol/L dutarlysin-1 and dutarlysin-3 effectively eradicated over 76 % of the mature biofilm. These dutarlysins exhibited potential broad-spectrum activity against hospital susceptible Gram-negative bacteria. These results supported the effectiveness of this artilysins discovery strategy and suggested dutarlysin-1 and dutarlysin-3 could be promising antimicrobial agents for combating P. aeruginosa.

Mesenchymal stem cell-derived exosomes ameliorate hypoxic pulmonary hypertension by inhibiting the Hsp90aa1/ERK/pERK pathway.

Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 hours a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) was used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway.

Efficient determination of critical water activity and classification of hydrate-anhydrate stability relationship.

For a pair of hydrated and anhydrous crystals, the hydrate is more stable than the anhydrate when the water activity is above the critical water activity (awc). Conventional methods to determine awc are based on either hydrate-anhydrate competitive slurries at different aw or solubilities measured at different temperatures. However, these methods are typically resource-intensive and time-consuming. Here, we present simple and complementary solution- and solid-based methods and illustrate them using carbamazepine and theophylline. In the solution-based method, awc can be predicted using intrinsic dissolution rate (IDR) ratio or solubility ratio of the hydrate-anhydrate pair measured at a known water activity. In the solid-based method, awc is predicted as a function of temperature from the dehydration temperature and enthalpy obtained by differential scanning calorimetry (DSC) near a water activity of unity. For carbamazepine and theophylline, the methods yielded awc values in good agreement with those from the conventional methods. By incorporating awc as an additional variable, the hydrate-anhydrate relationship is categorized into four classes based on their dehydration temperature (Td) and enthalpy (ΔHd) in analogy with the monotropy/enantiotropy classification for crystal polymorphs. In Class 1 (ΔHd< 0 and Td ≥ 373 K), no awc exists. In Class 2 (ΔHd>0andTd≥373K), awc always exists under conventional crystallization conditions. In Class 3 (ΔHd<0andTd<373K), awc exists when T>Td. In Class 4 (ΔHd>0andTd<373K), awc exists only when T

Transcriptome analysis reveals the effect of cold storage time on the expression of genes related to oxidative metabolism in Chinese black truffle.

Chinese black truffle (Tuber indicum) is a hypogenous fungus of great value due to its distinctive aroma. In this study, both transcriptome and physicochemical analyses were performed to investigate the changes of nutrients and gene expression in truffle fruiting bodies during cold storage. The results of physicochemical analysis revealed the active metabolism of fruiting bodies in cold storage, showing the decreased contents of protein and soluble sugar, the variations in both polyphenol oxidase activity and total phenol content, and the detrimental effect of reactive oxygen species production caused by heavy metals (cadmium and lead) in truffles. Transcriptome analysis identified a total of 139,489 unigenes. Down-regulated expression of genes encoding the catalase-like domain-containing protein (katE), glutaredoxin protein (GRX), a copper/zinc superoxide dismutase (Sod_Cu), and aspartate aminotransferase (AAT) affected the degradation metabolism of intracellular oxides. Ribulose-5-phosphate-3-epimerase (RPE) was a key enzyme in response to oxidative stress in truffle cells through the pentose phosphate pathway (PPP). A total of 51,612 simple sequence repeats were identified, providing valuable resources for further genetic diversity analysis, molecular breeding, and genetic map-ping in T. indicum. Transcription factors GAL4 and SUF4-like protein were involved in glucose metabolism and histone methylation processes, respectively. Our study provided a fundamental characterization of the physicochemical and molecular variations in T. indicum during the cold storage at 4°C, providing strong experimental evidence to support the improvement of storage quality of T. indicum.

Factors influencing the job embeddedness of new graduate nurses: A multicentre cross-sectional study.

AIM: To identify factors associated with job embeddedness from the perspective of retaining new graduate nurses. DESIGN: The study was cross-sectional in design. METHODS: Convenience and stratified sampling were used to recruit 415 newly graduated nurses from 12 tertiary hospitals in China. Anonymized data were collected through self-designed sociodemographic questionnaires, job embeddedness scale, feedback-seeking behaviour scale, authentic leadership perception scale and decent work scale. Appropriate indicators were used for descriptive statistics and t-tests, ANOVA, Pearson correlation analysis and multiple linear regression to examine the influencing factors. RESULTS: The study showed that monthly income level, decent labour, authentic leadership and feedback-seeking behaviour were significant predictors of job embeddedness among new graduate nurses. CONCLUSION: The job embeddedness of new graduate nurses is moderate. Nursing managers need to construct reasonable and fair compensation incentives, adopt positive leadership styles and encourage proactive feedback-seeking behaviours to improve the job embeddedness of new graduate nurses and alleviate the nursing talent shortage. IMPACT: Exploring the factors influencing the job embeddedness of new graduate nurses provides a reference for establishing new graduate nurse retention strategies to help promote the career development of new graduate nurses and alleviate the nursing brain drain. REPORTING METHOD: We adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A sensitive sandwich-type electrochemical aptasensing platform based on Ti3C2Tx/MoS2/MWCNT@rGONR composites for simultaneous detection of kanamycin and chloramphenicol in food samples.

A Ti3C2Tx/MoS2/MWCNT@rGONR nanocomposite was prepared for the first time for building a sensitive electrochemical aptasening platform to simultaneously detect kanamycin (Kana) and chloramphenicol (Cap). Owing to their accordion-like structure, rich surface groups, and high charge mobility, Ti3C2Tx/MoS2/MWCNT@rGONR composites provided a spacious covalent immobilization surface and a better electrochemical aptasensing platform. The aptamers of Kana and Cap used in sensors enhance the selectivity. Furthermore, TiP, an ion exchanger, was used for loading more different metal ions functioning as labels to form a sandwich-type sensor together with Ti3C2Tx/MoS2/MWCNT@rGONR, improving the electrochemical sensitivity and obtaining a highly distinguishable signal readout. Under the optimized conditions, the sensor has good detection limits of 0.135 nmol L-1 and 0.173 nmol L-1 for Kana and Cap, respectively, at the same linearity concentration of 0.5-2500 nmol L-1. Finally, it was successfully applied for detection in milk and fish meat, and the results were compared with the standard method HPLC, indicating its great potential for food safety monitoring.

An Ultramicroelectrode Electrochemistry and Surface Plasmon Resonance Coupling Method for Cell Exocytosis Study.

Exocytosis of a single cell has been extensively researched in recent years due to its close association with numerous diseases. However, current methods only investigate exocytosis at either the single-cell or multiple-cell level, and a method for simultaneously studying exocytosis at both levels has yet to be established. In this study, a combined device incorporating ultramicroelectrode (UME) electrochemistry and surface plasmon resonance (SPR) was developed, enabling the simultaneous monitoring of single-cell and multiple-cell exocytosis. PC12 cells were cultured directly on the SPR sensing Au film, with a carboxylated carbon nanopipette (c-CNP) electrode employed for electrochemical detection in the SPR reaction cell. Upon exocytosis, the released dopamine diffuses onto the inner wall of c-CNP, undergoing an electrochemical reaction to generate a current peak. Concurrently, exocytosis can also induce changes in the refractive index of the Au film surface, leading to the SPR signal. Consequently, the device enables real-time monitoring of exocytosis from both single and multiple cells with a high spatiotemporal resolution. The c-CNP electrode exhibited excellent resistance to protein contamination, high sensitivity for dopamine detection, and the capability to continuously monitor dopamine exocytosis over an extended period. Analysis of both SPR and electrochemical signals revealed a positive correlation between changes in the SPR signal and the frequency of exocytosis. This study introduces a novel method and platform for the simultaneous investigation of single-cell and multiple-cell exocytosis.

Identification of distinct symptom profiles in prostate cancer patients with cancer-related cognitive impairment undergoing androgen deprivation therapy: A latent class analysis.

Objective: To identify latent classes of cognitive impairment and co-occurring symptoms (fatigue, pain, sleep disturbance, depression) as clusters in patients with prostate cancer undergoing androgen deprivation therapy and to explore the predictors among distinct latent classes. Methods: A total of 228 patients with prostate cancer were recruited in this cross-sectional study. The assessment instrument included the Perceived Cognitive Impairment Scale, the Fatigue Severity Scale, the Athens Insomnia Scale, the Brief Pain Inventory, the Patient Health Questionnaire-9, the UCLA Loneliness Scale, the International Physical Activity Questionnaire - Short Form, the Charlson comorbidity index, and General Information questionnaire. The identification of different patient subgroups was done by the latent class analysis. Results: The study identified three distinct latent classes: all low symptoms (class 1, 32%), high depression symptoms (class 2, 37.7%), and high physical symptoms (fatigue, sleep disturbance, and pain) with high cognitive impairment (class 3, 30.3%). Patients who had higher Charlson comorbidity index (P = 0.003) scores were more likely to be classified in class 3. Patients with higher loneliness scores (P < 0.001; P < 0.001) were significantly more likely to fall into class two or three than in class 1. However, having a higher level of physical activity (P = 0.014; P < 0.001) increased the likelihood of being in class 1. Conclusions: This study exhibited the inter-individual variability of symptom experience in prostate cancer patients with cognitive impairment undergoing androgen deprivation therapy. The result suggests that more emphasis should be placed on screening for fatigue, sleep disturbance, and pain, and future interventions should focus on loneliness and physical activity.

Abdominal pain caused by Tibetan medicine: A case report of lead poisoning.

Nowadays, lead poisoning in children commonly occurs, but lead poisoning caused by the administration of Tibetan medicine is rarely reported. This report describes the diagnosis and management of lead poisoning in a 16-year-old girl presented with abdominal pain, vomiting, and anemia with limb numbness, who had a childhood history of epilepsy and took Tibetan medicine intermittently to control the symptoms. After admission into hospital, Computed tomography showed high-density shadows in the gastrointestinal tract. Video-Electroencephalography showed no signs of seizure. Reflux esophagitis was observed in gastroscopy. And no obvious abnormalities in the colonic mucosa through colonoscopy. Bone marrow smear test showed basophilic stippling in the erythrocytes. The blood and urine lead levels of 626 and 75.9 µg/L, respectively. We therefore considered lead poisoning, and the patient improved after chelation therapy. Due to its atypical clinical manifestations, lead poisoning is easily misdiagnosed. Thus, clinicians should pay more attention to this disease. When abdominal pain, anemia, and neurological symptoms are present, the possibility of lead poisoning should be considered.

Hederagenin reduces Aß-induced oxidative damage, decreases Aß deposition and promotes cell survival by the P13†K/Akt signaling pathway.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. ß-amyloid (Aß) is one of the typical pathological features of AD, and its accumulation leads to neuronal death from oxidative stress. Here, we found that hederagenin (HG), a natural product, exhibits anti-tumor, anti-inflammatory, anti-depressant, anti-neurodegenerative biological activities. However, whether HG has anti-Aß activity remains unclear. Based on the characteristics of HG, it is hypothesized that HG has biological activity against Aß injury. Therefore, Aß-injured SH-SY5Y cells were constructed, and the protective effect of HG against Aß injury was further evaluated using C. elegans. The results showed that HG increased superoxide dismutase activity, effectively reduced Aß-induced oxidative damage, and reduced apoptosis via the PI3 K/Akt signaling pathway. HG inhibited Aß deposition and delayed senescence and paralysis in the C. elegans strain, CL4176. HG showed inhibitory effects on Aß; therefore, more natural active products are expected to be applied in AD therapy.