Effectiveness of digital intelligence interventions on depression and anxiety in older adults: A systematic review and meta-analysis.

BACKGROUND: Depression and anxiety are common mental disorders in later life. Digital intelligence interventions overcome the limitations of conventional psychotherapy and offer new treatments for depression and anxiety. However, the effectiveness among older adults remains unclear. METHODS: Databases including Pubmed, Web of Science, the Cochrane Library, Medline, CINAHL, PsycINFO, and Embase were searched for Randomized Controlled Trials (RCTs) from inception to November 22, 2023. Statistical analyses were conducted using Stata 18.0 and Review Manager 5.4. RESULTS: The initial search found 9369 papers, with 21 meeting the inclusion criteria (e.g., RCTs involving older adults aged 50 and older that assessed digital intelligence interventions on depression and anxiety symptoms). Meta-analyses revealed that, compared to control groups, digital intelligence interventions significantly reduced depression symptoms (SMD: -0.58; 95 % CI: -0.80, -0.35) and anxiety symptoms (SMD: -0.39; 95 % CI: -0.58, -0.19). Subgroup analysis revealed that internet-based Cognitive Behavioral Therapy (iCBT), interventions lasting 7 to 10 weeks, and the use of the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder-7 (GAD-7) scales, especially in other regions, had the most pronounced effects. CONCLUSIONS: Digital intelligence interventions reduce depressive and anxious symptoms in older adults, supporting the development of evidence-based treatment guidelines in the digital era.

Clinical Features and a Prediction Model for Early Prediction of Composite Outcome in Chlamydia psittaci Pneumonia: A Multi-Centre Retrospective Study in China.

Introduction: C. psittaci pneumonia has atypical clinical manifestations and is often ignored by clinicians. This study analyzed the clinical characteristics, explored the risk factors for composite outcome and established a prediction model for early prediction of composite outcome among C. psittaci pneumonia patients. Methods: A multicenter, retrospective, observational cohort study was conducted in ten Chinese tertiary hospitals. Patients diagnosed with C. psittaci pneumonia were included, and their clinical data were collected and analyzed. The composite outcome of C. psittaci pneumonia included death during hospitalization, ICU admission, and mechanical ventilation. Univariate and multivariable logistic regression analyses were conducted to determine the significant variables. A ten-fold cross-validation was performed to internally validate the model. The model performance was evaluated using various methods, including receiver operating characteristics (ROC), C-index, sensitivity, specificity, positive/negative predictive value (PPV/NPV), decision curve analysis (DCA), and clinical impact curve analysis (CICA). Results: In total, 83 patients comprised training cohorts and 36 patients comprised validation cohorts. CURB-65 was used to establish predictive Model 1. Multivariate logistic regression analysis identified three independent prognostic factors, including serum albumin, CURB-65, and white blood cells. These factors were employed to construct model 2. Model 2 had acceptable discrimination (AUC of 0.898 and 0.825 for the training and validation sets, respectively) and robust internal validity. The specificity, sensitivity, NPV, and PPV for predicting composite outcome in the nomogram model were 91.7%, 84.5%, 50.0%, and 98.4% in the training sets, and 100.0%, 64.7%, 14.2%, and 100.0% in the validation sets. DCA and CICA showed that the nomogram model was clinically practical. Conclusion: This study constructs a refined nomogram model for predicting the composite outcome in C. psittaci pneumonia patients. This nomogram model enables early and accurate C. psittaci pneumonia patients' evaluation, which may improve clinical outcomes.

Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center.

The NLRP3 inflammasome is a multi-protein molecular machine that mediates inflammatory responses in innate immunity. Its dysregulation has been linked to a large number of human diseases. Using cryogenic fluorescence-guided focused-ion-beam (cryo-FIB) milling and electron cryo-tomography (cryo-ET), we obtained 3-D images of the NLRP3 inflammasome in situ at various stages of its activation at macromolecular resolution. The cryo-tomograms unexpectedly reveal dense condensates of the human macrophage NLRP3 inflammasome that form within and around the microtubule organizing center (MTOC). We also find that following activation, the trans-Golgi network disperses and 50-nm NLRP3-associated vesicles appear which likely ferry NLRP3 to the MTOC. At later time points after activation, the electron-dense condensates progressively solidify and the cells undergo pyroptosis with widespread damaged mitochondria and autophagasomal structures.

Transcriptome Analysis and Identification of Genes Associated with Cotton Seed Size.

Cotton seeds, as the main by-product of cotton, are not only an important raw material for edible oil and feed but also a source of biofuel. The quality of cotton seeds directly affects cotton planting and is closely related to the yield and fiber quality. However, the molecular mechanism governing cotton seed size remains largely unexplored. This study investigates the regulatory mechanisms of cotton seed size by focusing on two cotton genotypes, N10 and N12, which exhibit notable phenotypic variations across multiple environments. Developing seeds were sampled at various stages (5, 20, 30, and 35 DPA) and subjected to RNA-seq. Temporal pattern clustering and WGCNA on differentially expressed genes identified 413 candidate genes, including these related to sugar metabolism that were significantly enriched in transcriptional regulation. A genetic transformation experiment indicated that the overexpression of the GhUXS5 gene encoding UDP-glucuronate decarboxylase 5 significantly increased seed size, suggesting an important role of GhUXS5 in regulating cotton seed size. This discovery provides crucial insights into the molecular mechanisms controlling cotton seed size, helping to unravel the complex regulatory network and offering new strategies and targets for cotton breeding to enhance the economic value of cotton seeds and overall cotton yield.

Design of a Membrane-Anchored DNAzyme-Based Molecular Machine for Enhanced Cancer Therapy by Customized Cascade Regulation.

Synthetic DNAzyme-based structures enable dynamic cell regulation. However, engineering an effective and targeted DNAzyme-based structure to perform customizable multistep regulation remains largely unexplored. Herein, we designed a membrane-anchored DNAzyme-based molecular machine to implement dynamic inter- and intracellular cascade regulation, which realizes efficient T-cell/cancer cell interactions and subsequent receptor mediated cancer cell uptake. Using CD8+ T-cells and HeLa cancer cells as a proof of concept, we demonstrate that the designed DNAzyme-based molecular machine enables customized cascade regulation including (1) specific recognition between T-cells and cancer cells, (2) specific response and fluorescence sensing upon extracellular stimuli, and (3) cascade regulation including intercellular distance shortening, cell-cell communication, and intracellular delivery of anticancer drugs. Together, this work provides a promising pathway for customized cascade cell regulation based on a DNAzyme-based molecular machine, which enables enhanced cancer therapy by combining T-cell immunotherapy and chemotherapy.

Simultaneous Detection of Multiple Respiratory Pathogens Using an Integrated Microfluidic Chip.

Respiratory pathogens pose significant challenges to public health, demanding efficient diagnostic methods. This study presents an integrated microfluidic chip for the simultaneous detection of multiple respiratory pathogens. The chip integrates magnetic bead-based nucleic acid extraction and purification, acoustic streaming-driven mixing, liquid equalization, and multiplex PCR amplification with in situ fluorescence detection. Nucleic acid extraction takes only 12 min, yielding results comparable to commercial kits. Efficient mixing of magnetic beads is achieved through a combination of designed micropillars and bubble-trapping array structures. The micropillars maintain the aqueous phase in the mixing chamber, while the bubble-trapping arrays enable stable formation of bubbles, serving as a micromixer under the acoustic field. To prevent cross-contamination, an oil-encapsulated water droplet system is incorporated throughout nucleic acid extraction and PCR amplification. This assay displays remarkable multiplex analysis capability on a single chip, enabling the simultaneous detection of 12 common respiratory pathogens with a low detection limit of 10 copies/µL. Moreover, this method demonstrates excellent practical applicability in clinical nasal samples. Compared to many microfluidic chip-based molecular biology methods, the assay exhibits comparable or superior multipathogen analysis capability, sensitivity, and speed, completing the sample-to-answer process in approximately 70 min. This integrated microfluidic device offers a promising multiplex molecular diagnosis platform for on-site simultaneous detection of multiple pathogens.

Understanding the relationship between smartphone distraction, social withdrawal, digital stress, and depression among college students: A cross-sectional study in Wuhan, China.

Background: Smartphone distraction considerably affects the depression level of college students. These two variables are highly associated with social withdrawal and digital distress. However, the underlying mechanisms of how social withdrawal and digital stress were involved in the relationship between smartphone distraction and depression remain unclear. Methods: A cross-sectional survey was conducted in seven colleges of Wuhan, Hubei Province, from September to November 2021. Participants were selected using convenience sampling. Smartphone distraction, social withdrawal, digital stress, and depression level were assessed using the Smartphone Distraction Scale (SDS), 25-item Hikikomori Questionnaire (HQ-25), Multidimensional Digital Stress Scale (DSS), and the Patient Health Questionnaire-9 (PHQ-9), respectively. All scales demonstrated good reliability in this study, the reliability of each scale was 0.920, 0.884, 0.959, and 0.942. Results: The final analysis included 1184 students (692 males and 492 females), aged between 17 and 37 years. Participants were from various academic disciplines, including medical and non-medical. The findings revealed that smartphone distraction had a significant direct effect on depression (c = 0.073, 95 % CI: 0.037 to 0.108, p < 0.001) and three significant indirect mediation effects: (1) social withdrawal (B = 0.083, 95 % CI: 0.066 to 0.101, p < 0.001), accounting for 27.76 % of the total effect; (2) digital stress (B = 0.109, 95 % CI: 0.088 to 0.132, p < 0.001), accounting for 36.45 % of the total effect; and (3) the chain mediating roles of social withdrawal and digital stress (B = 0.034, 95 % CI: 0.026 to 0.043, p < 0.001), accounting for 11.37 % of the total effect. The total mediating effect was 75.59 %. Limitations: This study is based on cross-sectional data, which limits the causality inference. Conclusions: These findings suggest that educational institutions should identify college students with excessive smartphone use early and provide timely interventions to minimize negative outcomes. It is also significant to reduce the risk of social withdrawal and digital stress to maintain the physical and mental health development of college students.

The chain mediating role of rumination and social withdrawal in the relationship between smartphone distraction and depression among Chinese nursing students.

Smartphone distraction (SD) is closely related to depression, and the prevalence of SD among nursing students is gradually increasing. However, the potential mechanism of the effect of SD on nursing students' depression is unclear. A total of 574 nursing students were assessed using Smartphone Distraction Scale, Ruminative Response Scale, Hikikomori Questionnaire, and Patient Health Questionnaire-9. The results indicated that SD among nursing students had an impact on depression through four pathways: (1) SD was positively associated with depression (ß = 0.353, P < 0.001); (2) Rumination (ß = 0.199, 95% CI: 0.081 to 0.162) and social withdrawal (ß = 0.061, 95% CI: 0.034 to 0.091) mediated the effects of SD on depression, respectively; and (3) Rumination and social withdrawal played a chain mediating role in the effect of SD on nursing students' depression (ß = 0.027, 95% CI: 0.015 to 0.042). The negative impact of SD on nursing students' mental health should not be taken lightly. Schools and hospitals should guide nursing students to use smartphones correctly, including providing mental health education and professional psychological counselling; families could play a supervisory role and communicate regularly to understand the psychological state and learning of nursing students. These measures can help nursing students cope with stress and reduce the risk of depression.

Deciphering the dynamic expression network of fiber elongation and the functional role of the GhTUB5 gene for fiber length in cotton based on an introgression population of upland cotton.

INTRODUCTION: Interspecific introgression between Gossypium hirsutum and G. barbadense allows breeding cotton with outstanding fiber length (FL). However, the dynamic gene regulatory network of FL-related genes has not been characterized, and the functional mechanism through which the hub gene GhTUB5 mediates fiber elongation has yet to be determined. METHODS: Coexpression analyses of 277 developing fiber transcriptomes integrated with QTL mapping using 250 introgression lines of different FL phenotypes were conducted to identify genes related to fiber elongation. The function of GhTUB5 was determined by ectopic expression of two TUB5 alleles in Arabidopsis and knockout of GhTUB5 in upland cotton. Yeast two-hybrid, split-luciferase and pull-down assays were conducted to screen for interacting proteins, and upstream genes were identified by yeast one-hybrid, dual-LUC and electrophoretic mobility shift assays. RESULTS: The 32,612, 30,837 and 30,277 genes expressed at 5, 10 and 15 days postanthesis (dpa) were grouped into 19 distinct coexpression modules, and 988 genes in the MEblack module were enriched in the cell wall process and exhibited significant associations with FL. A total of 20 FL-QTLs were identified, each explaining 3.34-16.04 % of the phenotypic variance in the FL. Furthermore, several FL-QTLs contained 15 genes that were differentially expressed in the MEblack module including the tubulin beta gene (TUB5). Compared with the wild type, the overexpression of GhTUB5 and GbTUB5 in Arabidopsis suppressed root cell length but promoted cellulose synthesis. Knockout of GhTUB5 resulted in longer fiber lines. Protein-based experiments revealed that GhTUB5 interacts with GhZFP6. Additionally, GhTUB5 was directly activated by GhHD-ZIP7, a homeobox-leucine zipper transcription factor, and its paralogous gene was previously reported to mediate fiber elongation. CONCLUSION: This study opens a new avenue to dissect functional mechanism of cotton fiber elongation. Our findings provide some molecular details on how GhTUB5 mediates the FL phenotype in cotton.

Sphingosine Promotes Fiber Early Elongation in Upland Cotton.

Sphingolipids play an important role in cotton fiber development, but the regulatory mechanism is largely unclear. We found that serine palmitoyltransferase (SPT) enzyme inhibitors, myriocin and sphingosine (dihydrosphingosine (DHS) and phytosphingosine (PHS)), affected early fiber elongation in cotton, and we performed a sphingolipidomic and transcriptomic analysis of control and PHS-treated fibers. Myriocin inhibited fiber elongation, while DHS and PHS promoted it in a dose-effect manner. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we found that contents of 22 sphingolipids in the PHS-treated fibers for 10 days were changed, of which the contents of 4 sphingolipids increased and 18 sphingolipids decreased. The transcriptome analysis identified 432 differentially expressed genes (238 up-regulated and 194 down-regulated) in the PHS-treated fibers. Among them, the phenylpropanoid biosynthesis pathway is the most significant enrichment. The expression levels of transcription factors such as MYB, ERF, LBD, and bHLH in the fibers also changed, and most of MYB and ERF were up-regulated. Auxin-related genes IAA, GH3 and BIG GRAIN 1 were up-regulated, while ABPs were down-regulated, and the contents of 3 auxin metabolites were decreased. Our results provide important sphingolipid metabolites and regulatory pathways that influence fiber elongation.

[Analysis of Reproductive Tract Microecological Changes During the Frozen-Thawed Embryo Transfer Cycle and Clinical Pregnancy Outcomes]. / æ¿€ç´ æ›¿ä»£å†»èƒšç§»æ¤å‘¨æœŸç”Ÿæ®–é“å¾®ç”Ÿæ€å˜åŒ–ä¸Žå¦Šå¨ ç»“å±€åˆ†æž.

Objective: This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes. Methods: A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods. Results: 1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (P<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (P≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including Peptoniphilus, Enterocloster, Finegoldia, Klebsiella, Anaerobutyricum, Agathobaculum, Sporanaerobacter, Bilophila, Prevotella, and Anaerococcus in the pregnant group (P<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (P<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (P<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially Klebsiella. Conclusions: Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

Association between the triglyceride-glucose (TyG) index and stroke risk in Chinese normal-weight adults: a population-based study.

BACKGROUND: Identifying high-risk populations and promoting stroke prevention measures can be achieved through studies on stroke and its risk factors. As a new alternative indicator of insulin resistance (IR), the triglyceride glucose (TyG) index may potentially increase stroke risk. However, the evidence confirming this association is inadequate and inconsistent, possibly due to variations in stroke assessment criteria or characteristics of the study populations. This study aims to evaluate the association between the TyG index and stroke risk level among individuals with normal-weight. METHODS: A total of 30,895 participants aged ≥ 40 years with normal-weight were enrolled in this study. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Normal-weight was described as a body mass index (BMI) of 18.5-<24.0 kg/m2. Stroke risk was assessed by the Stroke Risk Assessment Scale, developed by the China National Stroke Screening and Prevention Project. To evaluate the associations between the TyG index and stroke risk level, multivariate logistic regression models were employed. RESULTS: Results showed that when the TyG index was considered as a continuous variable, each one unit increase in the TyG index was associated with a significantly higher risk of stroke [Moderate-risk (OR, 2.15; 95% CI, 2.03-2.28; P<0.001); High-risk (OR, 3.83; 95% CI, 3.57-4.10; P<0.001)]. Compared with Q1 of the TyG index, Q4 was significantly associated with moderate stroke risk (OR, 2.73; 95% CI, 2.50-2.99; P<0.001) and high stroke risk (OR, 5.39; 95% CI, 4.83-6.01; P<0.001). The continuous TyG index was an important risk factor for high stroke risk in the metabolically obese, normal-weight (MONW) individuals (OR, 3.44;95% CI, 2.92-4.06; P < 0.001). In the MONW individuals, when Q1 was used as a reference, participants in Q4 (OR, 5.33; 95% CI, 4.19-6.78; P < 0.001) was significantly associated with high stroke risk. Subgroup analysis showed significant interaction in the age and sex subgroups in the overall population (Pinteraction <0.001). CONCLUSION: The risk of stroke is increased with the TyG index among Chinese adults of normal weight; hence, the index may be an important indicator for identifying high-risk stroke populations among individuals with normal body weight.

Exosomes from Hypoxia Preconditioned Muscle-Derived Stem Cells Enhance Cell-Free Corpus Cavernosa Angiogenesis and Reproductive Function Recovery.

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns. Therefore, acellular tissue regeneration may avoid these issues. Exosomes are used from muscle-derived stem cells (MDSCs) to modify 3D-printed hydrogel scaffolds for acellular tissue regeneration. Hypoxia-preconditioned MDSC-derived exosomes are obtained to enhance the therapeutic effect. In contrast to normoxic exosomes (N-Exos), hypoxic exosomes (H-Exos) are found to markedly enhance the proliferation, migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). High-throughput sequencing analysis of miRNAs isolated from both N-Exos and H-Exos revealed a significant upregulation of miR-21-5p in H-Exos following hypoxic preconditioning. Further validation demonstrated that the miR-21-5p/PDCD4 pathway promoted the proliferation of HUVECs. Epigallocatechin gallate (EGCG) is introduced to improve the mechanical properties and biocompatibility of GelMA hydrogels. EGCG-GelMA scaffolds loaded with different types of Exos are transplanted to repair rabbit penile corpora cavernosa defects, observed the blood flow and repair status of the defect site through color Doppler ultrasound and magnetic resonance imaging, and ultimately restored the rabbit penile erection function and successfully bred offspring. Thus, acellular hydrogel scaffolds offer an effective treatment for penile corpora cavernosa defects.

Combined analysis of estradiol and ß-hCG to predict the early pregnancy outcome of FET: a retrospective study.

BACKGROUND: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and ß-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and ß-hCG levels on early reproductive outcomes 12 days after embryo transfer. METHODS: A total of 1521 patients with ß-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and ß-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and ß-hCG concentrations. RESULTS: Notable distinctions were observed in the serum E2 and ß-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and ß-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and ß-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and ß-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. CONCLUSIONS: Serum E2 and ß-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E2 and ß-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs.

An integrated strategy for quality control of Pseudobulbus Cremastrae seu Pleiones based on Q-marker.

Pseudobulbus Cremastrae seu Pleiones (PCsP), a traditional Chinese medicine known as ‶Shan-Ci-Gu″, possesses properties for clearing heat, counteracting toxicity, dissipating phlegm, and resolving masses. As a TCM with multiple bases, the dried pseudobulbs of Pleione bulbocodioides (PB), Pleione yunnanensis (PY) and Cremastra appendiculata (CA) are considered to be the official sources of PCsP. Additionally, several unofficial substitutes are also available in the market. To enhance the quality control of PCsP, an integrated strategy based on Q-marker was proposed. Initially, a study of integrating plant metabolomics, target isolation, structure identification, and activity testing afforded five Q-markers, including three new compounds. Furthermore, a quality evaluation method using a single standard to determine multi-components (SSDMC) based on Q-marker was established, which could effectively distinguish PB from CA and the counterfeit herbs. Finally, the transitivity of Q-markers was explored through a representative Chinese compound prescription containing PCsP. The results indicated that the identified Q-markers together with the established analysis methods could be effectively applied for quality control of PCsP and its preparations.

Exploring amyotrophic lateral sclerosis patients' experiences of psychological distress during the disease course in China: a qualitative study.

OBJECTIVE: This study aims to explore the psychological distress course of Chinese amyotrophic lateral sclerosis (ALS) patients after the onset of the disease and to provide targeted nursing guidance. DESIGN: The interview content was analysed qualitatively. We used seven steps of Colaizzi's method to analyse the participants' data. SETTING: Wuhan, China, Traditional Chinese Medicine Hospital. PARTICIPANTS: A semistructured face-to-face interview were performed among 22 people with ALS from the motor neuron disease rehabilitation centre of a tertiary Chinese medicine hospital in China. RESULT: This study included a total of 22 participants, from whom three main themes regarding the psychological distress trajectory of ALS patients were extracted from the interview data: 'Time begins to run out' include tormented and restless waiting and shock and doubt in ALS disease confirmation, 'Family out of control' include the burden of stigma and function loss, the burden of missing family roles, the burden of marriage's emotional needs and the burden of offspring health, 'Way forward' include struggle between live and death and struggle between quality of life and the value of life. CONCLUSION: This study outlines the psychologically distressing journey of ALS patients. Studies have pointed out the need for targeted care to address patients' various sources of psychological distress to improve their quality of life and coping ability, increase their psychological resilience and reconstruct their life beliefs.

The Clinical Characteristics and Antimicrobial Resistance of Staphylococcus aureus Isolated from Patients with Staphylococcal Scalded Skin Syndrome (SSSS) in Southwestern China.

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissue secretions, and the drug sensitivity of S. aureus to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using t tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.

Analysis of Distribution and Drug Susceptibility Test Results of Pathogenic Bacteria in Diabetic Foot Ulcers.

INTRODUCTION: This study aimed to determine the pathogen distribution and drug susceptibility of diabetic foot wound secretions in a tertiary hospital in a coastal area of southeastern China to guide clinical antibiotic selection. METHODS: A retrospective analysis was conducted on 212 patients with diabetic foot hospitalized at Xiamen Third Hospital from 2018 to 2023, and foot wound secretions were collected for microbial culture and drug susceptibility testing. RESULTS: Among 212 cases of patients with diabetic foot wound secretions, 163 cases (76.9%) were cultured with pathogenic bacteria, and a total of 207 strains of pathogenic bacteria were cultured, including 75 strains (36.23%) of Gram-positive (G+) bacteria, 118 strains of Gram-negative (G-) bacteria (57.00%), 14 strains of fungi (6.76%), 120 cases of single microorganism infection (73.62%), 43 cases of mixed infection (26.38%), and 15 strains of multidrug-resistant bacteria (7.25%). The top three pathogenic bacteria were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. G+ bacteria were dominated by S. aureus. Drug susceptibility results showed that G+ bacteria were highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. Among G- bacterial infections, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Proteus were the major species. Drug susceptibility testing indicated that carbapenems such as imipenem and ertapenem were the most effective antibacterial drugs against G- strains, followed by amikacin, piperacillin, and tazabactams to which these bacteria were also relatively sensitive, while resistance to penicillins and first-generation cephalosporins increased significantly. We isolated one strain of pathogenic bacteria from a Wagner grade 1 ulcer, which was G+ bacteria. In Wagner grade 2 ulcers, the distribution of pathogenic bacteria was mainly G+ bacteria. In Wagner grade 3 and 4 ulcers, the distribution of pathogenic bacteria was mainly G- bacteria, and the increased rate of mixed infection was mainly due to mixed infection of G+ and G-. Two strains of pathogenic bacteria were isolated at Wagner grade 5, which were mixed infections of G+ and G-. CONCLUSIONS: Pathogenic bacteria in diabetic foot wounds are predominantly G- bacteria, followed by G+ bacteria. As the Wagner ulcer grade increases, the distribution of pathogenic bacteria changes from G+ bacteria to G- bacteria, and the mixed infection rate increases. G+ bacteria are highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. G- bacteria are more sensitive to the antimicrobial drugs ertapenem, imipenem, amikacin, piperacillin tazobactam, and have high resistance to penicillin and first-generation cephalosporins.

Abietane diterpenoids from Caryopteris incana (Thunb.) Miq. And their HIF-2α inhibitory activities in vitro.

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A-K (1-11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7, 9, 15, and 16 showed significant inhibitory effects with IC50 values ranging from 12.73 to 23.80 µM. The preliminary structure-activity relationship of these compounds was also discussed.

Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers.

The unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells. A lipid nanoparticle encapsulating nucleoside-modified mRNA which encodes a BZLF1-specific transcriptional activator (mTZ3-LNP) is synthesized for EBV-targeted therapy. Compared with conventional chemical inducers, mTZ3-LNP more efficiently activates EBV lytic gene expression in EBV-associated epithelial cancers. Here we show the potency and safety of treatment with mTZ3-LNP to suppress tumor growth in EBV-positive cancer models. The combination of mTZ3-LNP and ganciclovir yields highly selective cytotoxic effects of mRNA-based lytic induction therapy against EBV-positive tumor cells, indicating the potential of mRNA nanomedicine in the treatment of EBV-associated epithelial cancers.