A Novel Ultrasound Method of Evaluating Dynamic Extrusion of Lateral Meniscus in Healthy Population: Different Patterns of Dynamic Extrusion Revealed Between Lateral and Medial Meniscus.

OBJECTIVES: To establish a reliable ultrasound (US) method of evaluating dynamic extrusion of lateral meniscus in healthy population, and to investigate the pattern of dynamic meniscus extrusion (ME) in lateral meniscus under loading conditions. METHODS: The lateral ME was examined via US method in unloaded, double-leg standing, and single-leg standing positions. Two different US measurement methods were compared to the magnetic resonance imaging (MRI) results to determine the optimal measurement methods. The US results obtained by different researchers were tested for interobserver consistency and the results obtained by the same researcher on two separate days were tested for intraobserver consistency. The patterns of dynamic extrusion were compared between medial and lateral sides. RESULTS: A total of healthy 44 volunteers were included in the study, with 86 knees assessed by US, and 25 knees evaluated by MRI. The US evaluation of dynamic lateral ME demonstrated excellent interobserver and intraobserver reliability. The US measurements using method A were consistent with the MRI results with no significant difference (P = .861, intraclass correlation coefficient [ICC] = 0.868), while method B underestimated the lateral ME compared to MRI (P = .001, ICC = 0.649). Lateral ME decreased slightly from unloaded (1.0 ± 0.8 mm) to single-leg standing position (0.8 ± 0.8 mm), whereas medial ME increased significantly in both double-leg and single-leg standing positions (2.4 ± 0.7 mm, 2.6 ± 0.7 mm). CONCLUSION: A novel US evaluation method of lateral ME was established with reliable and accurate results compared to the MRI. Lateral ME in healthy populations decreased slightly as the loadings increased, which was different from the pattern of dynamic extrusion in medial meniscus.

Do social economic status modify the association between air pollution and depressive or anxiety symptoms? A big sample cross-sectional study from the rural areas of Central China.

BACKGROUND: Fewer studies have examined the relationship between air pollution and depressive or anxiety symptoms in rural residents. Social economic status (SES), as an important indicator of the current state of socioeconomic development, we know little about how it modifies the relationship between air pollution and symptoms of depression or anxiety. METHODS: The patient health questionnaire (PHQ-2) and generalized anxiety scale (GAD-2) were used to learn about the prevalence of depressive and anxiety symptoms, the social economic status of the participants was categorized into two levels: lower and higher, and a binary logistic regression model was used to analyze the relationship between air pollution and residents' symptoms of depression or anxiety. RESULTS: A total of 10,670 adults were enrolled in this study, of which a total of 1292 participants suffered from depressive symptoms and 860 suffered from anxiety symptoms. Short-term exposure to PM2.5 and O3, singly or in combination, may be associated with the onset of depression symptoms, and there was a significant interaction between SES and exposure to PM2.5 or O3. Residents of areas with higher SES may have a lower risk of suffering from anxiety symptoms after O3 exposure compared to participants living in lower SES. LIMITATIONS: The study was a cross-sectional study, which may have lowered the quality level of the evidence. CONCLUSIONS: Short-term PM2.5 and O3 exposure may be associated with an increased prevalence risk of depressive symptoms. Higher levels of SES may reduce the adverse effects of air pollution on depressive or anxiety symptoms.

Isolation and characterization of a novel Bacillus cereus bacteriophage vBce-DP7.

Foodborne pathogens have become a major concern for public health. Bacillus cereus, a representative foodborne pathogen, is particularly challenging due to its ability to cause food poisoning and its resilient spores that are difficult to completely eradicate. Therefore, it is crucial to develop measures to prevent and control B. cereus. Bacteriophages, which are high specific towards their host strains and cannot infect eukaryotes, have proven to be effective in combating foodborne pathogens and are safe for human use. In this study, we isolated and characterized a novel bacteriophage named vBce-DP7 that specifically targets B. cereus strains belonging to three different sequence types (STs). Phage vBce-DP7 is a lytic one and has a short latent time of only 15 min. Moreover, it exhibites a good temperature tolerance, retaining high activity across a broad range of 4-55 ℃. Additionally, its activity remains unaffected within a wide pH range spanning from 2 to 10. Interestingly, with only 4 % genetic similarity with known bacteriophages, vBce-DP7 shows a possible classification on a family level though it shares many similar functional proteins with Salasmaviridae bacteriophages. Taken together, vBce-DP7 demonstrates its significant potential for further exploration in terms of phage diversity and its application in controlling B. cereus.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Dual-Lumen Extracorporeal Membrane Oxygenation Cannulation Technique Using Only Transthoracic Echocardiography - A Case Series.

BACKGROUND: Bicaval dual lumen cannula (DLC) is gaining popularity in veno-venous extracorporeal membrane oxygenation (V-V ECMO) for having less recirculation and facilitating mobilization. It is usually inserted under fluoroscopic or transesophageal echocardiographic guidance to prevent potentially fatal complications. Thus, their utilization was limited during the COVID-19 outbreak due to stringent quarantine policy and manpower shortage, especially when emergency insertion was required. PURPOSE: To describe our experience on DLC insertion using transthoracic echocardiography alone during the pandemic, with a focus on safety considerations by using detail step-by-step procedural guide. OUTCOME: Four patients were performed V-V ECMO using the transthoracic echocardiographic-guided DLC cannulation technique during the fifth wave of the COVID-19 outbreak, with no cannulation-related complications. CONCLUSION: Transthoracic echocardiographic guidance for DLC insertion is feasible and probably safe with a detailed guide, which can be adopted as a supplementary tool during future endemic outbreaks.

Impact of a 12-wk physical conditioning program on the aerobic capacity of aviation cadets.

BACKGROUND: Flight cadets need to have good physical fitness to cope with the challenges of flying missions. The continuous development of science and technology has led to the constant upgrading of fighter jets and the improvement of their performance, which has resulted in new and higher requirements for the physical fitness of flight personnel. The traditional physical training mode, method, and assessment have been used for many years and do not meet current fitness needs. AIM: To investigate the impact of a 12-wk comprehensive anti-G fitness training program on the aerobic capacity of aviation cadets and to evaluate its effectiveness. METHODS: Fifty-five cadets were randomly assigned to control and experimental groups using a randomized, single-blind design. The control group maintained their existing training regimen, while the experimental group participated in a 12-wk comprehensive training intervention. The training program comprised strength training twice per week, high-intensity interval training three times per week, and supplemental nutritional and psychological support. Maximal oxygen uptake (VO2max), lower limb strength, and hemoglobin levels were measured at baseline, at 6 wk and 12 wk post-intervention. RESULTS: Repeated measures analysis of variance revealed significant differences of both VO2max and relative VO2 in both groups across time points (P < 0.05). However, no significant time-group interaction was observed (P > 0.05). Paired t-tests comparing baseline and 12-wk results showed that VO2max and relative VO2 were significantly higher in the experimental group than the control group (P < 0.05). This suggests that the training program effectively enhanced the aerobic capacity of the experimental group. Key indicators of aerobic capacity, bilateral lower limb strength and hemoglobin levels, were also significantly different over time and between groups (P < 0.05). No significant differences were noted in heart-rate metrics (P > 0.05). CONCLUSION: A 12-wk comprehensive anti-G fitness training program significantly improved the aerobic capacity of aviation cadets, thereby enhancing their overall capacity and laying a physiological foundation for enduring high-G flights.

Structural insights into the binding of nanobodies to the staphylococcal enterotoxin B.

Staphylococcal Enterotoxin Type B (SEB), produced by Staphylococcus aureus bacteria, is notorious for inducing severe food poisoning and toxic shock syndrome. While nanobody-based treatments hold promises for combating SEB-induced diseases, the lack of structural information between SEB and nanobodies has hindered the development of nanobody-based therapeutics. Here, we present crystal structures of SEBNb3, SEBNb6, SEBNb8, SEBNb11, and SEB-Nb20 at resolutions ranging from 1.59 Što 2.33 Å. Crystallographic analysis revealed that Nb3, Nb8, Nb11, and Nb20 bind to SEB at the T-cell receptor (TCR) interface, while Nb6 binds at the major histocompatibility complex (MHC) interface, suggesting their potential to inhibit SEB function by disrupting interactions with TCR or MHC molecules. Molecular biological analyses confirmed the thermodynamic and kinetic parameters of Nb3, Nb5, Nb6, Nb8, Nb11, Nb15, Nb18, and Nb20 to SEB. The competitive inhibition was further confirmed by cell-based experiments demonstrating nanobody neutralization. These findings elucidate the structural basis for developing specific nanobodies to neutralize SEB threats, providing crucial insights into the underlying mechanisms and offering significant assistance for further optimization towards future therapeutic strategies.

Benefits of exercise on cognitive impairment in alcohol use disorder following alcohol withdrawal.

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two-bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain-derived neurotrophic factor in the hippocampus were quantified using enzyme-linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain-derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD.

The promotion of biofilm dispersion: a new strategy for eliminating foodborne pathogens in the food industry.

Food safety is a critical global concern due to its direct impact on human health and overall well-being. In the food processing environment, biofilm formation by foodborne pathogens poses a significant problem as it leads to persistent and high levels of food contamination, thereby compromising the quality and safety of food. Therefore, it is imperative to effectively remove biofilms from the food processing environment to ensure food safety. Unfortunately, conventional cleaning methods fall short of adequately removing biofilms, and they may even contribute to further contamination of both equipment and food. It is necessary to develop alternative approaches that can address this challenge in food industry. One promising strategy in tackling biofilm-related issues is biofilm dispersion, which represents the final step in biofilm development. Here, we discuss the biofilm dispersion mechanism of foodborne pathogens and elucidate how biofilm dispersion can be employed to control and mitigate biofilm-related problems. By shedding light on these aspects, we aim to provide valuable insights and solutions for effectively addressing biofilm contamination issues in food industry, thus enhancing food safety and ensuring the well-being of consumers.

Correlation between climatic environment and characteristic components of 14 kinds of huajiao by thermal analysis techniques, GC-MS and HS-IMS.

Huajiao (Zanthoxylum bungeanum Maxim.) is extensively cultivated in various countries, including China, Korea, and India, owing to its adaptability to diverse environments. This study comprehensively analyzed the volatile substance composition of 14 varieties of red huajiao with distinct geographical origins. Thermal analysis methods, gas chromatography-mass spectrometry (GC-MS), and headspace-ion mobility chromatography (HS-IMS) were employed to evaluate the total volatile substance composition and content. The study revealed minor variations in water content, volatile matter content, and fractions among the geographically sourced huajiao samples. Utilizing correlation analysis based on GC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) with HS-IMS, a robust classification method for the 14 types of huajiao was developed. Applying the variable importance in the projection (VIP) method, seven distinctive components were identified as potential markers for distinguishing the geographical origins of red huajiao. By integrating climatic and topographical factors of the 14 huajiao varieties, the correlation analysis of GC-MS, and OPLS-DA classification outcomes from HS-IMS elucidated the influence of geo-environmental factors on huajiao components and contents. This research provides insights into the impact of diverse geographic environments on the constituents and characteristics of huajiao. It offers valuable guidance for selecting optimal cultivation locations to enhance huajiao quality, aiding consumers in making informed choices.

Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides.

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), ß-1,4-Gal(p), and ß-1,4-Gal(p)A, and two branched chains of ß-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and ß-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.

Metal nanowire-based transparent electrode for flexible and stretchable optoelectronic devices.

High-quality transparent electrodes are indispensable components of flexible optoelectronic devices as they guarantee sufficient light transparency and electrical conductivity. Compared to commercial indium tin oxide, metal nanowires are considered ideal candidates as flexible transparent electrodes (FTEs) owing to their superior optoelectronic properties, excellent mechanical flexibility, solution treatability, and higher compatibility with semiconductors. However, certain key challenges associated with material preparation and device fabrication remain for the practical application of metal nanowire-based electrodes. In this review, we discuss state-of-the-art solution-processed metal nanowire-based FTEs and their applications in flexible and stretchable optoelectronic devices. Specifically, the important properties of FTEs and a cost-benefit analysis of existing technologies are introduced, followed by a summary of the synthesis strategy, key properties, and fabrication technologies of the nanowires. Subsequently, we explore the applications of metal-nanowire-based FTEs in different optoelectronic devices including solar cells, photodetectors, and light-emitting diodes. Finally, the current status, future challenges, and emerging strategies in this field are presented.

A Prelimbic Cortex-Thalamus Circuit Bidirectionally Regulates Innate and Stress-Induced Anxiety-Like Behavior.

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.

Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes.

Early insulin therapy is capable to achieve glycemic control and restore ß-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Development and validation of a nomogram for tracheotomy decannulation in individuals in a persistent vegetative state: A multicentre study.

BACKGROUND: Decannulation for people in a persistent vegetative state (PVS) is challenging and relevant predictors of successful decannulation have yet to be identified. OBJECTIVE: This study aimed to explore the predictors of tracheostomy decannulation outcomes in individuals in PVS and to develop a nomogram. METHOD: In 2022, 872 people with tracheostomy in PVS were retrospectively enrolled and their data was randomly divided into a training set and a validation set in a 7:3 ratio. Univariate and multivariate regression analyses were performed on the training set to explore the influencing factors for decannulation and nomogram development. Internal validation was performed using 5-fold cross-validation. External validation was performed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) on both the training and validation sets. RESULT: Data from 610 to 262 individuals were used for the training and validation sets, respectively. The multivariate regression analysis found that duration of tracheostomy tube placement≥30 days (Odds Ratio [OR] 0.216, 95 % CI 0.151-0.310), pulmonary infection (OR 0.528, 95 %CI 0.366-0.761), hypoproteinemia (OR 0.669, 95 % CI 0.463-0.967), no passive standing training (OR 0.372, 95 % CI 0.253-0.547), abnormal swallowing reflex (OR 0.276, 95 % CI 0.116-0.656), mechanical ventilation (OR 0.658, 95 % CI 0.461-0.940), intensive care unit (ICU) duration>4 weeks (OR 0.517, 95 % CI 0.332-0.805), duration of endotracheal tube (OR 0.855, 95 % CI 0.803-0.907), older age (OR 0.981, 95 % CI 0.966-0.996) were risk factors for decannulation failure. Conversely, peroral feeding (OR 1.684, 95 % CI 1.178-2.406), passive standing training≥60 min (OR 1.687, 95 % CI 1.072-2.656), private caregiver (OR 1.944, 95 % CI 1.350-2.799) and ICU duration<2 weeks (OR 1.758, 95 % CI 1.173-2.634) were protective factors conducive to successful decannulation. The 5-fold cross-validation revealed a mean area under the curve of 0.744. The ROC curve C-indexes for the training and validation sets were 0.784 and 0.768, respectively, and the model exhibited good stability and accuracy. The DCA revealed a net benefit when the risk threshold was between 0 and 0.4. CONCLUSION: The nomogram can help adjust the treatment and reduce decannulation failure. REGISTRATION: Clinical registration is not mandatory for retrospective studies.