The causal relationship between immune cells and Sjögren's syndrome: a univariate, multivariate, bidirectional Mendelian randomized study.

Introduction: Immune cells are involved in the onset and progression of Sjögren's syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated. Methods: We conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS. Results: After false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS. Conclusion: These findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.

A Ratiometric Fluorescence Probe Based on Silver Nanoclusters and CdSe/ZnS Quantum dots for the Detection of Hydrogen Peroxide by Aggregation and Etching.

In this study, a ratiometric fluorescence nanoprobe is developed for the analysis of hydrogen peroxide (H2O2). Silver nanoclusters (AgNCs) were synthesized by chemical reduction method using sodium borohydride (NaBH4) as reducing agent, and were coupled with CdSe/ZnS quantum dots (QDs) to form the ratiometric fluorescence nanoprobe silver nanoclusters-quantum dots (AgNCs-QDs). The effect of the volume ratio of CdSe/ZnS QDs to AgNCs on the fluorescence ratio of AgNCs-QDs was investigated. The fluorescence characterization results show that two emission peaks of AgNCs-QDs are located at 473 nm and 661 nm, respectively. Transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS) results show that H2O2 can cause the fluorescence probe to aggregate, while etching AgNCs to produce silver ions, which together cause the fluorescence of the QDs in the ratiometric fluorescent probe to be quenched. Based on this strategy, the fluorescence intensity ratio of the two emission peaks F473/F661 exhibits a strong linear correlation with the concentration of H2O2. The detection range is 3.32 µM ~ 2.65 mM with a detection limit of 3.32 µM. In addition, the ratiometric fluorescence probe can specifically recognize H2O2 and has excellent anti-interference performance and good fluorescence stability. Importantly, the probe was utilized for the detection of H2O2 in serum, showing the possibility of the probe in clinical detection applications.

Preparation of Autoclavable and Injectable Silk Fibroin Cryogels for Tissue Engineering Applications.

A cryogel is a supermacroporous gel network that is generated at subzero temperatures by polymerizing monomers or gelating polymeric precursors. Since cryogels possess inherent characteristics such as interconnected macroporous structures, excellent mechanical properties, and high resistance to autoclave sterilization, they are highly desirable for tissue engineering and regenerative medicine. Silk fibroin, a natural protein obtained from Bombyx mori silkworms, is an excellent raw material for cryogel preparation. The aim of this study is to establish a controlled method for preparing silk fibroin cryogels with suitable properties for application as tissue engineering scaffolds. Using a dual crosslinking strategy consisting of low-temperature radical polymerization coupled with methanol-induced conformational transformation, porous cryogels are prepared. The cryogels display many unique characteristics, such as an interconnected macroporous structure, a high water absorption capacity, water-triggered shape memory, syringe injectability, and strong resilience to autoclave sterilization. Furthermore, the cryogels demonstrate excellent biocompatibility and cell affinity, facilitating cell adhesion, migration, and proliferation. The interconnected supermacroporous architecture resembling the native extracellular matrix, together with their unique physical properties and autoclaving stability, suggests that cryogels are promising candidate scaffolds for tissue engineering and cell therapy.

Gait speed at the acute phase predicted health-related quality of life at 3 and 12 months after stroke: a prospective cohort study.

OBJECTIVE: To investigate the association between acute-phase gait speed and health-related quality of life (HRQoL) at 3 and 12 months post-stroke. DESIGN: Prospective cohort study. SUBJECTS/PATIENTS: 1,475 patients with first-ever ischaemic stroke. METHODS: The patients were divided into 3 groups according to tertiles of gait speed, namely ≤0.8, 0.8-1.1, ≥1.1 m/s. Gait speed was assessed by the 10-m walking test within 2 weeks of hospitalization for acute stroke and before the rehabilitation programme. HRQoL measurements include the 3-level EuroQol five dimensions (EQ-5D-3L) index and EuroQoL visual analogue scale (EQ-VAS) scores. Linear and logistic regression analyses were used to identify associations between gait speed and HRQoL. RESULTS: Adjusted for all covariates, the highest gait speed tertile group were associated with higher EQ-5D-3L index (B = 0.0303 and B = 0.0228, respectively, p < 0.001), and higher EQ-VAS (B = 3.3038 and B = 3.8877, respectively, p < 0.001), and lower odds of having problems with mobility (OR = 2.55 [95% CI: 0.141-0.458] and 0.485 [0.289-0.812], respectively, p < 0.01), self-care (OR = 0.328 [95% CI: 0.167-0.646] and 0.412 [0.217-0.784], respectively, p < 0.01), and usual activities (OR = 0.353 [95% CI: 0.211-0.590] and 0.325 [0.198-0.536], respectively, p < 0.0001) at 3 and 12 months, and pain/discomfort at 12 months (OR = 0.558 [95% CI:0.335-0.930], p < 0.05). CONCLUSION: Acute-phase gait speed was predictive of post-stroke HRQoL at 3 and 12 months, especially when associated with domain-specific EQ-5D-3L.

Influence of implant distribution on the biomechanical behaviors of mandibular implant-retained overdentures: a three-dimensional finite element analysis.

OBJECTIVE: To assess stress distribution in peri-implant bone and attachments of mandibular overdentures retained by small diameter implants, and to explore the impact of implant distribution on denture stability. METHODS: Through three-dimensional Finite Element Analysis (3D FEA), four models were established: three models of a two mandibular implants retained overdenture (IOD) and one model of a conventional complete denture (CD). The three IOD models consisted of one with two implants in the bilateral canine area, another with implants in the bilateral lateral incisor area, and the third with one implant in the canine area, and another in the lateral incisor area. Three types of loads were applied on the overdenture for each model: a 100 N vertical load and a inclined load on the left first molar, and a100N vertical load on the lower incisors. The stress distribution in the peri-implant bone, attachments, and the biomechanical behaviors of the overdentures were analyzed. RESULTS: Despite different distribution of implants, the maximum stress values in peri-implant bone remained within the physiological threshold for all models across three loading conditions. The dispersed implant distribution design (implant in the canine area) exhibited the highest maximum stress in peri-implant bone (822.8 µe) and the attachments (275 MPa) among the three IOD models. The CD model demonstrated highest peak pressure on mucosa under three loading conditions (0.8188 Mpa). The contact area between the denture and mucosa of the CD model was smaller than that in the IOD models under molar loading, yet it was larger in the CD model compared to the IOD model under anterior loading. However, the contact area between the denture and mucosa under anterior loading in all models was significantly smaller than those under molar loading. The IOD in all three models exhibited significantly less rotational movement than the complete denture. Different implant positions had minimal impact on the rotational movement of the IOD. CONCLUSION: IOD with implants in canine area exhibited the highest maximum stress in the peri-implant bone and attachments, and demonstrated increased rotational movement. The maximum principal stress was concentrated around the neck of the small diameter one-piece implant, rather than in the abutment. An overdenture retained by two implants showed better stability than a complete denture.

Silk fibroin/methacrylated gelatine/hydroxyapatite biomimetic nanofibrous membranes for guided bone regeneration.

By mimicking in vivo bionic microenvironment and promoting osteogenic differentiation, the hybrid organic-inorganic nanofibrous membranes provide promising potential for guided bone regeneration (GBR) in the treatment of clinical bone defects. To develop a degradable and osteogenic membrane for GBR by combining the natural biomacromolecule silk fibroin (SF) and gelatine with the bioactive nano hydroxyapatite (nHA), the anhydride-modified gelatine-nano hydroxyapatite (GelMA-nHA) composites were synthesized in situ and introduced into silk fibroin to prepare nanofibrous membranes with different ratios using electrospinning and photocrosslinking. The nanofibrous membranes, particularly those with a mass ratio of 7:2:1, were found to exhibit satisfactory elongation at break up to 110 %, maintain the nanofibrous structure for up to 28 days, and rapidly form bone-like apatite within 3 days, thus offering advantages when it comes to guided bone regeneration. In vitro cell results showed that the SF/GelMA/nHA membranes had excellent biocompatibility and enhanced osteogenic differentiation of hBMSCs. In vivo studies revealed that the hybrid composite membranes can improve bone regeneration of critical-sized calvarial defects in rat model. Therefore, the novel hybrid nanofibrous membrane is proposed to be a alternative candidate for creating a bionic microenvironment that promotes bone regeneration, indicating their potential application to bone injury treatment.

An Integrated Clinical and Computerized Tomography-Based Radiomic Feature Model to Separate Benign from Malignant Pleural Effusion.

INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.

Low HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) Score Increases the Risk of Post-Stroke Cognitive Impairment: A Multicenter Cohort Study.

Objective: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is a novel indicator that measures systemic inflammation and nutritional status that has not been correlated with the risk of post-stroke cognitive impairment in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Study participants were recruited from 40 stroke centers in China. The HALP score was derived using a weighted sum of hemoglobin, albumin, lymphocytes and platelets, and study participants were categorized into 4 groups of equal sizes based on quartiles cutoffs of the HALP score. The Montreal Cognitive Assessment (MoCA)-Beijing Cognitive Assessment Scale (MoCA-Beijing) was performed at 2 weeks and 12 months following stroke onset. Post-stroke cognitive impairment was considered in patients with MoCA-Beijing≤22. Multiple logistic regression methods were employed to evaluate the relationship between the HALP score and the subsequent risk of developing post-stroke cognitive impairment. Results: The study population comprised 1022 patients (mean age 61.6±11.0 years, 73% men). The proportion of individuals with MoCA-Beijing≤22 at 2 weeks was 49.2% and 32.4% at one year. Patients in the lowest quartile of HALP score (<36.56) were observed to harbor the highest risk of post-stroke cognitive impairment at 12 months post-stroke/TIA compared to those in the highest quartile (odds ratio=1.59, 95% CI=1.07-2.37, p=0.022), and lower domain scores for executive function, naming, and attention. There were no statistically significant differences between patients in the different quartiles of HALP score and HALP score at 2 weeks post-stroke/TIA. Conclusion: The HALP score is a simple score that could stratify the risk of post-stroke cognitive impairment in stroke/TIA patients to facilitate early diagnosis and interventions.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application.

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

A comprehensive review of toxicity of coal fly ash and its leachate in the ecosystem.

Coal fly ash (CFA), a byproduct of coal combustion, is a hazardous industrial solid waste. Its excessive global production, coupled with improper disposal practices, insufficient utilization and limited awareness of its inherent hazards, poses a significant threat to both ecological environment and human health. Based on the physicochemical properties of CFA and its leachates, we elucidate the forms of CFA and potential pathways for its entry into the human body, as well as the leaching behavior, maximum tolerance and biological half-life of toxic elements present in CFA. Furthermore, we provide an overview of current strategies and methods for mitigating the leaching of these harmful elements from CFA. Moreover, we systemically summarize toxic effect of CFA on organisms across various tiers of complexity, analyze epidemiological findings concerning the human health implications resulting from CFA exposure, and delve into the biotoxicological mechanisms of CFA and its leachates at cellular and molecular levels. This review aims to enhance understanding of the potential toxicity of CFA, thereby promoting increased public awareness regarding the disposal and management of this industrial waste.

Latent profile analysis of psychological needs thwarting in Chinese school teachers: longitudinal associations with problematic smartphone use, psychological distress, and perceived administrative support.

Introduction: In light of the significant impact that teachers have on education quality and student growth, their mental health warrants special attention. With the increasing popularity of Information and Communication Technology (ICT) and the rise of online teaching during the pandemic, teachers have become a group prone to developing problematic smartphone use (PSU). Psychological need thwarting (PNT) has been shown to be closely related to PSU, psychological distress, and perceived administrative support. However, most previous studies have adopted a variable-centered approach, which may overlook the possibility that the three basic needs are not closely associated and could form distinct profiles. Therefore, this study aims to apply latent profile analysis to identify different PNT profiles and their associations with PSU, psychological distress, and perceived administrative support. Methods: A longitudinal survey was conducted using convenience and purposive sampling methods. The survey involved 1,642 primary and middle school teachers working in China over a two-month interval, with the first assessment in November 2021 (Time 1) and the second in January 2022 (Time 2). Results: The results indicate that a three-profile model, intricately based on the PNT data gathered at Time 1, is most optimal: Class 1 is labeled as 'High autonomy-High competence and Moderate relatedness thwarting', Class 2 as 'High autonomy-High competence and High relatedness thwarting', and Class 3 as 'Low psychological needs thwarting'. Distinct associations were observed among the three profiles concerning PSU, psychological distress, and perceived administrative support. Specifically, in terms of PSU, the score of Class 2 was higher than Class 1, with that of Class 3 being the lowest at Time 1, while at Time 2 no significant difference was found between any two of these three groups; in terms of distress, the scores of the three profiles were arranged from high to low as Class 2, 1, and 3 at both time points; and in terms of perceived administrative support, the order was just the opposite, with 3, 1, and 2 from high to low at both Time 1 and Time 2. Conclusion: Notably, the consistent ranking of the three classes in terms of psychological distress and administrative support suggests a lasting influence of PNT. Future studies should explore this enduring impact further by employing additional longitudinal data sets and examining potential mediators or moderators beyond the current study's scope.

[Clinical Features and Surgical Outcomes of 15 Cases of Intracranial Alveolar Echinococcosis]. / 15ä¾‹é¢ å† æ³¡åž‹æ£˜çƒèš´ç— çš„ä¸´åºŠç‰¹ç‚¹åŠæ‰‹æœ¯ç–—æ•ˆåˆ†æž.

Objective: To investigate the surgical treatment strategy of intracranial alveolar echinococcosis (AE) and the clinical outcomes. Methods: The clinical and follow-up data of 15 intracranial AE patients who underwent surgical treatment in the Departments of Neurosurgery of Sichuan Provincial People's Hospital (SPPH) and People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture (a branch hospital of SPPH) between March 2017 and January 2021 were retrospectively analyzed. Full follow-up data were available for each of the 15 cases. The clinical and imaging characteristics, general surgical information, and surgical outcomes were analyzed. Results: In the 15 patients, there were a total of 50 intracranial lesions, with an average of (3.3±3.1)/case. Four cases had solitary intracranial lesions, while 11 cases had multiple lesions, with the number of intracranial lesions per case ranging from 2 to 13. All patients with solitary intracranial lesions received total resection. In 6 patients with multiple intracranial lesions, only the largest lesion was surgically removed, and in 5 patients, 2 to 3 adjacent lesions were surgically removed. All but one patient had extracranial lesions in their liver, lungs, kidneys, adrenal glands, and thoracic vertebrae. The patients were followed up for 12 to 58 months after surgery, with the mean follow-up time being (28.1±13.4) months. Among the 15 cases, 13 showed stable intracranial condition during postoperative follow-up. Intracranial lesions recurred in 2 patients who had deep lesions accompanied by dissemination to the subarachnoid space. Two patients died during follow-up. Conclusion: Microsurgical treatment of intracranial AE is effective, but total surgical resection is difficult to accomplish when patients have echinococcosis lesions located at a depth, especially when the lesions are spreading to the subarachnoid space. The prognosis of patients is closely associated with the extent of lesion invasion and the control of systemic hydatid lesions, especially those in the liver.

Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.