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Yan-Tao Ma,1,2,* Li-Hui Li,2,3,* Qi Han,1 Xiao-Lei Wang,1 Pei-Yu Jia,1 Qiang-Min Huang,2 Yong-Jun Zheng1 1Department of Pain Management, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Sport Rehabilitation, School of Kinesiology, Shanghai University of Sport, Shanghai, People’s Republic of China; 3School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong-Jun Zheng; Qiang-Min Huang Email zhengyongjun1971@126.com; huaqia404@aliyun.comPurpose: To investigate the effects of trigger point dry needling (TrP-DN) on exercise-induced patellofemoral pain syndrome (PFPS).Patients and Methods: In this randomized, single-blind, parallel-group trial, 50 patients with PFPS were randomly allocated to the following two groups: the TrP-DN group (n = 25) and the Sham needling group (n = 25). Patients in both groups were asked to perform a stretching exercise of the quadriceps daily after needling. The needling group received a single session of TrP-DN to trigger points (TrPs) in the vastus medialis oblique (VMO), vastus lateralis (VL), and rectus femoris muscles (once a week for 6 weeks), and the Sham group received placebo needling. Visual analogue scale (VAS) for pain intensity and Kujala questionnaire for the functional status were assessed before treatment, 3 and 6 weeks after treatment, and at the 3-month follow-up. The ratio of the myoelectric amplitude of the vastus medialis oblique and vastus lateralis muscles (VMO/VL) was assessed before treatment and 6 weeks after treatment.Results: There was no significant difference in the general data between the two groups. The VAS scores and Kujala scores in the TrP-DN group were significantly improved and increased at the 3-week treatment visit, 6-week treatment visit, and 3-month follow-up compared to the scores before treatment; and the scores in the Sham group were only significantly improved at the 3-week treatment visit, and 6-week treatment visit. VAS scores in the TrP-DN group were significantly lower and Kujala scores were significantly higher at the 6-week treatment visit and the 3-month follow-up compared to those in the Sham group. The VMO/VL ratio in the TrP-DN group was significantly increased at the 6-week treatment visit compared to that before treatment.Conclusion: TrP-DN at the quadriceps combined with stretch can reduce the pain, and improves the clinical symptoms and function, the VMO/VL ratio, and the coordination of VMO and VL in patients with PFPS.Keywords: patellofemoral pain syndrome, myofascial trigger points, stretching

Peripheral nerve injury (PNI) can cause nerve demyelination, neuronal apoptosis, axonal atrophy, inflammatory infiltration, glial scar formation, and other pathologies that can lead to sensory and motor dysfunction and seriously affect the psychosomatic health of patients. There is currently no effective treatment method, so exploring a promising treatment method is of great significance. Several studies have revealed the therapeutic roles of Schwann cells (SCs) and their exosomes in nerve injury repair. Exosomes are extracellular nanovesicles secreted by cells that act as key molecules in intercellular communication. Progress has been made in understanding the role of exosomes derived from SCs (SC-EXOs) in peripheral nerve regeneration, including the promotion of axonal regeneration and myelin formation, anti-inflammation, vascular regeneration, neuroprotection, and neuroregulation. Therefore, in this paper, we summarize the functional characteristics of SC-EXOs and discuss their potential therapeutic effects on PNI repair as well as some existing problems and future challenges., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice., Competing Interests: Declaration of competing interest We confirmed that the paper has been seen and admitted by co-authors, approved the submission to the journal. We confirmed that there are no conflicts of interest in this paper. Thank you very much., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The risk of new-onset hypertension is influenced by habitual fish oil supplementation, but whether the association is modified by genetic predisposition is unknown., Methods: A total of 213,604 participants without hypertension were identified at baseline from the UK Biobank between 2006 and 2010. The weighted polygenetic risk score (PRS) comprising 118 identified single-nucleotide polymorphisms (SNPs) was used to quantify genetic susceptibility. Cox regression models were applied to determine the association between fish oil supplementation, PRS, and hypertension and evaluate the effect modification of genetic susceptibility., Results: During a median follow-up of 13.8 years, 18,498 new-onset hypertension cases were identified. Approximately 30.6 % (65,452) of participants were habitual fish oil users. The hazard ratio (HR) of habitual fish oil users for hypertension was 0.94 (95 % confidence interval [CI], 0.91-0.98). Fish oil nonusers with a high genetic risk had an increased risk of hypertension (HR, 1.52; 95 % CI, 1.41-1.64) compared to fish oil users with a low genetic risk. In addition, an interaction on the additive scale between the fish oil use and intermediate or high levels of genetic susceptibility was observed. The interactive effects accounted for approximately 7 % and 22 % of the risk of developing hypertension, respectively., Conclusions: This cohort study indicates regular fish oil supplementation could be beneficial in preventing hypertension, particularly among individuals with intermediate or high genetic susceptibility on an additive scale., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified (< 65 vs ≥ 65 years) associations of weight change with all-cause and cause-specific mortality in a large sample of Chinese adults., Methods: Our cohort study included 746,991 adults aged at least 45 years from the Shenzhen Healthcare Big Data Cohort in China. BMI change were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by > 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders., Results: During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54-1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52-1.84), CVD mortality (HR: 1.55, 95% CI: 1.34-1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33-1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04-1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04-1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12-1.44). For participants < 65 years, only more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.41, 95% CI: 1.12-1.77), non-communicable disease mortality (HR: 1.43, 95% CI: 1.13-1.81), and cancer mortality (HR: 1.79, 95% CI: 1.29-2.47)., Conclusions: Weight loss and excessive weight gain were associated with increased risks of mortality among older adults, while only excessive weight loss was associated with increased risks of mortality among middle-aged adults., (© 2024. The Author(s).)

Recent empirical research posits a link between lymphocyte subgroups and both the incidence and prognosis of sepsis. Nevertheless, the potential influence of multiple confounding variables obscures any clear causative correlation. Utilizing a 2-sample Mendelian randomization approach, we conducted a meta-analysis of lymphocyte subgroups. In a genome-wide association study, flow cytometry was applied to a lymphocyte subgroup comprising 3757 Sardinians to identify genes influenced by blood immune cells. The sepsis meta-analysis data were sourced from the UK Biobank database, including 11,643 treatment groups and 47,841 control groups. Inverse variance-weighted, Mendelian randomization-Egger regression, weighted median, simple mode, and weighted mode methods were deployed to ascertain the causative relationship between lymphocyte subgroup and sepsis. Cochran Q test, the Mendelian randomization-Egger intercept test, and funnel plots were leveraged to assess the robustness of study findings. The inverse variance-weighted analysis disclosed that the absolute count of CD4 regulatory T cells (CD4 Treg AC) within the lymphocyte subgroup has a causative link to an elevated risk of sepsis, with an odds ratio of 1.08 and a 95% confidence interval of 1.02 to 1.15 (P = .011). Compared to individuals not subjected to this factor, those exposed to CD4 Treg AC have a marginally elevated sepsis risk by approximately 0.08%. No causative relationships were observed between sepsis risk and the absolute counts of other lymphocyte subgroups such as CD8+ T cells, CD4+ CD8dim T cells, natural killer T cells, B cells (B cell absolute count), and HLA DR+ natural killer cells. The 2-sample Mendelian randomization study indicated a causal relationship between the level of CD4 Treg AC and the increased risk of sepsis. The elevation in circulating lymphocyte subgroups suggests higher susceptibility to sepsis, affirming the immune susceptibility inherent to this condition. The findings from our study may propose potential targets for diagnosis and intervention of sepsis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported., Purpose: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ., Methods: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses., Results: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840)., Conclusion: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning., (© 2024 American Association of Physicists in Medicine.)

Introduction: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function., Methods: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed., Results: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05)., Discussion: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment., Highlights: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In this study, a convenient chitosan oligosaccharide laser lithograph (COSLL) technology was developed to fabricate laser-induced graphene (LIG) electrodes and flexible on-chip microsupercapacitors (MSCs). With a simple one-step CO 2 laser, the pyrolysis of a chitosan oligosaccharide (COS) and in situ welding of the generated LIGs to engineering plastic substrates are achieved simultaneously. The resulting LIG products display a hierarchical porous architecture, excellent electrical conductivity (6.3 Ω sq -1 ), and superhydrophilic properties, making them ideal electrode materials for MSCs. The pyrolysis-welding coupled mechanism is deeply discussed through cross-sectional analyses and finite element simulations. The MSCs prepared by COSLL exhibit considerable areal capacitance of over 4 mF cm -2 , which is comparable to that of the polyimide-LIG-based counterpart. COSLL is also compatible with complementary metal-oxide-semiconductor (CMOS) and micro-electro-mechanical system (MEMS) processes, enabling the fabrication of LIG/Au MSCs with comparable areal capacitance and lower internal resistance. Furthermore, the as-prepared MSCs demonstrate excellent mechanical robustness, long-cycle capability, and ease of series-parallel integration, benefiting their practical application in various scenarios. With the use of eco-friendly biomass carbon source and convenient process flowchart, the COSLL emerges as an attractive method for the fabrication of flexible LIG on-chip MSCs and various other advanced LIG devices.

Background: Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19., Methods: We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications., Results: 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography., Conclusion: Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Background: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake., Methods: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality., Results: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality., Conclusions: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.

Background: There is limited understanding regarding prospective associations of insomnia symptoms and trajectories with functional disability. We aimed to investigate the associations of insomnia symptoms and trajectories with functional disability., Method: A total of 13 197 participants were eligible from the Health and Retirement Study. Insomnia symptoms included non-restorative sleep, difficulty initiating sleep, early morning awakening, and difficulty maintaining sleep. We also identified four distinct trajectories of insomnia symptoms: low, decreasing, increasing, and high insomnia symptoms. Functional status was assessed through activities of daily living (ADL) and instrumental activities of daily living (IADL)., Results: Participants experiencing one (HR, 1.21; 95% CI, 1.13-1.29), two (HR, 1.43; 95% CI, 1.29-1.57), or three to four (HR, 1.41; 95% CI, 1.25-1.60) insomnia symptoms had a higher risk of ADL disability than asymptomatic respondents. Similarly, participants with one or more insomnia symptoms had a higher risk of IADL disability. Furthermore, using the trajectory with low insomnia symptoms as the reference, decreasing insomnia symptoms (HR, 1.22; 95% CI, 1.12-1.34), increasing insomnia symptoms (HR, 1.21; 95% CI, 1.05-1.41), and high insomnia symptoms (HR, 1.36; 95% CI, 1.18-1.56) were all associated with an increased risk of ADL disability., Conclusion: Both a single measurement and dynamic trajectory of insomnia symptoms are associated with the onset of ADL disability. Increased awareness and management of insomnia symptoms may contribute to the prevention of functional disability occurrence., (© 2024. The Author(s).)

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 μg/m 3 increase in PM 2.5 , PM 2.5-10 , PM 10 , NO 2 , and NO x , respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage., (© 2024. The Author(s).)

Background: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value., Aim: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI)., Methods: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort ( n = 220) or a validation cohort ( n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA)., Results: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model ( P = 0.005) and the radiomic model ( P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process., Conclusion: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases., Objective: This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR)., Methods: hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro., Results: hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, the CM derived from hAMSCs pretreated with RAW264.7-CM markedly inhibited the expressions of fibrogenesis genes such as αSMA and COL3 in 3T3 cells., Conclusion: Our results demonstrated that hAMSCs effectively alleviated ISO-induced cardiac hypertrophy and fibrosis, and improved the cardiac functions in mice, and the underlying mechanisms might be related to inhibiting the inflammation and fibrosis during the ventricular remodeling through promoting the polarization of CD206 hi IL-10 hi macrophages in heart tissues. Our study strongly suggested that by taking the advantages of the potent immunosuppressive and anti-inflammatory effects, hAMSCs may provide an alternative therapeutic approach for prevention and treatment of VR clinically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To examine for the in vitro existence of contractile nodules on the taut band of muscle fibers where myofascial trigger points (MTrPs) are located (using cell culture)., Methods: Sixteen male Sprague-Dawley rats (7 weeks old) were randomly divided into experimental and control groups. A blunt striking injury and eccentric exercise were applied to the gastrocnemius muscle of rats in the experimental group once a week for 8 weeks to establish an MTrP model. Subsequently, the rats were reared normally and rested for 4 weeks. After modeling, the skeletal muscles at the MTrPs (and non-MTrPs at the same anatomical position) were extracted from the two groups of rats for in vitro cell culture experiments of single muscle fibers. Potential contractile nodules in the MTrP group were exposed to different concentrations of acetylcholinesterase, whereas non-MTrP cells were exposed to acetylcholine. The morphological changes of muscle cells in each group were observed., Results: By culturing MTrP cells in vitro , large contractile nodules remained in single MTrP muscle fibers, whereas some contractile nodules were twisted and deformed. After the addition of different acetylcholinesterase concentrations, no obvious morphological changes were observed in the contractile nodules in the MTrP group. After the non-MTrP cells were exposed to different acetylcholine concentrations, no significant morphological changes were observed in the single muscle fibers., Conclusion: MTrP cells can continue to maintain contractile morphology in vitro , but whether the recovery of such contractile nodules is related to acetylcholine remains uncertain., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Proton pump inhibitors (PPIs) are widely prescribed for gastroesophageal reflux disease and peptic ulcer disease. However, the association between the regular PPIs use and the risk of cardiovascular disease (CVD) outcomes remains unclear. We aimed to determine whether regular proton pump inhibitors (PPIs) use is associated with an altered incidence of cardiovascular disease (CVD) in the general population., Methods: This prospective cohort study included 459,207 participants (mean [SD] age, 56.2 [8.1] years) from the UK Biobank study without prevalent CVD who enrolled between 2006 and 2010 and were followed until 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD and its components (coronary heart disease [CHD], stroke, heart failure, atrial fibrillation, and venous thromboembolism) were obtained using Cox proportional hazards models with adjustment for potential confounding factors, including demographic factors, lifestyle behaviors, prevalent comorbidities, and clinical indicators for PPIs use., Results: During the follow-up period, we recorded 26,346 incident CVD events (including 13,749 CHD events, 4144 stroke events, 5812 atrial fibrillation events, 1159 heart failure events, and 4206 venous thromboembolism events). The fully adjusted HRs (and 95% CIs) associated with PPIs users compared to nonusers were 1.44 (95% CI 1.39-1.50) for incident CVD, 1.65 (95% CI 1.57-1.74) for CHD, 1.21 (95% CI 1.09-1.33) for stroke, 1.17 (95% CI 1.08-1.28) for atrial fibrillation, 1.61 (95% CI 1.37-1.89) for heart failure, and 1.36 (95% CI 1.24-1.50) for venous thromboembolism., Conclusions: Regular PPIs use was associated with higher risk of CVD outcomes. Clinicians should therefore exercise caution when prescribing PPIs., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Pneumothorax is a common complication induced by computed tomography (CT)-guided percutaneous needle biopsy, with a frequency of 17-40.4%. It remains debatable how to predict and prevent the occurrence of post-biopsy pneumothorax. In a real-world setting, we investigated the characteristics associated with pneumothorax in primary lung nodule biopsy., Methods: This clinical registry cohort study recorded patients with newly diagnosed pulmonary nodules from 10 medical centers from April 2021 to April 2022, and the data were input into the electronic data capture (EDC) system. The eligibility criteria for participants included being within the age range of 18 to 80 years and expressing a willingness to undergo percutaneous puncture biopsy, among other requirements. Conversely, the exclusion criteria included an inability to cooperate throughout the biopsy process and the emergence of new health issues during the study duration resulting in attendance delays, among other factors. This study collected data from 924 patients, out of which 593 were included after exclusion. The essential characteristics, imaging features of pulmonary nodules, and technical factors associated with percutaneous biopsy were recorded. T -tests or one-way analysis of variance (ANOVA) were performed for continuous variables and Pearson's χ 2 test, likelihood ratio, or Fisher's exact test were applied for categorical variables for comparison as appropriate, followed by multivariate logistic regression., Results: The overall incidence of pneumothorax was 13.0% (77/593), among which timely pneumothorax was 10.3% (61/593), delayed pneumothorax was 2.7% (16/593), and the rate of chest tube placement was 3.4% (20/593). There was no significant difference in the incidence of pneumothorax in a needle size range of 16-19 G (P=0.129), but the incidence of pneumothorax was lower with 17 G needles than with 18 G. An increased morbidity of pneumothorax was correlated with age (P=0.003), emphysema (P=0.006), and operation time (P=0.002). There was no significant increase in the incidence of pneumothorax between 1 or 2 passes through the pleura (P=0.062). However, multiple pleural passes (3 times) increased the chances of pneumothorax significantly (P=0.022). These risk factors have a certain clinical value in predicting the incidence of post-biopsy pneumothorax, and the area under the curve (AUC) was 0.749., Conclusions: The most common post-biopsy complication, pneumothorax, was managed conservatively in most cases. A maximum of two pleural passes does not increase the incidence of pneumothorax, and the 17 G needle is more suitable for percutaneous biopsy of pulmonary nodules in the real world., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-891/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Although observational studies have indicated that plasma lipids are associated with an increased risk of sepsis, due to confounders and reverse causality, the causal relationship remains unclear. This study was designed to assess the causal effects of plasma lipid levels on sepsis. We used a 2-sample Mendelian randomization (MR) method to evaluate the causal effect of plasma lipids on sepsis. MR analysis employs methods such as inverse variance weighted, MR-Egger regression, weighted median regression (WME), simple mode and weighted mode. The inverse variance weighted (IVW) method was predominantly utilized to assess causality. Heterogeneity was affirmed by Cochran Q test, while pleiotropy was corroborated by MR-Egger regression analysis. The robustness and reliability of the results were demonstrated through "leave-one-out" sensitivity analysis. Instrumental variables included 226 single-nucleotide polymorphisms (SNPs), comprising of 7 for triglyceride (TG), 169 for high-density lipoprotein cholesterol (HDL-C), and 50 for low-density lipoprotein cholesterol (LDL-C). The risk of sepsis appeared to increase with rising LDL-C levels, as indicated by the inverse variance weighted analysis (OR 1.11, 95% CI from0.99 to1.24, P = 0.068). However, no causality existed between LDL-C, HDL-C, TG and sepsis. Two-sample MR analysis indicated that increased LDL-C level is a risk factor for sepsis, while TG and HDL-C levels have protective effects against sepsis. However, no significant causal relationship was found between TG, HDL-C, and LDL-C levels and sepsis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs)., Methods: Overall, 260 patients with LEVVs participated in this study. LEVVs were selected based on diagnostic criteria of Clinical, Etiology, Anatomy, and Pathophysiology levels 2-5 and classified into six types on the basis of their anatomical positions. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient. An in-house evaluation was used to estimate the proportion of varicose veins in the lower limbs and their accompanying symptoms. The treatment effect was evaluated before each treatment and at 1-year follow-up., Results: The mean evaluation score of LEVVs before the treatment course was 3.66 ± 1.19. After the course, this reduced to 1.18 ± 0.97, with the following response rates: 85% for excellent and good and 15% for medium. After 1-year follow-up, the mean evaluation score of all patients was 1.11 ± 0.92, with the following response rates: 87% for excellent and good, and 13% for medium., Conclusions: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Extensions of mesenchymal stem cells (MSCs) in vitro may lead to the loss of their biological functions. However, hypoxic culturation has been shown to enhance the proliferation, survival, and immunomodulatory capacity of MSCs., Objective: We aimed to investigate the effects of long-term hypoxic cultivation on the properties of human umbilical cord-derived MSCs (hUCMSCs) and the therapeutic effects of their extracellular vesicles (EVs) in allergic rhinitis (AR)., Methods: Proliferation, senescence, telomerase activity and multipotent properties of hUCMSCs were analyzed under long-term culturation of hypoxia (1%) or normoxia (21%), and the therapeutic effects of their conditional medium (CM) and EVs were evaluated in OVA-induced AR mice. Effects of hypoxia-EVs (Hy-EVs) or normoxia-EVs (No-EVs) on human monocyte-derived dendritic cells (DCs) were investigated, and the possible mechanisms of Hy-EVs in induction of immunotolerance were further explored., Results: Long-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs. Hy-CM and Hy-EVs showed better therapeutic effects in AR mice compared to No-EVs, seen as improvement of AR-related behaviors such as rubbing and sneezing, and attenuation of inflammation in nasal tissues. In addition, Hy-EVs significantly reduced the expressions of HLA-DR, CD80, CD40, and CD83 induced by OVA plus LPS in DCs, inhibiting the maturation of DCs. Furthermore, we observed that VEGF was remarkably enriched in Hy-EVs, but not in No-EVs, and the inhibition of DCs maturation was markedly neutralized by VEGF antibodies, suggesting that VEGF derived from Hy-EVs was responsible for the inhibition of DCs maturation., Conclusion: Our results demonstrated that long-term hypoxia significantly promoted the proliferation, inhibited cell senescence, maintained the multipotent status of hUCMSCs, and hypoxia treated hUCMSCs-derived EVs enhanced their therapeutic effects in AR mice through VEGF-mediated inhibition of DCs maturation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006-2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM 2.5 and PM 10 ), nitrogen dioxide (NO 2 ), and nitrogen oxides (NO X ). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM 2.5 , PM 10 , NO 2 , and NO X increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65-0.76) for PM 2.5 , 0.69 (95 % CI: 0.64-0.75) for PM 10 , 0.70 (95 % CI: 0.64-0.75) for NO 2 , and 0.70 (95 % CI: 0.64-0.75) for NO X . No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the combined relationship between night shifts and lifestyle risks with incident dementia or their potential interactions. To evaluate the association of night shifts and lifestyle risks with incident dementia and further analyze their interactions., Methods: A total of 276 059 participants were included in this study from the UK Biobank cohort. Cox proportional hazards models were used to investigate the combined association of night shifts and lifestyle risks with incident dementia., Results: Participants with always night shifts and 3 or 4 unhealthy lifestyle factors had the highest risk of incident all-cause dementia (hazard ratio: 3.15, 95% confidence interval [CI]: 1.74-5.69). An additive interaction was found between night shifts and lifestyle risks for incident all-cause dementia (p < .001), with a relative excess risk due to the interaction of 0.14 (95% CI: 0.11-0.45). The attributable proportions of the combined effect on the incidence of all-cause dementia were 22.6% (95% CI: 20.91%-26.75%) for night shift work, 65.0% (95% CI: 63.12%-69.80%) for unhealthy lifestyle factors, and 12.1% (95% CI: 8.67%-18.04%) for their interaction., Conclusions: Both night shifts and lifestyle risks were associated with a higher risk of incident dementia. The combined impact was higher than the increase in the risks related to each single factor. Our results indicated that most incident dementia cases might be prevented by a healthy lifestyle, and the benefits would be greater among night shift workers. Further studies are needed to confirm our results and explore the underlying mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To examine the association of serum 25-hydroxyvitamin D (25[OH]D) with colorectal cancer (CRC) risk in adults with type 2 diabetes (T2D)., Methods: Using UK Biobank data, this study included 18,453 adults with T2D. Serum 25(OH)D concentrations were determined by the chemiluminescent immunoassay method. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcomes., Results: During a median follow-up of 8.8 years, there were 284 incident CRC cases. Compared with adults with serum 25(OH)D concentrations <25.0 nmol/L, the adjusted HRs (95% CIs) for lower to higher serum 25(OH)D concentrations (25.0 to <50.0, 50.0 to <75.0, and ≥75.0 nmol/L) were 0.61 (0.46-0.82), 0.50 (0.34-0.74), and 0.53 (0.30-0.94), respectively (P trend  = 0.001). The risk of CRC decreased by 19.0% for per 1-SD increment in serum 25(OH)D concentrations. A nonlinear association of serum 25(OH)D concentrations with CRC risk was observed using a restricted cubic spline analysis (P nonlinearity = 0.002)., Conclusions: Higher serum 25(OH)D concentrations were significantly and nonlinearly associated with a lower risk of CRC. These findings highlight the potential benefits of maintaining adequate vitamin D levels in CRC prevention among adults with T2D., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Early neurological deterioration after hematoma evacuation is closely associated with a poor prognosis in patients with intracerebral hemorrhage. However, the relationship between body temperature after hematoma evacuation and early neurological deterioration remains unclear. Therefore, this study aims to explore the possible relationship between body temperature and early neurological deterioration in patients with intracerebral hemorrhage after hematoma evacuation., Methods: We retrospectively collected data from patients with cerebral hemorrhage at our institute between January 2017 and April 2022. The Student's t -test, Mann-Whitney U-test, and χ 2 Test and Fisher's exact test were used to analyze the clinical baseline data. A univariate logistic regression model was used to evaluate the association between the body temperature indices and early neurological deterioration. The predictive power was assessed using the area under the Receiver Operating Characteristic (ROC) curve. The secondary outcome was a poor functional outcome., Results: Among 2,726 patients with intracerebral hemorrhage, 308 who underwent hematoma evacuation were included in the present analysis. A total of 82 patients (22.6%) developed early neurological deterioration. Univariate analysis showed that sex ( p  = 0.041); body temperature at 6 h ( p  = 0.005), 12 h ( p  = 0.01), and 24 h ( p  = 0.008) after surgery; duration of fever ( p  = 0.008); and fever burden ( p  < 0.001) were associated with early neurological deterioration. Multivariate logistic regression showed that fever burden was independently associated with early neurological deterioration (OR = 1.055 per °C × hour, 95%CI 1.008-1.103, p  = 0.020). ROC showed that fever burden (AUC = 0.590; 95%CI: 0.514-0.666) could predict the occurrence of early neurological deterioration., Conclusion: Fever burden is associated with early neurological deterioration in intracerebral hemorrhage patients undergoing hematoma evacuation. Our findings add to previous evidence on the relationship between the fever burden and the occurrence of early neurological deterioration in patients with intracerebral hemorrhage. Future studies with larger sample sizes are required to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Xiong, He, Wang, Chen, Chen, Huang, Huang, Pan, Hu, He and Zheng.)

The association between long-term joint exposure to all kinds of ambient air pollutants and the risk of mortality is not known. Our study prospectively assessed the joint associations of various air pollutants with cause-specific and all-cause mortality risk and identified potential modifying factors affecting these associations. A total of 400,259 individuals aged 40-70 years were included in this study. Information on PM 10 , PM 2.5-10 , PM 2.5 , NO 2 , and NO x was collected. A weighted air pollution score was calculated to assess joint exposure to the above air pollutants. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During a median of 12.0 years (4,733,495 person-years) of follow-up, 21,612 deaths were recorded, including 7097 deaths from cardiovascular disease and 11,557 deaths from cancer. The adjusted HRs of all-cause mortality were 1.39 (95% CI: 1.29-1.50), 1.86 (95% CI: 1.63-2.13), 1.12 (95% CI: 1.10-1.14), and 1.04 (95% CI: 1.03-1.05) for every 10-ug/m 3 increase in PM 10 , PM 2.5 , NO 2 , and NO x , respectively. The adjusted HRs associated with the air pollution score (the highest quintile versus the lowest quintile) were 1.24 (95% CI: 1.19-1.30) for all-cause mortality, 1.33 (95% CI: 1.23-1.43) for cardiovascular mortality, and 1.16 (95% CI: 1.09-1.23) for cancer mortality. Furthermore, we found that the air pollution score was associated with a linear dose-response increase in mortality risk (all P for linearity < 0.001). The findings highlight the importance of a comprehensive assessment of various air pollutants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (T H 2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box-binding protein-1 (XBP1) in the induction of the T H 2 cell response through its role in generating TIM4 + DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2-XBP1-TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant T H 2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for T H 2 cell responses by inducing the development of TIM4 + DCs, which depends on the IL-2-XBP1-SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of T H 2 cell-dependent inflammation or allergic diseases.

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Background: COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness., Methods: A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated., Results: Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated., Conclusion: Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination., (© 2023. The Author(s).)

Background: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA., Methods: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up., Results: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG., Conclusions: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months., Trial Registration: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432., (© 2023. The Author(s).)

Background: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear., Objective: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition., Methods: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms., Results: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings., Conclusions: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition., Competing Interests: Conflicts of Interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Postoperative neurocognitive disorder (PND) is a disease that frequently develops in older patients during the perioperative period. It seriously affects the quality of life of the affected patients. Despite advancements in understanding PND, this disorder's mechanisms remain unclear, including pathophysiological processes such as central synaptic plasticity and function, neuroinflammation, excitotoxicity, and neurotrophic support. Growing evidence suggests that microenvironmental changes are major factors for PND induction in older individuals. Exosomes are carriers for transporting different bioactive molecules between nerve cells in the microenvironment and maintaining intercellular communication and tissue homeostasis. Studies have shown that exosomes and microRNAs (miRNAs) are involved in various physiological and pathological processes, including neural processes related to PND, such as neurogenesis and cell death, neuroprotection, and neurotrophy. This article reviews the effects of exosomes and miRNAs on the brain microenvironment in PND and has important implications to improve PND diagnosis, as well as to develop targeted therapy of this disorder., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution., Methods: UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM 2.5 , PM coarse (PM 2.5-10 ), PM 10 , and NO 2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs)., Results: During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79-0.86) and 0.73 (95% CI, 0.70-0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM 2.5 , PM coarse , PM 10 , and NO 2 ) were 1.19 (1.14-1.24), 1.06 (1.02-1.11), 1.13 (1.08-1.18), and 1.19 (1.14-1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend < 0.05)., Conclusion: A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas., (© 2022. The Author(s).)

Introduction: Lower limb dysfunction is among the common sequelae of patients who had a poststroke and often results in the reduction of the quality of life. This study aims to assess the short and interim-term efficacy of dry needling (DN) intervention on lower extremity function, balance and gait in lower limb dysfunction after stroke., Methods and Analysis: This protocol entails an assessor and statistician-blinded, single-centre study with a randomised controlled trial. Forty-four patients who had a poststroke will be randomly allocated (1:1) to either the conventional treatment group (n=22) or the DN group (n=22). The conventional treatment group will receive conventional rehabilitation treatment once a day for 40 min each time. The treatment will be performed five times a week for 2 weeks. In the DN group, participants will be treated with DN on the basis of the conventional treatment. The intervention will be performed thrice a week for 2 weeks. The primary outcome that determines the efficacy of lower limb dysfunction will be the change in the Fugl-Meyer Assessment of Lower Extremity scale. The secondary indicators include the range of motion of knee and ankle joints, limits of stability, modified Clinical Test of Sensory Interaction on Balance, Timed Up and Go test, Modified Ashworth Scale and Barthel Index. Results will be evaluated at baseline, at 24 hours after intervention, at 2 weeks after intervention and at 3-month follow-up. Data will be released after the completion of the study. Adverse events will be reported., Ethics and Dissemination: The experiment was approved by the Ethical Committee of Shanghai Tong Ren Hospital in October 2021 (approval number: 202105702). The results of this study will be published in peer-reviewed journals., Trial Registration Number: ChiCTR2000040754., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Postoperative cognitive dysfunction (POCD), especially in elderly patients, is a serious complication characterized by impairment of cognitive and sensory modalities after surgery. The pathogenesis of POCD mainly includes neuroinflammation, neuronal apoptosis, oxidative stress, accumulation of Aβ, and tau hyperphosphorylation; however, the exact mechanism remains unclear. Non-coding RNA (ncRNA) may play an important role in POCD. Some evidence suggests that microRNA, long ncRNA, and circular RNA can regulate POCD-related processes, making them promising biomarkers in POCD diagnosis, treatment, and prognosis. This article reviews the crosstalk between ncRNAs and POCD, and systematically discusses the role of ncRNAs in the pathogenesis and diagnosis of POCD. Additionally, we explored the possible mechanisms of ncRNA-associated POCD, providing new knowledge for developing ncRNA-based treatments for POCD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, He, Chen, Wang, Huang, Shi, Lin and He.)

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status ( P for interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Background: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without., Objective: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality., Design: Prospective cohort study., Setting: Data were extracted from the UK Biobank., Participants: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018., Measurements: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated., Results: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee., Limitation: Exposure assessed at baseline might not capture changes in intake over time., Conclusion: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death., Primary Funding Source: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

Treatments with abiotic elicitors can efficiently induce the accumulation of specialized metabolites in plants. We used a combined omics approach to analyze the elicitation effects of MeJa, AgNO 3 , and PEG on camptothecin (CPT) biosynthesis in Camptotheca acuminata plantlets. Untargeted analyses revealed that treatments with MeJa, AgNO 3 , and PEG significantly inhibited the photosynthetic pathway and promoted carbon metabolism and secondary metabolic pathways. The CPT levels increased by 78.6, 73.3, and 50.0% in the MeJa, AgNO 3 , and PEG treatment groups, respectively. Using C. acuminata plantlets after elicitation treatment, we mined and characterized 15 new alkaloids, 25 known CPT analogs and precursors, 9 iridoid biosynthetic precursors, and 15 tryptamine biosynthetic precursors based on their MS/MS fragmentation spectra. Using 32 characterized genes involved in CPT biosynthesis as bait, we mined 12 prioritized CYP450 genes from the 416 CYP450 candidates that had been identified based on co-expression analysis, conserved domain analysis, and their elicitation-associated upregulation patterns. This study provides a comprehensive perspective on CPT biosynthesis in C. acuminata plantlets after abiotic elicitation. The findings enable us to elucidate the previously unexplored CYP450-mediated oxidation steps for CPT biosynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pu, Gao, Wang, Zhang, Shan, Chen, Zhang, Wang, Wen, Luo and Huang.)

Tripartite motif containing 65 (TRIM65) is an E3 ubiquitin ligase that has been implicated in a variety of cellular processes as well as tumor progression, but its biological role and the underlying mechanism in cervical cancer is unclear. Here, we reported that TRIM65 expression in human cervical cancer tissues was significantly higher than that in the adjacent normal cervical tissues, and TRIM65 knockdown enhanced autophagic flux and cell apoptosis, but not cell cycle, to dramatically inhibit the proliferation and migration of cervical cancer cells. Furthermore, our experiments showed that TRIM65 exhibited oncogenic activities via directly targeting p53, a tumor suppressor and a common upsteam regulator between autophagy and apoptosis, promoting ubiquitination and proteasomal degradation of p53. Taken together, our studies demonstrated that TRIM65 knockdown promotes cervical cancer cell death through enhancing autophagy and apoptosis, suggesting that TRIM65 may be a potential therapeutic target for cervical cancer clinically., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Mao, Guan, Huang, Yu, Wu, Tan, Zhang, Huang, Deng and Xin.)

Background: Little is known about the role of dietary diversity changes in affecting cognitive function among older people. Therefore, we aimed to evaluate the associations between dietary diversity scores (DDS) changes with cognitive impairment among older adults in a large prospective cohort., Methods: Cognitive function was assessed using the Mini-Mental State Examination questionnaire at baseline and follow-up. A total of 9726 participants without Parkinson's disease, dementia, or cognitive impairment were enrolled at baseline. Nine food groups were collected using simplified FFQ at baseline and follow-up surveys. Then nine food groups change patterns and DDS change patterns (overall, plant-based and animal-based) were assessed. The associations of above DDS changes patterns with subsequent cognitive impairment were evaluated. A multivariable-adjusted Cox proportional hazards model was used to estimate HRs and 95%CIs., Results: We documented 2805 cognitive impairments during 52,325 person-years of follow-up. Compared to high-to-high overall DDS change patterns, the multivariable adjusted HRs (95%CI) for high-to-medium, medium-to-medium, medium-to-low, low-to-medium and low-to-low DDS change patterns were 1.33 (1.12-1.57), 1.11 (0.94-1.32), 1.61 (1.39-1.86), 2.00 (1.66-2.40), 2.30 (1.90-2.78) and 2.80 (2.23-3.53), respectively. Compared with participants with stable DDS change pattern, those who in large improvement of DDS had a 13% lower risk of cognitive impairment (HRs, 0.87; 95%CI: 0.78-0.98). The associations of plant-based DDS, animal-based DDS, or nine food groups DDS change patterns with cognitive impairment were in a similar direction to the main result., Conclusions: Protective associations between maintaining high DDS and a reduced risk of cognitive impairment were observed. In contrast, lowering or maintaining a lower DDS increases the risk of cognitive impairment.

Background: Non-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019-2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza., Methods: We used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore., Results: We found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019-2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50-99.48% during the period of compulsory interventions in the 2019-2020 season compared to the same period in preceding years in the four countries., Conclusion: These findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Song, Liang, Ye, Li, Zhang, Zhong, Zhang, Liu, Shen, Chen, Liu, Yang and Mao.)