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Abstract Mitochondrial dysfunction is a significant contributor to podocyte injury in diabetic kidney disease (DKD). While previous studies have shown that PVT1 might play a vital role in DKD, the precise molecular mechanisms are largely unknown. By analyzing the plasma and kidney tissues of DKD patients, we observed a significant upregulation of PVT1 expression, which exhibited a positive correlation with albumin/creatinine ratios and serum creatinine levels. Then, we generated mice with podocyte-specific deletion of PVT1 (Nphs2-Cre/Pvt1 flox/flox ) and confirmed that the deletion of PVT1 suppressed podocyte mitochondrial dysfunction and inflammation in addition to ameliorating diabetes-induced podocyte injury, glomerulopathy, and proteinuria. Subsequently, we cultured podocytes in vitro and observed that PVT1 expression was upregulated under hyperglycemic conditions. Mechanistically, we demonstrated that PVT1 was involved in mitochondrial dysfunction by interacting with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission. Additionally, the release of mtDNA and mtROS from damaged mitochondria triggered inflammation in podocytes. Subsequently, we verified the important role of TRIM56 in vivo by constructing Nphs2-Cre/Trim56flox/flox mice, consistently with the results of Nphs2-Cre/Pvt1 flox/flox mice. Together, our results revealed that upregulation of PVT1 could promote mitochondrial dysfunction and inflammation of podocyte by modulating TRIM56, highlighting a potential novel therapeutic target for DKD.

Abstract Background Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI.

Abstract Background This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . Methods A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. Results During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = − 0.346, P

Background: Studies have shown that abnormal temperature at night is a risk factor for respiratory health. However, there is limited evidence on the impact of hot and cold nights on cause-specific diseases such as pneumonia, which is a leading cause of morbidity and mortality in children. Methods: We collected daily data on pneumonia hospitalisations in children under five years from 2011 to 2017 in three low-, middle- and high-income countries (Bangladesh, China, and Australia). The intensity of hot and cold nights was measured by excess temperature. A space–time-stratified case-crossover analysis was used to estimate the association between hot and cold nights and childhood pneumonia hospitalisations. We further estimated the fraction of childhood pneumonia hospitalisations attributable to hot and cold nights. Results: Both hot and cold nights were associated with an increased risk of hospitalisations for childhood pneumonia in low-, middle-, and high-income countries, with a greater disease burden from hot nights. Specifically, the fraction of childhood pneumonia attributable to hot nights was the largest in Australia [21.2%, 95% confidence interval (CI): 11.8%-28.1%], followed by Bangladesh (15.2%, 95% CI: 4.1%–23.8%) and China (2.7%, 95% CI: 0.4%-4.7%). Additionally, the fraction of childhood pneumonia attributable to cold nights was 1.3% (95% CI: 0.4%-2.0%) in Bangladesh and 0.4% (95% CI: 0.1%-0.7%) in China. Conclusion: This multi-country study suggests that hot and cold nights are not only associated with a higher risk of pneumonia hospitalisations in children but also responsible for substantial fraction of hospitalisations, with a greater impact from hot nights.

Background: The climate change scenario has witnessed an increase in extreme temperature events (ETEs), including heat waves and cold spells, and a heightened occurrence of compounding with fine particulate matter (PM2.5). However, the impact of this phenomenon on the sensitivity to thyroid hormones (THs) in humans is unclear, especially in a group as specific as schizophrenia. Methods: A longitudinal study was constructed using longitudinal measurements of thyroid function in schizophrenia in the Anhui Mental Health Center. The latent growth mixture model was applied to assess the optimal trajectory of change in impaired THs sensitivity. We then used logistic regression to explore associations between heat waves, cold spells, and PM2.5 with impaired THs sensitivity trajectories in the total population and different gender and age subgroups. Furthermore, the effect of the frequency, intensity, and duration of ETEs in the above associations was explored, as well as an assessment of the interaction between ETEs and PM2.5. Results: Among 931 participants, we identified two classifications of trajectories of impaired THs sensitivity: “Low-stable” (n = 836, 89.80 %) and “Rise-slight down” (n = 95, 10.20 %). Logistic regression showed significant associations between each additional day of heat waves (≥3 days with temperature thresholds above the 95th percentile) and cold spells (≥3 days with temperature thresholds below the 5th percentile) and “Rise-slight down” trajectory, with odds ratios (95 % confidence intervals) of 1.06 (1.02, 1.10) and 1.19 (1.14, 1.24), respectively, and the strength of this association increased with the intensity and duration of ETEs. Subgroup analyses indicated that the association was more pronounced in males and the age group above 40 years. Furthermore, PM2.5 was found to interact with heat waves, with high concentrations exacerbating the effects of heat waves. Conclusions: Our findings suggest that mitigating both ETEs and PM2.5 exposures may bring health co-benefits in preventing thyroid impairment in schizophrenia.

Abstract Existing formulas cannot fully explain the variation of resting metabolic rate (RMR). This study aims to examine potential influencing factors beyond anthropometric measurements and develop more accurate equations using accessible parameters. 324 healthy adults (230 females; 18–32 years old) participated in the study. Height, fat-free mass (FFM), fat mass (FM) and RMR were measured. Menstrual cycle, stress levels, living habits, and frequency of consuming caffeinated foods were collected. Measured RMR were compared with predictive values of the new equations and previous 11 equations. Mean RMR for men and women was 1825.2 ± 248.8 and 1345.1 ± 178.7 kcal/day, respectively. RMR adjusted for FFM0.66FM0.066 was positively correlated with BMI. The multiple regression model showed that RMR can be predicted in this population with model 1 (with FFM, FM, age, sex and daily sun exposure duration) or model 2 (with weight and height replacing FFM and FM). The accuracy was 75.31% in the population for predictive model 1 and 70.68% for predictive model 2. The new equations had overall improved performance when compared with existing equations. The predictive formula that consider daily sun exposure duration improve RMR prediction in young adults. Additional investigation is required among individuals in the middle-aged and elderly demographic.

ObjectivesThis study aimed to investigate the link between 25-hydroxy vitamin D and serum asprosin in individuals with type 2 diabetes within the community. The goal was to provide a foundation for clinical interventions.MethodsBetween November 2019 and July 2021, data from 463 patients with type 2 diabetes were consistently gathered at a community health service station in Southeast Shanxi Province. General information and laboratory metrics were compiled, including serum asprosin levels. The participants were categorized based on three serum asprosin quantiles, allowing for a comparison of various factors among the groups. The correlation between serum asprosin levels and other factors was analyzed. Employing a general linear model, the connection between 25-hydroxy vitamin D and serum asprosin levels was studied. Utilizing three quantiles of 25-hydroxy vitamin D, serum asprosin was treated as the dependent variable, while 25-hydroxy vitamin D served as the independent variable for linear regression analysis.ResultsAs serum asprosin increased, there were gradual increments in age, disease duration, SBP, BMI, WC, creatinine, and SUA levels (P

Abstract Aim of this comparative cross-sectional study was to evaluate the effect of anterior teeth retraction and related hard and soft tissue change under physiologic anchorage control in patients with chief complain of protrusive teeth. 68 Class I or II orthodontic patients undergoing four-premolar extraction and requiring maximum or medium anchorage were included. Patients were treated with physiologic anchorage control technique (PASS group, n = 34, 18.6 ± 7.7 years, 10 male and 24 female) and self-ligation technique (Damon group, n = 34, 17.5 ± 5.4 years, 13 male and 21 female), respectively. TADs were used for anchorage reinforcement in Damon group. Pre- and post-treatment cephalograms were collected. Twenty-six skeletal, dental and soft tissue items were measured and analyzed using a blinded method. T test and paired rank-sum test were used for statistical analysis. The baseline characteristics were similar between groups (P > 0.05). After treatment, inter-group comparison showed statistically significant differences in the decrease of skeletal measurements ∠ANB (− 0.73 ± 1.05° in PASS group and − 0.25 ± 0.84° in the Damon group), Wits value (− 2.56 ± 2.29 mm in PASS group and − 0.47 ± 2.15 mm in Damon group) and soft tissue measurement UL-E (− 2.75 ± 1.36 mm in PASS group and − 2.03 ± 1.30 mm in Damon group) and the increase of FCA and Z angle, which was 2.03 ± 2.12°and 9.52 ± 4.78°in PASS group and 0.97 ± 2.12°and 6.96 ± 4.43°in Damon group, respectively (P

Background: Climate change has shifted and will continue to alter the patterns of daytime and nighttime temperatures. However, it remains unclear whether hot days and nights, as well as cold days and nights, have varying impacts on mental disorders. Methods: Daily hospital-based data on 1.2 million outpatient visits for mental disorders were obtained from 15 Chinese cities (2011-2015). The index of hot day excess, hot night excess, cold day excess, and cold night excess were used to measure the intensity of hot/cold days and nights. Firstly, a distributed lag non-linear model was used to estimate the risk of mental disorders associated with hot/cold days and nights for each city. Secondly, city-specific estimates were pooled by multivariate meta-analysis to obtain national effect estimates. Thirdly, the attributable fraction of mental disorders was estimated for the nation, genders, age groups, heating methods, and air conditioning penetration rates. Results: Our findings revealed that both hot and cold nights were associated with a higher risk of mental disorders compared to hot and cold days. The attributable fraction of mental disorders was higher for cold (night: 25.74%; day: 19.65%) in contrast to heat (night: 16.91%; day: 7.24%). Males, the elderly, cities using central heating, and cities with low air conditioning penetration rates were vulnerable to cold nights. Conclusions: This nationwide study highlights the adverse effects and significant burden of hot and cold nights on mental disorders. It underscores the potential for mitigating these impacts through the adoption of air conditioning, particularly in southern cities across China.

Abstract Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ADTC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Abstract Background Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk. Methods Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger’s test. Results In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66–0.93, P = 0.006; P Q = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11–1.71, P = 0.004, P Q = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041). Conclusion The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

Abstract Objectives This study aimed to investigate vertical changes in the maxillary central incisor and the maxillary first molar, along with alterations in the mandibular plane angle during space closure using miniscrew sliding mechanics. Methods Twenty adult patients treated at Peking University Hospital of Stomatology between 2008 and 2013 were included. Digital dental models and craniofacial cone-beam computed tomography (CBCT) scans were obtained at the start of treatment (T0) and immediately after space closure (T1). Stable miniscrews were used for superimposing maxillary digital dental models (T0 and T1), and vertical changes in the maxillary first molar and the maxillary central incisor were measured. Three-dimensional changes in the mandibular plane were assessed through CBCT superimposition. Results The maxillary central incisor exhibited an average extrusion of 2.56 ± 0.18 mm, while the maxillary first molar showed an average intrusion of 1.25 ± 1.11 mm with a distal movement of 0.97 ± 0.99 mm. Additionally, the mandibular plane angle decreased by an average of 0.83 ± 1.65°. All three indices exhibited statistically significant differences. Conclusion During space closure using the miniscrew sliding technique, significant changes occurred in both the sagittal and vertical dimensions of the upper dentition. This included extrusion of the maxillary central incisors, intrusion of the maxillary first molars, and a slight counterclockwise rotation of the mandibular plane.

AbstractContext Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of safflower (Carthamus tinctorius L., [Asteraceae]) for traumatic brain injury (TBI) treatment.Objective To explore the therapeutic effects and underlying mechanisms of HSYA on post-TBI neurogenesis and axon regeneration.Materials and methods Male Sprague-Dawley rats were randomly assigned into Sham, controlled cortex impact (CCI), and HSYA groups. Firstly, the modified Neurologic Severity Score (mNSS), foot fault test, hematoxylin-eosin staining, Nissl’s staining, and immunofluorescence of Tau1 and doublecortin (DCX) were used to evaluate the effects of HSYA on TBI at the 14th day. Next, the effectors of HSYA on post-TBI neurogenesis and axon regeneration were screened out by pathology-specialized network pharmacology and untargeted metabolomics. Then, the core effectors were validated by immunofluorescence.Results HSYA alleviated mNSS, foot fault rate, inflammatory cell infiltration, and Nissl’s body loss. Moreover, HSYA increased not only hippocampal DCX but also cortical Tau1 and DCX following TBI. Metabolomics demonstrated that HSYA significantly regulated hippocampal and cortical metabolites enriched in ‘arginine metabolism’ and ‘phenylalanine, tyrosine and tryptophan metabolism’ including l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. Network pharmacology suggested that neurotrophic factor (BDNF) and signal transducer and activator of transcription 3 (STAT3) were the core nodes in the HSYA-TBI-neurogenesis and axon regeneration network. In addition, BDNF and growth-associated protein 43 (GAP43) were significantly elevated following HSYA treatment in the cortex and hippocampus.Discussion and conclusions HSYA may promote TBI recovery by facilitating neurogenesis and axon regeneration through regulating cortical and hippocampal metabolism, BDNF and STAT3/GAP43 axis.

Abstract Background Among all types of mental disorders, individuals with schizophrenia exhibit the highest frequency of aggressive behavior. This disrupts the healthcare environment and poses threats to family life and social harmony. Present approaches fail to identify individuals with schizophrenia who are predisposed to aggressive behavior. In this study, we aimed to construct a risk prediction model for aggressive behavior in stable patients with schizophrenia, which may facilitate early identification of patients who are predisposed to aggression by assessing relevant factors, enabling the management of high-risk groups to mitigate and prevent aggressive behavior. Methods A convenience sample of stable inpatients with schizophrenia were selected from Daqing Municipal Third Hospital and Chifeng Municipal Anding Hospital from March 2021 to July 2023. A total of 429 patients with stable schizophrenia who met the inclusion criteria were included. A survey was conducted with them using a questionnaire consisting of general information questionnaire, Positive and Negative Symptom Scale, Childhood Trauma Questionnaire-Short Form, Connor-Davidson Resilience Scale and Self-esteem Scale. Patients enrolled in this study were divided into aggressive and non-aggressive groups based on whether there was at least one obvious and recorded personal attack episode (including obvious wounding and self-injurious behavior) following diagnosis. Binary Logistic regression was used to determine the influencing factors, and R software was used to establish a nomogram model for predicting the risk of aggressive behavior. Bootstrap method was used for internal validation of the model, and the validation group was used for external validation. C statistic and calibration curve were used to evaluate the prediction performance of the model. Results The model variables included Age, Duration of disease, Positive symptom, Childhood Trauma, Self-esteem and Resilience. The AUROC of the model was 0.790 (95% CI:0.729–0.851), the best cutoff value was 0.308; the sensitivity was 70.0%; the specificity was 81.4%; The C statistics of internal and external validation were 0.759 (95%CI:0.725–0.814) and 0.819 (95%CI:0.733–0.904), respectively; calibration curve and Brier score showed good fit. Conclusions The prediction model has a good degree of discrimination and calibration, which can intuitively and easily screen the high risk of aggressive behavior in stable patients with schizophrenia, and provide references for early screening and intervention.

Abstract In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.

Directional fracture blasting technology of the slit charge has broad application prospects in the drilling and blasting construction of the layered rock mass. In this paper, the method of model experiment and numerical simulation is used to preliminarily explore the fracture damage characteristics of slit charge blasting in the layered rock mass. The results show that the blasting effect of the slit charge in the layered rock mass is significantly different from that of the unlayered rock mass, and the pressure relief of the blasting gas at the layer is the main factor affecting the blasting effect. The length of directional cracks in the slit direction is significantly larger than that in other directions, and the directional fracture effect of the slit charge in the layered rock mass can still be played well. However, both the directional crack length and the damage range of rock mass in the slit direction gradually decrease along the detonation direction. In addition, the damage value of a single-layer rock mass also decreases gradually along the detonation direction. In engineering practice, the directional fracture effect of the layered rock mass can be improved by detonating at both ends of the slit charge at the same time.

Abstract The Multi-purpose Time Projection Chamber (TPC) for nuclear AsTrophysical and Exotic beam experiments (MATE) is being upgraded for the decay and active target experiments at the Heavy Ion Research Facility in Lanzhou (HIRFL). We have developed a gating grid driver to control the transitions between the closed and open states of the gating grid of the MATE-TPC to detect interesting rare decay events from a large amount of implanted ions. The gating grid driver is mainly composed of a digital control unit and a high-voltage switch unit. The digital control unit responds to the external trigger and generates control signals for the operation of the high-voltage control part based on the presetting instruction. The high-voltage switch unit is connected to two negative high voltages with different values and changes the voltages of neighboring wires of the gating grid based on the request for closing or opening the gate. A 500 ns switching time of the gating grid driver has been achieved from the closed to open state. The duration of the open state can be adjusted from 1 µs to 99 ms based on the experimental requirements. This gating grid driver can be used in a particle detector with a high voltage bias of up to ± 3000 V.

Background: In the era characterized by global environmental and climatic changes, understanding the effects of PM2.5 components and heatwaves on schizophrenia (SCZ) is essential for implementing environmental interventions at the population level. However, research in this area remains limited, which highlights the need for further research and effort. We aim to assess the association between exposure to PM2.5 components and hospitalizations for SCZ under different heatwave characteristics. Methods: We conducted a 16 municipalities-wide, individual exposure-based, time-stratified, case-crossover study from January 1, 2017, to December 31, 2020, encompassing 160736 hospitalizations in Anhui Province, China. Daily concentrations of PM2.5 components were obtained from the Tracking Air Pollution in China dataset. Conditional logistic regression models were used to investigate the association between PM2.5 components and hospitalizations. Additionally, restricted cubic spline models were used to identify protective thresholds of residential environment in response to environmental and climate change. Results: Our findings indicate a positive correlation between PM2.5 and its components and hospitalizations. Significantly, a 1 μg/m3 increase in black carbon (BC) was associated with the highest risk, at 1.58% (95%CI: 0.95–2.25). Exposure to heatwaves synergistically enhanced the impact of PM2.5 components on hospitalization risks, and the interaction varied with the intensity and duration of heatwaves. Under the 99th percentile heatwave events, the impact of PM2.5 and its components on hospitalizations was most pronounced, which were PM2.5 (2–4d: 4.59%, 5.09%, and 5.09%), sulfate (2–4d: 21.73%, 23.23%, and 25.25%), nitrate (2–4d: 17.51%, 16.93%, and 20.31%), ammonium (2–4d: 27.49%, 31.03%, and 32.41%), organic matter (2–4d: 32.07%, 25.42%, and 24.48%), and BC (2–4d: 259.36%, 288.21%, and 152.52%), respectively. Encouragingly, a protective effect was observed when green and blue spaces comprised more than 17.6% of the residential environment. Discussion: PM2.5 components and heatwave exposure were positively associated with an increased risk of hospitalizations, although green and blue spaces provided a mitigating effect.

Objective To investigate the correlation between long-term glycemic variability and cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods This retrospective analysis includes 222 patients hospitalized at Second Affiliated Hospital of Anhui Medical University from June 2021 to June 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). All patients were categorized into the MCI group and the non-MCI group based on their MoCA score. Long-term blood glucose fluctuations were measured using glycated hemoglobin A1c standard deviation (HbA1c-SD) and fasting plasma glucose standard deviation (FPG-SD). The study compared general clinical data, blood biochemical indicators, and glycemic variability indicators between the two groups. The differences between the groups were compared using t-test, Chi-Square Test, or Mann–Whitney U test. Kendall’s correlation analysis, multivariate logistic regression analysis and ROC curve correlation analysis were further used to analyze the correlation and diagnostic power. Results The differences in age, MoCA scores, MMSE scores, HOMA-β, HbA1c-M, HbA1c-SD, FPG-M, FPG-SD, eGFR, Smoking, GLP-1RA and SGLT-2i usage were statistically significant between the two groups (P

Abstract Background Chronic inflammatory pain (CIP) frequently coincides with depression among patients. The onset and development of pain and depression are associated with altered neural synaptic plasticity. Electroacupuncture (EA) can effectively relieve CIP and depression. However, the underlying mechanisms have not been fully illustrated. Objective To explore whether EA can relieve CIP and depression by regulating hippocampal synaptic plasticity, and the present study offers foundational evidence for the efficacy of EA in treating CIP‐related depression (CIPD). Methods Rats were divided into four groups: 0.9% normal saline group, complete Freund's adjuvant (CFA) group, CFA + duloxetine group, and CFA + EA group. Pain hypersensitivity was detected by mechanical withdrawal threshold and thermal paw withdrawal latency, and the depression level was gauged using the open field test, the sucrose preference test, and the forced swimming test. The morphology of the hippocampal neurons was observed using Nissl staining. The protein expression levels of synuclein (Syn), postsynaptic density protein‐95 (PSD‐95), brain‐derived neurotrophic factors (BDNFs), tyrosine‐protein kinase B (TrKB), p‐TrkB, cAMP response element binding protein (CREB), and p‐CREB were measured by western blotting and immunofluorescence staining. BDNF and TrkB mRNA expression were detected using quantitative real‐time polymerase chain reaction (PCR) (qRT‐PCR). The content of 5‐hydroxytryptamine (5‐HT) and γ‐aminobutyric acid (GABA) was detected using enzyme‐linked immunosorbent assay, and the glutamic acid (Glu) content was determined using the ultraviolet colorimetry method. The hippocampal neuron ultrastructure was observed using transmission electron microscopy. Results EA could alleviate CIP and related depressive behaviors as well as protect the hippocampal neuronal structure from damage and regulate 5‐HT/GABA/Glu levels in the hippocampus. Additionally, EA could significantly increase the expression of synapse‐associated proteins such as PSD‐95 and Syn by activating the BDNF/TrKB/CREB signaling pathway. Conclusion EA improves pain and depressive behaviors in CIPD rats, and the mechanism may be related to synaptic plasticity mediated by the BDNF/TrKB/CREB signaling pathway.

Abstract Background The oral bioavailability and blood–brain barrier permeability of many herbal products are too low to explain the significant efficacy fully. Gut microbiota and liver can metabolize herbal ingredients to more absorbable forms. The current study aims to evaluate the ability of a novel biotransformation-integrated network pharmacology strategy to discover the therapeutic mechanisms of low-bioavailability herbal products in neurological diseases. Methods A study on the mechanisms of Astragaloside IV (ASIV) in treating intracerebral hemorrhage (ICH) was selected as an example. Firstly, the absorbed ASIV metabolites were collected by a literature search. Next, the ADMET properties and the ICH-associated targets of ASIV and its metabolites were compared. Finally, the biotransformation-increased targets and biological processes were screened out and verified by molecular docking, molecular dynamics simulation, and cell and animal experiments. Results The metabolites (3-epi-cycloastragenol and cycloastragenol) showed higher bioavailability and blood–brain barrier permeability than ASIV. Biotransformation added the targets ASIV in ICH, including PTK2, CDC42, CSF1R, and TNF. The increased targets were primarily enriched in microglia and involved in cell migration, proliferation, and inflammation. The computer simulations revealed that 3-epi-cycloastragenol bound CSF1R and cycloastragenol bound PTK2 and CDC42 stably. The In vivo and in vitro studies confirmed that the ASIV-derived metabolites suppressed CDC42 and CSF1R expression and inhibited microglia migration, proliferation, and TNF-α secretion. Conclusion ASIV inhibits post-ICH microglia/macrophage proliferation and migration, probably through its transformed products to bind CDC42, PTK2, and CSF1R. The integrated strategy can be used to discover novel mechanisms of herbal products or traditional Chinses medicine in treating diseases. Graphical Abstract

Background: The Global Registry of Acute Coronary Events (GRACE) score is a powerful tool used to predict in-hospital mortality after acute myocardial infarction (AMI) and does not include a glycometabolism-related index. We investigated whether the addition of the stress hyperglycemia ratio (SHR) provides incremental prognostic value in addition to the GRACE score. Methods: A retrospective cohort of 613 AMI patients was enrolled in the present analyses. The patients were stratified according to the primary endpoint (in-hospital mortality) and the tertiles of the SHR. Results: During hospitalization, 40 patients reached the primary endpoint, which was more frequently observed in patients with a higher SHR. The SHR, but not admission blood glucose (ABG), adjusted for the GRACE score independently predicted in-hospital mortality [odds ratio 2.5861; 95% confidence interval (CI), 1.3910–4.8080; P = 0.0027]. The adjustment of the GRACE score by the SHR improved the predictive ability for in-hospital death (an increase in the C-statistic value from 0.787 to 0.814; net reclassification improvement, 0.6717, 95% CI 0.3665–0.977, P

Abstract Aim The triglyceride–glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown. Methods A total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score. Results After adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020–3.6786, P 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups. Conclusions A higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.

The aim of this study is to explore the mechanism of IL-17A infection in the development of bacterial mastitis in dairy cows. In this study, RT-qPCR and ELISA were used to measure the promoting effect of IL-17A on the generation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (IL-8). In addition, Western blot (WB) was applied to measure the influences of IL-17A on the inflammation-related ERK and p38 proteins in the MAPK pathways. The results show that under the stimulation of LPS on cow mammary epithelial cells (CMECs), cytokines IL-1β, IL-6, IL-8, TNF-α, and IL-17A will exhibit significantly increased expression levels (p < 0.05). With inhibited endogenous expression of IL-17A, cytokines IL-1β, IL-6, IL-8, and TNF-α will present reduced genetic expression (p < 0.01), with reduced phosphorylation levels of ERK and p38 proteins in the MAPK signaling pathways (p < 0.001). Upon the exogenous addition of the IL-17A cytokine, the genetic expression of cytokines IL-1β, IL-6, IL-8, and TNF-α will increase (p < 0.05), with increased phosphorylation levels of the ERK and p38 proteins in the MAPK signaling pathways (p < 0.001). These results indicate that under the stimulation of CMECs with LPS, IL-17A can be expressed together with relevant inflammatory cytokines. Meanwhile, the inflammatory responses of mammary epithelial cells are directly proportional to the expression levels of IL-17A inhibited alone or exogenously added. In summary, this study shows that IL-17A could be used as an important indicator for assessing the bacterial infections of mammary glands, indicating that IL-17A could be regarded as one potential therapeutic target for mastitis.

BackgroundFibrinogen is a potential risk factor for the prognosis of CAD and is associated with the complexity of CAD. There is limited research specifically investigating the predictive role of fibrinogen in determining the severity of CAD among patients with T2DM, as well as its impact on the prognosis following PCI.MethodsThe study included 675 T2DM patients who underwent PCI at the Third People’s Hospital of Chengdu between April 27, 2018, and February 5, 2021, with 540 of them remaining after exclusions. The complexity of CAD was assessed using the SYNTAX score. The primary endpoint of the study was the incidence of MACCEs.ResultsAfter adjusting for multiple confounding factors, fibrinogen remained a significant independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 1.184, 95% CI 1.022-1.373, P = 0.025). Additionally, a dose-response relationship between fibrinogen and the risk of complicated CAD was observed (SYNTAX score > 22; nonlinear P = 0.0043). The area under the receiver operating characteristic curve(AUROC) of fibrinogen for predicting mid/high SYNTAX score was 0.610 (95% CI 0.567–0.651, P = 0.0002). The high fibrinogen group (fibrinogen > 3.79 g/L) had a higher incidence of calcified lesions and an elevated trend of more multivessel disease and chronic total occlusion. A total of 116 patients (21.5%) experienced MACCEs during the median follow-up time of 18.5 months. After adjustment, multivariate Cox regression analysis confirmed that fibrinogen (HR, 1.138; 95% CI 1.010-1.284, P = 0.034) remained a significant independent risk factor for MACCEs. The AUROC of fibrinogen for predicting MACCEs was 0.609 (95% CI 0.566-0.650, P = 0.0002). Individuals with high fibrinogen levels (fibrinogen > 4.28 g/L) had a higher incidence of acute myocardial infarction (P < 0.001), MACCEs (P < 0.001), all-cause death (P < 0.001), stroke (P = 0.030), and cardiac death (P = 0.002). Kaplan-Meier analysis revealed a higher incidence of MACCEs in the high fibrinogen group (Log-Rank test: P < 0.001).ConclusionsElevated fibrinogen levels were associated with increased coronary anatomical complexity (as quantified by the SYNTAX score) and a higher incidence of MACCEs after PCI in patients with T2DM.

The large-scale production of human pluripotent stem cells (hPSCs), including both embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), shows potential for advancing the translational realization of hPSC technology. Among multiple cell culture methods, suspension culture, also known as three-dimensional (3D) culture, stands out as a promising method to fulfill the large-scale production requirements. Under this 3D culture condition, cell expansion and the preservation of pluripotency and identity during long-term culture heavily relies on the culture medium. However, the xenogeneic supplements in culture medium remains an obstacle for the translation of cell and gene therapy applications from bench to bedside. Here, we tested human platelet lysate (hPL), a xeno-free and serum-free biological material, as a supplement in the 3D culture of hPSCs. We observed reduced intercellular variability and enhanced proliferation in both hESC and hiPSC lines. These cells, after extended culture in the hPL-supplemented system, maintained pluripotency marker expression, the capacity to differentiate into cells of all three germ layers, and normal karyotype, confirming the practicability and safety of hPL supplementation. Furthermore, through RNA-sequencing analysis, we found an upregulation of genes associated with cell cycle regulations in hPL-treated cells, consistent with the improved cellular division efficiency. Taken together, our findings underscore the potential of hPL as a xeno-free and serum-free supplement for the large-scale production of hPSCs, which holds promise for advancing clinical applications of these cells.

Abstract Background Central sensitization is one of the important mechanisms underlying neuropathic and radicular pain due to cervical spondylotic radiculopathy (CSR). Recent studies have shown that the calmodulin‐dependent protein kinase II (CaMKII)/cAMP‐response element binding protein (CREB)/brain‐derived neurotrophic factor (BDNF) signaling pathway mediates central sensitization through its involvement in spinal cord synaptic plasticity. Our group has previously found that electroacupuncture (EA) has a good analgesic effect on CSR. However, the central analgesic mechanism of EA for CSR is not yet clear. Methods The rats were randomly divided into Blank group, Sham‐operated group, CSR group, and EA group. We prepared the CSR rat model using the fish wire extrusion method. The behavioral and mechanical pain thresholds of the rats in each group were measured 5 days after successful modeling and 7 days after the intervention. The first intervention was started 5 days after successful modeling, and the EA group was treated by acupuncture at the bilateral LI4 and LR3 points on the same side as one group, connected to a G6805‐I electroacupuncture apparatus with continuous waves at 1.5 Hz. The remaining groups were not subjected to EA intervention. The treatment was administered once a day for 7 consecutive days and then executed. We used WB, immunofluorescence, and qRT‐PCR to detect the expression of CaMKII/CREB/BDNF signaling pathway‐related factors in the synaptic of rat spinal cord in each group. Results EA improved pain threshold and motor function in CSR rats, inhibited the expression of BDNF, P‐TrkB, CAMKII, and P‐CREB in spinal cord synapses, reduced the expression of pain factor c‐fos and postsynaptic membrane protein molecule neuroligin2, exerted a modulating effect on spinal cord synaptic plasticity in CSR rats, and suppressed the overactive synaptic efficacy. Conclusion EA mediates central sensitization and exerts analgesic effects on CSR by modulating spinal synaptic plasticity, which may be related to the inhibition of CaMKII/CREB/BDNF signaling pathway.

Background: Epidemiological studies show that outdoor artificial light at night (ALAN) is linked to metabolic hazards, but its association with metabolic syndrome (MetS) remains unclear. We aimed to investigate the association of outdoor ALAN with MetS in middle-aged and elderly Chinese. Methods: From 2017–2020, we conducted a cross-sectional study in a total of 109,452 participants living in ten cities of eastern China. MetS was defined by fasting blood glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), blood pressure (BP), and waist circumference (WC). In 2021, we followed up 4395 participants without MetS at the baseline. Each participant's five-year average exposure to outdoor ALAN, as well as their exposure to green space type, were measured through matching to their address. Generalized linear models were used to assess the associations of outdoor ALAN with MetS. Stratified analyses were performed by sex, age, region, physical activity, and exposure to green space. Results: In the cross-sectional study, compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratios (ORs) of MetS were 1.156 [95 % confidence interval (CI): 1.111–1.203] and 1.073 (95 %CI: 1.021–1.128) respectively in the third and fourth quantiles (Q3, Q4) of outdoor ALAN exposure. The follow-up study found that, compared to the first quantile (Q1) of outdoor ALAN exposure, the OR of MetS in Q4 of ALAN exposure was 1.204 (95 %CI: 1.019–1.422). Adverse associations of ALAN with MetS components, including high FG, high TG, and obesity, were also found. Greater associations of ALAN with MetS were found in males, the elderly, urban residents, those with low frequency of physical activity, and those living in areas with low levels of grass cover and tree cover. Conclusions: Outdoor ALAN exposure is associated with an increased MetS risk, especially in males, the elderly, urban residents, those lacking physical activity, and those living in lower levels of grass cover and tree cover.

Introduction Heatwave is a major global health concern. Many countries including China suffered a record-breaking heatwave during the summer of 2022, which may have a significant effect on population health or health information-seeking behaviours but is yet to be examined.Methods We derived health information-seeking data from the Baidu search engine (similar to Google search engine). The data included city-specific daily search queries (also referred to Baidu Search Index) for heat-sensitive diseases from 2021 to 2022, including heatstroke, hospital visits, cardiovascular diseases and diabetes, respiratory diseases, mental health and urological diseases. For each city, the record-breaking heatwave days in 2022 were matched to days in the same calendar month in 2021.Results The 2022 record-breaking heatwave hit most cities (83.64%) in Mainland China. The average heatwave duration was 13 days and the maximum temperature was 3.60°C higher than that in 2021 (p

Objective To evaluate the reliability and validity of the Chinese version of the Children's Depression Inventory (CDI) in Chongqing primary school students aged 6~13 years, and analyze their depression situation. Methods Cluster sampling was used to conduct psychological assessment on 30 088 students aged 6~13 years from 56 primary schools in an urban area of Chongqing during December 2020 and January 2021. Cronbach's α coefficient, Pearson correlation analysis, exploratory factor analysis and confirmatory factor analysis were used to test the reliability and validity of CDI. ANOVA test and t test were used to analyze the depression of students. Results ① The reliability analysis showed that the total internal consistency coefficient of CDI was 0.830, the α coefficient of each subscale was 0.488~0.752, and the partial correlation coefficient was 0.867. In the validity analysis, content validity showed that, except for item 26, the correlation coefficients between the other items and the total score were ≥0.349, with statistical significance (P < 0.01). The structural validity showed that the five-factor model fitted well after modification. ② The total score of depression was 10.97±7.86, and that of the boys was 10.66±7.56, which was significantly lower than that of the girls (11.29±8.16, P < 0.001). According to their age and sex, the overall depression of primary school students presented a three-stage distribution, and the age of 10 years was the demarcation point of the difference between the boys and girls. Conclusion The CDI scale has good reliability and validity in Chongqing primary school students aged 6~13 years, but some contents still need to be modified. Depression situation differs from different age and gender.

Abstract Background The Global Registry of Acute Coronary Events (GRACE) score derived from clinical parameters at the time of hospital discharge is a powerful predictor of long-term mortality and reinfarction after acute coronary syndrome (ACS). The triglyceride glucose (TyG) index, which is a simple and reliable surrogate marker of insulin resistance, has been demonstrated to be an independent predictor of long-term adverse major adverse cardiac events, irrespective of diabetes mellitus. We investigate whether the addition of the TyG index improves the predictive ability of the GRACE score after percutaneous coronary intervention (PCI) in ACS patients regardless of diabetes mellitus. Method A retrospective cohort of 986 ACS patients undergoing PCI was enrolled in the present analyses. The GRACE score for discharge to 6 months and the TyG index were calculated. The primary endpoint was the composite of MACEs, including all-cause death and nonfatal myocardial infarction. Patients were stratified according to the primary endpoint and the tertiles of the TyG index. Cumulative curves were calculated using the Kaplan–Meier method. Multivariate Cox regression was adopted to identify predictors of MACEs. The predictive value of the GRACE score alone and combined with the TyG index or fasting blood glucose (FBG) was estimated by the area under the receiver‑operating characteristic curve, likelihood ratio test, Akaike’s information criteria, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Internal validation was assessed using the means of bootstrap method with 1000 bootstrapped samples. Results During a median follow-up of 30.72 months ((interquartile range, 26.13 to 35.07 months), 90 patients developed MACEs, more frequently in the patients with a higher TyG index. Multivariate Cox hazards regression analysis found that the TyG index, but not FBG was an independent predictor of MACEs (hazard ratio 1.6542; 95% CI 1.1555–2.3681; P = 0.006) in all types of ACS regardless of diabetes mellitus when included in the same model as GRACE score. Furthermore, Kaplan–Meier analysis revealed that the incidence of the primary endpoint rose with increasing TyG index tertiles (log-rank, P

Abstract Endothelial dysfunction is common in patients with chronic kidney disease (CKD), but the mechanism is unknown. In this study, we found that the circulating ANRIL level was increased and correlated with vascular endothelial dysfunction in patients with CKD, also negatively correlated with plasma brain-derived neurotrophic factor (BDNF) concentration. We constructed the ANRIL knockout mice model, and found that ANRIL deficiency reversed the abnormal expression of BDNF, along with endothelial nitric oxide synthase (eNOS), vascular adhesion molecule 1 (VCAM-1) and Von Willebrand factor (vWF). Meanwhile, mitochondrial dynamics-related proteins, Dynamin-related protein 1 (Drp1) and mitofusins (Mfn2) level were also recovered. In addition, in vitro, serum derived from CKD patients and uremia toxins induced abnormal expression of ANRIL. By making use of the gain- and loss-of-function approaches, we observed that ANRIL mediated endothelial dysfunction through BDNF downregulation. To explore the specific mechanism, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) were used to explore the binding of ANRIL to histone methyltransferase Enhancer of zeste homolog 2 (EZH2). Further experiments found increased EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) levels at the BDNF promoter region. Collectively, we demonstrated that ANRIL mediate BDNF transcriptional suppression through recruitment of EZH2 to the BDNF promoter region, then regulated the proteins expression related to endothelial function and mitochondrial dynamics. This study provides new insights for the study of endothelial dysfunction in CKD.

Abstract Background The residual SYNTAX score (rSS), a quantitative measure of angiographic completeness of revascularization after percutaneous coronary intervention (PCI), and the triglyceride–glucose index (TyG index), a reliable surrogate marker of insulin resistance, have been regarded as independent predictors of major adverse cardiac events (MACEs) after PCI. Whether a combination of the rSS and the TyG index improves the predictive ability for MACEs in patients with type 2 diabetes mellitus (T2DM) undergoing PCI remains unknown. Methods A total of 633 consecutive patients with T2DM who underwent PCI were included in the present analyses. Patients were stratified according to the optimal cutoff point value of the TyG index, or the rSS determined by receiver‑operating characteristic (ROC) curve analysis. The primary endpoint was the composite of MACEs, including all-cause death, nonfatal myocardial infarction, and unplanned repeat revascularization. Cumulative curves were calculated using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of MACEs. The predictive value of the TyG index combined with the rSS was estimated by the area under the ROC curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results During a median follow-up of 18.83 months, 99 patients developed MACEs, more frequently in the patients with a higher TyG index or rSS. Multivariate Cox hazards regression analysis revealed that both the TyG index and rSS were independent predictors of MACEs (hazard ratio 1.8004; 95% CI 1.2603–2.5718; P = 0.0012; 1.0423; 95% CI 1.0088–1.0769; P = 0.0129, respectively). Furthermore, Kaplan–Meier analysis demonstrated that both the TyG index and the rSS were significantly associated with an increased risk of MACEs (log-rank, all P

In this paper, a novel terahertz refractive index sensor consisting of two asymmetric distributed Bragg reflectors (DBRs) attached to graphene in the cavity, is proposed. Based on finite difference time domain simulation, Tamm plasmon polariton mode excited at the interface between the DBR and the graphene is coupled with the resonance modes of the cavity, which helps to improve the sensing performance. In its reflection spectra, there are three dips with the bandwidths of 1.82, 3.95 and 3.86 GHz at 1.04 THz, 3.00 THz and 3.13 THz after simulation optimization. And the corresponding sensitivities and the figure of merit can achieve 1.02, 2.58, 3.00 THz/RIU, and 559.34, 652.15, 776.17 RIU−1, respectively. Due to its high sensing performance and simple structure, the tri-band sensor may pave the way for the research on the detection of multimodal microscale analytes.

Atherosclerosis (AS) is a multifactorial chronic disease with great harm to the health of human being, which is a basic pathogenesis of many cardiovascular diseases and ultimately threatens human life. Abnormal blood lipid level is one of the most common diagnostic indicators of AS in clinic, and lipid metabolism disorder is often observed in patients with AS. Cholesterol is an important lipid in the human body, which is of great significance for maintaining normal life activities. Generally, cholesterol is transported to peripheral tissues by low-density lipoprotein (LDL), and then transported to the liver by high-density lipoprotein (HDL) via its cholesterol reverse transport function, and finally discharged. Under oxidative stress condition, LDL is commonly oxidized to the form ox-LDL, which is ingested by macrophages in large quantities and further forms foam cells, disrupting the normal metabolic process of cholesterol. Importantly, the foam cells are involved in forming atherosclerotic plaques, whose rupture may lead to ischemic heart disease or stroke. Furthermore, ox-LDL could also promote the development of AS by damaging vascular endothelium, promoting the migration and proliferation of smooth muscle cells, and activating platelets. Therefore, inhibiting LDL oxidation may be an effective way to improve lipid metabolism and prevent AS. In recent years, increasing studies have shown that herbal medicines have great potentiality in inhibiting LDL oxidation and reducing ox-LDL induced foam cell formation. Accordingly, this paper summarized current research on the inhibitory effects of herbal medicines against LDL oxidation and foam cell formation, and made a brief description of the role of cholesterol and LDL in lipid metabolism disorder and AS pathogenesis. Importantly, it is suggested that herbal medicines could inhibit LDL oxidation and regulate cholesterol homeostasis via downregulation of CD36 and SR-A, whereas upregulation of ABCA1 and ABCG1.

BackgroundStrengthening and maintaining the intrinsic capacity (IC) of the older adults is the key to preventing and delaying disability and promoting healthy aging.ObjectiveThis study explores the relationship between social isolation, perceived stress, health promotion behavior, and IC of the left-behind older adults in rural areas and analyzes the chain mediating effect of perceived stress and health promotion behavior among social isolation and IC.MethodsFrom March 2021 to May 2022, a multi-stage sampling method was used to recruit participants from rural areas in Heilongjiang Province, China. The data were collected by the simplified version of the Lubben Social Network Scale, the Chinese Perceived Stress Scale, the Health-Promoting Lifestyle Profile-Chinese, and the Integrated Care for Older People (ICOPE) screening tool. We used the PROCESS macro for SPSS to determine the mediating effect of perceived stress and health-promoting behavior between social isolation and IC.ResultSocial isolation score was positively correlated with health-promoting behavior (r = 0.78, p < 0.01) and IC (r = 0.67, p < 0.01), whereas it was negatively correlated with perceived stress (r = −0.63, p < 0.01). Perceived stress was negatively correlated with health-promoting behavior (r = −0.62, p < 0.01) and IC (r = −0.43, p < 0.01). The health-promoting behavior and IC were positively correlated (r = 0.56, p < 0.01). Bootstrapping values indicated that the chain-mediating effect of perceived stress and health-promoting behavior was statistically significant.ConclusionConsequently, to improve the IC of the left-behind older adults, we should focus more on reducing the degree of social isolation of the left-behind older adults and improving their perceived stress and health-promoting behavior.

Abstract Background To establish the digital diagnostic templates by cluster analysis based on a set of cephalometric films and evaluate the outcome of the different treatment methods in the patients affiliated to the same cephalometric morphology template (CMT). These templates could be used for the automatic diagnosis of dentofacial deformities and prediction of treatment outcomes in the future. Methods In this study, we assessed the coordinates of 60 different landmarks on the cephalograms of 2249 patients (14.35 ± 4.99 years, range from 7 to 62) with dentofacial deformities. The cephalometric data were subjected to dentist for clustering without a priori pattern definitions to generate biologically informative CMTs. Three templates were selected to evaluate the treatment outcome of patients affiliated to the same CMT. Results The cluster analysis yielded 21 distinct groups. The total discriminant accuracy was 89.1%, while the cross-validation accuracy was 85.0%, showing that the clusters were robust. All CMTs were automatically created and drawn using a computer, based on the average coordinates of each cluster. Individuals affiliated to the same CMT showed similar dentofacial features. We also evaluated differences in the outcomes of patients affiliated to the same CMT. Conclusions Our results demonstrated the utility of clustering methods for grouping dentofacial deformities with similar dentofacial features. Clustering methods can be used to evaluate the differences in the outcomes of patients affiliated to the same CMT, which has good clinical application value.

Abstract Background Current findings on the impact of weather conditions on osteoarthritis (OA) and rheumatoid arthritis (RA) are sparse and not conclusive. This study aimed to investigate the relationship between temperature change and OA/RA admission. Methods Daily OA/RA admission, meteorological data and pollutants from 1 January 2014 to 31 December 2017 in Hefei, China, were collected. We quantified the relationship between ambient temperature and OA/RA admission using a distributed lag nonlinear model (DLNM). Stratified analyses by gender and age were also examined. Results Temperature decrease was significantly associated with RA admission (25th percentile of temperature versus 50th percentile of temperature), with the acute and largest effect at current days lag (RR: 1.057, 95%CI: 1.005–1.111). However, no significant association between temperature and OA admission was observed. When conducting subgroup analyses by individual characteristics, we found that females and patients aged 41–65 years were more vulnerable to temperature decrease than males, patients aged 0–40 and ≧66 years, respectively. Conclusions This study suggested that temperature decrease was a risk factor for increases in RA admission. Females and patients aged 41–65 years were particularly vulnerable to the effect of temperature decrease.

Background: More studies focus on reporting the effects of ambient air pollution on physical activity while ignoring the hazards of indoor air pollution caused by household solid fuel use. Moreover, the impact of individual cognitive and depressive status on the health effects of air pollution is often overlooked. Objective: We examined the association between household solid fuel and activities of daily living (ADL) trajectories, and further examined this association in homogeneous subgroups of cognitive or depressive trajectories. Methods: Participants were from the China Health and Retirement Longitudinal Study, which conducted four waves of surveys from 2011 to 2018. We collected information on participants' household fuel use, then the ADL, cognitive and depressive performances were assessed in each wave. The latent growth mixture model (LGMM) was used to identify the optimal trajectory class for ADL, cognition, and depression. Then, the multinomial logistic regression was used to assess the association between solid fuel use and ADL trajectories in total population, as well as subgroups with different cognitive or depression trajectories. Furthermore, we examined the association between switching household fuel types and ADL trajectories across the four-wave survey. Results: The study sample included 7052 participants. We identified three ADL trajectory classes in total population: “Low-stable”, “Moderate-anterior rise”, and “Moderate-posterior rise”. The multinomial logistic regression results showed that solid fuel use was associated with elevated odds for the adverse ADL trajectories, and this association was still shown in homogeneous subgroups of cognitive or depressive trajectories, while some effects were less significant. In addition, the risk of adverse ADL trajectories generally increases with the times of solid fuel use across the four-wave survey. Conclusions: For middle and older adults in China, household solid fuel use was not conducive to physical activity development, which inspires that a further transformation to cleaner fuels is an important intervention.

Summary: Background: A growing number of studies have reported an increased risk of cardiovascular disease (CVD) and respiratory disease (RD) within hours after exposure to ambient air pollution or temperature. We assemble published evidence on the sub-daily associations of CVD and RD with ambient air pollution and temperature. Methods: Databases of PubMed and Web of Science were searched for original case-crossover and time-series designs of English articles examining the intra-day effects of ambient air pollution [particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5), ≤10 μm (PM10), 2.5–10μm (PM10-2.5), and < 7 μm (SPM), O3, SO2, NO2, CO, and NO] and temperatures (heat and cold) on cardiorespiratory diseases within 24 h after exposure in the general population by comparing with exposure at different exposure levels or periods. Meta-analyses were conducted to pool excess risks (ERs, absolute percentage increase in risk) of CVD and RD morbidities associated with an increase of 10 μg/m3 in particulate matters, 0.1 ppm in CO, and 10 ppb in other gaseous pollutants. Findings: Final analysis included thirty-three papers from North America, Europe, Oceania, and Asia. Meta-analysis found an increased risk of total CVD morbidity within 3 h after exposure to PM2.5 [ER%: 2.65% (95% CI: 1.00% to 4.34%)], PM10-2.5 [0.31% (0.02% to 0.59%)], O3 [1.42% (0.14% to 2.73%)], and CO [0.41% (0.01% to 0.81%)]. The risk of total RD morbidity elevated at lag 7–12 h after exposure to PM2.5 [0.69% (0.14% to 1.24%)] and PM10 [0.38% (0.02% to 0.73%)] and at lag 12–24 h after exposure to SO2 [2.68% (0.94% to 4.44%)]. Cause-specific CVD analysis observed an increased risk of myocardial infarction morbidity within 6 h after exposure to PM2.5, PM10, and NO2, and an increased risk of out-of-hospital cardiac arrest morbidity within 12 h after exposure to CO. Risk of total CVD also increased within 24 h after exposure to heat. Interpretation: This study supports a sudden risk increase of cardiorespiratory diseases within a few hours after exposure to air pollution or heat, and some acute and highly lethal diseases such as myocardial infarction and cardiac arrest could be affected within a shorter time. Funding: The National Natural Science Foundation of China (Grant No. 42105165; 81773518), the High-level Scientific Research Foundation of Anhui Medical University (Grant No. 0305044201), and the Discipline Construction of Anhui Medical University (Grant No. 0301001836).

Background: Growing studies suggest that air pollution exposure is an emerging driver for neurological diseases, but existing evidence on the association between air pollution and epilepsy is scarce. Here, we aimed to quantitatively estimated the short-term effects of various air pollutants on childhood epilepsy hospitalizations in China. Methods: We obtained daily electronic health records on childhood epilepsy hospitalizations and air pollutants (PM2.5, PM10-2.5, PM10, SO2, NO2, O3) from 2016 through 2018 in 10 cities of Anhui Province in China. In the first stage, a space–time-stratified case-crossover analysis was employed to evaluate the short-term association of childhood epilepsy hospitalizations with each air pollutant in Anhui Province. In the second stage, short-term effect of air pollution on childhood epilepsy morbidity reported in Anhui Province and in previous studies was pooled with a random-effect meta-analysis model to get the overall effect of different air pollutants in eastern China. Results: This study included 8,181 childhood epilepsy patients from 10 cities in Anhui province of China. The first stage case-crossover analysis in Anhui province found significant associations between higher concentrations of all air pollutants (except O3) and increased risk of childhood epilepsy hospitalizations. Each 10 μg/m3 increase in PM2.5, PM10-2.5, PM10, SO2, and NO2 concentrations was associated with an increase of 1.1 % [95 % confidence interval (CI): 0.1 %-2.1 %], 1.7 % (95 %CI: 0.5 %-2.9 %), 0.8 % (95 %CI: 0.1 %-1.4 %), 8.5 % (95 %CI: 1.5 %-16.0 %), and 4.3 % (95 %CI: 2.3 %-6.3 %) in epilepsy hospitalizations, respectively. We also observed greater effects of particulate matter in cold season. The second stage meta-analysis that additionally included two prior studies with 43,002 patients from other 11 cities found a marginally significant increase in childhood epilepsy attacks associated with PM2.5, PM10, and NO2 in eastern China. Conclusions: Short-term exposure to both particulate matter and gaseous air pollution was associated with an increased risk of childhood epilepsy exacerbation in eastern China. Our findings suggest that air pollution exposure especially in cold season needs to be considered by children’s parents or guardians to prevent epilepsy attacks.

Although exposure to fine particulate matter (PM2.5) has been associated with cognitive decline, little is known about which PM2.5 constituents are more harmful. Recent study on the association between PM2.5 and sleep quality prompted us to propose that sleep quality may mediate the adverse effects of PM2.5 components on cognitive decline. Understanding the association between PM2.5 constituents and cognitive function, as well as the mediating role of sleep quality provides a future intervention target for improving cognitive function. Using data involving 1834 participants from a multicenter cross-sectional study in nine cities of the Beijing-Tianjin-Hebei (BTH) region in China, we undertook multivariable linear regression analyses to quantify the association of annual moving-average PM2.5 and its chemical constituents with cognitive function and to assess the modifying role of exposure characteristic in this association. Besides, we examined the extent to which this association of PM2.5 constituents with cognitive function was mediated via sleep quality by a mediation analysis. We observed significantly negative associations between an increase of one interquartile range increase in PM2.5 [−0.876 (95 % CI: −1.205, −0.548)], organic carbon [−0.481 (95 % CI: −0.744, −0.219)], potassium [−0.344 (95 % CI: −0.530, −0.157)], iron [−0.468 (95 % CI: −0.646, −0.291)], and ammonium ion [−0.125 (95 % CI: −0.197, −0.052)] and cognitive decline. However, we didn’t find any individual components more harmful than PM2.5. Poor sleep quality partially mediated the estimated associations, which were explained ranging from 2.28 % to 11.99 %. Stratification analyses showed that people living in areas with lower greenspace were more susceptible to specific PM2.5 components. Our study suggests that the adverse effect of suffering from PM2.5 components is more pronounced among individuals with poor sleep quality, amplifying environmental inequalities in health. Besides reducing environmental pollution, improving sleep quality may be another measure worth considering to improve cognition if our research is confirmed in the future.

A real-time digital time-stamp sorting algorithm used in the In-Beam positron emission tomography (In-Beam PET) is presented. The algorithm is operated in the field programmable gate array (FPGA) and a small amount of registers, MUX and memory cells are used. It is developed for sorting the data of annihilation event from front-end circuits, so as to identify the coincidence events efficiently in a large amount of data. In the In-Beam PET, each annihilation event is detected by the detector array and digitized by the analog to digital converter (ADC) in Data Acquisition Unit (DAQU), with a resolution of 14 bits and sampling rate of 50 MS/s. Test and preliminary operation have been implemented, it can perform a sorting operation under the event count rate up to 1 MHz per channel, and support four channels in total, count rate up to 4 MHz. The performance of this algorithm has been verified by pulse generator and 22Na radiation source, which can sort the events with chaotic order into chronological order completely. The application of this algorithm provides not only an efficient solution for selection of coincidence events, but also a design of electronic circuit with a small-scale structure.

Background The school entry vaccination record check strategy (SECS) is an appropriate opportunity to recommend vaccines for students to improve vaccination coverage (VC). However, it is only utilized for providing necessary catch-up vaccination for students who are missing the Expanded Program on Immunization (EPI) vaccines in China. We aimed to address that gap and quantify the relationship between the SECS policy and the increase of coverage in varicella vaccine (VarV). Methods We employed a pretest and posttest quasi-experimental design to examine the effect of the upgraded SECS policy on the change of VarV coverage in newly enrolled students in Lu’an, 2019–2020. Results Eight hundred participants were randomly divided into the control group (C group, 31.8%), the telephone-based intervention group (T group, 31.2%), and the written notification intervention group (W group, 37.0%). Totally, 84 students received VarV during the study period, with a VC of 10.5%. The possibility of vaccination in the T group (RR = 4.9, 95% CI:2.2–10.9) and W group (RR = 5.2, 95% CI:2.4–11.5) was significantly higher than that in the C group (p

As a novel transition metal dichalcogenide material with high carrier mobility, adjustable band gap and excellent stability, the photocarrier ultrafast dynamics of PtSe2 films with the different thickness is researched by ultrafast transient absorption spectrum and optical pump and terahertz probe spectrum. The experimental results show that the few-layer PtSe2 films present semiconductor phase which exhibits a triple exponential decay process, while multi-layer of PtSe2 films present semi-metallic phase which exhibits a double exponential decay process. And the principle of light response and carrier dynamics of PtSe2 films after excitation is analyzed, one found that the defect state carrier recombination exists in all samples. The carrier relaxation is dominated by Auger exciton–exciton annihilation in few-layer PtSe2 film, and the defect state of multiple-layer PtSe2 film plays a dominant role in the photo carrier relaxation, which is promising to a further application in modulators and detectors for characterizing the transition from semiconductor to semi-metal by controlling its film thickness.

Cell types have been established during organogenesis based on early mouse embryos. However, our understanding of cell types and molecular mechanisms in the early embryo development of Mongolian sheep has been hampered. This study presents the first comprehensive single-cell transcriptomic characterization at E16 in Ujumqin sheep and Hulunbuir short-tailed sheep. Thirteen major cell types were identified at E16 in Ujumqin sheep, and eight major cell types were identified at E16 in Hulunbuir short-tailed sheep. Function enrichment analysis showed that several pathways were significantly enriched in the TGF-beta signaling pathway, the Hippo signaling pathway, the platelet activation pathway, the riboflavin metabolism pathway, the Wnt signaling pathway, regulation of the actin cytoskeleton, and the insulin signaling pathway in the notochord cluster. Glutathione metabolism, glyoxylate, and dicarboxylate metabolism, the citrate cycle, thyroid hormone synthesis, pyruvate metabolism, cysteine and methionine metabolism, thermogenesis, and the VEGF signaling pathway were significantly enriched in the spinal cord cluster. Steroid biosynthesis, riboflavin metabolism, the cell cycle, the Hippo signaling pathway, the Hedgehog signaling pathway, the FoxO signaling pathway, the JAK-STAT signaling pathway, and the Wnt signaling pathway were significantly enriched in the paraxial mesoderm cluster. The notochord cluster, spinal cord cluster, and paraxial mesoderm cluster were found to be highly associated with tail development. Pseudo-time analysis demonstrated that the mesenchyme can translate to the notochord in Ujumqin sheep. Molecular assays revealed that the Hippo signaling pathway was enriched in Ujumqin sheep. This comprehensive single-cell map revealed previously unrecognized signaling pathways that will further our understanding of the mechanism of short-tailed sheep formation.

Background: As a classical biomarker associated with hypertension, the prognostic value of homocysteine (Hcy) in the intermediate-term outcome of acute coronary syndrome (ACS) remains controversial. This study aimed to investigate the role of homocysteine in ACS patients with different blood pressure statuses. Methods: A total of 1288 ACS patients from 11 general hospitals in Chengdu, China, from June 2015 to December 2019 were consecutively included in this observational study. The primary endpoint was defined as all-cause death. Secondary endpoints included cardiac death, nonfatal myocardial infarction (MI), unplanned revascularization and nonfatal stroke. The patients in the hypertension group (n = 788) were further stratified into hyperhomocysteinemia (H-Hcy, n = 245) and normal homocysteinaemia subgroups (N-Hcy, n = 543) around the cut-off value of 16.81 µmol/L. Similarly, the nonhypertensive patients were stratified into H-Hcy (n = 200) and N-Hcy subgroups (n = 300) around the optimal cut-off value of 14.00 µmol/L. The outcomes were compared between groups. Results: The median follow-up duration was 18 months. During this period, 78 (6.05%) deaths were recorded. Kaplan‒Meier curves illustrated that H-Hcy had a lower survival probability than N-Hcy in both hypertension and nonhypertension groups (p < 0.01). Multivariate Cox regression analysis revealed that H-Hcy was a predictor of intermediate-term mortality in ACS, regardless of blood pressure status. Conclusions: Elevated Hcy levels predict intermediate-term all-cause mortality in ACS regardless of blood pressure status. This association could be conducive to risk stratification of ACS. Clinical Trial Registration: The study was registered in the Chinese Clinical Trials Registry in China (ChiCTR1900025138).

BackgroundThere are few studies reported on the acceptance of heterologous booster vaccination for the COVID-19 vaccine among healthcare workers (HCWs) and the general population. We aimed to address that gap and explore determinant factors of acceptance of the heterologous booster vaccination.MethodsWe conducted a cross-sectional study to examine the prevalence and determinant factors of the acceptance of heterologous booster vaccination for the COVID-19 vaccine among HCWs and the targeted population.ResultsA total of 364 HCWs and 1,898 targeted populations were investigated in our study. 76.4% HCWs would recommend heterologous booster vaccination to their patients and 59.8% targeted population endorsed a clear willingness to receive this strategy. Compared with the adenoviral vector vaccine (AD5-nCOV), recombinant protein vaccine (ZF2001) was more preferred by HCWs (79.1%) and the targeted population (72.0%) as a heterologous booster vaccine. HCWs who did not work in the vaccination clinics were more likely to recommend heterologous booster vaccination (OR = 3.3, CI: 1.5–7.3). The targeted population aged 18–59 years (OR = 1.5, 95% CI:1.1–2.3), had a positive attitude toward COVID-19 vaccination (OR = 3.8, 95% CI: 1.7–8.6), had confidence in the safety of COVID-19 vaccines (OR = 6.6, 95% CI: 4.2–10.2), followed the recommendation of HCWs (OR = 33.6, 95% CI: 22.0–51.2), took initiative in collecting booster shots information (OR = 2.1, 95% CI: 1.5–3.0), and were familiar with the heterologous strategy (OR = 1.9, 95% CI: 1.1–3.1) were more likely to choose heterologous booster vaccination. The history of side effects of inactivated COVID-19 vaccine was a negative factor in choosing heterologous booster vaccination (OR = 0.4, 95% CI: 0.4–1.0).ConclusionsThe heterologous booster vaccination strategy on the COVID-19 vaccine could be widely accepted among HCWs, whereas its acceptance among targeted population was only moderate. Public authorities should make efforts to communicate the public about the effectiveness and safety of the heterologous booster vaccination which could help increase their willingness to get vaccinated.

Background: Evidence suggests that particulate matter (PM) with smaller particle sizes (such as PM1, PM with an aerodynamic diameter≤1 µm) may have more toxic health effects. However, the short-term association between PM1 and asthma mortality remains largely unknown. Objective: This study aimed to examine the short-term effects of PM1 and PM2.5 on asthma mortality, as well as to investigate how neighborhood characteristics modified this association. Methods: Daily data on asthma mortality were collected from 13 cities in Jiangsu Province, China, between 2016 and 2017. A time-stratified case-crossover design was attempted to examine the short-term effects of PM1 and PM2.5 on asthma mortality. Individual exposure levels of PM1 and PM2.5 on case and control days were determined based on individual’s residential addresses. Stratified analyses by neighborhood characteristics (including green space, tree canopy, blue space, population density, nighttime light and street connectivity) were conducted to identify vulnerable living environments. Results: Mean daily concentrations of PM1 and PM2.5 on case days were 33.8 μg/m3 and 54.3 μg/m3. Each 10 μg/m3 increase in three-day-averaged (lag02) PM1 and PM2.5 concentrations were associated with an increase of 6.66% (95%CI:1.18%,12.44%) and 2.39% (95%CI: 0.05%−4.78%) asthma mortality, respectively. Concentration-response curves showed a consistent increase in daily asthma mortality with increasing PM1 and PM2.5 concentrations. Subgroup analyses indicated that the effect of PM1 appeared to be evident in neighborhood characteristics with high green space, low urbanization level and poor street connectivity. Conclusion: This study suggested an association between short-term PM1 and PM2.5 exposures and asthma mortality. Several neighborhood characteristics (such as green space and physical supportive environment) that could modify the effect of PM1 on asthma mortality should be further explored.

Since the hydraulic axial piston pump is the engine that drives hydraulic transmission systems, it is widely utilized in aerospace, marine equipment, civil engineering, and mechanical engineering. Operating safely and dependably is crucial, and failure poses a major risk. Hydraulic axial piston pump malfunctions are characterized by internal concealment, challenging self-adaptive feature extraction, and blatant timing of fault signals. By completely integrating the time-frequency feature conversion capability of synchrosqueezing wavelet transform (SWT), the feature extraction capability of VGG11, as well as the feature memory capability of the long short-term memory (LSTM) model, a novel intelligent fault identification method is proposed in this paper. First, the status data are transformed into two dimensions in terms of time and frequency by using SWT. Second, the depth features of the time–frequency map are obtained and dimensionality reduction is carried out by using the deep feature mining capability of VGG11. Third, LSTM is added to provide the damage identification model for long-term memory capabilities. The Softmax layer is utilized for the intelligent evaluation of various damage patterns and health state. The proposed method is utilized to identify and diagnose five typical states, including normal state, swash plate wear, sliding slipper wear, loose slipper, and center spring failure, based on the externally observed vibration signals of a hydraulic axial piston pump. The results indicate that the average test accuracy for five typical state signals reaches 99.43%, the standard deviation is 0.0011, and the average test duration is 2.675 s. The integrated model exhibits improved all-around performance when compared to LSTM, LeNet-5, AlexNet, VGG11, and other typical models. The proposed method is validated to be efficient and accurate for the intelligent identification of common defects of hydraulic axial piston pumps.