[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study].

Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P=0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Association between Resting Heart Rate and Machine Learning-Based Brain Age in Middle- and Older-Age.

BACKGROUND: Resting heart rate (RHR), has been related to increased risk of dementia, but the relationship between RHR and brain age is unclear. OBJECTIVE: We aimed to investigate the association of RHR with brain age and brain age gap (BAG, the difference between predicted brain age and chronological age) assessed by multimodal Magnetic Resonance Imaging (MRI) in mid- and old-aged adults. DESIGN: A longitudinal study from the UK Biobank neuroimaging project where participants underwent brain MRI scans 9+ years after baseline. SETTING: A population-based study. PARTICIPANTS: A total of 33,381 individuals (mean age 54.74 ± 7.49 years; 53.44% female). MEASUREMENTS: Baseline RHR was assessed by blood pressure monitor and categorized as <60, 60-69 (reference), 70-79, or ≥80 beats per minute (bpm). Brain age was predicted using LASSO through 1,079 phenotypes in six MRI modalities (including T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI, and resting-state fMRI). Data were analyzed using linear regression models. RESULTS: As a continuous variable, higher RHR was associated with older brain age (ß for per 1-SD increase: 0.331, 95% [95% confidence interval, CI]: 0.265, 0.398) and larger BAG (ß: 0.263, 95% CI: 0.202, 0.324). As a categorical variable, RHR 70-79 bpm and RHR ≥80 bpm were associated with older brain age (ß [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957]) and larger BAG (0.256 [0.105, 0.407] / 0.638 [0.436, 0.839]), but RHR< 60 bpm with younger brain age (-0.324 [-0.500, -0.147]) and smaller BAG (-0.230 [-0.392, -0.067]), compared to the reference group. These associations between elevated RHR and brain age were similar in both middle-aged (<60) and older (≥60) adults, whereas the association of RHR< 60 bpm with younger brain age and larger BAG was only significant among middle-aged adults. In stratification analysis, the association between RHR ≥80 bpm and older brain age was present in people with and without CVDs, while the relation of RHR 70-79 bpm to brain age present only in people with CVD. CONCLUSION: Higher RHR (>80 bpm) is associated with older brain age, even among middle-aged adults, but RHR< 60 bpm is associated with younger brain age. Greater RHR could be an indicator for accelerated brain aging.

[Spatial and temporal distribution characteristics research of esophageal cancer in China].

Objectives: To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China. Methods: The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio (LLR) and relative risk (RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results: From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions: The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Diabetes and long duration leading to speech-, low/mid-, and high- frequency hearing loss: current evidence from the China National Health Survey 2023.

PURPOSE: To examine the effect of diabetes, duration of diabetes, and blood glucose on speech-, low/mid-, and high-frequency hearing loss. METHODS: In this cross-sectional study, 2821 participants aged 20-87 years in the China National Health Survey were included. Diabetes was defined as valid fasting blood glucose (FBG) of ≥ 7.0 mmol/L, a self-reported history of diabetes or the use of anti-diabetic medications. Speech-(500, 1000, 2000, and 4000 Hz), low/mid- (500, 1000 and 2000 Hz), and high-frequency (4000, 6000, and 8000 Hz) hearing loss was defined as pure tone average of responding frequencies > 20 dB HL in the better ear, respectively. RESULTS: In fully adjusted models, for speech-, low/mid-, and high-frequency hearing loss, compared with no diabetes, those with diabetes (OR[95%CI]: 1.44 [1.12, 1.86], 1.23 [0.94, 1.61], and 1.75 [1.28, 2.41], respectively) and with diabetes for > 5 years duration (OR[95%CI]: 1.63 [1.09, 2.42], and 1.63 [1.12, 2.36], 2.15 [1.25, 3.70], respectively) were at higher risk. High FBG level was associated with a higher risk of speech-, low/ mid-, and high-frequency hearing loss. And there were stronger associations between HL and diabetes, longer duration and higher in "healthier population" (no hypertension, no dyslipidemia and younger age). CONCLUSION: Diabetes, longer duration, and higher FBG level were independently associated with hearing loss for speech-, low/mid- and high-frequency hearing loss, particularly in higher frequency and "healthier population". Paying more attention to hearing loss in those populations could lower the burden of hearing loss.

Brittle-Ductile Threshold in Lithium Disilicate under Sharp Sliding Contact.

Computer-aided design (CAD)/computer-aided manufacturing (CAM) milling and handpiece grinding are critical procedures in the fabrication and adjustment of ceramic dental restorations. However, due to the formation of microfractures, these procedures are detrimental to the strength of ceramics. This study analyzes the damage associated with current brittle-regime grinding and presents a potential remedy in the application of a safer yet still efficient grinding regime known as "ductile-regime grinding." Disc-shaped specimens of a lithium disilicate glass-ceramic material (IPS e.max CAD) were obtained by cutting and crystallizing the lithium metasilicate CAD/CAM blanks (the so-called blue blocks) following the manufacturer's instructions. The discs were then polished to a 1 µm diamond suspension finish. Single-particle micro-scratch tests (n = 10) with a conical diamond indenter were conducted to reproduce basic modes of deformation and fracture. Key parameters such as coefficient of friction and penetration depth were recorded as a function of scratch load. Further, biaxial flexure strength tests (n = 6) were performed after applying various scratch loads to analyze their effects on ceramic strength. Scanning electron microscopy (SEM) and focused ion beam (FIB) were used to characterize surface and subsurface damage. Statistical analysis was performed using one-way analysis of variance and Tukey tests. While the SEM surface analysis of scratch tracks revealed the occurrence of both ductile and brittle removal modes, it failed to accurately determine the threshold load for the brittle-ductile transition. The threshold load for brittle-ductile transition was determined to be 70 mN based on FIB subsurface damage analyses in conjunction with strength degradation studies. Below 70 mN, the specimens exhibited neither strength degradation nor the formation of subsurface cracks. Determination of the brittle-ductile thresholds is significant because it sets a foundation for future research on the feasibility of implementing ductile-regime milling/grinding protocols for fabricating damage-free ceramic dental restorations.

Molecular and transcriptomic analysis of the ovary during laying and brooding stages in Zhedong white geese (Anser cygnoides domesticus).

1. This study investigates the molecular mechanisms affecting brooding in Zhedong white geese by examining differences in reproductive endocrine levels, ovarian histology and transcriptomics.2. Twenty 18-month-old Zhedong white geese were selected to examine their ovaries using histological, biochemical, molecular biological, and high-throughput sequencing techniques during the laying and brooding periods.3. The results showed that the number of atretic follicles and apoptotic cells in the ovaries increased significantly (p < 0.05), the levels of follicle-stimulating hormone, luteinising hormone, gonadotropin-releasing hormone and oestradiol decreased significantly (p < 0.05), and the level of prolactin increased significantly (p < 0.01) during the brooding stage.4. In broody geese, the expression of CASP3, CASP9, P53, BAX, and Cyt-c were considerably higher (p < 0.05), but BCL2 expression was significantly lower (p < 0.05).5. In ovarian tissues, 260 differentially expressed lncRNAs, 13 differentially expressed miRNA and 60 differentially expressed mRNA were all discovered using transcriptome sequencing analysis. Functional enrichment analysis revealed that the differentially expressed mRNA and non-coding RNA target genes were primarily involved in ECM-receptor interaction, cell adhesion, cardiac muscle contraction, mTOR signalling, and the calcium signalling pathway.6. In conclusion, follicular atrophy and apoptosis occurred in the ovaries and serum reproductive hormone levels were significantly changed during the brooding period of Zhedong white geese. COL3A1, COL1A2, GRIA1, RNF152, miR-192, and miR-194 may be important candidates for the regulation of brooding behaviour, with the mTOR signalling pathway playing a key role.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Low Temperature Dynamic Polaron Liquid in a Manganite Exhibiting Colossal Magnetoresistance.

Polarons-fermionic charge carriers bearing a strong companion lattice deformation-exhibit a natural tendency for self-localization due to the recursive interaction between electrons and the lattice. While polarons are ubiquitous in insulators, how they evolve in transitions to metallic and superconducting states in quantum materials remains an open question. Here, we use resonant inelastic x-ray scattering to track the electron-lattice coupling in the colossal magneto-resistive bi-layer manganite La_{1.2}Sr_{1.8}Mn_{2}O_{7} across its metal-to-insulator transition. The response in the insulating high-temperature state features harmonic emissions of a dispersionless oxygen phonon at small energy transfer. Upon cooling into the metallic state, we observe a drastic redistribution of spectral weight from the region of these harmonic emissions to a broad high energy continuum. In concert with theoretical calculations, we show that this evolution implies a shift in electron-lattice coupling from static to dynamic lattice distortions that leads to a distinct polaronic ground state in the low temperature metallic phase-a dynamic polaron liquid.

[The development and future of sports medicine in China].

This article mainly introduces the development history and current situation of sports medicine in China, and deeply analyzes the problems that have emerged during the current development process, and proposes corresponding solutions. Based on this, the article proposes five key directions for the development of sports medicine, which are: developing arthroscopic minimally invasive techniques, ensuring the guarantee work for competitive sports, attaching great importance to the development of sports rehabilitation, vigorously carrying out exercise prescription and exercise assessment work, and emphasizing the training and education of sports medicine professionals. Finally, the article looks forward to the future development of sports medicine from three aspects: popularizing and expanding the influence of sports medicine through popular science promotion, improving the quality and safety of sports through health management and disease prevention, and achieving precise diagnosis and treatment through scientific research and innovation. It is hoped that this article will provide reference for the development of sports medicine in China.

[Analysis of clinical effect of arthroscopic release at different time in treating knee adhesion after arthroscopic surgery].

Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.

[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[Preoperative prediction of HER-2 expression status in breast cancer based on MRI radiomics model].

Objective: This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer. Methods: A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness. Results: The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model (P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model (P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort (P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort (P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions: T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

The top 100 most cited articles on intramedullary nail fixation from 2018-2022: a bibliometric and visualized analysis.

OBJECTIVE: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years. MATERIALS AND METHODS: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space. RESULTS: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency". CONCLUSIONS: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Dynamics of the Deformable Fluid Interface Interacting with an Approaching Solid under the Electrostatic Field.

A theoretical model was developed to describe the dynamics of a deformable fluid interface interacting with an approaching solid without contact by both the attractive electrostatic and van der Waals (i.e., vdW) interaction, analogous to the situation in the experiments by electric force microscopy (i.e., EFM) or electric-surface force apparatus (i.e., E-SFA) involved in the soft fluid interface. On the basis of this model, a numerical study of the deformation of the fluid interface, the force-vs-separation behavior, and the critical limiting conditions of contact has systematically been carried out. Our results show that the surface pressure induced by the electrostatic interaction plays a more prominent role in the deformation of the fluid interface than the vdW interaction does, and there exists a principal length scale associated with the relative strength of the electrostatic field to the surface tension, affecting the fluid interface shape under the electrostatic field. It was also shown that both the force-distance curves and the corresponding curves of fluid interface deformation peak versus distance for various electrostatic fields satisfy the universal scaling power law. Moreover, an analytical solution to the Euler-Lagrange differential equation governing the deformation of the fluid interface under the external electric field is obtained, and two extended formulas for explicitly describing the principal length scales that respectively characterize the lateral and longitudinal deformations of the fluid interface were determined.

[Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer].

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.