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.

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.

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.

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.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer.

AIM: To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. MATERIALS AND METHODS: A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. RESULTS: The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). DISCUSSION: Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.

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.

Severity of abdominal obesity and cardiometabolic diseases in US adults.

OBJECTIVES: To determine the prevalence of cardiometabolic diseases (CMDs) among adults with abdominal obesity and to evaluate the necessity of differentiating severity of abdominal obesity. STUDY DESIGN: Cross-sectional study and prospective cohort study. METHODS: National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2020 were included for cross-sectional analyses. Class I, II and III abdominal obesity were created by dividing waist circumference within sex-specific abdominal obesity range into tertiles. Age-standardized prevalence of CMDs was estimated and differences by severity of abdominal obesity were compared using Poisson regressions. Prospective analyses were performed using NHANES data between 1988 and 2018 with linked mortality data. Cox proportional hazards models were used to assess the association between severity of abdominal obesity and mortality. RESULTS: Among 23,168 adults included (mean age: 47.8 years, 49.3% men), 13,307 (57.4%) had abdominal obesity. Among adults with abdominal obesity, the estimated prevalence of diabetes was 17.3% (95% confidence interval: 16.3%, 18.2%), hypertension 39.3% (38.2%, 40.3%), dyslipidemia 59.5% (58.0%, 61.1%), cardiovascular disease 9.0% (8.3%, 9.8%), chronic kidney disease 16.8% (15.9%, 17.7%) and non-alcoholic fatty liver disease 39.9% (38.4%, 41.4%). The estimated prevalence was 55.5% (53.8%, 57.2%) for having ≥2 CMDs. Compared with class I abdominal obesity, class III abdominal obesity was related to a 43%-184% higher prevalence of CMDs and a 44% higher risk of all-cause mortality. CONCLUSIONS: The prevalence of CMDs was high and multimorbidity of CMDs was common among US adults with abdominal obesity. The prevalence of CMDs and risk of mortality differed significantly by severity of abdominal obesity.

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.

[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

[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.

[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.

[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.

[Clinical characteristics of posterior malleolus fracture in adults].

Objective: To explore the latest clinical characteristics and development trends of posterior malleolus fracture. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to December 2022 were reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture with a mean age of (48.7±15.6) years were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59 years. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). The number of cases according to different fracture types showed the following descending order: trimalleolar fracture-supination extorsion (335 cases, 71.0%), bimalleolar fracture (60 cases, 12.7%), trimalleolar fracture-pronation extorsion (43 cases, 9.1%), posterior malleolus+tibial shaft fracture (19 cases, 4.0%), simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi Ⅰ, Ⅱ and Ⅲ type of posterior malleolus fractures was 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji ⅡA type represented the highest number of cases (249 cases, 52.8%), followed by the ⅡB type (120 cases, 25.4%), Ⅰ type (54 cases, 11.4%), ⅢB type (36 cases, 7.6%), and ⅢA type (13 cases, 2.8%). However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions from the year of 2014 to 2022 (all P>0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination extorsion, Haraguchi Ⅰ type and Tongji ⅡA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59 years. There has been no significant change in the development trend of clinical characteristics of posterior malleolus fractures in recent years.

[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.

[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.

[Update in interstitial lung disease 2023].

The notable advances in interstitial lung disease (ILD) published in Chinese and international authoritative journals from November 2022 to October 2023 were systematically reviewed in our annual review. The year 2023 brought significant advances about mechanism, diagnosis and treatment of idiopathic pulmonary fibrosis, connective tissue diseases associated ILD, sarcoidosis, progressive pulmonary fibrosis and rare ILDs. The related global and/or Chinese commentaries and guidelines were also reviewed in our paper. We also highlighted the important findings of epidemiologic and health economic data on idiopathic pulmonary fibrosis and sarcoidosis.

[Clinical analysis of COVID-19 in patients with preexisting interstitial lung abnormalities].

Objective: To describe the clinical characteristics of SARS-CoV-2 infected patients with interstitial lung abnormalities (ILA) during the COVID-19 pandemic. Methods: We respectively enrolled ILA patients who had been regularly followed up in Peking Union Medical College Hospital for more than six months since January 2021. Clinical data of these ILA patients were collected after the outbreak of COVID-19 pandemic (from December 2022 to January 2023), thirty-eight patients with preexisting ILA were enrolled. Among them, there were 34 ILA patients (20 males and 14 females) who were infected with SARS-CoV-2 during this period, with an average age of (64.0±8.8) years old (range: 41-80). There were 12 (35.3%) ILA patients who were suffered from COVID-19(pneumonia group) and others were the non-pneumonia group. The clinical characteristics, including vaccination status, features of COVID-19 and outcomes of the two groups were compared. Results: Regarding the subcategories of ILA, there were 7 cases of subpleural fibrotic ILA, 10 cases of subpleural non-fibrotic ILA, and 17 cases of non-subpleural ILA. Before SARS-CoV-2 infection, the average pulse oxygen saturation at rest was (97.38±0.87)% (range: 96%-99%); average forced vital capacity (FVC) was (97.6±18.1)% predicted (range: 65%-132%); and average diffusion capacity for carbon monoxide (DLCO) was (76.2±16.3)% predicted (range: 53%-108%). Nineteen patients had been vaccinated with 3 doses of SARS-CoV-2 vaccines, and 5 of them developed COVID-19. One patient had received one dose of vaccine and did not develop COVID-19. The other 14 patients had not been vaccinated, and seven of them developed COVID-19. Of the 12 patients with COVID-19, six were diagnosed with severe COVID-19, and the other 6 ILA patients were diagnosed with moderate COVID-19. Among them, 1 patient was complicated by deep vein thrombosis of left lower limb. All 6 patients with severe COVID-19 who were cured after systemic corticosteroids. As for the other six moderate COVID-19 patients, all were cured and/or improved greatly: two were treated with short-term oral corticosteroids, one was prescribed a dose of compound betamethasone, and the other two were not treated with systemic corticosteroids. Conclusion: Patients with ILA were predisposed to develop COVID-19 after infection with SARS-CoV-2, and more than half of them had severe COVID-19.

[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.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Understanding primary care transformation and implications for ageing populations and health inequalities: a systematic scoping review of new models of primary health care in OECD countries and China.

BACKGROUND: Many countries have introduced reforms with the aim of primary care transformation (PCT). Common objectives include meeting service delivery challenges associated with ageing populations and health inequalities. To date, there has been little research comparing PCT internationally. Our aim was to examine PCT and new models of primary care by conducting a systematic scoping review of international literature in order to describe major policy changes including key 'components', impacts of new models of care, and barriers and facilitators to PCT implementation. METHODS: We undertook a systematic scoping review of international literature on PCT in OECD countries and China (published protocol: https://osf.io/2afym ). Ovid [MEDLINE/Embase/Global Health], CINAHL Plus, and Global Index Medicus were searched (01/01/10 to 28/08/21). Two reviewers independently screened the titles and abstracts with data extraction by a single reviewer. A narrative synthesis of findings followed. RESULTS: A total of 107 studies from 15 countries were included. The most frequently employed component of PCT was the expansion of multidisciplinary teams (MDT) (46% of studies). The most frequently measured outcome was GP views (27%), with < 20% measuring patient views or satisfaction. Only three studies evaluated the effects of PCT on ageing populations and 34 (32%) on health inequalities with ambiguous results. For the latter, PCT involving increased primary care access showed positive impacts whilst no benefits were reported for other components. Analysis of 41 studies citing barriers or facilitators to PCT implementation identified leadership, change, resources, and targets as key themes. CONCLUSIONS: Countries identified in this review have used a range of approaches to PCT with marked heterogeneity in methods of evaluation and mixed findings on impacts. Only a minority of studies described the impacts of PCT on ageing populations, health inequalities, or from the patient perspective. The facilitators and barriers identified may be useful in planning and evaluating future developments in PCT.