Machine learning framework develops neutrophil extracellular traps model for clinical outcome and immunotherapy response in lung adenocarcinoma.

Neutrophil extracellular traps (NETs) are novel inflammatory cell death in neutrophils. Emerging studies demonstrated NETs contributed to cancer progression and metastases in multiple ways. This study intends to provide a prognostic NETs signature and therapeutic target for lung adenocarcinoma (LUAD) patients. Consensus cluster analysis performed by 38 reported NET-related genes in TCGA-LUAD cohorts. Then, WGCNA network was conducted to investigate characteristics genes in clusters. Seven machine learning algorithms were assessed for training of the model, the optimal model was picked by C-index and 1-, 3-, 5-year ROC value. Then, we constructed a NETs signature to predict the overall survival of LUAD patients. Moreover, multi-omics validation was performed based on NETs signature. Finally, we constructed stable knockdown critical gene LUAD cell lines to verify biological functions of Phospholipid Scramblase 1 (PLSCR1) in vitro and in vivo. Two NETs-related clusters were identified in LUAD patients. Among them, C2 cluster was provided as "hot" tumor phenotype and exhibited a better prognosis. Then, WGCNA network identified 643 characteristic genes in C2 cluster. Then, Coxboost algorithm proved its optimal performance and provided a prognostic NETs signature. Multi-omics revealed that NETs signature was involved in an immunosuppressive microenvironment and predicted immunotherapy efficacy. In vitro and in vivo experiments demonstrated that knockdown of PLSCR1 inhibited tumor growth and EMT ability. Besides, cocultural assay indicated that the knockdown of PLSCR1 impaired the ability of neutrophils to generate NETs. Finally, tissue microarray (TMA) for LUAD patients verified the prognostic value of PLSCR1 expression. In this study, we focus on emerging hot topic NETs in LUAD. We provide a prognostic NETs signature and identify PLSCR1 with multiple roles in LUAD. This work can contribute to risk stratification and screen novel therapeutic targets for LUAD patients.

Diamond-Like Carbon: A Surface for Extreme, High-Wear Environments.

In this study, we present an in-depth characterization of a diamond-like carbon (DLC) film, using a range of techniques to understand the structure and chemistry of the film both in the interior and particularly at the DLC/air surface and DLC/liquid interface. The DLC film is found to be a combination of sp2 and sp3 carbon, with significant oxygen present at the surface. The oxygen seems to be present as OH groups, making the DLC somewhat hydrophilic. Quartz-Crystal Microbalance (QCM) isotherms and complementary neutron reflectivity data indicate significant adsorption of a model additive, bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) surfactant, onto the DLC from water solutions and indicate the adsorbed film is a bilayer. This initial study of the structure and composition of a model surfactant is intended to give a clearer insight into how DLC and additives function as antiwear systems.

Whole-volume diffusion kurtosis magnetic resonance (MR) imaging histogram analysis of non-small cell lung cancer: correlation with histopathology and degree of tumor differentiation.

AIMS: To evaluate the role of diffusion kurtosis imaging (DKI) histogram analysis in the characterization of non-small cell lung cancer (NSCLC) and to correlate DKI parameters with tumor cellularity. MATERIALS AND METHODS: Sixty-four patients with pathologically diagnosed NSCLCs were evaluated by DKI on a 3-T scanner. Regions of interest (ROIs) were drawn on the map of b1000 manually. All NSCLCs were histologically graded according to the degree of tumor differentiation. Tumor cellularity was measured by the nuclear-to-cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN), the expression of Ki-67 was detected using the streptavidin-peroxidase method. Histogram analysis was performed using voxel-based on raw data from each ROI. RESULTS: NSCLCs were classified as grades 1, 2, and 3 according to differentiation degree. Histogram parameters of apparent diffusion coefficient (ADC) and DKI could discriminate between different grades of tumors (p<0.001). Receiver operating characteristic (ROC) curve analysis showed that Kapp 75th exhibited the best performance with an AUC of 0.936 and sensitivity/specificity of 95.74%/80% (p<0.001) in distinguishing grade 1 from grade 2, ADC mean exhibited the best performance with an AUC of 0.923 and sensitivity/specificity of 92.33%/86.67% (p<0.001) in distinguishing grade 2 from 3. N/C ratio and Ki-67 changed significantly with grade (p<0.01). Negative correlations were found between the ADC mean and the N/C ratio, Ki-67, Dapp mean and N/C ratio, whereas Kapp mean and N/C ratio, Ki-67 were positively correlated. CONCLUSIONS: DKI histogram analysis could quantitatively characterize NSCLC with different grades by probing non-Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor.

Quantitative CT features on admission combined with laboratory biomarkers for predicting severe acute pancreatitis.

AIM: To assess the association of quantitative computed tomography (CT) features on admission with acute pancreatitis (AP) severity, and to explore the performance of combined CT and laboratory markers for predicting severe AP (SAP). MATERIALS AND METHODS: Data from 208 AP patients were reviewed retrospectively. Pancreas volume, the area of extrapancreatic inflammation, extrapancreatic fluid collection volume, and number were calculated based on CT images on admission. Laboratory biomarkers within 24 h of admission were collected. Interobserver agreement for CT measurements was measured by calculating interclass correlation coefficient (ICC). The associations of quantitative CT features with AP severity were evaluated. Predictive models for SAP were constructed based on CT and laboratory markers. Performances of single marker and the models were evaluated using receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). RESULTS: Pancreas volume, area of extrapancreatic inflammation, extrapancreatic fluid collection volume, and number were significantly different between severe and non-severe AP groups. In predicting SAP, the AUCs of quantitative CT indicators ranged from 0.72 to 0.79; the AUCs of laboratory biomarkers were between 0.53 and 0.66. The combined model of area of extrapancreatic inflammation, serum calcium, and haematocrit yielded an AUC of 0.84, significantly higher than that of the laboratory model, single CT, or laboratory marker. Interobserver agreements for quantitative CT indicators were excellent, with ICC ranging from 0.91 to 0.98. CONCLUSION: Quantitative CT features on admission were significantly associated with AP severity; the combination of extrapancreatic inflammation area, serum calcium, and haematocrit could be taken as a new method for predicting SAP.

Factors influencing the detection rate of fumarate peak in 1H MR spectroscopy of fumarate hydratase-deficient renal cell carcinoma at 3 T MRI.

AIM: To identify factors that may be associated with fumarate detection rate in 1H-magnetic resonance spectroscopy (MRS) in fumarate hydratase-deficient renal cell carcinoma (FH-RCC). MATERIALS AND MEHODS: Between February 2018 and March 2022, 16 FH-RCC patients with 30 lesions underwent 1H-MRS. Detection results were classified as having a detected fumarate peak (n=12), undetected peak (n=10), or technical failure (n=8). Factors including tumour size, tumour location, treatment history, and metastasis status were collected and analysed. A Bayesian logistic regression model was applied to evaluate the association between these factors and the detection result. RESULTS: Bayesian analysis demonstrated significant associations between fumarate detection results and the following factors: long-axis diameter (odds ratio [OR] of 1.64; 95% confidence interval [CI] of 1.07-2.53), short-axis diameter (OR of 1.90; 95% CI of 1.19-3.06), voxel size (OR of 2.85; 95% CI of 1.70-4.75), treatment history (OR of 0.35; 95% CI of 0.21-0.58), non-metastatic state (OR of 2.45; 95% CI of 1.48-4.06), and lymph node metastasis (OR of 0.35; 95% CI of 0.21-0.58). Technical failure results were associated with factors such as treatment history (OR of 2.59; 95% CI of 1.37-4.66), non-metastatic state (OR of 0.36; 95% CI of 0.19-0.66), and lymph node metastasis (OR of 2.61; 95% CI of 1.39-4.74). CONCLUSION: Tumour size, treatment history, and metastasis character were associated with the detection of abnormal fumarate accumulation. This finding will serve as a reference for interpreting 1H-MRS results and for selecting suitable scenarios to evaluate FH-RCC.

[Analysis of ultrasound images features and diagnostic model establishment of alveolar soft part sarcoma and intramuscular capillary-type hemangiomas].

Objective: The ultrasonography features of alveolar soft part sarcoma (ASPS) and intramuscular capillary-type hemangiomas (ICTH) were analyzed, and the diagnostic model of ASPS was established. Methods: A cross-sectional study was carried out. The clinical data of 52 patients [28 males and 24 females, aged (20.7±15.1) years] with pathologically confirmed ASPS and ICTH admitted to People's Hospital of Henan Province from January 2005 to February 2023 were included in the study. According to pathological types, the patients were divided into ASPS group and ICTH group. Clinical data of patients were retrospectively collected, and meaningful indicators in the univariate analysis were included in the regression analysis for screening. After comprehensive consideration of clinical significance and statistical significance, eligible indicators were selected for inclusion in the regression analysis. Binary logistic regression analysis was used to screen the factors that distinguished the pathological types of ASPS and ICTH, and the diagnostic model was established. The area under receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic effectiveness of the diagnostic model in distinguishing ASPS from ICTH. Results: There were 20 patients in ASPS group, 10 males and 10 females, aged (26.9±13.5) years, and 32 patients in ICTH group, 18 males and 14 females, aged (16.8±15.0) years. The age difference between the ASPS group and the ICTH group was statistically significant (P<0.05), and there were statistically significant differences in the ultrasound imaging features of "clear boundary" "peripheral lobe" "thin blood vessels inside the lesion are straight and out of shape" "intra-lesion liquification" "peripheral thick blood vessels" and "peripheral muscle fiber disruption" between the two groups (all P<0.001).Variables with clinical and statistical significance were selected as independent variables. Binary logistic regression analysis showed that peripheral muscle fiber interruption (OR=97.358, 95%CI:6.833-1 387.249) and internal thin blood vessels were flat and out of shape (OR=0.052, 95%CI:0.003-0.921) was the correlation factor to distinguish the pathological types of ASPS and ICTH. Two ultrasonic image features of "peripheral muscle fiber interruption" and "internal thin blood vessels are straight and out of shape" were used to establish the diagnostic model. The sensitivity of "peripheral muscle fiber interruption" diagnostic model was 81.3%, and the specificity was 95.0%. The AUC was 0.811(95%CI: 0.761-0.954). The sensitivity, specificity and AUC of the diagnosis model of "internal thin vessels with flat misshape" were 90.0%, 96.9% and 0.934(95%CI: 0.830-0.984). The sensitivity, specificity and AUC of the combined diagnosis model of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" were 96.9%, 90.0% and 0.974(95%CI:0.877-0.999). Conclusion: Ultrasonography can be used to distinguish ASPS from ICTH, and the combined diagnostic model based on the two ultrasonic imaging features of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" can further improve the diagnostic efficiency.

[Mid-term efficacy evaluation of ABO incompatible living relative kidney transplantation based on protocol biopsy].

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.

[Observation of the consistency between intellectualized and manual-based cognitive assessment tools in the outpatient clinic].

Objective: The intellectualized versions of the Montreal Cognitive Assessment Scale (MoCA) and the Mini-mental State Examination (MMSE) (i-MoCA/i-MMSE) were developed. The validity of this system was evaluated in a clinical sample through comparing with the manual-based assessments. Methods: A total of 88 patients [aged (66.82±11.37) years, 30 males and 58 females] were enrolled in the outpatient clinic of Xuanwu Hospital of Capital Medical University with complaints of cognitive decline, from February to October 2023. All participants completed manual-based and intellectualized assessments in a randomized order, with an interval of 2 weeks to control for the practice effect. The reliability of the intellectualized version of assessments was evaluated based on the manual-based version using the Concordance correlation coefficient (CCC). The difference between the intellectualized and the manual-based assessments was tested by the Repeated ANCOVA with demographic information controlled. The accuracy of evaluation of the i-MoCA and i-MMSE was analyzed by the Receiver Operating Characteristic (ROC) analysis. Results: High concordance was observed between the intellectualized version and the manual-based assessments (CCCMoCA=0.87, CCCMMSE=0.83). Controlling for basic demographic information, there was no significant difference in the scores of the intellectualized version and the manual-based assessments (all P>0.05). The accuracy of i-MoCA in screening patients with cognitive impairment was 94.3% (sensitivity=94.6%, specificity=78.1%), while the accuracy of i-MMSE in screening patients with cognitive impairment was 94.9% (sensitivity=94.9%, specificity=77.6%). In addition, the majority of subdomains measured by the cognitive assessments exhibited high consistency across the intellectualized the manual-based versions (CCCMoCA=0.32-0.78; CCCMMSE=0.54-0.79). Conclusion: Both the i-MoCA and i-MMSE showed high consistency and diagnostic accuracy with the manual-based versions in terms of overall cognitive function and subdomains.

[Association between CD4+T lymphocyte and body composition with physical frailty among elderly HIV-infected patients in Chongqing City].

Objective: To identify the association between CD4+T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods: From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition. Results: The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×107 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [OR (95%CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [OR (95%CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group (Pinteraction<0.05). Conclusion: The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

[Clinicopathological characteristics of angioimmunoblastic T-cell lymphoma with B-cell proliferation or neoplasms].

Objective: To investigate the clinical, pathological and immunophenotypic features, and differential diagnosis of angioimmunoblastic T-cell lymphoma (AITL) with B-cell proliferation or neoplasms. Methods: Eight qualified cases were collected from the Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China from January 2019 to July 2023. One case was diagnosed with AITL and diffuse large B-cell lymphoma (DLBCL) and the other seven cases were diagnosed with AITL and B-cell proliferation. Clinical characteristics and pathological morphology were summarized. Immunohistochemical analysis, fluorescence in situ hybridization and gene rearrangement detection were performed. Results: The patients' average age was 58 years. Five of them were male. Biopsies of the enlarged cervical lymph nodes showed structural destruction and exhibited various histologic patterns. Some cases revealed Burkitt-like morphology, a moderate tumor volume and slightly irregular nuclei. Some cases showed prominent nucleoli. High endothelial venules and expanded follicular dendritic cells were detected. Tumor cells derived from T-follicular helper (TFH) cells were positive for two or more TFH biomarkers. Nodular or diffuse patchy proliferation of B cells was noted around the tumor tissue, which was initially considered as B-cell lymphoma. All of the 8 cases showed monoclonal rearrangements of the T-cell receptor genes while 5 of them also showed clonal rearrangements of the Ig genes. Seven of the 8 cases were subject to the detection of C-MYC gene breakage and were all negative. EBV-positive cells were seen in 6 cases. Neoplastic B cells were positive for C-MYC (>40%), while proliferative B cells were negative for C-MYC (<40%). Conclusions: The histological morphology of AITL with B-cell proliferation or lymphoma may be different from AITL. An integrated analysis, incorporating clinical, morphologic, immunophenotypic, and molecular assessment, helps reach an accurate diagnosis. This group of cases demonstrated the clinical and pathological characteristics of AITL accompanied by B-cell proliferation and B-cell lymphoma. The findings suggest that C-MYC maybe a feasible indicator for distinguishing B-cell proliferation from B-cell lymphoma, and provide a simple and feasible immunohistochemical marker for the diagnosis and research of composite lymphoma.

[Radiological assessment of interstitial lung disease: what can lung ultrasound do?]

The use of lung ultrasound in the screening, diagnosis, and evaluation of interstitial lung disease has been relatively well studied, but has not been widely accepted and applied in clinical practice. There are also some differences in the examination methods applied in these studies. This paper summarized the application, advantages, and disadvantages of lung ultrasound in the diagnosis and follow-up of interstitial lung disease by comprehensively reviewing the examination methods, research results and progress of new technologies of lung ultrasound in interstitial lung disease.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[The development and innovation of clinical nutrition].

The strategy of nutrition therapy in the treatment of diseases is constantly optimized with the development and innovation of the concept and technology in the field of clinical nutrition, especially the rise of multi-disciplines such as imaging omics and artificial intelligence and the latest discoveries of clinical trials. Precise nutrition assessment, diversified products, multimodal nutrition therapy throughout the process and intelligent compliance management have efficiently improved the effect of nutrition therapy. The implementation of personalized and precise nutrition therapy still needs further investigation.

[Differential analysis of aqueous humor metabolomics between presenile cataract and senile cataract].

Objective: To explore the differences in metabolites and metabolic pathways in the aqueous humor between patients with presenile cataracts and senile cataracts. Methods: This metabolomic study was conducted at Tianjin Medical University Eye Hospital from August 2020 to September 2022. Eight patients with presenile cataracts (8 eyes) and 8 patients with senile cataracts (9 eyes) were included. Data were collected, including age, gender, preoperative uncorrected visual acuity, intraocular pressure, lens dysfunction index, and axial length. Aqueous humor and anterior capsule tissue samples were obtained during cataract surgery. Metabolites in the aqueous humor were detected using Liquid Chromatography-Mass Spectrometry in a non-targeted approach. The principal component analysis, differential analysis, clustering analysis, and correlation analysis were performed to identify differentially expressed metabolites. These metabolites were ranked based on the fold change (FC). The receiver operating characteristic (ROC) curve analysis and metabolic enrichment analysis were used to identify differential pathways and potential biomarkers for presenile cataracts. Immunohistochemistry was conducted on anterior capsule tissues, and pyruvate levels were measured by colorimetry to validate metabolomic results. Results: Patients with presenile cataracts included 7 males and 1 female, with a mean age of (37.50±4.90) years. Patients with senile cataracts were 7 males and 1 female, with a mean age of (73.44±5.22) years. Except for age, there were no significant differences in baseline data (P>0.05). A total of 347 differential metabolites were identified, 10 of which were potential biomarkers for presenile cataract according to the ROC curve analysis (all P<0.05), including propoxycaine (log2FC=7.26), 2-methyl-2, 3, 4, 5-tetrahydro-1, 5-benzodiazepine-4-ketone (log2FC=6.35), l-pyroglutamic acid (log2FC=-1.72), leanly-proline (log2FC=-0.77), and choline (log2FC=-0.56) in the positive ion mode, and N-phenylacetyl glutamine (log2FC=-1.84), pyruvate (log2FC=1.07), ascorbic acid (log2FC=0.92), pseudouracil nucleoside (log2FC=-0.68), and palmitic acid (log2FC=-0.51) in the negative ion mode. The metabolic enrichment analysis identified 72 differential pathways (32 cationic and 40 anionic), with significant differences in glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle (P<0.05). The experimental validation showed reduced lactate dehydrogenase and increased pyruvate levels in patients with presenile cataracts (P<0.05). Conclusions: Pyruvate and nine other metabolites may serve as potential biomarkers for presenile cataracts. Pathways involving glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle are notably dysregulated in patients with presenile cataracts.

[Correlation between serum growth differentiation factor 11 level and severity of coronary artery disease in patients with acute myocardial infarction].

Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

Identification of novel characteristic biomarkers and immune infiltration profile for the anaplastic thyroid cancer via machine learning algorithms.

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and lethal malignant cancer. In recent years, the application of molecular-driven targeted therapy and immunotherapy has markedly improved the prognosis of ATC. This study aimed to identify characteristic genes for ATC diagnosis and revealed the role of ATC characteristic genes in drug sensitivity and immune cell infiltration. METHODS: We downloaded ATC RNA-sequencing data from the GEO database. Following the combination and normalization of the dataset, we first divided the combined datasets into the training cohort and the validation cohort. We identified differentially expressed genes (DEGs) in ATC by differential expression analysis in the training cohort. We used two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) to identify ATC characteristic genes. The CIBERSORT algorithm was performed to calculate the abundance of various immune cells in ATC. Finally, we validated the expression of ATC characteristic genes by quantitative RT-PCR (RT-qPCR) in ATC cell lines and immunohistochemistry (IHC). RESULTS: A total of 425 DEGs were identified in the training cohort, including 240 upregulated genes and 185 downregulated genes. Four ATC characteristic genes (ADM, PXDN, MMP1, and TFF3) were identified, and their diagnostic value was validated in the validation cohort (AUC in ROC analysis > 0.75). We established a practical gene expression-based nomogram to accurately predict the probability of ATC. We also found that ATC characteristic biomarkers are associated with the tumor immune microenvironment and drug sensitivity. CONCLUSION: ADM, PXDN, MMP1, and TFF3 might serve as potential ATC diagnostic biomarkers and may be helpful for ATC molecular targeted therapy and immunotherapy.

[The safety and efficacy of prophylactic hyperthermic intraperitoneal chemotherapy for elderly patients with locally advanced gastric cancer: a propensity score matching analysis].

Objective: To evaluate the safety and efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) on elderly patients diagnosed with locally advanced gastric cancer based on a propensity score matching analysis. Methods: Clinical data of elderly patients with locally advanced gastric cancer who underwent radical gastrectomy in Beijing Hospital from January 2017 to December 2021 were retrospectively collected. According to whether HIPEC was used, the patients were divided into HIPEC group (radical gastrectomy combined with HIPEC) and control group (radical gastrectomy alone), and 29 patients in HIPEC group and 122 patients in control group. After 1∶1 matching of PSM, there were 28 patients in each group. The clinicopathological data, surgical data, postoperative recovery and long-term survival of the two groups were compared and analyzed. Results: Before PSM, the mean age in the HIPEC group was (70.7±4.0) years, and in the control group was (73.1±5.8) years (P=0.011). After PSM, the mean age in the HIPEC group was (70.9±3.9) years, and it was (71.8±5.4) years in the control group (P=0.739). Before PSM, the incidence of postoperative complications was 20.7% (6 cases) in the HIPEC group and 26.2% (32 cases) in the control group (P=0.639). After PSM, the incidence of postoperative complications was 21.4% (6 cases) in the HIPEC group and 14.3% (4 cases) in the control group (P=0.730). Before PSM, the mean duration of hospitalization after radical gastrectomy was (13.6±7.6) days in HIPEC group and (16.2±13.0) days in control group, respectively (P=0.312). After PSM, the mean duration of hospitalization after radical gastrectomy was (13.7±7.8) days in HIPEC group and (15.4±9.7) days in control group, respectively (P=0.479). Before PSM, the 1-and 3-year overall survival rates of the HIPEC group were 88.2% and 69.7%, and 88.0% and 66.1% for control group, respectively, with no statistical difference between the two groups in overall survival (P=0.499). After PSM, the 1-and 3-year overall survival rates of the HIPEC group were 86.8% and 69.7%, and 93.1% and 67.5% for control group, respectively, with no statistical difference between the two groups in overall survival (P=0.425). Before PSM, the 1-and 3-year disease-free survival rates of the HIPEC group were 88.2% and 67.1%, and 87.8% and 64.3% for control group, respectively, with no statistical difference between the two groups in disease-free survival (P=0.863). After PSM, the 1-and 3-year disease-free survival rates of the HIPEC group were 88.2% and 62.8%, and 93.7% and 64.7% for control group, respectively, with no statistical difference between the two groups in disease-free survival (P=0.804). Conclusions: Radical surgery combined with HIPEC for elderly patients with gastric cancer does not increase postoperative complications and postoperative recovery time. However, there was no significant difference in overall survival and disease-specific survival between the two groups.

[Analysis of prognosis and related factors in oldest-old patients with left-side or right-side colon cancer after hemicolectomy].

Objective: This study aimed to explore the difference of prognosis in oldest-old colon cancer patients between the left-side and right-side hemicolectomy. Methods: A total of 238 oldest-old (≥75 years old) colon cancer patients who received surgical treatment in Gastrointestinal Surgery Department of Beijing Hospital from December 2010 to December 2020 were retrospectively collected. They were divided into right-side hemicolectomy (RCC) group (130 cases) and left-side hemicolectomy (LCC) group (108 cases) by surgical methods. The difference in postoperative short-term complications and long-term prognosis was compared between the two groups, and the related factors of postoperative death was analyzed using multivariate Cox regression model. Results: The age of 238 oldest-old patients with colon cancer ranged from 75 to 93 years old (80.5±3.7). There were 128 males and 110 females. The ages of patients in the LCC group and RCC group were (80.4±3.7) and (80.6±3.7) years old (P=0.699), respectively. There was no significant difference in gender, body mass index (BMI) and co-existing chronic diseases between two groups (P>0.05). The proportion of the duration of surgery exceeding 170 min in the LCC group was significantly higher than that in the RCC group (56.5% vs 43.1%, P=0.039). The incidence of postoperative short-term complications in RCC group was slightly higher than LCC group (P>0.05), and there was no significant difference in overall survival (OS), tumor-specific survival (CSS) and disease-free survival (DFS) between two groups. However, the two groups had different prognostic risk factors, pathological Ⅳ stage (HR=28.970,95%CI:1.768-474.813,P=0.018), intraoperative bleeding (HR=2.297,95%CI:1.351-3.907,P=0.002) and cancer nodules (HR=2.044,95%CI:1.047-3.989,P=0.036) were independent prognostic risk factors in LCC group. Underweight (HR=0.428,95%CI:0.192-0.955,P=0.038), overweight(HR=0.316,95%CI:0.125-0.800,P=0.015),obesity (HR=0.211,95%CI:0.067-0.658,P=0.007), lymph node metastasis (HR=2.682,95%CI:1.497-4.807,P=0.001), tumor nodule (HR=2.507,95%CI:1.301-4.831,P=0.027) and postoperative length of stay of 9 days (HR=1.829,95%CI:1.070-3.128,P=0.006) were independent risk factors for poor prognosis in RCC group. Conclusions: The duration of surgery of oldest-old colon cancer patients in the LCC group was longer than that in the RCC group. However, there was no significant difference in the incidence of postoperative complications between the two groups. High pathological stage, more intraoperative bleeding and cancer nodules were independent prognostic risk factors in the LCC group. Abnormal BMI, lymph node metastasis, cancer nodules and postoperative length of stay were independent risk factors for poor prognosis in the RCC group.

[Progress of lung organoids in lung epithelial repair and regenerative medicine].

The mechanical barrier of lung is made up of epithelial cells which participate in gas exchange. Some of these cells have stem cell potential and are known as lung epithelial stem cells. They play an important role in maintaining lung homeostasis and repairing injured epithelial cells. Organoids are derived from pluripotent stem cells or adult stem cells cultured in a three-dimensional manner in vitro. Their structure and function are very similar to original tissues or organs. They can also self-renew, proliferate, and differentiate. Lung organoids can simulate the structure and function of epithelial cells in vitro. They provide an ideal model for the study of lung epithelial stem cells, which repair epithelial cells in vitro. Meanwhile, they provide an ideal graft for regenerative medicine. Around the lung organoids, this review concludes the mechanisms involved in lung epithelial stem cells repairing epithelial cells, summarizes their applications in regenerative medicine, and provides related reference for the therapy of lung diseases.

[Progress on health-related quality of life and its influencing factors in patients with tuberculosis sequelae].

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.