ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective To analyze the current status of dietary quality in patients with chronic atrophic gastritis (CAG), and to explore the influencing factors of dietary quality. Methods A retrospective study was conducted on 550 patients with CAG admitted to the hospital from April 2021 to April 2024. Self-made basic data questionnaire, dietary balance index (DBI), and hospital anxiety and depression scale-anxiety subscale (HADS-A) were used for investigation. Multivariate linear regression analysis was applied to analyze the influencing factors of DBI-lower bound score (LBS). Results The average score of DBI-LBS in 550 patients with CAG was (31.45±8.53) points. There were significant differences in DBI-LBS scores among CAG patients in terms of age, body mass index (BMI), Helicobacter pylori (HP) infection, marital status, drinking history, smoking history, CAG severity, HADS-A score and concurrent gastrointestinal diseases (P<0.05). Multivariate linear regression analysis of the above influencing factors indicated that BMI, smoking history, HADS-A score and CAG severity were independent influencing factors of DBI-LBS score in CAG patients (P<0.05). Conclusion The general dietary quality is not optimistic in CAG patients, showing a moderate deficiency in dietary intake. BMI, disease severity and psychological status of patients are independent factors affecting dietary quality.

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective:This study aims to develop a rapid identification technique for various genotypes of extended-spectrum β-lactamase (ESBL) producing Escherichia coli using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) in conjunction with machine learning algorithms. Methods:A total of 158 Escherichia coli strains were isolated from the clinical laboratory of the First Hospital of Jilin University from August 2018 to December 2022. Polymerase chain reaction (PCR) was employed to detect the CTX-M-1, CTX-M-8, CTX-M-9, and SHV genes. Mass spectral data of the bacterial strains were acquired by MALDI-TOF MS with a cooperative matrix of (E)-propyl α-cyano-4-hydroxycinnamate (CHCA-C3). Models based on random forest (RF), logistic regression (LR), and support vector machine (SVM) algorithms were constructed. The performance of the constructed models was evaluated using metrics including accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Mass spectral peaks exhibiting sensitivity and specificity exceeding 80% in the models were designated as characteristic peaks. To validate the efficacy of the cooperative matrix of CHCA-C3, clinical isolates of ESBL-producing Escherichia coli were analyzed by MALDI-TOF MS using the conventional CHCA matrix for comparative purposes. Results:Among the 158 strains of Escherichia coli, 91 strains produced ESBL, all of which were CTX-M genotype. The AUC values for the respective models were as follows: CTX-M-1 genotype exhibited AUC values of 0.98 for LR, 1.00 for RF, and 0.73 for SVM; CTX-M-9 genotype exhibited AUC values of 0.93 for LR, 0.99 for RF, and 0.76 for SVM; for CTX-M-8, all models achieved an AUC of 1.00, indicating excellent classification performance with respect to accuracy, specificity, and sensitivity. The characteristic mass spectral peaks associated with each genotype included: CTX-M-1 genotype at m/z 6 390; CTX-M-8 genotype at m/z 5 224, m/z 5 393, and m/z 9 021; CTX-M-9 genotype at m/z 5 161 and m/z 5 273. In the MALDI-TOF MS analysis conducted with the conventional CHCA matrix, the characteristic peak at m/z 9 021 for CTX-M-8 was the only one detected, with the characteristic peaks for CTX-M-1 and CTX-M-9 remaining undetected. Conclusion:The application of cooperative matrix of CHCA-C3 in conjunction with MALDI-TOF MS and machine learning algorithms facilitates the rapid and precise identification of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. This approach offers a feasible solution for evidence-based clinical therapy and the control of healthcare-associated infections.

Objective To systematically analyze the changes in clinical indicators including blood leukocytes and neutrophils,liver and kidney functions,coagulation function,lipids,and levels of thyroid hormones and antibodies in Graves'ophthalmopathy(GO)patients who had undergone effective treatment with tocilizumab(TCZ)and to explore their clinical significance.Methods Eighty-five patients with moderately or severely active GO who were effectively treated with TCZ were enrolled.Early morning fasting blood was collected and tested for routine blood,biochemical routine,coagulation function,thyroid hormone and antibodies,and basic information such as gender,age,duration of the disease,history of smoking,comorbidities,and medications were also collected from all patients,so changes in the clinical indicators before and after the treatment could be analyzed and correlation analyses could be carried out.Results Patients with moderately to severely active GO treated with TCZ showed a significant decrease in absolute blood leukocyte and neutrophil values compared with before,and a significant decrease in liver function(alanine transaminase,aspartate aminotransferase,creatinine),cholesterol(total cholesterol,high-density lipoprotein and low-density lipoprotein)levels were significantly higher than before,and concentrations of coagulation parameters[prothrombin time,activated partial thromboplastin time,fibrinogen(FIB)and D-dimer]were significantly decreased.The concentrations of thyroid hormone and thyroid-stimulating hormone levels increased significantly,and the antibody titer of thyrotropin receptor antibody(TRAB)was significantly down-regulated after treatment.TRAB levels were significantly correlated with FIB before treatment.Conclusion Thyroid function and antibody levels improved after TCZ treatment in patients with moderately to severely active GO,but blood leukocytes,liver function and coagulation function changed significantly compared with before.The results of this study confirm the therapeutic effect of TCZ on immune disorders in GO ophthalmopathy,while underscoring the importance of monitoring potential adverse effects in clinical treatment.

Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.