Objective: Intrathyroid thymic carcinoma（ITTC） is a rare thyroid tumor that lacks typical clinical manifestations and imaging features, making preoperative diagnosis challenging.The primary treatment for ITTC is radical surgery; however, the effectiveness of adjuvant radiotherapy and chemotherapy post-surgery is not well-established. This paper presents a case of ITTC , analyzing the clinical data and correlating it with the literature to explore the clinical manifestations, diagnostic approach, treatment, and prognosis of ITTC.
Humans ; Prognosis ; Thymoma ; Thymus Neoplasms/diagnosis* ; Thyroid Neoplasms/pathology*

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

OBJECTIVE: To evaluate the prognosis of septic right ventricular dysfunction (SRVD) based on bedside ultrasound and explore its risk factors. METHODS: A prospective observational study was conducted involving septic and septic shock patients admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from February 2021 to January 2022. Tricuspid annular plane systolic excursion (TAPSE) was measured by M-mode ultrasound within 24 hours after ICU admission. According to the results of TAPSE, the subjects were divided into SRVD group (TAPSE < 16 mm) and non-SRVD group (TAPSE ≥ 16 mm). The gender, age, occurrence of septic shock, underlying diseases, source of patients, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, maximal body temperature within 24 hours after ICU admission, location and number of infections, duration of mechanical ventilation, and 28-day mortality were collected. Hemodynamic parameters, organ function indexes, oxygen therapy parameters and arterial blood gas analysis indexes were recorded within 24 hours after ICU admission. The differences of the above indexes between the two groups were compared. Binary multivariate Logistic regression analysis was used to screen out the independent risk factors for SRVD, and a nomogram of SRVD risk factors was drawn. RESULTS: 116 patients with sepsis and septic shock were enrolled, of which 24 (20.7%) had SRVD and 92 (79.3%) had no SRVD. Compared with the non-SRVD group, the patients in the SRVD group had higher emergency transfer and infection site ≥ 2 ratio, APACHE II score, SOFA score, higher cardiac troponin I (cTnI), myoglobin (Mb), MB isoenzyme of creatine kinase (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum creatinine (SCr), arterial blood lactic acid (Lac) and lower left ventricular ejection fraction (LVEF), platelet count (PLT) within 24 hours after ICU admission, and higher proportion of norepinephrine application and continuous renal replacement therapy (CRRT). Binary multivariate Logistic regression analysis showed that LVEF [odds ratio (OR) = 0.918, 95% confidence interval (95%CI) was 0.851-0.991, P = 0.028], PLT (OR = 0.990, 95%CI was 0.981-0.999, P = 0.035), SCr (OR = 1.008, 95%CI was 1.001-1.016, P = 0.025), and the usage of norepinephrine (OR = 15.198, 95%CI was 1.541-149.907, P = 0.020) were independent risk factors for SRVD in patients with sepsis and septic shock. Based on the above four independent risk factors, a nomogram of SRVD risk factors was drawn. The results showed that the score was 64 when LVEF was 0.50, 18 when SCr was 100 μmol/L, 85 when PLT was 100×10⁹/L, and 39 when norepinephrine was used. When the total score reached 253, the risk of SRVD was 88%. Compared with non-SRVD group, the duration of mechanical ventilation in SRVD group was slightly longer [hours: 80.0 (28.5, 170.0) vs. 47.0 (10.0, 135.0), P > 0.05], and the 28-day mortality was significantly higher [41.7% (10/24) vs. 21.7% (20/92), P < 0.05]. CONCLUSIONS Patients with sepsis may have right ventricular dysfunction, impaired renal function and increased mortality in the early stage. The decrease in LVEF and PLT, the increase in SCr and the application of norepinephrine are independent risk factors for SRVD in patients with sepsis.
Humans ; Prognosis ; Ventricular Dysfunction, Right/diagnostic imaging* ; Risk Factors ; Prospective Studies ; Intensive Care Units ; Shock, Septic ; Male ; Ultrasonography ; Female ; Sepsis/complications* ; Middle Aged ; Point-of-Care Systems ; Aged ; Logistic Models ; APACHE

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Objective:To explore the effect of hyperbaric oxygen (HBO) combined with Saccharomyces boulardii in ulcerative colitis (UC) and effect of serum asymmetric dimethylarginine (ADMA). Methods:A total of 100 patients with UC admitted to the First Hospital of Yulin from August 2021 to August 2023 were prospectively selected as the study objects and divided into control group and observation group according to random number table method, with 50 cases in each group. The control group was treated with mesalazine + Saccharomyces boulardii sachets, and the observation group was treated with mesalazine + Saccharomyces boulardii sachets + HBO, and both groups were treated for 60 d. The clinical efficacy and the levels of intestinal flora, ADMA, intestinal mucosal barrier function indexes, inflammatory factors and immune function indexes before and after treatment were compared between the two groups, and the occurrence of adverse reactions were compared between the two groups. Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 74.00%(37/52) vs. 50.00%(26/52), there was statistical difference ( χ2 = 5.19, P<0.05). After treatment, the number of Enterococcus and Escherichia coli in the observation group were lower than those in the control group: (4.37 ± 0.91) lgcfu/g vs. (7.95 ± 1.32) lgcfu/g, (6.17 ± 0.92) lgcfu/g vs. (9.36 ± 1.35) lgcfu/g; and the number of Lactobacillus and Bifidobacterium were higher than those in the control group: (10.24 ± 2.57) lgcfu/g vs. (8.38 ± 1.48) lgcfu/g, (10.72 ± 3.15) lgcfu/g vs. (8.69 ± 2.64) lgcfu/g, there were statistical differences ( P<0.05). After treatment, the level of ADMA in the observation group was lower than that in control group: (0.51 ± 0.08) μmol/L vs. (0.85 ± 0.12) μmol/L; and the intestinal mucosal barrier function indexes of diamine oxidase, D-lactic acid and endotoxin were lower than those in the control group: (5.82 ± 1.13) U/L vs. (7.13 ± 1.89) U/L, (3.96 ± 0.42) mmol/L vs. (4.38 ± 0.85)mmol/L, (0.18 ± 0.02) kEU/L vs. (0.23 ± 0.04) kEU/L, there were statistical differences ( P<0.05). After treatment, the inflammatory factor C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group: (4.84 ± 0.68) mg/L vs. (7.16 ± 0.82) mg/L, (13.24 ± 1.98) ng/L vs. (17.61 ± 2.25) ng/L, (22.13 ± 4.16) μg/L vs. (29.36 ± 5.37) μg/L; and IL-10 was higher than that in the control group:(15.35 ± 2.98) ng/L vs. (11.27 ± 3.26) ng/L, there were statistical differences ( P<0.05). After treatment, the immune function indexes CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group: 0.563 ± 0.063 vs. 0.459 ± 0.052, 0.420 ± 0.049 vs. 0.383 ± 0.053, 1.35 ± 0.32 vs. 1.16 ± 0.26, there werestatistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:HBO combined with Saccharomyces boulardii can significantly improve clinical symptoms, reduce intestinal mucosal damage and improve intestinal microenvironment in UC patients.

Objective:To analyze the coordination between the growth of per capita health expenditure and per capita gross domestic product (GDP) in China from 2012 to 2021, and to explore the changes and regional disparities in the health consumption elasticity coefficient.Methods:Descriptive analysis was used to compare the average annual growth rates of per capita health expenditure and per capita GDP between 2012-2019, Pearson correlation analysis was conducted to test the relationship between the two variables. The health consumption elasticity coefficient was calculated as the ratio of the growth rates of health expenditure to GDP, and its temporal changes and regional distribution characteristics were analyzed.Results:After adjusting for price factors, the average annual growth rate of per capita health expenditure in China from 2012 to 2021 was 9.11%, higher than that of per capita GDP (6.11%), with no correlation between the two variables ( r=0.30, P>0.05). The national average health consumption elasticity coefficient was 1.49, lower than that in 2012-2019 (1.60), indicating an improvement in coordination. Compared with developed countries, China′s elasticity coefficient was at a moderate level. Conclusions:Overall, the growth of health expenditure in China remains faster than that of economic growth, with certain regional differences, but the degree of coordination has improved compared with the previous period.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective To evaluate the application value of superb microvascular imaging(SMI)in pre-dicting ovarian cancer staging.Methods One hundred and thirty-six patients with ovarian cancer who under-went surgical treatment in our hospital from March 2019 to May 2024 were enrolled.Transvaginal,transab-dominal low-frequency,and transabdominal high-frequency two-dimensional grayscale imaging,Color Doppler Flow Imaging(CDFI),and SMI were performed before surgery for staging prediction.Taking surgical-patho-logical staging as the gold standard,the sensitivity,specificity,and accuracy of the combined application of transvaginal SMI,transabdominal low-frequency SMI,and transabdominal high-frequency SMI for predicting ovarian cancer staging were calculated.The receiver operating characteristic(ROC)curve was established,the area under the ROC curve(AUC)was calculated,and the diagnostic efficacy of SMI for predicting ovarian cancer staging was determined.Results The combined application of transvaginal SMI,transabdominal low-frequency SMI,and transabdominal high-frequency SMI for predicting ovarian cancer staging showed that sen-sitivity was 89.35%,92.36%,81.65%,and 83.21%for stages Ⅰ,Ⅱ,Ⅲ,Ⅳ,respectively;specificity was 86.93%,84.29%,83.39%,and 82.88%;accuracy was 92.50%,94.38%,80.15%,and 84.96%;and AUC was 0.799,0.760,0.695,and 0.727.Conclusion SMI has a high application value in predicting the stage of ovarian cancer,especially for stage Ⅰ and stage Ⅱ ovarian cancer.

OBJECTIVE To investigate the expression of long non-coding RNA(lncRNA)HOXC13-AS in head and neck squamous cell carcinoma tissues and its effects on tumor cell proliferation and migration in head and neck tumor cell lines.METHODS Clinical samples from 26 patients with laryngeal squamous cell carcinoma and 4 patients with hypopharyngeal squamous cell carcinoma who were treated surgically in the Second Hospital of Jilin University from March 2024 to December 2024 were collected as research subjects.Head and neck squamous cell carcinoma tissue specimens and corresponding adjacent tissue specimens were selected.The expression of HOXC13-AS in 30 cases of head and neck squamous cell carcinoma tissues and corresponding adjacent tissues was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Clinical data were collected to analyze the correlation between HOXC13-AS expression and various clinical pathological factors.siRNA technology was used to interfere with the expression of HOXC13-AS in laryngeal cancer cell line TU212 and hypopharyngeal squamous cell line FaDu.Cell Counting Kit-8(CCK-8)assay was used to detect cell proliferation ability,and cell scratch assay was used to detect cell migration ability.RESULTS The expression level of lncRNA HOXC13-AS in head and neck squamous cell carcinoma tissues(12.60±11.26)was significantly higher than that in corresponding adjacent tissues(1.40±0.61),with a statistically significant difference(t=5.485,P<0.001).The expression of HOXC13-AS in head and neck squamous cell carcinoma tissues was closely related to T stage(P=0.004),lymph node metastasis(P=0.006),and clinical stage(P=0.007)of patients.CCK-8 results showed that the absorbance values of TU212 cell line groups at 24,48,and 72 h were si-NC group(0.373±0.010,0.738±0.026,1.003±0.124),si-HOXC13-AS-1 group(0.365±0.015,0.686±0.019,0.935±0.028),and si-HOXC13-AS-2 group(0.364±0.024,0.700±0.026,0.943±0.053),with statistically significant differences(F24 h=0.484,F48 h=7.893,F72 h=1.345,P<0.01);the absorbance values of FaDu cell line groups at 24,48,and 72 h were si-NC group(0.727±0.054,0.834±0.072,1.224±0.127),si-HOXC13-AS-1 group(0.532±0.005,0.650±0.079,1.021±0.044),and si-HOXC13-AS-2 group(0.647±0.088,0.687±0.025,1.074±0.055),with statistically significant differences(F24 h=16.143,F48 h=14.259,F72 h=9.409,P<0.001).Cell scratch assay showed that the migration rates of TU212 cell line groups at 12 and 24 h were si-NC group(38.971%±3.824%,69.185%±0.469%),si-HOXC13-AS-1 group(18.182%±2.580%,33.378%±2.302%),and si-HOXC13-AS-2 group(25.017%±0.288%,48.413%±0.805%),with statistically significant differences(F12 h=47.295,F24 h=471.745,P<0.0001);The migration rates of FaDu cell lines in each group at 12 and 24 hours were as follows:si-NC group(39.067%±3.196%,58.222%±0.448%),si-HOXC13-AS-1 group(13.689%±0.132%,39.358%±3.985%),and si-HOXC13-AS-2 group(23.335%±0.680%,35.526%±0.758%),with statistically significant differences(F12 h=138.1,F24 h=101.749,P<0.0001).CONCLUSION HOXC13-AS is significantly upregulated in head and neck squamous cell carcinoma tissues and cells,and is associated with the clinical pathological characteristics of patients.Silencing HOXC13-AS can significantly inhibit the proliferation and migration of head and neck tumor cells.

Objective To evaluate the effect of pneumatic logistics transport system(PTS)on the trans-portation efficiency of the transferred samples and the accuracy of the results.Methods The transportation speed,temperature and humidity change of PTS were analyzed by temperature and humidity transmitter.Anti-coagulant samples containing disodium ethylenediaminetetraacetate(EDTA-K2),sodium citrate,lithium hepa-rin and samples containing inert separation gel coagulant were selected.and used respectively for complete blood cell analysis,prothrombin time(PT),activated partial prothrombin time(APTT),troponin T(TnT)and other myocardial markers,as well as the detection of items such as glucose(Glu)and lactate dehydrogen-ase(LDH).According to the transfer mode,they were divided into the manual transfer group and the PTS transfer group,and according to the number of PTS transfers,they were divided into the one-time transfer group,the three-time transfer group and before transfer(control).The differences among each group were statistically analyzed,and 1/3 allowable total error(1/3TEa)was adopted as the criterion for determining the clinical application value.Results There was no statistically significant difference in the changes of tempera-ture and humidity during the transportation process of PTS compared with manual transportation(P＞0.05),but it was significantly faster than manual transportation in terms of transportation time(P＜0.05).Com-pared with before transfer,the differences between the PT,APTT,Glu and LDH items in the one-time trans-fer group and the three-time transfer group were statistically significant(P＜0.01),and their deviations were all much greater than 1/3TEa.However,in the plasma samples,compared with before transport,there were statistically significant differences in Glu and LDH between the one-time transfer group and the three-time transfer group(P＜0.05),but the deviations were all less than 1/3TEa.For the items of TnT,red blood cell count and hematocrit,compared with before transfer,there were statistically significant differences between some groups of the one-time transfer group and the three-time transfer group(P＜0.05),but the deviations were all less than 1/3TEa.Conclusion PTS can significantly improve the transportation efficiency of sam-ples,but it significantly affects the detection of Glu and LDH in plasma samples,which can be improved by u-sing serum sample transportation instead.In addition,PTS also affects the detection of PT and APTT,and it is not recommended to use PTS to transport coagulation specimen.