Objective To explore the clinical value of artificial intelligence (AI) quantitative parameters in distinguishing pathological grades of stageⅠ invasive adenocarcinoma (IAC). Methods Clinical data of patients with clinical stageⅠ IAC admitted to Yantaishan Hospital Affiliated to Binzhou Medical University from October 2018 to May 2023 were retrospectively analyzed. Based on the 2021 WHO pathological grading criteria for lung adenocarcinoma, IAC was divided into gradeⅠ, grade Ⅱ, and grade Ⅲ. The differences in parameters among the groups were compared, and logistic regression analysis was used to evaluate the predictive efficacy of AI quantitative parameters for grade Ⅲ IAC patients. Parameters were screened using least absolute shrinkage and selection operator (LASSO) regression analysis. Three machine learning models were constructed based on these parameters to predict grade Ⅲ IAC and were internally validated to assess their efficacy. Nomograms were used for visualization. Results A total of 261 IAC patients were included, including 101 males and 160 females, with an average age of 27-88 (61.96±9.17) years. Six patients had dual primary lesions, and different lesions from the same patient were analyzed as independent samples. There were 48 patients of gradeⅠ IAC, 89 patients of grade Ⅱ IAC, and 130 patients of grade Ⅲ IAC. There were statitical differences in the AI quantitive parameters such as consolidation/tumor ratio (CTR), ect among the three goups. (P<0.05). Univariate analysis showed that the differences in all variables except age were statistically significant (P<0.05) between the group gradeⅠ+grade Ⅱand the group grade Ⅲ . Multivariate analysis suggested that CTR and CT standard deviation were independent risk factors for identifying grade Ⅲ IAC, and the two were negatively correlated. Grade Ⅲ IAC exhibited advanced TNM staging, more pathological high-risk factors, higher lymph node metastasis rate, and higher proportion of advanced structure. CTR was positively correlated with the proportion of advanced structures in all patients. This correlation was also observed in grade Ⅲ but not in gradeⅠand grade ⅡIAC. CTR and CT median value were selected by using LASSO regression. Logistic regression, random forest, and XGBoost models were constructed and validated, among which, the XGBoost model demonstrated the best predictive performance. Conclusion Cautious consideration should be given to grade Ⅲ IAC when CTR is higher than 39.48% and CT standard deviation is less than 122.75 HU. The XGBoost model based on combined CTR and CT median value has good predictive efficacy for grade Ⅲ IAC, aiding clinicians in making personalized clinical decisions.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

Objective:To discuss the feasibility of offering specialized courses of critical care medicine in undergraduate clinical medicine education, so as to alleviate the shortage of critical care medicine staffs and lay a foundation for improving the success rate for the treatment of critical cases.Methods:The undergraduates majoring in clinical medicine from 2008 to 2011 in Guizhou Medical University (the former Guiyang Medical College) were enrolled. After they had been enrolled in the undergraduate education for 3 years and were ready for Grade four, which meant basic medicine teaching had been completed and clinical medicine teaching was about to start, they were introduced and preached to each discipline, including critical care medicine. The undergraduates were free to choose professional direction of clinical training in Grade four. Students majoring in clinical medicine from 2012 to 2014 were free to choose their major direction when they entered the school.Results:From September 2011 to July 2019, the university had cultivated 246 undergraduates majoring in clinical critical care medicine from 2008 to 2014, and the critical care medicine professional team of affiliated hospital had undertaken 540 teaching hours. By July 2019, all students had graduated on time, with an employment rate of 100%. Forty students took postgraduate programs in our school and other schools, accounting for 16.3%.Conclusions:Professional education of critical care medicine in the undergraduate course of clinical medicine can mobilize students' interest in learning and subjective initiative, which is conducive to career selection. During the clinical training, the students can identify and timely cure critical care cases in the early stage, and partly alleviate the current shortage of critical care medical staffs.

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.
3T3 Cells ; Adenylate Kinase ; Adipocytes ; metabolism ; Animals ; Down-Regulation ; Fibroblast Growth Factors ; metabolism ; Leptin ; metabolism ; MAP Kinase Signaling System ; Mice ; Phosphorylation ; Signal Transduction

Objective To investigate the regulatory role of recombinant Trichinella spiralis cysteine protease inhibitors (rTs-Cys) in induction of polarization of bone marrow-derived macrophages (BMDMs) in vitro. Methods BMDMs were captured and cultured in conditioned medium for 7 days. Then, mature BMDMs were harvested and assigned into four groups. Cells in Group A (negative control) were given 10 ng/mL IFN-γ combined with 100 ng/mL LPS, cells in Group B (positive control) were treated with IL-4 and IL-10 (at 10 ng/mL both), and cells in Group C (recombinant protein alone) were stimulated with 1 μg/mL rTs-Cys, while cells in Group D (protein co-culture) were simultaneously treated with 1 μg/mL rTs-Cys, 10 ng/mL IFN-γ and 100 ng/mL LPS. Cells and culture supernatant were collected 24 hour post-treatment, and the proportions of F4/80⁺, CD11b⁺, CD206⁺ and CD11c⁺ cells were detected by flow cytometry. The levels of interleukin IL-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10 and transforming growth factor-β (TGF-β) in the cell culture supernatant were measured by ELISA and the CD86⁺ and CD206⁺ phenotypes were identified by immunofluorescent staining. Results Flow cytometry detected no significant difference in the proportion of F4/80⁺ CD11b⁺ CD11c⁺ cells among the four groups (F = 46.184, P < 0.001), and a lower proportion of F4/80⁺ CD11b⁺ CD11c⁺ cells was seen in groups C and D than in group A (all P values < 0.001). There was a significant difference in the proportion of F4/80⁺ CD11b⁺ CD206⁺ cells among the four groups (F = 11.032, P < 0.001), and a greater proportion of F4/80⁺ CD11b⁺ CD206⁺ cells was seen in groups C and D than in group A (all P values < 0.01). Immunofluorescent staining showed higher CD206⁺ expression and lower CD86⁺ expression in groups C and D than in Group A. There were significant differences in the IL-6 and (F = 3.950, P < 0.001) and TNF-α (F = 205.827, P < 0.001) levels in the cell culture supernatants among the four groups, and significantly lower IL-6 and TNF-α levels were measured in groups C and D than in Group A (both P < 0.05). There were significant differences in the IL-10 and (F = 8.274, P < 0.001) and TGF-β (F = 13.559, P < 0.01) levels in the cell culture supernatants among the four groups, and greater IL-10 and TGF-β levels were measured in Group C than in Group A (both P values < 0.01). In addition, the TGF-β level was significantly higher in Group D than in Group A (P < 0.05); however, there was no significant difference in the IL-10 level between groups D and A (P > 0.05). Conclusion rTs-Cys may induce the polarization of BMDMs to antiinflammatory M2 macrophages in vitro and inhibit the activation of M1 macrophages.

PURPOSE: The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years. MATERIALS AND METHODS: Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis–free survival (DMFS) were served as the clinical outcome. RESULTS: After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods. CONCLUSION: The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS.
Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Retrospective Studies ; Survival Rate

The study used use bimolecular marking methods to evaluate the lignans of Magnolia officinalis and M. officinalis var. biloba. First, we compare the chemical constituents between M. officinalis and M. officinalis var.biloba. There were significant differences in concentration of magnolignan I between leaves of these two varieties. Then we further select the p-hydroxyphenyl lignin to mining the key enzyme genes of biosynthesis from Magnolia transcriptome, and screened an encoding cinnamyl alcohol dehydrogease gene as the candidate marker of bimolecular marking methods of Magnolia quality by comparing of the expression level and structure variation in homologous gene between M. officinalis and M. officinalis var.biloba. The established method provides the technical support for bimolecular marking methods of Magnolia quality evaluation.

Objective To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1(MCP-1) expression in human umbilical vein endothelial cells(HUVECs)and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB(NF-κB).Methods Grouping: (1)Blank control group;(2)BSA group;(3)AGE group:cells were incubated with different concentrations of AGE(10-4,10-3, 10-2 and 10-1g/L)for 24 hours; (4)AGE+Atorvastatin group: cells were incubated with different concentrations of atorvastatin(0.1,1,10 μmol/L)for 1 hour,then incubated with AGE (10-1 g/L) for 24 hours; (5)PPAR-γ agonist(15 d-PGJ2)group: cells were incubated with 15 d-PGJ2(10 μmol/L)for 1 hour,then incubated with AGE (10-1g/L) for 24 hours;(6)PPAR-γ inhibitor(GW9662)group:cells were incubated with GW9662(5000 nmol/L)for 1 hour,then incubated with atorvastatin (1 μmol/L)and AGE (10-1g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein;RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ;Western blot was performed to detect NF-κB p65 protein.Results (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE(10-1g/L)significantly downregulated the expression of PPAR-γ mRNA(0.22±0.08 vs. 0.69±0.09, P<0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78±0.06 vs. 0.31±0.01,P<0.01) and nonphospho-NF-κB p65 protein (1.61±0.16 vs. 0.59±0.14,P<0.01) comparaed with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21±0.01 vs. 0.78±0.06, P<0.01),nonphospho-NF-κB p65 protein (0.67±0.14 vs. 1.61±0.16,P<0.01)and MCP-1 mRNA (0.17±0.02 vs. 0.93±0.12, P<0.01)compared with AGE(10-1g/L)group. (4) PPAR-γ inhibitor antagonized the effect of atorvastatin on the expression of phospho-NF-κB p65 protein, nonphospho-NF-κB p65 protein and MCP-1 mRNA stimulated by AGE in HUVECs(P<0.01).Conclusion The anti-inflammatory properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to the effect on upregulation of PPAR-γ and downregulation of NF-κB signaling pathway.

OBJECTIVETo investigate the effects of adenovirus-mediated human tissue kallikrein (Ad-hKLK1) gene transfer on platelet-derived growth factor-BB (PDGF-BB)-induced migration of vascular smooth muscle cells from spontaneously hypertensive rats (VSMC(SHR)).

METHODSA bicistronic recombinant adenovirus vector (Ad-hKLK1) carrying the target hKLK1 gene and the reporter gene EGFP was constructed. VSMCs isolated from the thoracic aorta of male SHR were passaged, and the quiescent VSMC(SHR) in passages 3-6 seeded in 6-well plates were treated with Ad-hKLK1 and control virus. Human PDGF-BB or icatibant Hoe140, a BK B2 antagonistat, was used as the chemoattractant and placed in the bottom chamber of the Boyden chamber. The mRNA expressions of bradykinin B1 receptor and B2 receptor were detected by RT-PCR in VSMC(SHR).

RESULTShKLK1 gene transfer significantly inhibited PDGF-BB-induced migration of VSMC(SHR), with the peak inhibition rate of 34.6% (P<0.001). PDGF-BB significantly increased the mRNA expression of B2 receptor but not B1 receptor in VSMC(SHR).

CONCLUSIONShKLK1 gene transfer can inhibit the migration of VSMC(SHR) induced by PDGF-BB, and the inhibitory effects may be not mediated by bradykinin B2 receptor.

Adenoviridae ; genetics ; metabolism ; Animals ; Aorta, Thoracic ; cytology ; Cell Movement ; drug effects ; genetics ; Cells, Cultured ; Gene Transfer Techniques ; Humans ; Hypertension ; pathology ; Male ; Muscle, Smooth, Vascular ; cytology ; Platelet-Derived Growth Factor ; pharmacology ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Inbred SHR ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology ; Tissue Kallikreins ; biosynthesis ; genetics