ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.

ObjectiveTo explore the effects of Yimei Baijiang formula （YMBJF） on colitis-associated colorectal cancer （CAC） and the nuclear factor kappaB （NF-κB） signaling pathway in mice. MethodsSixty male Balb/c mice of 4-6 weeks old were randomized into 6 groups： Normal， model， capecitabine （0.83 g·kg^-1）， and low-， medium-， and high-dose （4.63， 9.25， 18.50 g·kg^-1， respectively） YMBJF. The mouse model of CAC was established by combining azoxymethane （AOM， 10 mg·kg^-1） and dextran sulfate sodium （DSS， 2%）. At the 5^th week after the start of modeling， the capecitabine group and the YMBJF groups were respectively administrated with the corresponding doses of drugs by gavage once a day for a total of 6 weeks. The body weights and general conditions of mice were measured and observed， and the disease activity index （DAI） was scored. The tumors in the colorectal tissue were counted， and the colorectal length was measured. The histological features of the colorectal tissue in each group of mice were observed by hematoxylin-eosin （HE） staining. The levels of inflammatory cytokines including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression and localization of proliferating cell nuclear antigen-67 （Ki67）， proliferating cell nuclear antigen （PCNA）， and phosphorylated nuclear transcription factor-κB p65 （p-NF-κB p65） proteins were observed by immunohistochemistry （IHC）. The apoptosis of tumor cells was observed by the TUNEL assay. The mRNA levels of IL-6，IL-1β， TNF-α， nuclear transcription factor-κB p65 （NF-κB p65）， NF-κB inhibitor alpha （IκBα）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the colorectal tissue were quantified by Real-time polymerase chain reaction（Real-time PCR）. The protein levels of NF-κB p65， phosphorylated （p）-NF-κB p65， IκBα， p-IκBα， Bcl-2， and Bax in the colorectal tissue were determined by Western blot. ResultsCompared with the model group， each YMBJF group showed decreases in DAI and tumor number （P0.01）， and the medium-dose and high-dose YMBJF groups showed increases in colorectal length （P0.05）. In addition， each YMBJF group showed alleviated colorectal mucosal pathological injury， declined levels of IL-6， IL-1β， and TNF-α in the serum （P0.05）， reduced expression of Ki67 and PCNA （P0.01）， and down-regulated expression of p-NF-κB p65 （P0.05）. The apoptosis in the medium-dose and high-dose YMBJF groups increased （P0.01）. Each YMBJF group and the capecitabine group showed down-regulated mRNA levels of IL-1β， TNF-α， IL-6， NF-κB p65， and Bcl-2 （P0.05） and up-regulated mRNA levels of IκBα and Bax （P0.05）. The mRNA level of IκBα was up-regulated， and that of Bcl-2 was down-regulated （P0.05） in the high-dose YMBJF group. The protein levels of p-IκBα and Bcl-2 were down-regulated （P0.05） in each YMBJF group. The protein levels of IκBα and Bax were up-regulated in the medium-dose and high-dose YMBJF groups （P0.01）， while those of NF-κB p65 and p-NF-κB p65 were down-regulated （P0.05）. ConclusionYMBJF can reduce the number of tumors， reduce the levels of inflammatory factors， promote tumor cell apoptosis， and inhibit tumor cell proliferation by regulating the direct effector molecules of the NF-κB signaling pathway in the mouse model of CRC.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

Objective:To investigate the value of gadoxetate disodium-enhanced MRI combined with T 1 mapping in preoperative prediction of cytokeratin 19 (CK19) and glypican-3 (GPC3) positive dual-phenotype hepatocellular carcinoma (DPHCC). Methods:This case-control study included retrospectively enrolled patients with pathologically confirmed HCC from Central People′s Hospital of Zhanjiang (training set, n=85; December 2020 to July 2022) and the Second Affiliated Hospital, School of Medicine, South China University of Technology (test set, n=35; April 2023 to April 2024). Patients were categorized into CK19 and GPC3 positive DPHCC group (training set=19, test set=11) and non-DPHCC group (training set=66, test set=24) based on postoperative immunohistochemical staining. All patients received preoperative MRI scans, including gadoxetate disodium-enhanced imaging and T 1 mapping. Clinical data were collected, qualitative MRI features were evaluated, and quantitative parameters were measured, including signal intensity, T 1 values, apparent diffusion coefficient (ADC), tumor-to-liver ADC ratio (rADC), tumor-to-liver signal intensity ratio, and T 1 relaxation time reduction rate (ΔT 1%). Statistical comparisons between groups were performed using independent t-tests, Mann-Whitney U tests, or χ2 tests. Multivariate logistic regression identified independent predictors of CK19 and GPC3 positive DPHCC, and a combined model was constructed. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC), with DeLong test comparing model performance. Results:Significant intergroup differences were observed in alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, DWI target sign, rADC, hepatobiliary-phase T 1 (T 1HBP), and ΔT 1% ( P<0.05). Multivariate analysis identified AFP>20 ng/ml ( OR=5.835, 95% CI 1.019-33.397, P=0.048), DWI target sign ( OR=13.408, 95% CI 2.216-81.131, P=0.005), and ΔT1%≤31% ( OR=14.429, 95% CI 2.166-96.125, P=0.006) as independent predictors of DPHCC. The AUC values of the aforementioned three independent predictors and the combined model for predicting DPHCC were 0.641 (95% CI 0.530-0.742), 0.679 (95% CI 0.569-0.777), 0.740 (95% CI 0.634-0.829), and 0.886 (95% CI 0.799-0.945) in the training set, and 0.568 (95% CI 0.390-0.743), 0.669 (95% CI 0.490-0.818), 0.689 (95% CI 0.511-0.843), and 0.824 (95% CI 0.658-0.931) in the test set, respectively. The DeLong test results showed that in the training set, the diagnostic performance of the combined model was superior to those of the three individual features ( Z=3.68, P<0.001; Z=3.15, P=0.002; Z=3.15, P=0.002). In the test cohort, the combined model demonstrated better diagnostic performance than AFP>20 ng/ml and ΔT 1%≤31% ( Z=2.15, P=0.032; Z=2.12, P=0.034), while no statistically significant difference was observed compared with the DWI target sign ( Z=1.77, P=0.076). Conclusion:The integrated model incorporating clinical data, gadoxetate disodium-enhanced MRI, and T 1 mapping parameters effectively predicts CK19 and GPC3 positive DPHCC.

Radiotherapy,as one of the important means of treating cancer,is more prone to medical errors than other treatment methods due to its involvement of a wide variety of equipment,high demands for personnel collaboration,and relatively complex treatment processes.Therefore,the establishment of an effective reporting and learning system for adverse events of radiotherapy is of great significance for ensuring patients'safety and improving healthcare quality.The International Atomic Energy Agency(IAEA)has established the Safety Reporting And Learning System For Radiotherapy(SAFRON),which constructed comprehensive database and formulated standard procedures of reporting event and analytical methods through collected and analyzed the worldwide cases of adverse event of radiotherapy.At the same time,the SAFRON system emphasizes the cultivation for safety culture,and encourages healthcare professionals to actively report adverse events,and creates a non-punitive learning environment to learn from mistakes and prevent the recurrence of similar incidents.This review introduced the structure and usage method of reporting and learning system of adverse event of SAFRON radiotherapy,so as to understand the using processes,system architecture and security culture of that,which can provide references for the establishment and use of reporting and learning system of adverse event of department,and promote continuous improvement of healthcare quality.

Objective:To analyze the clinical efficacy of asymmetric T 1 transpedicular wedge resection Smith-Petersen osteotomy (T 1 SPO) in the treatment of stiff cervical thoracic lateral kyphosis deformity. Methods:This is a retrospective case series study. The clinical data of nine patients with stiff cervical thoracic kyphosis who underwent asymmetric T 1 SPO corrective treatment from June 2012 to October 2022 were collected. There were 7 males and 2 females, aged 45 to 68 years. The surgery time, intraoperative blood loss, and complications were recorded. The chin brow vertical angle (CBVA), cervical thoracic kyphosis Cobb angle, cervical thoracic scoliosis Cobb angle, and cervical thoracic sagittal axis (C 2-T 1 sagittal vertical axis, SVA) before surgery, after surgery, and at the last follow-up were measured and the correction rates were calculate. Results:All 9 patients successfully completed the surgery. The operation time ranged from 245 to 320 minutes, and the intraoperative blood loss was 1 400 to 2 200 ml. All patients were followed up for 24 to 48 months. The preoperative CBVA was 93.7° to 112.0°, which improved to 25.2° to 31.7° at the last follow-up, with an correction rate of 73.4%. The preoperative cervicothoracic kyphosis Cobb angle was -57.0° to -16.6°, which improved to 10.3° to 18.5° at the last follow-up, with an correction rate of 166.7%. The preoperative scoliosis Cobb angle was 13.0° to 16.5°, which improved to 2.2° to 3.8° at the last follow-up, with an correction rate of 84.9%. The preoperative SVA was 7.8 to 12.5 cm, which improved to 4.5 to 6.8 cm at the last follow-up, with an correction rate of 42.3%. One patient experienced numbness and weakness in the left hand after surgery, which recovered after 3 months. One patient had poor healing of the surgical incision, which healed after symptomatic treatment. During the follow-up, the coronal and sagittal balance of all patients was maintained, and no other neurological complications occurred. There were no cases of screw loosening, broken screws, or broken rods, or other internal fixation failures.Conclusion:The application of asymmetric T 1 SPO technique in the treatment of stiff cervical thoracic lateral kyphosis deformity can achieve relatively satisfactory correction effects.

Objective:To compare the uncertainty of dose calibration systems between EBT4 and EBT3 films, and to evaluate the effectiveness and accuracy of EBT4 films in radiotherapy dose measurements.Methods:EBT4 and EBT3 films were irradiated with clinical 6 MV photon beams at doses ranging from 0 to 1,600 MU. Films were scanned after resting for 0 and 24 h to establish dose calibration functions based on net optical density. The dose uncertainties introduced by function fitting, dose resolution, film non-uniformity, scan repeatability, and scanner non-uniformity during calibration of the two films were obtained through experimental tests and mathematical calculations. Independent-sample t-tests were used to compare differences in fitting uncertainty and dose resolution between the two films, while homogeneity of variance tests were used to compare differences in film non-uniformity and scan repeatability. The combined total uncertainty was then calculated and compared. Finally, the total combined uncertainty was calculated by integrating all individual sources of uncertainty and compared between the two films. Results:Within the absorbed dose range of 1-12 Gy, EBT4 films exhibited significantly lower dose uncertainties from function fitting and dose resolution than EBT3 films at the same standing time ( P<0.01). No significant differences were observed between the two films in terms of non-uniformity and scan repeatability ( P>0.05). The total dose uncertainties of EBT4 and EBT3 films at 0 h standing were 5.65% and 7.87%, respectively, while the total uncertainties at 24 h standing were 4.73% and 6.33%, respectively. Overall, the dose calibration system of EBT4 films demonstrated consistently lower total uncertainty. Conclusion:Under identical conditions, EBT4 films demonstrate superior and more stable dose uncertainty compared with EBT3 films, thereby meeting the clinical requirements for radiation dose measurements with higher precision.

Objective:To explore the effects and potential mechanisms of chemokine-like factor-like MARVEL transmembrane domain-containing Protein 3 (CMTM3) on the proliferation and migration of glioblastoma (GBM) cells.Methods:Using CMTM3 expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we analyzed the differential expression of CMTM3 in GBM tissues and its impact on the prognosis of GBM patients. Immunohistochemical staining and protein content determination of CMTM3 was performed on GBM and adjacent non-cancerous tissue samples from 11 GBM patients who underwent surgical treatment at the Affiliated Hospital of Guizhou Medical University between November 3, 2022 and March 15, 2023. Additionally, the expression of CMTM3 was validated in GBM cell lines U87, U251, LN229, and the human astrocyte (NHA) cell line using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Stable cell lines with silenced and overexpressed CMTM3 (sh-CMTM3 group and OE-CMTM3 group) were constructed using U251 cells. The effect of CMTM3 expression on cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to examine the impact of CMTM3 expression on the cell cycle. Transwell assays were conducted to evaluate the influence of CMTM3 expression on cell migration. Bioinformatics analysis, Western blotting, NF-κB activation-nuclear translocation assays, and the NF-κB pathway inhibitor pyrrolidine dithiocarbamate ammonium (PDTC) were used to validate the effect of CMTM3 on the NF-κB pathway. Finally, a subcutaneous tumorigenesis assay in nude mice was performed to observe the impact of CMTM3 expression on the in vivo growth of U251 cells. Results:Bioinformatics analysis revealed that CMTM3 is highly expressed in GBM tissues. Patients with a high CMTM3 expression had lower overall survival (OS) and disease-free survival (DFS) rates compared with those with a low CMTM3 expression (with P values of 0.010 and 0.032, respectively). Among the 11 GBM pathological specimens, 10 samples exhibited higher CMTM3 protein expression levels in the cancerous tissue compared with the adjacent non-cancerous tissue. The average CMTM3 protein expression in these samples was 0.44±0.09, significantly higher than that in the adjacent non-cancerous tissues (0.12±0.02, P＜0.001). In one sample, the difference in CMTM3 protein expression between the cancerous and adjacent non-cancerous tissues was not statistically significant ( P=0.750).The RT-qPCR results showed that the mRNA expression level of CMTM3 in NHA cells was 1.0±0.1, whereas in GBM cells U87, LN229, and U251, the levels were 2.1±0.3, 3.4±0.5, and 3.7±0.8, respectively, all significantly higher than that in NHA cells (all P＜0.01). Western blot results demonstrated that the protein expression levels of CMTM3 in GBM cells U87, LN229, and U251 were 1.5±0.2, 1.8±0.2, and 1.9±0.1, respectively, also higher than that in NHA cells (0.7±0.2, all P＜0.01), with the highest level observed in U251 cells. The CCK-8 assay, Flow cytometry, and Transwell migration experiments indicated that cell viability was inhibited in the sh-CMTM3 group, with an increase in the proportion of cells in the G 0/G 1 phase ( P＜0.01) and a decrease in the S phase ( P＜0.01), and the number of migrated cells was 233.6±35.5, lower than that in the sh-NC group ( P＜0.001). Conversely, the OE-CMTM3 group showed enhanced cell viability, a reduction in the proportion of cells in the G 0/G 1 phase ( P＜0.01), and an increase in the S phase ( P＜0.01), and the number of migrated cells was 1212.0±20.8, higher than that in the OE-NC group ( P＜0.001). However, in the OE-CMTM3+PDTC group, cell viability, cell cycle distribution (G 1, S, and G 2 phases), and cell migration numbers showed no significant changes (all P＞0.05). Western blot analysis and NF-κB activation-nuclear translocation assay results indicated that in the sh-CMTM3 group, the p-p65/p65 ratio was 0.51±0.04 and the p-IκBα/IκBα ratio was 0.39±0.03, both lower than those in the sh-NC group (both P＜0.01). The cytoplasmic staining rate was (49.29±1.98)%, higher than that in the sh-NC group ( P＜0.01). In the OE-CMTM3 group, the p-p65/p65 ratio was 2.27±0.10 and the p-IκBα/IκBα ratio was 2.14±0.15, both higher than those in the OE-NC group (both P＜0.01). The cytoplasmic staining rate was (18.96±1.44)%, lower than that in the OE-NC group ( P＜0.01). In the OE-CMTM3+PDTC group, there were no significant differences in the p-p65/p65 ratio, p-IκBα/IκBα ratio, and cytoplasmic staining rate compared with the OE-NC group (all P＞0.05). The subcutaneous tumorigenesis assay in nude mice showed that the tumor volume in the sh-CMTM3 group was (408.9±96.2) mm3, smaller than that in the sh-NC group ( P=0.003). The tumor volume in the OE-CMTM3 group was (1 514.5±251.5) mm3, larger than that in the OE-NC group ( P=0.005). Conclusions:In GBM, CMTM3 is highly expressed and negatively correlated with both OS and DFS of patients. CMTM3 regulates the proliferation and migration abilities of U251 cells through the NF-κB signaling pathway.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.