Objective:This study aims to investigate the role of fatty acid-binding protein 4 (FABP4) in endothelial-to-mesenchymal transition (EndMT) during the formation of idiopathic pulmonary fibrosis (IPF) and its possible mechanism, and to evaluate the therapeutic potential ofFABP4 inhibitor BMS309403.Methods:A bleomycin (BLM)-induced mouse model of pulmonary fibrosis was established for in vivo experiments.hematoxylin-eosin(HE)and Masson staining were used to assess the histopathological changes and collagen deposition in lung tissue, while western blotting (WB) was used to assess EndMT-related protein expression in lung tissue.In vitro, human umbilical vein endothelial cells (HUVEC) were treated with transforming growth factor-β (TGF-β) to induce the EndMT model.After intervention with FABP4 protein or BMS309403, the expression levels of EndMT related genes and peroxisome proliferator-activated receptor γ (PPAR γ) were detected.Results:BLM-induced mice showed significant pulmonary fibrosis, inflammatory infiltration, and EndMT (upregulated expression of Fibronectin and α-SMA proteins expression, downregulated expression of VE cadherin and CD31 proteins), and BMS309403 treatment significantly alleviated these pathological changes.In vitro experiments confirmed that TGF-β could successfully induce EndMT in HUVECs, FABP4 enhanced the induction effect of TGF-β on EndMT, and BMS309403 could effectively reverse this effect.The co-treatment with TGF-β and FABP4 significantly inhibited the expression of PPARγ, BMS309403 significantly alleviated these changes.Conclusions:FABP4 may promote pulmonary fibrosis progression by facilitating EndMT through the PPARγ signaling pathway.FABP4 may serve as a promising therapeutic target for IPF.

Objective To analyze the changes in angiopoietin-2(Ang-2)levels before and after microwave ablation(MWA)in patients with high-risk pulmonary nodule and its impact on postoperative recurrence.Method A total of 94 patients with high-risk pulmonary nodules admitted to Guizhou Aerospace Hospital from December 2019 to December 2021 were included and categorized into a recurrence group(n=30)and a non-recurrence group(n=64).Clinical data was compared between the two groups.Pearson correlation analysis was used to analyze the correlation between pre-treatment angiopoietin-2(Ang-2)levels and CT parameters.Logistic regression model,restricted cubic splines,threshold effect analysis,and receiver operating characteristic(ROC)curve were used to analyze the relationship between pre-treatment Ang-2 levels and postoperative recurrence.Kaplan-Meier survival curves were used to analyze the differences in overall survival among patients with different Ang-2 levels.Cox regression model was used to analyze the factors affecting patients'survival.Result Compared to pre-treatment levels within the same group,Ang-2 levels in both groups decreased significantly,with statistically significant differences(P<0.05).Pearson correlation analysis showed that pre-treatment Ang-2 levels were positively correlated with BF,BV,PS,and MTT.Ang-2 level was independently associated with postoperative recurrence.Results of ROC analysis indicated that pre-treatment Ang-2 had certain predictive value for postoperative recurrence(area under the curve=0.789).Restricted cubic spline analysis revealed a nonlinear dose-response relationship between pre-treatment Ang-2 and postoperative recurrence(P<0.05).Threshold effect analysis identified that the inflection point of Ang-2 affecting recurrence as 1905.41 pg/mL.Survival analysis demonstrated that the median overall survival of patients in the Ang-2<1905.41 pg/mL group was longer than that in the Ang-2≥1905.41 pg/mL group(P=0.039).Furthermore,Ang-2≥1905.41 pg/mL was an independent factor affecting patients'survival time.Conclusion The levels of Ang-2 decreased significantly in patients with high-risk pulmonary nodules after MWA,and pre-treatment Ang-2 level has certain predictive value for postoperative recurrence.

Objective:This study aims to investigate the role of fatty acid-binding protein 4 (FABP4) in endothelial-to-mesenchymal transition (EndMT) during the formation of idiopathic pulmonary fibrosis (IPF) and its possible mechanism, and to evaluate the therapeutic potential ofFABP4 inhibitor BMS309403.Methods:A bleomycin (BLM)-induced mouse model of pulmonary fibrosis was established for in vivo experiments.hematoxylin-eosin(HE)and Masson staining were used to assess the histopathological changes and collagen deposition in lung tissue, while western blotting (WB) was used to assess EndMT-related protein expression in lung tissue.In vitro, human umbilical vein endothelial cells (HUVEC) were treated with transforming growth factor-β (TGF-β) to induce the EndMT model.After intervention with FABP4 protein or BMS309403, the expression levels of EndMT related genes and peroxisome proliferator-activated receptor γ (PPAR γ) were detected.Results:BLM-induced mice showed significant pulmonary fibrosis, inflammatory infiltration, and EndMT (upregulated expression of Fibronectin and α-SMA proteins expression, downregulated expression of VE cadherin and CD31 proteins), and BMS309403 treatment significantly alleviated these pathological changes.In vitro experiments confirmed that TGF-β could successfully induce EndMT in HUVECs, FABP4 enhanced the induction effect of TGF-β on EndMT, and BMS309403 could effectively reverse this effect.The co-treatment with TGF-β and FABP4 significantly inhibited the expression of PPARγ, BMS309403 significantly alleviated these changes.Conclusions:FABP4 may promote pulmonary fibrosis progression by facilitating EndMT through the PPARγ signaling pathway.FABP4 may serve as a promising therapeutic target for IPF.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

OBJECTIVE：To observe therapeutic efficacy and safe ty of Huhuang burn liniment on the prevention and treatment of radiation dermatitis patients with nasopharyngeal carcinoma （NPC）. METHODS ：Totally 129 NPC patients were collected from our hospital during Aug. 2018-Feb. 2020. They were numbered according to the order of radiotherapy ，the ones with odd number were included into observation group （65 cases）and the ones with even number into control group （64 cases）. Both groups received routine radiotherapy and skin nursing. Control group were evenly smeared with Shirun shaoshang cream in the radiation field during radiotherapy ，and observation group were smeared with Huhuang burn liniment. The smearing area should be 1 cm beyond the edge of radiation field ，3 times a day until the end of stage 1 radiotherapy（33-38 times in total ）. The skin lesions of the two groups were observed ；the appearance time and healing time of skin lesion ，RTOG score and NRS score were recorded. The levels of serum cytokines （TNF-α，IL-6，IL-8 and IL- 10）were detected in 2 groups at 0，15th and 30th time of radiotherapy. The occurrence of ADR was recorded in 2 groups during treatment. RESULTS ：The appearance time of skin lesion in observation group was significantly longer than control group ；the healing time of skin lesion in observation group was significantly shorter than control group （P＜0.01）. RTOG grading of radiodermatitis in the two groups was mainly grade 1，but no grade 3 or 4 was found. There was no significant difference in the proportion of patients with differen RTOG grades （P＞0.05）. The highest NRS score of control group and observation group were 3 and 2 points respectively ，and the proportions of patients with 0-3 points in the two groups were statistically significant （P＜0.05）. There was no significant difference in serum cytokine levels between @qq.com 2 groups at 0 time of radiotherapy （P＞0.05）. The serum cytokine levels of 2 groups were increased significantly at 15th @qq.com time of radiotherapy ， but t he observation group was significantly lower than control group at the same period （P＜0.05 or P＜0.01）. At 30th time of radiotherapy ，the cytokine levels of 2 groups decreased significantly ，compared with 15th time of radiotherapy ，the observation group was significantly lower than the control group at the same period （P＜0.05 or P＜0.01）；the levels of TNF-α，IL-6 and IL- 10 in control group as well as the level of IL- 6 in observation group were significantly higher than the same group at 0 time of radiotherapy （P＜0.05 or P＜0.01）. There was no ADR such as allergy ，rash，smear site infection in the two groups during the treatment. CONCLUSIONS ：Huhuang burn liniment has a good effect of preventing and treating radiation dermatitis of NPC patients ，delays the occurrence of skin lesion，shortens the healing time of skin lesion ，relieves pain and reduces the level of serum cytokines with good safety.