Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective:To evaluate the improvement in the outcome of intracapsular condylar fractures(ICFs)treatment with pre-cise soft tissue reduction in combination with open reduction and internal fixation(PSTR-ORIF)by comparson with traditional open reduction and internal fixation(T-ORIF).Methods:40 patients with ICFs were treated by T-ORIF and PSTR-ORIF(n=20)re-spectively.Preoperative and 6-month postoperative whole-mouth panoramic tomography,CT and MRI imaging data were analyzed,the repositioning of the soft and hard tissues of temporomandibular joints(TMJs),the Helkimo index,clinical symptoms and subjec-tive symptoms were compared between the 2 groups.Results:In PSTR-ORIF(26 sides)and T-ORIF(27 sides)groups,the rate of complete anatomical restoration of fractured segments at 6 months after surgery was 96.15％and 81.48％,and the overall effective rate of ICF articular disc restoration was 96.15％and 74.07％respectively,the height of the ascending mandibular branch was bet-ter restored in patients with B-type fracture after surgery(P＜0.05).At 6 months postoperatively,patients in the PSTR-ORIF group showed significant improvement in mouth opening,mandibular anterior extension distance,and lateral movement compared with the T-ORIF group(P＜0.05).The Helkimo index showed that the PSTR-ORIF group got a significant improvement in the complaint symptom index score and the clinical symptom index score compared with the T-ORIF group(P＜0.05).Conclusion:PSTR-ORIF is more effective than T-ORIF in the treatment of ICFs for the healing of condylar fractures,restore postoperative TMJ mobility and reduce the postoperative joint discomfort through good repositioning of soft tissues.

Objective:To evaluate the improvement in the outcome of intracapsular condylar fractures(ICFs)treatment with pre-cise soft tissue reduction in combination with open reduction and internal fixation(PSTR-ORIF)by comparson with traditional open reduction and internal fixation(T-ORIF).Methods:40 patients with ICFs were treated by T-ORIF and PSTR-ORIF(n=20)re-spectively.Preoperative and 6-month postoperative whole-mouth panoramic tomography,CT and MRI imaging data were analyzed,the repositioning of the soft and hard tissues of temporomandibular joints(TMJs),the Helkimo index,clinical symptoms and subjec-tive symptoms were compared between the 2 groups.Results:In PSTR-ORIF(26 sides)and T-ORIF(27 sides)groups,the rate of complete anatomical restoration of fractured segments at 6 months after surgery was 96.15％and 81.48％,and the overall effective rate of ICF articular disc restoration was 96.15％and 74.07％respectively,the height of the ascending mandibular branch was bet-ter restored in patients with B-type fracture after surgery(P＜0.05).At 6 months postoperatively,patients in the PSTR-ORIF group showed significant improvement in mouth opening,mandibular anterior extension distance,and lateral movement compared with the T-ORIF group(P＜0.05).The Helkimo index showed that the PSTR-ORIF group got a significant improvement in the complaint symptom index score and the clinical symptom index score compared with the T-ORIF group(P＜0.05).Conclusion:PSTR-ORIF is more effective than T-ORIF in the treatment of ICFs for the healing of condylar fractures,restore postoperative TMJ mobility and reduce the postoperative joint discomfort through good repositioning of soft tissues.

Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Aim To preliminarily evaluate the effects of hypobaric hypoxia on organism damage in rats with post-traumatic stress disorder(PTSD),with a view to laying a foundation for drug research in plateau PTSD.Methods The rats were randomly divided into four groups,namely,the control(Control)group,the sin-gle-prolonged stress(SPS)group,the hypobaric hy-poxia(HH)group and the single-prolonged stress combined with hypobaric hypoxia(SPS+HH)group.The PTSD model was firstly constructed using the SPS method for rats in the SPS and SPS+HH groups.On the second day,rats in the HH group and SPS+HH group were placed in a low-pressure hypoxia chamber at a simulated altitude of 6000 m for 14 days.General condition,behavior,blood tests,and histomorphology were examined in order to evaluate the damage caused by low pressure hypoxia in PTSD rats.Results The body mass of rats in the SPS+HH group was signifi-cantly reduced;the feces were partly hard and lumpy,and some of them were seen to have high viscosity.Anxiety-like and depression-like behaviors were ob-served in all groups except in the control group,in which hypobaric hypoxia aggravated the behavioral ab-normalities in SPS rats.Rats in both the SPS and SPS+HH groups had coagulation dysfunction and abnor-mally increased blood viscosity,which was significantly abnormal in the SPS+HH group;erythrocytes,hemo-globin,and erythrocyte specific volume in whole blood of rats in the SPS+HH group were significantly in-creased compared with those of rats in the SPS group;and serum TP,LDH and GLU levels were abnormal in rats in the SPS+HH group.Dilated and congested blood vessels were seen in hippocampal tissue,conges-ted central veins were seen in hepatic tissue,and dilat-ed and congested liver sinusoids with mild granuloma-tous degeneration of hepatocytes were seen in rats of the SPS+HH group.Conclusion Hypobaric hypoxia exacerbates depression-like and anxiety-like behaviors in PTSD rats,as well as hematological indices and his-tomorphometric abnormalities in PTSD rats.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.