Objective : To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells. Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results : Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration. Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.

Objective To explore the role and mechanism of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in remifentanil (REM) resistance to hepatic ischemia-reperfusion injury (HIRI). Methods Forty SD rats were randomly divided into sham surgery group, HIRI group, HIRI+REM group, HIRI+PGC-1α inhibitor SR-18292 (HIRI+SR-18292) group and HIRI+REM+SR-18292 group, 8 rats in each group. HIRI rat models were constructed using non-invasive arterial clip occlusion method, and REM or SR-18292 were intravenously injected before surgery. The liver function indicators and liver tissue adenosine triphosphate (ATP) levels in the serum of rats were detected by assay kits. The activity levels of mitochondrial respiratory chain complexes Ⅲ and Ⅳ (COX-Ⅲ, COX-Ⅳ) in rat liver tissue were assessed by colorimetric methods. The pathological changes in rat liver tissue were observed by hematoxylin-eosin staining. Reactive oxygen species (ROS) and oxidative stress-related indicators in rat liver tissue were measured using the fluorescent probe (DCFH-DA) method and colorimetric methods. The mitochondrial DNA (mtDNA) copies and the expression levels of PGC-1α, nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) messenger RNA (mRNA) in rat liver tissue were quantified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). And the protein expression levels of PGC-1α, NRF-1 and TFAM in rat liver tissue were assessed by Western blotting. Results Compared with the sham group, rats in the HIRI group showed increased pathological scores and hepatic cell necrosis in liver tissue, elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and increased levels of ROS and malondialdehyde (MDA) in liver tissue. Additionally, there was a decrease in ATP content and the activity levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), COX-Ⅲ and COX-Ⅳ in liver tissue, as well as a decrease in mtDNA copies and the expression levels of PGC-1α, NRF-1 and TFAM mRNA and protein (all P<0.05). Compared with the HIRI group, rats in the HIRI+REM group exhibited decreased pathological scores and hepatic cell necrosis, reduced levels of serum ALT and AST, and decreased levels of ROS and MDA in liver tissue. There was also an increase in ATP content and the activity levels of SOD, GSH-Px, COX-Ⅲ and COX-Ⅳ in liver tissue, as well as an increase in mtDNA copies and the expression levels of PGC-1α, NRF-1 and TFAM mRNA and protein (all P<0.05). In contrast, rats in the HIRI+SR-18292 group showed increased pathological scores and hepatic cell necrosis, elevated levels of serum ALT and AST, and increased levels of ROS and MDA in liver tissue. There was a decrease in ATP content and the activity levels of SOD, GSH-Px, COX-Ⅲ and COX-Ⅳ in liver tissue, as well as a decrease in mtDNA copies and the expression levels of PGC-1α, NRF-1 and TFAM mRNA and protein (all P<0.05). Compared with the HIRI+REM group, rats in the HIRI+REM+SR-18292 group had increased pathological scores and hepatic cell necrosis, elevated levels of serum ALT and AST, and increased levels of ROS and MDA in liver tissue. There was a decrease in ATP content and the activity levels of SOD, GSH-Px, COX-Ⅲ and COX-Ⅳ in liver tissue, as well as a decrease in mtDNA copies and the expression levels of PGC-1α, NRF-1 and TFAM mRNA and protein (all P<0.05). Conclusions PGC-1α plays a role in regulating the process of REM resistance to HIRI by promoting mitochondrial biogenesis and reducing the levels of oxidative stress.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Objective:To evaluate the association between body mass index (BMI) and bone mineral density of calcaneus in adults.Methods:Data of the second resurvey of China Kadoorie Biobank study from Tongxiang of Zhejiang Province were used. A total of 2 896 participants aged 44-84 years were included in the final analysis. Overweight was defined as 23.0 kg/m 2≤BMI<25.0 kg/m 2, and obesity was defined as BMI ≥25.0 kg/m 2 based on the criteria recommended by WHO/West Pacific Region. Multiple linear regression model was used to evaluate the association between BMI and calcaneus bone mineral density. Restricted cubic splines were used to investigate the dose-response relationship between BMI and calcaneus bone mineral density. Results:The calcaneus bone mineral density in the study subjects were as follow ( x± SE): the broadband ultrasound attenuation was (109.4±12.1) dB/MHz, the speed of ultrasound was (1 545.9±33.8) m/s, and the stiffness index was 85.7±15.8. After adjusting for socio-demographic factors, lifestyle, waist circumference, diabetes and hypertension prevalence, BMI was positively associated with calcaneus stiffness index in non-overweight and non-obese adults, with β of 2.30 (95% CI: 1.11-3.49) for men ( P<0.001) and 1.08 (95% CI: 0.38-1.78) for women ( P=0.003), respectively. In addition, BMI was positively associated with calcaneus stiffness index in overweight and obese women ( β=0.90, 95% CI: 0.38-1.42) ( P<0.001), and null association was found in overweight and obese men ( β=0.06, 95% CI: -0.92-1.04) ( P=0.900). Restricted cubic spline model showed a nonlinear dose-response relationship between BMI and calcaneus stiffness index. Conclusion:Non-linear association was found between BMI with calcaneus bone mineral density in adults.

OBJECTIVE T o compare the biological characteristics,drug resistance and pathogenicity between two strains of mucoid Pseudomonas aeruginosa and the standard strain PAO1.METHODS The strains were identified,and biofilms were detected by 96-well plates method.The bacterial drug resistance was detected by fully automatic drug susceptibility analysis system,the expression levels of RNA of virulence factors were detected by real-time fluorescent quantitative polymerase chain reaction(RT-PCR);the models of rats with pneumonia infection were established through liquid aerosol lung delivery method,the survival status of the rats was observed,and the lev-els of cytokines in bronchoalveolar lavage fluid(BALF)were detected.RESULTS NY4593,NY4605 and PAO1 strains were successfully isolated and identified.NY4593 and NY4605 showed high-yield biofilms,while PAO1 showed low-yield biofilms.The drug resistance rates of NY4593 and NY4605 were remarkably higher than those of the PAO1.The expression levels of exoT and exoY gene RNA of the NY4593 and NY4605 strains were higher than those of the PAO1 strains(P＜0.05);the expression level of exoS gene RNA of the NY4605 was lower than that of the PAO1(P＜0.05).Under the same infection dose,the PAO1 showed more powerful pathogenicity,and the secretion volumes of inflammatory factors interleukin-6(IL-6),interleuki-1β(IL-1β)and interleukin-17A(IL-17A)of the PAO1 were(2858.00±150.30)pg/ml,(7821.00±761.20)pg/ml and(1079.00±225.40)pg/ml respectively,remarkably higher than those of the NY4593 and NY4605(P＜0.05).CONCLUSION The clini-cal mucoid NY4593 and NY4605 remarkably differ from PAO1 in biology and pathogenicity.The study may facilitate deep understanding of the mechanisms of PA infection and provide guidance for clinical treatment,prevention and control.

Objective:To summarize the technical difficulties, key points and cosmetic effects of Ti-loop patch application in breast shaping of immediate reconstruction with omental flap transplantation after mastectomy.Methods:The clinical data of 90 cases with breast cancer who underwent immediate breast reconstruction by using laparoscopically harvested omental flap alone or combined with prosthesis after nipple and areola complex sparing mastectomy from May. 2020 to Jan. 2023 in Hunan Cancer Hospital was retrospectively analyzed. All patients were female between 16 and 55 years old with the average age of 42. Their courses of the disease range from 5 to 26 months with the mean of 15.5 months. These patients received mastectomy with conservation of nipple and areola, and then the greater omentum with right pedicle were harvested laparoscopically. Ti-loop patch was used to hang and fix the greater omentum as a support. 27 patients accepted immediate breast reconstruction with pedicled greater omentum alone, while 63 subjects with greater omentum and gel prosthesis. Among them, contralateral breast contraction and lift was operated on 9 cases.Results:All the pedicled greater omentum successfully survived, and wound surfaces of donor and recipient sites healed at stage I. Axillary lymph node dissection and postoperative radiotherapy were performed on 14 patients with positive pathological examination of sentinel lymph nodes. Breasts of two patients were found to be smaller after postoperative radiotherapy. All 90 subjects were followed up for 5 to 32 months, and the average follow-up period was 16.4 months. The reconstructed breasts were good in shape and tactile sensation. Only punctate scars were observed in donor sites of abdomen. All patients recovered with no upper limb lymphedema, no short and long term complications in abdomen, and only one patient had papillary recurrence without distant metastasis.Conclusions:The omental flap is hard to be sutured and shaped in the reconstructed breast, while easily to be avulsed and form hematoma. The application of Ti-loop patch, which could semi-surround and wrap the greater omentum, and suspend and fix it on the chest wall in upper pole of the breast as a support, can significantly improve the reconstruction effect.

Objective:To summarize the technical difficulties, key points and cosmetic effects of Ti-loop patch application in breast shaping of immediate reconstruction with omental flap transplantation after mastectomy.Methods:The clinical data of 90 cases with breast cancer who underwent immediate breast reconstruction by using laparoscopically harvested omental flap alone or combined with prosthesis after nipple and areola complex sparing mastectomy from May. 2020 to Jan. 2023 in Hunan Cancer Hospital was retrospectively analyzed. All patients were female between 16 and 55 years old with the average age of 42. Their courses of the disease range from 5 to 26 months with the mean of 15.5 months. These patients received mastectomy with conservation of nipple and areola, and then the greater omentum with right pedicle were harvested laparoscopically. Ti-loop patch was used to hang and fix the greater omentum as a support. 27 patients accepted immediate breast reconstruction with pedicled greater omentum alone, while 63 subjects with greater omentum and gel prosthesis. Among them, contralateral breast contraction and lift was operated on 9 cases.Results:All the pedicled greater omentum successfully survived, and wound surfaces of donor and recipient sites healed at stage I. Axillary lymph node dissection and postoperative radiotherapy were performed on 14 patients with positive pathological examination of sentinel lymph nodes. Breasts of two patients were found to be smaller after postoperative radiotherapy. All 90 subjects were followed up for 5 to 32 months, and the average follow-up period was 16.4 months. The reconstructed breasts were good in shape and tactile sensation. Only punctate scars were observed in donor sites of abdomen. All patients recovered with no upper limb lymphedema, no short and long term complications in abdomen, and only one patient had papillary recurrence without distant metastasis.Conclusions:The omental flap is hard to be sutured and shaped in the reconstructed breast, while easily to be avulsed and form hematoma. The application of Ti-loop patch, which could semi-surround and wrap the greater omentum, and suspend and fix it on the chest wall in upper pole of the breast as a support, can significantly improve the reconstruction effect.

Objective:To evaluate the association between body mass index (BMI) and bone mineral density of calcaneus in adults.Methods:Data of the second resurvey of China Kadoorie Biobank study from Tongxiang of Zhejiang Province were used. A total of 2 896 participants aged 44-84 years were included in the final analysis. Overweight was defined as 23.0 kg/m 2≤BMI<25.0 kg/m 2, and obesity was defined as BMI ≥25.0 kg/m 2 based on the criteria recommended by WHO/West Pacific Region. Multiple linear regression model was used to evaluate the association between BMI and calcaneus bone mineral density. Restricted cubic splines were used to investigate the dose-response relationship between BMI and calcaneus bone mineral density. Results:The calcaneus bone mineral density in the study subjects were as follow ( x± SE): the broadband ultrasound attenuation was (109.4±12.1) dB/MHz, the speed of ultrasound was (1 545.9±33.8) m/s, and the stiffness index was 85.7±15.8. After adjusting for socio-demographic factors, lifestyle, waist circumference, diabetes and hypertension prevalence, BMI was positively associated with calcaneus stiffness index in non-overweight and non-obese adults, with β of 2.30 (95% CI: 1.11-3.49) for men ( P<0.001) and 1.08 (95% CI: 0.38-1.78) for women ( P=0.003), respectively. In addition, BMI was positively associated with calcaneus stiffness index in overweight and obese women ( β=0.90, 95% CI: 0.38-1.42) ( P<0.001), and null association was found in overweight and obese men ( β=0.06, 95% CI: -0.92-1.04) ( P=0.900). Restricted cubic spline model showed a nonlinear dose-response relationship between BMI and calcaneus stiffness index. Conclusion:Non-linear association was found between BMI with calcaneus bone mineral density in adults.

OBJECTIVE T o compare the biological characteristics,drug resistance and pathogenicity between two strains of mucoid Pseudomonas aeruginosa and the standard strain PAO1.METHODS The strains were identified,and biofilms were detected by 96-well plates method.The bacterial drug resistance was detected by fully automatic drug susceptibility analysis system,the expression levels of RNA of virulence factors were detected by real-time fluorescent quantitative polymerase chain reaction(RT-PCR);the models of rats with pneumonia infection were established through liquid aerosol lung delivery method,the survival status of the rats was observed,and the lev-els of cytokines in bronchoalveolar lavage fluid(BALF)were detected.RESULTS NY4593,NY4605 and PAO1 strains were successfully isolated and identified.NY4593 and NY4605 showed high-yield biofilms,while PAO1 showed low-yield biofilms.The drug resistance rates of NY4593 and NY4605 were remarkably higher than those of the PAO1.The expression levels of exoT and exoY gene RNA of the NY4593 and NY4605 strains were higher than those of the PAO1 strains(P＜0.05);the expression level of exoS gene RNA of the NY4605 was lower than that of the PAO1(P＜0.05).Under the same infection dose,the PAO1 showed more powerful pathogenicity,and the secretion volumes of inflammatory factors interleukin-6(IL-6),interleuki-1β(IL-1β)and interleukin-17A(IL-17A)of the PAO1 were(2858.00±150.30)pg/ml,(7821.00±761.20)pg/ml and(1079.00±225.40)pg/ml respectively,remarkably higher than those of the NY4593 and NY4605(P＜0.05).CONCLUSION The clini-cal mucoid NY4593 and NY4605 remarkably differ from PAO1 in biology and pathogenicity.The study may facilitate deep understanding of the mechanisms of PA infection and provide guidance for clinical treatment,prevention and control.