Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To analyze the impact of problem-based simulation training combined with hierarchical management on the core competencies of elderly nursing staff.Methods:A total of 150 elderly patient nurses who worked in Sichuan Science City Hospital from June 2021 to March 2022 were subjected to a 6-month problem-based simulation training combined with hierarchical management since March 2022. The professional nursing abilities, core nursing abilities, nursing quality, and satisfaction of nursing staff with teaching were compared before and after training. Paired t-test was performed using SPSS 23.0. Results:The theoretical scores and skill operations of nursing staff for elderly patients were higher after the training than before the training ( P<0.05). The clinical nursing ability, critical thinking in scientific research, leadership ability, interpersonal relationships, professional development ability, educational guidance, ethics, legal practice score, and overall core competency score of nursing staff for elderly patients were all higher than before training ( P<0.05). The basic nursing care, nursing service attitude, nurse patient communication, document writing, and nursing operation scores of nursing staff for elderly patients were higher than before training ( P<0.05). The scores of humanistic care, dietary guidance, life care, and rehabilitation guidance all increased ( P<0.05). Conclusions:The problem-based simulation training combined with hierarchical management can improve the professional ability, core nursing ability, and nursing quality of nursing staff for elderly patients. Both patients and nursing staff acknowledge the effectiveness of this nursing approach.

Objective To investigate the presence of pepsin and trypsin in the middle ear effusion of children with acute suppurative otitis media(ASOM).Methods Middle ear effusion samples were collected from 71 children with ASOM at Children's Hospital of Xuzhou.According to the characteristics of the middle ear effusions,the effu-sion was divided into serous and mucous types.The pH testing,Western Blotting(WB),and enzyme-linked immu-nosorbent assay(ELISA)were performed.Results ① There were 49.29％(35/71)of ASOM patients had a posi-tive RSI score(＞13).② The positive rate of pepsin in ASOM children was 49.29％(35/71),and the positive rate of trypsin was 42.25％(30/71).In addition,the positive rate of pepsin in RSI-positive children was 100％(35/35),and the positive rate of trypsin was 60％(21/35).There was no significant difference in the positive rate of pepsin and trypsin between serous and mucous middle ear effusion(P＞0.05).③ The pepsin concentration was 47.80(39.80,69.30)ng/ml and the trypsin concentration was 291.87±20.45 ng/ml in middle ear effusion of chil-dren with ASOM who had a positive WB test,and the trypsin concentration was significantly higher than pepsin(P＜0.05).There was no significant difference between the pepsin and the trypsin concentrations in serous and mu-cous middle ear effusion(P＞0.05).④ The pH value of mucous middle ear effusion was 7.39±0.28,and the pH value of serous middle ear effusion was 7.36±0.26.There was no significant difference between the pH value in se-rous and mucous middle ear effusion(P＞0.05).Conclusion The detection rates of pepsin and trypsin in middle ear effusion of children with ASOM were high which has important diagnostic value for children with ASOM combined with LPRD.

Objective To explore indicators of risks for preoperative adverse cardiovascular events(PACE)in elderly patients who underwent non-cardiac surgery(NCS).Methods The clinical data of elderly patients who had undergone NCS at Tianjin Medical University General Hospital from January 2022 to March 2024 were analyzed retrospectively,including gender,age,medical history,operation ways,and preoperative creatinine(Cr),hypersensitive C-reactive protein(hs-CRP),hypersensitivity cTnT(hs-cTnT),MB isoenzyme of creatine kinase(CK-MB),N-terminal pro-brain natriuretic peptide(NT-proBNP)and D-Dimer,prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib).To measure the revised cardiac risk index(RCRI),the 30-day prognosis of the patients was followed up.Patients were divided into PACE group and non-PACE group according to the occurrence of PACE,and the clinical data between the two groups were compared.Multiple Logistics regression was used to identify independent risk factors for PACE,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of each risk factor for PACE risk in elderly patients underwent NCS.Results A total of 112 elderly patients underwent NCS were enrolled,including 9 cases in the PACE group(incidence rate 8.03%)and 103 cases in the non-PACE group.Patients'age(years old:75.1±6.4 vs.69.4±7.2,P=0.002),preoperative incidence of coronary heart disease[44.4%(4/9)vs.28.2%(29/103),P=0.004],incidence of heart failure[22.2%(2/9)vs.6.8%(7/103),P=0.003],NT-proBNP[(ng/L):485.17(196.10,787.53)vs.98.41(73.81,160.35),P=0.001],hs-cTnT[(μg/L):0.043(0.023,0.087)vs.0.005(0.003,0.008),P=0.002],and D-Dimer[(μg/L):2 953(2 674,3 570)vs.514(260,1 010),P=0.001]levels in the PACE group were significantly higher than those in the non-PACE group,the proportion of RCRI 2-3 scores in PACE group were significantly higher than those in non-PACE group[2 scores:44.4%(4/9)vs.18.4%(19/103),3 scores:33.3%(3/9)vs.14.6%(15/103),P=0.047].As shown in multiple Logistic regression analysis,age,preoperative NT-proBNP levels and RCRI scores≥2 were independent risk factors affecting the prognosis for PACE occurrence[odds ratio(OR)and 95%confidence interval(95%CI)were 1.163(1.032-1.310),1.021(1.008-1.031)and 1.261(1.003-1.585),P values were 0.013,0.001,0.048,respectively].As shown in ROC curve analysis,age,NT-proBNP and RCRI had predictive value for the occurrence of PACE in NCS patients,the area under the curve(AUC)and 95%CI of age,NT-proBNP and RCRI were 0.795(0.675-0.915),0.908(0.838-0.979)and 0.735(0.556-0.912),with P=0.030,<0.001 and 0.020 respectively.The optimal cut-off values were:age≥69.5 years(sensitivity was 88.9%,specificity was 56.3%);NT-proBNP≥177.0 ng/L(sensitivity was 88.9%,specificity was 83.5%);RCRI≥1.5 points(sensitivity was 77.8%,specificity was 67.0%).Conclusions Age,NT-proBNP levels and RCRI have certain predictive values for the occurrence of PACE in NCS patients undergoing NCS,advanced age,higher NT-proBNP levels,and elevated RCRI scores were associated with increased PACE risk in elderly patients undergoing NCS.While age showed high sensitivity but limited specificity,combining NT-proBNP(with high diagnostic accuracy)and RCRI(with objective scoring)improved preoperative PACE risk prediction.

Objective To explore indicators of risks for preoperative adverse cardiovascular events(PACE)in elderly patients who underwent non-cardiac surgery(NCS).Methods The clinical data of elderly patients who had undergone NCS at Tianjin Medical University General Hospital from January 2022 to March 2024 were analyzed retrospectively,including gender,age,medical history,operation ways,and preoperative creatinine(Cr),hypersensitive C-reactive protein(hs-CRP),hypersensitivity cTnT(hs-cTnT),MB isoenzyme of creatine kinase(CK-MB),N-terminal pro-brain natriuretic peptide(NT-proBNP)and D-Dimer,prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib).To measure the revised cardiac risk index(RCRI),the 30-day prognosis of the patients was followed up.Patients were divided into PACE group and non-PACE group according to the occurrence of PACE,and the clinical data between the two groups were compared.Multiple Logistics regression was used to identify independent risk factors for PACE,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of each risk factor for PACE risk in elderly patients underwent NCS.Results A total of 112 elderly patients underwent NCS were enrolled,including 9 cases in the PACE group(incidence rate 8.03%)and 103 cases in the non-PACE group.Patients'age(years old:75.1±6.4 vs.69.4±7.2,P=0.002),preoperative incidence of coronary heart disease[44.4%(4/9)vs.28.2%(29/103),P=0.004],incidence of heart failure[22.2%(2/9)vs.6.8%(7/103),P=0.003],NT-proBNP[(ng/L):485.17(196.10,787.53)vs.98.41(73.81,160.35),P=0.001],hs-cTnT[(μg/L):0.043(0.023,0.087)vs.0.005(0.003,0.008),P=0.002],and D-Dimer[(μg/L):2 953(2 674,3 570)vs.514(260,1 010),P=0.001]levels in the PACE group were significantly higher than those in the non-PACE group,the proportion of RCRI 2-3 scores in PACE group were significantly higher than those in non-PACE group[2 scores:44.4%(4/9)vs.18.4%(19/103),3 scores:33.3%(3/9)vs.14.6%(15/103),P=0.047].As shown in multiple Logistic regression analysis,age,preoperative NT-proBNP levels and RCRI scores≥2 were independent risk factors affecting the prognosis for PACE occurrence[odds ratio(OR)and 95%confidence interval(95%CI)were 1.163(1.032-1.310),1.021(1.008-1.031)and 1.261(1.003-1.585),P values were 0.013,0.001,0.048,respectively].As shown in ROC curve analysis,age,NT-proBNP and RCRI had predictive value for the occurrence of PACE in NCS patients,the area under the curve(AUC)and 95%CI of age,NT-proBNP and RCRI were 0.795(0.675-0.915),0.908(0.838-0.979)and 0.735(0.556-0.912),with P=0.030,<0.001 and 0.020 respectively.The optimal cut-off values were:age≥69.5 years(sensitivity was 88.9%,specificity was 56.3%);NT-proBNP≥177.0 ng/L(sensitivity was 88.9%,specificity was 83.5%);RCRI≥1.5 points(sensitivity was 77.8%,specificity was 67.0%).Conclusions Age,NT-proBNP levels and RCRI have certain predictive values for the occurrence of PACE in NCS patients undergoing NCS,advanced age,higher NT-proBNP levels,and elevated RCRI scores were associated with increased PACE risk in elderly patients undergoing NCS.While age showed high sensitivity but limited specificity,combining NT-proBNP(with high diagnostic accuracy)and RCRI(with objective scoring)improved preoperative PACE risk prediction.

Objective:To explore the correlation between lean nonalcoholic fatty liver disease (NAFLD) and metabolic indicators in a young and middle-aged population undergoing physical examination.Methods:It was a cross-sectional study. A total of 8 250 individuals who underwent routine physical examinations at the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University from January to December 2021 and met the inclusion and exclusion criteria were selected as the research subbjects. The general examination, fasting blood glucose, blood lipids, liver function, renal function, and fasting color ultrasound examination results were analyzed retrospectively to assess the correlation between lean NAFLD and major metabolic indicators using independent sample t-test, chi-square test, and multivariable logistic regression. Results:The prevalence of lean NAFLD was higher in men than in women (50.7% vs. 49.3%, χ2=97.261, P<0.001). After stratifying the age of onset of lean NAFLD, the peak age of onset was found to be between 45 and 59 years, with the prevalence gradually increasing with age. When stratified by body mass index (BMI), the peak incidence of lean NAFLD was observed in individuals with a BMI of ≥20 and <23 kg/m 2, with the prevalence showing a significant upward trend as BMI increased. The systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and serum uric acid in lean NAFLD groupwere all significantly higher than those in lean non-NAFLD group (all P<0.01), and the level of high density lipoprotein was significantly lower than that of lean non-NAFLD group ( t=23.755, P<0.001). The logistic analysis showed that systolic blood pressure ( OR=1.258, 95% CI: 1.081-1.465), diastolic blood pressure ( OR=1.282, 95% CI: 1.056-1.557), total cholesterol ( OR=1.712, 95% CI: 1.525-1.923), triglyceride ( OR=4.115, 95% CI: 3.621-4.676), alanine aminotransferase ( OR=1.467, 95% CI: 1.104-1.950), γ-glutamyltransferase ( OR=1.482, 95% CI: 1.242-1.769), fasting blood glucose ( OR=2.479, 95% CI: 2.092-2.939) and serum uric acid ( OR=1.390, 95% CI: 1.236-1.563) were independent metabolic risk factors for lean NAFLD (all P<0.05). Conclusions:The levels of various metabolic markers in young and middle-aged patients with lean NAFLD increase, and the risk of lean NAFLD increases. Metabolic markers are helpful to screen people at risk of lean NAFLD.

OBJECTIVE To investigate the protective effect of sodium-glucose cotransporter 2 inhibitors empagliflozin (EMPA) and dapagliflozin(DAPA) on palmitic acid(PA)-induced injury of rat H9c2 cardiomyocytes and its possible mechanism. METHODS H9c2 myocardial cell injury was induced by PA. CCK-8 method was used to screen the optimal dosage of PA, EMPA and DAPA. The protein expression levels of TLR4, p-AKT, p-mTOR, Nrf2 and HO-1 were detected by Western blotting. The expressions of IL-1β, IL-6, TNF-α were detected by ELISA. ROS levels in PA-induced H9c2 cardiomyocytes were determined by fluorescence microscopy and flow cytometry. RESULTS The survival rate of H9c2 cardiomyocytes decreased significantly after treatment of PA 100 μmol·L-1 for 24 h(P<0.01), the expression of IL-1β, IL-6, TNF-α, TLR4, p-mTOR and ROS were significantly increased(P<0.01), and the protein expression of p-AKT, Nrf2 and HO-1 was significantly decreased(P<0.01). Compared with the model group, the cell survival rate was significantly increased after EMPA and DAPA treatment(P<0.01), the expression of IL-1β, IL-6, TNF-α, TLR4, p-mTOR and ROS levels were significantly decreased(P<0.05 or P<0.01), and the protein expression of p-AKT, Nrf2 and HO-1 was significantly up-regulated(P<0.05 or P<0.01). CONCLUSION EMPA and DAPA have protective effects on PA-induced cardiomyocyte injury, and the mechanism may be related to down-regulation of TLR4 and p-mTOR protein expression, enhancement of AKT protein phosphorylation, activation of Nrf2/HO-1 pathway, and inhibition of ROS generation.

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.

The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team’s role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.