Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Infrared spectroscopy technology has many advantages such as high efficiency and non-destructiveness,and has an important research and application value in the field of petroleum pollutant classification and detection.In this study,a petroleum pollutant classification method by combing the discrete wavelet transform(DWT)algorithm and a one-dimensional convolutional neural network based on the Inception module(Inception-1D-CNN)was proposed.Firstly,the DWT algorithm was used to denoise the original infrared spectral data to eliminate the interference information caused by experimental environment,instrument error and manual operation.Then,the inception-1D-CNN model was used to obtain multi-scale infrared spectroscopy feature information,and then classify the petroleum pollutants.Experimental results showed that compared with preprocessing methods such as standard normal variable(SNV),adaptive iteratively reweighted penalized least squares(AirPLS),and Savitzky-Golay smoothing(S-G),the prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 3×1 was 86.6%,which was 6.6%,6.6%and 3.3%higher,respectively.The prediction accuracy of DWT algorithm combined with 1D-CNN model with a convolutional kernel size of 5×1 was 93.3%,which was 10.0%,7.0%and 3.3%higher,respectively.The prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 7×1 was 90.0%,which was 6.7%,10.0%and 3.4%higher,respectively.The prediction accuracy of the DWT algorithm combined with the inception-1D-CNN model was 100.0%,which was 10.0%,10.0%and 3.4%higher,respectively.Therefore,the DWT algorithm combined with the inception-1D-CNN model could accurately classify and predict petroleum pollutants,and provided a certain basis for the subsequent treatment of oil spills on the sea surface.

Objective:To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention(MSPI)in the clinical practice teaching of andrological nursing care.Methods:Using the Hamilton Depression Scale(HAMD),we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from De-cember 2021 to December 2022.We equally randomized the subjects into an experimental and a control group,the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention.Results:Compared with the baseline,the HAMD scores were significantly decreased in the experimental group after intervention(12.4±2.1 vs 8.9±2.4,P＜0.01),but increased in the controls(13.1±1.8 vs 14.7±1.9,P＜0.01);the skill scores dramatically increased in the experimental group(82.6±4.7 vs 91.2±2.4,P＜0.01),but decreased in the control group after intervention(81.0±3.5 vs 80.4±2.7,P=0.28).Conclusion:MSPI can significantly enhance the learning enthusiasm of nursing students in a short period,re-duce their psychological stress and improve teaching outcomes.This approach,combining psychology with teaching,can also strength-en the mental resilience of nursing students and better confront them with future professional challenges.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Nucleophosmin ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Leukemia, Myeloid, Acute/genetics* ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*