ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus （T2DM） rats based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） axis. MethodSix ZDF （fa/+） rats were as assigned to the blank group， and 30 ZDF （fa/fa） rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling， the rats were randomly divided into the model group， metformin group （0.18 g·kg^-1）， and low， medium， and high dose groups of modified Dahuang Huanglian Xiexintang （0.54， 1.08， 2.16 g·kg^-1）， with six rats in each group. After 12 weeks of drug intervention， the body mass， liver mass， fasting blood glucose （FBG）， and oral glucose tolerance test （OGTT） levels were measured. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， low-density lipoprotein cholesterol （LDL）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the activity of superoxide dismutase （SOD）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， and the level of malondialdehyde （MDA） in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group， the model group showed a significant increase in body mass， liver mass， and liver index （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight， liver mass， and liver index （P<0.01）. Compared with the normal group， the model group showed significantly increased TC， TG， and LDL levels （P<0.01）， and significantly decreased HDL levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels （P<0.01）， and significantly reduced TG levels （P<0.05）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels （P<0.05）. The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels （P<0.05）. Compared with the normal group， the model group showed significantly increased ALT and AST activities （P<0.01）. Compared with the model group， all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities （P<0.05） and significantly reduced AST activities （P<0.01）. Compared with normal group， the model group showed significantly increased FBG at all time points （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8， 10， 12 weeks. The OGTT results showed that compared with the normal group， the model group had significantly increased blood glucose at all time points （P<0.01）. Compared with the model group， the metformin group showed significantly reduced blood glucose at all time points （P<0.01）， and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90， 120 min （P<0.01）. HE pathology showed clear and regular liver cell structure in the normal group， while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang， with fewer necrotic cells. Compared with the normal group， the model group showed significantly reduced SOD and GSH-Px levels （P<0.01）， and significantly increased ROS and MDA levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels （P<0.01）， and significantly reduced MDA levels （P<0.01）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels （P<0.05）. Compared with the normal group， the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels （P<0.05）. Immunohistochemistry showed that compared with the normal group， the model group had significantly reduced positive expression of Nrf2 and HO-1 （P<0.05）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1， with a significant increase in brown-yellow granules around the cell nucleus （P<0.05）. Western blot results showed that compared with the normal group， the model group had significantly reduced protein expression of Nrf2 and HO-1 （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 （P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.

Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Objective:To study the expression of microRNA (miRNA)-4783-3p in liver cancer tissue and its effect on the proliferation and migration of liver cancer Huh-7 cells.Methods:The cBioPortal database was used to analyze the expression of miR-4783-3p in liver cancer tissues and adjacent tissues. In strict accordance with the instructions of Lipofectamine? 2000 transfection kit, miR-4783-3p overexpression mimics or overexpression control mimics were transfected into Huh-7 cells respectively, namely overexpression group and control group. The proliferation of Huh-7 cells was analyzed by CCK-8 assay, and the migration of Huh-7 cells was analyzed by cell scratch method. The targeting relationship between miR-4783-3p and insulin-like growth factor binding protein 2 ( IGFBP2) mRNA was detected by dual-luciferase reporter gene assay. RT-qPCR was used to detect the expression of IGFBP2 mRNA. Western-blotting was used to detect the expression of IGFBP2 protein and EGFR-STAT3 molecular pathway proteins. Results:The expression of miR-4783-3p in liver cancer tissues was significantly lower than that in adjacent tissues ( P<0.01). Compared with the control group, the proliferation ability of Huh-7 cells in the overexpression group was significantly decreased ( P<0.05). The scratch healing rates of Huh-7 cells in the control group and the overexpression group were (67.71±9.04)% and (29.58±10.51)%, respectively, and the scratch healing rate in the overexpression group was significantly lower ( P<0.01). miR-4783-3p targeted and bound to IGFBP2 mRNA ( P<0.01). The expression of IGFBP2 mRNA in the control and overexpression groups was 5.76±1.44 and 0.99±0.47, respectively, and miR-4783-3p negatively regulated the expression of IGFBP2 mRNA ( P<0.01). Compared with the control group, the expressions of IGFBP2 protein and EGFR-STAT3 molecular pathway protein were decreased in the overexpression group. Conclusions:miR-4783-3p is lowly expressed in liver cancer tissues. miR-4783-3p can attenuate the proliferation and invasion ability of liver cancer Huh-7 cells by inducing the low expression of IGFBP2 gene.

OBJECTIVE: To investigate the clinical value of hemoglobin to serum creatinine ratio (Hb/SCr) combined with blood uric acid (SUA) in predicting in-hospital mortality after emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: The clinical data of AMI patients who underwent emergency PCI in the First Affiliated Hospital of Kangda College of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. The general information, underlying medical history, blood routine, liver and kidney function, blood coagulation routine, SUA and other indicators were collected from patients. The primary composite endpoint was defined as in-hospital death, including in-hospital all-cause death during PCI and 15-day post-procedure hospitalization. Multivariate Logistic regression was used to analyze factors associated with in-hospital death after emergency PCI in patients with AMI. Multivariate Logistic regression was used to analyze the independent related factors and construct a risk prediction model. The Hosmer-Lemeshow method and receiver operator characteristic curve (ROC curve) were used to test the goodness of fit and predictive effect of the model and correlates, respectively. RESULTS: A total of 1 976 patients were enrolled, 92 died in hospital and 1 884 survived. SUA was higher in the death group than that in the survival group (μmol/L: 476.88±132.04 vs. 354.87±105.31, P < 0.01), and the Hb/SCr ratio was significantly lower than that in the survival group (13.84±5.48 vs.19.20±5.74, P < 0.01). Pearson analysis showed a linear negative correlation between SUA and Hb/SCr ratio (r = -0.502, P < 0.01). Logistic regression risk model analysis finally included age [odds ratio (OR) = 0.916], Hb/SCr ratio (OR = 0.182), white blood cell count (WBC, OR = 2.733), C-reactive protein (CRP, OR = 3.611), SUA (OR = 4.667), blood glucose (Glu, OR = 2.726), homocysteine (Hcy, OR = 2.688) 7 factors to construct a risk prediction model, which were independent correlation factors for in-hospital death in AMI patients after emergency PCI (all P < 0.05). Hosmer-Lemeshow test verified the fitting effect of the model, and the result showed P = 0.447. The area under the ROC curve (AUC) of the model for predicting in-hospital death in AMI patients after emergency PCI was 0.764 [95% confidence interval (95%CI) was 0.712-0.816, P = 0.001]. When the cut-off value was 0.565 8, the sensitivity was 70.7%, the specificity was 70.2%, and the Yoden index was 0.410. When Hb/SCr ratio+SUA, SUA, Hb/SCr ratio, Hb and SCr were used to predict in-hospital death in AMI patients after emergency PCI, the AUC of Hb/SCr ratio+SUA was the largest, which was 0.810. When the optimal cut-off value was -0.847, the sensitivity was 77.7%, the specificity was 74.5%, and the Youden index was 0.522. CONCLUSIONS Age, SUA, Hb/SCr ratio, WBC, CRP, Glu, and Hcy are independent risk factors for in-hospital death after emergency PCI in AMI patients. The lower the Hb/SCr ratio and the higher the SUA at admission, the higher the risk of in-hospital death after emergency PCI in AMI patients. Hb/SCr ratio combined with SUA has a higher predictive value for in-hospital death after emergency PCI in AMI patients than single index, which is helpful for early identification of high-risk patients.
Humans ; Hospital Mortality ; Uric Acid ; Creatinine ; Percutaneous Coronary Intervention ; Retrospective Studies ; Myocardial Infarction/therapy* ; Prognosis

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

OBJECTIVE：To establish the fingerprint of crude/vinegar-processed Corydalis yanhusuo decoction pieces and their dispensing granules，and to determine the contents of five alkaloids （protopine，tetrahydropalmatine，corydaline，berberine hydrochloride，palmatine hydrochloride ）. METHODS ：HPLC method was adopted. The determination was performed on Agilent TC-C18 column with mobile phase consisted of 0.1％ phosphoric acid solution-methanol （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 280 nm，and the column temperature was 30 ℃. The sample size was 10 μL. Using palmatine hydrochloride as reference ， Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition） was used to establish the fingerprint of 11 059） batches of C. yanhusuo decoction pieces ，7 batches of crude . yanhusuo dispensing granules ， 12 batches of vinegar- processed C. yanhusuo decoction pieces and 11 batches of vinegar-processed C. yanhusuo dispensing granules. The same HPLC method was adopted to determine the contents of protopine， tetrahydropalmatine， corydaline， berberine hydrochloride and palmatine hydrochloride in 41 batches of crude/ vinegar-processed C. yanhusuo decoction pieces and their dispensing granules. RESULTS ：There were 12 and 20 common peaks for crude C. yanhusuo decoction pieces and its dispensing granules ，and 14 and 16 common peaks for vinegar-processed C. yanhusuo decoction pieces and its dispensing granules. The similarity of each batch of same type were 0.529-0.981，0.342-0.985， 0.711-0.999，0.437-0.998，respectively. The linear range of protopine ，tetrahydropalmatine，corydaline，berberine hydrochloride and palmatine hydrochloride were 1.9-38.0，2.0-40.0，2.2-44.0，2.6-52.0，2.3-46.0 μg/mL（R2＞0.999 0）. The recoveries were 100.12％-100.98％（RSD＝1.05％-1.90％，n＝9）. RSDs of precision ，reproducibility，stability（24 h）and durability tests were all lower than 2.0％. The average contents of five alkaloids in different batches of crude/vinegar-processed C. yanhusuo decoction pieces and its dispensing granules were 0.24-0.46，0.37-0.82，0.24-0.58，0.07-0.75，0.24-0.76 mg/g. RSDs were 12.27％-147.48％. CONCLUSIONS：The fingerprint of crude/vinegar-processed C. yanhusuo decoction pieces and its dispensing granules is established successfully. The similarities of fingerprint are different before and after processing with vinegar ，and the contents of five alkaloids in C. yanhusuo decoction pieces and its dispensing granules are greatly different.

Objective: To analyze the influence of cognition on suicidal ideation in patients with major depressive disorder. Methods: A total of 108 inpatients with major depressive disorder from January 2017 to September 2018 in Beijing Huilongguan Hospital were enrolled.They were divided into suicidal ideation group (n=42) and non-suicidal ideation group (n=66) by the self-rating idea of suicide scale (SIOSS). Cognition was assessed by Repeatable Battery for the Assessment of Neuropsychological Status(RBANS). The general situation was assessed by self-made general situation questionnaire.The related factors were analyzed by Logistic regression. Results: (1) The rate of suicidal ideation was 44.4% in patients with major depressive disorder.(2) The total score of RBANS and five-factor scores of RBANS in suicidal ideation group were lower than those in non-suicidal ideation group(total RBANS score(63.0±7.9) vs (73.8±7.7); immediate memory: (62.7±8.8) vs (70.8±7.6); visual span: (67.2±10.0) vs (72.7±9.8); speech function: (83.3±13.8) vs (91.5±4.5); attention: (85.3±11.9) vs (99.9±8.5); delayed memory: (53.5±7.7) vs (62.3±9.7), F=6.335-46.660, P<0.05). (3)Logistic regression showed, years of education were risk factors for suicidal ideation(β=0.289, P=0.013, OR=1.335, 95%CI=1.063-1.676), RBANS attention factor(β=-0.161, P=0.000, OR=0.851, 95%CI=0.778-0.931)and RBANS delayed memory factor score(β=-0.151, P=0.006, OR=0.860, 95%CI=0.772-0.957)were protective factors for suicidal ideation. Conclusion Cognitive function has an impact on suicide ideation of depressive patients, mainly attention and delayed memory are protective factors for suicide ideation.

BACKGROUNDIdiopathic pulmonary fibrosis (IPF) is a lethal chronic interstitial lung disease (ILD) of unknown cause and having a variable and unpredictable course. This study aimed to summarize the clinical features and follow-up outcomes and to identify potential factors useful for the assessment of prognosis in IPF.

METHODSTwo hundred and ten patients hospitalized and diagnosed as IPF in our unit from January 1999 to June 2007 were enrolled into this study. The baseline demographic, clinical, radiologic and physiologic characteristics were summarized. Clinical follow-up data until February 2010 were collected, and the median survival time and 1-, 2-, and 5-year survival rates, as well as the influences of the summarized baseline variables on the prognosis were analyzed.

RESULTSThe age at diagnosis as IPF was (64 ± 10) years, the duration before diagnosis of 106 patients (50%) was shorter than 2 years, and 73% were males. One hundred and forty-five patients (69%) had a history of smoking with a median pack-year of 18. Eighty-nine patients (42%) had emphysema and 62 patients (29%) pulmonary arterial hypertension (PAH). One hundred and twenty-four patients were followed up, of which 99 patients died from various causes including respiratory failure related to IPF (93%). The follow-up period was (21 ± 23) months. The median survival time was 38 months. The 1-, 2-, and 5-year survival rates were 61%, 52%, and 39%, respectively. Multivariate analysis showed clubbing, PAH, duration from initial onset to diagnosis, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) were independent prognostic indicators of IPF.

CONCLUSIONIPF patients who have clubbing, PAH, a higher FEV1/FVC, and a short duration from initial onset to diagnosis have a poorer outcome.

Aged ; Emphysema ; diagnosis ; mortality ; physiopathology ; Female ; Humans ; Hypertension, Pulmonary ; diagnosis ; pathology ; physiopathology ; Idiopathic Pulmonary Fibrosis ; diagnosis ; mortality ; physiopathology ; Male ; Middle Aged

Objective To evaluate the optimal surgical approach for huge liver neopiasms in the caudate lobe.Methods Thirty-three patients with huge liver neplasms（≥10cm) underwent caudate lobectomy at a single tertiary referral center between January 2001 and June 2007.The surgical out-comes of pateints who underwent isolated caudate lobectomy or caudate lobectomy combined with partial hepatectomy were compared.Result Fifteen（45.5％）of 33 patients underwent isolated total or partial caudate lobectomy（group A）,whereas 18（54.5％) had total or partial caudate lobectomy cellular carcinoma (HCC) (51.5％),followed by hemangioma(21.2％),intrahepatic cholangiocarcinoma(9.1％),angiomyolipoma(6.1％),hepatic adenoma (3％),focal nodular hyperplasia(3％),colorectal liver metastases(3％)and sarcoma(3％).The median diameter of the tumour was 12.3 (range,10.2-21)cm.Patients in group A had significantly longer operative time (280 minutes vs.170 minutes),longer length of hospital stay (17 days vs.12 days)and more blood loss(1250 ml vs.670 ml) than patients in group B.There was no perioperative death in the 2 groups of pateints.Complication rates in group A and group B were 26.7％ and 16.7％ respectively.There was no disease-related death in patients with benign lesions.The1-,3- and 5-year disease-free survivals of patients with malignant lesions in group A and group B were 25.9％,0％,0％and 74.3％,46.7％,31.2％,respectively.The 1-,3- and 5-year overrall survivals were 68.6％,19.7％,0％ and 100％,66.5％,41.8％,respecively.Conclusion The approach to caudate lobectomy depends on the size and location of the lesion and the liver functional reserve.For patients with sufficient liver functional reserve,caudate lobectomy combined with partial hepatectomy is preferred because it is technically less demanding.For patienls with marginal liver functional reserve,isolated caudate lobectomy is the only viable surgical option.