Identification of potential diagnostic and prognostic biomarkers for papillary thyroid microcarcinoma (PTMC) based on TMT-labeled LC-MS/MS and machine learning.

OBJECTIVES: To explore the molecular mechanisms underlying aggressive progression of papillary thyroid microcarcinoma and identify potential biomarkers. METHODS: Samples were collected and sequenced using tandem mass tag-labeled liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) were identified and further analyzed using Mfuzz and protein-protein interaction analysis (PPI). Parallel reaction monitoring (PRM) and immunohistochemistry (IHC) were performed to validate the DEPs. RESULTS: Five thousand, two hundred and three DEPs were identified and quantified from the tumor/normal comparison group or the N1/N0 comparison group. Mfuzz analysis showed that clusters of DEPs were enriched according to progressive status, followed by normal tissue, tumors without lymphatic metastases, and tumors with lymphatic metastases. Analysis of PPI revealed that DEPs interacted with and were enriched in the following metabolic pathways: apoptosis, tricarboxylic acid cycle, PI3K-Akt pathway, cholesterol metabolism, pyruvate metabolism, and thyroid hormone synthesis. In addition, 18 of the 20 target proteins were successfully validated with PRM and IHC in another 20 paired validation samples. Based on machine learning, the five proteins that showed the best performance in discriminating between tumor and normal nodules were PDLIM4, ANXA1, PKM, NPC2, and LMNA. FN1 performed well in discriminating between patients with lymph node metastases (N1) and N0 with an AUC of 0.690. Finally, five validated DEPs showed a potential prognostic role after examining The Cancer Genome Atlas database: FN1, IDH2, VDAC1, FABP4, and TG. Accordingly, a nomogram was constructed whose concordance index was 0.685 (confidence interval: 0.645-0.726). CONCLUSIONS: PDLIM4, ANXA1, PKM, NPC2, LMNA, and FN1 are potential diagnostic biomarkers. The five-protein nomogram could be a prognostic biomarker.

[Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma].

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR+/IG-, 26.3% (5/19) TCR+/IG+, 10.5% (2/19) were TCR－/IG－, and 5.3% (1/19) TCR－/IG+. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR－/IG－, 1 case with TCR－/IG+, and 1 case with TCR+/IG+; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR－/IG－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION: Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

Observation of the short-term curative effect of using SuperPATH approach to treat elderly femoral neck fractures with schizophrenia.

As China enters an aging society, the incidence of femoral neck fractures is increasing year by year. For some patients, total hip arthroplasty (THA) is the treatment of choice for displaced femoral neck fractures. Schizophrenia is a common combination of elderly patients with femoral neck fractures, and there are few reports on the treatment. This study describes the short-term efficacy of the supercapsular percutaneously assisted (SuperPATH) approach in the treatment of patients suffered with displaced femoral neck fractures combined with schizophrenia. A retrospective analysis of 20 elderly patients with displaced femoral neck fractures combined with schizophrenia who underwent THA using the SuperPATH approach. Record demographic data, postoperative reexamination of X-ray film to observe the position and the loosening condition of the prosthesis, the length of hospitalization, complications in the hospital and after discharge. The Harris score of hip joint function was used to evaluate postoperative hip joint function. The average age of the 20 patients was 73.1 years. All patients were followed up by outpatient clinic or telephone. The follow-up time was 3-12 months, with an average of 9.2 months. There was no incision infection, no tissue structure damage such as important nerves and blood vessels, and no complications such as early dislocation, loosening of the joint prosthesis, and deep vein thrombosis of lower extremities. The efficacy of the last follow-up was evaluated according to the Harris score of hip joint function: an average of 91 points (78-98 points); 13 cases were excellent, 5 cases were good, and 2 cases were fair. The SuperPATH approach has the advantages of less surgical damage, shorter recovery time, good surgical safety, preserving the normal tension of the muscles around the hip joint, and reducing the incidence rate of early postoperative dislocation of the joint prosthesis. The THA of the SuperPATH approach can treat patients with displaced femoral neck fractures combined with schizophrenia safely and effectively.

[Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report].

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

[Prognostic value of perioperative change of neutrophil elastase and myeloperoxidase in coronary circulation on perioperative myocardial injury and clinical outcome of patients underwent surgical valve replacement].

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 µg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) µg/L vs. (447.2±135.9) µg/L, P<0.01) and NE ((417.0±83.1)µg/L vs. (341.0±68.3)µg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.

CTNNBIP1 modulates keratinocyte proliferation through promoting the transcription of ß-catenin/TCF complex downstream genes.

BACKGROUND: During psoriasis initiation and development, deregulations in signalling pathways and gene expression are observed. METHODS: Herein, we downloaded seven sets of microarray mRNA expression profiles showing differentially expressed genes in psoriasis lesion skin and non-lesion skin tissues and three sets of RNA-seq data and analysed these online data attempting to screen for crucial genes related to keratinocyte proliferation and psoriasis development. The expression of CTNNBIP1 in psoriasis patients and IMQ mouse model skin tissues were examined by RT-PCR, immunoblotting and IHC. The functions of CTNNBIP1 on HaCaT cell proliferation, apoptosis and ß-catenin/TCF complex were measured by MTT, EdU, flow cytometry, IF, luciferase assays and immunoblotting. RESULTS: The expression of catenin beta interacting protein 1 (CTNNBIP1) was remarkably downregulated within psoriasis lesion skin tissue samples compared to that within non-lesion skin tissues based on both online data and experimental results. In response to a period of different therapies, respectively, CTNNBIP1 expression could be rescued in lesion skin tissues. Within IMQ-induced psoriasis-like dermatitis in mice, CTNNBIP1 silence further aggravated psoriatic phenotypes. In human immortalized keratinocytes, HaCaT cells, CTNNBIP1 silence significantly inhibited cell apoptosis and promoted cell proliferation. Regarding the molecular mechanism, CTNNBIP1 silence in HaCaT cells promoted ß-catenin nucleus translocation, enhanced the transcriptional activity of TCF4 and increased ß-catenin/TCF complex downstream c-Myc and cyclin D1 proteins, and also increased the expression of cell proliferation marker ki-67. In contrast to CTNNBIP1, the expression of c-Myc and cyclin D1 showed to be dramatically upregulated within psoriasis lesion tissue samples than that within non-lesion tissue samples. Within tissues, c-Myc and cyclin D1 showed to be negatively correlated with CTNNBIP1, respectively. CONCLUSIONS: We identify CTNNBIP1 as an abnormally downregulated gene in psoriasis. CTNNBIP1 silence significantly disturbs the proliferation of keratinocytes through promoting the transcription of ß-catenin/TCF complex downstream genes.

[Analysis of risk factors for lymphoma patients dying of cardiovascular disease].

Objective: To understand and explore the risk factors of the death of lymphoma patients from cardiovascular disease. Methods: The medical records and death information of 1 173 patients with lymphoma were collected, cases that died from cardiovascular disease were screened. A binary logistic regression model was used to analyze the independent risk factors of patients with lymphoma died from cardiovascular disease. Results: Among 1 173 patients with lymphoma, 75 (6.4%) died of cardiovascular disease, including 27 cases of coronary heart disease, 25 cases of stroke, 7 cases of hypertension, 5 cases of sudden cardiac death, 4 cases of pulmonary embolism, 3 cases of heart failure, 4 cases of others. Among the patients who survived for more than 5 years, 16.1% (35/217) died of cardiovascular disease. Among those who survived for more than 10 years, 11.7% (7/60) died of cardiovascular disease. Multivariate Logistic regression analysis showed that the primary site of lymphoma (OR=0.521, P=0.039), stage (stage Ⅱ: OR=2.487, P=0.016; stage Ⅲ: OR=3.233, P=0.002) and cardiovascular toxicity in the course of diagnosis and treatment (OR=3.019, P=0.001) are independent influencing factors for the death of cardiovascular disease in patients with lymphoma. Patients whose primary sites of lymphoma were lymph nodes had lower risk of dying from cardiovascular disease, while the patients with stage Ⅱ to Ⅲ stage and cardiovascular toxicity during diagnosis and treatment had higher risk of dying from cardiovascular disease. Conclusions: Cardiovascular disease is an important factor affecting the survival of patients with lymphoma. With the extension of survival time, the risk of dying from cardiovascular disease increases significantly. The primary site, tumor stage, and cardiovascular toxicity that occur during the diagnosis and treatment may be the independent influencing factors for patients with lymphoma that die from cardiovascular disease.

[Analysis of the characteristics of second primary malignancy affecting the survival of lymphoma patients].

Objective: To analyze the characteristics of the second primary tumor affecting the survival of patients with lymphoma, and to explore the risk factors of death from the second primary tumor. Methods: The medical records and related death information of 1 173 lymphoma patients who had already died with known causes were collected. The basic causes of death and the characteristics of patients who died of the second primary tumor were analyzed. Cox regression model was used to analyze the risk factors of lymphoma patients who died of the second primary tumor. Results: Among the 1 173 patients who had died, 94 (8.0%) died of the second primary tumor, 935 (79.7%) died of the primary lymphoma and 144 (12.3%) died of other diseases. The second primary tumor accounted for 17.5% (38/217) of all causes of death in patients with the survival period of more than 5 years, and the second primary tumor accounted for 28.3% (17/60) of all causes of death in patients with the survival period of more than 10 years. Among 94 cases who died of second primary tumors, 31 died of lung cancer, 15 died of gastric cancer, 13 died of liver cancer, 9 died of pancreatic cancer, 6 died of colorectal cancer, 6 died of second primary lymphoma and 14 died of other types of tumors. Univariate Cox regression analysis showed that age, first-line treatment effect, and chest or mediastinal radiotherapy were associated with the death from second primary tumors for lymphoma patients (all P<0.05). Multivariate Cox regression analysis showed that the effect of first-line treatment (P=0.030) and the chest or mediastinal radiotherapy (P=0.039) were independent factors for the death of lymphoma patients from the second primary tumor. Conclusions: The second primary tumor is an important factor affecting the survival of lymphoma patients, and the risk of death from second primary tumors increases significantly over time. The effect of first-line treatment and radiotherapy in the chest or mediastinum are independent factors for the death of lymphoma patients from the second primary tumor.

[Cyclopexy on cyclodialysis cleft guided by anterior segment optic coherence tomography].

Objective: To analyze the accuracy of cyclopexy on traumatic cyclodialysis cleft guided by anterior segment optic coherence tomography (AS-OCT). Methods: Fifty-six eyes of 56 consecutive patients[41 males, 15 females, with a mean age of (43.14±13.85) years]who diagnosed with traumatic cyclodialysis cleft confirmed by ultrasound biomicroscopy (UBM) and underwent cyclopexy surgery at Shanxi Eye Hosiptal from July 2013 to February 2016 were included in the study. Patients were measured with the AS-OCT system before cyclopexy. AS-OCT findings of the cyclodialysis clefts were recorded. Localizing and suturing the clefts was guided by AS-OCT imaging. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP) and anterior chamber depth (ACD) were recorded and analyzed. Results: Imaging of preoperative AS-OCT of the 56 eyes showed an annular ciliary body detachment, a cyclodialysis cleft and shallow anterior chamber. The ciliary body detachment detected by AS-OCT showed an echo free zone between the annular ciliary body and the sclera. The cyclodialysis cleft showed a new pathway between the anterior chamber and the suprachoroidal space. AS-OCT imaging showed that the extent of cyclodialysis clefts ranged from 30 degrees to 240 degrees, which had a 0 degree to 20 degrees difference compared with UBM imaging. Localizing and suturing of the cyclodialysis clefts was guided by AS-OCT imaging. The best corrected visual acuity (BCVA) was 0.21±0.17 at baseline and 0.29±0.21 at five days postoperatively. The initial and final BCVA showed a remarkable difference after treatment (t=-4.98, P<0.01). The mean intra-ocular pressure (IOP) was (8.33±2.29) mmHg before surgery and (15.40±2.34) mmHg at five days postoperatively. There was a significant difference of IOP between preoperative and postoperative period (t=-16.590, P<0.01). The mean ACD was (1.94±0.45) mm preoperatively and (2.69±0.44) mm at five days postoperatively. There was also a significant difference of ACD between preoperative and postoperative period (t=-10.276, P<0.01). The postoperative reexamination found that ciliary body detachment or cyclodialysis clefts was not observed in the 56 eyes by AS-OCT. Conclusions: As a non-invasive method, AS-OCT is accurate, correlating well with UBM in the examination of cyclodialysis cleft, and can localize the extent of clefts before cyclopexy.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

[Clinical features of acute diffuse pulmonary exudative disorders].

Objective: To analyze the clinical features of acute diffuse pulmonary exudative disorders. Methods: The data were collected from patients who were hospitalized in respiratory intensive care unit (RICU) of Beijing Chaoyang Hospital affiliated to the Capital Medical University during January 2009 to December 2011, and had acute clinical course with imaging findings of diffuse pulmonary infiltrated shadows (similar to acute respiratory distress syndrome (ARDS)). The causes of disease and clinical features were analyzed. Results: A total of 86 patients with acute diffuse pulmonary exudative disorders were included. Sixty-two (72.1%) were males, with a mean age of (58.6±16.4) years old; 24(27.9%) were females, with a mean age of (48.2±18.3) years old. The duration of the disease before administration was (11.5±5.2) days, and RICU stay was (15.5±9.5) days, with hospital mortality of 40.7% and the average hospitalization cost of 101 thousand RMB. The main cause was infection, which occurred in 53 cases (61.6%) (virus in 21 cases, bacteria in 14 cases, fungus in 11 cases, pneumocystis in 15 cases and others in 3 cases, mixed infection in 11 cases). Interstitial pneumonia occurred in 12 cases (idiopathic interstitial pneumonia in 9 cases: cryptogenic organizing pneumonia in 3 cases, the acute exacerbation of idiopathic pulmonary fibrosis in 3 cases, nonspecific interstitial pneumonia in 1 case, acute interstitial pneumonia in 2 cases, and connective tissue disease in 3 cases), aspiration pneumonia in 10 cases, acute left heart failure in 6 cases, and exogenous pulmonary ARDS in 5 cases. Conclusions: The main cause of acute diffuse pulmonary exudative disorders is pulmonary infection, followed by interstitial pneumonia. The hospital mortality and hospitalization cost are high.

[Feasibility and value of index of microcirculatory resistance in patients with acute myocardial infarction after primary percutaneous coronary intervention].

Objective: To evaluate the feasibility of detecting index of microcirculatory resistance (IMR) and the relationship between IMR and left ventricular (LV) systolic function after acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The patients with first AMI received primary PCI in Peking University Third Hospital were enrolled from January 2014 to March 2016. IMR were measured immediately after PCI by using pressure/temperature wire. The relationship between IMR and left ventricular ejection fraction (LVEF) assessed by echocardiography at first day and 6 months after admission was evaluated. Results: Twenty-eight patients with anterior wall AMI were enrolled, with an average age (56±13) years. The success rate of IMR detection was 100%. The mean IMR was (33±18 )mmHg·s. There was no complication related to intravenous adenosine triphosphate (ATP) (140 µg· kg(-1)· min(-1)). The IMR was negatively correlated with TIMI blood flow grade after primary PCI (r=-0.386, P=0.043), and positively correlated with female gender, CK peak value and TnT peak value (r=0.430, P=0.022; r=0.431, P=0.025; r=0.434, P=0.024). After 6 months of follow-up, no adverse cardiovascular events (including cardiac death, nonfatal myocardial infarction, malignant arrhythmia, unplanned revascularization, hospitalization for unstable angina pectoris and severe heart failure requiring hospitalization) occurred. LVEF increased significantly compared with the first day after PCI (0.54±0.08 vs 0.47±0.06, P=0.001), and IMR was negatively correlated with LVEF after 6 months (r=-0.477, P=0.014). Multivariable linear regression analysis showed that CK peak and IMR were predictors of LVEF after six months ( ß=-0.595, t=-3.814, P=0.01; ß=-0.352, t=-2.26, P=0.036). Conclusions: Immediate detection of IMR in patients with anterior wall AMI after PCI is safe and feasible. The immediate IMR after PCI reflects the extent of myocardial necrosis and myocardial perfusion, and is a predictor of LVEF at 6 months after PCI.

[The Changes of HIF-1α and VEGF-A in Myocardial Tissue of Rats with Arrhythmias].

OBJECTIVES: To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency. METHODS: The arrhythmia was induced by CaCl2, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats. RESULTS: The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time. CONCLUSIONS: The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.

There is no correlation between sublineages and drug resistance of Mycobacterium tuberculosis Beijing/W lineage clinical isolates in Xinjiang, China.

The Beijing/W lineage strains are the major prevalent strains in China. The prevalence, mortality and drug-resistant rates of tuberculosis in Xinjiang, Northwestern China are higher than in other parts of the country. Our previous study results showed that the dominant strains of Mycobacterium tuberculosis (MTB) were 'Beijing/W lineage' MTB in Xinjiang; those strains had no significant correlation with drug resistance. We investigated whether the prevalence of 'Beijing/W lineage' sublineage strains was associated with drug resistance. We collected 478 sputum specimens from patients with pulmonary tuberculosis. Beijing/W strains and their sublineages were identified by distinguishing five specific large sequence polymorphisms, using polymerase chain reaction. All strains were subjected to a drug susceptibility test using the proportion method on Löwenstein-Jensen culture medium. In total, 379 clinical isolates of MTB were isolated and identified, 57·26% of these isolates were identified as Beijing/W strains, of which 11·06% isolates were in sublineage 105, 14·74% isolates in sublineage 207, 69·59% isolates in sublineage 181, and 4·61% isolates in sublineage 150. None of the isolates was in sublineage 142. Our data showed there were four sublineages of Beijing/W isolates in Xinjiang province, China. However, there were no correlations between drug resistance and the sublineages of Beijing/W strains.

[Myocardial protection of remote ischemic postconditioning during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction].

OBJECTIVE: To evaluate the cardioprotection of remote ischemic postconditioning (RIPostC) in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: Forty-six STEMI patients undergoing primary PCI at Peking University Third Hospital from January to April 2014 were randomized to RIPostC group (n=23) and control group (n=23).The RIPostC protocol was started within 1 min after reflow by thrombus aspiration or balloon inflation and consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower left limb. The enzymatic infarct size, rate of complete ST segment resolution, corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) in infarct-related artery (IRA) and plasma levels of malondialdehyde(MDA), endothelin-1(ET-1), tumor necrosis factor α (TNFα) of the two groups were compared. RESULTS: There was no significant difference in enzymatic infarct size between the two groups (P>0.05). The rate of complete ST-segment resolution was significantly higher in RIPostC group than in control group (60.9%vs. 30.4%,P=0.04). There was a trend toward lower CTFC in RIPostC group than that in control group, but the difference was not statistically significant(28 ± 11 vs. 33 ± 11, P = 0.10). However, in the subgroup of anterior wall myocardial infarction CTFC in RIPostC group was significantly lower, compared with control group (25±9 vs. 39±10, P=0.01).There were lower plasma levels of MDA,ET-1,TNFα in RIPostC group than in control group at different time points after primary PCI (P<0.05). CONCLUSION: In STEMI patients undergoing primary PCI, RIPostC may improve myocardial perfusion and attenuate ischemia reperfusion injury with the underlying mechanisms involving reduction of oxidative stress, protection of endothelial function and inhibition of inflammatory response.

[An intelligent model for classifying supraventricular tachycardia mechanisms based on 12-lead wearable electrocardiogram devices].

OBJECTIVE: To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT) using 12-lead wearable electrocardiogram devices. METHODS: A total of 356 samples of 12-lead supraventricular tachycardia (SVT) electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model, and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October, 2021 to March, 2023 were selected as the testing set. The changes in electrocardiogram parameters before and during induced tachycardia were compared. Based on multiscale deep neural network, an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated. The 3-lead electrocardiogram signals from Ⅱ, Ⅲ, and Ⅴ1 were extracted to build new classification models, whose diagnostic efficacy was compared with that of the 12-lead model. RESULTS: Of the 101 patients with SVT in the testing set, 68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study. The pre-trained model achieved a high area under the precision-recall curve (0.9492) and F1 score (0.8195) for identifying AVNRT in the validation set. The total F1 scores of the lead Ⅱ, Ⅲ, Ⅴ1, 3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597, 0.6061, 0.3419, 0.6003 and 0.6136, respectively. Compared with the 12-lead classification model, the lead-Ⅲ model had a net reclassification index improvement of -0.029 (P=0.878) and an integrated discrimination index improvement of -0.005 (P=0.965). CONCLUSION: The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Author Correction: LncRNA HOTAIRM1 inhibits the progression of hepatocellular carcinoma by inhibiting the Wnt signaling pathway.

Correction to: European Review for Medical and Pharmacological Sciences 2018; 22 (15): 4861-4868-DOI: 10.26355/eurrev_201808_15622-PMID: 30070317, published online 15 August 2018. After publication, the authors found some mistakes in the article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15622.

LncRNA HOTAIRM1 inhibits the progression of hepatocellular carcinoma by inhibiting the Wnt signaling pathway.

OBJECTIVE: To explore the possible role of long non-coding RNA (lncRNA) HOTAIRM1 in the pathogenesis of hepatocellular carcinoma (HCC) and its underlying mechanism. PATIENTS AND METHODS: LncRNA HOTAIRM1 expressions in 30 pairs of hepatocellular carcinoma tissues and paracancerous tissues were detected by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). The survival analysis and receiver operating characteristic (ROC) curve were introduced to explore the relationship between lncRNA HOTATRM expressions and prognosis of HCC patients. The correlation between overall survival and clinical variables of HCC patients was estimated by single-factor and multiple-factor regression analysis, respectively. Overexpression plasmid of lncRNA HOTAIRM1 was designed and transfected into HCC cells according to the instructions of Lipofectamine 2000. Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Moreover, expressions of apoptosis-related genes and the Wnt pathway-related proteins were detected by Western blot. RESULTS: Lower lncRNA HOTAIRM1 expressions were observed in the HCC tissues than those of the paracancerous tissues. ROC curve indicated a high sensitivity and specificity of lncRNA HOTAIRM1 for HCC. PFS in HCC patients was correlated with tumor size and lncRNA HOTAIRM1 expression, whereas not correlated with age, sex, GGT, AFP, Child-Pugh grade, HBsAg, cirrhosis, number of tumors, micro-vessel metastasis, tumor differentiation, and TNM stage of HCC. Overexpression of HOTAIRM1 led to decreased proliferative ability and increased apoptosis of HepG2 and HHCC cells. In addition, overexpressed lncRNA HOTAIRM1 remarkably increased the expression of apoptosis promotor Bax, but decreased the expressions of apoptosis inhibitors Bcl-2 and Bid. Meanwhile, expressions of related proteins in the Wnt pathway were decreased as well. CONCLUSIONS: HOTAIRM1, which was downregulated in HCC, might inhibit the proliferative ability and promote the apoptosis of HCC cells by suppressing the Wnt pathway, thereby inhibiting the progression of hepatocellular carcinoma.

Dl-3-n-butylphthalide protects the blood brain barrier of cerebral infarction by activating the Nrf-2/HO-1 signaling pathway in mice.

OBJECTIVE: The aim of this study was to explore whether Dl-3-n-butylphthalide (DBT) could protect blood-brain barrier (BBB) of mice with experimental cerebral infarction and the relevant mechanism. MATERIALS AND METHODS: Adult male CD-1 mice were selected as the study objects. The permanent middle cerebral artery occlusion (MCAO) model was prepared by Longa's modified suture-occluded method. The mice were randomly divided into 3 groups: the sham operation group (Sham group), the cerebral infarction model group (CI group) and the DBT (120 mg/kg) intervention group (DBT group). Neurologic function deficits were evaluated by Longa's modified scoring method after 24 h of permanent MCAO. The wet and dry weight method was used for measuring water content in brain tissues. 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining method was applied to determine the volume of cerebral infarction. Changes in the protein and messenger ribonucleic acid (mRNA) expression levels of matrix metallopeptidase 9 (MMP-9), claudin-5, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), NF-E2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in ischemic brain tissues were detected using immunohistochemistry, Western blotting and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Ultrastructure changes in BBBs were observed under an electron microscope. RESULTS: DBT improved the neurologic function deficits of mice and reduced the infarction volume of mice with cerebral infarction. DBT alleviated edema and decreased the permeability of BBBs of mice with cerebral infarction. DBT down-regulated the expression of MMP-9 and up-regulated the expression of claudin-5 in brain tissues of mice with cerebral infarction. DBT increased the expressions of VEGF and GFAP. DBT improved the ultrastructure in capillary endothelial cells of BBBs and increased the expressions of Nrf-2 and HO-1. CONCLUSIONS: DBT may protect BBB by activating the Nrf-2/HO-1 signaling pathway, thus achieving its protective effect on the brain.