[Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model].

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

[Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy].

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)µm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

MiR-135b-5p affected malignant behaviors of ovarian cancer cells by targeting KDM5B.

The article "MiR-135b-5p affected malignant behaviors of ovarian cancer cells by targeting KDM5B, by R. Ren, J. Wu, M.-Y. Zhou, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3548-3554-DOI: 10.26355/eurrev_202004_20815-PMID: 32329828" has been withdrawn from the authors stating that "some data cannot be repeated by our further research". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20815.

Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway.

The article "Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway, by J. Wu, M.-Y. Zhou, X.-P. Yu, Y. Wu, P.-L. Xie, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6991-6996-DOI: 10.26355/eurrev_201908_18739-PMID: 31486499" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18739.

Psychological support and the COVID-19 - A short report.

OBJECTIVE: The World Health Organization reported a cluster of cases of pneumonia of unknown cause detected on December 31, 2019 in China. Unfortunately, a 34-year-old Italian nurse has committed suicide after testing positive for coronavirus. It was the second case of suicide by a nurse in an Italian hospital and occurred only a few days after the first suicide. These consecutive suicides have aroused concern, and it is necessary to investigate the psychological issues of the medical staff in Italy regarding the COVID-19.

[Progress in diagnosis and treatment of rectal neuroendocrine neoplasms].

Neuroendocrine neoplasms (NENs) are relatively rare heterogeneous tumors that originate from peptidergic neurons and neuroendocrine cells and have been referred to as "carcinoids" in the past. Although this type of tumor had been previously considered to be indolent tumor with a low degree of malignancy, with the development of medicine and clinical study, researchers found that NENs had the potential to metastasize. They can occur in any part of the body where neuroendocrine cells are distributed and gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are the most common type of NENs.Due to the improvement of techniques such as endoscopy and imaging, the incidence of rectal neuroendocrine tumors(R-NENs) and the number of related clinical researches have both increased significantly in recent years. Although researches in Chinese and foreign medical centers are mostly retrospective studies of small samples and the efficacies of different treatment methods are still under debating and lack of sufficient medical evidence to support, the diagnosis and treatment of this disease is gradually becoming standardized according to the proposal of corresponding guidelines. The recent advances in the epidemiology, diagnosis and treatment of rectal neuroendocrine neoplasms are reviewed in this paper.

Internet+ and COVID-19 - A short report.

OBJECTIVE: COVID-19 broke out in China at the end of 2019 and spread rapidly around the world. The World Health Organization designated COVID-19 as a global pandemic on March 11, 2020. China has adopted its own country-specific comprehensive prevention and control measures, and, as a result, the domestic COVID-19 epidemic became effectively controlled in China in mid-March 2020. During the COVID-19 epidemic, remarkable changes have taken place in China's domestic learning, living, and working methods, primarily in terms of the synergy between the Internet Plus (Internet+) strategy and the leadership of the Chinese government.

MiR-135b-5p affected malignant behaviors of ovarian cancer cells by targeting KDM5B.

OBJECTIVE: The aim of this study was to investigate the potential effect of microRNA-135b-5p (miR-135b-5p) on the development of ovarian cancer (OC) and to explore the relevant mechanism. PATIENTS AND METHODS: The expression of miR-135b-5p in OC tissues and cells was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). MicroRNA online prediction websites were used to screen the potential targets of miR-135b-5p. Subsequently, luciferase reporter gene assay and Western blot (WB) were performed for further confirmation. In addition, the effects of miR-135b-5p on cell function were analyzed by relevant experiments in vitro. RESULTS: MiR-135b-5p was lowly expressed in both OC tissues and cell lines. Combined with online prediction software, luciferase reporter gene assay and WB, KDM5B was predicted and verified as a downstream target gene of miR-135b-5p. Down-regulating the expression of KDM5B by over-expressing miR-135b-5p in OC cells could effectively control the proliferation and apoptosis of OC cells. Cell proliferation was significantly reduced, while cell apoptosis was promoted after miR-135b-5p mimics transfection in OC cells. CONCLUSIONS: By targeting KDM5B, miR-135b-5p exerted an excellent anti-cancer effect in OC cells. Our findings indicated that miR-135b-5p/KDM5B might become a feasible and new target of OC treatment.

Mask crisis during the COVID-19 outbreak.

On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.

[Analysis of common gynecological diseases in 1142 married female workers].

Objective: To understand the prevalence of gynecologic diseases among married female workers. Methods: The data of married female workers who underwent occupational health examination in a physical examination center from January to December 2017 were collected. The relationship between the detection of common gynecological diseases, age and occupational types examined by gynecological routine, TCT, breast B-mode ultrasound, uterus and appendix B-mode ultrasound were analyzed. Results: Among the 1142 female workers, the total detection rate of reproductive tract infections was 67.25% (768/1142), the total detection rate of breast-related diseases was 75.22% (859/1142) ; the total detection rate of gynecological tumors and benign lesions was 14.71% (168/1142). The detection rate of breast hyperplasia was the highest 67.08% (766/1142), followed by vaginitis 51.66% (590/1142). Among the abnormalities detected in breast-related diseases, gynecological tumors and benign lesions, the highest detection rate was found in public institutions (85.66% and 27.13%), and the lowest was found in factory workers (70.24% and 7.89%). With the increase of age, the detection rate of breastrelated diseases (breast hyperplasia, breast cyst), gynecological tumors, benign lesions (uterine myoma), and Nessler's cyst abnormalities in married female workers increased (χ(2)(trend)=7.647、21.653、107.411、53.802, P<0.05), while the detection rate of columnar epithelium of cervix decreased (χ(2)(trend)=7.404, P<0.05). There was no significant difference in the total detection rate of reproductive tract infectious diseases (vaginitis, cervical polyps, cervical hypertrophy) among married famale workers of different ages (P<0.05) . Conclusion: The common gynecological diseases of married female workers are affected by many factors such as age and occupation. Health examination and health education should be carried out regularly to reduce the incidence of gynecological diseases among female workers according to different ages and occupations.

Long noncoding RNA OR3A4 promotes the migration and invasion of melanoma through the PI3K/AKT signaling pathway.

OBJECTIVE: Recent studies have revealed the crucial role of long non-coding RNAs (lncRNAs) in tumor progression. This study aims to identify the biological function of lncRNA OR3A4 in the progression of melanoma. PATIENTS AND METHODS: OR3A4 expression in melanoma cells and tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The regulatory effects of OR3A4 on melanoma cells were identified by performing transwell assay and wound healing assay in vitro. The underlying mechanism of OR3A4 in mediating the progression of melanoma was explored by RT-qPCR and Western blot. RESULTS: OR3A4 expression was remarkably upregulated in melanoma tissues compared with normal tissues. Moreover, migration and invasion of melanoma cells were inhibited after knockdown of OR3A4 in vitro, which were promoted after overexpression of OR3A4. Furthermore, the targeted proteins in phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway were downregulated after knockdown of OR3A4 in vitro, which were upregulated by overexpressed OR3A4. CONCLUSIONS: OR3A4 could promote the invasion and migration of melanoma cells by inducing the PI3K/AKT signaling pathway, which may offer a new therapeutic intervention for melanoma patients.

[Efficacy and safety of transthoracic echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation for the treatment of patients with obstructive hypertrophic cardiomyopathy].

Objective: To investigate the safety and efficacy of transthoracic echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Nine HOCM patients with interventricular septal thickness ≥15 mm and ≤25 mm who were treated with PIMSRA between October 2016 to March 2017 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled,and the clinical data were retrospectively analyzed.Interventricular septum thickness, left ventricular outflow tract diameter and maximum gradient were measured by transthoracic echocardiography immediately after procedure, at 1 month, 3 months and 6 months after operation.Symptoms and New York Heart Association (NYHA) functional class were assessed, and provoked left ventricular outflow tract gradient and exercise time were measured after 6 months. Results: The anterior interventricular septum ((21.5±2.6) mm vs. (24.7±2.7) mm, P<0.05) and posterior interventricular septum (21.1±2.5) mm vs. (22.6±3.3) mm, P<0.05) were significantly increased,left ventricular outflow tract diameter was widened ((8.2±3.4) mm vs. (4.8±2.2) mm, P<0.05), left ventricular outflow tract gradient ((26.8±19.6) mmHg (1 mmHg=0.133 kPa) vs. (83.3±32.4) mmHg, P<0.05) and mitral regurgitation (2.0±1.9) ml vs. (3.2±3.0) ml, P<0.05) were significantly decreased immediately after ablation compared with pre-operation values. Anterior interventricular septum, posterior interventricular septum and left ventricular outflow tract gradient further decreased after 1 month ((17.5±2.0) mm vs. (24.7±2.7) mm, P<0.05; (16.9±2.1) mm vs. (22.6±3.3) mm, P<0.05; (11.6±4.0) mmHg vs. (26.8±19.6) mmHg, P<0.05, respectively) compared with values immediately after ablation. Anterior interventricular septum and posterior interventricular septum decreased after 3 and 6 months ((14.8±1.7) mm and (13.4±2.0) mm vs. (17.5±2.0) mm, all P<0.05; (12.9±1.9) mm and (12.3±2.4) mm vs. (16.9±2.1) mm, all P<0.05, respectively) compared with values at 1 month after ablation.There were no significantly difference in left ventricular outflow tract gradient at 3 and 6 months post procedure compared with 1 month after ablation (all P>0.05). Compared with pre-operation, provoked left ventricular outflow tract gradient decreased ((25.5±11.4) mmHg vs. (147.8±58.0) mmHg, P<0.01), and total exercise time increased ((9.3±1.6) minutes vs. (6.7±1.6) minutes, P=0.03) at 6 months after operation.The symptoms were disappeared in 5 patients. There were 2 cases with NYHA class Ⅱ and 7 cases with NYHA class Ⅲ before operation,while there were 6 patients with NYHA classⅠ and 3 patients with NYHA class Ⅱ at 6 months after operation (P<0.01). Conclusion: Transthoracic echocardiography-guided PIMSRA is a safe and effective new treatment approach for patients with obstructive hypertrophic cardiomyopathy.

[The inhibition effects of apatinib on cell proliferation, migration and apoptosis in esophageal carcinoma via Ras/Raf/MEK/ERK and JAK2/STAT3 pathways].

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 µmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 µmol/L and 40 µmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 µmol/L, 20 µmol/L and 40 µmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 µmol/L and 40 µmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 µmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 µmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

Effects of dietary Mn-methionine supplementation on the egg quality of laying hens.

This study was conducted to investigate the effects of dietary manganese-methionine (Mn-Met) supplementation on the egg quality of laying hens. A total of 480 Jinghong-1 strain layers aged 53 wk were divided into 5 groups with 6 replicates of 16 layers. Birds in the control group were fed a diet supplemented with 60 mg Mn/kg in the form of MnSO4; the birds in other 4 experimental groups were fed a diet supplemented with 20, 40, 60, and 80 mg Mn/kg as Mn-Met, respectively. Dietary Mn-Met treatments significantly affected (P < 0.05) the albumen height, yolk color, and Haugh unit compared to those of the control diet. The Mn contents in the eggshell increased (P < 0.01) significantly by increasing the Mn-Met supplementation, whereas Mn content in eggshell was triple that in the yolk or albumen. Compared with the 60 mg/kg Mn-Met group, the transverse surface in the control group had (P < 0.01) a greater width of mammillary cones, and there were obvious cracks on the outer surface in the control. There was no difference (P > 0.05) in the eggshell gland (ESG) in the expression of calbindin-D28k (CaBP-D28k) mRNA in response to any diet treatment. In conclusion, dietary Mn-Met supplementation increased internal egg quality and the ultrastructure of the eggshell. Compared to the control, 60 mg/kg Mn-Met treatment resulted in improving egg quality, and 20 mg/kg Mn-Met treatment had similar effects the control treatment had on the egg quality. This indicates that the inorganic Mn can be replaced by the lower concentration of Mn-Met.