Influence of recombinant human B-type natriuretic peptide on improving ventricular function in patients with ST elevation myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effect of recombinant human B-type natriuretic peptide (rhBNP) on improving ventricular function in patients with ST-elevation myocardial infarction (STEMI). PATIENTS AND METHODS: In this retrospective study, 96 patients with STEMI admitted to Cangzhou Central Hospital from June 2017 to June 2019 were recruited and randomized to either a control group or an experimental group, with 48 patients in each group. Patients in both groups were given conventional pharmacological therapy, and an emergency coronary intervention was performed within 12 hours. Patients in the experimental group received rhBNP intravenously postoperatively, whereas patients in the control group received an equal amount of 0.9% NaCl solution through an intravenous drip. Postoperative recovery indicators were compared between the two groups. RESULTS: Patients treated with rhBNP showed better postoperative respiratory frequency, heart rate, blood oxygen saturation, pleural effusion, acute left heart remodeling after surgery and central venous pressure at 1-3 days after surgery than those without (p<0.05). Early diastolic blood flow velocity/early diastolic motion velocity (E/Em) and wall-motion score indices (WMSI) of patients in the experimental group were markedly lower compared to the control group one week after surgery (p<0.05). Patients receiving rhBNP had better left ventricular ejection fraction (LVEF) and WMSI six months after surgery and higher left ventricular end diastolic volume (LVEDV) and LVEF one week after surgery than the controls (p<0.05). Administration of rhBNP for patients with STMI provided a higher treatment safety by significantly reducing the incidence of left ventricular remodeling and complication than conventional medication (p<0.05). CONCLUSIONS: Intervention with rhBNP in STEMI patients could effectively inhibit ventricular remodeling, alleviate symptoms, reduce adverse complications and improve ventricular function.

Does endoplasmic reticulum stress stimulate the apoptosis of granulosa cells in polycystic ovary syndrome?

The aim of this study was to determine whether endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa cells in patients with polycystic ovary syndrome (PCOS). A total of 116 patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles at the Binzhou Medical University Hospital IVF Center between September 2019 and January 2020 were enrolled in the study. Apoptosis of the granulosa cells in each patient was analyzed using flow cytometry, and progesterone and estrogen levels in the cell-culture fluid were measured by enzyme-linked immunosorbent assay. The expressions of X-box-binding protein 1 (XBP1(s)), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), B-cell CLL/lymphoma 2 protein (Bcl-2), and Bcl-2 associated X protein (Bax) at the gene or protein level were analyzed using quantitative real-time polymerase chain reaction and Western blotting, respectively. In patients with PCOS, body mass index and basal serum concentrations of luteinizing hormone, testosterone (T), and anti-Mullerian hormone significantly increased (P < 0.05). The number of oocytes retrieed and the rate of clinical pregnancy after the first frozen embryo transfer also significantly increased (P < 0.05). Although apoptosis rate in the granulosa cells significantly increased in patients with PCOS, progesterone (P) and estrogen (E2) levels in the cell-culture fluid significantly decreased (P < 0.05). The apoptosis of granulosa cells was also found to affect blastocyst formation. Furthermore, the messenger ribonucleic acid (mRNA) expressions of XBP1(s), ATF6, CHOP, and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). The protein expressions of CHOP and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). After treatment of the granulosa cells with tauroursodeoxycholic acid, apoptosis rate and mRNA or protein expressions of XBP1(s), CHOP, and Bax significantly decreased, while the expression of Bcl-2 and levels of progesterone and estrogen significantly increased (P < 0.05). We conclude that ER stress could induce the apoptosis of granulosa cells in patients with PCOS. Cell apoptosis may decrease the number of blastocysts formed.

The role of miR-99b in mediating hepatocellular carcinoma invasion and migration.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of miR-99b in mediating hepatocellular carcinoma invasion and migration, by C.-J. Liu, J.-H. Yang, F.-Z. Huang, J.-H. Yang, C.-P. Liu, X.-H. Mao, W.-M. Yi, X.-B. Shen, C. Peng, M.-F. Chen, B. Jiang, J.-S. Wu, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2273-2281-DOI: 10.26355/eurrev_201804_14815-PMID: 29762829" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14815.

53BP1 regulates cell cycle arrest in esophageal cancer model.

OBJECTIVE: This study aims to investigate effects of checkpoint kinase, mediator of DNA damage checkpoint 1 (MDC1) and p53-binding protein 1 (53BP1) silencing on p53, checkpoint kinase 1 and 2 (CHK1 and CHK2), and CHK2-T68 expression. MATERIALS AND METHODS: Eca109 cells were divided into untransfected Eca109, Blank-vector, MDC1-RNAi transfection, and 53BP1-RNAi transfection group. Streptavidin-peroxidase (SP) immunohistochemical assay was used to examine CHK2-T68 expression. About 4 groups were used to establish esophageal carcinoma nude-mouse models, and assigned as Eca-109 control (or Eca-109 plus 15 Gy γ-rays irradiation, Eca-109+IR), Blank-vector (or Blank-vecor+IR), 53BP1-RNAi (or 53BP1-RNAi+IR), and MDC1-RNAi group (or MDC1-RNAi+IR group) by injecting. The expression of p53, CHK1, CHK2 were evaluated using SP immunohistochemical assay. RESULTS: 53BP1 and MDC1 down-regulation significantly inhibited expression of CHK2-T68 in Eca-109 cells compared to untreated group (p<0.05). There were significant differences for CHK2-T68 expressions in different time and groups (p<0.05). 53BP1 down-regulation significantly reduced p53 and enhanced CHK1 and CHK2 expression compared to that of Eca-109 control group (p<0.05) in Eca-109 cells. 53BP1 down-regulation significantly regulated CHK1, CHK2, and p53 in xenograft nude mice models exposed to γ-ray irradiation compared to that of untreated group (p<0.05). p53 was negatively correlated with CHK1 and CHK2 in xenograft nude mice models. CONCLUSIONS: 53BP1 regulated the cell cycle arrest by modulating p53, CHK1, and CHK2 expression in both Eca-109 cells and xenograft nude mice models.

The role of miR-99b in mediating hepatocellular carcinoma invasion and migration.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults with a high rate of malignancy. The potent invasion and migration of HCC mainly impact the prognosis and recurrence of the disease. Our previous study found that miR-99b was highly expressed in HCC, and its expression was associated with vascular invasion. It was speculated that miR-99b may play a role in HCC invasion and migration, while the specific mechanism remains unclear. MATERIALS AND METHODS: qRT-PCR was applied to detect expressions of miR-99b and KAI1 genes in L02, HepG2, and MHCC97H cells. HepG2 cells were transfected with miR-99b inhibitor, miR-99b mimic, and NC. Flow cytometry was used to test cell cycle and apoptosis. Dual-luciferase reporter gene assay was adopted to validate the target gene of miR-99b. Wound healing assay was used to detect cell migration. Transwell assay was performed to detect cell invasion. Western blot was performed to detect KAI1, E-cadherin, and N-cadherin expressions. Immunofluorescence assay was adopted to test Vimentin expression. RESULTS: The level of miR-99b was reduced in L02 while up-regulated in MHCC97H. By contrast, the expression of KAI1 was increased in L02 but declined in MHCC97H. The transfection of miR-99b mimic inhibited HepG2 apoptosis and accelerated cell cycle. MiR-99b suppressed KAI gene expression through targeting its 3'-UTR. MiR-99b mimic or si-KAI1 transfection promoted cell invasion and migration, while their simultaneous action significantly enhanced cell invasion and migration. The overexpression of miR-99b or knockdown of KAI1 significantly weakened HepG2 cell adhesion, reduced E-cadherin expression, upregulated N-cadherin and Vimentin, and promoted cell epithelial-mesenchymal transition (EMT). CONCLUSIONS: MiR-99b contributes to promoting function in HCC migration and invasion through inhibiting KAI1 expression.

Clinicopathological and prognostic significance of preoperative serum epidermal growth factor levels in patients with oral squamous cell carcinoma.

Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls. Patients with higher levels of EGF were more likely to have neck lymph node metastasis (P=0.026), advanced stage cancer (P=0.04), and a worse survival status (P=0.0019). Multivariate analysis using the Cox proportional hazards model indicated that the EGF level was an independent predictor of poor survival (hazard ratio 1.99, P=0.018). Patients with higher preoperative serum EGF levels had significantly poorer cancer-specific survival by Kaplan-Meier analysis (P=0.032). This study indicates that a higher preoperative serum EGF level is associated with neck lymph node metastasis, more advanced stage, and poor survival. EGF should be considered as a potential prognostic biomarker and a therapeutic target for patients with oral cancer.

Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma.

Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.

[Radiological analysis of coronal and sagittal spinopelvic parameters in patients with degenerative lumbar kyphoscoliosis].

Objective: To review and compare radiological parameters between degenerative lumbar kyphoscoliosis (DLKS) and degenerative lumbar kyphosis (DLK), and analyze the relationships between coronal and sagittal deformities and compensatory mechanisms of sagittal balance. Methods: A total of 82 patients with lumbar degenerative deformities were enrolled for our radiographic study at Department of Spinal Surgery, Peking University People's Hospital from January 2016 to May 2017. These patients were divided into two groups: DLKS group (39 patients) with lumbar coronal and sagittal deformities, and DLK group (43 patients) just with lumbar sagittal deformity. Complete spinopelvic radiographic parameters were compared. Results: The Cobb angle and lumbar lordosis of DLKS group were (23.0±11.8)° and (18.2±12.1)°, while the lumbar lordosis of DLK group was (20.4±10.2)°. In DLKS group, Cobb angle had correlations with lumbar lordosis(r=-0.338, P=0.035), and central sacral vertical line distance had significant correlations with thoracolumbar junctional angle (r=0.488, P=0.002) . Moreover, no significant differences of all sagittal spinopelvic parameters were found between two groups (P>0.05). In DLKS group, significant correlations between lumbar lordosis and sacral slope (r=0.617, P=0.000), and correlations between lumbar lordosis and thoracic kyphosis(r=-0.363, P=0.023) were observed. In DLK group, lumbar lordosis showed significant correlations with thoracic kyphosis(r=-0.341, P=0.025) and sacral slope (r=0.772, P=0.000). According to Nash-Moe grading scale of apical vertebral rotation, 10 patients were with Ⅰ-Ⅱ grade while 29 patients with Ⅲ-Ⅴ grade in DLKS group. Conclusions: Both as typical lumbar degenerative deformities, there are some correlations between scoliosis and kyphosis. However, coronal scoliosis may not influent sagittal morphological parameters for DLKS patients. Thoracic curve changes and pelvic backtilt are both important for maintaining the sagittal balance in patients with degenerative lumbar kyphoscoliosis.

[Clinical efficacy of one-lung ventilation in treatment of children postoperatively intractable atelectasis].

Objective: To investigate the effect of fiberoptic bronchoscope-guided one-lung ventilation (OLV) on treatment of intractable atelectasis in children. Method: This retrospective cohort study was conducted in Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University from December 2014 to May 2017. Six patients with intractable atelectasis of left lung were included. Three cases were male and three female with the age from 1.5 to 11.0 years. The endotracheal tube was intubated to the left main bronchus for OLV by the guidance of fiberoptic bronchoscopy. The effect of treatment by monitoring the chest imaging after treatment was evaluated. Result: Six pediatric patients were successfully cured by OLV. The duration of OLV ranged from 1.5 to 30.0 hours, and the intervals of OLV were usually 3 to 5 days. Each patient received 6 to 20 OLV treatments. Chest images showed the left lung reexpanded obviously after OLV treatments. Five patients successfully weaned from invasive ventilation and were discharged. Another patient turned better, discharged from hospital with noninvasive ventilation and weaned from noninvasive ventilation one month later after discharge. During the procedure of OLV, the vital signs of all patients were stable and no complication occurred. Conclusion: OLV with selective bronchial intubation guided by fiber bronchoscope is a safe and effective treatment for intractable atelectasis in children.

[The imaging analysis of the age-related changes on maxillary sinus].

Objective:The aim of this study is to investigate the age-related changes rules of maxillary sinus.Method:The 540 patients (1 080 sides) with normal data of deputy sinus in spiral CT were enrolled,including 270 cases of male and female,age from 7 to 81 years old.They are divided into 9 groups according to the age:Group A at the age of 7-12 years old,Group B at the age of 13-17,Group C at the age of 18-20 years old,Group D at the age of 21-24 years old,Group E at the age of 25-28 years,Group F at the age of 29-35 years old,Group G at the age of 36-40 years old,Group H at the age of 41-65 years old,and Group I is more than 65 years old.By the gender,the patients in each group was divided into male and female groups.There are 30 cases in each group(60 sides).The volumes and the three-dimensional diameters of the maxillary sinus were measured,and the coefficient of gasification of them were calculated.Result:The maxillary sinus volume and 3 D lines have almost the same change trend along with the age between the male and female group;From 7 to 20 ages,they are increased linearly,13 to 17 fastest-growing;18 to 20 years old reached to peak;declined slightly in 21-28 years old,29-35 a second growth peak,and 36 to 40 years old have fallen sharply,to reaching a steady state after 41 years old;The gasification coefficient has no difference among all groups.Conclusion:The volume changes with the age-related on maxillary sinus is in the adolescent stage.It reaches a steady state in the middle and old age stage,and gasification coefficient on maxillary sinus has no age-related changes among all groups.

Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study.

BACKGROUND: The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial. AIM: To investigate the risk of HCC in CHC patients who develop new onset diabetes. METHODS: We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009). CONCLUSION: Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.

A case of bone marrow infection by Staphylococcus saccharolyticus.

We report a case of fatal bone marrow infection caused by Staphylococcus saccharolyticus in a 26 year old female. The causative organism was isolated by anaerobic culture on blood agar, and was identified by PCR amplification of the gap gene and genotyping of the resultant sequence.

Integrative molecular profiling of routine clinical prostate cancer specimens.

BACKGROUND: Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. PATIENTS AND METHODS: We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. RESULTS: We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. CONCLUSIONS: Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.

Extracorporeal hepatic resection and autotransplantation for primary gastrointestinal stromal tumor of the liver.

We report a case of primary gastrointestinal stromal tumor of the liver. A 60-year-old woman with a large mass in the liver was asymptomatic with no hepatic virus infection and negative tumor markers. Because the tumor was unresectable by conventional means, we used extracorporeal hepatic resection and autotransplantation (ECHRA) for operation. The pathology showed a gastrointestinal stromal tumor that was diagnosed based on positive immunostaining for c-kit and CD34. Mutation analysis revealed an acquired mutation in exon 11 of c-kit. As we know, this is the eighth case of a primary hepatic extragastrointestinal stromal tumor reported previously in English, and the first case of which that was treated with ECHRA.

Clinicopathological features of thirty patients with primary breast lymphoma and review of the literature.

Primary breast lymphoma (PBL) is a rare disease accounting for 0.4-0.5 % of all breast malignancies. Accumulating evidence indicates that the diagnosis, prognostic factors, and optimal management of PBL are difficult. The present study aims to investigate the clinicopathological features and optimal treatment of PBL and to evaluate the institutional experience in this patient population. A total of 30 patients with PBL from January 2002 to December 2012 treated in He'nan Province Tumor Hospital were selected. The patients' clinical and pathological characteristics, treatment and response data, patterns of recurrence, and outcomes were retrospectively analyzed, and the relevant literatures were reviewed. All the cases were female, and the median age was 45. Diffuse large B cell lymphoma was the most common histological subtype seen in 23 of 30 patients. With a median follow-up time 32 months, median OS was 42 months (95 % CI 25-58 months), with 5-year OS rates 48 % (95 % CI 36-59 %). The median PFS was 14 months (95 % CI 6-30 months), with 5-year PFS rates 32 % (95 % CI 20-45 %). The prognostic factors that retained statistical significance for OS were IPI (P < 0.001), age (P = 0.04), and stage (P < 0.001). For PFS, significant prognostic factors were IPI (P = 0.01), radiotherapy given (P = 0.02) and stage (P = 0.02). PBL appears to have a worse prognosis. The present treatment method for PBL is a comprehensive way of diagnostic surgery together with radiotherapy and chemotherapy.

Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study.

BACKGROUND: As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors. METHODS: We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM. RESULTS: Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine. CONCLUSIONS: This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.