CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are common male diseases whose incidence rates gradually increase with age. They seriously affect men's physical health and quality of life. This study aimed to identify new biomarkers for the diagnosis of BPH and PCa. METHODS: Two datasets, GSE28204 and GSE134051 (including human PCa and BPH), were downloaded from the GEO database. The batch effect was removed for merging, and then differential gene expression analysis was conducted to identify BPH and PCa cases. The diagnostic biomarkers of BPH and PCa were further screened using machine learning and bioinformatics. ROC curves were drawn to evaluate the diagnostic accuracy of the selected biomarkers. An online website and qPCR were used to preliminarily explore the expression levels of PCa biomarkers. The correlations between the expression of biomarkers and the tumor microenvironment, tumor mutation load and immunotherapy drugs were evaluated. RESULTS: We identified fifteen genes (CHRDL1, DES, FLNC, GSTP1, MYL9, TGFB3, NEFH, TAGLN, SPARCL1, SYNM, TRPM8, HPN, PLA2G7, ENTPD5 and GPR160) as critical diagnostic biomarkers. After reviewing the literature on all selected biomarkers, we found few studies on the four genes CHRDL1, NEFH, TAGLN and SYNM in BPH or PCa. We defined these four genes as new potential diagnostic biomarkers (NPDBs) of BPH and PCa. All NPDBs were downregulated in PCa patients and PCa cell lines and upregulated in BPH patients and cell lines. When the immune landscape and mutation frequencies were analyzed, the results showed that the tumor microenvironment (TME), immune landscape, tumor mutation burden, and drug response were significantly correlated with NPDB expressions. CONCLUSIONS: We found four new diagnostic markers of BPH and PCa, which may facilitate the early diagnosis, treatment, and immunotherapeutic responses assessment and may be of major value in guiding clinical practice.

Icotinib, an EGFR tyrosine kinase inhibitor, as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma: a multicenter, open-label, single-arm, phase II study (ICAPE).

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

Identification of biomarkers associated with the feed efficiency by metabolomics profiling: results from the broiler lines divergent for high or low abdominal fat content.

BACKGROUND: Improving feed efficiency (FE) is one of the main objectives in broiler breeding. It is difficult to directly measure FE traits, and breeders hence have been trying to identify biomarkers for the indirect selection and improvement of FE traits. Metabolome is the "bridge" between genome and phenome. The metabolites may potentially account for more of the phenotypic variation and can suitably serve as biomarkers for selecting FE traits. This study aimed to identify plasma metabolite markers for selecting high-FE broilers. A total of 441 birds from Northeast Agricultural University broiler lines divergently selected for abdominal fat content were used to analyze plasma metabolome and estimate the genetic parameters of differentially expressed metabolites. RESULTS: The results identified 124 differentially expressed plasma metabolites (P < 0.05) between the lean line (high-FE birds) and the fat line (low-FE birds). Among these differentially expressed plasma metabolites, 44 were found to have higher positive or negative genetic correlations with FE traits (|rg| ≥ 0.30). Of these 44 metabolites, 14 were found to display moderate to high heritability estimates (h2 ≥ 0.20). However, among the 14 metabolites, 4 metabolites whose physiological functions have not been reported were excluded. Ultimately, 10 metabolites were suggested to serve as the potential biomarkers for breeding the high-FE broilers. Based on the physiological functions of these metabolites, reducing inflammatory and improving immunity were proposed to improve FE and increase production efficiency. CONCLUSIONS: According to the pipeline for the selection of the metabolite markers established in this study, it was suggested that 10 metabolites including 7-ketocholesterol, dimethyl sulfone, epsilon-(gamma-glutamyl)-lysine, gamma-glutamyltyrosine, 2-oxoadipic acid, L-homoarginine, testosterone, adenosine 5'-monophosphate, adrenic acid, and calcitriol could be used as the potential biomarkers for breeding the "food-saving broilers".

Ureteroscopic holmium laser to transect the greater omentum to remove an abdominal drain: Four case reports.

BACKGROUND: Drainage tube removal is difficult when the greater omentum becomes incarcerated in the drainage tube through the side holes. Currently, known removal methods are either ineffective or will cause additional damage to the patient in a secondary operation. Ureteroscopy and the holmium laser have been used in various surgical techniques in urology, and in theory, they are expected to be a good strategy for solving the problem of tissue incarceration. CASE SUMMARY: Four patients diagnosed with difficult removal of an abdominal drainage tube following abdominal surgery are reported. All patients underwent surgery to remove the incarcerated greater omentum in the drainage tube using a holmium laser and a ureteroscope, and a new 16-F drain was then placed in the abdominal or pelvic cavity. The efficacy of this technique was evaluated by intraoperative conditions, success rate, and operating time; safety was evaluated by perioperative conditions and the probability of postoperative complications. All four operations went smoothly, and the drains were successfully removed in all patients. The average operating time was 24.5 min. Intraoperatively, the average irrigation volume was 892.0 mL, the average drainage volume was 638.5 mL, and no bleeding or damage to surrounding tissues was observed. Postoperatively, the average drainage volume was 32.8 mL and the new drains were removed within 36 h. All patients were able to get out of bed and move around within 12 h. Their visual analogue pain scores were all below 3. The average follow-up duration was 12.5 mo and no complications such as fever or bleeding were noted. CONCLUSION: Ureteroscopic holmium laser surgery is an effective, safe and minimally invasive technique for removing drains where the greater omentum is incarcerated in the abdominal drain.

Modified bladder outlet obstruction index for powerful efficacy prediction of transurethral resection of prostate with benign prostatic hyperplasia.

BACKGROUND: The correlation between modified bladder outlet obstruction index (MBOOI) and surgical efficacy still remains unknown. The purpose of the study was to investigate the clinical value of the MBOOI and its use in predicting surgical efficacy in men receiving transurethral resection of the prostate (TURP). METHODS: A total of 403 patients with benign prostate hyperplasia (BPH) were included in this study. The International Prostate Symptom Score (IPSS), quality of life (QoL) index, transrectal ultrasonography, and pressure flow study were conducted for all patients. The bladder outlet obstruction index (BOOI) (PdetQmax-2Qmax) and MBOOI (Pves-2Qmax) were calculated. All patients underwent TURP, and surgical efficacy was accessed by the improvements in IPSS, QoL, and Qmax 6 months after surgery. The association between surgical efficacy and baseline factors was statistically analyzed. RESULTS: A comparison of effective and ineffective groups based on the overall efficacy showed that significant differences were observed in PSA, Pves, PdetQmax, Pabd, BOOI, MBOOI, TZV, TZI, IPSS-t, IPSS-v, IPSS-s, Qmax, and PVR at baseline (p < 0.05). Binary logistic regression analysis suggested that MBOOI was the only baseline parameter correlated with the improvements in IPSS, QoL, Qmax, and the overall efficacy. Additionally, the ROC analysis further verified that MBOOI was more optimal than BOOI, TZV and TZI in predicting the surgical efficacy. CONCLUSION: Although both MBOOI and BOOI can predict the clinical symptoms and surgical efficacy of BPH patients to a certain extent, however, compared to BOOI, MBOOI may be a more useful factor that can be used to predict the surgical efficacy of TURP. Trial registration retrospectively registered.

Effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in Balb/c mice after sciatic nerve injury.

OBJECTIVE: To investigate the effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in mice with sciatic nerve injury, and to explore the relationship between PSD-95 protein and myelin regeneration after nerve myelin injury. METHODS: One hundred twenty-seven male adult Balb/c mice were selected and randomly divided into high, medium and low 7,8-dihydroxycoumarin dose groups and blank control group. Anastomosis was then carried out for the amputated right sciatic nerve, and intraperitoneal injection of 7,8-dihydroxycoumarin was applied postoperatively. At weeks 1, 2, 4 and 8 after surgery, nervous tissues from the injury side were taken for immunohistochemical Luxol Fast Blue staining, so as to observe the morphological changes of the locally injured nerve myelin. Meanwhile, PSD-95 mRNA and protein expression were determined using real-time PCR and western blotting. RESULTS: The nerve myelin recovery in injury side of mice at all time points showed a definite dose-effect relationship with the dose of 7,8-dihydroxycoumarin. Moreover, 7,8-dihydroxycoumarin could inhibit the PSD-95 mRNA level and protein expression. At the same time, there was a dose-effect of the inhibition. CONCLUSIONS: 7,8-Dihydroxycoumarin can affect nerve recovery in mice with sciatic nerve injury, which shows a definite dose-effect relationship with its dose. Besides, PSD-95 protein expression can suppress the regeneration of the injured nerve myelin.

[Bladder outlet obstruction index alone is not reliable for the diagnosis of benign prostate hyperplasia].

OBJECTIVE: To evaluate the clinical application value of the bladder outlet obstruction index (BOOI) in the diagnosis of BPH. METHODS: We retrospectively analyzed the urodynamic parameters and BOOI of 199 cases of BPH diagnosed from July 2016 to September 2018, which were divided into a BOO (n = 119), a suspected BOO (n = 39) and a non-BOO group (n = 41) based on the BOOI. We obtained the prostate volume (PV), IPSS, IPSS-voiding symptom score (IPSS-VS), quality of life score (QOL), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients, compared them among the three groups and analyzed their correlation to BOOI using Pearson's linear correlation analysis. RESULTS: No statistically significant differences were observed in age (P = 0.195), PSA (P = 0.380), IPSS (P = 0.380), IPSS-VS (P = 0.380), QOL (P = 0.380), Qmax (P = 0.380) and PVR (P = 0.912) among the three groups of patients, but PV was remarkably larger in the BOO than in the suspected BOO and non-BOO groups (ï¼»58.8 ± 30.0ï¼½ vs ï¼»49.8 ± 33.9ï¼½ and ï¼»45.5 ± 26.0ï¼½ ml, P = 0.031). Pearson's linear correlation analysis showed that BOOI was not correlated significantly to IPSS (r = －0.020, P = 0.778), IPSS-VS (r= －0.013, P = 0.853), QOL (r = －0.107, P = 0.132), Qmax (r = －0.130, P = 0.066) or PVR (r = －0.056, P = 0.433), nor obviously to PV (|r| = 0.178<0.4) though with P = 0.012. CONCLUSIONS: BOOI is not significantly correlated to PV, IPSS, IPSS-VS, QOL, Qmax or PVR, and therefore BOO cannot be diagnosed exclusively with BOOI.

Utilities and placement skills of the incision protective sleeve in video-assisted thoracoscopic surgery (VATS).

BACKGROUND: The incision protective sleeve can protect incisions and help to establish an operating port and thus has been widely applied in thoracic surgeries. However, its other utilities are often neglected. This article explores the additional functions and placement techniques of incision protective sleeves in video-assisted transthoracic surgery (VATS). METHODS: Operators with different surgical experience were divided into three groups: resident group, attending surgeon group, and professor group. Each group independently chose one of the four surgical maneuvers, and the incision protective sleeve was placed during the operation. Up to 200 operations were randomly selected in each group, and the patients' gender, age, incision site, incision length, the operator's experience, and the time and technique of incision protective sleeve placement were recorded. CT was performed to measure the thickness of chest wall and the width of intercostal spaces. Data were analyzed using SPSS 21.0 software package. Multivariate linear regression analysis was performed was performed for the time required for incision protective sleeve placement. RESULTS: The operator's experience was inversely related to the time required for incision protective sleeve placement, width of intercostal spaces was negatively correlated with operative time, chest wall thickness and incision length were positively correlated with operative time. Among the maneuvers, incision protective sleeve placement skills were significant different. CONCLUSIONS: The placement of the incision protective sleeve for VATS is affected by multiple factors, which are not only related to the patient's condition, chest wall thickness and intercostal space, but also closely related to the operator's experience and the manipulation adopted.

Inhibition of miR-203 Ameliorates Osteoarthritis Cartilage Degradation in the Postmenopausal Rat Model: Involvement of Estrogen Receptor α.

miR-203 is known to target estrogen receptor α (ERα) in various cancer cell lines, such as MCF-7. However, whether miR-203 regulates ERα and contributes to the onset and progression of osteoarthritis (OA) is poorly understood. A combined protocol of the bilateral ovariectomy and the intra-articular monosodium iodoacetate injection was applied to establish a postmenopausal OA model in rats. Real-time quantitative polymerase chain reaction was used to detect miR-203 and mRNAs and Western blotting was exploited to quantify the expression levels on the protein level. Enzyme-linked immunosorbent assays were deployed to detect the expression of matrix metalloproteinase-1 (MMP-1), MMP-3, prostaglandin E2 (PGE2), and collagen type II degradation (CTX-II) in serum samples. Dual-luciferase reporter assay was utilized to confirm the direct binding of miR-203 on ERα in postmenopausal OA rats. Expression of miR-203 was elevated; while ERα mRNA and protein were downregulated in postmenopausal OA rats, compared with sham rats. Dual-luciferase reporter assay confirmed miR-203 bound and negatively regulated ERα, resulting in promoted cellular inflammation and cartilage destruction in postmenopausal OA rats. Suppression of miR-203 using a specific inhibitor ameliorated cartilage degradation in postmenopausal OA rats. miR-203 is pivotal in the onset and progression of OA in the postmenopausal rat model, and holds promise for a therapeutic target of OA treatment.

The value of diffusion tensor tractography delineating corticospinal tract in glioma in rat: validation via correlation histology.

BACKGROUND: An assessment of the degree of white matter tract injury is important in neurosurgical planning for patients with gliomas. The main objective of this study was to assess the injury grade of the corticospinal tract (CST) in rats with glioma using diffusion tensor imaging (DTI). METHODS: A total 17 rats underwent 7.0T MRI on day 10 after tumor implantation. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were acquired in the tumor, peritumoral and contralateral areas, and the ADC ratio (ipsilateral ADC/contralateral ADC) and rFA (relative FA = ipsilateral FA/contralateral FA) in the peritumoral areas were measured. The CST injury was divided into three grades and delineated by diffusion tensor tractography reconstruction imaging. The fiber density index (FDi) of the ipsilateral and contralateral CST and rFDi (relative FDi = ipsilateral FDi/contralateral FDi) in the peritumoral areas were measured. After the mice were sacrificed, the invasion of glioma cells and fraction of proliferating cells were observed by hematoxylin-eosin and Ki67 staining in the tumor and peritumoral areas. The correlations among the pathology results, CST injury grade and DTI parameter values were calculated using a Spearman correlation analysis. One-way analysis of variance was performed to compare the different CST injury grade by the rFA, rFDi and ADC ratio values. RESULTS: The tumor cells and proliferation index were positively correlated with the CST injury grade (r = 0.8857, 0.9233, P < 0.001). A negative correlation was demonstrated between the tumor cells and the rFA and rFDi values in the peritumoral areas (r = -0.8571, -0.5588), and the proliferation index was negatively correlated with the rFA and rFDi values (r = -0.8571, -0.5588), while the ADC ratio was not correlated with the tumor cells or proliferation index. The rFA values between the CST injury grades (1 and 3, 2 and 3) and the rFDi values in grades 1 and 3 significantly differed (P < 0.05). CONCLUSIONS: Diffusion tensor imaging may be used to quantify the injury degrees of CST involving brain glioma in rats. Our data suggest that these quantitative parameters may be used to enhance the efficiency of delineating the relationship between fiber tracts and malignant tumor.

Expert consensus on image-guided radiofrequency ablation of pulmonary tumors: 2018 edition.

Lung cancer ranks first in incidence and mortality in China. Surgery is the primary method to cure cancer, but only 20-30% of patients are eligible for curative resection. In recent years, in addition to surgery, other local therapies have been developed for patients with numerous localized primary and metastatic pulmonary tumors, including stereotactic body radiation therapy and thermal ablative therapies through percutaneously inserted applicators. Percutaneous thermal ablation of pulmonary tumors is minimally invasive, conformal, repeatable, feasible, cheap, has a shorter recovery time, and offers reduced morbidity and mortality. Radiofrequency ablation (RFA), the most commonly used thermal ablation technique, has a reported 80-90% rate of complete ablation, with the best results obtained in tumors < 3 cm in diameter. Because the clinical efficacy of RFA of pulmonary tumors has not yet been determined, this clinical guideline describes the techniques used in the treatment of localized primary and metastatic pulmonary tumors in nonsurgical candidates, including mechanism of action, devices, indications, techniques, potential complications, clinical outcomes, post-ablation surveillance, and use in combination with other therapies. In the future, the role of RFA in the treatment of localized pulmonary tumors should ultimately be determined by evidence from prospective randomized controlled trials comparing sublobar resection or stereotactic body radiation therapy.