HT-2 toxin impairs porcine oocyte in vitro maturation through disruption of endomembrane system.

HT-2 toxin is a type of mycotoxin which is shown to affect gastric and intestinal lesions, hematopoietic and immunosuppressive effects, anorexia, lethargy, nausea. Recently, emerging evidences indicate that HT-2 also disturbs the reproductive system. In this study, we investigated the impact of HT-2 toxin exposure on the organelles of porcine oocytes. Our results found that the abnormal distribution of endoplasmic reticulum increased after HT-2 treatment, with the perturbation of ribosome protein RPS3 and GRP78 expression; Golgi apparatus showed diffused localization pattern and GM130 localization was also impaired, thereby affecting the Rab10-based vesicular transport; Due to the impairment of ribosomes, ER, and Golgi apparatus, the protein supply to lysosomes was hindered, resulting in lysosomal damage, which further disrupted the LC3-based autophagy. Moreover, the results indicated that the function and distribution of mitochondria were also affected by HT-2 toxin, showing with fragments of mitochondria, decreased TMRE and ATP level. Taken together, our study suggested that HT-2 toxin exposure induces damage to the organelles for endomembrane system, which further inhibited the meiotic maturation of porcine oocytes.

Biomechanical evaluation of Percutaneous endoscopic posterior lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion: a biomechanical analysis.

In order to analyze and evaluate the stability of lumbar spine and the risk of cage subsidence after different minimally invasive fusion operations, two finite element models Percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and minimally invasive transforaminal lumbar interbody Fusion (MIS-TLIF) were established. The results showed that compared with MIS-TLIF, PE-PLIF had better segmental stability, lower pedicle screw rod system stress, and lower risk of cage subsidence. The results suggest that the cage with appropriate height should be selected to ensure the segmental stability and avoid the risk of the subsidence caused by the cage with large height.

[Protective mechanism of electroacupuncture combined with acellular nerve allografts on spinal ganglia in rats with sciatic nerve injury].

OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groups， with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structure， the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.

Cardiac arrest caused by the application of pituitrin during laparoscopic myomectomy.

BACKGROUND: Pituitrin injection solution is an indispensable hemostatic utilized in clinical practice and is widely used in myomectomy. However, there have been reports of adverse reactions leading to gastrointestinal injury, hyponatremia and hypokalemia, anaphylaxis, cardiac arrest, etc. Thus, the safety of pituitrin should be taken seriously. CASE PRESENTATION: In the present study, three cases of cardiac arrest caused by pituitrin injection during laparoscopic myomectomy, who were successfully resuscitated in our hospital, are reported. CONCLUSION: The clinical data and surgical procedures in the patient should be analyzed to find the causes of cardiac arrest. Medication and resuscitation should be summarized to ensure the safety of the patient.

Transcriptional progressive patterns from mild to severe renal ischemia/reperfusion-induced kidney injury in mice.

The renal ischemia/reperfusion (I/R)-induced acute kidney injury incidence after nephron-sparing surgery for localized renal tumors is 20%, but the biological determinant process of postoperative acute kidney injury remains unclear. Using Gene Expression Omnibus database (GSE192883) and several bioinformatics analyses (discrete time points analysis, gene set enrichment analysis, dynamic network biomarker analysis, etc), combined with the establishment of the I/R model for verification, we identified three progressive patterns involving five core pathways confirmed using gene set enrichment analysis and six key genes (S100a10, Pcna, Abat, Kmo, Acadm, and Adhfe1) verified using quantitative polymerase chain reaction The dynamic network biomarker (DNB) subnetwork composite index value is the highest in the 22-min ischemia group, suggesting the transcriptome expression level fluctuated sharply in this group, which means 22-min ischemia is an critical warning point. This study illustrates the core molecular progressive patterns from mild to severe I/R kidney injury, laying the foundation for precautionary biomarkers and molecular intervention targets for exploration. In addition, the safe renal artery blocking time of nephron-sparing surgery that we currently accept may not be safe anymore.

Percutaneous Endoscopic Posterior Lumbar Interbody Fusion with Unilateral Laminotomy for Bilateral Decompression Vs. Open Posterior Lumbar Interbody Fusion for the Treatment of Lumbar Spondylolisthesis.

Background: Endoscopic lumbar interbody fusion is a new technology that is mostly used for single-segment and unilateral lumbar spine surgery. The purpose of this study is to introduce percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) with unilateral laminotomy for bilateral decompression (ULBD) for lumbar spondylolisthesis and evaluate the efficacy by comparing it with open posterior lumbar interbody fusion (PLIF). Methods: Twenty-eight patients were enrolled in PE-PLIF with the ULBD group and the open PLIF group. The perioperative data of the two groups were compared to evaluate the safety of PE-PLIF with ULBD. The visual analog scale (VAS) back pain, VAS leg pain, and Oswestry Disability Index (ODI) scores of the two groups preoperatively and postoperatively were compared to evaluate clinical efficacy. Preoperative and postoperative imaging data were collected to evaluate the effectiveness of the operation. Results: No differences in baseline data were found between the two groups (p > 0.05). The operation time in PE-PLIF with the ULBD group (221.2 ± 32.9 min) was significantly longer than that in the PLIF group (138.4 ± 25.7 min) (p < 0.05), and the estimated blood loss and postoperative hospitalization were lower than those of the PLIF group (p < 0.05). The postoperative VAS and ODI scores were significantly improved in both groups (p < 0.05), but the postoperative VAS back pain score in the PE-PLIF group was significantly lower than that in the PLIF group (p < 0.05). The excellent and good rates in both groups were 96.4% according to MacNab's criteria. The disc height and cross-sectional area of the spinal canal were significantly improved in the two groups after surgery (p < 0.05), with no difference between the groups (p > 0.05). The fusion rates in PE-PLIF with the ULBD group and the PLIF group were 89.3% and 92.9% (p > 0.05), respectively, the cage subsidence rates were 14.3% and 17.9% (p > 0.05), respectively, and the lumbar spondylolisthesis reduction rates were 92.72 ± 6.39% and 93.54 ± 5.21%, respectively (p > 0.05). Conclusion: The results from this study indicate that ULBD can be successfully performed during PE-PLIF, and the combined procedure is a safe and reliable treatment method for lumbar spondylolisthesis.

Deep-learning-based analysis of preoperative MRI predicts microvascular invasion and outcome in hepatocellular carcinoma.

BACKGROUND: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC. METHODS: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated, and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression. RESULTS: Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and a-fetoprotein (AFP) were independently associated with MVI: DL-MVI (odds ratio [OR] = 35.738; 95% confidence interval [CI] 14.027-91.056; p < 0.001), AFP (OR = 4.634, 95% CI 2.576-8.336; p < 0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824. CONCLUSIONS: Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.

A Comprehensive Risk Assessment Model for Ovarian Cancer Patients with Phospho-STAT3 and IL-31 as Immune Infiltration Relevant Genes.

INTRODUCTION: Ovarian carcinoma is a malignant tumor with a high mortality rate and a lack of effective treatment options for patients at advanced stages. For improving outcomes and helping patients with poor prognosis, choose a suitable therapy and an excellent risk assessment model and new treatment options are needed. MATERIALS AND METHODS: Ovarian cancer gene expression profile of GSE32062 was downloaded from the NCBI GEO database for screening differentially expressed genes (DEGs) between well and poor prognosis groups using limma package in R (version 3.4.1). Prognosis-related genes and clinical prognostic factors were obtained from univariate and multivariate Cox regression analyses, and a comprehensive risk assessment model was constructed using a Pathway Dysregulation Score (PDS) matrix, Cox-Proportional Hazards (Cox-PH) regression, as well as L1-least absolute shrinkage and selection operator (L1-LASSO) penalization. Then, significant DEGs were converted to pathways and optimal prognosis-related pathways were screened. Finally, risk prediction models based on pathways, genes involved in pathways, and comprehensive clinical risk factors with pathways were built. Their prognostic functions were assessed in verification sets. Besides, genes involved in immune-pathways were checked for immune infiltration using immunohistochemistry. RESULTS: A superior risk assessment model involving 9 optimal combinations of pathways and one clinical factor was constructed. The pathway-based model was found to be superior to the gene-based model. Phospho-STAT3 (from JAK-STAT signaling pathway) and IL-31 (from DEGs) were found to be related to immune infiltration. CONCLUSION: We have generated a comprehensive risk assessment model consisting of a clinical risk factor and pathways that showed a possible bright foreground. The set of significant pathways might play as a better prognosis model which is more accurate and applicable than the DEG set. Besides, p-STAT3 and IL-31 showing correlation to immune infiltration of ovarian cancer tissues may be potential therapeutic targets for treating ovarian cancers.

Incremental effect of liraglutide on traditional insulin injections in rats with type 2 diabetes mellitus by maintaining glycolipid metabolism and cardiovascular function.

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia, damaged insulin secretion and insulin resistance with high morbidity and mortality. Liraglutide (liragl) and insulin are effective hypoglycemic agents used in T2DM treatment. The potential effect of liragl in combination with insulin on T2DM remains unclear. The aim of the current study was to explore effects of liragl combined with insulin on glycolipid metabolism and cardiovascular function in rats with diabetes. A diabetes model was established in Sprague Dawley rats exposed to a high calorie and high sugar diet in conjunction with intraperitoneal injections of streptozotocin. Results indicated that liragl or insulin used alone decreased glucose and elevated insulin and c-peptide levels. However, their combination revealed greater effects. A significant increase in high-density lipoprotein cholesterol levels along with a decrease in total cholesterol, triglycerides and low-density lipoprotein cholesterol were observed in liragl- and insulin-treated rats compared with STZ-induced diabetes rats. Furthermore, co-administration of liragl and insulin significantly decreased sterol regulatory element-binding protein 1 levels and increased adenosine 5'-monophosphate kinase-α1 and carnitine palmitoyltransferase 1 expression. Combining liragl with insulin reduced myocardial hypertrophy level and gaps between cardiomyocytes compared with liragl or insulin treatment alone. Caspase-3 expression was significantly decreased by combination treatment of liragl and insulin. Oxidative damage was significantly decreased by co-administration of liragl and insulin through enhancing superoxide dismutase expression and reducing malondialdehyde. Furthermore, combination of liragl and insulin significantly reduced myocardial enzyme expression, including myoglobin, creatine kinase-muscle/brain and cardiac troponin I. In summary, the current study demonstrated synergistic effects of liragl and insulin injections on a T2DM rat model by maintaining glycolipid metabolism and cardiovascular function.

Potential of Ablation Therapy during Hepatocellular Carcinoma.

BACKGROUND: This study explored the potential of ablation therapy on membrane fluidity changes in diethylnitrosamine (DEN) induced hepatic cancer. METHODS: Male Wistar rats were segregated into four groups viz., normal control, DEN treated, ablation therapy treated, and DEN ablation therapy treated. We assessed the viscosities as well as fluidity parameters in isolated brush border membranes using the membrane extrinsic fluorophore pyrene. RESULTS: DEN treatment successfully induced hepatic cancer in the livers of rats and ablation therapy worked well in terms of therapy. DEN treatment resulted in a significant rise in lipid peroxidation (LPO) and significant decrease in the, reduced glutathione levels (GSH). A significant decrease was also noticed in the activities of glutathione reductase (GR), glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) following DEN treatment. On the other hand, ablation therapy treatment to DEN-treated rats resulted in a significant decrease in the LPO levels but caused a significant rise in the levels of GSH. Moreover, the activities of GR, GST, SOD, CAT, and GPx showed significant improvement after ablation therapy treatment. The results further demonstrated a marked decrease in membrane microviscosity following DEN treatment. On the other hand, a significant increase was noticed in both excimer/monomer ratio and fluidity parameter in DEN-treated rats. However, membrane microviscosity and the fluidity alterations were significantly restored back to near normal with ablation therapy treatment. CONCLUSIONS: The study, therefore, concluded that ablation therapy holds good therapeutic potential against DEN-induced hepatic cancer.

Identification of Differentially Expressed Genes between Original Breast Cancer and Xenograft Using Machine Learning Algorithms.

Breast cancer is one of the most common malignancies in women. Patient-derived tumor xenograft (PDX) model is a cutting-edge approach for drug research on breast cancer. However, PDX still exhibits differences from original human tumors, thereby challenging the molecular understanding of tumorigenesis. In particular, gene expression changes after tissues are transplanted from human to mouse model. In this study, we propose a novel computational method by incorporating several machine learning algorithms, including Monte Carlo feature selection (MCFS), random forest (RF), and rough set-based rule learning, to identify genes with significant expression differences between PDX and original human tumors. First, 831 breast tumors, including 657 PDX and 174 human tumors, were collected. Based on MCFS and RF, 32 genes were then identified to be informative for the prediction of PDX and human tumors and can be used to construct a prediction model. The prediction model exhibits a Matthews coefficient correlation value of 0.777. Seven interpretable interactions within the informative gene were detected based on the rough set-based rule learning. Furthermore, the seven interpretable interactions can be well supported by previous experimental studies. Our study not only presents a method for identifying informative genes with differential expression but also provides insights into the mechanism through which gene expression changes after being transplanted from human tumor into mouse model. This work would be helpful for research and drug development for breast cancer.

Radioactive seed implantation and lobaplatin chemotherapy are safe and effective in treating patients with advanced lung cancer.

UNLABELLED: Objecive: To investigate the clinical safety and efficacy of CT-guided 125iodine (125I) seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol in treating patients with advanced lung cancer. MATERIALS AND METHODS: Patients with advanced lung cancer and treated with spiral CT-guided 125I seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol were recruited. RESULTS: Of the 36 patients, there were 40 nidi in total. The contrast-enhanced CT evaluation was conducted 60 d after treatment. Response evaluation suggested that 4 patients achieved complete remission (CR), 24 partial remission (PR), 4 stable disease (SD) and 4 progression disease (PD), with a total response rate of 77.8% (28/36). CONCLUSIONS: CT-guided 125I seed implantation combined with percutaneous intra-tumor injection of chemotherapy emulsion of lobaplatin and lipiodol are safe and effective in treating patients with advanced lung cancer.

Application of lobaplatin in trans-catheter arterial chemoembolization for primary hepatic carcinoma.

OBJECTIVE: To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery. METHODS: 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response. RESULTS: The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance. CONCLUSIONS: Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.