Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer.

BACKGROUND: This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC). METHODS: EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's performance. RESULTS: The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram's specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram's AUC was 0.949. CONCLUSION: A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.

U0126 and BAY11-7082 Inhibit the Progression of Endometriosis in a Rat Model by Suppressing the MEK/ERK/NF-κB Pathway.

Endometriosis is an aggressive disease. It is the main cause of chronic pelvic pain, dysmenorrhea, and infertility, affecting the well-being of women. This study aimed to explore the role of U0126 and BAY11-7082 in endometriosis (EMs) treatment in rats by targeting the MEK/ERK/NF-κB pathway. The EMs model was generated and the rats were divided into model, dimethyl sulfoxide, U0126, BAY11-708, and control groups (Sham operation group). After 4 weeks of treatment, the rats were sacrificed. Compared with model group, U0126 and BAY11-7082 treatment significantly inhibited ectopic lesion growth, glandular hyperplasia, and interstitial inflammation. Compared to control group, PCNA and MMP9 levels were significantly increased in the eutopic and ectopic endometrial tissues of model group; the levels of MEK/ERK/NF-κB pathway proteins also increased significantly. Compared with model group, MEK, ERK, and NF-κB levels decreased significantly after U0126 treatment and NF-κB protein expression decreased significantly after BAY11-7082 treatment, with no significant difference in MEK and ERK levels. The proliferation and invasion activities of eutopic and ectopic endometrial cells also significantly decreased after U0126 and BAY11-7082 treatment. In summary, our results showed that U0126 and BAY11-7082 inhibited ectopic lesion growth, glandular hyperplasia, and interstitial inflammatory response in EMs rats by inhibiting the MEK/ERK/NF-κB signaling pathway.

The role of Connexin26 regulated by MiR-2114-3p in the pathogenesis of ovarian cancer.

OBJECTIVES: The purpose of our research was to determine the expression of Cx26 and miR-2114-3p, and their effects on proliferation, migration, and invasion in ovarian cancer and their mechanisms. MATERIALS AND METHODS: Transcriptome sequencing was performed and differentially expressed Cx26 was screened. The mRNA and protein levels of Cx26 in EOC and normal ovarian tissues were verified. The relationship between Cx26 levels and prognostics was analyzed. Cx26 Lentiviral vectors were constructed to detect its effect on ovarian cancer. WB verified that PI3K/AKT pathway was the possible signal pathway regulated by Cx26. The interaction between miR-2114-3p and Cx26 was detected by double luciferase reporter assay and qrt-PCR. CCK8, clone formation, transwell, and flow cytometry assays were conducted in cells transfected miR-2114-3p plasmids. The vivo experiment investigated the effects of Cx26 on subcutaneous tumor growth, PI3K expression, proliferation proteins Ki67 and PCNA. RESULTS: Cx26 was up-regulated in EOC tissue and cell lines, and was associated with poor prognosis of ovarian cancer, while miR-2114-3p was down-regulated in EOC cell lines. Cx26 was a direct target of miR-2114-3p. Cx26 overexpression and miR-2114-3p inhibition promoted the growth, motility, invasiveness, and S phase arrest of EOC cells. Additionally, Cx26 could activated PI3K pathway whatever in vivo and in vitro. CONCLUSIONS: Dysregulation of Cx26 is critical in EOC patients. Manipulation of this mechanism may influence the survival of EOC patients. MiR-2114-3p regulates the tumor-promoting activity of Cx26 in EOC. By inhibiting the PI3K pathway or knocking down Cx26 effectively inhibits tumor growth in EOC cells and Nude mouse model.

Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway in vivo and in vitro.

CONTEXT: Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear. OBJECTIVE: To investigate the effects of JA on amino acid neurotransmitters and microglia activation in vivo and in vitro. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of N-methyl-d-aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels. RESULTS: JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA. DISCUSSION AND CONCLUSIONS: JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.

Value of the risk of ovarian malignancy algorithm index in predicting the recurrence of epithelial ovarian cancer.

Aim: This study aimed to assess the predictive and diagnostic value of the risk of ovarian malignancy algorithm (ROMA) index for epithelial ovarian cancer (EOC) recurrence. Materials & methods: The clinical features and follow-up data of 159 EOC cases were studied. The ROMA index was calculated by serum CA125 and HE4 levels with menopausal status. Recurrence-free survival was evaluated for an end point. Results: The ROMA was strongly associated with clinical characteristics. The ROMA index above the cutoff value (34.71%) was significantly associated with recurrence-free survival. The ROMA index had a significantly higher sensitivity (90.59%) than CA125 (84.71%) and HE4 (80.80%) for recurrence diagnosis, and its optimal cutoff value was 17.07%. Conclusion: The primary ROMA index is a predictive factor in EOC recurrence and has better performance in the diagnosis of EOC recurrence.

Knockdown of ribosomal protein S6 suppresses proliferation, migration, and invasion in epithelial ovarian cancer.

BACKGROUND: Ovarian cancer typically is diagnosed late because insensitivity and lack of specificity of current biomarkers prior to its clinical detection. Ribosomal protein S6 (RPS6) is a ribosomal protein involved in the ribosomal 40S subunit, but its biological role in epithelial ovarian cancer (EOC) is still unknown. RESULTS: RPS6 was elevated in EOC compared to normal ovarian tissues and adenomas. Higher expression of RPS6 predicted worse prognosis in EOC. The level of RPS6 was correlated with clinical stage, histological type and pathological grade. Knockdown of RPS6 reduced the proliferation of ovarian cancer cell lines SKOV-3 and HO8910, and inhibit the migration and invasion ability. It revealed that cells arrested at G0G1 phase after knockdown of RPS6, and the expressions of CyclinD1, Cyclin E, CDK2, CDK4, CDK6 and pRb were also reduced. CONCLUSIONS: RPS6 is involved in EOC and knockdown of RPS6 could inhibit the proliferation, invasion and migration ability of EOC in vitro by inducing G0/G1 phase arrest. RPS6 is expected to be a novel biomarker and molecular target to the EOC.

Research on the Recognition Performance of Bionic Sensors Based on Active Electrolocation for Different Materials.

Underwater object identification by optical sensors is usually difficult in turbid or dark environments. The objective of this paper was to identify different underwater materials using active electrolocation technology. We proposed a bionic sensor inspired by the weakly electric fish. The material identification was completed by analyzing electric signal images, since the electric signal changes when different materials are identified. Firstly, the effective lift-off distance for identification was researched. The materials used in this paper can be effectively identified by the sensor at a lift-off distance of 10 mm. Furthermore, the performance of the sensor for identifying and locating was studied in the presence of multiple materials. The results indicated that the sensor can effectively identify and locate the objects when the distance between objects is greater than 30 mm, while the location error is less than 5% in most cases. Our research proves that the bionic sensor we made can effectively recognize different materials underwater in short-range, which is about 10 mm. Therefore, we expect that the bionic sensor we made can be utilized as a useful tool for underwater object identification.

Consistency of postoperative pain assessments between nurses and patients undergoing enhanced recovery after gynaecological surgery.

AIMS AND OBJECTIVES: To explore the consistency of pain intensity and pain location assessed by nurses and patients in gynaecology undergoing enhanced recovery after surgery pathway. BACKGROUND: Several studies have shown that clinical nurses' assessment of patients' pain is not always accurate. Little is known about the accuracy of nurses' pain assessments for gynaecological patients. Postoperative pain assessment and management is an essential part of enhanced recovery after surgery. DESIGN: Comparative cross-sectional study. METHODS: A total of 160 patients were recruited and only 85 patients and 17 nurses participated. Patients and nurses recorded pain scores (using an 11-point Numeric Rating Scale) and pain location (incision pain, surgical area pain in the abdominal cavity, other pain or no pain) on Pain Assessment Forms at 4 hr after surgery and on the first and second postoperative days. We used the STROBE guidelines to report our study. RESULTS: The patients' pain score was higher than that of nurses from 4 hr to second day after laparoscopic surgery at rest. The pain scores of both nurses and patients decreased over this period of time. All the intraclass correlation coefficients were between 0.214-0.296. At the three time points, surgical area pain in the abdominal cavity and abdominal incision pain were the main pain areas. All the kappa coefficients were between 0.164-0.255. CONCLUSIONS: The consistency of postoperative pain assessment about pain score and pain location between nurses and patients was not high. We should attach importance to systematic pain assessment, and more detailed enhanced recovery after surgery pathways should be developed about pain assessment. RELEVANCE TO CLINICAL PRACTICE: Continuing education for nurses regarding pain assessment is necessary. Nurses should accept the patient's self-reported pain. There should be a step that gives more time for pain assessment in enhanced recovery after surgery pathways.

Research on Finite Element Model Modification of Carbon Fiber Reinforced Plastic (CFRP) Laminated Structures Based on Correlation Analysis and an Approximate Model.

Carbon fiber reinforced plastic (CFRP) laminated structures have been widely used in modern engineering due to their excellent material properties, especially in the aerospace and shipping industries. This requires a high-accuracy finite element model of CFRP laminated structures. However, it is difficult to master the mechanical properties of CFRP structures comprehensively and accurately due to influences from multiple aspects, such as dispersion of material properties, uncertainty of manufacturing technologies, etc. Therefore, a finite element model modification method of CFRP laminated structures based on correlation analysis and an approximate model was proposed. Aiming at minimizing the difference between the analysis model and the measured inherent frequency, the proposed method improves the finite element modeling accuracy of CFRP laminated structures, by iterative optimization based on a global optimization algorithm. In order to solve the problem of high spatial dimension and slow searching in modification of CFRP laminated structure models, the Pearson correlation analysis method was used to screen the material parameters which exert significant impacts on frequency characteristics to reconstruct the searching space. Based on significance parameters, an approximate response model of the CFRP laminated structural system was established. Meanwhile, the modeling accuracy of different orders of response surface models (RSM) and a radial basis function (RBF) neural network model was analyzed, and the best approximate modeling scheme was obtained. The approximate model was updated based on the multi-island genetic algorithm (MIGA) to modify the finite element model of the CFRP laminated structure model. The maximum error and mean error of the updated model are 1.47% and 0.45%. It was proved that the material parameters modified by the proposed method are applicable to simulation analysis of the CFRP laminated structure.

The combined expressions of B7H4 and ACOT4 in cancer-associated fibroblasts are related to poor prognosis in patients with gastric carcinoma.

B7H4 is a member of the B7 family, which is expressed on antigen-presenting cells (APCs) and which negatively regulates the immune response of T cells through the inhibition of their proliferation, cytokine production, and cell cycle progression. Acyl-CoA thioesterase 4 (ACOT4) is an isoform of the ACOTs family that catalyzes the hydrolysis of fatty acyl-CoA to CoA-SH and free fatty acids. An abnormal metabolism of lipids and fatty acids is observed during tumor progression. In our study, a tissue microarray was constructed from 288 cases of gastric adenocarcinoma (GC). ACOT4 expression in cancer-associated fibroblasts (CAFs) and B7H4 expression in cancer tissues were analyzed by immunohistochemistry. The correlations among B7H4 in GC cells, ACOT4 in CAFs, and survival were analyzed. The results showed that the expression rate of B7H4 in tumor cells and ACOT4 in CAFs in 288 tissues was 71.9% (207/288) and 26.4% (76/288), respectively, and a Kaplan-Meier survival analysis showed that a low expression of ACOT4 in fibroblasts was positively correlated with poor survival. However, in a subgroup showing a high ACOT4 expression, the overall survival rate was associated with a high expression of B7H4 and correlated with poor prognosis in GC. In conclusion, ACOT4 expression in CAFs could be an independent prognostic factor for GC patients, and the co-expression with B7H4 in cancer tissues was significantly correlated with GC patients' prognosis. This evidence can represent a comprehensive prediction and a targeted therapy for gastric cancer patients. Tumor immunotherapy targeting might be affected by tumor microenvironment metabolism.

Buformin increases radiosensitivity in cervical cancer cells via cell-cycle arrest and delayed DNA-damage repair.

IMPACT STATEMENT: Our idea originated in the thought of discovering new effects of old drugs. Although this study is a basic research, it is very close to clinical treatment. Flow cytometry and immunofluorescence were used to verify that buformin increases radiosensitivity. We aimed to address one of the thorniest problems in treatment process. Based on discovering new effects of old drugs, it is feasible to use buformin as an anticancer drug in clinical application. This will provide new ideas for clinical treatment.

Serine protease isoforms in Gloydius intermedius venom: Full sequences, molecular phylogeny and evolutionary implications.

Nine distinct venom serine proteases (vSPs) of Gloydius intermedius were studied by transcriptomic, sub-proteomic and phylogenetic analyses. Their complete amino acid sequences were deduced after Expression Sequence Tag (EST) analyses followed by cDNA cloning and sequencing. These vSPs appear to be paralogs and contain the catalytic triads and 1-4 potential N-glycosylation sites. Their relative expression levels evaluated by qPCR were grossly consistent with their EST hit-numbers. The major vSPs were purified by HPLC and their N-terminal sequences matched well to the deduced sequences, while fragments of the minor vSPs were detected by LC-MS/MS identification. Specific amidolytic activities of the fractions from HPLC and anion exchange separation were assayed using four chromogenic substrates, respectively. Molecular phylogenetic tree based on the sequences of these vSPs and their orthologs revealed six major clusters, one of them covered four lineages of plasminogen activator like vSPs. N-glycosylation patterns and variations for the vSPs are discussed. The high sequence similarities between G. intermedius vSPs and their respective orthologs from American pitvipers suggest that most of the isoforms evolved before Asian pitvipers migrated to the New World. Our results also indicate that the neurotoxic venoms contain more kallikrein-like vSPs and hypotensive components than the hemorrhagic venoms. SIGNIFICANCE: Full sequences and expression levels of nine paralogous serine proteases (designated as GiSPs) of Gloydius intermedius venom have been studied. A kallikrein-like enzyme is most abundant and four isoforms homologous to venom plasminogen-activators are also expressed in this venom. Taken together, the present and previous data demonstrate that the neurotoxic G. intermedius venoms contain more hypotensive vSPs relative to other hemorrhagic pitviper venoms and the pitviper vSPs are highly versatile and diverse. Their structure-function relationships remain to be explored and compared. A novel, simplified phylogenetic tree based on the sequences of GiSPs and their closely related orthologs from other pitvipers reveals six major subtypes and offers a better understanding of vSP duplication and evolution in pitvipers of both the Old and New Worlds. It is well known that specific vSPs are potential therapeutic or diagnostic agents that target the plasma proteins or coagulation factors. Our results not only render deeper insights into the variation and evolution of vSPs, but may help to choose right venoms for the development of better therapeutic leads.

Transcriptome and proteome of the highly neurotoxic venom of Gloydius intermedius.

The venomics of Gloydius intermedius were investigated using expressed sequence tags (ESTs) analyses, 2D gel-electrophoresis combined with MALDI-TOF/TOF, and LC-MS/MS. A total of 1920 ESTs from the venom gland cDNA library were sequenced; 74% of them belonged to toxin-families. The four most abundant families among the toxin transcripts were: serine protease (SP, 36.2%), bradykinin potentiating peptide (25.3%), l-amino acid oxidase (LAAO, 13.1%), and phospholipase A2 (PLA2, 9.9%). Moreover, the full sequences of four PLA2s, eight SPs, cysteine-rich secretory protein (CRISP), C-type-lectin-like-protein (CTLP), hyaluronidase, metalloproteinase, and nerve growth factor were deduced from the cDNA sequences. Excluding the CRISP and hyaluronidase, most of the G. intermedius venom proteins bear 92-99% sequence identities to those of other pitviper venoms. The most abundant components are PLA2s (37%), SPs (20%) and LAAO (6%), while metalloproteinase, CTLP, and other components each account for <3% of the total venom proteins. The abundance of Gintexin (a crotoxin-like neurotoxin) and low levels of hemorrhagic metalloproteases, disintegrins and CTLPs highlight the great venom differences between G. intermedius and other hemorrhagic pitvipers. The bimorphism of hemorrhagic and neurotoxic venoms among Gloydius is confirmed; our results shed more lights on the co-evolution of both neurotoxicity and hypotension in some viperid venoms.

Association of tea consumption and the risk of oral cancer: a meta-analysis.

OBJECTIVES: Epidemiological studies evaluating the association of tea consumption and the risk of oral cancer risk have produced inconsistent results. Thus, we conducted a meta-analysis to assess the relationship between tea consumption and oral cancer risk. METHODS: Pertinent studies were identified by a search in PubMed, Web of Knowledge and Wan Fang Med Online. The fixed or random effect model was used based on heterogeneity test. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Finally, 14 articles with 19 studies comprising 4675 oral cancer cases were included in this meta-analysis. The relative risk (95% confidence interval) of oral cancer for the highest versus the lowest category of tea consumption was 0.853 (0.779-0.934), and the association was significant between oral cancer risk and green tea consumption [0.798 (0.673-0.947)] but not in the black tea consumption [0.953 (0.792-1.146)]. The associations were also significant in Asian and Caucasian. CONCLUSIONS: Our analysis indicated that tea consumption may have a protective effect on oral cancer, especially in green tea consumption.

[Pharmacognostical study on seven species from Astragalus genus in Yunnan].

OBJECTIVE: For the identification and utilization of the Astragalus plants from Yunnan, pharmacognostical studies were systematically performed for seven Astragalus plants which were selected from four subgenera of Astragalus genus. METHODS: Standard pharmacognosy methods and HPLC method were adopted, and microscopic characteristics and major chemical constituents of the test plant samples were compared. RESULTS: There were differences in root transverse section, powder and chemical constituents of the seven Astragalus plants. CONCLUSION: This study can provide the pharmacognosy experimental basis for the future study of Astragalus plants.