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Laboratory experiments, numerical simulations and fracturing technology were combined to address the problems in shale oil recovery by CO2 injection. The laboratory experiments were conducted to investigate the displacement mechanisms of shale oil extraction by CO2 injection, and the influences of CO2 pre-pad on shale mechanical properties. Numerical simulations were performed about influences of CO2 pre-pad fracturing and puff-n-huff for energy replenishment on the recovery efficiency. The findings obtained were applied to the field tests of CO2 pre-pad fracturing and single well puff-n-huff. The results show that the efficiency of CO2 puff-n-huff is affected by micro- and nano-scale effect, kerogen, adsorbed oil and so on, and a longer soaking time in a reasonable range leads to a higher exploitation degree of shale oil. In the “injection + soaking” stage, the exploitation degree of heavy hydrocarbons is enhanced by CO2 through its effects of solubility-diffusion and mass-transfer. In the “huff” stage, crude oil in large pores is displaced by CO2 to surrounding larger pores or bedding fractures and finally flows to the production well. The injection of CO2 pre-pad is conducive to keeping the rock brittle and reducing the fracture breakdown pressure, and the CO2 is liable to filter along the bedding surface, thereby creating a more complex fracture. Increasing the volume of CO2 pre-pad can improve the energizing effect, and enhance the replenishment of formation energy. Moreover, the oil recovery is more enhanced by CO2 huff-n-puff with the lower shale matrix permeability, the lower formation pressure, and the larger heavy hydrocarbon content. The field tests demonstrate a good performance with the pressure maintained well after CO2 pre-pad fracturing, the formation energy replenished effectively after CO2 huff-n-puff in a single well, and the well productivity improved.

Invasive papillary carcinoma is a rare form of breast cancer that is more likely to occur in postmenopausal women. Previous studies have been limited to case reports and small retrospective studies, leading to low awareness of this type of tumor and difficult clinical management. According to the available literature, invasive papillary carcinoma exhibits unique pathological features and biological behaviors. Invasive papillary carcinoma is mostly luminal type, with a low rate of lymph node metastasis, which underlies its favorable prognosis. The effectiveness of adjuvant therapy in reducing tumor burden and improving prognosis in patients with invasive papillary carcinoma remains uncertain. Due to the rarity of the lesion, conducting prospective clinical trials is impractical. The use of biological models, such as organoids, can help alleviate the impact of the scarcity of this condition on research. In addition, invasive papillary carcinoma is affected by specific genomic events, and more extensive studies of gene expression profiling may provide molecular-level insights to make optimal therapeutic decisions.

Abstract Background Renal cell carcinoma (RCC) with haemangioblastoma-like characteristics is a type of RCC reported in recent years. RCC with (angio) leiomyomatous stroma (RCCLMS) was included as a provisional entity of the 2016 World Health Organization (WHO) classification. RCC with haemangioblastoma-like characteristics and leiomyomatous stroma is extremely rare. This is the first report of a rare tumour harbouring TSC2 and SETD2 variations. Case presentation The patient was a 38-year-old woman who presented with discomfort in the area of her right kidney. Ultrasound and enhanced CT showed a right renal mass, and clear cell renal cell carcinoma (CCRCC) was suspected; hence, robot-assisted laparoscopic nephron-sparing partial nephrectomy was performed. Gross examination revealed a well-circumscribed tumour measuring 2.0 cm × 1 cm × 0.7 cm under the renal capsule adjacent to the stripping edge that was greyish yellow and greyish red in colour. Histologic examination showed that the tumour consisted of three different structures: a CCRCC-like region, a haemangioblastoma-like region, and a focal leiomyomatous stroma component. Based on immunohistochemistry, the CCRCC-like region was diffusely strongly positive for AE1/AE3, vimentin, CAIX, PAX8, PAX2, CK7, and CAM5.2, partly positive for HNF1α, and negative for CD10, α-inhibin, NSE, S-100, CD34, and TFE3. The haemangioblastoma-like area was diffusely positive for vimentin, CAIX; partly positive for PAX8, PAX2, α-inhibin, and S-100; mostly positive for NSE; and slightly positive for HNF1α; the CD34 staining highlighted the complex capillary network. The Ki67 index was approximately 1–2% in the two above areas, and the leiomyomatous stroma was strongly positive for SMA. The whole-exon sequencing (WES) showed TSC2 and SETD2 variations. There was no progression after 18 months of follow-up. Conclusion We report for the first time a unique case of RCC with haemangioblastoma-like features and leiomyomatous stroma accompanied by rare molecular abnormalities. Whether this is a new tumour entity or a variant of clear cell carcinoma remains to be determined. The biological behaviour and clinical characteristics need to be further examined.

Abstract In the field of preference-based evolutionary multiobjective optimization, optimization algorithms are required to search for the Pareto optimal solutions preferred by the decision maker (DM). The reference point is a type of techniques that effectively describe the preferences of DM. So far, the reference point is either static or interactive with the evolutionary process. However, the existing reference point techniques do not cover all application scenarios. A novel case, i.e., the reference point changes over time due to the environment change, has not been considered. This paper focuses on the multiobjective optimization problems with dynamic preferences of the DM. First, we propose a change model of the reference point to simulate the change of the preference by the DM over time. Then, a dynamic preference-based multiobjective evolutionary algorithm framework with a clonal selection algorithm (ĝa-NSCSA) and a genetic algorithm (ĝa-NSGA-II) is designed to solve such kind of optimization problems. In addition, in terms of practical applications, the experiments on the portfolio optimization problems with the dynamic reference point model are tested. Experimental results on the benchmark problems and the practical applications show that ĝa-NSCSA exhibits better performance among the compared optimization algorithms.

Background Approximately 10–20% of patients diagnosed with prostate cancer (PCa) evolve into castration-resistant prostate cancer (CRPC), while nearly 90% of patients with metastatic CRPC (mCRPC) exhibit osseous metastases (BM). These BM are intimately correlated with the stability of the tumour microenvironment. Purpose This study aspires to uncover the metabolism-related genes and the underlying mechanisms responsible for bone metastatic prostate cancer (BMPCa). Methods Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets of PCa and BM were analyzed through R Studio software to identify differentially expressed genes (DEGs). The DEGs underwent functional enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), with key factors screened by a random forest utilized to establish a prognostic model for PCa. The study explored the relationship between DEGs and the stability of the immune microenvironment. The action and specificity of CRISP3 in PCa was validated through western blot analysis, CCK-8 assay, scratch assay, and cellular assay. Results The screening of GEO and TCGA datasets resulted in the identification of 199 co-differential genes. Three DEGs, including DES, HBB, and SLPI, were selected by random forest classification model and cox regression model. Immuno-infiltration analysis disclosed that a higher infiltration of naïve B cells and resting CD4 memory T cells occurred in the high-expression group of DES, whereas infiltration of resting M1 macrophages and NK cells was greater in the low-expression group of DES. A significant infiltration of neutrophils was observed in the high-expression group of HBB, while greater infiltration of gamma delta T cells and M1 macrophages was noted in the low-expression group of HBB. Resting dendritic cells, CD8 T cells, and resting T regulatory cells (Tregs) infiltrated significantly in the high-expression group of SLPI, while only resting mast cells infiltrated significantly in the low-expression group of SLPI. CRISP3 was established as a critical gene in BMPCa linked to DES expression. Targeting CRISP3, d-glucopyranose may impact tumour prognosis. During the mechanistic experiments, it was established that CRISP3 can advance the proliferation and metastatic potential of PCa by advancing epithelial-to-mesenchymal transition (EMT). Conclusion By modulating lipid metabolism and maintaining immunological and microenvironmental balance, DES, HBB, and SLPI suppress prostate cancer cell growth. The presence of DES-associated CRISP3 is a harbinger of unfavorable outcomes in prostate cancer and may escalate tumor proliferation and metastatic capabilities by inducing epithelial-mesenchymal transition.

Objective: To evaluate the effects of injectable platelet-rich fibrin (i-PRF) produced by a simple twice-centrifugation method combined with vacuum sealing drainage on wound inflammation and scar formation in chronic refractory wounds (CRW).Methods: A total of sixty-eight patients with CRW who were admitted to our hospital were enrolled in this study. They were then randomly divided into the study group (n = 34) with being treated using negative pressure sealing and drainage technology, and the control group (n = 34) with being treated using injectable platelet-rich fibrin in conjunction with negative pressure sealing and drainage technology. The following were the primary outcomes: scar conditions at 1 and 3 months after the wound was fully healed, wound healing time, hospitalization time, wound healing rate, incidence of adverse reactions, serum inflammatory indices, and pain levels were assessed 1 day before treatment and 14 days after treatment. The secondary outcomes were determined by comparing the proportion of positive bacterial cultures in the two groups on the day before therapy, as well as on the seventh and fourteenth days after treatment.Results: The wound healing time and hospital stay in the study group were significantly lower than that in the control group (all p < 0.001). The wound healing rate of the study group was significantly higher than that of the control group on the 14th day and 28th day after treatment (all p < 0.001). On the 14th day after treatment, the levels of WBC, CRP, and IL-6 in the study group were lower than those in the control group (all p < 0.001). The positive rate of bacterial culture in the study group was significantly lower than that in the control group on the 7th and 14th day after treatment (all p < 0.05). At 1 month and 3 months after treatment, the VSS score in the study group was lower than that in the control group (all p < 0.001). The total defect rate of the study group was also significantly lower than that of the control group (5.88% vs. 29.41%, p = 0.011).Conclusion: The i-PRF produced by simple twice-centrifugation method combined with VSD could reduce wound inflammation and improve scar formation in patients with CRW.

Occurrences of breast cancer and thyroid cancer metachronously or synchronously are common for women, but axillary lymph node metastasis from both cancers is rarely seen. We report a patient who had two metastatic lymph nodes from papillary thyroid carcinoma after axillary lymph node dissection with mastectomy. Papillary thyroid carcinoma diagnosis was ensured after thyroidectomy. A literature review revealed that even the co-occurrence of breast cancer and thyroid cancer is not rare, but the etiology behind this phenomenon is not elucidated well. Genetic disorders, thyroid dysfunction, and hormone receptors may be relevant. Considering the rareness of axillary lymph node metastasis of thyroid cancer, adjuvant therapy and surgery treatment for this kind of case should be considered elaborately.

Here, the authors discover that NGF, upregulated by transcription factor ZBTB46 in prostate cancer exposed to androgen therapy, promotes neuroendocrine differentiation. They show that NGF interacts with the GPCR CHRM4, that both NGF and CHRM4 are upregulated in highly metastatic prostate cancer and that targeting NGF reduces therapy resistance in a mouse xenograft model.

ObjectiveThis study was designed to investigate whether it is useful and necessary to add a T2 level thoracic paravertebral block (TPVB) based on brachial-cervical plexus block to avoid incomplete anesthesia in elderly patients undergoing deltopectoral approach proximal humeral fracture (PHF) surgery.Materials and MethodsThis study involved 80 patients scheduled for PHF surgery who were randomized to receive either IC block (combined interscalene brachial plexus with superficial cervical plexus block) or ICTP block (T2 TPVB supplemented with IC block). The primary outcome was the success rate of regional anesthesia. The patient who experienced incomplete block was administered with intravenous remifentanil for rescue, or conversion to general anesthesia (GA) if remifentanil was still ineffective. Secondary outcomes included requirements of rescue anesthesia, sensory block of the surgical region, the incidence of adverse reactions, and block procedure-related complications.ResultsThe success rate of regional anesthesia in the ICTP group was higher compared with the IC group (77.5 vs. 52.5%, p = 0.019). Intravenous remifentanil was required in 32.5% of patients in the IC group and 17.5% in the ICTP group, respectively. Conversion to GA was performed in 15% of patients in the IC group and 5% in the ICTP group. Sensory block at the medial proximal upper arm was achieved in 85% of patients in the ICTP group, whereas 10% in the IC group (p < 0.001). There was no difference between the groups with respect to the incidence of intraoperative adverse reactions. No block-related complications occurred in either group.ConclusionAdding a T2 TPVB is helpful to decrease, but not absolutely avoid the occurrence of incomplete regional anesthesia during PHF surgery in elderly patients. However, considering the potential risks, it is not an ideal option while a minor dose of remifentanil can provide a satisfactory rescue effect.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03919422.

Although circulating tumor cells (CTCs) have shown promise as potential biomarkers for diagnostic and prognostic assessment in gastric cancer (GC), determining the predictive and prognostic value of programmed death‐ligand 1 (PD‐L1)‐positive CTCs in patients with GC is a challenge. Here, we identified that the expression of total vimentin (VIM) protein was positively correlated with PD‐L1 and inhibited CD8+ T‐cell activation in patients with GC according to bioinformatics analysis. Notably, coexpression of PD‐L1 and cell‐surface VIM (CSV) was detected by immunofluorescence and immunohistochemistry assay in locally advanced GC tumor specimens and metastatic lymph nodes. Likewise, CSV expression level was significantly decreased after transiently knocking down PD‐L1 in GC cell lines. Based on our established CTC detection platform, CTCs were isolated from peripheral blood samples collected from 70 patients (38 resectable and 32 unresectable) with GC using magnetic positive selection and a CSV‐specific monoclonal antibody, 84‐1. CSV+PD‐L1+CTCs were observed in 50 of 70 (71%) GC patient samples, ranging from 0 to 261 mL−1. A higher number of CSV+PD‐L1+CTCs were significantly associated with a short survival duration and poor therapeutic response. This study demonstrated that detection of PD‐L1+CTCs using a CSV‐enrichment method has promising value as a clinically relevant prognostic marker for GC.

Abstract Background The innervation of the shoulder-upper-extremity area is complicated and unclear. Regional anesthesia with a brachial plexus and cervical plexus block is probably inadequate for the proximal humeral surgery. Missing blockade of the T1–T2 nerves may be the reason. We conduct this prospective randomized controlled trial (RCT) to explore whether an additional T2 thoracic paravertebral block (TPVB) can improve the success rate of regional anesthesia for elderly patients in proximal humeral fracture surgery. Methods/design The patients aged 65 years or older, referred for anterior-approach proximal humeral fracture surgery, will be enrolled. Each patient will be randomly assigned 1:1 to receive a combined interscalene brachial plexus with superficial cervical plexus block (IC) (combined interscalene brachial plexus with superficial cervical plexus block) or an IC block combined with thoracic paravertebral block (ICTP) block (combined thoracic paravertebral block with brachial plexus and superficial cervical plexus block). The primary outcome is the success rate of regional anesthesia without rescue analgesic methods. The secondary outcomes are as follows: sensory block at the surgical area, proportion of patients who need rescue anesthesia (intravenously administered remifentanil or conversion to general anesthesia), cumulative doses of intraoperative vasoactive medications and adverse events. The total sample size is estimated to be 80 patients. Discussion This RCT aims to confirm whether an additional T2 TPVB can provide better anesthetic effects of regional anesthesia with brachial and cervical plexus block in elderly patients undergoing proximal humeral surgery. Trial registration ClinicalTrials.gov, ID: NCT03919422. Registered on 19 April 2019.

BackgroundCombined anesthesia can be a promising option for hip surgery when neuraxial anesthesia is contraindicated. Lumbar and sacral plexus blocks, and femoral nerve and lateral femoral cutaneous (LFC) nerve blocks in combination with general anesthesia (GA) are commonly used in elderly patients undergoing arthroplasty for hip fracture surgery. However, no study has compared these two anesthetic strategies in the perioperative period.MethodsA total of 41 elderly patients scheduled for arthroplasty for hip fracture surgery were randomized into group A (n = 20) and group B (n = 21). Group A received femoral nerve block, LFC nerve blocks, and GA, and group B received lumbar plexus block, sacral plexus block, and GA. Primary outcomes were incidences of hemodynamic events and changes in blood pressure (BP) and heart rate (HR). Secondary outcomes included time and drug consumption, infusion and bleeding volume, eyes opening time after surgery, and postoperative quality recovery rate.ResultsCompared with group B, group A showed a lower incidence of intraoperative hypotension (p < 0.001), higher BP [including mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP)] following induction (IN), and higher HR from mid-surgery. Time required for nerve blockade (p < 0.001) and ephedrine consumption was significantly shorter in group A (p < 0.001), while sufentanil consumption was higher as compared to group B (p = 0.002). No significant differences in other intraoperative parameters and postoperative quality recovery rate were reported during the observation.ConclusionOur pilot data indicate that compared with lumbar and sacral plexus blocks, femoral nerve and LFC nerve blocks may provide more stable intraoperative hemodynamics and a comparable postoperative recovery for elderly patients undergoing arthroplasty for hip fracture under GA. Further studies with a larger sample size are needed to derive stronger evidence.

This paper proposes a new definition method of currency, which further divides the current hot digital currency according to its legitimacy, encryption, centralization, and other characteristics. Among these, we are mainly interested in virtual cryptocurrencies. Virtual cryptocurrency is one of the application directions of blockchain technology. Its essence is a distributed shared ledger database, which generally has the characteristics of decentralization and non-tampering. The technologies supporting the practical application of virtual cryptocurrencies involve multiple scientific and technological fields such as mathematical algorithms, cryptography, Internet communication, and computer software. Since the launch of the first virtual cryptocurrency bitcoin in 2009, it has developed rapidly worldwide. As of August 1, 2021, more than 11,570 virtual cryptocurrencies have been publicly issued and traded globally, with a total value of over $1.68 trillion. This paper proposes the virtual cryptocurrency trading popularity value system as a standardized index for quantitative analysis of virtual cryptocurrency trading, and the virtual cryptocurrency trading index system as a barometer of the virtual cryptocurrency trading market. It has contributed schemes to the analysis of the market rules of virtual cryptocurrency transactions and the realization and early warning of abnormal virtual cryptocurrency transactions, which are the two main hot research directions of virtual cryptocurrency. To be specific, the popularity value of virtual cryptocurrency transactions provides parameters for analyzing individual virtual cryptocurrencies, and the popularity index of virtual cryptocurrency transactions provides parameters for analyzing the virtual cryptocurrency trading market, so as to prevent major risks of virtual cryptocurrency transactions.

Siberian ginseng, perennial herb belongs to Araliaceae family used in traditional medicines to treat hypertension, thrombus, inflammation and cancer. In the present study, we biosynthesized goldnanoparticles using Siberian ginseng aqeous extract in a cost effective manner. The synthesized Siberian ginseng gold nanoparticle (SG-GNPs) were characterized using UV-Vis spec, HR-TEM, XRD, FTIR, SAED analysis. UV-Vis spectroscopic analysis showed a surface Plasmon resonance peak at 538 nm which does not reduce till 30 days of incubation. The results of HR-TEM, XRD and SAED confirm the spherical shape, crystalline nature and the size of the synthesized gold nanoparticles. The FTIR results prove that the biological components present in the Siberian ginseng had reduced the gold ions to synthesis gold nanoparticles. After characterization, the efficacy of SG-GNPS against the melanoma, a deadliest skin carcinoma, was assessed in vitro using B16 murine melanoma cells. The CC50 dose of SG-GNPs against B16 cells were assessed with MTT assay and the anticancer activity was evaluated using Rhodamine 123, H2DCFDA and dual staining techniques. The induction of apoptosis by SG-GNPs against melanoma cells were confirmed with q-PCR analysis. The results of staining techniques prove that SG-GNPs increase the reactive oxygen species and decreased the mitochondrial membrane potential. It is further confirmed by the results of q-PCR analysis which shows increased apoptotic Bid, Bad, Casp3, Casp 9 genes and decreased antiapoptotic Bcl2 gene expression in SG-GNPs treated cells. Our results authentically prove the biosynthesized SG-GNPs induces apoptosis in melanoma cells and it possesses anticancer property.

Acidizing technology is an effective reformation method of oil and gas reservoirs. It can also remove the reservoir pollution near wellbore zones and enhance the fluid transmissibility. The optimal injection rate of acid is one of the key factors to reduce cost and improve the effect of acidizing. Therefore, the key issue is to find the optimal injection rate during acid corrosion in fractured carbonate rock. In this work, a novel reactive flow mathematical model based on two-scale model and discrete fracture model is established for fractured carbonate reservoirs. The matrix and fracture are described by a two-scale model and a discrete fracture model, respectively. Firstly, the two-scale model for matrix is combined with the discrete fracture model. Then, an efficient numerical scheme based on the finite element method is implemented to solve the corresponding dimensionless equations. Finally, several important aspects, such as the influence of the injection rate of acid on the dissolution patterns, the influence of fracture aperture and fracture orientations on the dissolution structure, the breakthrough volume of injected acid, and the dynamic change of fracture aperture during acidizing, are analyzed. The numerical simulation results show that there is an optimal injection rate in fractured carbonate rock. However, the fractures do not have an impact on the optimal acid injection rate, they only have an impact on the dissolution structure.

Photodetectors based on two dimensional (2D) materials still suffer from low performance. Here, the authors tackle this issue by introducing a reconfigurable design enabled by locally tuning the doping of a 2D molybdenum disulfide film through the polarization of an underlying ferroelectric material.

Background Studies have shown that E3 ubiquitin ligase CBLL1 plays multiple roles in development and tumorigenesis. CBLL1 is over‐expressed in colon cancer and associated with cancer cell proliferation. While, the overexpression of CBLL1 inhibited the estrogenic dependent cell proliferation and migration in ER alpha dependent breast cancer cell MCF‐7. Methods We used an immunohistochemical method to detect CBLL1 expression in human NSCLC and corresponding normal lung tissues and analyzed its relationship with clinicopathological parameters. Moreover, we investigated the role of CBLL1 in NSCLC cell behavior by inhibiting its expression in A549 and H1299 cells. Results In this study, we found that CBLL1 was frequently upregulated in non‐small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. We found that the high expression of CBLL1 was associated with the tumor size in NSCLC tissues. It has been recently reported that CBLL1 promotes cell proliferation and invasion in A549 and H460 cells. Our results confirmed that CBLL1 promoted the proliferation by promoting G1/S cell cycle transition in NSCLCs cells. Moreover, CBLL1 knockdown inhibited cell invasion via increased E‐cadherin protein expression, and decreased expression of MMP2 and MMP9 in NSCLC cell lines. The protein expression of E‐cadherin was increased after CBLL1 depletion while the E‐cadherin mRNA was not affected after knockdown of the endogenous CBLL1. Conclusion These results provide important insights for using CBLL1 as an oncogenic marker gene in the development and progression of non‐small cell lung cancer.

PurposeThis study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).Materials and MethodsWe collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate-specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.ResultsAmong the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 months, 95% CI: 15.3–19.9 months) had significantly worse survival compared with usual CRPC patients (median OS: 23.6 months, 95% CI: 21.3-25.9 months, log-rank P = 0.001), especially in metastasis cases (median OS: 15.7 months, 95% CI: 13.3-18.0 months) and patients with small cell carcinoma component (median OS: 9.7 months, 95% CI: 8.2–11.2 months). Prostate adenocarcinoma with diffuse NE differentiation (median OS: 18.8 months, 95% CI: 15.3–22.3 months) had poor outcome than those with usual CRPC (P = 0.027), while there was no significant change in the focal NE differentiation (median OS: 22.9 months, 95% CI: 18.1–27.7 months, P = 0.136). In the unadjusted model, an excess risk of overall death was observed in T-NEPC with PSA negative (HR = 2.86, 95% CI = 1.39–6.73). Among 476 NEPC cases in the SEER database from 2004 to 2017, we observed a higher hazard of overall death in patients aged 65 years and older (HR = 1.35, 95% CI = 1.08–1.69), patients with PSA ≤ 2.5 ng/ml (HR = 1.90, 95%CI = 1.44–2.52), patients with PSA 2.6–4.0 ng/ml (HR = 2.03, 95%CI = 1.38–2.99), stage IV tumor (HR = 2.13, 95%CI = 1.47–3.08) and other races (HR = 1.85, 95%CI = 1.17–2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.ConclusionT-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.

Summary: Cancer progression to an aggressive phenotype often co-opts aspects of stem cell biology. Here, we developed gene signatures for normal human stem cell populations to understand the relationship between epithelial cancers and stem cell transcriptional programs. Using a pan-cancer approach, we reveal that aggressive epithelial cancers are enriched for a transcriptional signature shared by epithelial adult stem cells. The adult stem cell signature selected for epithelial cancers with worse overall survival and alterations of oncogenic drivers. Lethal small cell neuroendocrine lung, prostate, and bladder cancers transcriptionally converged onto the adult stem cell signature and not other stem cell signatures tested. We found that DNA methyltransferase expression correlated with adult stem cell signature status and was enriched in small cell neuroendocrine cancers. DNA methylation analysis uncovered a shared epigenomic profile between small cell neuroendocrine cancers. These pan-cancer findings establish a molecular link between human adult stem cells and aggressive epithelial cancers. : Smith et al. use a systems-level, human pan-stem cell approach to find that aggressive epithelial cancers, independent of tissue of origin, activate an adult stem cell expression program. They report that small cell neuroendocrine cancers from different tissues are molecularly linked to adult stem cells through a shared transcriptional and epigenomic profile. Keywords: stem cell signature, pan-cancer, neuroendocrine prostate cancer, small cell lung cancer, adult stem cells

Oxidative stress plays a critical role in the etiology and pathogenesis of neurodegenerative disorders, and the molecular mechanisms that control the neuron response to ROS have been extensively studied. However, the oxidative stress-effect on miRNA expression in hippocampal neurons has not been investigated, and little is known on the effect of ROS-modulated miRNAs on cell function. In this study, H2O2 was used to stimulate the mouse primary hippocampal neurons to develop an oxidative stress cell model. The alterations of miRNAs expression were detected by microarray analysis and five miRNAs were validated by real-time RT-PCR. The bioinformatic analysis of deregulated miRNAs was performed to determine their potential roles in the pathogenesis of neurological disorders. We found that H2O2 mediated a total of 101 deregulated miRNAs, which mainly took part in the regulation of the MAPK pathway. Among them, miR-135b and miR-708 were up-regulated significantly and their targets were predicted to be involved in DNA recombination, protein ubiquitination, protein autophosphorylation and development of neurons. These results demonstrated that oxidative stress alters the miRNA expression profile of hippocampal neurons, and the deregulated miRNAs might play a potential role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD).

Background and objective It has been proven that lymph node metastasis was closely related to prognosis of lung cancer. Interleukin-7 (IL-7) and interleukin-7 receptor (IL-7R) could promote lymph node metastasis through vascular endothelial growth factor-D (VEGF-D). The aim of this study is to explore the expressions of IL-7 and IL-7R in lung cancer and the relationship between them with lymph node metastasis and prognosis in non-small cell lung cancer (NSCLC). Methods The expressions of IL-7 and IL-7R in 95 cases of NSCLC were detected with immunohistochemistry method and the relationship between IL-7 and IL-7R and their impact on lung cancer patients’ outcomes were analyzed. Results In 95 cases of NSCLC, the high expression rates of IL-7, IL-7R and VEGF-D were 63.16%, 61.05% and 58.95%. The expressions of IL-7 and IL-7R were correlated closely with clinic stage and lymph node metastasis, but had no relationship with age, gender, histological type and differentiation degree. The lymphatic vessel density (LVD) mean of the group with high expressions of IL-7 and IL-7R was higher than that with low or negative expressions of IL-7 and IL-7R, and they were significant different in statistics. Log-rank analysis showed that the postoperative survival period was significantly shorter in high expression groups IL-7, IL-7R and VEGF-D comparing with that in low or negative groups. Conclusion The high expression of IL-7 and IL-7R is highly positie correlated with clinic stage, lymph node metastasis, VEGF-D, LVD and poor prognosis in Non-small cell lung cancer.

Background and objective It has been proven that MTA2 was expressed in many tumor cell lines and was correlated with tumor invasion and metastasis. The aim of this study is to investigate the expression of MTA2 protein in non-small cell lung cancer (NSCLC) and to explore the relationship between the expression of MTA2 and the pathological features. Methods The expression of MTA2 protein in 110 cases of NSCLC and 34 cases corresponding lung tissues was detected with immunohistochemistry method. The relationship between the expression of MTA2 and the pathological features in NSCLC was analyzed statistically. Results There was no expression of MTA2 protein in cancer collateral branch trachea epithelial and alveolar epithelial, but there was some expression in partial NSCLC. The positive rate of MTA2 was 58.18% (64/110) in 110 NSCLC cases. The expression of MTA2 had negative correlation with differentiation degree of NSCLC but had positive correlation with clinical stage and lymph node metastasis (P < 0.05), moreover, it had no obvious correlation with age, gender and pathological type (P > 0.05). Conclusion There was some expression of MTA2 in partial NSCLC and it was correlated with differentiation degree, clinical stage and lymph node metastasis. The results show that the occurrence and development of lung cancer may be related with MTA2. MTA2 may act as a new symbol and target in the treatment of lung cancer.

Background and objective MicroRNAs (miRNAs) are endogenous, non-coding small RNA in eukaryotes. They recognize their target sites by incomplete base pairing and posttranscriptionally regulate gene expression, and function on a lot of complex vital processes of organisms. The objective of this work is to study how hsa-miR-125a-5p enhances the invasive ability of lung cancer cells. Methods The target gene and its target sites of hsa-miR-125a-5p were predicted by microRNA.org. We investigated Rock-1 mRNA and protein expressions by RT-PCR and Western blot according to the result of prediction further. The invasive ability of A549 cells, which were transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide after being blocked by anti-Rock-1, was observed by Transwell. Results With RT-PCR and Western blot, Rock-1 mRNA and protein were both increased in A549 cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide and were both decreased in the cells which transfected with antisense vs control groups. The invasive ability of A549 cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide were weakened after being blocked by anti-Rock-1, vs non-blocking group by Transwell test. Conclusion hsa-miR-125a-5p could up-regulate Rock-1 and enhance invasion in lung cancer cells.

Background and objective MicroRNAs (miRNAs) are short non-coding RNAs that posttranscriptionally regulate gene expression by partially binding complementary to target sites in mRNAs. Although some impaired miRNA regulations have been observed in many human cancers, the functions of miR-125a are still unclear. The aim of this study is to investigate the expression of hsa-miR-125a-5p in NSCLC cell lines and the relationship between hsa-miR-125a-5p and the invasion of lung cancer cells. Methods The expression of hsa-miR-125a-5p and the effectiveness for a given period time after being transfected sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide, which were 24 h, 36 h, 48 h, 60 h and 72 h, were examined by realtime PCR. Meanwhile, we investigated the modification of invasive ability in A549 and NCI-H460 cells by transwell. Results Real-time PCR showed that hsa-miR-125a-5p was poorly-expressed in 6 lung cancer cell lines, especially in LH7, NCI-H460, SPC-A-1 and A549. The highest expression of hsa-miR-125a-5p occurred in the cells transfected with sense hsa-miR-125a-5p 2’-O-methyl oligonucleotide 36 h. Furthermore, the invasive abilities of A549 and NCI-H46O were enhanced by up-regulating hsa-miR-125a-5p. Conclusion hsa-miR-125a-5p was poorly-expressed in lung cancer cells and it could enhance lung cancer cell invasion by up-regulating hsa-miR-125a-5p.

Background and objective Heparanase has been thought to be a good molecular marker of tumor, and the heparanase expression level was correlated closely with tumor metastasis. In this study, we investigate the effects of heparanase on angiogenesis and lymphangiogenesis of lung cancer and the relationship between heparanase expression and vascular endothelial growth factor (VEGF), vascular endothelial growth factor-C (VEGF-C). Methods Immunohistochemistry was used to detect the expression of heparanase, VEGF, VEGF-C protein and microvascular density (MVD), lymphatic vessel density (LVD) in 115 cases of non-small cell lung cancer (NSCLC) and 45 cases of adjacent normal tissue samples. Results Our results showed that heparanase expression was significantly increased in 91 (79.13%) of the 115 cases and correlated with lymph node metastasis (node positive rate 87.0%; node negative rate 36.8%; P=0.003). Heparanase positive expression cases have significantly higher concentration of microvascular density (MVD) and lymphatic vessel density (LVD) as compared with heparanase negative expression cases (P

Background and objective Angiogenesis depends on the interaction of a variety of promoting factors and inhibiting factors. Vascular endothelial growth factor (VEGF) and Notch signaling pathway take part in this process. This experiment investigates the expression of Notch ligand DLL4 and VEGF in lung adenocarcinoma and theirrelationship with angiogenesis in tumor. Methods Immunohistochemical method was used to detect DLL4, VEGF and CD34 protein expression in 80 cases of lung adenocarcinoma (including bronchioloalveolar carcinoma and common lung adenocarcinoma) paraffin section tissues. Results The expression of DLL4 and VEGF was closely related to tumordiameter, clinical stage, histological grade and lymph node metastasis, the VEGF expression rate in DLL4 positive expression cases was significantly more than the DLL4 negative cases, the correlation between microvascular density and DLL4, VEGF co-expression was more significant, the expression of DLL4 in common lung adenocarcinoma was significantly higher than that in bronchioloalveolar carcinoma. Conclusion The prognosis of lung adenocarcinoma is significant correlated with the angiogenesis, high expression of DLL4 is closely related to the metastasis and the prognosis.

Background and objective CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxiainducible factor 1α (HIF-1α) and hypoxia inducible factor 2α (HIF-2α) protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC. Methods T he levels of expressions of CCR7, HIF-1α and HIF-2α protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1α siRNA、HIF-2α siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1α, HIF-2α were respectively analyzed. Results Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1α, HIF-2α was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1α and HIF-2α protein were found to be 75.53% (71/94), 54.25% (51/ 94) and 70.21% (66/94) in non small celllung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P 0.05). Furthermore, A significant correlation were found among CCR7, Hif-1α and HIF-2α (r =0.272, P

Background and objective It has been proven that suppressor of cytokine signaling 3 (SOCS3) contributes to inhibition of cell overgrowth, induction of apoptosis and stabilization. In the present study, we addressed the SOCS3 expression in non-small cell lung cancer (NSCLC) and explored the relationship between SOCS3 expression and lymph node metastases as well as clinicopathological characteristics in lung cancer patients. Methods Western blotting analysis was used to examine the expression of SOCS3 in 30 NSCLCs and non-tumor tissues. The methylated status of SOCS3 gene was determined by methylation-specific PCR (MSP) assay in the same 30 samples. Immunohistochemical staining was applied to determine SOCS3 expression in 90 NSCLC sections and the correlation of SOCS3 expression with lymph node metastases and clinicopathological characteristics was also analyzed. Results SOCS3 expression was much lower in 30 NSCLCs than tnat in non-tumorous counterparts of the same case (optical density were 26.3±12.3 and 78.4±14.5 respectively, P=0.000) by western blotting analysis. MSP showed that the methylated rate of SOCS3 gene was (20/30) 66.7% in NSCLCs, and (4/30) 13.3% in non-tumors, and SOCS3 expression was negatively correlated with methylation (r=-0.454, P=0.012). Furthermore, SOCS3 expression was observed in non-tumorous epithelial cells by immunohistochemiscal analysis, and the positive rate of SOCS3 expression in 90 NSCLC samples was (41/90) 45.6%. SOCS3 expression rate was lower in NSCLCs with lymph node metastases (35.4%) compared with non-metastatic NSCLCs (57.1%, P=0.039), and in NSCLCs of stage Ⅲ (36.4%) than in stage Ⅰ+Ⅱ (60.0%, P=0.028). SOCS3 expression was not correlated with histological type or differentiation (P>0.05). Conclusion The results of this study suggest that Down-regulation of SOCS3 expression in NSCLC associated with methylation might be correlated with lymph node metastases as well as clinicopathological stage of NSCLCs.

Paraplegia is a rare postoperative complication. We present a case of acute paraplegia after elective gastrectomy surgery because of cervical disc herniation. The 73-year-old man has the medical history of cervical spondylitis with only symptom of temporary pain in neck and shoulder. Although the patient’s neck was cautiously preserved by using the Discopo, an acute paraplegia emerged at about 10 hours after the operation. Severe compression of the spinal cord by herniation of the C4-C5 cervical disc was diagnosed and emergency surgical decompression was performed immediately. Unfortunately the patient showed limited improvement in neurologic deficits even after 11 months.

Background and objective It has been proven that hypoxia could promote tumor cells invasion and metastasis by different mechanisms, but the relationship between hypoxia and CCR7 have not been reported. The aim of this investigate is to evaluate the effects of hypoxia on the expression of CCR7 and the invasiveness of lung adenocarcinoma A549 cells. Methods A549 cells were incubated at either normoxia (37 ℃, 5%CO2, 21%O2) or hypoxia(37 ℃, 5%CO2, 1%O2) condition for 4 h,12 h, 24 h. The expressions of CCR7 mRNA and protein levels were observed by RT-PCR and Western blotting; Cells invasiveness was measured by matrigel invasion assay. Results RT-PCR and Western blotting showed that the expression of CCR7 was detected in lung adenocarcinoma A549 cells, CCR7 mRNA and protein expression level were increased with culture time along either in normoxia or hypoxia condition; Furthermore,compared with normoxia group, the CCR7 mRNA and protein expression level in hypoxia group was increased (P

The objective of the current study was to determine the clinical significance of junctional adhesion molecule A (JAM-A) in patients with non-small cell lung cancer (NSCLC) and the biological function of JAM-A in NSCLC cell lines. We showed that JAM-A is predominantly expressed in cell membranes and high expression of JAM-A occurred in 37% of lung tumor specimens compared to corresponding normal tissues. High expression of JAM-A was significantly correlated with TNM stage (P = 0.021), lymph node metastasis (P = 0.007), and decreased overall survival (P = 0.02), In addition, we observed that silencing JAM-A by small interfering RNA inhibited tumor cell proliferation and induced cell cycle arrest at the G1/S boundary. Western blotting analysis revealed that knockdown of JAM-A decreased the protein levels of cyclin D1, CDK4, 6, and P-Rb. Thus, JAM-A plays an important role in NSCLC progression.

MicroRNA-449a is expressed at a low level in several tumors and cancer cell lines, and induces G1 arrest, apoptosis, and senescence. To identify the function of miR-449a in non-small cell lung cancer (NSCLC), we discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. We also investigated the impact of miR-449a on migration and invasion in NSCLC cells. The expression of miR-449a in NSCLC tissues and cell lines was detected using RT-qPCR. In vitro, gain-of-function, loss-of-function experiments, and fluorescence assays were performed to identify the potential target of miR-449a and the function of miR-449a in NSCLC cells. MiR-449a was downregulated in both NSCLC tissues and cell lines. Moreover, a low expression level of miR-449a appeared to be correlated with lymph node metastasis and poor survival. In vitro, miR-449 regulated cell migration and invasion in NSCLC cells as a potential tumor suppressor, at least in part by targeting c-Met. Furthermore, reciprocal expression of miR-449a and c-Met was shown in NSCLC tissue samples. This study indicates that miR-449a might be associated with NSCLC progression, and suggests a crucial role for miR-449a in NSCLC.