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Abstract Background The tumor microenvironment (TME) provides a region for intricate interactions within or between immune and non-immune cells. We aimed to reveal the tissue architecture and comprehensive landscape of cells within the TME of colorectal cancer (CRC). Methods Fresh frozen invasive adenocarcinoma of the large intestine tissue from 10× Genomics Datasets was obtained from BioIVT Asterand. The integration of microarray-based spatial transcriptomics (ST) and RNA sequencing (RNA-seq) was applied to characterize gene expression and cell landscape within the TME of CRC tissue architecture. Multiple R packages and deconvolution algorithms including MCPcounter, XCELL, EPIC, and ESTIMATE methods were performed for further immune distribution analysis. Results The subpopulations of immune and non-immune cells within the TME of the CRC tissue architecture were appropriately annotated. According to ST and RNA-seq analyses, a heterogeneous spatial atlas of gene distribution and cell landscape was comprehensively characterized. We distinguished between the cancer and stromal regions of CRC tissues. As expected, epithelial cells were located in the cancerous region, whereas fibroblasts were mainly located in the stroma. In addition, the fibroblasts were further subdivided into two subgroups (F1 and F2) according to the differentially expressed genes (DEGs), which were mainly enriched in pathways including hallmark-oxidative-phosphorylation, hallmark-e2f-targets and hallmark-unfolded-protein-response. Furthermore, the top 5 DEGs, SPP1, CXCL10, APOE, APOC1, and LYZ, were found to be closely related to immunoregulation of the TME, methylation, and survival of CRC patients. Conclusions This study characterized the heterogeneous spatial landscape of various cell subtypes within the TME of the tissue architecture. The TME-related roles of fibroblast subsets addressed the potential crosstalk among diverse cells.

Objectives This study aims to assess the association between adjuvant radiotherapy and the development of second primary malignancies (SPMs) and identify its determinants in patients who have undergone surgical treatment for gastric cancer.Design Retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) database.Setting Cohorts (18 registries, 2000–2018, from SEER) were screened for any malignancy that developed after sufficient latency from diagnosis of surgically treated non-metastatic gastric cancer.Participants 24 777 surgically treated gastric cancer cases were included in the cohort. Among them, 6128 patients underwent adjuvant radiotherapy.Outcome measures The cumulative incidence of SPMs was estimated using Fine and Gray’s competing risk model and the radiotherapy-correlated risks were calculated using Poisson regression analysis.Results Among patients with sufficient latency, there was no significant association between radiotherapy and the risk of developing second primary solid malignancies (relative risk=1.05, 95% CI 0.83 to 1.33) or haematological malignancies (relative risk=1.17, 95% CI 0.62 to 2.11). Interestingly, radiotherapy was associated with a reduced cumulative incidence of second lung and bronchus cancer compared with no radiotherapy, with a 15-year incidence of 1.4%–3.17% (p

Abstract CD8+ exhausted T cells (CD8+ Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+ Tex related genes in ovarian cancer (OC). The CD8+ Tex related prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+ T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis and its related genes in OCa is unclear. Using the GSE14407 dataset, we analyzed the expression and correlation of cuproptosis-related genes (CRGs) between tumor and normal groups. From the TCGA-OV dataset, we identified 20 cuproptosis-related long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. OCa patients were divided into early-stage and late-stage groups to analyze CuLncs expression. Cluster analysis classified patients into two clusters, with Cluster1 having a poorer prognosis. Significant differences in “Lymphatic Invasion” and “Cancer status” were observed between clusters. Seven CRGs showed significant expression differences, validated using the human protein atlas (HPA) databases. Immune analysis revealed a higher ImmuneScore in Cluster1. GSEA identified associated signaling pathways. LASSO regression included 11 CuLncs to construct and validate a survival prediction model, classifying patients into high-risk and low-risk groups. Correlations between riskScore, Cluster phenotype, ImmuneScore, and immune cell infiltration were explored. Cell experiments showed that knocking down AC023644.1 decreases OCa cell viability. In conclusion, we constructed an accurate prognostic model for OCa based on 11 CuLncs, providing a basis for prognosis assessment and potential immunotherapy targets.

Summary: Lymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was related to LNM. s-MDK combined with serum-squamous cell carcinoma antigen(s-SCCA) improved the diagnostic accuracy of CSCC LNM. These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.

Over two decades from 1949 until the resumption of the diplomatic relations between these two countries in 1972, West German companies never gave up on the Chinese market despite substantial difficulties caused by Cold War frictions. This paper exams the payment transactions and terms of credits for financing industrial projects between the PRC and West German companies.

The biomedical literature is a vast and invaluable resource for biomedical research. Integrating knowledge from the literature with biomedical data can help biological studies and the clinical decision-making process. Efforts have been made to gather information from the biomedical literature and create biomedical knowledge bases, such as KEGG and Reactome. However, manual curation remains the primary method to retrieve accurate biomedical entities and relationships. Manual curation becomes increasingly challenging and costly as the volume of biomedical publications quickly grows. Fortunately, recent advancements in Artificial Intelligence (AI) technologies offer the potential to automate the process of curating, updating, and integrating knowledge from the literature. Herein, we highlight the AI capabilities to aid in mining knowledge and building the knowledge base from the biomedical literature.

Objective To understand the current status of research on lung cancer immunotherapy to provide a reference for further investigation and future topic selection in this field. Methods CiteSpace visualization analysis software was used to analyze 400 Chinese studies in CNKI and 5 001 English studies in the Web of Science database from 2005 to 2021, with "lung cancer" and "immunotherapy" as keywords. Keyword co-occurrence analysis was performed on 17 English studies of "Lung Cancer" "Immunotherapy" and "Single cell sequencing" in the Web of Science database. Results "Non-small cell lung cancer" "immunosuppressants" "PD-L1" "dendritic cells" and "cytokine-induced killer cells" are current research hotspots in lung cancer immunotherapy. Monoclonal antibody drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are hotspot drugs. Immunotherapy combined with chemotherapy as well as PD-L1 expression have become the focus of continuous research. The majority of studies on lung cancer immunotherapy are conducted in the United States, followed by China. Conclusion Lung cancer immunotherapy has gradually become a research hot spot in China. In the future, in-depth research is needed to provide cutting-edge directions for lung cancer immunotherapy.

In order to facilitate the selection of basic parameters in the initial design stage of face gear, and simplify the process of solving meshing strength of face gear pair. By referring to the existing strength calculation formula of the standard spur gear, the analytical calculation models of contact stress and bending stress of full tooth height of face gear were established. The curvature of tooth surface was solved by the basic parameters of the gear, and the contact stress of tooth surface was solved by the Hertz contact theory. The tooth thickness at the dangerous section of gear teeth was determined by the 30° tangent method, and the stress calculation coefficient table was given based on the expression of basic parameters of gear pair, finally, the analytical calculation formula of tooth root bending stress was deduced. Taking face gear pair with a certain design parameter as an example, the results obtained from the analytical calculation models were compared with those from the finite element simulation to verify the accuracy of models. On this basis, a simplified formula for calculating the strength of face gear was given which can be directly solved by the basic parameters of gear.

Abstract Tuberculosis (TB) patients who develop venous thromboembolism (VTE) have poor clinical outcomes. This study aimed to explore the risk factors and the prognosis of TB patients with VTE. A total of 11 267 with TB patients from the Zhejiang University‐affiliated Chest Hospital, China, were enrolled between January 2016 and January 2020. A total of 107 TB patients with VTE were selected as the VTE group. Patients in the control group were randomly screened in a 1:1 ratio between the VTE and control groups. Univariate and multivariate logistic regression analysis was used to evaluate the factors associated with VTE in TB patients. Of the 214 patients, 145 (60.17%) were male, 69 (32.2%) were female, with an average age of 62.21 ± 19.35. The incidence of VTE in TB patients was 0.95%. Using a univariate analysis, it was found that age, fever, dyspnea, lower limb edema, respiratory failure, malignant tumor, prothrombin time, activated partial thromboplastin time, D—dimer, and hemoglobin levels were different between the two groups (P

Background: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. Methods: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan–Meier analysis and Cox proportional hazards models. Results: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p < 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21–0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. Conclusions: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion.

Background: Many studies have confirmed that diabetes was associated with prognosis in many malignant cancer types. However, the impact of diabetes on ampullary carcinoma (AC) has not been investigated. Methods: A total of 266 AC patients in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. The postoperative complication rate, postoperative recurrence rate, and long-term survival were compared between the diabetes group and the no diabetes group. Results: A total of 32 AC patients (12.03%) were diagnosed with diabetes before surgery. In total, 111 patients (41.73%) had one or more postoperative complications, and there was no perioperative death. There was no statistically significant difference regarding postoperative complications between the diabetes group and the no diabetes group. Altogether, 120 patients (45.11%) experienced postoperative recurrence. Multivariate analysis revealed that diabetes was an independent risk factor for the recurrence (OR: 2.384, 95% CI: 1.065–5.336, p = 0.035), OS (HR: 1.597, 95% CI: 1.005–2.537, p = 0.047), and RFS (HR: 1.768, 95% CI: 1.068–2.925, p = 0.027) in AC patients after curative pancreatoduodenectomy. Conclusions: Diabetes may adversely affect the recurrence of patients with AC after curative pancreaticoduodenectomy, leading to an increased risk of poor prognosis in early-stage patients. Further studies involving a large sample size are needed to validate our results.

Abstract As the predominant stroma cells of tumor microenvironment (TME), cancer associated fibroblasts (CAFs) are robust tumor player of different malignancies. However, less is known about the regulatory mechanism of CAFs on promoting progression of ovarian cancer (OvCA). In the present study, the conditioned medium of primary CAFs (CAF-CM) from OvCA was used to culture cell lines of epithelial ovarian cancer (EOC), and showed a potent role in promoting proliferation, migration and invasion of cancer cells. Mass spectrum (MS) analysis identified that Collapsin response mediator protein-2 (CRMP2), a microtubule-associated protein involved in diverse malignancies, derived from CAFs was a key regulator responsible for mediating these cell events of OvCA. In vitro study using recombinant CRMP2 (r-CRMP2) revealed that the protein promoted proliferation, invasion, and migration of OvCA cells through activation of hypoxia-inducible factor (HIF)-1α-glycolysis signaling pathway. The CRMP2 was abundantly expressed in OvCA, with a well correlation with metastasis and poor prognosis, as analyzed from 118 patients’ samples. Inhibition of the CRMP2 derived from CAFs by neutralizing antibodies significantly attenuated the tumor size, weights, and metastatic foci numbers of mice in vivo. Our finding has provided a novel therapeutic clue for OvCA based on TME.

Abstract Aplastic anemia (AA) is a blood disorder resulted from over-activated T-cell related hematopoietic failure, with the characterization of hypocellularity and enhanced adipogenic differentiation of mesenchymal stroma cells (MSCs) in bone marrow (BM). However, little is known about the relationship between immune imbalance and polarized adipogenic abnormity of BM microenvironment in this disease entity. In the present study, we differentiated BM-MSCs into osteoblastic or adipogenic lineages to mimic the osteo-adipogenic differentiation. Activated CD8+ T cells and interferon-γ (IFN-γ) were found to stimulate adipogenesis of BM-MSCs either in vitro or in vivo of AA mouse model. Interestingly, myeloid-derived suppressive cells (MDSCs), one of the immune-regulating populations, were decreased within BM of AA mice. We found that it was not CD11b+Ly6G+Ly6C- granulocytic-MDSCs (gMDSCs) but CD11b+Ly6G-Ly6C+ monocytic-MDSCs (mMDSCs) inhibiting both T cell proliferation and IFN-γ production via inducible nitric oxide synthetase (iNOS) pathway. Single-cell RNA-sequencing (scRNA-seq) of AA- and mMDSCs-treated murine BM cells revealed that mMDSCs transfusion could reconstitute BM hematopoietic progenitors by inhibiting T cells population and signature cytokines and decreasing immature Adipo-Cxcl12-abundant reticular cells within BM. Multi-injection of mMDSCs into AA mice reduced intra-BM T cells infiltration and suppressed BM adipogenesis, which subsequently restored the intra-BM immune balance and eventually prevented pancytopenia and hypo-hematopoiesis. In conclusion, adoptive transfusion of mMDSCs might be a novel immune-regulating strategy to treat AA, accounting for not only restoring the intra-BM immune balance but also improving stroma’s multi-differentiating microenvironment.

It was generally believed that the prognosis of gastric neuroendocrine carcinoma (GNEC) was worse than gastric adenocarcinoma (GAC). However, almost all previous studies compared the prognosis of GNEC and GAC based on East Asians. In this study, we evaluated the clinicopathological features and prognosis of GNEC and GAC in Whites. Patients with GNEC and GAC were identified from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching (PSM) analysis to match the age, sex, TNM stage, and treatments received between GNEC and GAC, then compared the overall survival (OS) and cancer-specific survival (CSS) in the two types. A total of 392 cases of GNEC and 12,835 cases of GAC in Whites were recognized. After PSM, the 5-year OS rates of GNEC and GAC were 50.3% and 43.0%, respectively (p = 0.010). The 5-year CSS rates of GNEC and GAC were 57.4% and 50.1%, respectively (p = 0.012). Besides, multivariable cox regression analyses showed that GNEC was an independent predictor of improved OS (HR 0.719; 95% CI 0.607–0.853) and CSS (HR 0.691; 95% CI 0.571–0.835) in the matched data. The prognosis of GNEC was better than GAC in Whites, showing significant ethnic differences. Appropriate treatments and follow-up strategies for GNEC in Whites are probably different from East Asians. The potential genetic and molecular mechanisms need to be further explored.

In recent years, photobiomodulation (PBM) has attracted widespread attention for the treatment of various causes of pain and inflammation. Primary dysmenorrhea (PD) is a common gynecological condition characterized by severe menstrual pain, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. The present study from the perspective of light morphology aimed to bypass the heat risk limitation and evaluate the efficacy and safety of pulsed 630 nm PBM therapy for reducing pain associated with PD. The pulse light parameters were designed according to the transmittance of red light. In this randomized, cross-over design, sham-controlled study, 46 women with PD were included and randomly assigned to either pulsed 630 nm light therapy or white light sham control therapy. The intervention lasted for 20 min per day and was administered for 7 consecutive days before and during menstruation. The results showed that the pulsed 630 nm PBM treatment demonstrated a significant reduction in pain levels compared to the placebo treatment (p < 0.001), with 55.00% of active treatment participants experiencing a pain intensity differential concentration exceeding 50.00%. Moreover, participants reported an improved quality of life during the active treatment phase and generally preferred it as a more effective method for relieving PD. No adverse events or side effects were reported throughout the trial. Based on the results, pulsed 630 nm LED therapy showed significant relief of menstrual pain compared to white light placebo treatment and improved quality of life under certain circumstances. Therefore, this study proposes that pulsed red light PBM therapy may be a promising approach for future clinical treatment of PD.

Drift tube is one of the core components of proton transfer reaction mass spectrometer (PTR-MS). Technical innovation of the drift tube is one of the important ways to improve the performance of the instrument. In recent years, focusing drift tube (FDT) has been paid more and more attention because of its high ion utilization ratio. In this work, the design and simulation of a FDT combined with a radio frequency quadrupole and a resistor glass tube was reported. The quadrupole was used to provide an RF focusing field, and the resistor glass tube was used to generate a uniformly distributed DC gradient electric field. Based on the designed 3D structure, the simulation model was built in SIMION 8.1 and the parameters such as the diameter of the quadrupole, the frequency and the voltage amplitude of the RF field were simulated systematically with three kinds of ions (m/z 19, 55 and 100). The results showed that the introduction of the RF field was very effective in reducing the radius of the ion beam, and the rod with larger diameter was beneficial to improve the ion focusing efficiency, especially for the ions with low mass-charge ratio. When the frequency was about 2 MHz, the focusing efficiency was the highest. With the increase of the voltage amplitude, the radius of ion beam decreased rapidly and finally tended to smooth. In addition, more than 85% of the ions could successfully pass through the sampling orifice with a diameter of 1.0 mm, and the transport efficiency was about 28 times higher than that of the traditional drift tube. In this study, structural design, SIMION modeling and ion transmittance of RF quadrupole focusing drift tube (RFQ-FDT) were described in detail, hoping to provide some technical support for follow-up research.

Aiming at the problem that the surrounding rock of the advancing roadway at the east wing of -550 m level is not easy to be stable when the tunnel is advanced in a short distance under goaf in Liangbei Mine, the stress distribution law and deformation characteristics of the goaf and coal pillar formed by two adjacent working faces at different times on the surrounding rock near the advancing roadway were analyzed by numerical simulation. Based on the support principle of multi-level coupling bearing structure, the corresponding deformation control countermeasures and support schemes were proposed and applied in the field. The results show that with the advance of the working face, the stress recovery zone of the raw rock of the floor strata in the goaf diffuses from the middle of the goaf to the surrounding areas, and the plastic failure zone is distributed in an “inverted saddle” shape; under the influence of the stress produced by the disturbance process of progressive compaction of the adjacent unstable goaf and the stress concentration of the coal pillar, the plastic failure zone of the tunnel is asymmetrically distributed; based on the zoning characteristics of broken zone, plastic zone and elastic zone formed by the failure of roadway surrounding rock, the supporting strategy of making full use of internal and external support to form multi-level coupled bearing structure is put forward. The multi-level coupling control technology of “high strength anchor-mesh-cable + reinforcement of shallow and deep surrounding rock by staged grouting + shotcreting” in shallow and deep surrounding rocks has achieved good application results in the field.

The quality problem of head width narrow appears on one hot rolled strip line sometime. In order to using the real data,in this paper the dynamic time warping was firstly utilized to transfer the different length data to the same length,and then the feature selection method based on information entropy was applied to analyze the order of important about process parameters that effect on the quality. The first several process parameters were selected as the causes of head width narrow of hot rolled strip. The results show that the feature selection method based on information entropy can track the causes of the head width narrow of hot rolled strip effectively to adjust the process. In the future,the methods can be applied in other quality diagnosis,other processes or other application fields.

Abstract Argonaute proteins (Agos) from thermophiles function as endonucleases via guide-target base-pairing cleavage for host defense. Since guides play a key role in regulating the catalytic specificity of Agos, elucidating its underlying molecular mechanisms would promote the application of Agos in the medical sciences. Here, we reveal that an Ago from Pyrococcus furiosus (PfAgo) showed a stepwise endonuclease activity, which was demonstrated through a double-stranded DNA cleavage directed by a single guide DNA (gDNA) rather than a canonical pair of gDNAs. We validated that the cleavage products with 5'-phosphorylated ends can be used as a new guide to induce a new round of cleavage. Based on the reprogrammable capacity of Ago’s stepwise activity, we established a rapid and specific platform for unambiguous multiplex gene detection, termed Renewed-gDNA Assisted DNA cleavage by Argonaute (RADAR). Combined with a pre-amplification step, RADAR achieved sensitivity at the femtomolar level and specificity with at least a di-nucleotide resolution. Furthermore, RADAR simultaneously discriminated among multiple target sequences simply by corresponding multiple guides. We successfully distinguished four human papillomavirus serotypes from patient samples in a single reaction. Our technique, based on the unique properties of Ago, provides a versatile and sensitive method for molecular diagnosis.

With the rapid development of high-throughput sequencing technology represented by the second generation sequencing technology, whole-genome detection technology has been able to detect data from multiple levels, such as genome, transcriptome and epigenome. Biomass is a complicated regulatory system, involving many levels of complicated regulatory mechanism. Considering the limitation of single omics data analysis in exploring pathogenic factors, integrative multi-omics analysis with linear or nonlinear relationship can provide a new method for the study of the disease. Integrative analysis of multiple omics has widely used in various diseases, including lung cancer, and DNA or gene molecular level is particularly important as a basis for intermolecular correlations and complex networks. Hence, this paper briefly describes integrative analysis of genome, transcriptome and epigenome in lung cancer.

Solving the switching angles in real time is the key point to apply selective harmonic elimination (SHE) to engineering project. In this paper, a real time algorithm is presented to solve the SHE equations for two level inverters, which can be easily implemented on the micro-controllers and includes two computing stages, the offline computing stage and the online computing stage. In the offline stage, the SHE equations are transformed into an equivalent polynomial system which includes a set of univariate linear equations and a univariate high order equation by using symmetric polynomials and Groebner bases theory. Then, the univariate linear equations are stored into the micro-controllers and solved online according to the input modulation indices, and their solutions are used to construct a univariate high order polynomial equation whose real roots are actually the solutions for the original SHE equations. In order to find all the real roots of this constructed high order polynomial equation, the Sturm theorem is used to isolate every real root into non overlapping intervals and then the secant method is applied to every interval to find the exact real root, i.e., the final solutions for the SHE equations. Compared to the traditional numerical method, the executing efficiency is increased 20 times on STM32F407. Finally, a two-level inverter test platform is built based on the proposed algorithm, and the experimental results show that the algorithm is effective.

Abstract Purpose The purpose of this study is to come up with new methods to quantitate the blood loss under endoscope and explore the influence of blood loss on percutaneous endoscopic lumbar discectomy (PELD). Methods Clinical research and in vitro experiment are combined. In the in vitro experiment, 2.0-ml blood was diluted in different ratio to simulate the rinse solution of PELD, the hematocrit method (HCT-M) and red blood cell count method (RBC-M) were came up to estimate blood loss and the new methods were calibrated with the direct measurement method (Direct-M). In clinical research, 74 patients with L5/S1 disk herniation were treated with PELD, and HCT-M and the empirical method (EMP-M) were used to estimate the blood loss under endoscope. According to blood loss, all patients were divided into group A (≤ 10 ml) and group B (> 10 ml). The blood loss, operation time, fluoroscopy frequency, visual analog scale (VAS), and Oswestry Disability Index (ODI) scores were compared between the two groups. Results In the in vitro experiment, the hematocrit of the rinse solution was always stable over time. The estimated blood loss by HCT-M was stable and quite approximate to actual blood volume (2.0 ml) whatever the blood dilution ratio, while according to RBC-M, the estimated blood loss was close to the actual blood volume only when the dilution ratio was greater than 300 times. In clinical research, the blood loss estimated by HCT-M was higher than that by EMP-M in both groups (P < 0.05). There was a significant difference between group A and group B in blood loss (7.40 ± 1.61 vs 19.91 ± 10.94 ml), operation time (80.51 ± 34.70 vs 136.51 ± 41.88 min), and fluoroscopy frequency (6.92 ± 1.52 vs 11.11 ± 2.32 times) (P < 0.05). The VAS and ODI scores in group B were higher than that in group A 1 week after operation (P < 0.05); however, the scores were not different between the two groups at pre-operation (P > 0.05). Conclusion HCT-M is a reliable method to estimate endoscopic blood loss in PELD. The amount of endoscopic blood loss affects the operative procedure in operation time and fluoroscopy frequency, as well as clinical effects in VAS and ODI scores after operation in short term.

Objective: Cyclophosphamide (CTX), which is commonly used in clinical chemotherapy, has a damaging effect on ovarian follicles. This study aimed to establish a new method to count the number of follicles in mouse ovaries using benzyl alcohol–benzyl benzoate (BABB)-based tissue-clearing technology and evaluate the follicle-damaging effects of different doses of CTX. Methods: C57BL/6 mice were divided into four groups and administered intraperitoneal injections of 0, 40, 80, or 120 mg/kg CTX. The serum levels of estradiol (E2) and follicle-stimulating hormone (FSH) were detected using an ELISA kit. Mouse ovaries were subjected to BABB clearing and labeled with DAPI, β-actin, and DDX4 to observe the ovarian structure and follicles. A three-dimensional software, Imaris, was used to reconstruct the ovarian structure and automatically count the number of follicles. The effects of different CTX doses on the total follicle number and estrous cycle were determined. Results: As the CTX dose increased, E2 levels in CTX mice declined from 212.3 to 57.7 pg/mL; the FSH levels increased from 3.2 to 29 ng/mL. Mouse ovaries became transparent after BABB treatment. After fixation, microscopy, and Imaris processing, immunofluorescence signals of β-actin and DAPI from all levels in intact ovaries could be obtained and follicle number in half ovaries could be automatically counted using anti-DDX4 antibody labeling. In the NC, CTX40, CTX80, and CTX120 groups, the proportion of mice in the diestrus phase was 26.67%, 51.67%, 73.33%, and 95.00%, respectively, and the total follicle number was 2,603, 1,761, 1,043, and 262, respectively. E2 levels were positively correlated with follicle number and FSH levels were negatively correlated with follicle number, indicating that the damaging effect of CTX on follicle number may be dose dependent. Conclusion: BABB can be used to clear intact ovaries from adult mice, and follicle number in half ovaries can be automatically counted. The damaging effect of CTX on follicles and the endocrine system is dose dependent.

Intrauterine adhesion is a severe complication after intrauterine operation, Various adjuvant therapies failed to improve clinical symptoms and pregnancy rates among patients with moderate-to-severe intrauterine adhesion. At present, hyaluronic acid gel is widely used in the primary prevention of adhesion after hysteroscopic adhesiolysis. However, its efficacy is still under debate. Therefore, the aim of this study was to systematically evaluate the efficacy of hyaluronic acid gel in preventing the recurrence of intrauterine adhesion after hysteroscopic adhesiolysis. The Cochrane Library, Embase, and PubMed databases were used to search for articles published before July 31, 2018, using the following terms: hyaluronic acid, intrauterine adhesions, Asherman's syndrome, IUA, hysteroscopy, and hysteroscopic adhesiolysis. Studies on therapies after hysteroscopic adhesiolysis were collected. The recurrence rate of and pregnancy rate in the presence of intrauterine adhesion after hysteroscopic adhesiolysis were analyzed by RevMan 5.3 software. A total of 6 articles were selected, which included 394 patients who were subjected to hysteroscopic adhesiolysis. The meta-analysis results showed that (1) no statistically significant difference was found between hyaluronic acid gel use and without its use on the score of intrauterine adhesion after hysteroscopic adhesiolysis [the mean difference (MD) = −0.89, 95% confidence interval (CI) (−2.53–0.76), P = 0.29], neither a statistically significant difference was observed between the same groups on the recurrence rate of intrauterine adhesion [odds ratio (OR) = 0.75, 95% CI (0.31–1.81), P = 0.53]; (2) subgroup analysis showed that hyaluronic acid gel could reduce the rate of intrauterine adhesion recurrence in randomized controlled trials [OR = −0.28, 95% CI (0.14–0.56), P = 0.0006]. However, the recurrence rate of intrauterine adhesion after the use of hyaluronic acid gel was not statistically significant in non-randomized controlled experiments [OR = 1.53, 95% CI (0.79–2.95), P = 0.21]; (3) hyaluronic acid gel did not result in a significant effect on pregnancy rate after intrauterine adhesion separation [OR = 2.02, 95% CI (0.53–7.66), P = 0.3]. In conclusion, hyaluronic acid gel could reduce the recurrence rate of intrauterine adhesion, but had no significant effect on the postoperative pregnancy rate. Keywords: Hyaluronic acid gel, Hysteroscopic adhesiolysis, Intrauterine adhesion, Recurrence, Pregnancy

Based on the stress characteristics of primary solidified shell in the mold, formation model of the shell’s sticker is established according to the theory of mechanical strength, and the mechanism and internal factors of the shell tearing are analyzed by the model. Furthermore, based on the measured data of many stickers in a slab-continuous caster, the influence of casting process factors on the sticker is analyzed statistically. The possible causes for the stickers in the studied caster are discussed. The results provide a reference for optimizing the continuous casting production process and effectively preventing the occurrence of the sticker from the source.

Objective To explore the relationship between clinicopathological characteristics and lymph node metastasis in early-stage cervical cancer patients, and to establish a nomogram model to predict lymph node metastasis in early-stage cervical cancer patients undergoing radical hysterectomy without lymphadenectomy. Methods We retrospectively analyzed clinical pathological data of 432 patients with early-stage cervical cancer undergoing hysterectomy and lymphadenectomy in the First Affiliated Hospital of Fujian Medical University. Logistic regression analysis was used to determine the risk factors for lymph node metastasis of early-stage cervical cancer. A nomogram model for predicting the risk of lymph node metastasis was established, and the predictive performance and compliance of the model were evaluated using the consistency index (C-index) and the calibration curve. Results Among 432 patients with early-stage cervical cancer, 84 patients had lymph node metastasis, with a positive rate of 19.4%. Multivariate analysis showed tumor diameter>3cm, parametrial spread and lymphovascular space invasion were high risk factors for lymph node metastasis of early-stage cervical cancer; OR values were 1.98(95%CI: 1.17-3.34), 2.64(95%CI: 1.28-5.44) and 4.77(95%CI: 2.60-8.75). The accuracy of nomogram used to predict the risk of lymph node metastasis was 0.687. Conclusion A nomogram, constructed based on tumor diameter>3cm, parametrial spread and lymphovascular space invasion, could be used to guide if further treatment is required for early-stage cervical cancer patients who have undergone radical hysterectomy without lymphadenectomy.

The paper presents the domestic and overseas current status of the steel applied to aircraft landing gear in combination of the design concept and requirements for aircraft landing gear. The application features and concept of the steel used for landing gear are summarized and the domestic and overseas status are compared. For the moment, the low-alloy ultra-high strength steel and high-alloy ultra-high strength steel are all being used in the material system for aircraft landing gear steel, and the complete technical system for its anti-fatigue manufacturing is built. At present, China's development and application of high strength steel applied to aircraft landing gear is at the world advanced level. At last, the prospect for future development is analyzed.

Objective The aim of this study is to investigate the roles of Notch signaling and autophagy on mineral trioxide aggregate (MTA) induced differentiation of human dental pulp cells (hDPCs). Methods Third molars from healthy human were collected and hDPCs were isolated by a combined digestion of collagenase Ⅰ and dispaseⅡ. Real time PCR were used to test the mRNA expression levels of alkaline phosphatase (ALP), runt⁃related transcription factor 2 (Runx2) and dentin sialophoprotein (DSPP) in MTA treated hDPCs in different time (24 h, 3 d and 7 d). The mineral⁃ ization nodules formed by hDPCs with or without MTA treatment were detected by Von Kossa staining. Expressions of Notch1, Jagged1, Hes1, LC3Ⅱ/LC3 Ⅰand p62 in wild type and MTA treated hDPCs were detected by western blotting. Results MTA extracted in a concentration of 0.1 mg/mL could promote the differentiation of hDPCs. Compared with that of wild type hDPCs, the expressions of Notch1, Hes1, or Jagged1 and p62 (P＜0.01) in MTA treated hDPCs were significantly increased. MTA treatment showed inhibition effects on autophagy flux similar to Bafilomycin A1, a specific inhibitor of fusion between autophagosomes and lysosomes. Conclusion MTA could promote hDPCs differentiation with highly relevant in stimulating Notch1⁃Jagged1⁃Hes1 signaling and inhibition of autophagy flux.