Search

The goal of this study was to identify genes that were differentially methylated and differentially expressed and their related signaling pathways in ovarian endometriosis tissue. First, the DNA methylation and gene expression profiles in the endometrial tissue of patients with ovarian endometriosis were studied using Illumina 450K methylation microarray analysis and the GSE141549 gene expression dataset. Second, differentially methylated and differentially expressed genes, herein referred to as differentially methylated/expressed genes, were identified and protein-protein interaction networks and functional analysis of these genes were determined. Third, qPCR and immunohistochemistry of patient samples was used to confirm the differential expression of a subset of differentially methylated/expressed genes. Finally, the GSE7305 dataset was used confirm the expression profile of differentially methylated/expressed genes and to determine the potential usefulness of these genes for diagnosis of endometriosis. A total of 37 hypermethylated low-expression genes and 66 hypomethylated high-expression genes were identified in ovarian endometriosis patients. Protein-protein interaction and functional analysis highlighted 8 hypermethylated low-expression genes (KRT19, KRT8, ESR1, PRL, SFN, IL20RA, IL2RB, and PAX8) and 4 hypomethylated high-expression genes (CYP11A1, NR5A1, ME1, and GSTM1). Significantly, both of these gene sets had a diagnostic value for patients with ovarian endometriosis. Signaling pathways that were identified included JAK-STAT (involving IL20RA and IL2RB), prolactin (involving PRL and ESR1), Staphylococcus aureus infection (involving KRT19), viral protein interaction with cytokine and cytokine receptor (involving IL20RA and IL2RB), cytokine-cytokine receptor interaction (involving IL20RA and IL2RB), and drug metabolism-cytochrome P450 (involving GSTM1). The differentially methylated/expressed genes and enriched signaling pathways identified in this study are likely to be associated with the process of ovarian endometriosis.

This paper studies a wireless power communication network(WPCN) based on orthogonal frequency division multiplexing (OFDM) with time reversal(TR). In this paper, the " Harvest Then Transmit " protocol is adopted, and the transmission time block is divided into three stages, the first stage is for power transmission, the second stage is for TR detection, and the third stage is for information transmission. The energy limited access point (AP) and the terminal node obtain energy from the radiofrequency signal sent by the power beacon (PB) to assist the terminal data transmission. The energy limited AP and the terminal node obtain energy from the radio frequency signal sent by the PB to assist the terminal data transmission. In the TR phase and the wireless information transmission (WIT) phase, the terminal transmits the TR detection signal to the AP using the collected energy, and the AP uses the collected energy to transmit independent signals to a plurality of terminals through OFDM. In order to maximize the sum rate of WPCN, the energy collection time and AP power allocation are jointly optimized. Under the energy causal constraint, the subcarrier allocation, power allocation and time allocation of the whole process are studied, and because of the binary variables involved in the subcarrier allocation, the problem belongs to the mixed integer non-convex programming problem. the problem is transformed into a quasiconvex problem, and then binary search is used to obtain the optimal solution. The simulation results verify the effectiveness of this scheme. The results show that the proposed scheme significantly improves the sum rate of the terminal compared to the reference scheme.

To observe the efficacy of acupuncture on symptom burden in patients with gastric cancer during adjuvant chemotherapy after gastrectomy.A total of 58 patients were randomized into a high-dose acupuncture group (19 cases, 5 cases dropped off), a low-dose acupuncture group (20 cases, 6 cases dropped off) and a control group (19 cases, 2 cases dropped off). Conventional chemotherapy and antiemetic treatment were adopted in the control group. On the basis of the treatment in the control group, acupuncture was applied 7 times each chemotherapy cycle for totally 21 times in the high-dose acupuncture group, and 3 times each chemotherapy cycle for totally 9 times in the low-dose acupuncture group. Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc. were selected in the two acupuncture groups, as well as back-The symptom burden was worst within 7 days of each cycle of chemotherapy in the 3 groups. After the 3rd chemotherapy cycle, the total score of ESAS in the low-dose acupuncture group was lower than the control group (Acupuncture shows promising effect in controlling symptom burden during adjuvant chemotherapy in gastric cancer patients after gastrectomy.

High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 (The mRNA and protein expression ofThis study showed that

China has 287 million migrant workers and identifying and preventing their unemployment risk holds theoretical and practical significance. This study collected data in 2019 to explore the structure of migrant workers’ perception of unemployment risk. In the first stage of this study, in-depth interviews and grounded theory analysis were conducted and an interpretation framework for migrant workers’ unemployment risk perception (URP) was developed. In the second stage, a URP scale for migrant workers was developed and then tested and verified using a questionnaire survey and factor analysis. The results showed that the URP of migrant workers is composed of many dimensions: mental, financial, relationship, citizenization and re-migration.

Epidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.In this cross-sectional study, adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (80 beats/min).Among 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08-1.13), 1.36 (1.33-1.39), 1.68 (1.64-1.72), 2.01 (1.96-2.07) and 2.58 (2.50-2.67), respectively (There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Background: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. Methods: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). Results: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. Conclusion: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

MBLS10A-200 magnesium-lithium (Mg-Li) alloy is a novel ultralight material, with the density, tensile strength and elongation rate of 1.5 g/cm3, 160 MPa and 60%, respectively. At present, the material is increasingly widely applied in structures with complex shapes of various fields such as aeronautics, astronautics and electronic engineering. At present, the industrial circle has put forward increasingly urgent demand for the welding technique of MBLS10A-200 alloy and the protection technology for corrosion resistance of the welded joints of the alloy. However, related research is rarely reported. Laser welding of MBLS10A-200 Mg-Li alloy with 5 mm in thickness was studied to further obtain the butt joint, with the elongation rate of about 54% and the same strength as base metal (BM). Moreover, the corrosion resistance of laser welded joint was detected by using electrochemistry method. During the experiment, it can be found that the corrosion resistance of metals in the welded seam zone (WSZ) was far higher than that of the BM. The corrosion current density of metals in WSZ was about 10-5 A/cm2, which declined by two orders of magnitude compared with BMs which were about 10-7 A/cm2 and the charge transfer resistance of welded seam zone increased by 4.8 times compared with BMs.

In Part Ⅰ of this series, it can be found that the corrosion resistance of metals in the welded seam zone (WSZ) was far higher than that of the base metal (BM) of MBLS10A-200 Mg-Li alloy. Therefore, the feasibility of improving the corrosion resistance of MBLS10A-200 Mg-Li alloy through laser surface melting (LSM) was further explored. Meanwhile, laser shock peening (LSP) treatment was also used for contrast. The results showed that the surface melted zone with the corrosion resistance through LSM superior to that of metals in WSZ of MBLS10A-200 alloy through laser welding can be prepared by controlling heat input through increasing the scanning speed of laser beam, while LSP has limited impact on the electrochemical corrosion resistance of MBLS10A-200 alloy. The corrosion current density (Jcorr) of the samples subjected LSM declined by two orders of magnitude compared with the base metal (BM) while the charge transfer resistance increased by 17 times compared with BM. An analysis indicated that owing to the fast cooling rate during laser processing, the multi-phase microstructures (i.e. α phase, β phase and Li2MgAl) of BM were transformed into β single-phase microstructure in WSZ and surface melted zone. In this way, not only solid solution strengthening of the metals in WSZ was realized but also the micro-galvanic coupling generated due to the difference of electric potentials of multi-phase microstructures were reduced, thus improving the corrosion resistance of surface melted zone.

Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3–10 μM) dose- dependently inhibited the expression levels of IL-6, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-β-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.

Along with increasing research on acupuncture for chronic pain, the validity of sham acupuncture (SA) has also been argued.Nine databases were searched for randomized controlled trials (RCTs) from the inception date to July 5, 2022. Using Markov Chain Monte Carlo methods, a Bayesian multiple treatment network meta-analysis (NMA) with random-effects model was conducted.A total of 62 RCTs with 6806 patients and four kinds of treatments (real acupuncture (RA), non-acupuncture (NA), penetrative SA (PSA) and non-penetrative SA (NPSA)) were included. The results indicated that both NPSA and PSA were not superior to NA in improving chronic pain (NPSA: MD -4.77 [95% CI, -11.09 to 1.52]; PSA: MD, -4.96 [95% CI, -10.38 to 0.48]). After combining NPSA and PSA into the SA group, the weak trend of pain relief from SA was still not statistically significant (MD, -4.91 [95% CI, -9.93 to 0.05]). NPSA and PSA had similar effects (MD, 0.18 [95% CI, -5.45 to 5.81]). RA was significantly associated with pain relief, compared with NPSA and PSA (NPSA: MD, -12.03 [95% CI, -16.62 to -7.41]; PSA: MD, -11.85 [95% CI, -15.48 to -8.23]). The results were generally consistent regardless of pain phenotype, frequency, duration, acupuncture methods, analgesic intake, or detection bias.These results suggested that acupuncture was significantly associated with reduced chronic pain. The two kinds of placebo acupuncture, NPSA and PSA, have similar effects. Both NPSA and PSA, with a weak but not significant effect, are appropriate to be inert placebo controls in RCTs for chronic pain.

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of采用文献调研和德尔菲专家共识，总结针刺治疗癌痛的重要穴位，为制订《针刺治疗癌痛临床实践指南》提供证据基础。通过系统检索中、英文数据库，纳入针刺治疗癌痛的临床研究28项，归纳分析选穴方法和高频使用的穴位，据此设计德尔菲调查问卷，对30名国内外针灸、肿瘤相关领域专家进行两轮问卷调查。认为针刺治疗癌痛应采用个性化取穴方案，取穴以足三里、合谷、太冲、三阴交、阳陵泉和阿是穴为主。结合临床研究证据与专家调研结果得出针刺治疗癌痛的重要穴位，然而临证选穴仍有待进一步研究和细化。.

To explore the relationship between effect of induction chemotherapy and prognosis in acute myeloid leukemia (AML) patients.The clinical data of 146 adult AML patients treated in Affiliated Hospital of Chifeng University from March 2015 to March 2018 were enrolled and retrospectively analyzed. Day 14 bone marrow biopsy (D14BM) cellularity and blast proportion, daily peripheral blood blast (PBB) clearance rate, time to PBB clearance and etc. were primarily observed after induction chemotherapy. All the patients were divided into Non-relapse survival group, Relapse survival group, Non-relapse death group and Relapse death group according to survival and recurrence situation during 2-year follow-up. The survival of the patients was analyzed by Kaplan-Meier. Univariate analysis of prognostic factors were performed by ordinal Logistic regression, and ROC curve was used to assess the prediction efficiency of those factors for the 2-year overall survival (OS) and relapse of the patients.A total of 138 patients were included since 8 cases failed to be assessed clinically. Their 2-year OS rate was 65.94%. Age of the patients in Non-relapse survival group was lower than that in Relapse death group. The D14BM cellularities in Non-relapse survival group and Relapse survival group were lower than those in Relapse death group (P0.05). Daily PBB clearance rates in Non-relapse survival group and Relapse survival group were higher than those in Non-relapse death group and Relapse death group (P0.05). There was a statistical difference among the four groups in the number of cycles of induction chemotherapy (P0.05). The survival rate within 2 years in the patients with D14BM cellularity≤10% was higher than that in patients with cellularity10%, while it was higher in patients with daily PBB clearance rate20% than those with clearance rate≤20% (P0.05). Age (HR=1.102, P=0.000), D14BM cellularity (HR=1.252, P=0.000) and the cycles of induction chemotherapy≥3 (HR=1.703, P=0.000) were the risk factors affecting the prognosis of AML patients, while daily PBB clearance rate was a protective factor (HR=0.799, P=0.000). The AUC of age, daily PBB clearance rate and D14BM cellularity in predicting 2-year OS of AML patients was 0.738, 0.817 and 0.807, respectively, whereas in predicting relapse within 2 years it was 0.691, 0.647 and 0.711, respectively. There was no statistical difference among the three factors in the sensitivity of 2-year OS (68.11%, 85.12%, 74.49%) and 2-year relapse (50.00%, 64.13%, 61.60%) (P0.05).Bone marrow biopsy results and PBB clearance rate are related to prognosis in AML patients, which can offer certain predictive value in assessing 2-year OS of patients.AML患者诱导化疗疗效与预后关系分析.探讨急性髓系白血病（AML）患者诱导化疗的治疗效果与预后的关系。.收集并回顾性分析2015年3月至2018年3月本院收治的146例AML成年患者的临床资料，主要观察指标为诱导治疗d 14骨髓（D14BM）增生程度及原始细胞的比例，外周血白血病细胞（PBB）清除时间及日减少率等。根据随访2年患者的存活和复发情况分为无复发存活组、复发存活组、无复发死亡组、复发死亡组。采用Kaplan-Meier法行生存分析，有序Logistic回归分析对预后相关因素行单因素分析，绘制ROC曲线并评估上述指标对患者2年总生存期（OS）和复发的预测效能。.共纳入138例患者，2年OS率65.94%；无复发存活组年龄低于复发死亡组，无复发存活组和复发存活组D14BM增生度低于复发死亡组（均P0.05）；无复发存活组和复发存活组PBB日减少率均高于无复发死亡组和复发死亡组（均P0.05）；4组化疗次数比较差异有统计学意义（P0.05）；D14BM增生≤10%的患者2年内存活率高于增生10%的患者，PBB日减少率20%的患者存活率高于≤20%者（均P0.05）；年龄（HR=1.102，P=0.000）、D14BM增生度（HR= 1.252，P=0.000）、化疗次数≥3次（HR=1.703，P=0.000）为影响AML患者预后的危险因素，而PBB日减少率（HR= 0.799，P=0.000）为保护因素；年龄、PBB日减少率、D14BM增生度预测患者2年OS的AUC分别为0.738、0.817、 0.807，预测患者2年内复发的AUC分别为0.691、0.647、0.711，三者预测患者2年OS（68.11%、85.12%、74.49%）和2年内复发（50.00%、64.13%、61.60%）的敏感性均无明显差异（P0.05）。.骨髓活检结果、PBB清除率与AML患者预后相关，可为患者2年OS提供一定预测价值。.

Background: Computerized clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs testing in pragmatic trials. Methods: The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care practices in China. For each city-based stage, practices are randomly assigned to either implementation of the CDSS for hypertension management (which guides physicians treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided. In a separate sub-study conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual- antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the change in blood pressure from the first visit after site randomization to 9 months.Discussion: The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The sub-study, LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.Trial registration: ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.

Owing to the high morbidity and mortality, novel biomarkers in the occurrence and development of colorectal cancer (CRC) are needed nowadays. In this study, the CRC-related datasets were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. After screening the differentially expressed genes (DEGs) in R software, a total of 238 upregulated and 199 downregulated DEGs were revealed simultaneously. Then the Kaplan-Meier survival analysis and Cox regression analysis were used to reveal the prognostic function of these DEGs. Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) were two outstanding independent overall survival (OS) and relapse-free survival (RFS) prognostic genes of CRC in TCGA database. We next verified the expression of NXPE4 and PARM1 messenger RNA (mRNA) levels were significantly lower in CRC tumor tissue than in the adjacent noncancerous tissue in our clinical samples, and NXPE4 mRNA expression level was related to the tumor location and tumor size, while PARM1 was related to tumor location, lymph nodes metastasis, and tumor size. This study demonstrated that NXPE4 and PARM1 might be two potential novel prognostic biomarkers for CRC.

Context Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. Objectives This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. Methods In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. Results Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). Conclusion EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

An n-GaO x thin film is deposited on a single-crystal boron-doped diamond by RF magnetron sputtering to form the pn heterojunction. The n-GaO x thin film presents a small surface roughness and a large optical band gap of 4.85 eV. In addition, the band alignment is measured using x-ray photoelectron spectroscopy to evaluate the heterojunction properties. The GaO x /diamond heterojunction shows a type-II staggered band configuration, where the valence and conduction band offsets are 1.28 eV and 1.93 eV, respectively. These results confirm the feasibility of the use of n-GaO x as a termination structure for diamond power devices.

More than 20 types of ALK fusion variant subtypes have been identified, including different fusion partner genes or EML4-ALK fusions with different breakpoints. However, different ALK fusions show different sensitivities to ALK-tyrosine kinase inhibitors (ALK-TKIs) and the emergence of rare fusions brings great challenges to the target therapy in clinic. We report a rare EML4-ALK (E6;A18) fusion in a patient with lung adenocarcinoma that responded well to alectinib. This is the second case of this rare variant reported but the first report of response to an ALK-TKI. This evidence is the first to show that alectinib may be effective for this rare fusion type of non–small cell lung cancer, and these findings have important implications for drug selection in patients with this subtype. Further studies are needed to understand the function of this variant.

Two novel acylated steroidal sapogenins, 3

The efficient and rational development of tight gas reservoirs, most of which are deposit of multiple layers, is becoming a new global focus. The major tight gas reservoirs in China have multiple production layers. Gas wells are completed with multiple fracture treatments, and are commingled production. It is very difficult to effectively evaluate the single-layer production contribution and the use of each layer’s reserves. This paper presents an approach to solve the problem, which is basically based on the application of Pearson correlation analysis, catastrophe theory, and linear interpolation to calculate the single-layer production allocation rates. The method can quickly evaluate the stratified production of a large number of gas wells at different times through a computer program. The error of method validation, comparing the method prediction value with the production test data, is less than 10%. In field application, after the gas flows the discharge boundary, the production of the main layer will decrease due to the decrease in gas production of the multi-layer gas well, and other non-main layers may rise or have little change. In another case, the non-main layer can produce more natural gas for the gas well increases production. The method will also provide guidance for optimizing the perforation section of a gas well. Additionally, based on the production of a single gas well, the cumulative gas production of each layer can be calculated to evaluate the dynamic reserves of each layer and analyze the reserves utilization of each single layer. This work will finally provide guidance for gas well encryption to improve the multi-layer tight gas reservoir recovery.

Shenmu Gas Field is a multilayer tight sandstone gas reservoir with low vertical well production. The task of gas field productivity construction is heavy. It is an effective way to increase the production of a single well by excavating local superior areas and implementing horizontal well development. Therefore, it is necessary to evaluate the adaptability and establish the reservoir limits of horizontal well in Shenmu Gas Field. Systematically study the superposition mode and development scale of reservoir sand bodies, and use the reserve concentration to divide the multi-layer gas reservoirs into three types, and they are single-layer, double-layer and multi-layer, respectively. The numerical simulation method is used to compare the development effects of horizontal wells and vertical wells, to determine the reserves concentration limits and reserves physical property limits of horizontal well development. The selection criteria for geological targets suitable for horizontal well is established. The research shows that ① A large-scale composite effective reservoir is formed in the local area of the Taiyuan Formation and Shan2 Formation in Shenmu Gas Field, with a length of 1600–3200 m and a width of 800–2000 m, and it has the geological conditions for horizontal well development; ② the reserve concentration in the main development zone of the horizontal well should be over 75%, and it should have a continuous effective thickness of 5.0 m, The permeability ratio between the primary and the secondary layer should be between 0.8 and 3.9; ③ the Shenmu Gas Field is generally not suitable for large-scale horizontal well overall development, but is suitable for centralized development in local single-layer advantageous areas. The research result can provide technical support for the horizontal wells of similar gas reservoirs at home and abroad, and are of great significance for the efficient development of gas fields.

To analyze vascular damage-related risk factors for ED in patients with type 2 diabetes mellitus (DM) and develop a nomogram for the prediction of the factors.A total of 181 patients with type 2 DM were included for sexual function assessment, and the clinical data on vascular damage were retrieved from the patients system. After preprocessing, the data were described by the number and percentage of different types of cases and subjected to statistical analysis with the R software. The Lasso regression model was used to optimize feature selection. On the premise of the sample size required for logistic regression analysis according to the number of events per variable, multivariable logistic regression analysis was performed on the selected variables and a nomogram was developed for diabetes-induced erectile dysfunction (DIED). Then, the performance of the nomogram was evaluated with respect to its calibration, discrimination and clinical utility using Harrell's concordance index (C-index), the calibration plot and decision curve analysis, as well as bootstrapping for internal validation.ED was diagnosed in 90 (49.7%) of the 181 patients. The risk factors subjected to logistic regression analysis included the duration of DM (OR = 4.440, 95% CI: 1.594－13.105; OR = 7.667, 95% CI: 1.444－48.733), status of carotid intima-media thickness (c-IMT) (OR = 3.767, 95% CI: 1.194－12.691), diabetic retinopathy (DR) (OR = 5.382, 95% CI: 1.373－28.301), diabetic kidney disease (DKD) (OR = 4.959, 95% CI: 1.156－27.728), low-density lipoprotein cholesterol (LDL-C) (OR = 8.210, 95% CI: 2.027－43.507), red blood cell distribution width (RDW) (OR = 2.418, 95% CI: 1.021－5.826), and plasma fibrinogen (Fbg) (OR = 4.649, 95% CI: 2.001－11.339). The C-index of the DIED model was 0.911 (95% CI: 0.869－0.954). The curve representing the performance of the nomogram fit in well with that representing a perfect prediction by the calibration plot. Decision curve analysis indicated that the nomogram was clinically useful for predicting DIED in the type 2 DM patients at the possibility threshold of 6% to 93%.A nomogram was preliminarily developed for predicting the risk of DIED in type 2 DM patients with respect to the seven independent influencing factors, including the duration of DM, status of c-IMT, DR, DKD, LDL-C, RDW, and Fbg.

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs.

Background Alzheimer’s disease (AD) is characterized by progressive memory loss and cognitive impairment. The aggregation of amyloid β (Aβ) and hyperphosphorylated tau protein are two major pathological features of AD. Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) has been indicated in Aβ pathology; however, whether and how it affects tau pathology are not yet clear. Methods The role of NOX2 in cognitive function, amyloid plaque formation, and tau hyperphosphorylation were examined in APP/PS1 transgenic mice mated with p47phox-deficient mice (with deletion of the gene of neutrophil cytosolic factor 1, Ncf1) and/or in p47phox-deficient mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ). The cognitive and non-cognitive functions in these mice were assessed by Morris water maze, Rotarod test, open field, and elevated plus maze. Aβ levels, amyloid plaques, p47phox expression, and astrocyte activation were evaluated using immunofluorescence staining, ELISA, and/or Western blotting. Cultured primary neuronal cells were treated with okadaic acid or conditioned media (CM) from high glucose-stimulated primary astrocytes. The alteration in tau pathology was determined using Western blotting and immunofluorescence staining. Results Deletion of the gene coding for p47phox, the organizer subunit of NOX2, significantly attenuated cognitive impairment and tau pathology in these mice. p47phox deficiency decreased the activation of astrocytes but had no effect on Aβ levels and amyloid plaque formation in the brains of aged APP/PS1 mice, which displayed markedly increased expression of p47phox in neurons and astrocytes. Cell culture studies found that neuronal p47phox deletion attenuated okadaic acid-induced tau hyperphosphorylation at specific sites in primary cultures of neurons. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in primary neurons, whereas this effect was absent from p47phox-deficient astrocytes. Conclusions These results suggest that p47phox is associated with cognitive function and tau pathology in AD. p47phox expressed in neurons contributes to tau hyperphosphorylation directly, while p47phox in astrocytes affect tau hyperphosphorylation by activating astrocytes indirectly. Our results provide new insights into the role of NOX2 in AD and indicate that targeted inhibition of p47phox may be a new strategy for the treatment of AD.

A phytochemical investigation on the 75% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides resulted in the isolation of three new lycodine alkaloids, 16-hydroxy-9-oxo-lycocasuarinine...

Aim: The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Methods: A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. 21 polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay. Results: The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9.76 vs 23.36%, p = 0.049; 9.76 vs 26.09%, p = 0.045; respectively). Compared with the AA genotype, rs4244809 GG genotype was associated with significantly reduced risk of platinum resistance (adjusted OR: 0.30; 95% CI: 0.10–0.91; p = 0.033). Further stratified analyses revealed that the SNPs of rs3842761 and rs4244809 were greatly related to PR risk in FIGO stage III–IV (rs3842761GG/CC+CG: adjusted OR: 0.15; 95% CI: 0.02–1.21; rs4244809 GG/AA+AG: adjusted OR: 0.24; 95% CI: 0.07–0.84; respectively) and serous adenocarcinoma subgroups (rs3842761 GG/CC+CG: adjusted OR: 0.21; 95% CI: 0.05–0.94; rs4244809 GG/AA+AG: adjusted OR: 0.19; 95% CI: 0.04–0.5; respectively), while rs7924316 polymorphism was associated with reduced risk of PR in serous adenocarcinoma subgroup as analyzed by a recessive model (rs7924316 GG/TT+TG: adjusted OR: 0.22; 95% CI: 0.05–0.98). In addition, both TCT haplotypes of rs3741206/rs3842761/rs7924316 and TC haplotype of rs3741206/rs3842761 were associated with elevated risk of PR (for the TCT haplotype of rs3741206/rs3842761/rs7924316: p = 0.049; OR: 1.69; 95% CI: 1.00–2.87; for the TC haplotype of rs3741206/rs3842761: p = 0.044; OR: 1.71; 95% CI: 1.01–2.88). Conclusion: These results suggest that polymorphisms in IGF2/H19 gene locus are associated with PR risk in EOC.

Breast cancer (BC) is the most malignant tumor in women. The molecular mechanisms underlying tumorigenesis still need to be further elucidated. It is necessary to investigate novel candidate genes involved in breast cancer progression and prognosis. In this study, we commit to explore candidate genes that associate with prognosis and therapy in BC by a comprehensive bioinformatic analysis. Four GEO datasets (GSE5764, GSE7904, GSE20711, and GSE29431) and the BC-related transcriptome data in TCGA database were downloaded and used to identify the differently expressed genes (DEGs). The function of DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. Prognostic candidate genes were identified through survival analysis. In addition, potential therapeutic targets were identified by constructed gene-drug interaction network through Comparative Toxicogenomics Database. A total of 547 DEGs (302 up and 245 down) were identified. Three core-subnetwork and 25 hub genes were identified in PPI network. Seven genes (namely COL12A1, QPRT, MRPL13, KRT14, KRT15, LAMB3, and MYBPC1) were identified as crucial prognostic candidate genes, which significantly associated with breast cancer overall survival. Furthermore, two representative candidate genes (COL12A1 and LAMB3) were optionally chosen for verification by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR). What's more, the gene-drugs interaction analysis indicates several antitumor drugs that could affect the expression of these prognostic markers, such as doxorubicin, cisplatin, and tamoxifen. These results identified seven crucial candidate genes that may serve as prognosis biomarkers and novel therapeutic targets of breast cancer, which may facilitate further understanding the molecular pathogenesis and providing potential therapeutic strategies for BC.

Background: Traditional Chinese Medicine (TCM) prescriptions should be decided according to the TCM treatment principle, and the warming-yang or cooling-heat should be the guide of treatment principle outline. Methods: In order to identify which treatment principle, warming-yang or cooling-heat should be combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC), we combined the typical warming-yang drug, Shen-fu (SF), and the typical cooling-heat drug, Qing-kai-ling (QKL) with gefitinib in resistant NSCLC models. Results: The results demonstrated that QKL combined with gefitinib induced significantly increased cell viability inhibition and apoptosis in A549 cell line and significantly smaller tumor volume and lower tumor weight in H1975 xenograft transplanted nude mice. On the contrary, SF combined with gefitinib had significant antagonism effect on both cell viability inhibition and apoptosis in vitro , and on tumor weight in vivo . EGFR phosphorylation inhibition and the downstream PI3K/AKT and RAS/RAF/ERK pathway inhibition served an important role in the synergism effect between QKL and gefitinib in H1975 xenograft transplanted nude mice. Conclusions: The present study indicated that cooling-heat TCM treatment principle may reverse or delay NSCLC resistance to EGFR-TKIs, and combination of them warrants further study.

Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes.A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database.The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively).TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.

Background and Aim: We have previously shown that high-mobility group box 1 (HMGB1) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods: Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 (BRG1) was examined by immunohistochemistry. Results: The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions: Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1-mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.

Rattus norvegicus, or the rat, has been widely used as animal models for a diversity of human diseases in the last 150 years. The rat, as a disease model, has the advantage of relatively large body size and highly similar physiology to humans. In drug discovery, rat models are routinely used in drug efficacy and toxicity assessments. To facilitate molecular pharmacology studies in rats, we present the predicted rat interactome database (PRID), which is a database of high-quality predicted functional gene interactions with balanced sensitivity and specificity. PRID integrates functional gene association data from 10 public databases and infers 305 939 putative functional associations, which are expected to include 13.02% of all rat protein interactions, and 52.59% of these function associations may represent protein interactions. This set of functional interactions may not only facilitate hypothesis formulation in molecular mechanism studies, but also serve as a reference interactome for users to perform gene set linkage analysis (GSLA), which is a web-based tool to infer the potential functional impacts of a set of changed genes observed in transcriptomics analyses. In a case study, we show that GSLA based on PRID may provide more precise and informative annotations for investigators to understand the physiological mechanisms underlying a phenotype and lead investigators to testable hypotheses for further studies. Widely used functional annotation tools such as Gene Ontology (GO) analysis, and Database for Annotation, Visualization and Integrated Discovery (DAVID) did not provide similar insights. Database URL: http://rat.biomedtzc.cn

Lung cancer organoids (LCOs) have sprung up in more and more researching fields, because of their ability to recapitulate the three-dimensional structure and functions of the in vivo counterpart organs. However, the culture system for LCOs is still immature, resulting in limited success rate and low tumor purity when culturing LCOs. This is mainly due to the deficiency of an optimal formula of culture medium specially for LCOs. Various cytokines and small molecules have been added in the LCOs culturing system. Compound screening, considering both the mechanism of these molecules and the complexity of lung cancer types is warranted to optimize LCOs culture medium. As methods to culture LCOs increase in sophistication, this model will undoubtedly stand its ground in the coming years in every aspect of cancer researches, especially with major advantages in the field of personalized medicine and tumor microenvironment researches.

Purpose The research of long non-coding RNAs (lncRNAs) has become a new passion with the discovery of abundant new lncRNAs and extensive investigation of their roles in various diseases, especially in cancers. Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) emerges as a hotspot, which has been reported to be involved in dysregulation of cell signaling and closely correlated with cancer development, progression, and response to therapy. This review is a brief update of the current knowledge related to the role of MALAT1 in cancer-associated molecular pathways and pathophysiology and possible determinants for MALAT1 to function as a biomarker, aiming to stimulate the basic investigation of lncRNA MALAT1 as well as its translation to clinical applications. Methods We have selected vast literature from electronic databases including studies associated with its clinical significance and the pivotal functions in cancer processes such as cell proliferation, apoptosis, metastasis, immunity, angiogenesis, and drug resistance. Results Studies have shown that aberrant expression of MALAT1 is related to cancer pathophysiology with the potential to be translated clinically and MALAT1 can regulate cancer processes by interacting with molecules, such as proteins, RNAs and DNAs, and further altering different signal pathways. Conclusion MALAT1 lncRNA promises to be a potential biomarker for cancer diagnosis as well as prognosis. Additionally, it might be a therapeutic target for human cancers.

During this study the viability of Saccharomyces Boulardii Bld-3 during passage through the upper GIT under fed and fasted conditions was evaluated. For this purpose, a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) was used, which allows to re-create the physiological conditions that are representative of the human GIT. Furthermore, the aim of this study was also to study the modulatory effect of the Saccharomyces Boulardii Bld-3 on the colonic microbiota composition and activity after passage of the strain through the fed or fasted upper GIT or when delivered directly to the colon. For this purpose, four different types of short-term colonic batch experiments were performed that simulate the colonic fermentation process.

Mobility and flexibility of anterior mitral leaflet (AML) are considered to be the important factor for mitral valve (MV) repair in rheumatic population, we try to use the bending angle of AML to quantify its' mobility and flexibility and investigate whether it can predict the success of rheumatic MV repair or not.Total 54 patients underwent rheumatic MV surgeries with mild lesions of subvalvular apparatus from August, 2017 to November, 2017 at the author institution, we divided the patients into MV repair and MV replacement groups which included directly MV replacement and repair attempt but failed repairing transfer to replacement intraoperatively. Patients' MV structure was carefully evaluated on transthoracic echocardiography (TTE) and scored by the Wilkins score (WS) preoperatively. The bending angle of AML was measured during systole and diastole at different level before surgery.The differences of patients' demographic characteristics between repair group and replacement group were not statistically significant (P value0.05) and the differences among B-angle, T-angle, Bs-angle, C-angle of AML between repair group and replacement groups were not statistically significant (P value0.05). Only BT-angle in repair group was significantly larger than that of replacement group (21.56°±3.84°, 10.29°±6.02°, respectively, P0.001), therefore the BT-angle was tested as a predictor of reparability by observing the receiver operating characteristic (ROC) curve (ROC area: 0.944, standard error: 0.06, 95% CI: 0.826-1), BT-angle of AML on preoperative transthoracic echo of 15.5° or more predicts feasibility of rheumatic MV repair with 100% sensitivity and 85.7% specificity in patients with mild lesions of subvalvular apparatus. Logistic regression for a single area of calcification (diameter0.8 cm) at commissure were shown that: β: 0.08, Exp (β): 1.083, P: 0.7770.05, the minor single calcified area at commissure had no effect on reparability of rheumatic MV disease. The differences of total WS and each component score between repair group and replacement group were not statistically significant (P value0.05). By observing the ROC curve for total WS (ROC area: 0.508), the WS cannot be a predictor for the rheumatic MV repair.The bending angle of AML which was considered as quantification of mobility and flexibility of AML can be a predictor for MV repair in patients with rheumatic heart disease (RHD). The small single area of commissural calcification had no effect on reparability of rheumatic MV disease. WS cannot appropriately predict the outcome of rheumatic MV repair.

The in vivo determination of selenomethionine (SeMet) converted from selenium-enriched yeast (SeY) rather than the determination of in vitro hydrolyzed SeMet is a better parameter for the evaluation of SeY quality. A UPLC-MS/MS method was developed for the quantification of SeMet in rat plasma and the oral bioavailability of SeMet converted from SeY in rats. After a simple extraction with perchloric acid, SeMet and the internal standard methylselenocysteine (MSC) were separated on a C18 column with isocratic elution of water:acetonitrile:formic acid (99:1:0.1, v/v/v) and detected in the multiple reaction monitoring mode. The method was accurate (92.6-104.3%) and precise (1.8-11.0%), and the recovery was 79.4-95.4%. It was successfully applied to pharmacokinetic and bioavailability studies of SeY in rats following the intravenous administration of SeMet and intragastric administration of SeY. SeMet in vivo, converted from SeY, is reported for the first time, and the results suggested that the SeY bioavailability in rats is 87%.

Herein, we successfully designed a ventilation system for a new 350-MW air-cooled turbogenerator based on a reasonable lectotype choice and optimization analysis. Fluid field and thermal analysis based on computational fluid dynamics were performed to guide the optimization of cooling structures and ensure temperature rise under the limit of insulation grade B. The measured values obtained from recent factory assembly-type testing were found to coincide with the design expectations for generator efficiency and temperature rise. The results confirmed the feasibility of a multi-chamber forward-flow cooling path for 400-MVA-class air-cooled generators.