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Objective: To analyze the effects of twirling reinforcing and reducing manipulations on protein expression in parietal cortex of spontaneously hypertensive rats (SHRs), and elucidate the main mechanisms and differences between two manipulations in hypertension treatment. Methods: Rats were randomly divided into the control, model, twirling reinforcing manipulation (TRFM), and twirling reducing manipulation (TRDM) groups. The control and model groups received catch and fixation stimulations once a day for 14 days. The TRFM and TRDM groups were intervened once a day for 20 min for 14 days. On days 0, 2, 6, 10, and 14 after acupuncture, rat systolic blood pressures (SBPs) were measured. Differential protein (DP) expression in the rat parietal cortices was detected. Thereafter, GO functional significance and KEGG pathway enrichment analyses were performed. Results: Compared with the model group, SBP of rats in the TRDM and TRFM groups decreased on days 6 and 10 of acupuncture, respectively (P = .009; P

BackgroundSarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis.MethodsOne hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models.ResultsSarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p < 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002).ConclusionsSarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.

In the present paper, we consider the high dimensional classification problem, which has become much important in many modern statistical studies and applications. We develop new classifie...

The article is concerned with studying the inclusive globalization strategy of «One Belt, One Road». It is defined that this initiative should contribute to the so-called rebirth of the great Chinese nation and serve the realization of the following goals: formation of a wealthy middle class and the building of a democratic socialist State. The Silk Road Economic Belt aims to promote the free movement of economic factors, efficient allocation of resources, deepen market integration, and support the coordination of economic policies of countries along the «One Belt, One Road» initiative, expanding and deepening regional cooperation, creating an inclusive and balanced architecture of regional cooperation in which all parties obtain benefits and opportunities for sustainable development. It is defined that to date there are already such results of cooperation between countries within the framework of the «One Belt, One Road» initiative: Asian Infrastructure Investment Bank (AIIB) – an international financial organization, which aims to promote international financial cooperation in the Asia-Pacific region, to finance projects from constructing roads and airports to sphere of services; The University Alliance of the New Silk Road (UANSR), whose tasks are defined as follows: improving the quality of education at universities in the countries that have joined the alliance; facilitating the economic growth of the Silk Road Economic Belt countries; establishing international relationships between universities in conducting joint research in the economic and political sectors; cultural activities to help strengthen diplomatic ties between the countries; developing educational exchange programs between universities; Strategic Union of Higher Education Institutions and the Tourism Union of the «One Belt, One Road» Cities. The cooperation of countries within the «One Belt, One Road» initiative is developing and deepening very quickly, which leads to interest in further study of this problematics.

Fenestration is a rare congenital abnormality that refers to a segmental duplication of arteries. It is still not clear about the role of fenestrations in the etiology and pathological evolution of vascular diseases. This study aims to investigate the hemodynamic influence brought by various sizes and locations of fenestration in basilar artery models. A series presumptive fenestration models were established based on a normal basilar artery model with various sizes and locations. Identical boundary conditions were utilized in the computational fluid dynamics simulations and different flow patterns in the fenestration and bifurcation regions were comprehensively analyzed. Wall shear stress (WSS)-related parameters such as oscillatory shear index (OSI) and aneurysm formation index (AFI) were computed and compared. The value of WSS on fenestration increased by the fenestration's tortuosity, and nearly-circular fenestration suffered higher WSS than narrow-strips one. Also, high OSI and low AFI value mainly occurred in the bifurcation region, indicating a high level of turbulence and high risk of aneurysm formation. The location of fenestration mainly changed the impact force of blood flow on the bifurcation and the disorder characteristics of blood flow, while the size of fenestration changed the WSS distribution on the proximal inner wall and bifurcation region of fenestration. In summary, the nearly-circular fenestration should be stratified carefully which may results in a high risk inducing unfavorable vascular wall remodeling.

Background Immune checkpoint inhibitors (ICIs) were approved to have a significant antitumor activity in various tumor types. In practice, some patients do not seem to benefit from ICIs but rather to have accelerating disease. The aim of this study was to evaluate hyperprogression in patients with malignant tumors of digestive system treated with ICIs. Methods Medical records from consecutive patients with malignant tumors of digestive system treated with ICIs in Peking University Cancer Hospital were retrospectively collected. Tumor growth kinetics (TGK) on immunotherapy and TGK pre-immunotherapy were collected and TGK ratio (TGKR) was calculated. Hyperprogression was defined as TGKR≥2. Results From August 2016 to May 2017, 25 evaluable patients were identified from 45 patients with malignant tumors of digestive system. Five patients were considered as having hyperprogression. Three of 5 were neuroendocrine carcinomas (NECs) and the other 2 were adenocarcinomas. Four of 5 were treated with programmed cell death ligand 1 (PD-L1) inhibitor, the other one was treated with PD-L1 inhibitor combined with cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitor. Pseudoprogression was observed in 2 patients. Conclusions Hyperprogression was observed in a fraction of patients with malignant tumors of digestive system treated with ICIs. Further investigation is urgently needed.

Management of esophageal squamous cell carcinoma remains challenging, because detection often occurs at advanced stages and because of the high incidence of lymph node metastasis. This article focuses on whether lymphopenia is associated with response and tumor progression in patients with advanced esophageal squamous cell carcinoma who received concurrent chemotherapy., Background. Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). Materials and Methods. A total of 286 patients with stage II–IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count

This paper describes the implementation of a miniaturized quad flat no-lead (QFN)-packaged bandpass filter (BPF) with a combination of an intertwined circular spiral inductor and two types of integrated center-located capacitors using gallium-arsenide-based integrated passive device (IPD) fabrication technology. Air-bridge structures were introduced into the outer circular spiral inductor to save space and to provide the filter with a compact chip area of 1192.5 × 1012.7 μm2. An equivalent circuit was modeled, the current density and variable dimensional parameters were simulated, and the fabrication process was introduced to achieve a better understanding of the IPD BPF. The proposed device was packaged using the QFN-packaging technology and was measured to possess a single passband with a central frequency of 1.91 GHz (return loss: 28.8 dB) and a fractional bandwidth of 72.69% (insertion loss: 0.62 dB). One transmission zero was obtained on the right side of the passband at 4.78 GHz with an amplitude of 35.95 dB. The fabricated BPF can be used in various L-band applications, such as mobile service, satellite navigation, telecommunications, and aircraft surveillance, due to its miniaturized chip size and high-performance characteristics.

Wei-Hong Qi,1,* Wei-Juan Miao,2,* Yu-Zhi Ji,1 Chao Li,1 Jun-Huan Wang1 1Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China; 2Department of Obstetrics, Ri-Zhao People’s Hospital, Ri Zhao, 276800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Hong QiDepartment of Obstetrics, Affiliated Hospital of Qingdao University, No. 59 of Haier Road, LaoShan District, Qingdao, Shandong, 266000, People’s Republic of ChinaTel +86 532-82913296Fax +86 532-82913018Email qiweihong45@163.comObjective: This study aimed to investigate the analgesic effect of transcutaneous electrical acupoint stimulation (TEAS) on labor.Methods: Primiparas with single birth and head presentation were enrolled in this study and randomly divided into three groups: TEAS group (n = 76), patient-controlled epidural analgesia (PCEA) group (n = 75), and control group without any analgesic measures (n = 78).Results: Compared with the control group, the visual analog scores of the TEAS group and the PCEA group at each time point decreased (P < 0.01). The decrease was greater in the PCEA group than that in the TEAS group (P < 0.01). At 120 minutes after analgesia, there were significant differences in plasma β-endorphin content between the TEAS group, PCEA group, and control group (P < 0.01). The difference between the PCEA group and the control group was statistically significant (P < 0.01). Among the parturients having a vaginal delivery, the duration of the first stage of labor was significantly shorter in the TEAS group and control group than in the PCEA group (P < 0.01). The duration of the second stage of labor was significantly shorter in the TEAS group than in the PCEA group (P < 0.01). Oxytocin usage rate during labor was significantly lower in the TEAS group and control group than in the PCEA group (P < 0.01), and adverse reactions were significantly fewer in the TEAS group and control group than in the PCEA group (P < 0.01).Conclusion: The duration of the first and second stage of labor is significantly shorter in the TEAS group than in the PCEA group. TEAS does not increase the use rate of oxytocin or the rate of cesarean section and will not bring about obvious maternal or fetal adverse reactions.Keywords: labor analgesia, transcutaneous electrical acupoint stimulation, patient-controlled epidural analgesia, visual analog score of pain, β-endorphin

Hypertension is one of the primary risk factors for cardiovascular diseases. Numerous proteins serve a critical role in hypertension. Acupuncture has been widely used as a treatment for hypertension in China. The results of the current study suggested that electroacupuncture (EA), twirling reinforcing manipulation (TRFM) and twirling reducing manipulation (TRDM) may be useful in the treatment of hypertension. Additionally, proteome analysis of spontaneously hypertensive rats treated with EA, TRFM and TRDM was performed. There were 117 (EA group), 61 (TRFM group) and 86 (TRDM group) differentially expressed proteins (DEPs) identified in the respective experimental groups compared with the model group. Moreover, parallel reaction monitoring assays were used to validate the reliability of the DEPs. The majority of the results were consistent with previous proteomics results, in particular that for expression of neudesin neurotrophic factor (NENF). NENF may potentially represent an antihypertensive drug target.

Sporotrichosis is a fungal disease of the human and other mammals, caused by a complex of Sporothrix schenckii. The disease follows the traumatic inoculation to lead to fixed lesions, regional lymphangitic lesions, or even disseminated lesions including internal involvement, which depends on host immunological status and strain virulence. In this work, we observed the role of CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines in the cellular immunity regulation on mice model sporotrichosis. The experiments showed that there was more CD4+ T cells apoptosis, by endogenous apoptosis signaling pathway (P < .05), and more conversions of Th1/Th2-type cytokines in more severe and longer duration groups (P < .05). Meanwhile, the trends of the conversions of Th1/Th2-type cytokines were almost consistent with the CD4 + T cell's apoptosis in the corresponding groups. These findings suggest that CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines are contributing to promoting the progress of sporotrichosis.

Engineering technology is the practical application of technology in industrial production, and it is the means and method to use the research results of technological development to transform nature. Engineering and technical talents trained by vocational education should be proficient in the application of technology, have excellent professional skills and professional quality in line with the needs of engineering and technology. As the posts of industrial production are cross, hierarchical and integrated, it is very necessary and valuable to train engineering and technical talents in the way of stratification and connection. According to the current situation of connection between secondary and higher vocational education, taking engineering technology related majors as an example, an integrated framework of curriculum system for connection between secondary and higher vocational education is analyzed from three aspects: personnel cultivation objectives and specifications, educational system model and teaching plan. The integrated curriculum is divided into four modules: the common basic curriculum module, the professional platform curriculum module, the professional direction curriculum module and the independent direction curriculum module. On this basis, the strategy of curriculums connection between secondary and higher vocational education is expounded from the determination of the interface standard and the path of the module connection. Taking construction machinery product - paver as a typical case, the idea of curriculum connection is described. It effectively promoted the integrated design of curriculum system for the connection between secondary and higher vocational education, improved the training level of students' engineering technology application ability, and laid a good foundation for other aspects of cohesion between secondary and higher vocational education.

BACKGROUND Despite the promising results of immunotherapy in cancer treatment, new response patterns, including pseudoprogression and hyperprogression, have been observed. Radiomics is the automated extraction of high-fidelity, high-dimensional imaging features from standard medical images, allowing comprehensive visualization and characterization of the tissue of interest and corresponding microenvironment. This study assessed whether radiomics can predict response to immunotherapy in patients with malignant tumors of the digestive system. MATERIAL AND METHODS Computed tomography (CT) images of patients with malignant tumors of the digestive system obtained at baseline and after immunotherapy were subjected to radiomics analyses. Radiomics features were extracted from each image. The formula of the screened features and the final predictive model were obtained using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. RESULTS Imaging analysis was feasible in 87 patients, including 3 with pseudoprogression and 7 with hyperprogression. One hundred ten radiomics features were obtained before and after treatment, including 109 features of the target lesions and 1 of the aorta. Four models were constructed, with the model constructed from baseline and post-treatment CT features having the best classification performance, with a sensitivity, specificity, and AUC of 83.3%, 88.9%, and 0.806, respectively. CONCLUSIONS Radiomics can predict the response of patients with malignant tumors of the digestive system to immunotherapy and can supplement conventional evaluations of response.

BackgroundThis retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC).MethodsPatients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups.ResultsA total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%,p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%,p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%,p = 0.275).ConclusionCCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Objective. Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients who have pharmaco-resistant Dravet syndrome (DS). Plentiful efforts have been made for delivering VNS to DS patients, but its effectiveness still requires further verification. We investigated the effectiveness of the VNS treatment of DS patients using brain connectivity analysis with electroencephalography (EEG). Approach. Twenty pharmaco-resistant DS patients were selected to undergo VNS implantation and classified into responder and non-responder groups after 24 months post-VNS. The effect of VNS between 6 months pre- and 6, 12, and 24 months post-VNS in all patients, responders, and non-responders on four different frequency categories of four brain parameters were compared using resting-state EEG. Main results. In alpha and beta bands, all patients showed positive results for characteristic path length (CPL), global efficiency (GE), and transitivity after VNS treatment, and changes in betweenness centrality (BC) were not significant. The difference in transitivity between responders and non-responders is more pronounced than those in CPL and GE are, in both the alpha (p < 0.015) and beta (p < 0.001) bands. There was an obvious change in BC, especially in the alpha band, as the hubs tended to move from frontal lobe to parietal lobe for responders; however, there was no change for the non-responders. Significance. We investigated the alteration in brain connectivity of DS patients in alpha and beta bands during a long-term follow-up and found the responders have a decreased transitivity after the VNS treatment. Moreover, the hubs with high values in the alpha band tended to move from frontal lobe to parietal lobe for responders after VNS treatment.

This article presents a compact quad flat no-lead (QFN)-packaged second-order bandpass filter (BPF) with intertwined inductors, a dendritic capacitor, and four air-bridge structures, which was fabricated on a gallium arsenide (GaAs) substrate by integrated passive device (IPD) technology. Air-bridge structures were introduced into an approximate octagonal outer metal track to provide a miniaturized chip size of 0.021 &times, 0.021 &lambda, 0 (0.8 &times, 0.8 mm2) for the BPF. The QFN-packaged GaAs-based bandpass filter was used to protect the device from moisture and achieve good thermal and electrical performances. An equivalent circuit was modeled to analyze the BPF. A description of the manufacturing process is presented to elucidate the physical structure of the IPD-based BPF. Measurements were performed on the proposed single band BPF using a center frequency of 2.21 GHz (return loss of 26.45 dB) and a 3-dB fractional bandwidth (FBW) of 71.94% (insertion loss of 0.38 dB). The transmission zero is located at the 6.38 GHz with a restraint of 30.55 dB. The manufactured IPD-based BPF can play an excellent role in various S-band applications, such as a repeater, satellite communication, and radar, owing to its miniaturized chip size and high performance.

Koebner phenomenon refers to the emergence of new psoriatic lesions in the healthy skin regions following an injury/trauma to psoriatic patients. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes and on keloids suggest that the Koebner phenomenon may be responsible for these lesions. A number of agents/triggers have been reported to induce the development of new psoriatic lesions in healthy skin areas and these include, tattooing skin, radiations, skin incision, viral infections and striae etc. The different mechanisms that contribute in inducing the development of new psoriatic lesions as Koebernization include the involvement of mast cell-derived inflammatory mediators such as tryptase, IL-6, IL-8, IL-17, and IL-36γ. Moreover, an increased expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) also contribute in Koebernization. Apart from these, there is a critical role of α 2 β1 integrins, S100A7 (psoriasin) and S100A15 (koebnerisin), change in the ratio of CD4+/CD8+ T cells, down-regulation of mechanosensitive polycystin 1 protein, decrease in inflammation controlling atypical chemokine receptor 2 (ACKR2), reduced expression of N-methyl-d-aspartate (NMDA) receptors (NMDARs) on the keratinocytes and increase in levels of chemokines (CXCL8 and CCL20) in inducing formation of new psoriatic lesions. The present review discusses the role of Koebner phenomenon in the development of new psoriatic lesions. Moreover, it also describes the mechanisms involved in Koebernization in the form of discussion of different key targets that may be potentially modulated pharmacologically to attenuate/halt the development of new psoriatic lesions.

Integrated solar photovoltaic and thermal (PV/T) systems utilize the heat produced during photovoltaic power generation to heat water, which can then be used for heating and domestic water supply purposes. At the same time, the water is used to cool the solar panel, thereby enhancing the efficiency of power generation and consequently improving the overall utilization of solar energy. To realize real-time monitoring and display of the temperature and power generation of the integrated PV/T system, we designed a monitoring system based on a ForceControl configuration system. In this paper, we provide details of the construction of the system, including the establishment of the physical integrated PV/T system, the temperature data acquisition system, and the electric data acquisition system, as well as the design of a monitoring interface based on the ForceControl configuration software. Within this study, the system was also constructed and verified. The results indicated that the system can display parameters including temperature of the PV module rear panel, temperature of the water tank, and power generation in real time. Furthermore, its characteristics, including friendly interface, intuitive display, and high precision all make it an appropriate tool for monitoring integrated PV/T systems.

e16080 Background: Patients with advanced gastric or gastro-esophageal junction cancer have poor prognosis after progression on first-line chemotherapy. We investigated to combine second-line chemotherpy with third-line drugs, apatinib and anti-PD-1 antibody in these patients. Methods: This study is a single center, exploratory study in China. Eligible patients are adults with histologically confirmed advanced gastric or GEJ adenocancinoma, who were failure of first-line or second-line chemotherapy. Subjects receive chemotherapy, pacitaxol or iritecan (investigator choice), apatinib 250mg po qd, sintilimab 200mg ivd q3w. Response was assessed every 6 weeks. (RECIST version1.1) Primary endpoint was progression free survival (PFS). Results: Between May 30, 2019 and November 5, 2020, a total of 26 patients were enrolled in this study, and 4 (15.4%) patients were failure of second-line chemotherapy. There were 21 males and 5 females, and the median age was 61. The total number of treatment cycles was 140 and the median number was 5.5. Among 24 patients who were evaluated, partial response (PR) was obtained in 12 cases, stable disease (SD) in 8 cases and progressive disease (PD) in 4 cases. Objective response rate was 50.0%，and disease control rate was 83.3%. The median PFS was 7.06 months (95% CI 5.52-8.60), and the median overal survival has not yet been reached. The most common adverse events (AE) were leukopenia (61.5%), anemia (57.7%), neutropenia (53.8%), proteinuria (42.3%), alopecia (42.3%), hypothyroidism (38.5%), elevated alanine aminotransferase (34.6%), elevated aspartate aminotransferase (34.6%) and elevated alkaline phosphatase (34.6%), but most of them were grade 1 or 2, and the most common grade 3 or 4 treatment-related adverse events was neutropenia (11.5%). Conclusions: Chemotherapy, plus apatinib and sintilimab demonstrated promising activity and manageable safety profile as second- even third-line treatment in advanced gastric or GEJ cancer. Demographics and baseline characteristics.[Table: see text]

e16000 Background: Gastric cancer with elevated alpha-fetoprotein (AFP) is a special type of gastric cancer with elevated serum AFP. It is often misdiagnosed as primary hepatic cancer due to abnormal AFP and liver metastasis. The AFP level is related to the prognosis of these patients in whom there is prone to high HER2 positive rate. Therefore, anti-HER2 treatment is optional, as well as the emerging immunotherapy with immune checkpoint inhibitors. Methods: Gastric cancer patients with HER2 and serum AFP examination were collected in our hospital from May 2017 till now. Serum AFP level over 7 ng/ml was defined as elevated AFP. The clinical characteristics, treatments and survival of the patients with HER2 positive and elevated AFP were picked and analyzed. Results: Among 135 gastric cancer patients with elevated AFP, 16 (11.9%) were HER-2 positive (12 with HER2 3+, 3 with HER2 2+/FISH+ and 1 with HER2 gene amplification in NGS). The mean serum AFP is 201.4± 476.7ng/ml (range: 7.74 -1335). There were 9 males and 7 females. The mean age was 55 years (range: 38-90). The tumors were located in stomach cardia and fundus in 5 cases, body in 5 cases, antrum in 4 cases, body and antrum in 1 case and whole stomach in 1 case. There were 2 patients in stage III and 14 patients in stage IV with metastasis to lymph node metastasis in 15, liver in 9, abdominal cavity in 3 and peritoneum in 3. As for the treatments, three patients underwent surgery, one of whom with exploratory laparotomy (no antitumor treatment after surgery, died from infection). In 13 advanced patients, 12 patients received systemic antitumor therapies (8 with chemotherapy+Trastuzumab+ immunotherapy, 2 with chemotherapy+Trastuzumab, 1 with chemotherapy+ immunotherapy and 1 with chemotherapy). The chemotherapy regimens were XELOX in 5 cases, SOX in 4 cases and FLOT in 2 cases. The response rate was 50% (6 in 12 patients) and the disease control rate was 100%. The median PFS was 7.5 months in first line therapy with six patients without progression disease yet. The longest PFS with PR lasted for 16.5 months with chemotherapy, trastuzumab and immune checkpoint inhibitor. Conclusions: Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics. Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors. This combination is expected to become a new regimen to improve survival of such special patients.

e15560 Background: PD-1 blockade is particularly ineffective in patients with microsatellite stable (MSS) or mismatch repair (MMR)-proficient colorectal cancer (CRC). Regorafenib (R) has been shown to modulate anti-tumor immunity through different mechanisms, including the reduction of tumor-associated macrophages (TAMs) and lymphocyte activation or immunosuppressive cells, such as forkhead box P3 (Foxp3)+ CD25+ regulatory T cells (Tregs). Synergy between R and anti–PD-1/PD-L1 antibodies has been demonstrated in pre-clinical models compared to that of either treatment alone. Accordingly, this study attempted to evaluate the combined activity of regorafenib with an immune checkpoint inhibitor. Methods: This trial was a prospective, open-label, monocentric, nonrandomized, single arm study. This study included patients with non MSI-H mCRC who received R (80 mg QD 3weeks/4) and sintilimab (S)(200 mg every 3 weeks).The primary endpoint was the confirmed objective response rate (ORR).The secondary endpoints were progression free survival (PFS),overall survival (OS),disease control rate (DCR) and safety. Results: As of January 8, 2021, 24 patients (median age 59 years) with mCRC were enrolled and received treatment with R+S. RAS wild type was 50% of all patients. In addition, 83.3% of patients received two prior lines of treatment, while 58.3% had liver metastases at enrollment. Of the 24 patients, the best response was observed to be stable disease(SD) in six patients (25%) and progressive disease (PD)in four patients (16.7%). Another nine (37.5%) patients have yet to be evaluated. In the 15 evaluated patients, the ORR(RECIST version 1.1) was 33.3% , the DCR was 73.3%. Additionally, among the 10 evaluated patients with liver metastases, the ORR was 30% , the DCR was 80%. Among the nine evaluated patients with wild-type populations of k-ras, the ORR and DCR was found to be 44.4% and 66.7%, which was higher than the mutation patients. The median PFS was 4.2 (95% CI, 2.5, NA) months, the median OS was not reached. The most common grade 3/4 adverse events were palmar-plantar erythro-dysesthesia syndrome (4.2%), erythra (4.2%). No death was related to the treatment. Moreover, four (16.7%) patients were subject to at least 1 dose modification or treatment interruption. Conclusions: In this study, the combination of R+S achieved a similar ORR with REGONIVO. Furthermore, this combination was well tolerated and had a manageable safety profile. However, due to the limited sample size, some biases may be present. As a result, we will continue to expand the sample size for future verification. Clinical trial information: NCT04745130.

e16210 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 10%. Overexpression of c-Met is associated with the poor prognosis in patients with PDAC and it was noted that phosphorylation of c-Met is increased in gemcitabine-resistant PDAC. AL2846 is an oral c-Met inhibitor, which targets multiple receptor tyrosine kinases (RTK’s) primarily including c-Met, VEGFR1, KIT, Axl and RET. The combination of AL2846 with chemotherapy may improve the clinical efficacy of PDAC. Based on these consideration, a phase Ⅰ clinical trial was initiated to determine the maximum tolerated dose (MTD) of AL2846 in combination with gemcitabine in patients with advanced PDAC and to clarify the potential anti-tumor activity. Methods: Patients with untreated locally advanced or metastatic PDAC were enrolled to receive oral AL2846 once daily in a fasted state in combination with gemcitabine intravenous infusion over 30 min on days 1, 8, and 15 every 28 days. The starting dose level is AL2846 40 mg and gemcitabine 1000 mg/m2. Primary endpoint was the maximum tolerated dose (MTD), defined as the highest dose level at which ≤33 % of patients incurred a dose-limiting toxicity (DLT), and RP2D. Secondary endpoints included response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: As of January 1, 2021, a total of 15 patients with PDAC were enrolled and received 4 dose-levels of AL2846 (40 mg: n = 1; 60 mg: n = 6; 90 mg: n = 3; 120 mg: n = 5) treatment. DLTs occurred in 1 patient who experienced grade 3 abnormal liver function. The most common grade 3 or above drug-related adverse events were neutropenia (n = 7, 46.7%), thrombocytopenia (n = 5, 33.3%), leukopenia (n = 4, 26.7%), GGT increased (n = 4, 26.7%), hyperbilirubinemia (n = 3, 20.0%) and alkaline phosphatase increased (n = 3, 20.0%). Among the 15 patients available for efficacy evaluation, 1 patient (6.6%) achieved partial response who was at the dose levels of 90mg. There were 4 patients whose PFS was more than 5 months. Although there were no more than 2 DLT events, we chose 90 and 120 mg as the target dose for RP2D according to the dose reduction and proportion of gemcitabine. Conclusions: The RP2D of AL2846 in combination with standard dose of gemcitabine were 90 and 120 mg QD continuously. The results demonstrated that AL2846 in combination with gemcitabine was well tolerated at doses up to 120 mg. Further clinical studies about the efficacy of AL2846 in pancreatic cancer are in progress. Clinical trial information: CTR20201021.

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

With the development of information technology, databases have taken the place of the “card box” as an indexing device for some researchers. It cannot be denied that the grammatological studies based on databases have not only become an objective existence that cannot be ignored, but have also had fruitful achievements. However, the corresponding theoretical construction remains blank, which is unfavorable for the grammatology study based on databases to develop scientifically. Therefore, this paper attempts to discuss the following matters: the definition of “database grammatology”; the relationship between “database grammatology” and “corpus linguistics”; the feasibility of “database grammatology”; “database grammatology” and traditional grammatology; the database construction of “database grammatology”; and the academic quality pursuit of database grammatology study.

Objective: To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP). Methods: Thirty-six Wistar rats were randomized into three groups: the control group, model group, and model + acupuncture (AP) group (n = 12 rats per group). During the 11-day modeling period, the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure, and daily acupuncture intervention was applied simultaneously in the model + AP group; the control group did not experience modeling or acupuncture. Systolic pressure (SP) was measured the day before modeling began, and on the 3rd, 5th, 7th, 9th, and 11th day after modeling initiation. On the 12th day, histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1, and ANP was tested by quantitative real-time polymerase chain reaction (PCR). Results: SP was higher in the model group than the control group on the 3rd, 5th, 7th, 9th, and 11th days (all P

Purpose To report a case of surgical interventions for a patient with relapsing polychondritis who presented with late ocular complications. Observations A 44-year-old male was diagnosed to have relapsing polychondritis on the basis of recurrent acute auricular chondritis, deformity of the ear, saddle nose deformity and painful nasal chondritis, acute ocular inflammation with conjunctivitis, episcleritis and keratouveitis, laryngotracheal chondritis, erythema nodosum in the skin, a history of polyarthritis, and abnormal blood examination findings. The acute ocular and auricular inflammation was resolved with oral corticosteroid treatment. Intraocular pressure (IOP) of the left eye was 60 mmHg as measured by Goldmann applanation tonometer. Gonioscopic observation revealed the presence of peripheral anterior synechiae and plateau iris configuration. Express drainage screw implantation was applied to the left eye, because topical and systemic medicines failed to decrease the IOP. After 12 months, complicated cataract aggravated in the right eye, and phacoemulsification operation was performed with corticosteroids administered during the perioperative period. His corrected visual acuity was 20/20 for the right eye, and the IOP remained below 21 mmHg for the left eye. The patient has been healthy, without any recurrence, for 36 months. Conclusions and importance The present case of relapsing polychondritis is the first to be reported wherein late ocular complications were alleviated by surgical interventions. Routine use of corticosteroids is necessary for successful anti-glaucoma and phacoemulsification operations.

Background:Epidemiologic studies have investigated the association between nut intake and risk for multiple cancers. However, current findings are inconsistent and no definite conclusion has been drawn from prospective studies. We therefore conducted this meta-analysis to evaluate the relationship between nut consumption and risk of cancer.Methods:Prospective studies reporting associations between nut intake and risk for all types of cancer were identified by searching Web of Science and PubMed databases up to June 2019. Risk ratios (RR) and 95% confidence intervals (CI) were extracted and then pooled across the studies using a random-effect model. A dose–response analysis was modeled by performing restricted cubic splines when data were available.Results:Thirty-three studies that included more than 50,000 cancer cases were eligible for the analysis. When comparing the highest with the lowest category of nut intake, high consumption of nuts was significantly associated with decreased risk of overall cancer (RR = 0.90; 95% CI, 0.85–0.95). The protective effect of nut consumption was especially apparent against cancers from the digestive system (RR = 0.83; 95% CI, 0.77–0.89). Among different nut classes, significant association was only obtained for intake of tree nuts. We also observed a linear dose–response relationship between nut consumption and cancer: Per 20 g/day increase in nut consumption was related to a 10% (RR = 0.90; 95% CI, 0.82–0.99) decrease in cancer risk.Conclusions:Our analysis demonstrated an inverse association of dietary nut consumption with cancer risk, especially for cancers from the digestive system.Impact:This study highlights the protective effect of nuts against cancer.

In this work, a miniaturized bandpass filter (BPF) constructed of two spiral intertwined inductors and a central capacitor, with several interdigital structures, was designed and fabricated using integrated passive device (IPD) technology on a GaAs wafer. Five air-bridge structures were introduced to enhance the mutual inductive effect and form the differential geometry of the outer inductors. In addition, the design of the differential inductor combined with the centrally embedded capacitor results in a compact construction with the overall size of 0.037&lambda, 0 &times, 0.019&lambda, 0 (1537.7 &times, 800 &mu, m2) where &lambda, 0 is the wavelength of the central frequency. For the accuracy evolution of the equivalent circuit, the frequency-dependent lumped elements of the proposed BPF was analyzed and modeled through the segment method, mutual inductance approach, and simulated scattering parameters (S-parameters). Afterward, the BPF was fabricated using GaAs-based IPD technology and a 16-step manufacture flow was accounted for in detail. Finally, the fabricated BPF was wire-bonded with Au wires and packaged onto a printed circuit board for radio-frequency performance measurements. The measured results indicate that the implemented BPF possesses a center frequency operating at 2 GHz with the insertion losses of 0.38 dB and the return losses of 40 dB, respectively, and an ultrawide passband was achieved with a 3-dB fraction bandwidth of 72.53%, as well. In addition, a transmission zero is located at 5.32 GHz. Moreover, the variation of the resonant frequency with different inductor turns and metal thicknesses was analyzed through the simulation results, demonstrating good controllability of the proposed BPF.

This paper presents a miniaturized bandpass filter based on spiral inductor and center-embedded capacitor using integrated passive device (IPD) technology on a gallium arsenide (GaAs) substrate. The EM simulation and RF measurement results of the proposed design are accomplished using Advanced Design System (ADS) software and Agilent 8510C vector network analyzer (VNA), respectively. The measured results illustrate the proposed filter features a single passband with the central frequency of 1.36 GHz, and a 3-dB fractional bandwidth of 66.3%. And there is also a finite transmission zero locates at 3.71 GHz, and simulation and measurement result show good agreements. The proposed filter has a compact dimension with an overall size of 1292 × 700 μm2 resulting from the use of IPD technology and the intertwined spiral outer inductor.

AIM: To analyze the expression of uncoupling protein 2 (UCP2) in retinal pigment epithelium (RPE) cells at the different human age, further explore the possible new target of RPE cells protection. METHODS: Adult retinal pigment epithelial-19 (ARPE-19) cells and the primary RPE cells at the different age (9-20y, 50-55y, 60-70y, >70y) were cultured and harvested. The expression of UCP2 in these cells was detected by reverse transcription-polymerase chain reaction (RT-PCR), Western blot and confocal microscopy. RESULTS: Cells from the donors more than 60y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20y and 50-55y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60y. CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.

As one of the most commonly used devices in microwave systems, bandpass filters (BPFs) directly affect the performance of these systems. Among the processes for manufacturing filters, integrated passive device (IPD) technology provides high practicality and accuracy. Thus, to comply with latest development trends, a resonator-based bandpass filter with a high selectivity and a compact size, fabricated on a gallium arsenide (GaAs) substrate is developed. An embedded capacitor is connected between the ends of two divisions in a circular spiral inductor, which is intertwined to reduce its size to 0.024 &lambda, g &times, 0.013 &lambda, g with minimal loss, and along with the capacitor, it generates a center frequency of 1.35 GHz. The strong coupling between the two ports of the filter results in high selectivity, to reduce noise interference. The insertion loss and return loss are 0.26 dB and 25.6 dB, respectively, thus facilitating accurate signal propagation. The filter was tested to verify its high performance in several aspects, and measurement results showed good agreement with the simulation results.

The stock1 market is dynamic, noisy and hard to predict. In this paper, we explored four machine learning models using technical indicators as input features to predict the price trend 30 days later. The experimental dataset is Shanghai Stock Exchange(SSE) 50 index stocks. The result demonstrates that ANN performs better than the other three models and is promising to find some profitable patterns.

In the paper the authors proved that China’s growth towards dominance in international trade has begun recently, but, on average, the growth of China’s trade volume has doubled every four years over the past three decades. The paper analyses that the rapid growth of the Chinese economy provides all countries around the world especially neigh boring countries, with a chance of interconnected development, which had a decisive impact on the economic prosperity of the world economy at the end of the last and at the beginning of this century. The key priority of Chinese economic policy was called attracting FDI, but gradually it focused on foreign direct investment (FDI) from China. Therefore, the “one belt, one road” initiative has brought maximum effect not only on the country itself, but on the entire global economy, and has become the basis for multilateral economic development. Accordingly, we have come to the conclusion that the project the “one belt, one road” has a goal to strengthen the geopolitical cooperation between Asia and Europe, so it is Ukraine that is important in its implementation. Ukraine is a strategically important logistics hub between Asia and Europe. It is proved that Ukraine is now a promising country in Eastern Europe and has a significant deferred purchasing power potential, which will increase if the political and economic situation in the country stabilizes.

RBM15, an RNA-binding protein, plays important roles in the growth and apoptosis of cells, especially blood cells through regulating multiple signal pathways such as Notch and Wnt. An increasing body of evidence has suggested that RBM15 may play a key function on the development of various blood diseases, such as acute/chronic myeloid leukemia and kaposi's sarcoma. In this review, we will focus on the progress of the association between RBM15 and its related blood diseases.

Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill (YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated mRNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated mRNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 μg/L, P 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39-2.62, P 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1.

To assess the prevalence and causes of visual impairment (VI) in the elderly Chinese rural population in Shaanxi Province.A population-based, cross-sectional study design was used to determine the extent of VI in Chinese people over the age of 50 years in Shaanxi Province. Visual acuity and best-corrected visual acuity were measured using the logarithm of minimum angle of resolution chart. Blindness and low vision were defined according to WHO criteria. The major cause of VI was identified for all participants who were visually impaired.A total of 1912 residents completed a standard questionnaire and underwent a detailed eye examination, and the response rate was 90%. The overall prevalence of blindness and low vision were 1.5% and 8.2%. There was no statistically significant differences between genders in the prevalence of blindness and low vision (P > .05). The prevalence of blindness and low vision was higher among older individuals (P < .05) and lower (P < .05) among those with the highest education level. Cataract, corneal opacity, and glaucoma were considered as the main causes of blindness, which accounted for 67.9%, 10.7%, and 7.1%, respectively. Cataract, refractive error, and age-related macular degeneration were always considered as the leading causes of low vision, which accounted for 66%, 14.7%, and 5.8%, respectively.Cataract, corneal opacity, and glaucoma were the main causes of blindness and low vision in the population aged 50 years or more. The prevalence of these diseases that causes blindness and low vision was higher than that reported in other studies.

Oncogenic alterations in the BRAF gene are identified in an estimate of 50% of melanomas and cause melanoma development. BRAF kinase inhibitors (BRAFi), including vemurafenib and dabrafenib, were discovered and used in the clinical treatment of BRAF-mutant metastatic melanoma. Though, BRAFi's therapeutic advantages are short term and short-lived associated with drug resistance. Although a few pathways of developed BRAFi resistance have also been established, in approximately 40% of melanomas, the cause for inherited resistance remains unclear. Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma. In this study, we are exploring the compensatory alternative pathway followed by BRAFi/MEKi treated resistant cell for maintaining the long-term integrity and survival.

This paper reports on the use of gallium arsenide-based integrated passive device technology for the implementation of a miniaturized bandpass filter that incorporates an intertwined circle-shaped spiral inductor and an integrated center-located capacitor. Air-bridge structures were introduced to the outer inductor and inner capacitor for the purpose of space-saving, thereby yielding a filter with an overall chip area of 1178 &mu, m &times, 970 &mu, m. Thus, not only is the chip area minimized, but the magnitude of return loss is also improved as a result of selective variation of bridge capacitance. The proposed device possesses a single passband with a central frequency of 1.71 GHz (return loss: 32.1 dB), and a wide fractional bandwidth (FBW) of 66.63% (insertion loss: 0.50 dB). One transmission zero with an amplitude of 43.42 dB was obtained on the right side of the passband at 4.48 GHz. Owing to its miniaturized chip size, wide FBW, good out-band suppression, and ability to yield high-quality signals, the fabricated bandpass filter can be implemented in various L-band applications such as mobile services, satellite navigation, telecommunications, and aircraft surveillance.

Background: The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer, but causal variants have not been fully investigated. We intended to explore functional polymorphisms associated with non-small cell lung cancer (NSCLC) susceptibility and their relationship with telomere length in Chinese population. Methods: We conducted a targeted sequencing at 5p15.33 with 400 patients. Comparing with genotypic frequency in 1000 Genomes Project, we selected candidate variants and validated their associations with NSCLC in 985 cases and 970 controls. The relationships between susceptibility SNPs and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays were performed to reveal potential mechanisms. Findings: we identified 1478 variants through targeted sequencing and selected 17 candidate variants. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95% CI: 1.18-1.52, P = 7.78 × 10-6 )，rs10054203 (OR = 1.29, 95% CI: 1.13-1.46, P = 1.37 × 10-4 )，rs2736107 (OR = 1.28, 95% CI: 1.11-1.47, P = 5.14 × 10-4 ) and rs2853677 (OR = 1.23, 95% CI: 1.08-1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Functional exploration characterized rs7726159 promoted TERT transcription through disrupting transcription factor binding. Interpretation: The functional polymorphism, rs7726159, confers lung cancer susceptibility by disturbing telomere biology. Our study illustrated the functional significance of this variant in lung cancer initiation, which provides a new insight into the important role of telomere dysfunction in tumor progression. Funding Statement: This work was supported by the National Natural Science Foundation of China (81572071). Declaration of Interests: The authors declare that they have no potential conflicts of interest. Ethics Approval Statement: Written informed consent was obtained from each individual, and this study was approved by the Institutional Review Board of the Tongji Medical College, HUST.

The present study explores the correlation of human epidermal growth factor receptor-2 (HER-2) protein expression with sentinel lymph node (SLN) metastasis and prognosis of breast cancer. The breast cancer tissues and adjacent tissues were obtained from patients with primary breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of HER-2. Spearman correlation analysis was used to analyze the correlation of HER-2 expression with SLN metastasis. The disease-free survival (DFS) and overall survival (OS) of breast cancer patients were investigated. Univariate and multivariate analyses were performed to explore factors influencing SLN metastasis and prognosis of breast cancer. Compared with adjacent tissues, HER-2 expression was significantly up-regulated in breast cancer tissues. HER-2 expression was correlated with the pathological type, tumor node metastasis (TNM) staging, histological grade, blood vessel invasion, SLN metastasis, estrogen receptor (ER), and progesterone receptor (PR). The expression level of HER-2 was positively related to the SLN metastasis (r=0.548). Median DFS and OS were longer in patients with negative HER-2 expression than in patients with positive HER-2 expression. TNM staging, SLN metastasis, and expression levels of HER-2 and ER were independent factors for DFS of breast cancer patients, while TNM staging, blood vessel invasion, histological grade, SLN metastasis, and expression levels of HER-2 and PR were independent factors for OS of breast cancer patients. Our study suggests that high expression of HER-2 promoted SLN metastasis. HER-2 expression and SLN metastasis were the independent factors for the prognosis of breast cancer.

Serum α-fetoprotein- (AFP-) elevated gastric cancer is a rare tumor that has a poor prognosis due to high incidence of liver metastasis. This study sought to investigate the optimal treatment modality. A total of 319 gastric cancer patients with liver metastasis (GCLM) whose serum AFP levels were tested before treatment were enrolled in this study. They were classified as the serum AFP ≥ 20 ng/ml group (n=74) and the AFP n=245). Median OS of the AFP P=0.004). ORR of first-line chemotherapy was 43.3% and 56.1% of the two groups, respectively (P=0.024). Of patients who received doublet regimen, ORR of the AFP ≥ 20 ng/ml group was significantly lower (38.2 versus 56.9%, P=0.013), while in those received triplet regimens, ORR between two groups was similar (66.7% versus 66.7%, P=0.676). Moreover, for patients of the AFP ≥ 20 ng/ml group, those who reached PR had a longer survival period (15.4 m versus 9.4 m, P=0.017), and combined with local treatment for liver metastasis also seemed to improve prognosis (19.2 m versus 8.4 m, P=0.003). In conclusion, serum AFP-elevated GCLM had a poorer prognosis. Multimodality treatment including aggressive first-line chemotherapy with triplet regimen may be needed when treating them.

The ASP flooding is an effective method to enhance oil recovery. The main mechanism is to increase the viscosity of injection water by polymer, which reduces the mobility ratio of displacing fluid and displaced fluid so as to expand the sweep volume. The second mechanism is to improve the displacement efficiency by the combined interaction of surface active agent and alkali, which reduces the interfacial tension and improves the wettability of reservoir. The recovery of the ASP flooding usually can raise 10% more than the conventional polymer, but there are still a lot of underground crude oil residues after flooding. So we need take some other methods in order to further improve oil recovery factor. For the research of the ASP flooding microscopic remaining oil distribution, it is still blank all over the world. This paper studies on the microscopic remaining oil distribution after the ASP flooding by using both laser confocal technique and modern physics experiment simulation method. The result shows that the remaining oil is mainly Thin Film Type and Clusters Type, most of them are heavy oil which cannot be flooded easily. It can be a certain reference value for further study on the choices of enhanced oil recovery methods.

Understanding users&rsquo, continued usage intentions for online learning applications is significant for online education. In this paper, we explore a scale to measure users&rsquo, usage intentions of online learning applications and empirically investigate the factors that influence users&rsquo, continued usage intentions of online learning applications based on 275 participant data. Using the extended Technology Acceptance Model (TAM) and the Structural Equation Modelling (SEM), the results show that males or users off campus are more likely to use online learning applications, that system characteristics (SC), social influence (SI), and perceived ease of use (PEOU) positively affect the perceived usefulness (PU), with coefficients of 0.74, 0.23, and 0.04, which imply that SC is the most significant to the PU of online learning applications, that facilitating conditions (FC) and individual differences (ID) positively affect the PEOU, with coefficients of 0.72 and 0.37, which suggest that FC is more important to the PEOU of online learning applications, and that both PEOU and PU positively affect the behavioral intention (BI), with coefficients of 0.83 and 0.51, which indicate that PEOU is more influential than PU to users&rsquo, continued usage intentions of online learning applications. In particular, the output quality, perceived enjoyment, and objective usability are critical to the users&rsquo, continued usage intentions of online learning applications. This study contributes to the technology acceptance research field with a fast growing market named online learning applications. Our methods and results would benefit both academics and managers with useful suggestions for research directions and user-centered strategies for the design of online learning applications.

In order to meet the needs of recovery production of filtering and washing of fine powder of rare metal, a device has been developed which is a set ultra-fine filter, mixing washing, dry-pressed cake, cake discharge and microporous regeneration, etc. in one integral device, and all steps can be completed once using it in a confined space. In addition, a number of key technologies were advanced that can be realized by the device, including recycling technologies, polymer ultra-fine filter technology, equipment and structural design, workflow design, etc. The device has many advantages, such as high filtration precision, high recovery rate, high efficiency production, simple operation, high degree of automation and less environmental pollution. Fine powder of rare metal is generally prepared by electrochemical or chemical production method, wherein filtering and washing are two important processes. Filtering, washing, recovery technology and equipment progressiveness have a direct impact on products quality, resources loss, energy consumption, costs, environment and other problems. Design of a new ultra-precision filtering and washing equipment of fine powder of rare metal and its advanced recycling technology are of great significance.