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Background: Modern upgrades of power grids and a rapidly expanding economy complexify the uncertainties of electricity demand. Objective: The objective of the study is to have a more precise prediction on the demand side, which is beneficial in affirming the stable operation of the power system. Methods: This paper presents a combined electricity forecasting method based on the users clustering and stacking ensemble learning to mine underlying properties of different individual consumers. The preprocessed electricity consumption profiles are inputted into the DBSCAN clustering algorithm to obtain the clusters. The alternative models are tailored for different clusters in the stacking fusion framework for training and testing. Result: Experimental results on the operating data of Shandong Power Grid show that the proposed method has higher prediction accuracy and better generalization ability. Conclusion: The framework is of great significance for improving the level of power supply service.

Background. Non-small-cell lung carcinoma (abbreviated as NSCLC) progresses rapidly and lacks appropriate biological markers. Recent studies have shown that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) has potential application value for clinically diagnosing lung carcinoma. Thus, this study conducted a systematic review and meta-analysis for assessing if MALAT-1 has a relationship to NSCLC outcome. Methods. This study conducted the search of China National Knowledge Infrastructure, China Science and Technology Journal, SinoMed, EMBASE, Cochrane library, Web of Science, Wanfang database, and PubMed from inception to September, 1, 2021. The published article about MALAT-l expression for NSCLC patients was analyzed. We used combined hazard rates under the confidence interval of 95% for examining the relationship of MALAT-l and NSCLC.Results. In this meta-analysis, we found that 10 studies were included, and MALAT-1 expressions were distinctly related to an unfavorable overall survival (HR: 2.34 (1.65, 3.33); I2 = 76%). Considering the merger’s clinical heterogeneity, for meta-analysis, we used the random-effects method. Conclusion. Overexpression of MALAT-1 showed correlations to the less effective outcome of NSCLC. MALAT-1 might be a new NSCLC prognosis marker.

Objectives: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains. Methods: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies. Results: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus.Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13–18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P

Purpose To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. Methods The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. Results GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. Conclusion GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.

Background Epiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Whether EREG can stimulate the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) in inflammatory environment is not clear. The purpose of the present study is to investigate the role of EREG on the osteo/dentinogenic differentiation ability of DPSCs in inflammatory environment. Methods DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) were used to knock down EREG expression in DPSCs. Recombinant human EREG (rhEREG) protein was used in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real-time RT-PCR were performed to detect osteo/dentinogenic differentiation markers and related signalling pathways under normal and inflammatory conditions. Results EREG depletion promoted the ALP activity and mineralization ability of DPSCs. The expression of BSP, DMP-1, and DSPP was also enhanced. Moreover, 50 ng/mL rhEREG treatment decreased the osteo/dentinogenic differentiation potential of DPSCs, while treatment with 10 ng/mL TNF-α for 4 h increased the expression of EREG in DPSCs. Conversely, EREG knockdown rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanistic studies showed that EREG depletion activated the p38 MAPK and Erk signalling pathways in DPSCs under normal and inflammatory conditions. Conclusions Our results demonstrated that EREG could inhibit the osteo/dentinogenic differentiation potential of DPSCs via the p38 MAPK and Erk signalling pathways. Under inflammatory environment, EREG depletion enhanced osteo/dentinogenic differentiation potential of DPSCs by improving the expression of p-p38 MAPK and p-Erk.

Objective:The aim of this study was to assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with coronavirus disease 2019 (COVID-19).Methods:A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Illness Perception Questionnaire (IPQ), and Profile of Mood States (POMS) were used to measure the current status of participants.Results:The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r = 0.265; P = 0.004) and total score of disease-related knowledge (r = 0.206; P = 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r = −0.182; P = 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P < 0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P < 0.05).Conclusions:It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.

A few mode fiber temperature sensor filled with PDMS based on vernier effect is proposed. It uses single mode fiber (SMF), few mode fiber (FMF), and polydimethylsiloxane (PDMS) to form the SMF-air microcavity-FMF-PDMS-FMF structure. It is to slot the glass capillary tube, place the two FMFs in the slot at a suitable distance, and fill the slot with PDMS multiple times and seal it. The PDMS is used as a sensing microcavity. We insert the SMF from the other end of the glass capillary tube, adjust the distance, fix the SMF and seal the connection. Two end faces of the SMF and the first FMF form an air reference microcavity. Since the refractive index of each medium is different, multiple reflective surfaces are formed to reflect. Because the second FMF is infinitely long, whose right end is beveled, it is considered that the sensor has four reflected beams. When the temperature changes, the length and refractive index of the PDMS microcavity will change, which will cause a change in the interference spectrum of the sensor. And because the vernier effect is formed by the superposition of the two microcavities, the temperature sensitivity can be amplified and the temperature can be measured with high sensitivity. The experimental results show that in the range of 40–56°C, the transmission spectrum of the sensor appears red shift with the increase of temperature, and the temperature sensitivity can reach 3.89nm/°C. The sensor is simple to manufacture, has high sensitivity, and has good application prospects.

OBJECTIVE The psychological resilience of postoperative non-small cell lung cancer (NSCLC) patients is influenced by many factors. The purpose of this study is to investigate the current state of psychological resilience and identify its influencing factors in postoperative NSCLC patients. METHODS This descriptive cross-sectional study used a convenience sampling method and recruited 382 inpatients from two Class A hospitals in Hunan, China. The Connor-Davidson Resilience Scale (CD-RISC), Strategies Used by People to Promote Health (SUPHH), Medical Coping Modes Questionnaire (MCMQ), and Multidimensional Scale of Perceived Social Support (MSPSS) were used. RESULTS Postoperative NSCLC patients' psychological resilience was at a low level, with a score of (57.18 ± 8.55). Stepped Linear Regression showed that the related influencing factors of psychological resilience of postoperative NSCLC patients were age (β = -0.313, P

Objective: To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation (CUMS) combined with social isolation. Methods: Fifty male SD rats were randomly divided into a blank group, model group, fluoxetine group, Chaiqinwendan decoction group, and Fuhe decoction group. Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model. After 42 days of administration, a tail suspension test and high-performance liquid electrochemical detection (HPLC-ECD) were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine (NE), dopamine (DA), 5-hydroxytrytamine (5-HT), and metabolites in different brain regions of rats in each group before and after treatment. Results: Compared with the model group, the epinephrine (E) content in the Fuhe decoction group was highly significantly increased (P

Solid oxide fuel cells (SOFCs) as one of the clean electrochemical energy conversion devices have acquired increasing attention recently due to the high efficiency, low emission, and excellent fuel...

Objective To compare the clinical efficacy and safety of a personalized three‐dimensional (3D) printed dynamic anterior plate–screw system for the quadrilateral area (DAPSQ) titanium plate and a traditional DAPSQ reconstruction plate in the treatment of double‐column acetabular fractures. Methods This was a retrospective case‐control study. From May 2014 to January 2018, 43 patients with double‐column acetabular fractures underwent open reduction and internal fixation. Among these, 20 cases were fixed with a 3D printed DAPSQ plate (3D printed group) and 23 cases were fixed with a DAPSQ reconstruction plate (control group). The 3D printed group comprised 15 men and 5 women, with an average age of 50.1 ± 8.2 years. The control group comprised 16 men and 7 women, with an average age of 51.0 ± 8.6 years. The evaluation index included the surgical data (i.e. blood loss, operating time, duration of hospital stay, and intraoperative and postoperative complications), position and length of implants, reduction quality, hip function, and related complications. The reduction quality was evaluated using the Matta scoring standard and hip function was evaluated using the modified Merle d’Aubigné score. Results A total of 43 patients met the inclusion criteria. The mean postoperative follow up was 35.2 months in the 3D printed group and 36.9 months in the control group. There were no significant group differences in demographic data between the two groups. The position and length of the 3D printed implants were generally in accord with preoperative planning using a 3D pelvic model. Patients in the 3D printed group had significantly shorter operation time (223.2 vs 260.5 min, P 0.05). The general complication rate in the 3D printed group and the control group was 15% and 26.1%, respectively, but the difference between the two groups was not statistically significant. Conclusion Use of a personalized 3D printed DAPSQ plate has potential advantages in reducing the operation time and blood loss during the treatment of double‐column acetabular fractures.

Renewable and clean energy supplies are highly critical for the reduction of greenhouse emissions and environmental pollution to realize a sustainable society. Among various techniques for using sustainable energy sources, such as solar energy, photocatalysis plays a crucial role in solving global problems, such as the energy crisis and environmental pollution. Thus, the design and development of Earth-abundant, low-cost, high-performance photocatalysts for water splitting and wastewater treatment are critical. Among these photocatalysts, Ruddlesden–Popper (RP) perovskites have attracted increasing attention in photocatalysis as a result of their unique structural, electronic, and optical characteristics. In this review, the recent advances of RP perovskites in photocatalysis are presented. The review begins with an introduction of the unique features of RP perovskites that are suitable for photocatalysis, which is followed by a discussion of the use of typical RP-type perovskite oxides as photocatalysts by highlighting several useful design strategies. Finally, the conclusions of this review, along with current challenges and future directions for the design of RP perovskites for photocatalysis, are presented and discussed. This review aims to provide helpful guidance for the future development of RP-type perovskite oxides for photocatalysis-based water splitting and wastewater treatment.

Stroke is a major cause of death and disability in China, and no therapies have proven effective to prevent it. Popular belief holds that the lunar cycle affects human physiology, behavior, and health. The aim of our study is to determine whether the lunar cycle impacts the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)]. We retrospectively extracted the discharge registry data of all patients with first-ever acute stroke hospitalized in the affiliated hospital of Beijing University of Traditional Chinese Medicine during 2002-2015. The onset times of stroke were assigned to four primary lunar phases based on NASA definitions. Chi-square tests and multiple logistic regression analyses were used to estimate the association between the lunar cycle and stroke incidence with adjustment for age, sex and season. A total of 5,965 patients with stroke (4,909 admissions for ischemic stroke IS, 754 admissions for ICH, and 302 admissions for TIA) were evaluated in our study. Subgroup analysis indicated that the admission rates of different sexes for IS tended to have opposite variation during the four moon phases. More female patients were admitted during the new moon than in the first and third quarters, while fewer male patients were admitted during the new moon than in the first and third quarters (χ2 = 15.589, P = .001). Multiple logistic regression analyses revealed that men were more likely to be admitted for IS in the first quarter than during the new moon (odds ratio [OR] = 1.252, 95% confidence interval [CI] = 1.076-1.456) (P = .004), and a corresponding trend was also identified for the third quarter (OR = 1.235, 95% CI = 1.062-1.437) (P = .006). No significant gender differences were shown in ICH or TIA. No sex difference is obvious during the full moon. Moon phases seem to affect both genders, but in very different ways. It seems that the new moon is a protective factor for male ischemic stroke patients and a risk factor for female ones. Woman tends to be more vulnerable than ever at the new moon, so deserves more attention and care. The mechanisms underlying this observation are worth studying further.

To observe the effect of moxibustion at Feishu (BL 13) on related inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid of asthma model rats, and to explore the mechanism of moxibustion in treating asthma. A total of 48 Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a moxibustion group and a medication group, with 12 rats in each group. Except for the normal group, the rats in the other three groups were subjected to ovalbumin sensitization to stimulate the asthma. At the same time, rats in the moxibustion group received moxibustion at bilateral Feishu (BL 13), and rats in the medication group received dexamethasone by intragastric administration. Rats in the normal and the model groups only received the same fixation and normal saline by intragastric administration. After the interventions, the inspiratory resistance, the expiratory resistance, and the pulmonary compliance were measured for rats in each group; the numbers of the inflammatory cells in the bronchoalveolar lavage fluid were counted; the levels of the involved inflammatory factors in bronchoalveolar lavage fluid were detected; the pathological morphologies of the lung tissues were observed under light microscope. After modeling, compared with the normal group, the rats in the model group showed obvious asthma attack-like response, significantly increased inspiratory resistance and expiratory resistance (both P 0.05). Both moxibustion at Feishu (BL 13) and intragastric administration of dexamethasone can improve the asthma attack-like symptoms of ovalbumin-sensitized rats; regulating the inflammatory cell numbers and the inflammatory factor contents in the lung may be one mechanism of moxibustion in treating asthma.

Objective Patients with HER2-positive metastatic breast cancer (MBC) benefit from trastuzumab-based therapy but eventually develop intrinsic or acquired resistance. Whether plasma HER2 gene copy number (GCN) could predict survival after trastuzumab treatment remained controversial. We evaluated the prognostic value of plasma HER2 GCN using low-coverage whole-genome sequencing (LC-WGS). Methods The plasma was collected from HER2-positive MBC patients whose pre-therapeutic samples were available before first-line trastuzumab-based treatment. Plasma DNA was extracted and assessed by LC-WGS for HER2 GCN. The optimal cut-off point for HER2 GCN to shorter survival was determined by receiver operating characteristic (ROC) curve analysis. Results A total of 49 patients were retrieved from 2013 to 2017, among whom 21 had multiple organ involvement (≥3 sites). Variations of HER2 GCN in pre-therapeutic plasma ranged from 1.89 to 23.86 (median = 2.59). ROC analysis identified the optimal cut-off point for HER2 GCN as 2.82 (P = 0.005), with 23 patients had high-level HER2 GCN and 26 in the low-level group. Both progression-free survival (PFS, P = 0.032) and overall survival (OS, P = 0.006) were adversely associated with high-level HER2 GCN. In multivariate analyses, high HER2 GCN was independently associated with shorter PFS [hazard ratio (HR) = 2.042, P = 0.037], while both high HER2 GCN (HR = 4.909, P = 0.004) and more metastatic organs (HR = 4.019, P = 0.011) were negative prognostic factors for OS. Conclusion In this population of patients with HER2-positive MBC, individuals with high HER2 GCNs in plasma had worse prognosis after trastuzumab-based therapy. Plasma HER2 GCN may be a prognostic marker in these patients.

Objective: Findings on the effect of the lunar cycle on mental illness are conflicting. We investigated the association between the lunar cycle and a number of psychiatric presentations of schizophrenia and determined which subtypes were susceptible to lunar phases.Methods: We evaluated 13,067 patients admitted to Zhumadian Psychiatric Hospital between January 1, 2012, and December 31, 2017 (73 lunar cycles). Patients were retrospectively assigned to lunar phase based on their admission date: new moon +/- 1 day, first quarter +/- 1 day, full moon +/- 1 day, and third quarter +/- 1 day. The International Statistical Classification of Diseases, 10th revision (ICD-10), was used for diagnosis. We used a Chi-squared goodness of fit test to evaluate the distribution of admissions across the lunar phase and R*C Chi-squared tests to compare age, sex, birth season, and clinical subtype distributions by phase. We used multiple logistic regression to further identify the relationship between clinical subtype and lunar phase.Results: Psychiatric admissions for schizophrenia varied significantly across the lunar cycle (χ2 = 36.400, p .05).Conclusions: Psychiatric admissions for schizophrenia show lunar periodicities. People with schizophrenia tend to be stable in the new moon, but their condition is easily aggravated during the first quarter and full moon. Patients with paranoid schizophrenia are more susceptible to deterioration at the full moon, so merit more attention and care from communities, families, and hospitals.

BACKGROUND: Many studies have investigated the association between matrix metalloproteinase polymorphisms and lung cancer susceptibility. However, the results are still controversial. To clarify these associations, we conducted a meta-analysis. METHODS: A systematic search of studies was conducted in PubMed, Embase, and China National Knowledge Infrastructure. Overall and subgroup analysis stratified by ethnicity was conducted. OR with 95% CI was used to assess the strength of the association. Furthermore, false-positive report probability (FPRP) tests were also performed for associations obtained in this meta-analysis. RESULTS: Twenty-four studies, including 10,099 cases and 9,395 controls, were analyzed. Nine polymorphisms were reported. For MMP1 -1607 1G/2G and MMP7 -181 A/G, increased lung cancer risk was found in Asians. For MMP2 -1306 C/T and MMP2 -735 C/T, decreased lung cancer risk was found in both “diverse populations” and Asians. For MMP9 -1562, C/T decreased lung cancer risk was found in both “diverse populations” and Caucasians. For MMP13 -77A/G, the A/G genotype decreased lung cancer risk in Asians. However, only associations between MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -735 C/T, and MMP7 -181 A/G and lung cancer risk were considered noteworthy according to FPRP tests. There was no association between MMP3 -1171 5A/6A, MMP9 R279Q, and MMP12 -82A/G and lung cancer risk. CONCLUSIONS: Our meta-analysis suggested that MMP1 -1607 1G/2G and MMP7 -181 A/G were risk factors for lung cancer, while MMP2 -1306 C/T, MMP2 -735 C/T, MMP9 -1562 C/T, and MMP13 -77A/G might be protective factors. However, results for MMP9 -1562 C/T and MMP13 -77A/G should be interpreted with caution due to the probability of false-positive reports.

Background: Androgen receptor (AR) blocker has become an increased interest in the treatment of BC, in which about 60-80% patients showed AR positive. However, currently no AR blocker has been approved in mBC. GT0918 is a new chemical entity of AR blocker with possible AR down-regulation. This study is an open-label, single-center, dose escalation phase I trial to assess GT0918 in mBC female patients who have progressed after systemic treatments in China. The primary objectives are to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). The secondary objectives are to assess pharmacokinetics and pharmacodynamics of GT0918 with single and multiple dosage applications. (CTR20170757) Methods: Patients (pts) with historically confirmed mBC who had progressed after either chemotherapy, hormonal or targeted therapy, or could not tolerate currently standard therapies were eligible. With the starting dose at 100 mg of GT0918, the decision of dose escalation in the 3+3 design was based on the safety and tolerability assessments. GT0918 was administered orally once, followed by a 7-day off-treatment period for single dose PK analysis of drug elimination. Then GT0918 oral administration was resumed once daily for 28 consecutive days and multiple dose PK analysis was assessed at the end of first cycle (28 days). The first 28-days on treatment (cycle 1) was defined as DLT period. Pts manifesting an objective response or stable disease and likely to have clinical benefit from continued treatment were continued on GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 18 pts were enrolled and treated with GT0918 since 9/6/2017 as defined in protocol at five dose levels: 100 mg (n = 3), 200 mg (n = 4), 300 mg (n = 4), 400 mg (n = 4) and 500 mg (n = 3) (as to 7/2/2019). All pts progressed more than two lines of therapies with 83.3% (15/18) pts were treated ≥3rd lines. Out of 6 confirmed AR positive pts, two (33.3%) at 300 mg cohort had finished 17 and 19 cycles individually and continue treatment (as 7/2/19). No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03, including fatigue, hypertriglyceridemia, anemia, hypercholesterolemia, increased LDL, nausea, loss of appetite, increased ALT, increase of weight loss, constipation and thrombocytopenia. PK profile analysis showed that in the single-dose study, GT0918 showed a fast absorption profile. In the multiple-dose study, the steady-state serum concentration level of GT0918 and its main metabolite were attained at 21 days. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated in late-stage pts. No DLT has occurred at maximum dose 500 mg. Pts with AR positive biomarker could have better clinical outcomes with GT0918 treatment. GT0918 and its main metabolite exhibited a nonlinear pharmacokinetic profile over the dose range from 100mg to 500 mg. An expanded/phase Ib in AR positive mBC pts has launched in China to evaluate the anti-tumor activity and safety of GT0918. 200 mg and 300 mg were selected for dose expansion. Citation Format: Huiping Li, Ran Ran, Guohong Song, Hanfang Jiang, Ruyan Zhang, Yaxin Liu, Luping Meng, Phoebe Zhang, Ke Chen, Qiaoxia Zhou, Karl Zhou, Youzhi Tong. Evaluation of safety, pharmacokinetics and pharmacodynamics of proxalutamide (GT0918), a potent androgen receptor (AR) blocker, in patients with metastatic breast cancer (mBC): Phase I dose escalation trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-05.

Background: Angiogenesis is a key mechanism of tumour growth. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2) and blocks downstream signalling and inhibiting tumour angiogenesis. It was approved in China to treat gastric cancer in October 2014. However, as breast cancer with a chest wall metastasis (CWM) has rich vascular distribution, whether Apatinib is also effective for breast cancer with a chest wall metastasis remains unknown. Therefore, we designed this clinical study to address this question. Method: The trial involved four centres in China from September 2016 to July 2019. It enrolled patients (pts) who were diagnosed of HER2 negative breast cancer with CWM and experienced first line or could not afford standard treatment. The patients were given Apatinib 500mg/day (single or combined with endocrine therapy if hormone receptor positive (HR+)) until progression or side effect not tolerated. Each patient had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1.This study was approved by ethics committee at the Ethics Committee of Beijing Cancer Hospital, and all participants provided written informed consent. The trial was also Register to clinicaltrial.gov ( NCT02878057). Results: 30 pts were enrolled in the study with a median age of 50 (range 35-69) years old. Among the 30 pts, there were 23 ER positive pts (76.7%). 17 pts (56.7%) had more than 2 sites of metastasis, and 5 pts had invasive metastasis (16.6%). 15 pts (50%) were multi pre-treated. The response of 19 pts (63.3%) could be evaluated, and the overall response rate was 57.9% (no CR, 11 cases reached PR, 2 in HR-, 9 in HR+). and the median PFS was 8.6 months (range 0.5-29.5; 95% CI 0.0-18.7). The tumour in chest wall shrunk obviously. Side effects also existed. 15 pts (50%) had hypertension (grade 3: 6.7%); 10 pts (33.3%) had proteinuria (grade 3: 20%); 4 pts (13.3%) had fatigue (grade 3: 3.3%); 3 pts (10%) had bilirubin increase (grade 3: 6.7%). 8 pts discontinued the treatment due to side effects and 3 due to personal reasons. The Apatinib dose was reduced from 500mg to 250mg for most pts 18/30 (60%), and some pts took 500 mg and 250 mg every other day 10/30 (33.3). Conclusion: Apatinib was effective for pts with chest wall metastasis and pts could benefit from longer PFS. However, the side effects should be pay more attention from start on apatinib treatment. Citation Format: Huiping Li, Cuizhi Geng, Guohong Song, Hanfang Jiang, Zhongshen Tong, Junlan Yang, Ran Ran, Ruyan Zhang, Yaxin Liu, Xinyu Gui, Maorong Wei, Lu Xue. Apatinib in the treatment of HER-2 negative advanced breast cancer with chest wall metastasis multicenter phase II clinical study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-40.

Background: Fulvestrant 500mg has been proved better efficacy in breast cancer with hormone receptor positive (HR+),and then become an optional strategy for primary or second line treatment of HR+ positive metastasis breast cancer (MBC). Methods: In this real world study, we retrospectively analyzed the patients with HR+ HER 2 negative MBC who received fulvestrant 500mg treatment at Beijing cancer hospital during January 2015 to December 2018. Clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS) and adverse events were investigated. Results: There were 306 patients enrolled, median age was 48.7(range 20-75) years, median line of fulvestrant was 2.11(range 1-6), 68.3%(209/306) patients were involved with visceral metastasis. The CBR was 68.6%, median PFS was 8.41m (95%CI: 7.079m-9.743m, range 0.89m-80.16m). Among the patients received fulvestrant at the first line, the PFS was 10.55m(95%CI:6.46m-14.64m, range 0.92m-34.3m). The median OS hasn’t been obtained. In subgroup analysis, the patients without liver metastasis(12.49m vs. 4.60m, p4, 12.65m vs. 7.72m vs. 3.98m respectively, p2 lines, 14.06m vs. 7.79m vs. 3.52m respectively, p Conclusions: Fulvestrant was an effective and safe regimen in endocrine therapy for hormone receptor positive HER2 negative MBC. The patients who were in first line treatment, absence of liver metastasis and small tumor burden might be more benefit from fulvestrant. Corresponding authors: Huiping Li, huipingli2012@hotmail.com; Guohong Song, songguohong918@hotmail.com, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Beijing 100142, China Citation Format: Wen Lei, Huiping Li, Guohong Song, Ruyan Zhang, Ran Ran, Ying Yan. Efficacy observation of 306 patients with fulvestrant 500mg treatment in hormone-receptor positive HER2 negative metastasis breast cancer, a real world study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-20.

Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.

Background A brachial plexus block (BPB) provides anesthesia and analgesia with limited duration. Various opioids have been used as adjuvants of local anesthetics to improve the effects. Objective The objective of this study was to evaluate the safety and effectiveness of nalbuphine used as an adjuvant to local anesthetic during the supraclavicular BPB. Materials and methods In this prospective, double-blinded, randomized controlled study, 90 American Society of Anesthesiology (ASA) Physical Status I and II patients (aged 20 to 65 y) of either sex undergoing upper limb orthopedic surgeries under ultrasound-guided supraclavicular BPB were randomly allocated into 3 groups: group C (n=30), group NL (n=30), and group NH (n=30) for analyses. Each patient received 18 mL of 100 mg ropivacaine solution combined with 2 mL of normal saline, 2 mL of 10 mg nalbuphine, or 2 mL of 20 mg nalbuphine. The time of onset and block duration of sensory block (SB) and motor block (MB), duration of analgesia, hemodynamic variables, and any adverse effects were assessed. Results Compared with group C, the onset time of both SB and MB were significantly shortened. The SB and MB duration were significantly prolonged in group NL and group NH. There was no significant difference between the duration of analgesia in group NL and NH although the analgesia duration of both groups was longer than group C. But the incidence of side effects in group NH such as vomiting was significantly higher than group NL. Conclusions Nalbuphine is an effective adjuvant to 0.5% ropivacaine in ultrasound-guided supraclavicular BPB. The dosage of 10 mg improves the quality of the anesthesia with less incidence of side effects.

Hyperactivity of the hypothalamic-pituitary-adrenal axis and impairment of the central corticotropin-releasing factor system are factors in the pathogenesis of depression. Though several antagonists of the corticotropin-releasing factor 1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between corticotropin-releasing factor 1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of CP154526, a corticotropin-releasing factor 1 receptor blocker, which presented some signs of depression. Our results revealed that CP154526 (5 and 10 mg/kg) or fluoxetine (10 mg/kg) treatment notably improved the sucrose consumption, produced anti-depressive-like behavior in open-field test, as well as immobility time in forced swimming test. The levels of interleukin-6, interleukin-1β, tumor necrosis factor-α, and corticotropin-releasing hormone concentration in the serum were inhibited effectively by CP154526 or fluoxetine administration. Real-time quantitative PCR and western blot analysis showed the upregulated levels of brain-derived neurotrophic factor and growth associated protein 43 (GAP43) in the hypothalamus of the rats exposed to chronic unpredictable mild stress (CUMS), while different degrees of downregulation in their expression were detected after CP154526 (5 and 10 mg/kg) or fluoxetine (10 mg/kg) treatment, respectively. Thus, our data demonstrated that CP154526 exhibited antidepressant effect in CUMS rats, which might be mediated by decreasing the brain-derived neurotrophic factor and GAP43 expression in the hypothalamus.

Objective Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer. Methods This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity. Results Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg bid, with a half-life of 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (gBRCA Mut) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somaticBRCA Mut). Conclusions The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCA Mut and platinum-sensitive OC.

Background: Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2˗) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2˗ Chinese advanced breast cancer patients. Method: HR+/HER2˗ advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. Result: In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2˗ metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.

Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glubecame hypoactive after nerve injury. Although a brief activation of the MCC Cg2Gluto ZIGABAcircuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Gluconstitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Gluto ZIGABAcircuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENTGlutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Gluand the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Gluhave an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.

BACKGROUND The incidence of metabolic syndrome (MetS) is increasing, and n-3 polyunsaturated fatty acids (PUFAs) in salmon (Oncorhynchus) phospholipids can effectively reduce the risk of MetS. RESULTS Under the intervention of 4% salmon phospholipid, the levels of fasting blood glucose (FBG), insulin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the plasma of MetS mice, whereas adiponectin was significantly increased. By screening, we found that the 18 differential metabolites, consisting of seven triglycerides (TGs), six diglycerides (DGs), one phosphatidylethanolamine (PE), three sphingomyelins (SMs) and one eicosanoid, could be the key differential metabolites, and two metabolic pathways were significantly affected: glycerolipid metabolism and glycerophospholipid metabolism. CONCLUSION 4% salmon phospholipids could affect MetS by inhibiting insulin resistance, reducing inflammatory factors and promoting the synthesis of PE, yet the mechanism required further study. Our results could help in the treatment of MetS. © 2021 Society of Chemical Industry.

Background: Previous study have shown that seizures may occur as a result of vaccination. This study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated with COVID-19 and to provide reference opinions for PWE to receive COVID-19 vaccine.Methods: We retrospectively enrolled PWE patients who were vaccinated against COVID-19 in the epilepsy centers of nine hospitals in China. The binary logistic regression analysis included variables with a P-value less than 0.1 in the univariate analysis.Results: The study included 290 patients, of which 40 (13.8%) developed seizures within 14 days after vaccination, whereas 250 (86.2%) remained seizure-free. The binary logistic regression analysis revealed statistical significance in seizures within three months before vaccination (PConclusions: SARS-CoV-2 may induce epilepsy through an inflammatory cascade. It is recommended to provide the COVID-19 vaccine to seizure-free patients for at least three months before vaccination, and the vaccination is safer if EEG result is normal. During peri-vaccination period, all PWE should be prohibited from reducing ASM dosage. PWE with well-controlled seizures who have discontinued ASM might consider resuming ASM during the peri-vaccination period if their EEG results are aberrant.

Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies.Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province.Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination.Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.

OBJECTIVES Genetic factors play an important role in the onset of epilepsy, and the involvement of the RELN gene was recently discovered. This paper reports a family with a history of epilepsy caused by a heterozygous missense mutation in the RELN gene. METHODS After a clear diagnosis was made in the proband with a family history of epilepsy, gene sequencing was performed on the proband and his family members. RESULTS The proband was a 19-year-old male who presented with general convulsions during sleep lasting for about 1 min and was relieved spontaneously. His father and grandmother also experienced seizures. The gene sequencing results of the proband, his mother, and his grandmother showed that both the proband and his grandmother carried the same heterozygous missense mutation in the RELN gene (c.7909 C > T), unlike the proband's mother. DISCUSSION Mutations in the RELN gene can lead to the occurrence of benign epilepsy, though the specific type of seizures that it can cause is still unclear, and may increase the susceptibility to epilepsy. In addition, it may have potential anticancer effects.

Purpose: To assess neural changes in perceptual effects induced by myopic defocus and hyperopic defocus stimuli in ametropic and emmetropic subjects using functional magnetic resonance imaging (fMRI).Methods: This study included 41 subjects with a mean age of 26.0 ± 2.9 years. The mean spherical equivalence refraction was −0.54 ± 0.51D in the emmetropic group and −3.57 ± 2.27D in the ametropic group. The subjects were instructed to view through full refractive correction, with values of +2.00D to induce myopic defocus state and −2.00D to induce hyperopic defocus state. This was carried over in three random sessions. Arterial spin labeling (ASL) perfusion was measured using fMRI to obtain quantified regional cerebral blood flow (rCBF). Behavioral tests including distant visual acuity (VA) and contrast sensitivity (CS), were measured every 5 min for 30 min.Results: Myopic defocus induced significantly greater rCBF increase in four cerebral regions compared with full correction: right precentral gyrus, right superior temporal gyrus, left inferior parietal lobule, and left middle temporal gyrus (P < 0.001). The differences were less significant in low myopes than emmetropes. In the hyperopic defocus session, the increased responses of rCBF were only observed in the right and left precentral gyrus. Myopic defocused VA and CS improved significantly within 5 min and reached a plateau shortly after.Conclusion: This study revealed that myopic defocus stimuli can significantly increase blood perfusion in visual attention-related cerebral regions, which suggests a potential direction for future investigation on the relationship between retinal defocus and its neural consequences.

WHAT IS KNOWN AND OBJECTIVE To compare the effectiveness and safety of remimazolam tosylate and propofol for hysteroscopy. METHODS From November 2020 to June 2021, a total of 90 patients who underwent hysteroscopy were prospectively enrolled in this study. The patients were randomly assigned to three groups: propofol group (group A), low-dose remimazolam tosylate group (group B), and high-dose remimazolam tosylate group (group C), with 30 cases in each group. All cases received intravenous sufentanil 0.1ug/kg for analgesic preconditioning. Patients in group A were given 2 mg/kg propofol intravenously, and maintained at a rate of 5 mg/kg/h. Patients in groups B and C were given intravenous remimazolam tosylate 0.25 mg/kg. Group B was maintained with remimazolam tosylate at a rate of 0.48 mg/kg/h, while group C was at a rate of 0.6 mg/kg/h. The changes of heart rate (HR), mean arterial pressure (MAP) and saturation of peripheral oxygen (SpO2) were recorded after admission (T0), 1 min after anaesthesia (T1), dilation of the uterine cavity (T2), and the end of hysteroscopy (T3). In addition, Observer's Assessment of Alertness/Sedation Scale (OAA/S) at 1 min, 3 min, and 5 min after hysteroscopy, the incidence of adverse events, and the time from the end of the hysteroscopy to reach the discharge standard, were recorded. RESULTS AND DISCUSSION The success rate of sedation in each group was 100%. After administration, the adverse event incidence in group A was significantly higher than that in groups B and C (p

Purpose To determine the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screen on vancomycin duration in critically ill patients with suspected pneumonia. Methods This was a retrospective, quasi-experimental study at a 613-bed academic medical center with 67 intensive care beds. Adult patients admitted to the intensive care unit (ICU) between 2017 and 2019 for 24 hours or longer and empirically started on intravenous vancomycin for pneumonia were included. The primary intervention was the implementation of a MRSA nasal PCR screen protocol. The primary outcome was duration of empiric vancomycin therapy. Secondary outcomes included the rate of acute kidney injury (AKI), the number of vancomycin levels obtained, the rate of resumption of vancomycin for treatment of pneumonia, ICU length of stay, hospital length of stay, the rate of ICU readmission, and the rate of in-hospital mortality. Results A total of 418 patients were included in the final analysis. The median vancomycin duration was 2.59 days in the preprotocol group and 1.44 days in the postprotocol group, a reduction of approximately 1.00 day (P < 0.01). There were significantly fewer vancomycin levels measured in the postprotocol group than in the preprotocol group. Secondary outcomes were similar between the 2 groups, except that there was a lower rate of AKI and fewer vancomycin levels obtained in the postprotocol group (despite implementation of area under the curve–based vancomycin dosing) as compared to the preprotocol group. Conclusion The implementation of a pharmacist-driven MRSA nasal PCR screen was associated with a decrease in vancomycin duration and the number of vancomycin levels obtained in critically ill patients with suspected pneumonia.

PURPOSE To compare the survival outcome between radical hysterectomy and simple hysterectomy with radiation therapy in patients with stage II endometrial cancer. MATERIALS AND METHODS This is a retrospective cohort study based on the SEER database from January 1, 1988 to December 31, 2015. RESULTS Of 577 patients were enrolled in the study, 117 patients received radical hysterectomy and 460 patients received simple hysterectomy combined with vaginal brachytherapy. All patients received external beam radiation therapy after the surgery. The median follow-up duration was 82.77 ± 1.44 months. No differences were found on the baseline information between two groups. Both the 5-year overall survival (62.31% vs. 78.48%, p

Background Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients. Methods We conducted a case–control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique. Results There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group. Conclusions Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.

Recently, convolutional neural networks (CNNs) have been introduced to pansharpening for enhancing fusion accuracy and overcoming the drawbacks of the conventional methods. However, most of methods based on CNN fail to distinguish the difference of multispectral bands, and only use a uniform set of convolutional kernels to extract features. In this paper, we design a progressive, band-separated convolutional network architecture for discriminatively learning the features and relation among spectral bands, aiming to address the problem mentioned before. More specifically, the proposed architecture mainly consists of three aspects. First, to accurately preserve the spectral peculiarities, we divide the multispectral input image in terms of its bands into several groups. Second, our original panchromatic and multispectral inputs are filtered by a high-pass operation to further yield more spatial details. Third, we use a spectral fusion module (SFM) for each group and associate them to progressively assemble the whole architecture. It is worth mentioning that the architecture could be integrated into any other competitive CNNs to improve the performance. Both visual and quantitative experiments have demonstrated that our proposed method outperforms recent state-of-the-art pansharpening techniques.

Objective: This study aimed to investigate epidemiological characteristics, clinical manifestations, and long-term outcomes of patients with autoimmune encephalitis (AE) in the east of China.Methods: From January 2015 to December 2019, 226 potential AE patients were recruited from five clinical centers, and a total of 185 patients who met the diagnostic criteria were included in the study. We retrospectively reviewed clinical features, auxiliary examinations, details of treatments, and outcomes of AE, and identified risk factors of poor prognosis. Modified Rankin Scale scores were used to evaluate neurological function, and scores of 3–6 indicated a poor-prognosis.Results: Patients with five main subtypes of AE were enrolled in the study, as follows: anti-NMDAR (79), anti-LGI1 (55), anti-CASPR2 (30), anti-GABABR (16), and anti-AMPAR (5). Among 185 patients, 58.38% (108/185) were male and 41.62% (77/185) were female. The median age at disease onset was 41 years (interquartile range, 17–62). The most common clinical manifestations of AE were seizures (146, 78.92%) and memory deficit (123, 66.49%). A total of 95 (51.35%) patients had abnormal brain magnetic resonance imaging results. Electroencephalographic findings were abnormal in 131 (70.81%) patients, and 168 (90.81%) and 26 (14.05%) patients were treated with first- and second-line immunotherapies, respectively. All surviving patients were followed-up for at least 1 year (range 12–36 months). Good clinical outcomes were achieved in 117 (63.24%), while 68 (36.76%) patients had a poor prognosis. Further, 33 (17.84%) patients relapsed and 10 (5.41%) died within 1 year post-discharge. Older patients tended to have a poorer prognosis, and the occurrence of mental behavioral disorders, movement disorders, disturbance of consciousness, central hypoventilation, and tumors were overrepresented in the poor-prognosis group.Conclusions: AE is a treatable disease, and most patients have a good prognosis. There are differences in the clinical manifestations of patients with different AE subtypes. Some with AE will relapse, and long-term follow-up is of great significance for further research.

OBJECTIVE To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. METHODS We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. RESULTS Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p > .05). The value between SCLC and non-SCLC subgroup was significantly different (p

Utilizing the 1-3 piezoelectric composite and double-layer matching structure, the study discusses the research of piezoelectric air-coupled transducer from multi-layer parallel structure. The multi-layer parallel structure owns the benefits of better electrical impedance and larger piezoelectric strain constant and the experimental outcomes verify that it is effective to perfect the performance of piezoelectric air-coupled transducer. According to above research, this paper also presents a seven-element auto-focused air-coupled transducer. In the end, the internal defects of honeycomb composite are measured utilizing the seven-element auto-focused air-coupled transducer under pitch-catch mode.

Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease.Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)−4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25− cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells.Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05).Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.

The aim of this study was to investigate the effectiveness of cognitive behavioral therapy (CBT) on improving the cognitive function in minor depression (MiD) and major depression (MaD). The study will constitute a placebo-controlled single-blind parallel-group randomized controlled trial. The selected participants will be randomly allocated into one of two parallel groups with a 1:1 ratio: the CBT-based group and the general health education group. CBT significantly alleviated depressive symptoms of MiD and MaD at 12 weeks (p < 0.001), and the treatment effect was maintained for at least 12 months (p < 0.001). Interestingly, CBT significantly promotes more cognitive function of MiD and partial cognitive function of MaD at 12 weeks in the intervention group than in the control group (p < 0.01). CBT can alleviate depressive symptoms of both minor and MaDs. The effectiveness of CBT is different on improving the cognitive function in MiD and MaD.

Background Transcutaneous electrical acupoint stimulation (TEAS), which is also known as acupuncture-like transcutaneous electrical nerve stimulation (TENS), has been widely used in acute or chronic pain. However, previous research has not demonstrated that TEAS is effective for cancer-related pain. Opioid drugs are strongly recommended for treating cancer-related pain, but opioid-induced immunosuppression is still the most intractable drug-induced medical problem. Evaluating the efficacy and potential advantage of TEAS combined with opioid drugs in moderate and severe cancer-related pain in China is important because such studies are lacking. Methods/Design This trial is a multicenter, prospective randomized controlled clinical trial. In total, 160 patients who were enrolled from two hospitals in the Zhejiang Province (China) will be randomly allocated into two groups: a TEAS group and sham TEAS group without acupoint electrical stimulation. Both groups will receive a 21-day interval of chemotherapy and conventional cancer pain therapy. Fifteen treatment sessions will be performed over a three-week period. The primary outcomes will be measured by changes in the Numerical Rating Scale (NRS) scores and equivalent dosage of morphine at baseline, three weeks of treatment and one two-week follow-up. The secondary outcome measures include cellular immunity function, life quality assessment, opioids side effects assessment, and safety and compliance evaluation. Discussion This trial is expected to clarify whether TEAS is effective for cancer-related pain. These results demonstrate the advantage of TEAS combined with opioid drugs on improving immune function and decreasing opioid induced side effects. Trial registration Chinese Clinical Trial Registry, ChiCTR-13003803. Registered on 27 August 2013. Electronic supplementary material The online version of this article (10.1186/s13063-018-3145-y) contains supplementary material, which is available to authorized users.

Peroxiredoxin 3 (PRX3) is predominantly located in mitochondria and plays a major role in scavenging hydrogen peroxide of mitochondria. In the present study, we detected plasma PRX3 in pregnant women receiving oral glucose tolerance test at 24–28 gestational weeks. Plasma PRX3 was significantly increased about 1 h later than insulin secretion. In vitro detection of PRX3 in mouse islet cells showed up-regulation by more than 2-fold at 1 h and reached its top at 2 h of glucose stimulation, and the PRX3 level in cultured mediums was concomitantly elevated in a glucose concentration-dependent manner. In addition, both fasting plasma insulin and PRX3 were significantly higher in the subjects of term pregnancy as compared to that at 24–28 gestational weeks, and there was a positive correlation between plasma PRX3 and insulin. Our results indicate that PRX3 plays an active role in the response to insulin release. The positive association of plasma PRX3 and insulin suggest PRX3 to be a potential indicator of high insulin resistance.

Background Psychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research. Methods This study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0–2/9, F33.0–2/9), and SZ (F20–20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method. Results PMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019–2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168–1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492–0.741), were more often divorced (OR 3.087, 95% CI 1.168–10.096), had a younger age of onset (OR 0.934, 95% CI 0.914–0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492–0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267–0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD. Conclusions PMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.

Background: Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia.Methods: In this study, we recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment.Results: Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p < 0.05), while such association was not found in further multiple regression analysis.Conclusions: Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia.Trial Registration: Clinicaltrials.gov, NCT02880462. Registered August 26, 2016.

Purpose: Autoimmune encephalitis (AE) is a heterogeneous neurological autoimmune disorder associated with cognitive and psychiatric symptoms. It can be divided into several subtypes based on autoantibodies. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis (AMPAR-E) is one of the recently discovered AE subtypes, usually manifesting limbic encephalitis and with a good prognosis. Considering AMPAR-E has been described for the first time, only a few cases with similar antibodies have been reported clinically. We aimed to clarify the clinical course and prognosis of the disease in the light of previous reports.Patients and Methods: We collected data on the diagnosis and treatment of six cases of AMPAR-E, diagnosed at the Qilu Hospital of Shandong University in the past 5 years. We retrospectively analyzed the clinical characteristics of the patients and performed a follow-up of the disease.Results: The patients often presented with limbic encephalitis, which sometimes coexisted with tumors. In addition, immunotherapy had a significant effect on the disease. The clinical outcome was related to factors such as the age of onset, timing of treatment, and presence of tumors.Conclusion: In conclusion, specific antibody tests should be performed as early as possible in suspected cases. Clinicians should actively administer immunotherapy and the management of the co-tumor. In addition, repeat antibody tests and image examinations following discharge from the hospital guide the maintenance protocol of immunotherapy.

Aiming at the problem that the current visualization analysis method of power enterprise data assets does not consider the design of data visualization analysis model, which leads to the low accuracy of the line chart formed by visualization, this paper proposes a data assets hot spot visualization analysis method based on data platform. Starting from the three problems of data assets, such as lack, error and repetition, this paper preprocesses the data assets of power enterprises, adopts the technology of data middle platform, establishes the framework of data middle platform to mine the hot spots of data assets of power enterprises. This paper designed a data visualization analysis model, build the visualization system structure of electric power enterprise data assets hot, implements the hot visualization of electric power enterprise data assets. The experimental results show that the line chart formed by the visualization analysis method of power enterprise data assets hot spot has high accuracy.

Background: Early-stage osteoarthritis (OA) is characterized by articular subchondral bone resorption and emerging evidence suggests that mechanical overloading is likely involved. Here, we identified whether and why mechanical overloading could trigger subchondral bone resorption in early-stage OA. Methods: A new mechanical overloading monitoring system for real-time pressure measurement in situ in vivo and a numerically controlled loading device for tissue pressurized culture in vitro were developed. Micro-CT was used to analyze the alterations of microarchitecture in subchondral bone and TRAP staining was harnessed to measure osteoclast differentiation of macrophages. Real-time qPCR, Western blot, ELISA, and immunostaining were conducted to clarify the expression, location, and interaction of relative proteins. Findings: Temporomandibular joint disc displacement yielded about 5 times higher pressure on the articular surface than that of the controls, causing subchondral bone resorption in 3-7 days after disc displacement. RANTES was increased in synovial fluid in early-stage OA in human and expressed in condylar cartilage of rat OA model at 1 week after disc displacement. Mechanistically, RANTES could promote osteoclast recruitment and formation through binding to its receptors CCRs and activating Akt2 pathway. Either Blockade of CCRs or Knockdown of Akt2 rescued RANTES-mediated osteoclast differentiation in vitro . Knockdown of Akt2 prevented the early subchondral bone resorption in OA in vivo. Interpretation: This study unravels a novel mechanism that disc displacement-induced mechanical overloading activates the RANTES-CCRs-Akt2 axis, which plays a critical initial role for the early condylar bone resorption in OA. Funding Information: This work was supported by grants from the National Natural Science Foundation of China (82170979, 81970920, 81772873). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The approval of synovial fluid experimentations was obtained from the Biomedical Institutional Review Board of the Peking University School and Hospital of Stomatology (PKUSSIRB-201947100), and written informed consents were attained from all participants. The approval of animal studies was obtained from the Peking University Animal Ethics Committee (LA2019310).

Background Intercostal artery pseudoaneurysm is rare and at the risk of rupture. The aetiology is always reported to be iatrogenic and traumatic injury. Embolisation is the most common therapeutic method. Here, we report a case of spontaneous intercostal artery pseudoaneurysm and cured by combining covered stent grafting and surgical management. Case presentation A 60-year-old man complained of acute right back pain for 5 h. Computed tomography showed right massive hemothorax and a giant mass with distinct feeding vessel originated from the thoracic aorta within the right hemithorax. Thoracocentesis was performed, and then a covered stent was positioned across the origin of the feeding vessel. The patient was diagnosed with intercostal artery pseudoaneurysm. Finally, we successfully resected the pseudoaneurysm and ligated the proximal part of the artery. Histologic examination have proved the diagnosis. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. There is no recurrence reported during follow-up. Conclusions Spontaneous intercostal artery pseudoaneurysm is extremly rare. Delayed hemothorax due to rupture of the pseudoaneurysm may occur years after the formation. Early diagnosis is important and a combined treatment of endovascular intervention and surgical management is feasible, especially for the case of ruptured large tumour-like mass presentation of the pseudoaneurysm.