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The southern Great Xing’an Range (SGXR), located in the eastern segment of the Central Asian Orogenic Belt (CAOB), is one of the most economically important Cu–Mo–Fe–Sn–Pb–Zn–Ag metallogenic provinces in China. The newly discovered Panjiaduan Cu–Pb–Zn deposit (9.3 Mt; at 1.36% Cu, 2.90% Pb, 3.80% Zn and 38.12 g/t Ag), located in the SE segment of the SGXR, is primarily hosted in fracture zones in volcanic rocks and granodiorite of the Manitu Formation. Four paragenetic stages of metallic mineralization are identified: (I) quartz-pyrite-arsenopyrite; (II) quartz-polymetallic sulphide; (III) quartz-galena-sphalerite-argentite; and (IV) quartz-calcite-minor sulphide. The hydrothermal quartz contains three types of primary fluid inclusion (FIs): vapour-rich two-phase liquid-vapour (LV-type), liquid-rich two-phase liquid-vapour (VL-type) and three-phase liquid-vapour-solid FIs (SL-type). Stages I and II contain all types with homogenization temperatures (Th) of 324–386 °C and 276–334 °C as well as salinities of 0.7–38.0 wt% and 0.9–34.7 wt%, respectively, whereas stage III is composed of VL- and LV-type FIs with Th of 210–269 °C and salinities of 0.5–7.2 wt%. Only VL-type FIs occur in stage IV, with Th of 139–185 °C and salinities of 1.6–4.2 wt%. The δ18OH2O and δD values vary from −15.7 to 2.6‰ and −132.7 to −110.2‰, respectively, indicating predominant meteoric water with an initial magmatic source. The He–Ar isotopic compositions of the pyrite inclusions from the Panjiaduan Cu–Pb–Zn veins suggest that fluids were derived from the crust.

Compound 1 represents an unprecedented meroterpenoid featuring a unique tricyclo [3,3,1,01′,5′] decane central framework and 2 possesses a rare 6/6/5/4 tetracyclic carbon skeleton were isolated from Fissistigma bracteolatum.

Chemical investigation on the roots and rhizomes of Nardostachys chinensis Batal led to the isolation of twenty-one sesquiterpenoids with various carbocyclic skeletons including three eudesmane-type (1-2, 4), nine nardosinane-type (3, 5-12), and nine aristolane-type sesquiterprenoids (13-21). The structures of the new compounds 1 and 3, and the new natural product 2 were established by extensive spectroscopic analysis, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. Nitric oxide (NO) is one of the most important inflammatory modulators in many inflammatory diseases. Thus, inhibitory effects of compounds 1-21 on NO production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and compounds 13-15 displayed NO inhibitory activity with IC50 values of 2.67, 2.79, 9.87 μM, respectively. Moreover, a further study revealed that compound 13 exhibited anti-inflammatory activity via suppression of IL-6, IL-10, and IL-23.

Eleven new seco-guaianolide sesquiterpenoids (1–11) and two new guaianolide dimers (12 and 13), along with five known guaianolide derivatives were isolated from the aerial part of Achillea alpina L. Compounds 1–3 represented three unique 2,3-oxygen inserted guaianolides and 4–8 were five special 3-nor guaianolide sesquiterpenoids. Compounds 9–11 were three novel 1,10-seco-guaianolides, while 12 and 13 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures of 1–13 including their absolute configurations were determined by spectroscopic data analysis, combined with quantum electronic circular dichroism (ECD) calculations. To evaluate the hypoglycemic activity of 1–18, glucose consumption was used to investigate in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells, and compound 9 displayed the strongest reversal IR activity. A mechanistic study has revealed that the potential compound 9 appeared to be mediated hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.

Background Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. Methods sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and β-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0–35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. Results We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. Conclusions LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Introduction Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke. Methods We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. Results Significant treatment–time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P

Background The purpose of this study was to explore the prognostic factors of oesophageal signet ring cell (SRC) carcinoma and to construct a nomogram for predicting the outcome of SRC carcinoma of oesophagus. Methods A total of 968 cases of oesophageal SRC carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Cases were divided into training cohort and validation cohort. Univariate and multivariable Cox analyses was performed to select the predictors of overall survival (OS for the nomogram. The performance of nomogram was validated with Harrell's concordance index (C-index), calibration curves and decision curve analysis (DCA). Results The 1- and 5-year OS in the training cohort were 0.446 and 0.146, respectively, and the 1- and 5-year OS in the validation cohort were 0.459 and 0.138. The independent prognostic factors for establishing the nomogram were marital status, invasion of the surrounding tissue, lymph node metastasis, distant metastasis, surgery and chemotherapy. The Harrell's c-index value of the training cohort and validation cohort were 0.723 and 0.708. In the calibration curves, the predicted survival probability and the actual survival probability have a considerable consistency. DCA indicated the favourable potential clinical utility of the nomogram. Conclusions A nomogram to predict the OS of patients with oesophageal SRC carcinoma was established. The validation of the nomogram fully demonstrates its great performance.

Two new guaianolide-type sesquiterpenoids chrysanthemulides K and L (

BACKGROUND: Although many studies have reported that patients have undergone entire lung removal for lung cancer along with high operative mortality, the trends in the incidence and associated risk factors for operative death have not been explored in a national population-based study. In addition, a clinical decision-making nomogram for predicting postpneumonectomy mortality remains lacking. METHODS: A total of 10,337 patients diagnosed with lung cancer who underwent pneumonectomy between 1998 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Multivariate logistic regression analysis was used to identify risk factors for predicting operative mortality. Thereafter, these independent predictors were integrated into a nomogram, and bootstrap validation was applied to assess the discrimination and calibration. Additionally, decision curve analysis (DCA) was used to calculate the net benefit of this forecast model. RESULTS: The overall postpneumonectomy mortality between 1998 and 2016 was 10.3%, including a 30-day mortality of 4.2%; however, there were statistically significant decreases in the operative death rates from 8.8% in 1998 to 6.7% in 2016 (P=0.009). Higher operative mortality was associated with advanced patients (P

Background Millions of human beings have suffered in the epidemic of coronavirus disease 2019 (COVID-19), but until now the effective treatment methods have been limited. Aim This study aimed to evaluate the efficacy and safety of short-wave diathermy (SWD) treatment for moderate COVID-19 patients. Design A prospective, double-blind, randomized controlled clinical study. Setting Inpatients unit of a COVID-19 specialized hospital. Population Forty-two patients with moderate COVID-19 were randomly allocated at a 2:1 ratio to two groups: the SWD group and the control group. Methods Participants of the SWD group received SWD treatment, and participants of the control group received placebo SWD treatment for one session per day, 10 minutes per session, for no more than 14 days. Both groups were given standard care treatment. Primary outcome was the rate of clinical improvement according to a sevencategory ordinal scale. Secondary outcomes included the rate of computed tomography (CT) improvement and the rate of potential adverse events. Results Clinical improvement occurred in 92.6% of patients in the SWD group by day 14 compared with 69.2% of patients in the control group (P = 0.001). The Cox model indicated that the SWD group had a higher clinical improvement probability than the control group (Hazard Ratio, 3.045; 95% CI, 1.391-6.666; P = 0.005). Similarly, CT improvement occurred in 85.2 % of patients in the SWD group and 46.2 % of patients in the control group respectively by day 14 (P = 0.001). The Cox model indicated SWD group had a higher CT improvement probability than control group (Hazard Ratio, 3.720; 95% CI, 1.486-9.311; P = 0.005). There was no significant difference in adverse events between the SWD group and the control group (2 of 27 [7.4%] SWD vs. 1 of 13 [7.7%] control, P = 1.000), the most frequent of which were headache (1 of 27 [3.7%] SWD vs. 1 of 13 [7.7%] control patients) and dizziness (1 of 27 [3.7%] SWD vs. 0 of 13 [0%] control patients). Conclusions SWD is a valid and reliable adjuvant therapy with a favorable safety profile for moderate COVID-19 patients. Clinical rehabilitation impact Clinically relevant information is lacking regarding the efficacy and safety of SWD for patients with COVID-19. This study provides the first evidence that SWD is a promising adjuvant therapy for COVID-19.

Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke.We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks.Significant treatment-time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P 0.001, Cohen's d = 1.302) (P = 0.003, Cohen's d = 0.771), and this effect lasted until the third week (P = 0.001, Cohen's d = 0.860) (P = 0.027, Cohen's d = 0.550). The HAM-A and HAM-D scores did not change in the rTMS group when compared with the sham group (P = 0.341, Cohen's d = 0.224) (P = 0.356, Cohen's d = 0.217). The serum BDNF levels were significantly higher in the treated group (P = 0.048, Cohen's d = -0.487), and the resting motor threshold (RMT) decreased by 163.65%.Our findings indicate that rTMS applied over the upper extremity area of the motor cortex can effectively alleviate acute CPSP, possibly by influencing cortical excitability and serum BDNF secretion.This trial is registered with Clinical Trial Registry of China: Reg. No. ChiCTR-INR-17012880.

Stroke is always associated with a difficult functional recovery process. A brain-computer interface (BCI) is a technology which provides a direct connection between the human brain and external devices. The primary aim of this study was to determine whether training with a BCI-controlled robot can improve functions in patients with subacute stroke.Subacute stroke patients aged 32-68 years with a course of 2 weeks to 3 months were randomly assigned to the BCI group or to the sham group for a 4-week course. The primary outcome measures were Loewenstein Occupational Therapy Cognitive Assessment (LOCTA) and Fugl-Meyer Assessment for Lower Extremity (FMA-LE). Secondary outcome measures included Fugl-Meyer Assessment for Balance (FMA-B), Functional Ambulation Category (FAC), Modified Barthel Index (MBI), serum brain-derived neurotrophic factor (BDNF) levels and motor-evoked potential (MEP).A total of 28 patients completed the study. Both groups showed a significant increase in mean LOCTA (sham: P 0.001, Cohen's d = - 2.972; BCI: P 0.001, Cohen's d = - 4.266) and FMA-LE (sham: P 0.001, Cohen's d = - 3.178; BCI: P 0.001, Cohen's d = - 3.063) scores. The LOCTA scores in the BCI group were 14.89% higher than in the sham group (P = 0.049, Cohen's d = - 0.580). There were no significant differences between the two groups in terms of FMA-B (P = 0.363, Cohen's d = - 0.252), FAC (P = 0.363), or MBI (P = 0.493, Cohen's d = - 0.188) scores. The serum levels of BDNF were significantly higher within the BCI group (P 0.001, Cohen's d = - 1.167), and the MEP latency decreased by 3.75% and 4.71% in the sham and BCI groups, respectively.Training with a BCI-controlled robot combined with traditional physiotherapy promotes cognitive function recovery, and enhances motor functions of the lower extremity in patients with subacute stroke. These patients also showed increased secretion of BDNF.Chinese clinical trial registry: ChiCTR-INR-17012874.

We used a murine spontaneous osteosarcoma cell line with high metastatic potential, the K7M2 cell line to study the role of Notch signaling in the biological manifestations of osteosarcoma, to understand its underlying mechanism in the regulation of cell proliferation and migration, and to improve patient prognosis in cases of osteosarcoma through the discovery of novel therapeutic targets, First, Notch expression in K7M2 was determined by immunostaining, and the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) was used to inhibit proteolytic cleavage of the Notch intracellular domain (NICD), resulting in the inhibition of Notch activation. By using the Sulforhodamine B assay, colony-forming units assay, Brdu and Ki67 staining, and flow cytometry assays of apoptosis and cell cycle stage, DAPT was found to inhibit K7M2 proliferation in a dose-dependent manner. By using wound healing and transwell migration assays, DAPT was found to inhibit K7M2 migration in a dose-dependent manner as well. By using a combination of micro-Raman spectroscopy and K-means clustering analysis, we found that DAPT inhibit a variety of important cell metabolism-related components in most K7M2 cell structures. Then, DAPT was found to inhibit Notch1ICD expression in a concentration-dependent manner, and this expression was directly correlated with Phospho-Erk1/2 (p-Erk) by using Western blotting. To confirm this finding, we used the Notch signaling ligand Jagged1 to activate the Notch signaling pathway, which in turn up-regulated p-Erk, resulting in increased proliferation and migration of K7M2. Using the Erk pathway inhibitor U0126, we showed that p-Erk was downregulated and the proliferation and migration of K7M2 decreased along with it. Finally, we constructed a K7M2 mouse para-tibial tumor model and lung metastatic model. We found DAPT inhibits p-Erk in vivo, effectively controls tumor growth, reduces angiogenesis, reduces metastasis to the lungs, and improves overall survival. In summary, Notch signaling plays an oncogene role and promotes metastasis in osteosarcoma through p-Erk. DAPT effectively inhibits osteosarcoma proliferation and metastasis in vivo and in vitro by inhibiting Erk phosphorylation. Therefore, the inhibition of Notch activation resulted the down-regulation of phosphorylation of Erk pathway can be used as potential therapeutic targets in clinical treatment to improve osteosarcoma prognosis.

It is essential to make sure patients be actively involved in motor training using robot-assisted rehabilitation to achieve better rehabilitation outcomes. This paper introduces an attention-controlled wrist rehabilitation method using a low-cost EEG sensor. Active rehabilitation training is realized using a threshold of the attention level measured by the low-cost EEG sensor as a switch for a flexible wrist exoskeleton assisting wrist flexion/extension and radial/ulnar deviation. We present a prototype implementation of this active training method and provide a preliminary evaluation. The feasibility of the attention-based control was proven with the overall actuation success rate of 95%. The experimental results also proved that the visual guidance was helpful for the users to concentrate on the wrist rehabilitation training: two types of visual guidance, namely, looking at the hand motion shown on a video and looking at the user's own hand had no significant performance difference. A general threshold of a certain group of users can be utilized in the wrist robot control rather than a customized threshold to simplify the procedure.

Metal powder bed fusion (PBF) is an advanced metal additive manufacturing (AM) technology. Compared with traditional manufacturing techniques, PBF has a higher degree of design freedom. Currently, although PBF has received extensive attention in fields with high–quality standards such as aerospace and automotive, there are some disadvantages, namely poor process quality and insufficient stability, which make it difficult to apply the technology to the manufacture of critical components. In order to surmount these limitations, it is necessary to monitor the process. Online monitoring technology can detect defects in time and provide certain feedback control, so it can greatly enhance the stability of the process, thereby ensuring its quality of the process. This paper presents the current status of online monitoring technology of the metal PBF process from the aspects of powder recoating monitoring, powder bed inspection, building process monitoring, and melt layer detection. Some of the current limitations and future trends are then highlighted. The combination of these four–part monitoring methods can make the quality of PBF parts highly assured. We unanimously believe that this article can be helpful for future research on PBF process monitoring.

Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1β,2β:4β,5β-diepoxy-10β-hydroxy-6βH,7αH,11βH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 μM. Moreover, achigermalide D decreased the expression of IL-1β and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.

BACKGROUND Therapeutic options for patients with second lung tumor (SLT) after previous pneumonectomy for lung cancer are sparsely reported and controversial. This study aims to compare the short- and long-term outcomes of different treatment patterns in patient with resectable postpneumonectomy SLT. METHODS Patients received previous pneumonectomy and subsequently occurred resectable SLT were extracted from the Surveillance, Epidemiology, and End Results (SEER) database [1998-2016]. Treatment related mortality was compared using the Pearson chi-square test. Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for cancer-specific survival (CSS) and overall survival (OS). RESULTS Ninety-nine patients met the selection criteria with 5-year CSS and OS rates of 60.8% and 53.7%, respectively: 23 patients received no lung resection (nLR) and 76 patients received lung resection (LR). There was no statistically significant difference between nLR group and LR group in both treatment related mortality (0.0% vs. 2.6%, P=0.432), CSS (58.3% vs. 61.7%, P=0.633) and OS (55.3% vs. 53.3%, P=0.635). Patients with subsequent adenocarcinoma (P=0.001) and smaller tumor size of SLT (P

Investigation into the chemical diversity of

This work is to establish the fingerprint of Astragalus membranaceus var. mongholicus by HPLC-ELSD method, and to analyze the simulated wildness degree of A. membranaceus var. mongholicus in the genuine region of Inner Mongolia, Ningxia and Gansu. Compared with wild A. membranaceus var. mongholicus, the quality differences of A. membranaceus var. mongholicus in the genuine region were analyzed by identification of chromatographic peaks and similarity evaluation, cluster analysis(CA), principal components analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). HPLC fingerprints of A. membranaceus var. mongholicus in different genuine regions are established. The qualitative analysis of mass spectrometry identified 18 components. The similarity evaluation shows that the similarity of 32 batches of A. membranaceus var. mongholicus samples was 0.688-0.993. Among them, the similarity of samples in Shanxi, Inner Mongolia, Ningxia is 0.688-0.993, 0.835-0.989, 0.934-0.988, respectively and the similarity of samples in Gansu is 0.729-0.876 except No. 25 sample. The results of CA show that the samples of A. membranaceus var. mongholicus can be grouped into four categories according to the production area except the No. 11 and No. 25 samples. The results of PCA indicate that 32 batches of A. membranaceus var. mongholicus samples can be clustered according to quality and origin, and the quality of A. membranaceus var. mongholicus in Inner Mongolia is the closest to the wild breed. The results of OPLS-DA indicate that there are six components that can distinguish the wild and domestic A. membranaceus var. mongholicus, which are malonylastragaloside Ⅰ, astragaloside Ⅰ, calycosin-7-O-β-D-glycoside-6″-O-malonate, calycosin-7-O-β-D-glycoside, formononetin-7-O-β-D-glycoside-6″-O-malonate, and astrapterocarpan-3-O-β-D-glycoside-6″-O-malonate. The established method can be used to analyze differences between A. membranaceus var. mongholicus origin and planting environment, and can provide references for the protection and replacement of wild A. membranaceus var. mongholicus resources, and the cultivation, processing and production of A. membranaceus var. mongholicus.

ABSTACTA chemical investigation of the whole plant of traditional Chinese medicine

BACKGROUND Signet ring cell carcinoma is a rare type of oesophageal cancer, and we hypothesized that log odds of positive lymph nodes (LODDS) is a better prognostic factor for oesophageal signet ring cell carcinoma. AIM To explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors, log odds of positive LODDS and N stage. METHODS A total of 259 cases of oesophageal signet ring cell carcinoma after oesopha-gectomy were obtained from the Surveillance, Epidemiology, and End Results database between 2006 and 2016. The prognostic value of LODDS and N stage for oesophageal signet ring cell carcinoma was evaluated by univariate and multivariate analyses. The Akaike information criterion and Harrell’s C-index were used to assess the value of two prediction models based on lymph nodes. External validation was performed to further confirm the conclusion. RESULTS The 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) rates of all the cases were 41.3% and 27.0%, respectively. The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared (OS: 46.162, CSS: 41.178) than N stage (OS: 36.215, CSS: 31.583). Univariate analyses showed that insurance, race, T stage, M stage, TNM stage, radiation therapy, N stage, and LODDS were potential prognostic factors for OS (P < 0.1). The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection (P < 0.05), while N stage was not considered to be a significant prognostic factor (P = 0.122). Model 2 (LODDS) had a higher degree of discrimination and fit than Model 1 (N stage) (LODDS vs N stage, Harell’s C-index 0.673 vs 0.656, P < 0.001; Akaike information criterion 1688.824 vs 1697.519, P < 0.001). The results of external validation were consistent with those in the study cohort. CONCLUSION LODDS is a superior prognostic factor to N stage for patients with oesophageal signet ring cell carcinoma after oesophagectomy.

Neural stem and progenitor cells (NSPCs) are important for nerve regeneration after spinal cord injury (SCI). Their proliferation, however, is limited. In this study, we investigated the role of Notch1 signaling in NSPC proliferation using adult mouse spinal cord derived NSPCs. We observed that Notch1 promoted proliferation of NSPCs and that Notch1 overexpression led to an expansion of cells in the S-phase and increased cyclin D1 expression. When investigating the functional relationship between Notch1, p-p38 and Pax6, we found that Notch1 suppressed p-p38 while promoting Pax6 expression. Functional inhibition of p38 with SB202190 led to increased Pax6 expression and to proliferation, as determined by BrdU. Furthermore, we confirmed that Pax6 induced proliferation in adult mouse spinal cord derived NSPCs. In conclusion, we demonstrate that Notch1 promotes the proliferation of mouse spinal NSPCs via a p-p38-pax6-cyclin D1 signaling pathway. This pathway constitutes a promising new therapeutic target for SCI treatment.

The southern Great Xing’an Range (SGXR) is located in the eastern Central Asian Orogenic Belt (CAOB), and represents the most important Cu-Mo-Pb-Zn polymetallic mineral province in NE China. The Panjiaduan deposit in the SGXR is characterized by superimposing mineralization: (1) porphyry Mo ore hosted by syenogranite, and (2) superimposing vein-type Cu-Pb-Zn ore, hosted by fracture zones in the Manitu Formation volcanics and granodiorite. Two zircon U-Pb ages of 233.9 ± 2.8 Ma and 236.1 ± 2.8 Ma for the syenogranite (porphyry) ore host indicate that the porphyry Mo mineralization occurred in the Late Triassic, coeval with the adjacent Laojiagou porphyry Mo deposit. Sphalerite from the Cu-Pb-Zn ore veins yielded a Rb-Sr isochron age of 138.5 ± 3.5 Ma, suggesting Early Cretaceous overprinting mineralization. The syenogranite is geochemically similar to the ore-causative monzogranite at Laojiagou. They are unfractionated I-type granites, LILE- and LREE-enriched, and HFSE- and HREE-depleted. In addition, their magma source was likely derived from partial melting of the juvenile lower crust. Major sulfides (pyrite, molybdenite, and galena) from the porphyry ores have slightly lower δ34S values (−2.8 to −0.3 ‰) than the vein-type ore sulfides (pyrite, chalcopyrite, sphalerite, and galena) (1.5 to 5.3 ‰), although they are all close to the mantle δ34S values and thus suggests a magmatic sulfur source. Meanwhile, the Pb isotope compositions of the two ore types suggest that the Pb for the porphyry mineralization was likely derived from an orogenic Pb reservoir, while the latter may have crust-mantle mixed Pb source. We suggested that both mineralization events were formed in an extensional setting, induced by the post-collision tectonics after the Paleo-Asian Ocean closure and the Paleo-Pacific subduction rollback, respectively.

A chemical investigation of the whole plant of traditional Chinese medicine, Chrysanthemum indicum L., led to the discovery of six guaianolide-type sesquiterpenoids 1–6 with a 1,10-splited skeleton. The structure of the new compound 1 was established by extensive analysis of UV, IR, MS, NMR and ECD data. Compounds 3–6 are mutually stereoisomers with four chiral centers and their absolute configurations were determined by comparison of ECD spectra. The anti-inflammatory effects of these isolates on lipopolysaccharide (LPS)-induced nitric oxide (NO) were investigated in RAW 264.7 cells. Results showed that most of the compounds displayed NO production inhibitory activities with IC50 values ranged from 3.54 to 8.17 μM.

Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1–3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1–4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8–15.2 μM.

Objectives Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. Methods A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. Results The analysis showed significant treatment–time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen’s d = 1.135; P = 0.006, Cohen’s d = 0.616) and after one week (P < 0.001, Cohen’s d = 0.846; P = 0.012, Cohen’s d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen’s d = 0.539; P = 0.009, Cohen’s d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen’s d = 0.464). Conclusions These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.

We have studied the $\ensuremath{\gamma}p\ensuremath{\rightarrow}\ensuremath{\eta}\ensuremath{\phi}p$ reaction within the effective Lagrangian approach by considering the contribution of the intermediate state $\ensuremath{\phi}(2170)$ production, and the background contributions of $t$-channel ${\ensuremath{\pi}}^{0}$ and $\ensuremath{\eta}$ mesons exchanges with the intermediate states $N$ and $N(1535)$. Our calculations show that there may be a peak, at least a bump structure around 2180 MeV associated to the resonance $\ensuremath{\phi}(2170)$ in the $\ensuremath{\eta}\ensuremath{\phi}$ mass distribution. We suggest to search for the resonance $\ensuremath{\phi}(2170)$ in this reaction, which would be helpful to shed light on its nature.

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 μM.

Hand rehabilitation exoskeletons are in need of improving key features such as simplicity, compactness, bi-directional actuation, low cost, portability, safe human-robotic interaction, and intuitive control. This article presents a brain-controlled hand exoskeleton based on a multi-segment mechanism driven by a steel spring. Active rehabilitation training is realized using a threshold of the attention value measured by an electroencephalography (EEG) sensor as a brain-controlled switch for the hand exoskeleton. We present a prototype implementation of this rigid-soft combined multi-segment mechanism with active training and provide a preliminary evaluation. The experimental results showed that the proposed mechanism could generate enough range of motion with a single input by distributing an actuated linear motion into the rotational motions of finger joints during finger flexion/extension. The average attention value in the experiment of concentration with visual guidance was significantly higher than that in the experiment without visual guidance. The feasibility of the attention-based control with visual guidance was proven with an overall exoskeleton actuation success rate of 95.54% (14 human subjects). In the exoskeleton actuation experiment using the general threshold, it performed just as good as using the customized thresholds; therefore, a general threshold of the attention value can be set for a certain group of users in hand exoskeleton activation.

Cervical degenerative disease is one of the most common spinal disorders worldwide, especially in older people. Anterior cervical corpectomy and fusion (ACCF) is a useful method for the surgical treatment of multi-level cervical degenerative disease. Anterior cervical disc replacement (ACDR) is considered as an alternative surgical method. However, both methods have drawbacks, particularly the neck motion decrease observed after arthrodesis, and arthroplasty should only be performed on patients presenting with cervical disc disease but without any vertebral body disease. Therefore, we designed a non-fusion cervical joint system, namely an artificial cervical vertebra and intervertebral complex (ACVC), to provide a novel treatment for multi-level cervical degenerative disease. To enhance the long-term stability of ACVC, we applied a hydroxyapatite (HA) biocoating on the surface of the artificial joint. Thirty-two goats were randomly divided into four groups: a sham control group, an ACVC group, an ACVC-HA group, and an ACCF group (titanium and plate fixation group). We performed the prosthesis implantation in our previously established goat model. We compared the clinical, radiological, biomechanical, and histological outcomes among these four different groups for 24 weeks post surgery. The goats successfully tolerated the entire experimental procedure. The kinematics data for the ACVC and ACVC-HA groups were similar. The range of motion (ROM) in adjacent level increased after ACCF but was not altered after ACVC or ACVC-HA implantation. Compared with the control group, no significant difference was found in ROM and neutral zone (NZ) in flexion-extension or lateral bending for the ACVC and ACVC-HA groups, whereas the ROM and NZ in rotation were significantly greater. Compared with the ACCF group, the ROM and NZ significantly increased in all directions. Overall, stiffness was significantly decreased in the ACVC and ACVC-HA groups compared with the control group and the ACCF group. Similar results were found after a fatigue test of 5,000 repetitions of axial rotation. The histological results showed more new bone formation and better bone implant contact in the ACVC-HA group than the ACVC group. Goat is an excellent animal model for cervical spine biomechanical study. Compared with the intact state and the ACCF group, ACVC could provide immediate stability and preserve segmental movement after discectomy and corpectomy. Besides, HA biocoating provide a better bone ingrowth, which is essential for long-term stability. In conclusion, ACVC-HA brings new insight to treat cervical degenerative disease.

Dual-task performance is strongly affected by the direction of attentional focus. This study investigated neural control of a postural–suprapostural procedure when postural focus strategy varied. Twelve adults concurrently conducted force-matching and maintained stabilometer stance with visual feedback on ankle movement (visual internal focus, VIF) and on stabilometer movement (visual external focus, VEF). Force-matching error, dynamics of ankle and stabilometer movements, and event-related potentials (ERPs) were registered. Postural control with VEF caused superior force-matching performance, more complex ankle movement, and stronger kinematic coupling between the ankle and stabilometer movements than postural control with VIF. The postural focus strategy also altered ERP temporal-spatial patterns. Postural control with VEF resulted in later N1 with less negativity around the bilateral fronto-central and contralateral sensorimotor areas, earlier P2 deflection with more positivity around the bilateral fronto-central and ipsilateral temporal areas, and late movement-related potential commencing in the left frontal-central area, as compared with postural control with VIF. The time–frequency distribution of the ERP principal component revealed phase-locked neural oscillations in the delta (1–4 Hz), theta (4–7 Hz), and beta (13–35 Hz) rhythms. The delta and theta rhythms were more pronounced prior to the timing of P2 positive deflection, and beta rebound was greater after the completion of force-matching in VEF condition than VIF condition. This study is the first to reveal the neural correlation of postural focusing effect on a postural–suprapostural task. Postural control with VEF takes advantage of efficient task-switching to facilitate autonomous postural response, in agreement with the “constrained-action” hypothesis.