Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

Ethyl pyruvate (EP) has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI). Adult male rats were randomly divided into three groups: (1) Sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + EP group (n = 30 per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-α and IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain

Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials

ObjectiveBispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.MethodsPubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.ResultsFourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01).ConclusionThis analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768

An Improved Method for the Evaluation and Local Multi-Scale Optimization of the Automatic Extraction of Slope Units in Complex Terrains

Slope units (SUs) are sub-watersheds bounded by ridge and valley lines. A slope unit reflects the physical relationship between landslides and geomorphological features and is especially useful for landslide sensitivity modeling. There have been significant algorithmic advances in the automatic delineation of SUs. But the intrinsic difficulties of determining input parameters and correcting for unreasonable SUs have hindered their wide application. An improved method of the evaluation and local multi-scale optimization for the automatic extraction of SUs is proposed. The Sus’ groups more consistent with the topographic features were achieved through a stepwise approach from a global optimum to a local refining. First, the preliminary subdivisions of multiple SUs were obtained based on the r.slopeunit software. The optimal subdivision scale was obtained by a collaborative evaluation approach capable of simultaneously measuring objective minimum discrepancies and seeking a global optimum. Second, under the selected optimal scale, unreasonable SUs such as over-subdivided slope units (OSSUs) and under-subdivided slope units (USSUs) were further distinguished. The local average similarity (LS) metric for each SU was designed based on calculating the SU’s area, common boundary and neighborhood variability. The inflection points of the cumulative frequency curve of LS were calculated as the distinguishing intervals for those unrealistic SUs by maximum interclass variance threshold. Third, a new effective optimization mechanism containing the re-subdivision of USSUs and merging of OSSUs was put into effect. We thus obtained SUs composed of terrain subdivisions with multiple scales, which is currently one of the few available methods for non-single scales. The statistical distributions of density, size and shapes demonstrate the excellent performance of the refined SUs in capturing the variability of complex terrains. Benefiting from the sufficient integrating approach of diverse features for each object, it is a significant advantage that the processing object can be transferred from general entirety to each precise individual

A case of repeated intracerebral hemorrhages secondary to ventriculoperitoneal shunt

Ventriculoperitoneal shunt is a routinely performed treatment in neurosurgical department. Intracerebral hemorrhage, as a complication after shunt catheterization, is really rare but with high mortality. In this study, we reported a case of a 74-year-old man who suffered from repeated intracerebral hemorrhage after ventriculoperitoneal shunt. The first hemorrhage happened 63 h after the 1st surgery, and most hematomas were located in the ipsilateral occipital lobe and intraventricles, along the ventricular catheter. Fresh blood clot casts blocked the external ventricular draining catheter, which was inserted into the right front horn during the 3rd surgery, indicating new intraventricular bleeding happened. A large hematoma in ipsilateral frontal lobe was detected on the 3rd day after the removal of external ventricular draining catheter. Different hemorrhagic locations and time points were encountered on the same case. We discussed the possible causes of repeated hemorrhage for this case, and the pre-operative preparation including risk evaluation in future clinical work

An Improved Method for the Evaluation and Local Multi-Scale Optimization of the Automatic Extraction of Slope Units in Complex Terrains

Slope units (SUs) are sub-watersheds bounded by ridge and valley lines. A slope unit reflects the physical relationship between landslides and geomorphological features and is especially useful for landslide sensitivity modeling. There have been significant algorithmic advances in the automatic delineation of SUs. But the intrinsic difficulties of determining input parameters and correcting for unreasonable SUs have hindered their wide application. An improved method of the evaluation and local multi-scale optimization for the automatic extraction of SUs is proposed. The Sus’ groups more consistent with the topographic features were achieved through a stepwise approach from a global optimum to a local refining. First, the preliminary subdivisions of multiple SUs were obtained based on the r.slopeunit software. The optimal subdivision scale was obtained by a collaborative evaluation approach capable of simultaneously measuring objective minimum discrepancies and seeking a global optimum. Second, under the selected optimal scale, unreasonable SUs such as over-subdivided slope units (OSSUs) and under-subdivided slope units (USSUs) were further distinguished. The local average similarity (LS) metric for each SU was designed based on calculating the SU’s area, common boundary and neighborhood variability. The inflection points of the cumulative frequency curve of LS were calculated as the distinguishing intervals for those unrealistic SUs by maximum interclass variance threshold. Third, a new effective optimization mechanism containing the re-subdivision of USSUs and merging of OSSUs was put into effect. We thus obtained SUs composed of terrain subdivisions with multiple scales, which is currently one of the few available methods for non-single scales. The statistical distributions of density, size and shapes demonstrate the excellent performance of the refined SUs in capturing the variability of complex terrains. Benefiting from the sufficient integrating approach of diverse features for each object, it is a significant advantage that the processing object can be transferred from general entirety to each precise individual

Mapping Outburst Floods Using a Collaborative Learning Method Based on Temporally Dense Optical and SAR Data: A Case Study with the Baige Landslide Dam on the Jinsha River, Tibet

Outburst floods resulting from giant landslide dams can cause devastating damage to hundreds or thousands of kilometres of a river. Accurate and timely delineation of flood inundated areas is essential for disaster assessment and mitigation. There have been significant advances in flood mapping using remote sensing images in recent years, but little attention has been devoted to outburst flood mapping. The short-duration nature of these events and observation constraints from cloud cover have significantly challenged outburst flood mapping. This study used the outburst flood of the Baige landslide dam on the Jinsha River on 3 November 2018 as an example to propose a new flood mapping method that combines optical images from Sentinel-2, synthetic aperture radar (SAR) images from Sentinel-1 and a Digital Elevation Model (DEM). First, in the cloud-free region, a comparison of four spectral indexes calculated from time series of Sentinel-2 images indicated that the normalized difference vegetation index (NDVI) with the threshold of 0.15 provided the best separation flooded area. Subsequently, in the cloud-covered region, an analysis of dual-polarization RGB false color composites images and backscattering coefficient differences of Sentinel-1 SAR data were found an apparent response to ground roughness’s changes caused by the flood. We carried out the flood range prediction model based on the random forest algorithm. Training samples consisted of 13 feature vectors obtained from the Hue-Saturation-Value color space, backscattering coefficient differences/ratio, DEM data, and a label set from the flood range prepared from Sentinel-2 images. Finally, a field investigation and confusion matrix tested the prediction accuracy of the end-of-flood map. The overall accuracy and Kappa coefficient were 92.3%, 0.89 respectively. The full extent of the outburst floods was successfully obtained within five days of its occurrence. The multi-source data merging framework and the massive sample preparation method with SAR images proposed in this paper, provide a practical demonstration for similar machine learning applications using remote sensing

Suppression of JAK2/STAT3 signaling reduces end-to-end arterial anastomosis induced cell proliferation in common carotid arteries of rats.

BACKGROUND: JAK2/STAT3 pathway was reported to play an essential role in the neointima formation after vascular intima injury. However, little is known regarding this pathway to the whole layer injury after end-to-end arterial anastomosis (AA). Here, we investigated the role of JAK2/STAT3 pathway in common carotid arterial (CCA) anastomosis-induced cell proliferation, phenotypic change of vascular smooth muscle cells (VSMCs) and re-endothelialization. METHODS: CCAs of adult male Wistar rats were resected at 3, 7, 14, and 30 days after end-to-end CCA anastomosis. Activation of JAK2/STAT3 pathway was detected by Western blotting and Immunofluorescence, and expression of proliferating cell nuclear antigen (PCNA) was detected by Q-PCR and Western blotting. Under the treatment with AG490 (a JAK2 inhibitor), protein levels of JAK2, STAT3 and PCNA, morphological changes of artery, phenotypic change of VSMCs, and re-endothelialization were measured by Western blotting, H&E, Q-PCR, and Evans blue staining respectively. RESULTS: The protein levels of p-JAK2, p-STAT3, and PCNA were up-regulated, peaked on the 7(th) day in the vessel wall after AA. AG490 down-regulated the levels of p-JAK2, p-STAT3, and PCNA on the 7(th)-day-group, resulting in reduced vessel wall proliferation on the 7(th) and 14(th) day after AA. Besides, AG490 switched the phenotypic change of VSMCs after AA representing inhibited mRNA levels of synthetic phase markers (osteopoitin and SMemb) and up-regulated contractile phase markers (ASMA, SM2 and SM22α). Furthermore, AG490 did not affect the re-endothelialization process on all indicated time points after AA (the 3(rd), 7(th), 14(th), and 30(th) day). CONCLUSION: Our study indicated that JAK2/STAT3 signaling pathway played an important role on cell proliferation of the injured vessel wall, and probably a promising target for the exploration of drugs increasing the patency or reducing the vascular narrowness after AA

DataSheet_1_Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.docx

ObjectiveBispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.MethodsPubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.ResultsFourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P ConclusionThis analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.</p