Advancing the Boundary of Pre-trained Models for Drug Discovery: Interpretable Fine-Tuning Empowered by Molecular Physicochemical Properties.

In the field of drug discovery, a proliferation of pre-trained models has surfaced, exhibiting exceptional performance across a variety of tasks. However, the extensive size of these models, coupled with the limited interpretative capabilities of current fine-tuning methods, impedes the integration of pre-trained models into the drug discovery process. This paper pushes the boundaries of pre-trained models in drug discovery by designing a novel fine-tuning paradigm known as the Head Feature Parallel Adapter (HFPA), which is highly interpretable, high-performing, and has fewer parameters than other widely used methods. Specifically, this approach enables the model to consider diverse information across representation subspaces concurrently by strategically using Adapters, which can operate directly within the model's feature space. Our tactic freezes the backbone model and forces various small-size Adapters' corresponding subspaces to focus on exploring different atomic and chemical bond knowledge, thus maintaining a small number of trainable parameters and enhancing the interpretability of the model. Moreover, we furnish a comprehensive interpretability analysis, imparting valuable insights into the chemical area. HFPA outperforms over seven physiology and toxicity tasks and achieves state-of-the-art results in three physical chemistry tasks. We also test ten additional molecular datasets, demonstrating the robustness and broad applicability of HFPA.

Exosomal SOX21-AS1 Regulates EREG by Sponging miR-451a and Promotes the Malignancy of Pancreatic Ductal Adenocarcinoma.

The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have increased. Exosomes, as a regulatory mode of intercellular communication, contain lncRNAs. SOX21-AS1 has been studied in other cancers, and its expression is elevated in PDAC, but its role in PDAC remains unclear. First, we analyzed the expression of lncRNAs in PDAC tissues and nontumor tissues through the TCGA database. Next, the results of the RT-qPCR experiment confirmed the prediction that the expression of SOX21-AS1 was elevated in PDAC tissues. In vivo and in vitro cell function assays confirmed that the degree of malignancy of PDAC was proportional to the expression of SOX21-AS1. In addition, through exosome isolation and uptake experiments, we first found that PDAC could secrete exosomal SOX21-AS1 and play an angiogenic role in HUVECs. Subsequently, the relationship between SOX21-AS1, miR-451a and epiregulin (EREG) was verified through database prediction and analysis and RIP assays. Finally, functional recovery assays in vivo and in vitro verified that SOX21-AS1 regulates the expression of EREG through combination with miR-451a and thus promotes the malignancy of PDAC. SOX21-AS1 was upregulated in PDAC. The upregulation of SOX21-AS1 can stimulate the proliferation, migration, invasion, stemness and epithelial-mesenchymal transition (EMT) progression of PDAC cells. Furthermore, PDAC cells secrete exosomal SOX21-AS1, which is absorbed by HUVECs and promotes angiogenesis. Our study first identified that SOX21-AS1 promotes the malignancy of PDAC through the SOX21-AS1/miR-451a/EREG axis, and also that exosomal SOX21-AS1 promotes angiogenesis in PDAC.

Comparison of consistency in acute stroke: Automated ASPECT score software tools and manual consensus scores.

PURPOSE: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a standardized semi-quantitative scoring system. It is widely used to assess the extent of acute ischemic stroke (AIS). We evaluated the consistency of three automatic software packages with the overall and region-specific manual ASPECTS scores of AIS patients. METHODS: Retrospectively, we gathered patients who presented with stroke symptoms between February 2019 and June 2022, and 174 cases were eventually included in the trial. Two radiologists reviewed the NCCT images independently; After four weeks, the same two radiologists began randomly reviewing the DWI images, discussed different scores and give consistent results as ground truth. RESULTS: Median ASPECTS of the expert consensus reading was 7 (5-9). Good to excellent correlation of ASPECTS total scores among the three software tools (0.70, 0.74 and 0.83). Correlation among ground truth and Rapid-ASPECTS, RealNow-ASPECTS, ShuKun-ASPECTS (ICC = 0.51, Cronbach's α = 0.53), (ICC = 0.60, Cronbach's α = 0.70) and (ICC = 0.52, Cronbach's α = 0.64) respectively. The AUCs for Rapid, RealNow and ShuKun were 0.61, 0.67, and 0.62 respectively. The region-specific results showed a poor to good correlation. The correlations between the non-dominant and dominant cerebral hemispheres and the ground truth were statistically different (P < 0.05). CONCLUSIONS: Overall, the scoring consistency between the three automated scoring software and the ground truth is comparable, with RealNow-ASPECTS being no less consistent and effective than Rapid-ASPECTS and ShuKun-ASPECTS, and even better than both. But the consistency grade that still is developable.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: Radiological Findings and Radiological-pathological Correlation

Introduction: The objective of this study was to describe the CT and MRI features of sclerosing angiomatoid nodular transformation (SANT) of the spleen with pathologic correlation. Materials and Methods: Ten patients with surgically resected and pathologically confirmed SANTs were included. Clinical history was reviewed, and gross pathologic, histologic, and immunohistochemical findings were recorded. CT and MRI examinations were evaluated by two radiologists. Results: Patients included seven men and three women, with a mean age of 42.9±16.7 years. Pathologic features of SANTs involved multiple angiomatous nodules in a radiating pattern with a central stellate fibrous scar and evidence of hemosiderin deposition. 9 cases showed a lobulated demarcated margin, 8 cases a slight hypoattenuating, 1 isoattenuating, and 1 case with two lesions demonstrated a slight hyperattenuating margin, respectively. Multiple scattered punctate calcifications were involved in 2 cases. 5 cases manifested hypointensity on in-phase imaging, 1 iso-intensity, and 4 iso-hypointensity on out-of-phase imaging. Progressive and centripetal enhancement were exhibited in 10 cases, spoke-wheel pattern in 3 cases, and nodular enhancement in 4 cases, respectively. The central fibrous scar was identified in 8 cases during delayed enhancement. Conclusion: Characteristics of SANTs on CT/MRI reflected the underlying pathology. Hypointensity on DWI and T2WI, and change of signal on T1 chemicalshift imaging were found to be due to hemosiderin deposition and fibrous tissue. Typical feature was a solitary, round, lobulated mass with a fibrous scar. Progressive and centripetal enhancement, spoke-wheel pattern, nodular enhancement, and delayed enhancement of central fibrous scar were observed.

Evaluation of three-dimensional dual-energy CT cholangiopancreatography image quality in patients with pancreatobiliary dilatation: Comparison with conventional single-energy CT.

Objective: This study aimed to evaluate three-dimensional (3D) negative-contrast CT cholangiopancreatography (nCTCP) image quality using dual-energy CT (DECT) with iterative reconstruction (IR) technique in patients with pancreatobiliary dilatation compared with single-energy CT (SECT). Methods: Of the patients, 67 and 56 underwent conventional SECT (SECT set) and DECT with IR technique (DECT set), respectively. All patients were retrospectively analyzed during the portal phase to compare objective image quality and other data including patient demographics, hepatic and pancreatic parenchymal enhancement, noise, and attenuation difference (AD) between dilated ducts and enhanced hepatic parenchyma, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and CT volume dose index (CTDIvol). Two radiologists used the five-point Likert scale to evaluate the subjective image quality of 3D nCTCP regarding image noise, sharpness of dilated ducts, and overall image quality. Statistical analyses used the Mann-Whitney U test. Results: No significant difference in patient demographics in either CT set was showed during objective evaluation (p > 0.05). However, higher hepatic and pancreatic parenchymal enhancement, AD, SNR, and CNR and lower hepatic and pancreatic noise (p < 0.005) as well as CTDIvol (p = 0.005) on DECT than on SECT were observed. Higher mean grades on DECT than on SECT were showed for image noise (4.65 vs 3.92), sharpness of dilated ducts (4.52 vs 3.94), and overall image quality (4.45 vs 3.91; p < 0.001), respectively during subjective evaluation. Conclusion: A higher overall image quality and lower radiation dose on 3D nCTCP can be obtained by DECT with IR technique than with conventional SECT in patients with pancreatobiliary dilatation.

Biparametric magnetic resonance imaging-based radiomics features for prediction of lymphovascular invasion in rectal cancer.

BACKGROUND: Preoperative assessment of lymphovascular invasion(LVI) of rectal cancer has very important clinical significance. However, accurate preoperative imaging evaluation of LVI is highly challenging because the resolution of MRI is still limited. Relatively few studies have focused on prediction of LVI of rectal cancer with the tool of radiomics, especially in patients with negative statue of MRI-based extramural vascular invasion (mrEMVI).The purpose of this study was to explore the preoperative predictive value of biparametric MRI-based radiomics features for LVI of rectal cancer in patients with the negative statue of mrEMVI. METHODS: The data of 146 cases of rectal adenocarcinoma confirmed by postoperative pathology were retrospectively collected. In the cases, 38 had positive status of LVI. All patients were examined by MRI before the operation. The biparametric MRI protocols included T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). We used whole-volume three-dimensional method and two feature selection methods, minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO), to extract and select the features. Logistics regression was used to construct models. The area under the receiver operating characteristic curve (AUC) and DeLong's test were used to evaluate the diagnostic performance of the radiomics based on T2WI and DWI and the combined models. RESULTS: Radiomics models based on T2WI and DWI had good predictive performance for LVI of rectal cancer in both the training cohort and the validation cohort. The AUCs of the T2WI model were 0.87 and 0.87, and the AUCs of the DWI model were 0.94 and 0.92. The combined model was better than the T2WI model, with AUCs of 0.97 and 0.95. The predictive performance of the DWI model was comparable to that of the combined model. CONCLUSIONS: The radiomics model based on biparametric MRI, especially DWI, had good predictive value for LVI of rectal cancer. This model has the potential to facilitate the clinical recognition of LVI in rectal cancer preoperatively.

Morphological and Structural Network Analysis of Sporadic Alzheimer's Disease Brains Based on the APOE4 Gene.

BACKGROUND: Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD. OBJECTIVE: Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOEɛ4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI). METHODS: All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls. RESULTS: The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus. CONCLUSION: There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOEɛ4 allele effects.

Preoperative evaluation of malignant pancreatobiliary obstruction: A novel technique for multiphase fusion 3D CT images.

The purpose of this article is to describe a novel technique of multiphase fusion three-dimensional (3D) images in patients with malignant pancreatobiliary obstruction. Multiphase fusion 3D images of CT arteriography, portovenography and hepatic venography combined with negative-contrast CT cholangiopancreatography can be done with enhanced multiphase CT scan using intravenous contrast agent at once. This technique may be feasible for one-stop evaluation of malignant pancreatobiliary obstruction.

A Novel Laser Angle Selection System for Computed Tomography-Guided Percutaneous Transthoracic Needle Biopsies.

Purpose: To evaluate a novel laser angle selection system (LASS) for improving the efficiency of a computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB). Methods: Thirty-eight patients referred for CT-guided PTNB were randomly separated into a LASS-assisted puncture group (18 patients) or conventional freehand control group (20 patients). The puncture time, number of control CT scans, and patients' radiation dose were compared for each group. Results: The lesion size, target-to-pleural distance, planned puncture depth, and angle of the two groups were not significantly different. LASS-assisted PTNB significantly reduced the number of control scans (1.7 ± 0.8 vs 3.5 ± 1.5, P < .001) and the mean operation time (12.0 ± 4.3 min vs 28.8 ± 13.3 min, P < .001) compared with the conventional method. The corresponding room time (27.1 ± 6.6 min vs 44.1 ± 14.4 min, P < .001) and total radiation dose (7.9 ± 1.0 mSv vs 10.1 ± 1.7 mSv, P < .001) of each procedure also decreased significantly. Fifty-six percent (10/18) of the operations hit the target on the first needle pass when using LASS compared with 10% (2/20) using the conventional method. Conclusions: Compared with a conventional method, this novel laser angle simulator improves puncture efficiency with fewer needle readjustments and reduces patient radiation dose.

Brain structural alterations detected by an automatic quantified tool as an indicator for MCI diagnosing in type 2 diabetes mellitus patients: A magnetic resonance imaging study.

Background and objectives: Type 2 diabetes mellitus (T2DM) is an important risk factors for mild cognitive impairment (MCI). Structural magnetic resonance imaging (sMRI) is an effective and widely used method to investigate brain pathomorphological injury in neural diseases. In present study, we aimed to determine the brain regional alterations that correlated to the incidence of MCI in T2DM patients. Materials and methods: Eighteen T2DM patients with and without MCI (DMCI/T2DM) respectively, and eighteen age/gender-matched healthy controls (HC) were recruited. Brain MRI imagines of all the individuals were subjected to automatic quantified brain sub-structure volume segmentation and measurement by Dr. brain ™ software. The relative volume of total gray matter (TGM), total white matter (TWM), and 68 pairs (left and right) of brain sub-structures were compared between the three groups. Cognitive function correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted in the MCI-related brain regions in T2DM patients, and we utilized a machine learning method to classify the three group of subjects. Results: 10 and 27 brain sub-structures with significant relative volumetric alterations were observed in T2DM patients without MCI and T2DM patients with MCI, respectively (p < 0.05). Compared with T2DM patients without MCI, eight critical regions include right anterior orbital gyrus, right calcarine and cerebrum, left cuneus, left entorhinal area, left frontal operculum, right medial orbital gyrus, right occipital pole, left temporal pole had significant lower volumetric ratio in T2DM patients with MCI (p < 0.05). Among them, the decrease of volumetric ratio in several regions had a positive correlation with Montreal Cognitive Assessment (MoCA) scores and Mini-Mental State Examination (MMSE) scores. The classification results conducted based on these regions as features by random forest algorithm yielded good accuracies of T2DM/HC 69.4%, DMCI/HC 72.2% and T2DM/DMCI 69.4%. Conclusions: Certain brain regional structural lesions occurred in patients with T2DM, and this condition was more serious in T2DM patients combined with MCI. A systematic way of segmenting and measuring the whole brain has a potential clinical value for predicting the presence of MCI for T2DM patients.

Associations of radiological features of adipose tissues with postoperative complications and overall survival of gastric cancer patients.

OBJECTIVES: To evaluate the associations of the radiological features of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) with the postoperative complications and overall survival (OS) of patients undergoing laparoscopic radical gastrectomy for gastric cancer. METHODS: One hundred forty-two patients underwent laparoscopic radical gastrectomy for gastric cancer from February 2013 to May 2016. The radiological features of SAT and VAT were studied by preoperative computed tomography, and the relationships between the parameters of adipose tissues and the intraoperative and postoperative conditions and OS rate of patients were evaluated. RESULTS: A positive linear correlation was found between VAT area and operation duration, and a negative linear correlation was found between VAT density and intraoperative blood loss (p < 0.05 in both). VAT area was an independent risk factor for postoperative complications. VAT area and VAT density were independent risk factors for OS in gastric cancer. CONCLUSIONS: A high VAT area was an independent risk factor for postoperative complications of gastric cancer, whereas a low VAT area and high VAT density were independent risk factors for poor prognosis in terms of OS in gastric cancer. KEY POINTS: • A large visceral adipose tissue (VAT) area is an unfavourable factor affecting the outcomes of radical gastrectomy for gastric cancer. • Low VAT density may be more likely to cause intraoperative bleeding. • VAT area and VAT density were independent risk factors for the OS of patients with gastric cancer.

Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis.

OBJECTIVES: To assess the predictive value of the combination of bone marrow (BM) proton density fat fraction (PDFF) and liver R2* for osteopenia and osteoporosis and the additional role of liver R2*. METHODS: A total of 107 healthy women were included between June 2019 and January 2021. Each participant underwent dual-energy X-ray absorptiometry (DXA) and chemical shift-encoded 3.0-T MRI. PDFF measurements were performed for each lumbar vertebral body, and R2* measurements were performed in liver segments. Agreement among measurements was assessed by Bland-Altman analysis. Receiver operating characteristic (ROC) curves were generated to select optimised cut-offs for BM PDFF and liver R2*. Univariable and multivariable logistic regressions were performed. The C statistic and continuous net reclassification improvement (NRI) were adopted to explore the incremental predictive ability of liver R2*. RESULTS: Bone mass decreased in 42 cases (39.3%) and nonbone mass decreased in 65 cases (60.7%). There were significant differences among the age groups, menopausal status groups, PDFF > 45.0% groups, and R2* > 67.7 groups. Each measurement had good reproducibility. The odds ratios (95% CIs) were 4.05 (1.22-13.43) for PDFF and 4.34 (1.41-13.35) for R2*. The C statistic (95% CI) without R2* was 0.888 (0.827-0.950), and with R2* was 0.900 (0.841-0.960). The NRI resulting from the combination of PDFF and R2* was 75.6% (p < 0.01). CONCLUSION: The predictive improvement over the use of BM PDFF and other traditional risk factors demonstrates the potential of liver R2* as a biomarker for osteopenia and osteoporosis in healthy women. KEY POINTS: • Liver R2* is a biomarker for the assessment of osteopenia and osteoporosis. • Liver R2* improved the ability to predict osteopenia and osteoporosis. • The intra- and interobserver measurements showed high agreement.

Diagnostic performance of MRI, SPECT, and PET in detecting renal cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignancies worldwide. Noninvasive imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), have been involved in increasing evolution to detect RCC. This meta-analysis aims to compare to compare the performance of MRI, SPECT, and PET in the detection of RCC in humans, and to provide evidence for decision-making in terms of further research and clinical settings. METHODS: Electronic databases including PubMed, Web of Science, Embase, and Cochrane Library were systemically searched. The keywords such as "magnetic resonance imaging", "MRI", "single-photon emission computed tomography", "SPECT", "positron emission tomography", "PET", "renal cell carcinoma" were used for the search. Studies concerning MRI, SPECT, and PET for the detection of RCC were included. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve (AUC), etc. were calculated. RESULTS: A total of 44 articles were finally detected for inclusion in this study. The pooled sensitivities of MRI, 18F-FDG PET and 18F-FDG PET/CT were 0.80, 0.83, and 0.89, respectively. Their respective overall specificities were 0.90, 0.86, and 0.88. The pooled sensitivity and specificity of MRI studies at 1.5 T were 0.86 and 0.94, respectively. With respect to prospective PET studies, the pooled sensitivity, specificity and AUC were 0.90, 0.93 and 0.97, respectively. In the detection of primary RCC, PET studies manifested a pooled sensitivity, specificity, and AUC of 0.77, 0.80, and 0.84, respectively. The pooled sensitivity, specificity, and AUC of PET/CT studies in detecting primary RCC were 0.80, 0.85, and 0.89. CONCLUSION: Our study manifests that MRI and PET/CT present better diagnostic value for the detection of RCC in comparison with PET. MRI is superior in the diagnosis of primary RCC.

Activatable UCL/CT/MR-enhanced in vivo imaging-guided radiotherapy and photothermal therapy.

Although sophisticated radiotherapy (RT) technology has been widely applied in clinical oncotherapy, unsatisfactory therapeutic effects due to hypoxic tumor microenvironments and complications are still prevalent. Herein, copper sulphide nanoparticles (CuS NPs) wrapped on the surface of upconversion nanoparticles (UCNPs) via manganese dioxide (MnO2) coatings were synthesized for O2 self-supplementing and enhanced combinational RT/photothermal therapy (PTT). In our design, the nanoplatforms can be rapidly enriched at tumor sites by the enhanced permeability and retention (EPR) effect and respond to the tumor microenvironment. The surface MnO2 coatings can interact with over-expressed H2O2 in tumors and cause an abundant generation of oxygen for hypoxic improvement, leading to an enhanced RT. More importantly, by irradiation with near-infrared light, the scattered CuS NPs can convert light energy into heat to destroy tumor cells and reinforce the therapeutic effects of RT. Furthermore, these NPs also displayed excellent performances in upconversion fluorescence imaging (UCL), computerized tomographic (CT) scanning and magnetic resonance imaging (MRI), demonstrating a potential imaging-guided cancer therapy system.

Clinical Value of Multi-Slice Spiral CT Angiography, Colon Imaging, and Image Fusion in the Preoperative Evaluation of Laparoscopic Complete Mesocolic Excision for Right Colon Cancer: a Prospective Randomized Trial.

PURPOSE: To evaluate the clinical value of CT angiography (CTA), CT colonography (CTC), and image fusion in the preoperative evaluation of laparoscopic complete mesocolic excision (CME) for right colon cancer. METHODS: In this randomized prospective study, 80 patients undergoing laparoscopic CME for right colon cancer were randomly divided into two groups: image fusion [the original images were reconstructed using CTA and CTC, then fused into three-dimensional images of the blood vessels and intestines (n = 40)] and control (without CTA and CTC reconstruction before surgery). All patients underwent plain and enhanced abdominal CT before surgery. RESULTS: In the image fusion group, the gastrocolic trunk of Henle was present in 33 cases, and its branches originated from the colon vein, right gastroepiploic vein, and superior anterior pancreaticoduodenal vein. Among these patients, 5 exhibited the right gastroepiploic vein and superior anterior pancreaticoduodenal vein; 21 exhibited a gastrointestinal trunk consisting of 2 or 3 branches of the right gastroepiploic vein, right colon vein, and middle colon vein; and 7 exhibited 3 or 4 gastro-pancreatic and colon trunks consisting of the right colon vein, middle colon vein, right gastroepiploic vein, and superior anterior pancreaticoduodenal vein. The correspondence with the anatomy actually observed during surgery was 100%. Compared with the conventional CT group, the duration of the operation in the image fusion group was shorter, with reduced intraoperative bleeding, and more lymph node dissection. There were no significant differences in the incidence of complications and length of hospital stay between the two groups (p > 0.05). CONCLUSIONS: For laparoscopic CME for right colon cancer, CTA, CTC, and image fusion were effective preoperative evaluation methods, which avoided some unseen dangers in the operation process and led to better therapeutic outcomes.

Efficacy of urapidil for the treatment of patients with senile hypertension and acute heart failure.

BACKGROUND: Previous clinical studies have reported that urapidil can effectively treat patients with senile hypertension (SH) and acute heart failure (AHF). However, no studies have systematically assessed the efficacy and safety of urapidil for patients with SH and AHF. Thus, this study will investigate the efficacy and safety of urapidil for SH and AHF. METHODS: In this study, we will search the following electronic databases from inception to the June 30, 2019: MEDLINE, EMBASE, Cochrane Library, Google scholar, Springer, WANGFANG, and China Knowledge Resource Integrated Database. We will search all these electronic databases without language limitations. We will also search grey records to avoid missing potential literature. In this study, only randomized controlled trials on assessing efficacy and safety of urapidil for SH and AHF will be considered. We will use RevMan 5.3 software and STATA 15.0 software to carry out statistical analysis. RESULTS: This study will evaluate the efficacy and safety of urapidil for SH and AHF by assessing all-cause mortality, change in body weight, urine output, change in serum sodium; and incidence of all adverse events. CONCLUSION: This study will provide latest evidence of the efficacy and safety of urapidil for patients with SH and AHF. DISSEMINATION AND ETHICS: This study will only analyze published data; therefore, no ethical approval is needed. The findings of this study will be published at peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019139344.

Efficacy of methylprednisolone for treatment of persistent vertigo.

BACKGROUND: This study will systematically investigate the efficacy and safety of methylprednisolone for treatment of persistent vertigo (PV). METHODS: All following electronic databases will be searched from inception to the June 30, 2019 without language restrictions: MEDILINE, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database. All randomized controlled trials focusing on assessing the efficacy and safety of methylprednisolone for patients with PV will be fully considered for inclusion. Cochrane risk of bias tool will be used for assessing methodological quality, and RevMan 5.3 software (Cochrane Community, London, UK) will be utilized for statistical analysis. RESULTS: This study will assess the efficacy and safety of methylprednisolone for PV via assessing primary outcome of vertigo, and secondary outcomes of somatization, depression, anxiety, health-related quality of life, and adverse events. CONCLUSION: This study will provide a high-quality evidence to judge whether methylprednisolone is an effective and safety therapy for patients with PV. DISSEMINATION AND ETHICS: No individual data will be utilized in this study, thus, it does not need ethical approval. The results of this study will be published at peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019138890.

Dual-response CuS@MnO2 nanoparticles with activatable CT/MR-enhanced in vivo imaging guided photothermal therapy.

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO2 coating, were employed for diagnosing and treating tumors. After reacting with an RGD peptide, the nanoparticles were able to target and focus on tumor sites. Once the nanoparticles were enriched in tumors by RGD targeting, the MnO2 coating decomposed to Mn2+ ions in the tumor microenvironment. Meanwhile, the decomposition of MnO2 allowed the dispersion of aggregated CuS NPs to enter deep tumors, and a 1064 nm laser with powerful penetration was utilized to activate CuS NPs in deep tumors for PTT. More importantly, the generated Mn2+ ions were used for stimuli-enhanced T1-weighted magnetic resonance imaging (T1-MRI) and agminated CuS NPs in tumors were accepted for computed tomography (CT) imaging. It was found that these nanocomposites can accurately indicate tumor sites after being intravenously injected, and in vitro and in vivo experiments illustrated the tremendous potential of these nanoplatforms for use in imaging-guided PTT against HepG2 tumors.

Associations between HMGB1 gene polymorphisms and susceptibility and clinical outcomes in Chinese Han sepsis patients.

OBJECTIVES: High mobility group box 1 protein (HMGB1) is an important late inflammatory mediator in the body. In recent years, studies have found that it plays an important pathogenic role in various diseases such as sepsis. However, it is unclear whether the genetic variation of the HMGB1 gene is related to the susceptibility to sepsis. This study investigated the relationship between susceptibility and outcome of the HMGB1 gene rs2249825, rs1045411, and rs1360485 single nucleotide polymorphisms (SNPs) in Chinese Han patients with sepsis. METHODS: The HMGB1 gene rs2249825, rs1045411, and rs1360485 genotypes were detected by the direct sequencing method in 345 patients with sepsis and 345 healthy controls. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The HMGB1 gene rs2249825 and rs1045411 site SNPs were associated with sepsis risk, but the rs1360485 site SNP was not associated with sepsis risk. Subjects with the HMGB1 gene rs2249825 and rs1045411 site mutations had higher serum HMGB1 levels, and patients with mutant genotype sepsis had higher APACHE II scores and lower 30-day survival rates. There were no correlations among the rs1360485 site SNP, sepsis risk, and patient 30-day survival. CONCLUSION: The HMGB1 gene rs2249825 and rs1045411 site SNPs are associated with susceptibility and outcomes of Chinese Han patients with sepsis. The rs2249825 locus C allele and the rs1045411 locus A allele are high risk factors for sepsis and severity in the Chinese Han population, and are associated with adverse outcomes in patients with sepsis.

Assessment of stereotactic radiosurgery treatment response for brain metastases using MRI based diffusion index.

INTRODUCTION: To investigate the clinical predictive values of the apparent diffusion coefficient (ADC) as a biomarker in radiation response of brain metastases. METHOD: Forty-one patients with brain metastases treated with stereotactic radiosurgery (SRS) were imaged at baseline, one month post SRS, and six months post SRS using diffusion weighted MRI. The mean of ADC for metastases and tumor volume was calculated. A diffusion index (DI) was generated using the sum of 1/ADC among all the voxels in a tumor. Tumor response status was determined by lesion volume measured at six month post-SRS, or the last available follow-up MRI. Logistic regression analysis was used to account for factors associated with tumor response at baseline and one month post SRS. RESULTS: A higher ADC mean distinguished responders from non-responders only at six month post SRS (p < 0.05). However, a lower DI distinguished a responder from non-responders on the baseline, one month post SRS and six months post SRS, indicating better diagnostic performance of the DI with regard to a non-invasive biomarker in monitoring SRS treatment response. A multivariate logistic regression analysis identified the DI as a predictor of tumor response at baseline and one month post SRS (p = 0.002 and p = 0.001, respectively). However, logistic regression analysis identified the ADC mean as a predictor of tumor response only at six months post SRS (p = 0.019). CONCLUSION: Our results support the hypothesis that ADC and tumor volume generated DT at baseline, one month and six months post SRS may be a promising biomarker predicting brain metastases' response. Specifically, a lower DI at baseline and one month distinguished responders from non-responders.