Platelet-to-lymphocyte ratio predicts tumor response and survival of patients with hepatocellular carcinoma undergoing immunotherapies.

BACKGROUND: Lymphocyte-related factors were associated with survival outcome of different types of cancers. Nevertheless, the association between lymphocytes-related factors and tumor response of immunotherapy remains unclear. METHODS: This is a retrospective study. Eligible participants included patients with unresectable or advanced hepatocellular carcinoma (HCC) who underwent immunotherapy as their first-line treatment. Radiological assessment of tumor response adhered to RECIST 1.1 and HCC-specific modified RECIST (mRECIST) criteria. Univariate and multivariate logistic analyses were employed to analyze clinical factors associated with tumor response. Kaplan-Meier survivial analysis were employed to compare progression-free survival (PFS) and overall survival (OS) across different clinical factors. Furthermore, patients who received treatment with either a combination of bevacizumab and anti-PD-1(L1) antibody (Beva group) or tyrosine-kinase inhibitor (TKI) and anti-PD-1 antibody (TKI group) were examined to explore the relation between clinical factors and tumor response. RESULTS: A total of 208 patients were enrolled in this study. The median PFS and OS were 9.84 months and 24.44 months,respectively. An independent factor associated with a more favorable tumor response to immunotherapy was identified when PLR<100. Patients with PLR<100 had longer PFS than other patients, while OS showed no significant difference. Further analysis revealed that PLR exhibited superior prognostic value in patients of the Beva group as compared to those in the TKI group. CONCLUSIONS: There exisits an association between PLR and tumor response as well as survival outcomes in patients receiving immunotherapy, particularly those treated with the combination of bevacizumab and anti-PD-1.

A Network Pharmacology-based Study on the Anti-aging Properties of Traditional Chinese Medicine Sisheng Bulao Elixir.

BACKGROUND: Traditional Chinese Medicine (TCM) has a rich history of use in preventing senescence for millennia in China. Nonetheless, a systematic method to study the antiaging properties and the underlying molecular mechanism of TCM remains absent. OBJECTIVE: The objective of this study is to decipher the anti-aging targets and mechanisms of Sisheng Bulao Elixir (SBE) using a systematic approach based on a novel aging database and network pharmacology. METHODS: Bioactive compounds and target proteins in SBE were identified via the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Aging-related proteins were uncovered through alignment with the Ageing Alta database. A compound-target (CT) protein network analysis highlighted key flavonoids targeting aging. Core aging-related proteins were extracted through protein-protein interaction (PPI) network analysis. Molecular docking validated binding activities between core compounds and aging-related proteins. The antioxidant activity of SBE was confirmed using an in vitro senescent cells model. RESULTS: A total of 39 active compounds were extracted from a pool of 639 compounds in SBE. Through a matching process with the Aging Alta, 88 target proteins associated with the aging process were identified. Impressively, 80 out of these 88 proteins were found to be targeted by flavonoids. Subsequently, an analysis using CT methodology highlighted 11 top bioactive flavonoids. Notably, core aging-related proteins, including AKT1, MAPK3, TP53, VEGFA, IL6, and HSP90AA1, emerged through the PPI network analysis. Moreover, three flavonoids, namely quercetin, kaempferol, and luteolin, exhibited interactions with over 100 aging-related proteins. Molecular docking studies were conducted on these flavonoids with their shared three target proteins, namely AKT1, HSP90AA1, and IL6, to assess their binding activities. Finally, the antioxidant properties of SBE were validated using an in vitro model of senescent cells. CONCLUSION: This study offers novel insights into SBE's anti-aging attributes, providing evidence of its molecular mechanisms. It enhances our understanding of traditional remedies in anti-aging research.

The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.

BACKGROUND: The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. METHOD: A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. RESULTS: After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). CONCLUSION: The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.

Remnant cholesterol has an important impact on increased carotid intima-media thickness in non-diabetic individuals.

To investigate the correlation the correlation between residual cholesterol (RC) and increased carotid intima-media thickness(cIMT) in non-diabetic individuals. This study included 1786 non-diabetic individuals who underwent carotid ultrasound. RC was calculated based on total cholesterol (TC), LDL-C, and high density lipoprotein cholesterol (HDL-C). The subjects were divided into the cIMT thickening group (cIMT ≥ 0.1 cm) and non-thickening group (cIMT < 0.1 cm) groups based on cIMT, binary logistic regression with different models and receiver operating characteristic (ROC) curves were adopted to evaluate the predictive ability of RC in cIMT. Of the research participants , their median age was 55 (49-51) years, 1121 (63%) were male, and 209 (12%) had hypertension, and people in the cIMT thickening group (925) were more likely to be older and male than those in the non-thickening group (843). Across the different RC subgroups, there was an increasing trend in maximum cIMT (P < 0.001) as RC levels increased within quartiles. RC was found to be an independent risk predictor for cIMT thickening (all P < in models 1-3); and this result persisted in the LDL-C normal subgroup (P = 0.002). The results suggested that RC was an independent predictor of cIMT thickening in non-diabetic individuals and had a strong atherogenic effect.

Flexible Sensors Array Based on Frosted Microstructured Ecoflex Film and TPU Nanofibers for Epidermal Pulse Wave Monitoring.

Recent advances in flexible pressure sensors have fueled increasing attention as promising technologies with which to realize human epidermal pulse wave monitoring for the early diagnosis and prevention of cardiovascular diseases. However, strict requirements of a single sensor on the arterial position make it difficult to meet the practical application scenarios. Herein, based on three single-electrode sensors with small area, a 3 × 1 flexible pressure sensor array was developed to enable measurement of epidermal pulse waves at different local positions of radial artery. The designed single sensor holds an area of 6 × 6 mm2, which mainly consists of frosted microstructured Ecoflex film and thermoplastic polyurethane (TPU) nanofibers. The Ecoflex film was formed by spinning Ecoflex solution onto a sandpaper surface. Micropatterned TPU nanofibers were prepared on a fluorinated ethylene propylene (FEP) film surface using the electrospinning method. The combination of frosted microstructure and nanofibers provides an increase in the contact separation of the tribopair, which is of great benefit for improving sensor performance. Due to this structure design, the single small-area sensor was characterized by pressure sensitivity of 0.14 V/kPa, a response time of 22 ms, a wide frequency band ranging from 1 to 23 Hz, and stability up to 7000 cycles. Given this output performance, the fabricated sensor can detect subtle physiological signals (e.g., respiration, ballistocardiogram, and heartbeat) and body movement. More importantly, the sensor can be utilized in capturing human epidermal pulse waves with rich details, and the consistency of each cycle in the same measurement is as high as 0.9987. The 3 × 1 flexible sensor array is employed to acquire pulse waves at different local positions of the radial artery. In addition, the time domain parameters including pulse wave transmission time (PTT) and pulse wave velocity (PWV) can be obtained successfully, which holds promising potential in pulse-based cardiovascular system status monitoring.

Crystal structure, assembly process, and single-molecule magnet behavior of a triangular prismatic {Co9} cluster.

Using the polydentate ligand of H4L with the CoII ion, a triangular prism-type nine-nucleus cluster [Co9(L)3(CH2OCH2OH)6]·3.5H2O ({Co9}-Eg, H4L = 6,6'-(1H,1'H-[3,3'-bi(1,2,4-triazole)]-5,5'-diyl)dipicolinic acid) was constructed. Ion fragmentation during the formation of the {Co9}-Eg cluster was tracked using time-dependent electrospray ionization mass spectrometry. In addition, we proposed two possible formation processes (i) H4L → CoL → Co2L → Co6L3 → Co7L3 → Co9L3 and (ii) H4L → CoL → Co2L → Co3L → Co5L2 → Co7L3 → Co9L3. Magnetic studies show that {Co9}-Eg exhibits slow relaxation under a static zero field at low temperature, which is the main characteristic of single molecule magnets (SMMs).

Auxiliary Segmentation Method of Osteosarcoma in MRI Images Based on Denoising and Local Enhancement.

Osteosarcoma is a bone tumor which is malignant. There are many difficulties when doctors manually identify patients' MRI images to complete the diagnosis. The osteosarcoma in MRI images is very complex, making its recognition and segmentation resource-consuming. Automatic osteosarcoma area segmentation can solve these problems to a certain extent. However, existing studies usually fail to balance segmentation accuracy and efficiency. They are either sensitive to noise with low accuracy or time-consuming. So we propose an auxiliary segmentation method based on denoising and local enhancement. The method first optimizes the osteosarcoma images, including removing noise using the Edge Enhancement based Transformer for Medical Image Denoising (Eformer) and using a non-parameter method to localize and enhance the tumor region in MRI images. Osteosarcoma was then segmented by Deep Feature Aggregation for Real-Time Semantic Segmentation (DFANet). Our method achieves impressive segmentation accuracy. Moreover, it is efficient in both time and space. It can provide information about the location and extent of the osteosarcoma as a basis for further diagnosis.

Confusing delayed hematemesis, unusual arterial hemorrhage after pancreaticoduodenectomy: a case report.

Pancreaticoduodenectomy (PD) is one of the most complex surgeries and is associated with a high rate of complications, including bleeding, delayed gastric emptying (DGE), and pancreatic fistula. Although the frequency of postoperative hemorrhage is not high, this complication results in severe adverse outcomes. A 67-year-old man was diagnosed with pancreatic cancer and underwent PD. On the tenth day after surgery, he developed hypovolemic shock with hematemesis. Urgent digital subtraction angiography identified the bleeding artery as the jejunal mesenteric artery at the afferent loop, and the bleeding artery was embolized with two coils. After digital subtraction angiography, the patient had an uneventful recovery with no further complications. Therefore, we concluded that it is possible that bleeding may occur in the afferent loop when hemorrhage occurs after PD.

Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis.

Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.

Advances of Light/Ultrasound/Magnetic-Responsive Nanoprobes for Visualized Theranostics of Urinary Tumors.

Light/ultrasound/magnetic-responsive nanomaterials exhibit excellent performance in imaging and therapy and play an important role in precision theranostics of tumors. In contrast to deep organs, urinary organs (such as bladder and prostate) can easily be studied via intervention mode, which has greatly brought promising applications of stimuli-responsive nanoprobes in visualized theranostics of urinary tumors. Therefore, it has been very critical to develop stimuli-responsive nanoprobes with high safety, stability, and reliability against urinary tumors. In this review, recent advances in light/ultrasound/magnetic-responsive nanoprobes in visualized theranostics of urinary tumors are summarized, including magnetic resonance/fluorescence/ultrasound/photoacoustic imaging and multimodal imaging, photothermal/photodynamic/sonodynamic therapy and combination therapy, and single-modal/multimodal-imaging-guided visualized theranostics. Finally, the future perspectives of light/ultrasound/magnetic-responsive nanoprobes against urinary tumors are also prospected.

A Flexible Pressure Sensor with a Mesh Structure Formed by Lost Hair for Human Epidermal Pulse Wave Monitoring.

Flexible pressure sensors with the capability of monitoring human vital signs show broad application prospects in personalized healthcare. In this work, a hair-based flexible pressure sensor (HBPS) consisting of lost hair and polymer films was proposed for the continuous monitoring of the human epidermal arterial pulse waveform. A macroscale mesh structure formed by lost hair provides a simplified spacer that endows the triboelectric-based flexible pressure sensor with sufficient contact-separation space. Based on this mesh structure design, the hair-based flexible pressure sensor can respond to the slight pressure change caused by an object with 5 mg weight and hold a stable output voltage under 1-30 Hz external pressure excitation. Additionally, the hair-based flexible pressure sensor showed great sensitivity (0.9 V/kPa) and decent stability after 4500 cycles of operation. Given these compelling features, the HBPS can successfully measure the human epidermal arterial pulses with obvious details at different arteries. The proposed HBPS can also be used to monitor the pulse signals of different subjects. Furthermore, the three different pulse wave transmission time (PTT) values (PTT-foot, PTT-middle, and PTT-peak) can be obtained by simultaneously monitoring human pulse and electrocardiogram signals, which has enormous application potential for assessing cardiovascular system health.

How Chinese Web Users Value Their Personal Information: An Empirical Study on WeChat Users.

PURPOSE: The purpose of the study is to investigate Chinese web users' monetary valuation of their personal information (PI) and its psychological driving factors, and thereby promote the establishment of the PI market in China. METHODS: In this study, a survey was conducted with 710 Chinese WeChat users to determine how they perceive the monetary value of their PI. RESULTS: The survey results demonstrate that the "endowment effect" exists among Chinese web users, indicating different allocations of PI property rights may elicit distinct outcomes. The results also reveal that Chinese web users' willingness-to-pay (WTP) is mainly driven by privacy concern and intimacy of disclosure, and their willingness-to-accept (WTA) is mainly driven by privacy concern, intimacy of disclosure and psychological ownership. CONCLUSION: The results imply that market players in China can use these driving factors to increase consumers' valuation of their PI to maintain a stable user base, and a portion of users will choose paid but privacy-guaranteed services to protect their PI. Furthermore, our findings indicate that when there is a formal monetary PI market, a privacy class may emerge.

Assessment of Vascular Network Connectivity of Hepatocellular Carcinoma Using Graph-Based Approach.

BACKGROUND: The angiogenesis of liver cancer is a key condition for its growth, invasion, and metastasis. This study aims to investigate vascular network connectivity of hepatocellular carcinoma (HCC) using graph-based approach. METHODS: Orthotopic HCC xenograft models (n=10) and the healthy controls (n=10) were established. After 21 days of modeling, hepatic vascular casting and Micro-CT scanning were performed for angiography, followed by blood vessels automatic segmentation and vascular network modeling. The topologic parameters of vascular network, including clustering coefficient (CC), network structure entropy (NSE), and average path length (APL) were quantified. Topologic parameters of the tumor region, as well as the background liver were compared between HCC group and normal control group. RESULTS: Compared with normal control group, the tumor region of HCC group showed significantly decreased CC [(0.046 ± 0.005) vs. (0.052 ± 0.006), P=0.026], and NSE [(0.9894 ± 0.0015) vs. (0.9927 ± 0.0010), P<0.001], and increased APL [(0.433 ± 0.138) vs. (0.188 ± 0.049), P<0.001]. Compared with normal control group, the background liver of HCC group showed significantly decreased CC [(0.047 ± 0.004) vs. (0.052 ± 0.006), P=0.041] and increased NSE [0.9938 (0.9936~0.9940) vs. (0.9927 ± 0.0010), P=0.035]. No significant difference was identified for APL between the two groups. CONCLUSION: Graph-based approach allows quantification of vascular connectivity of HCC. Disrupted vascular topological connectivity exists in the tumor region, as well as the background liver of HCC.

Feasibility of automatic detection of small hepatocellular carcinoma (≤2 cm) in cirrhotic liver based on pattern matching and deep learning.

Background and objective.Early detection of hepatocellular carcinoma (HCC) is crucial for clinical management. Current studies have reported large HCC detections using automatic algorithms, but there is a lack of research on automatic detection of small HCCs (sHCCs). This study is to investigate the feasibility of automatic detection of sHCC (≤2 cm) based on pattern matching and deep learning (PM-DL) model.Materials and methods. A retrospective study included 5376 image sets from 56 cirrhosis patients (28 sHCC patients with 32 pathologically confirmed lesions and 28 non-HCC cirrhosis patients) in the training-validation cohort to build and validate the model through five-fold cross-validation. In addition, an external test cohort including 6144 image sets from 64 cirrhosis patients (32 sHCC patients with 38 lesions and 32 non-HCC cirrhosis patients) was applied to further verify the generalization ability of the model. The proposed PM-DL model consisted of three main steps: 3D co-registration and liver segmentation, screening of suspicious lesions on diffusion-weighted imaging images based on pattern matching algorithm, and identification/segmentation of sHCC lesions on dynamic contrast-enhanced images with convolutional neural network.Results.The PM-DL model achieved a sensitivity of 89.74% and a positive predictive value of 85.00% in the external test cohort for per-lesion analysis. No significant difference was observed in volumes (P= 0.13) and the largest sizes (P= 0.89) between manually delineated and segmented lesions. The DICE coefficient reached 0.77 ± 0.16. Similar performances were identified in the validation cohort. Moreover, the PM-DL model outperformed Liver Imaging Reporting and Data System (LI-RADS) in sensitivity (probable HCCs: LR-5 or LR-4,P= 0.18; definite HCCs: LR-5,P< 0.001), with a similar high specificity for per-patient analysis.Conclusion. The PM-DL model may be feasible for accurate automatic detection of sHCC in cirrhotic liver.

Using Alizarin Red Staining to Detect Chemically Induced Bone Loss in Zebrafish Larvae.

Chemically induced bone loss due to lead (Pb) exposure could trigger an array of adverse impacts on both human and animal skeletal systems. However, the specific effects and mechanisms in zebrafish remain unclear. Alizarin red has a high affinity for calcium ions and can help visualize the bone and illustrate skeletal mineral mass. In this study, we aimed to detect lead acetate (PbAc)-induced bone loss in zebrafish larvae by using alizarin red staining. Zebrafish embryos were treated with a series of PbAc concentrations (0, 5, 10, 20 mg/L) between 2 and 120 h post fertilization. Whole-mount skeletal staining was conducted on larvae at 9 days post fertilization, and the total stained area was quantified using ImageJ software. The results indicated that the mineralized tissues were stained in red, and the stained area decreased significantly in the PbAc-exposure group, with a dose-dependent change in bone mineralization. This paper presents a staining protocol for investigating skeletal changes in PbAc-induced bone defects. The method can also be used in zebrafish larvae for the detection of bone loss induced by other chemicals.

Role of GH/IGF axis in arsenite-induced developmental toxicity in zebrafish embryos.

Growth hormone (GH)/insulin-like growth factor (IGF) axis plays a critical role in fetal development. However, the effect of arsenite exposure on the GH/IGF axis and its toxic mechanism are still unclear. Zebrafish embryos were exposed to a range of NaAsO2 concentrations (0.0-10.0 mM) between 4 and 120 h post-fertilization (hpf). Development indexes of survival, malformation, hatching rate, heart rate, body length and locomotor behavior were measured. Hormone levels, GH/IGF axis-related genes, and nerve-related genes were also tested. The results showed that survival rate, hatching rate, heart rate, body length and locomotor behavior all decreased, while deformity increased. At 120 hpf, the survival rate of zebrafish in 1.5 mM NaAsO2 group was about 70%, the deformity rate exceeded 20%, and the body length shortened to 3.35 mm, the movement distance of zebrafish decreased approximately 63.6% under light condition and about 52.4% under dark condition. The level of GH increased and those of IGF did not change significantly, while the expression of GH/IGF axis related genes (ghra, ghrb, igf2r, igfbp3, igfbp2a, igfbp5b) and nerve related genes (dlx2, shha, ngn1, elavl3, gfap) decreased. In 1.5 mM NaAsO2 group, the decrease of igfbp3 and igfbp5b was almost obvious, about 78.2% and 72.2%. The expression of nerve genes in 1.5 mM NaAsO2 group all have declined by more than 50%. These findings suggested that arsenite exerted disruptive effects on the endocrine system by interfering with the GH/IGF axis, leading to zebrafish embryonic developmental toxicity.

Possible differences in the mechanism of malignant transformation of HaCaT cells by arsenite and its dimethyl metabolites, particularly dimethylthioarsenics.

BACKGROUND: As a confirmed human carcinogen, arsenic can cause skin cancer, lung cancer, etc. However, its carcinogenic mechanism is still unclear. In recent years, the oxidative stress hypothesis has become widely accepted. In mammals it has been found that arsenic can be converted to dimethylarsinous acid (DMAIII) and dimethylmonothioarsinic acid (DMMTAV) through a series of methylation and redox reactions. DMAIII and DMMTAV are highly toxic. METHODS: Human keratinocytes (HaCaT) were exposed to different concentrations of NaAsO2 (IAsIII), DMMTAV and DMAIII for 24 h. Reactive oxygen species (hydrogen peroxide and superoxide), oxidative damage markers (8-hydroxydeoxyguanosine and malondialdehyde), and antioxidant markers (glutathione and superoxide dismutase) were measured. In addition, sulfane sulfurs were measured in HaCaT cells and a cell-free system. RESULTS: In the DMMTAV and DMAIII treatment groups, the levels of hydrogen peroxide and superoxide in HaCaT cells were higher than in the IAsIII treatment groups at the same dose. Levels of 8-OHdG and MDA in the DMMTAV and DMAIII treatment groups were also higher than those in the IAsIII treatment groups at the same dose. However, in the DMMTAV and DMAIII treatment groups, the levels of GSH and SOD activity were lower than that in the IAsIII treatment groups. In DMMTAV-treated HaCaT cells, sulfane sulfurs were produced. Further, it was found that DMMTAV could react with DMDTAV to form persulfide in the cell-free system, which may explain the mechanism of the formation of sulfane sulfurs in DMMTAV-treated HaCaT cells. CONCLUSIONS: DMMTAV and DMAIII more readily induce reactive oxygen species (ROS) and cause oxidative damage in HaCaT cells than inorganic arsenic. Further, the persulfide formed by the reaction of DMMTAV and DMDTAV produced from the metabolism of DMMTAV may induce a stronger reductive defense mechanism than GSH against the intracellular oxidative stress of DMMTAV. However, the cells exposed to arsenite are transformed by the continuous nuclear translocation of Nrf2 due to oxidative stress, and the persulfide from dimethylthioarsenics may promote Nrf2 by the combination with thiol groups, especially redox control key protein, Keap1, eventually cause nuclear translocation of sustained Nrf2.

The protective effect of silk fibroin on high glucose induced insulin resistance in HepG2 cells.

The therapeutic use of silk-derived materials such as fibroin in biomedicine is well-established in Southeast Asian countries. Studies indicated that silk fibroin (SF) peptide enhances insulin sensitivity and glucose metabolism phenomena associated with type 2 diabetes mellitus (T2DM) suggesting this peptide may be beneficial to treat this disease. However, the mechanisms underlying protective effect of SF in insulin-mediated hepatic metabolic dysfunction remains unclear. The aim of this study was to investigate the influence of SF on insulin resistant HepG2 cells which were used a model of T2DM. Treatment of cells with 30 mmol/L of glucose and 10-6 mol/L insulin for 48 h significantly reduced glucose consumptions and intracellular glycogen levels but increased triglyceride (TG) levels. SF or metformin alone elevated glucose consumptions and glycogen accumulation accompanied by lower TG content. Greater effects in these metabolic parameters were found when SF and metformin were combined. Treatment of insulin resistant cells with SF or metformin alone decreased levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6); whereas antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activity, as well as total antioxidant capacity (T-AOC) ability increased. The combination of SF and metformin produced greater changes in these parameters compared to metformin alone. Data indicated that the protective effect of SF or metformin in insulin resistant HepG2 cells involves inhibition of oxidant processes and that the combination of agents may prove more effective therapeutically.

Ultrasound-targeted microbubble enhances migration and therapeutic efficacy of marrow mesenchymal stem cell on rat middle cerebral artery occlusion stroke model.

To investigate the role of ultrasound-targeted microbubbles in the homing effect of bone marrow-derived mesenchymal stem cells (BMSCs) and in the therapeutic efficacy of BMSCs on the ischemic stroke. A middle cerebral artery occlusion (MCAO) model was induced by plug wire preparation. Seventy-two hours after MCAO, the treatment of BMSCs with ultrasound-targeted microbubble was assessed via modified neurological severity score (mNSS), infarct volumes, and cerebral edema. In addition, immunofluorescence was performed to analyze the homing effect of BMSCs with ultrasound-targeted microbubble. We find that BMSCs with ultrasound-targeted microbubble (BMMSCs with ultrasound-targeted microbubble [USMM] group) could significantly ameliorate mNSS, infarct volumes, and cerebral edema of MCAO compared with phosphate buffer saline group, BMSCs alone group (BMSC group), and BMSCs with Ultrasound group (Ultrasound group). Immunofluorescence analysis demonstrated that ultrasound-targeted microbubbles promoted the accumulation of BMSCs in rat MCAO brains. Our findings demonstrated that ultrasound-targeted microbubble could be an effective approach for the accumulation of BMSCs on ischemic stroke, and further improved the therapeutic efficacy of BMSCs on MCAO.

Cerebral venous sinus thrombosis complicated by seizures: a retrospective analysis of 69 cases.

Cerebral venous sinus thrombosis (CVST) is a rare ischemic cerebrovascular disease. The aim of this retrospective observational study was to investigate the risk factors for complication of cerebral venous sinus thrombosis by seizures and to explore the impact of such seizures on clinical outcomes. Patients with cerebral venous sinus thrombosis with or without epileptic seizures were retrospectively analyzed and compared in terms of clinical variables, causative factors, clinical presentation, and imaging data. In all, 69 patients with cerebral venous sinus thrombosis were enrolled in this study, 32 (46.38%) of whom had experienced secondary seizures. Compared with those with no seizures, significantly more patients with secondary seizures had hemiplegia (37.50 vs. 15.63%; P = 0.020), bleeding (29.40 vs. 10.81%; P = 0.047), lesions involving the frontal (31.25 vs. 10.81%; P = 0.023) and temporal lobe (43.75 vs. 8.11%; P = 0.005), and thrombosis in the superior sagittal sinus (65.63 vs. 40.54%; P = 0.036). Multivariate logistic regression analysis showed focal neurological deficits (P = 0.004, odds ratio = 5.16, 95% CI 1.99-15.76) and thrombosis of the superior sagittal sinus (P = 0.039, odds ratio = 0.13, 95% CI 0.04-0.37) were independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis. In addition, mortality rate (9.38 vs. 5.41%; P = 0.469) and 90-day excellent prognosis rate (81.25 vs. 86.47%; P = 0.793) did not differ significantly between patients with and without epileptic seizures. The presence of focal neurological deficits and thrombosis of the superior sagittal sinus are independent risk factors for secondary seizures in patients with cerebral venous sinus thrombosis, whereas mortality and 90-day prognosis have no correlation with secondary seizures.