Resveratrol inhibits TRAF6/PTCH/SMO signal and regulates prostate cancer progression.

Prostate cancer (PC) is one of the most common types of cancers among men, referring to the uncontrolled growth of the prostate gland. It is increasingly recognized that the interaction of the glioma-associated oncogene (GLI) pathway and androgen receptor affects PC progression. Nevertheless, the effects of resveratrol on PC progression via Hedgehog (HH) signaling remain unexplored. In this study, the castration-sensitive and castration-resistant xenograft models in mice are systematically established using two different PC cell lines (LNCaP and PC-3). Further, the Western blotting, immunohistochemistry, MTT, Transwell, and RT-qPCR analyses are performed to verify the mechanistic views of resveratrol on PC and HH signals in vitro and in vivo. Resveratrol showed epithelial-mesenchymal transition (EMT) progression, inhibiting the tumor size and expression levels of vimentin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) 7, as well as upregulating the expression profiles the E-cadherin and Annexin 2. Moreover, resveratrol inhibited the hedgehog (HH) signals and tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) levels exhibiting the therapeutic action on castration-sensitive and castration-resistant PC cell lines. In summary, the overexpression of TRAF6 enhanced the viability and EMT progression of cancer cells. The resveratrol could alleviate the TRAF6 effect and regulate the HH signal to affect PC progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00544-0.

To Explore the Diagnostic Value of Bulbocavernosus Muscle Reflex and Pudendal Somatosensory Evoked Potentials for Diabetic Neurogenic Bladder.

Objective: To explore the diagnostic value of bulbocavernosus muscle reflex and pudendal somatosensory evoked potentials for diabetic neurogenic bladder. Methods: From January 2021 to December 2021, 104 patients with type 2 diabetes mellitus admitted to the hospital were recruited, with 57 allocated to the case group and 47 to the control group. Outcome measures included bulbocavernosus muscle response, pudendal somatosensory evoked potentials, and bladder residual urine volume. The connection of bulbocavernosus muscle response and pudendal somatosensory evoked potentials with bladder residual urine volume was investigated using the Pearson analysis. Results: In both males and females, the latency of the left and right bulbocavernosus muscle reflexes in the case group was longer than in the control group, but the difference was not statistically significant (P > 0.05), and the wave amplitude of the left and right bulbocavernosus muscle reflexes was significantly smaller than that of the control group (P < 0.05). The diabetic neurogenic bladder was associated with a significantly longer latency and a smaller wave amplitude of pudendal somatosensory evoked potentials versus without neurogenic bladder (P < 0.05). Patients with a diabetic neurogenic bladder had more residual bladder urine volume versus those without (P < 0.05). Bladder residual urine volume was significantly positively correlated with bulbocavernosus muscle reflex and pudendal somatosensory evoked potential latency and negatively correlated with wave amplitude (P < 0.05). Conclusion: The bulbocavernosus muscle reflex and pudendal somatosensory evoked potentials demonstrate great potential as adjuncts to diagnose diabetic neurogenic bladder and correlate with ultrasound results in determining bladder function in patients.

Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis.

Acute liver failure (ALF) is a severe clinical syndrome characterized by massive death of hepatocytes in a short time, resulting in coagulopathy and hepatic encephalopathy, with a high mortality in patients without pre-existing liver disease. Effective treatment of ALF is currently limited to liver transplantation, highlighting the need for new target therapies. Here, we found that expression of hepatic tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor tumor necrosis factor receptor superfamily member 12A (Tnfrsf12a) were significantly increased during ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Inhibition of TWEAK/Tnfrsf12a axis markedly attenuated TAA or APAP-induced ALF. Moreover, our results demonstrated that TWEAK/Tnfrsf12a axis induced receptor-interacting protein kinase 1 (RIPK1)-dependent apoptosis of hepatocytes, instead of necroptosis or pyroptosis. Notably, hepatic TNFRSF12A and TWEAK levels were also significantly increased in liver biopsies from ALF patients. In summary, our results demonstrate that during ALF, TWEAK/Tnfrsf12a axis activates RIPK1 in hepatocytes, leading to RIPK1-dependent apoptosis and subsequent liver injury. Therefore, inhibition of either TWEAK/Tnfrsf12a axis or RIPK1-dependent apoptosis attenuates liver injury, providing a new potential therapeutic target for the treatment of ALF.

Does the Relationship Between Bone Cement and the Intravertebral Cleft of Kummell Disease Affect the Efficacy of PKP?

OBJECTIVE: To study the relationship between distribution of bone cement and intravertebral cleft of patients with Kummell disease on the clinical effect of percutaneous kyphoplasty (PKP). METHODS: According to the relationship between the distribution of bone cement and the cleft in the vertebrae, a total of 92 patients with Kummell disease who underwent PKP in our hospital were divided into 2 groups. Specifically, the bone cement of patients in group A was localized in the cleft of the vertebrae and did not infiltrate around the cleft, while that of group B patients not only filled the cleft of the vertebrae, but also distributed diffusely around the cleft of the vertebrae. The amount of bone cement injected, leakage rate, visual analogue scale (VAS) score, Oswestry Disability Index (ODI), and vertebral imaging changes before operation, and 2 days and 1 year after operation were compared between the 2 groups. RESULTS: The amount of bone cement injected and the permeability of bone cement in group B were higher than those in group A (P < 0.05). The scores of VAS and ODI in both groups were significantly improved after operation, but the two scores in group B were better than those in group A one year after operation. The height of anterior vertebral body and Cobb's angle of kyphosis in the 2 groups were significantly improved after operation, but 1 year after operation, those in group B were better than those in group A. CONCLUSIONS: PKP was an effective method for treating Kummell disease. At the same time, the relationship between the distribution of bone cement and the cleft in the vertebral body was an important factor affecting the curative effect after PKP. The effect of the distribution pattern of bone cement filled with intravertebral cleft and diffusely distributed around the fissures was better than that of bone cement confined in the vertebral cleft.

Uncovering the Key miRNAs and Targets of the Liuwei Dihuang Pill in Diabetic Nephropathy-Related Osteoporosis based on Weighted Gene Co-Expression Network and Network Pharmacology Analysis.

BACKGROUND: Diabetic nephropathy-related osteoporosis (DNOP) is the most common comorbid bone metabolic disorder associated with diabetes mellitus (DM). The Liuwei Dihuang Pill (LWD) is a traditional Chinese herbal medicine widely used to treat diabetic complications, including diabetic nephropathy (DN). This study aimed to identify the biomarkers of the mechanisms of DNOP in LWD with systems biology approaches. METHODS: Herein, we performed an integrated analysis of the GSE51674 and GSE63446 datasets from the GEO database via weighted gene co-expression network and network pharmacology (WGCNA) analysis. In addition, a network pharmacology approach, including bioactive compounds, was used with oral bioavailability (OB) and drug-likeness (DL) evaluation. Next, target prediction, functional enrichment analysis, network analysis, and virtual docking were used to investigate the mechanisms of LWD in DNOP. RESULTS: WGCNA successfully identified 63 DNOP-related miRNAs. Among them, miR-574 was significantly upregulated in DN and OP samples. A total of 117 targets of 22 components associated with LWD in DNOP were obtained. The cellular response to nitrogen compounds, the AGERAGE signaling pathway in diabetic complications, and the MAPK signaling pathway were related to the main targets. Network analysis showed that kaempferol and quercetin were the most significant components. MAPK1 was identified as a potential target of miR-574 and the hub genes in the protein-protein interaction (PPI) network. The docking models demonstrated that kaempferol and quercetin had a strong binding affinity for Asp 167 of MAPK1. CONCLUSION: This study demonstrated that miR-574 may play important roles in DNOP, and the therapeutic effects of kaempferol and quercetin on LWD in DNOP might be mediated by miR-574 by targeting MAPK1. Our results provide new perspectives for further studies on the anti-DNOP mechanism of LWD.

Tunable NH4F-Assisted Synthesis of 3D Porous In2O3 Microcubes for Outstanding NO2 Gas-Sensing Performance: Fast Equilibrium at High Temperature and Resistant to Humidity at Room Temperature.

NO2 gas sensors based on metal oxides under wild conditions are highly demanded yet an incomplete surface reaction and humidity interference on the gas-sensing performance limit their applications. Herein, we report three-dimensional (3D) porous In2O3 microcubes via a simple hydrothermal strategy to produce outstanding NO2 gas-sensing performance: fast equilibrium of the surface reaction at 150 °C and negligible humidity dependence on the NO2 gas sensing at room temperature. The 3D porous In2O3 microcubes with high surface areas, suitable pore sizes, rich oxygen vacancies, and high conductivity are testified. The underlying structural transformation mechanism for 3D porous In2O3 is investigated in detail. The as-made 3D porous In2O3 microcubic gas sensors present excellent gas-sensing performance to 50 ppm NO2 at 150 °C, including a high response value (2329), fast response/recovery time (10/9 s), a low detection limit (10 ppb), long-term stability (60 days), and strong selectivity. Furthermore, they exhibit relatively stable NO2 gas response under humidity variation (20-80%). The NO2 gas mechanism under the interference of water is also clarified.

Application of ultrasound during electrode implantation for sacral neuromodulation in patients with neurogenic bladder secondary to spinal cord disease: a retrospective study.

PURPOSE: To compare the use of intraoperative ultrasound with X-ray fluoroscopy during sacral neuromodulation lead electrode placement in patients with neurogenic bladder secondary to spinal cord disease. METHODS: We reviewed the medical records of 52 patients who underwent sacral neuromodulation (SNM) lead electrode implantation under fluoroscopy or ultrasound guidance from July 2016 to July 2019. The operating time, number of electrode contacts with stimulus responses, minimum voltage that causes a stimulus response, and rate of standard lead electrode placement were used to assess the differences between the two methods. All patients were evaluated by recording bladder diaries, postvoid residual volumes before and during the testing period. Permanent SNM implantation is acceptable if symptoms improve by at least 50%. RESULTS: The operating time decreased from 87.1 ± 25.19 min in the X-ray group to 68.2 ± 25.20 min (p < 0.05) in the ultrasound group. The number of electrode contacts with stimulus responses, rate of standard lead electrode placement, and implantable pulse generator (IPG) placement rate were not significantly different between the two groups (p > 0.05). There was no radiation exposure during the operation in the ultrasound group. No incisional infections, hematomas, or other critical complications were reported in either groups. CONCLUSION: Ultrasound can be applied to safely place lead electrode for sacral neuromodulation and leads to no radiation exposure to the patient, surgeon, and operating room staff and a shortened operating time while maintaining the same efficacy as X-ray.

Effect of Suanzaoren Tang on Energy Metabolism of Liver Mitochondria in Aged Rats with Chronic Rapid Eye Movement Sleep Deprivation and Its Mechanism / 中国实验方剂学杂志

Objective:To study the effect of Suanzaoren Tang on energy metabolism of liver mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation. Method:Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg^-1·d^-1）， and low- （6.48 g·kg^-1·d^-1） and high-dose （12.96 g·kg^-1·d^-1） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of <italic>D</italic>-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of liver mitochondria was observed under the transmission electron microscope. The content of adenosine triphosphate （ATP） in rat liver was detected by colorimetry， and the activities of ubiquinone oxidoreductase （complex Ⅰ）， succinate-ubiquinone oxidoreductase （complex Ⅱ）， ubiquinol-cytochrome c oxidoreductase （complex Ⅲ）， and cytochrome c oxidase （complex Ⅳ） in mitochondrial respiratory chain of rat liver were measured by colorimetry. The protein expression levels of citrate synthase （CS）， isocitrate dehydrogenase （IDH）， and ATP synthase， H⁺ transporting， mitochondrial F0 complex， subunit b， isoform 1 （ATP5F1） in rat liver were assayed by Western blot. Result:The mitochondrial damage in rat liver of the model group was more serious than that in the control group， manifested as mitochondrial swelling and deformation as well as cristae rupture and reduction. The comparison with the model group revealed that both the positive control and Suanzaoren Tang at the high dose obviously alleviated the mitochondrial swelling and deformation and reduced cristae rupture， with better improvements observed in the high-dose Suanzaoren Tang group. Compared with the control group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the model group were all significantly decreased （<italic>P<</italic>0.01）. Compared with the model group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the high-dose Suanzaoren Tang group were all significantly increased （<italic>P<</italic>0.05，<italic>P<</italic>0.01）. In the positive control group， the content of ATP， the activities of mitochondrial respiratory chain complexes I and Ⅲ， and the protein expression levels of CS and ATP5F1 in rat liver were significantly increased （<italic>P<</italic>0.05，<italic> P<</italic>0.01）. The activities of mitochondrial respiratory chain complexes Ⅰ and Ⅲ and the ATP5F1 protein expression in the low-dose Suanzaoren Tang group were significantly elevated （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Conclusion:Suanzaoren Tang alleviates the abnormal liver energy metabolism induced by chronic REM sleep deprivation in the elderly rats， which may be related to its enhancement of mitochondrial electron transport chain enzyme activities and the up-regulation of protein expression levels of CS， IDH and ATP5F1.

RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif.

Necroptosis is mediated by signaling complexes called necrosomes, which contain receptor-interacting protein 3 (RIP3) and upstream effectors, such as RIP1. In necrosomes, the RIP homotypic interaction motif (RHIM) of RIP3 and RIP1 forms amyloidal complex. But how the amyloidal necrosomes control RIP3 activation and cell necroptosis has not been determined. Here, we showed that RIP3 amyloid fibrils could further assemble into large fibrillar networks which presents as cellular puncta during necroptosis. A viral RHIM-containing necroptosis inhibitor M45 could form heteroamyloid with RIP3 in cells and prevent RIP3 puncta formation and cell necroptosis. We characterized mutual antagonism between RIP3-RHIM and M45-RHIM in necroptosis regulation, which was caused by distinct inter-filament interactions in RIP3, M45 amyloids revealed with atomic force microscopy. Moreover, double mutations Asn464 and Met468 in RIP3-RHIM to Asp disrupted RIP3 kinase-dependent necroptosis. While the mutant RIP3(N464D/M468D) could form amyloid as wild type upon necroptosis induction. Based on these results, we propose that RIP3 amyloid formation is required but not sufficient in necroptosis signaling, the ordered inter-filament assembly of RIP3 is critical in RIP3 amyloid mediated kinase activation and cell necroptosis.

ICP6 Prevents RIP1 Activation to Hinder Necroptosis Signaling.

Necroptosis is a type of programmed necrosis which depends on the activation of receptor-interacting protein kinase 3 (RIP3). Herpes simplex virus type 1 (HSV-1) is known to block necroptosis by the viral protein ICP6 in human cells, but its specific inhibitory mechanism is not fully understood. Here we reported that ICP6 could promote rather than suppress the formation of necrosome, the necroptosis signaling complex containing RIP3 and upstream regulator receptor-interacting protein kinase 1 (RIP1), but blocked RIP3 activation. Moreover, ICP6 could reduce the necroptosis-specific auto-phosphorylation of RIP1 regardless of the presence of RIP3. These results indicate that ICP6 block necroptosis through preventing RIP1 activation dependent signal transduction in necrosome.

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/ß-catenin signaling pathway in diabetic nephropathy-related osteoporosis.

The effects of Liuwei Dihuang pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. The present study aimed to evaluate the effects of LWDH on KDM7A and Wnt/ß-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week-old male Sprague-Dawley (SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/ß-catenin pathway-related proteins were determined by Western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1ß, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium and phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1 and ß-catenin were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/ß-catenin pathway.

Catalpol Promotes the Proliferation and Differentiation of Osteoblasts Induced by High Glucose by Inhibiting KDM7A.

INTRODUCTION: The protective effect of catalpol on diabetic osteoporosis (DOP) and its mechanism remain unclear. This study aimed to explore whether catalpol enhanced the proliferation and differentiation of MC3T3 cells induced by high glucose by inhibiting the expression of KDM7A. METHODS: MC3T3 cells were induced by high glucose (HG) and treated with different concentrations of catalpol. The proliferation and mineralization abilities of MC3T3-E1 cells were determined by CCK-8 assay and Alizarin Red Staining, respectively. The expression of differentiation-related osteogenic proteins, KDM7A and related proteins of Wnt/ß-catenin signaling pathway was analyzed by Western blot analysis. The alkaline phosphatase (ALP) activity was detected by ALP assay kits. RESULTS: MC3T3-E1 cells induced by high glucose showed decreased proliferation and mineralization abilities and decreased ALP activity, which were all reversed by the treatment of catalpol. High glucose induction inhibited the expression of KDM7A, Total-ß-catenin, Nuclear-ß-catenin and p-GSK3ß, which was reversed by the treatment of catalpol. And KDM7A interference up-regulated the expression of Total-ß-catenin, Nuclear-ß-catenin and p-GSK3ß, which was down-regulated by KDM7A overexpression. Furthermore, the proliferation and mineralization abilities and ALP activity were improved when treated with KDM7A interference and decreased when treated with KDM7A overexpression. However, SKL2001 could improve the proliferation and mineralization abilities and ALP activity of MC3T3-E1 cells. DISCUSSION: Catalpol promotes the proliferation and differentiation of osteoblasts induced by high glucose by regulating the Wnt/ß-catenin signaling pathway through KDM7A.

Effect and Mechanism of Modified Banxia Xiexintang on Depression During Perimenopause / 中国实验方剂学杂志

Objective::To observe the effect of modified Banxia Xiexintang on depression during perimenopause, in order to study itseffecton 5-hydroxytryptamine (5-HT) and proinflammatory factors. Method::One hundred and thirty-nine patients were randomly divided into control group (69 cases) and observation group (70 cases) by random number table.Patients in control group got tibolone tablets, 2.5 mg/time, 1 time/day, and paroxetine hydrochloride tablets, 20 mg/time, 1 time/day.In addition to the therapy in control group, patients in observation group were added with modified Banxia Xiexintang, 1 dose/day.The course of treatment was 8 weeks.And before and after treatment, Hamilton depression scale for-17 items (HAMD-17), Zung's self-rating depression scale (SDS), hamilton anxiety scale (HAMA), improvement Kupperman(KI), liver depression and spleen deficiency syndrome, menopause-specific quality of life questionnaire (MENQOL) and treatment emergent symptom scale (TESS) were scored, and levels of 5-HT, rain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected. Result::After treatment, scores of HAMD-17 and SDS in observation group were lower than those in control group (P<0.01). And the effect on trea depression in observation group was better than that in control group (Z=2.074, P<0.05). The degree of depression in observation group was ligher than that in control group (Z=2.157, P<0.05). And scores of HAMA, KI and liver depression and spleen deficiency syndrome were lower than those in control group (P<0.01). The severity of perimenopausal syndrome was ligher than that in control group (Z=2.046, P<0.05). And scores of vasomotor symptoms and psychological symptoms of MENQOL scale and the total scores were lower than those in control group (P<0.05). Levels of 5-HT and BDNF were higher than those in control group (P<0.01), while levels of IL-1β, TNF-α and TESS were lower than those in control group (P<0.01). Conclusion::In addition to theroutine western medicine, modified Banxia Xiexintang can alleviate the severity of depression, release the symptoms of depression, anxiety and perimenopausal syudrome(PMS), improve the quality of life, inhibit pro-inflammatory factors, and enhance the expressions of 5-HT and BDNF, with no adverse event.

Chemistry research on natural product derivatives of dihydro-β-agarofuran sesquiterpenoids / 中国中药杂志

Dihydro-β-agarofuran sesquiterpenoids possess chemical diversity and biodiversity. A dihydro-β-agarofuran sesquiterpenoid with only hydroxyl groups has been prepared by basic hydrolysis of crude extract of Euonymus bungeanus with 0.4% yield. Twelve derivatives were available in esterification, oxidation, decarboxylation, etc. Extensive ~1H-NMR,~(13)C-NMR, MS spectroscopic analyses and single-crystal X-ray diffraction analysis with Cu Kα radiation indicated that eleven derivatives were new compounds. The results will provide reference for chemistry study on natural product derivatives of dihydro-β-agarofuran sesquiterpenoids.

Nucleation density and pore size tunable growth of ZnO nanowalls by a facile solution approach: growth mechanism and NO2 gas sensing properties.

Nanowalls are novel nanostructures whose 3D porous network morphology holds great potential for applications as gas sensors. The realization of such a nanowall-based gas sensor depends directly on the comprehensive understanding of the growth mechanism of the nanowalls. We induced nucleation density and pore size evolution by increasing the dipping and growth times. The investigation indicates that the 3D porous ZnO nanowalls consist of a seed layer of ZnO nanoparticles and a growth layer of the vertically grown ZnO nanosheets. The seed layer nucleation density dominance is driven by the dipping time. The pore size and the height of the as-grown ZnO nanowalls are determined by varying the growth time. Possible growth mechanisms governing the physical characteristics of the synthesized ZnO nanostructures in the solution process are proposed and discussed. The gas sensor that was fabricated from the ZnO nanowall structure exhibited strong dependence on the microstructure, which was mainly determined by the preparation conditions.

The biological macromolecule Nocardia rubra cell-wall skeleton as an avenue for cell-based immunotherapy.

Promoting the antitumor effects of cell-based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell-wall skeleton (N-CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N-CWS can enhance the proliferation and viability of cytokine-induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL-staining and the Annexin V/propidium iodide assay revealed that after treatment with N-CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase-3 and caspase-9) and a downregulation of the antiapoptotic biomarker Bcl-2 in the tumor cells of the N-CWS-treated group, indicating that N-CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N-CWS. Our study provides evidence that N-CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.

On the Crossroad of Artificial Intelligence: A Revisit to Alan Turing and Norbert Wiener.

To give a high-level summary to current approaches for implementing artificial intelligence (AI), we explain the key commonalities and major differences between Turing's approach and Wiener's approach in this perspective. Especially, the problems, successful achievements, limitations, and future research directions of existing approaches that follow Weiner's ideas are addressed, respectively, aiming to provide readers with a good start point and a roadmap. Some other related topics, for example, the role of human experts in developing AI, are also discussed to seek potential solutions for some existing difficulties.

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

OBJECTIVE: To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. METHODS: Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. RESULTS: In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. CONCLUSIONS: We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC.

A Retrospective Study of Percutaneous Balloon Kyphoplasty for the Treatment of Symptomatic Schmorl's Nodes: 5-Year Results.

BACKGROUND Despite literature supporting the efficiency of percutaneous balloon kyphoplasty (PKP) in treating osteoporotic and malignant vertebral compression fractures, few reports exist that document its use for treatment of symptomatic Schmorl's nodes (SNs) refractory to conservative treatment. Patients with symptomatic SNs could have pain in the vertebrae similar to an acute vertebral compression fracture. MRI is very helpful in diagnosing symptomatic SNs when x-ray and CT scan are unremarkable. In painful cases, the vertebrae bone marrow around the SNs is hyperintense on T2-weighted subsequence. We evaluated the long-term safety and effectiveness of PKP for the treatment of symptomatic SNs not responding to conservative therapy. MATERIAL AND METHODS From January 2008 to December 2012, 32 patients suffering from symptomatic SNs underwent 43 PKP procedures. Outcome data, including mean height ratio of anterior and middle vertebral body, Visual Analog Scale (VAS score) for pain measurement, Oswestry Disability Indexes (ODI score) and SF-36 questionnaires for function measurement were recorded preoperatively, postoperatively, and at one month, six months, two years, and five years after treatment. RESULTS Thirty-two patients were treated successfully with PKP. Clinically asymptomatic cement leakage was observed in three (6.98%) of the treated vertebral bodies. The mean height ratio of anterior and middle vertebral bodies changed from 98.2±1.6% preoperatively to 98.5±1.4% postoperatively (p>0.05) and 98.3±1.5% preoperatively to 98.8±1.9% postoperatively (p>0.05). The mean VAS scores, ODI score, and SF-36 scores for physical function (PF), bodily pain (BF), social functioning (SF), and vitality (VT) all showed significant improvements (p<0.05). During the 5-year follow-up, the stabilization of the height of the vertebral body and functional improvements were all maintained. CONCLUSIONS PKP is a safe and effective procedure for the treatment of symptomatic SNs refractory to conservative therapy.