[Clinical features and spinal lesions in patients with chronic prostatitis/chronic pelvic pain syndrome].

Objective: To analyze the clinical features and spinal lesions related to micturitionin of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) patients. Methods: Patients with CP/CPPS were enrolled to this study at the outpatient department of Tongji Hospital between January and June 2019. The data of clinical features was collected and analyzed, including lower urinary tract symptoms(LUTS), bowel syndrome and pain over different parts of body, as well as lower urinary tract dysfunction, spinal lesions and pelvic organ morphological changes demonstrated by MRI. The potential role of spinal lesions in the development of CP/CPPS syndrome was investigated. Results: A total of 126 CP/CPPS patients were included, with an age［M（Q1，Q3）］of 41(31,53) years and a course of disease of 2(1,20) years. Among them, 126 (100.0%) were complicated with LUTS, 72(57.1%) with bowel dysfunction and 88(69.8%) with pain. MRI showed the cervical central disc herniation(126 cases, 100.0%), the ischemic changing in the cervical area of visceral efferant pathway(82 cases, 65.1%), the lumbar central disc herniation(65 cases, 51.6%), and the sacral nerve cysts(97 cases, 77.0%) are commonly seen. In addition, the morphological changes in the visceral organs containing smooth muscle were demonstrated, including thickened bladder wall(91 cases, 72.2%), distended seminal vesicles(70 cases, 55.6%) and distended sigmoid colon/rectum(59 cases, 46.8%). Conclusions: CP/CPPS patients were characterized by the co-existence of LUTS, bowel dysfunction and somatic pain in one individual. The presence of multi-organ symptoms, combined with the high prevalence of spinal lesions associated with micturition reflex, suggesting the potential role of the spinal lesions in the development of CP/CPPS.

Structural Characterization and Immune Activity Screening of Polysaccharides With Different Molecular Weights From Astragali Radix.

Saccharides are the most abundant substance with the strongest immunological activity in Astragali Radix (AR). However, systematic structure study and immunoactivity screening of polysaccharides with different molecular weights (Mw) in AR have yet to be conducted. In this study, Astragalus polysaccharides (APSs) were divided into three fragments of different Mw values, >2,000 kDa (APS-Ⅰ), about 10 kDa (APS-Ⅱ), and about 300 Da (APS-Ⅲ), by using ultrafiltration for the first time. The structural differences of the three products were determined on the basis of monosaccharide composition, FT-IR spectrum, linkage analysis, and nuclear magnetic resonance analysis. Cellular immune activity experiments in vitro and cyclophosphamide immunosuppression animal model experiments in vivo for nonspecific and specific immunoactivity screening were applied to identify the most immunogenic fragment in APSs. Linkage analysis results showed that APS-Ⅰ, APS-Ⅱ, and APS-Ⅲ have different attachment sites of monosaccharide residues. Immune screening experiments indicated that the Mw of the APSs influenced their activity, and APS-Ⅱ had the strongest immunoenhancing activity among the products. This research may serve as a reference for further study on APSs with different structures and immune activities, and as a guidance for the quality control of APSs and the development of new APS products.

Observation and analysis of clinical efficacy of melatonin on AOPP-induced delirium patients.

OBJECTIVE: To observe the clinical efficacy of melatonin on acute organophosphorus pesticide poisoning (AOPP). PATIENTS AND METHODS: In this randomized control trial, a total of 59 AOPP patients with subsequent delirium were randomly divided into two groups, the melatonin group (n=29) and the placebo-controlled group (n=30). Patients in the melatonin group (n=29) underwent oral administration of melatonin in addition to the symptomatic treatment, while those in the placebo-controlled group took a placebo in addition to the symptomatic treatment. Before and 12 weeks after treatment, adverse events of participants in both groups were classified according to their scores in the assessment of the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-SI) scale, and Treatment Emergent Symptom Scale (TESS). RESULTS: The excellence rates of patients in the melatonin group and the placebo-controlled group were 82.75% and 30.00%, respectively (χ2 = 17.054, p < 0 .01). No adverse events were identified in all participants. CONCLUSIONS: Melatonin may serve as an effective drug in the treatment of AOPP-induced deliration.

On the effects of glasses on the SAR in human head resulting from wireless eyewear devices at phone call state.

This paper evaluates the effects of glasses on the specific absorption rates (SAR) in the human head resulting from wireless eyewear device at phone call state. We mainly concentrate on the SAR in the eyes since their sensitivity to electromagnetic fields (EMF). We find wearing glasses obviously alters the distribution and magnitude of the SAR. The maximal SAR in the ocular tissues with glasses is even 6 times more than that without glasses. Wearing glasses also induce the new hotspot in the eyes which may cause the biggest SAR increment in the ocular tissues. Moreover, calculated results indicate that the maximal SAR is sensitive to the size of glasses and radiation frequency. Because of this, we believe wearing glasses may possibly increase the risk of health hazard to eyes of wireless eyewear device user. These calculated results could be a valuable reference for the glasses designer to reduce the SAR in the eyes.

Revealing extraordinary tensile plasticity in layered Ti-Al metal composite.

Layered Ti-Al metal composite (LMC) fabricated by hot-pressing and hot-rolling process displays higher ductility than that of both components. In this paper, a combination of digital image correlation (DIC) and X-ray tomography revealed that strain delocalization and constrained crack distribution are the origin of extraordinary tensile ductility. Strain delocalization was derived from the transfer of strain partitioning between Ti and Al layer, which relieved effectively the strain localization of LMC. Furthermore, the extensive cracks of LMC were restricted in the interface due to constraint effect. Layered architecture constrained the distribution of cracks and significantly relieved the strain localization. Meanwhile, the transfer of strain partitioning and constrained crack distribution were believed to inhibit the strain localization of Ti and change the deformation mechanisms of Ti. Our finding enriches current understanding about simultaneously improving the strength and ductility by structural design.

A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

Low regional cerebral blood flow in burning mouth syndrome patients with depression.

OBJECTIVES: The main aims of this study were to (i) investigate the emotional disorder status of patients with burning mouth syndrome (BMS) and (ii) detect regional cerebral blood flow in BMS patients with the application of combined single-photon emission computed tomography and computed tomography (SPECT/CT). SUBJECTS AND METHODS: The degree of pain was measured using the visual analysis scale, and emotional disorder with the self-rating anxiety scale, self-rating depression scale, and Hamilton depression rating scale in 29 patients with BMS and 10 healthy controls. SPECT/CT was performed in 29 patients with BMS and 10 healthy controls, and statistical parametric mapping method was used for between-group analyses. RESULTS: The incidence rate of depression in patients with BMS was 31.0%. Compared to the control group, patients with BMS displayed significantly different depression and anxiety scales (P < 0.05). Significantly lower regional cerebral blood flow in the left parietal and left temporal lobes was recorded for BMS patients with depression (P < 0.05). CONCLUSIONS: Patients with BMS experience more depression and anxious emotion. Moreover, depression in patients with BMS may be associated with lower regional cerebral blood flow in the left temporal and left parietal lobes.

Effects of intracavernous injection of P2X3 and NK1 receptor antagonists on erectile dysfunction induced by spinal cord transection in rats.

This study aimed to explore the effects of intracavernous injection (ICI) of P2X3 and NK1 receptor antagonists on erectile dysfunction (ED) induced by spinal cord transection in rats. Sixty male Sprague-Dawley (SD) rats were randomly divided into the following three groups (20 rats each group): sham operation group (C group), thoracic spinal cord transection group (T group) and sacral spinal cord transection group (S group). An ED model was established through complete transection of the thoracic or sacral spinal cord. Intracavernous pressure (ICP) with and without injection of P2X3 (Suramin) or NK1 (GR82334) receptor antagonists was recorded 3 weeks after surgery. Immunohistochemistry was employed to detect the expression of P2X3 and NK1 receptors in the dorsal root ganglion (DRG) and smooth muscle of corpus cavernosum. Data were processed with SPSS 17.0. ICI with Suramin (0.1, 0.3 and 1 mm) or GR82334 (0.1, 0.3 and 1 mm) increased ICP dose dependently in the T and S groups. The expression of P2X3 and NK1 receptors in DRG and smooth muscle of corpus cavernosum was up-regulated in the T and S groups. It is concluded that ICI of P2X3 and NK1 receptor antagonists may improve the recovery of erectile function in a rat model with ED after spinal cord transection.

Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway.

Borneol, a terpene and bicyclic organic compound found in several species, can easily penetrate the blood-brain barrier (BBB) and helps the absorption of many agents through BBB in the brain, but there has been no study about its direct action on neurons in the CNS. In the present study, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to investigate the neuroprotective effects of borneol and the related mechanisms. We demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential dissipation. The elevation of nitric oxide (NO), the increase of inducible nitric oxide synthase (iNOS) enzymatic activity and the upregulation of iNOS expression were also attenuated by borneol. The inhibition of caspase-related apoptotic signaling pathway was consistently involved in the neuroprotection afforded by borneol. Meanwhile, borneol inhibited proinflammatory factor release and IκBα degradation, and blocked nuclear transcription factor κappaB (NF-κB) p65 nuclear translocation induced by OGD/R. On the other hand, borneol did not show obvious effect on the inhibition of phospho-IKKα activation. Furthermore, it failed to affect the OGD/R-induced enhanced level of phospho-SAPK/JNK. In conclusion, our study indicated that borneol protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. The mechanisms of this reversal from OGD/R may be involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition of inflammatory factor release and depression of caspase-related apoptosis. Among these effects, the inhibition of IκBα-NF-κB and translocation signaling pathway might play a significant role in the neuroprotection of borneol.

Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis.

Magnolol and honokiol, main active compounds from the bark of Magnolia officinalis, have been found to have various pharmacological actions, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties, without appreciable toxicity. Recently, the anti-tumor activity of magnolol and honokiol has been extensively investigated. Magnolol and honokiol were found to possess anti-tumor activity by targeting the apoptosis pathways, which have been considered as targets for cancer therapies. This review will focus on the mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer that have been characterized thus far, including the death receptor mediated pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and regulation of apoptosis-related proteins. These breakthrough findings may have important implications for targeted cancer therapy and modern applications of traditional Chinese medicine.

The anti-amnesic effects of luteolin against amyloid beta(25-35) peptide-induced toxicity in mice involve the protection of neurovascular unit.

Luteolin (3',4',5,7-tetrahydroxyflavone) is an important member of the flavonoid family. It exhibits strongly anti-inflammatory, antioxidant and phytoestrogen-like activities. In the present study, we examined the anti-amnesic and protective effects of luteolin against Abeta(25-35)-induced toxicity in mice. Mice were given an i.c.v. injection of aggregated Abeta(25-35) peptide. The learning and memory impairments, ultrastructural changes of cerebral cortex, cerebrovascular dysfunction and neuronal changes were detected after oral administration of luteolin continuously for 8 days. Our results demonstrate that oral administration of luteolin for 8 days for those Abeta(25-35)-induced amnesic mice conferred robust neurovascular protection in Abeta(25-35)-induced amnesia, involving the improvement of the spatial learning and memory capabilities, the modulation of microvascular function, the increase of regional cerebral blood flow values, the clearance of reactive oxygen species, the improvement of cholinergic neuronal system, and the increase of brain-derived neurotrophic factor level and its receptor tyrosine kinase B expression in cerebral cortex.

Establishment of a cell-based assay to screen insulin-like hypoglycemic drugs.

This study sought to establish a cell based assay to screen insulin analogs. Previous studies have proposed that up-regulation of glucose consumption may have the same anti-diabetic effects as insulin. Here, the amount of glucose that disappeared in culture medium after incubation with insulin or drugs was determined and served as an indicator of the glucose consumption of the cells. In order to establish a cellular model to screen insulin analogs, the sensitivities of four cell lines - BALB/c 3T3, HepG2, NIH3T3, and Bel7402 - to insulin were evaluated by detecting glucose consumption after incubation with insulin (0-125 nM) for 24 h. BALB/c 3T3 was more sensitive to insulin than the other three cell lines. Insulin elevated glucose consumption of BALB/c 3T3 in a concentrationand time- manner. Glucose consumption of BALB/c 3T3 increased by 30% after incubation with insulin (30 nM) for 24 h. Insulin increased the proliferation of BALB/c 3T3 at 48 h. A model was established by detecting glucose consumption after treating BALB/c 3T3 with drugs for 24 h. Using the cell-based assay, we screened more than two thousand samples from Traditional Chinese Medicine (TCM). Five extracts exhibiting glucose absorbance in medium were identified, indicating a hit rate of 0.5%. Results suggested that a cell-based assay by detection of glucose consumption in BALB/c 3T3 was suitable for high-throughput screening and was feasible to identify insulin-like hypoglycemic drugs. Five hits were discovered from natural products. Further characterization of these active extracts could help to identify potential anti-diabetic drugs.

Target validation: A door to drug discovery.

From ancient times to today, drug discovery transitioned from serendipity to rationality over its long history. Proper drug target selection and validation are crucial to the discovery of new drugs. This review discusses the definition of drug targets and proposes several characteristics for drug targets. The limitations of the term 'target' itself are summarized. The drug target validation process is also discussed in detail and pitfalls during this process are outlined. Small active chemical compounds obtained from the target validation process are useful tools in target validation and target function research. The validation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as a new potential anti-atherosclerotic drug target is cited as an example in order to elucidate the target validation process.

Rapid detection of anabolic steroids in urine by protein arrays.

The purpose of this study was to develop a rapid and sensitive method utilizing the state-of-the-art protein arrays technique to detect urinary anabolic steroids (ASs) in athletes. Three experiments were designed to investigate the feasibility of the protein arrays for ASs testing. Firstly, androgen receptor (AR) and estrogen receptor (ER) protein arrays were prepared on polysaccharide-coated slides to investigate whether they can bind to ASs (affinity tests). Secondly, in comparison to adrenergic receptor (the receptor of beta-blockers) and opioid receptor (the receptor of narcotic analgesics) arrays, AR and ER protein arrays were used to test whether they can determine the ASs positive urine sample specifically (specific binding tests). At last protein arrays were used to estimate qualitatively the ASs in positive urine samples (qualitative tests). From the results of the affinity tests the shape of the dose-dependence curve suggested a positive cooperative binding of ASs with the protein arrays. The AR and ER protein arrays showed affinities for fluorescence labelled testosterone and estradiol that were similar to those of literatures (0.65 vs. 0.89 nM, 5.96 vs. 10.3 nM, respectively). Based on the data, the sensitivity of testing can reach 0.1 nM that was much better than the World Anti-Doping Code (WADA) standard. Specific binding tests showed that the prohibited substance in positive urine samples belonged to the anabolic estrogenic inhibitor of ASs. From the results of qualitative tests, we could estimate that there were anabolic androgenic steroids in the positive urine samples and their concentration was lower than 50 microM Methyltestosterone. The total time of the test process for ASs in urine needed less than 1 h. In summary, the present study showed that the protein arrays method provided a highly sensitive and rapid alternative to screen urine samples for the detection of the misuse of ASs in athletes and was suitable for testing in both weekly training sessions as well as large-scale competition events.

Formation mechanism of H2Ti3O7 nanotubes.

Formation mechanism of H2Ti3O7 nanotubes by single-step reaction of crystalline TiO2 and NaOH has been investigated via transmission electron microscopy examinations of series specimens with different reaction times and extensive ab initio calculations. It was found that the growth mechanism includes several steps. Crystalline TiO2 reacts with NaOH, forming a highly disordered phase, which recrystallized into some H2Ti3O7 thin plates. H-deficiency on the top surface leads to an asymmetrical environment for the surface Ti3O2-7 layer. The calculations of the surface tension, elastic strain energy, interlayer coupling energy, and Coulomb force indicated that the asymmetrical environment is the principal driving force of the cleavage of the single sheets of H2Ti3O7 from the plates and the formation of the multiwall spiral nanotubes.

The structure of trititanate nanotubes.

A comprehensive chemical and structural analysis is made of a new type of trititanate nanotube, which is synthesized via the reaction of TiO(2) particles with NaOH aqueous solution. It is found that the trititanate nanotubes are multi-walled scroll nanotubes with an inter-shell spacing of about 0.78 nm and an average diameter of about 9 nm. An atomic model of the nanotube is derived based on information from powder X-ray diffraction, selective-area electron diffraction, high-resolution electron microscopy and structure simulations. A model nanotube may be constructed by wrapping a (100) sheet of H(2)Ti(3)O(7) along [001] with the tube axis parallel to [010].

Salvianolic acid B protects the memory functions against transient cerebral ischemia in mice.

The objective of this work was to study the protective effects of salvianolic acid B (Sal B) on the dysfunctions of learning and memory induced by transient cerebral ischemia in mice. The mechanisms of its actions also were researched both in vivo and in vitro. The model of dysfunction of learning and memory induced by transient cerebral ischemia in mice was used. One trail passive avoidance tests were used to evaluate the learning and memory functions and experiments in vitro were employed to observe the antioxidative effects of Sal B. Cerebral transient ischemia would impair the function of memory in mice. In step down test. the error number and latency were 2.63 and 120.5 in control group and were 1.35 and 234.4 respectively in sham operated group (p < 0.05). In Sal B treated groups, the error number was less and latency was longer significantly than those of control group. Meanwhile. 3 and 10 mgkg(-1) of Sal B iv. reduced the malondialdehyde contents in cortex, hippocampus and striatum of cerebral transient ischemia rat ion vivo. Sal B 10--100 nmol L(-1) also inhibited lipid-peroxidation and scavenged free hydroxyl radicals in vitro. As conclusion. Sal B ameliorated learning and memory dysfunctions induced by cerebral transient ischemia. Its actions might be related to its antioxidant activity.

Salvianolic acid B protects brain against injuries caused by ischemia-reperfusion in rats.

AIM: To study the protective effects of salvianolic acid B (Sal B) against the ischemia-reperfusion induced rat brain injury. METHODS: Focal cerebral ischemia-reperfusion model in rats was employed to study the protective effects of Sal B. The behavioural tests were used to evaluate the damage to the central nervous system. Spectrophotometric assay methods were used to measure the activity of superoxide dismutase (SOD), contents of reduced glutathione (GSH), malondialdehyde (MDA), adenosine 5-triphosphorate (ATP), and lactate acid (LA) in experimental rats' brain homogenate. RESULTS: Focal cerebral ischemia-reperfusion resulted in abnormal behavior which could be alleviated by Sal B 10 mg.kg-1 i.v., and nimodipine (Nim) 4 mg.kg-1 i.p. At the same time, Sal B 10 mg.kg-1 and Nim 4 mg.kg-1 could inhibit the decrease in SOD, GSH, and ATP levels and the increase in MDA and LA levels caused by ischemia-reperfusion in brain. CONCLUSION: Sal B showed a protective action against the ischemia-reperfusion induced injury in rat brain by reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.

[Protective effects of salvianolic acid A against impairment of memory induced by cerebral ischemia-reperfusion in mice].

In the present experiments, an impairment of memory model was made by cerebral ischemia-reperefusion in mice. Sal A at the dosage of 3 and 10 mg.kg-1 i.v. was shown to improve the impairment of memory function induced by cerebral ischemia-reperefusion in step down and step through tests. In these tests, the number of errors of Sal A treated group was less and the latency was longer than that of control group. Meanwhile, Sal A 3 and 10 mg.kg-1 i.v. was found to reduce the MDA contents in the cortex, hippocampus and striatum of cerebral ischemia-reperfused rats in vivo. Sal A 10-100 nmol.L-1 was shown to inhibit the brain lipid-peroxidation and scavenge the free hydroxyl radical in vitro. These results indicate that the antagonistic effects of Sal A on impairment of learning and memory caused by cerebral ischemia-reperefusion may be related with its anti-oxidant activity.