[Nomographic Model for Predicting Severe Foot Pain in Nurses from Tertiary Hospitals in China].

Objective: To investigate the prevalence and common sites of severe foot pain among nurses, to define the risk factors of severe foot pain in nurses in tertiary hospital in China, and to construct a nomograph model for predicting individuals' risks for severe foot pain. Methods: Between August 2019 and December 2019, a stratified global sampling method was used to select 10691 nurses from 351 tertiary hospitals in China to investigate the incidence of severe foot pain among them. The variables that may affect the occurrence of severe foot pain were analyzed by single factor analysis to identify the influencing factors of severe foot pain in nurses. Furthermore, the independent risk factors of severe foot pain were analyzed by stepwise logistic regression analysis. The statistically significant factors identified in the multivariate regression analysis were incorporated into the nomograph prediction model. The predictive performance of the nomograph was measured by the consistency index (C-index) and calibrated with 1000 Bootstrap samples. Results: A total of 3419 nurses out of the 10691 had foot pain, resulting in an incidence of 31.98%. The incidence of severe pain (VAS score 7-10) was 2.27% (243 of 10691). The locations of severe pain were more commonly found in the soles and heels of both feet. Six factors, including age, education, the material of the work shoes, comfortableness of the work shoes, number of complications, and foot injure history, were incorporated in the nomograph predicting model. The C-index value was 0.706 and the standard curve fitted well with the calibrated prediction curve. Conclusion: The risk prediction model constructed in this study showed sound performance in predicting the risk of severe foot pain in nurses, and all the indicators involved are simple and the relevant data are easily obtained. The model can provide reference for preventing severe foot pain in nurses.

Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

[Research progress on mechanism of gastrodin and p-hydroxybenzyl alcohol on central nervous system].

Gastrodin(GAS) and p-hydroxybenzyl alcohol(HBA) are extracts of dried tubers of Gastrodia elata, which is the material basis for its efficacy and belongs to phenolic compounds. Modern pharmacology studies have shown that they have significant effects on central nervous system diseases, such as insomnia, convulsions, depression, ischemic stroke, anxiety, and cognitive impairment, and these diseases are closely related to neurotransmitters and cytokines. This paper described various mechanisms of GAS and HBA monomer components on the central nervous system. They alleviate hippocampal neuronal toxicity mainly by regulating a variety of neurotransmitters, such as acetylcholine, glutamic acid(GLU), γ-aminobutyric acid(GABA), serotonin(5-HT), dopamine(DA), norepinephrine(NE), 5-indoleacetic acid(5-HIAA), high vanillic acid(HVA) and dihydroxyphenylacetic acid(DOPAC), pro-inflammatory cell growth factors, such as IL-1ß, IL-6 and TNF-α and relevant receptor functions, and exert neuropharmacological effects by effectively increasing mRNA expressions of brain neurotrophic factors, such as BDNF and GDNF, and further inhibiting the apoptosis of damaged neurons. This paper summarized various mechanisms on the central nervous system, which provides a scientific basis for the further research of the neuropharmacological mechanism of GAS and HBA and the development of new drugs and functional food.

Sensitization of P2X3 receptors in insular cortex contributes to visceral pain of adult rats with neonatal maternal deprivation.

Aims Insular cortex is a brain region critical for processing of the sensation. Purinergic receptors are involved in the formation of chronic pain. The aim of the present study was to explore the role and mechanism of P2X3 receptors (P2X3Rs) in insular cortex in chronic visceral pain. Methods Chronic visceral pain in adult rats was induced by neonatal maternal deprivation and measured by detecting the threshold of colorectal distension. Western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction techniques were used to detect the expression and distribution of P2X3Rs. Synaptic transmission in insular cortex was recorded in brain slices by patch clamp techniques. Results Expression of P2X3Rs both at mRNA and protein levels in right hemisphere of insular cortex was significantly increased in neonatal maternal deprivation rats. In addition, P2X3Rs were expressed with NeuN or synaptophysin but not with glial fibrillary acidic protein and CD11b. The co-localization of P2X3Rs with NeuN or synaptophysin was greatly enhanced in right hemisphere of insular cortex in neonatal maternal deprivation rats. Furthermore, neonatal maternal deprivation markedly increased both the frequency and amplitude of miniature excitatory postsynaptic current in right hemisphere of insular cortex. Incubation of A347091 significantly decreased the frequency of spontaneous excitatory postsynaptic current and miniature excitatory postsynaptic current of insular cortex neurons of neonatal maternal deprivation rats. Incubation of P2X3Rs agonists α,ß-mATP remarkably increased the frequency of spontaneous excitatory postsynaptic current and miniature excitatory postsynaptic current of the right hemisphere of insular cortex neurons of healthy control rats. Importantly, injection of A317491 significantly enhanced the colorectal distension threshold of neonatal maternal deprivation rats, while injection of α,ß-mATP into right but not left insular cortex markedly decreased the colorectal distension threshold in healthy control rats. Conclusions Overall, our data provide integrated pharmacological, biochemical, and functional evidence demonstrating that P2X3Rs are physically and functionally interconnected at the presynaptic level to control synaptic activities in the right insular cortex, thus contributing to visceral pain of neonatal maternal deprivation rats.

Case report: lipid inclusion in glomerular endothelial and mesangial cells in a patient after contrast medium injection.

BACKGROUND: It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth. CASE PRESENTATION: A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy. However the patient didn't has any clinic clues of Fabry disease and other lysosomal storage disorders. Moreover in vitro cultured glomerular endothelial and mesangial cells we found CM triggers lipid aggregation along with the increased CD36 and decreased ABCA1 abundance. Thus this patient was administrated statin to correct the aberrant lipid trafficking, 2 months later at his next visit we found his renal function partially recovered with reduced proteinuria. CONCLUSIONS: Besides the well-known underlying mechanisms, CM may cause renal impairment by triggering the dysregulated transportation of lipid. Furthermore statin is suggested to be a very promising medicine to decrease side effects of CM.

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis.

Background Pain in patients with chronic pancreatitis is critical hallmark that accompanied inflammation, fibrosis, and destruction of glandular pancreas. Many researchers have demonstrated that stromal cell-derived factor 1 (also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) involved in mediating neuropathic and bone cancer pain. However, their roles in chronic pancreatic pain remain largely unclear. Methods Chronic pancreatitis was induced by intraductal injection of trinitrobenzene sulfonic acid to the pancreas. Von Frey filament tests were conducted to evaluate pancreas hypersensitivity of rat. Expression of CXCL12, CXCR4, NaV1.8, and pERK in rat dorsal root ganglion was detected by Western blot analyses. Dorsal root ganglion neuronal excitability was assessed by electrophysiological recordings. Results We showed that both CXCL12 and CXCR4 were dramatically up-regulated in the dorsal root ganglion in trinitrobenzene sulfonic acid-induced chronic pancreatitis pain model. Intrathecal application with AMD3100, a potent and selective CXCR4 inhibitor, reversed the hyperexcitability of dorsal root ganglion neurons innervating the pancreas of rats following trinitrobenzene sulfonic acid injection. Furthermore, trinitrobenzene sulfonic acid-induced extracellular signal-regulated kinase activation and Nav1.8 up-regulation in dorsal root ganglias were reversed by intrathecal application with AMD3100 as well as by blockade of extracellular signal-regulated kinase activation by intrathecal U0126. More importantly, the trinitrobenzene sulfonic acid-induced persistent pain was significantly suppressed by CXCR4 and extracellular signal-regulated kinase inhibitors. Conclusions The present results suggest that the activation of CXCL12-CXCR4 signaling might contribute to pancreatic pain and that extracellular signal-regulated kinase-dependent Nav1.8 up-regulation might lead to hyperexcitability of the primary nociceptor neurons in rats with chronic pancreatitis.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging.

BACKGROUND: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. METHODS: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. RESULTS: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. LIMITATIONS: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. CONCLUSION: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

[Pharmacokinetics and oral bioavailability of palmatine and jatrorrhizine in Huangteng in rats].

In this study, the total alkaloids of Huangteng were given to the rats by the methods of intragastric administration and tail vein. After the concentration changes of palmatine and jatrorrhizine in the plasma of rats were determined by RP-HPLC, pharmacokinetic parameters and oral bioavailability were calculated by 3P97 software. After the rats were pre-treated with total alkaloid 60 mg•kg⁻¹ by the methods of intragastric administration and tail vein, the main pharmacokinetic parameters were determined as follows： in the intragastric administration group, the Cmax of palmatine and jatrorrhizine were (0.91±0.06), (0.70±0.08) mg•L⁻¹; tmax of palmatine and jatrorrhizine were (35.24±0.83), (47.76±1.24) min; t1/2 of palmatine and jatrorrhizine were (187.03±1.53), (105.64±16.99) min, AUC of palmatine and jatrorrhizine were (280.30±18.69), (144.36±1.06) mg•min•L⁻¹; in the intravenous injection group, the t1/2 of palmatine and jatrorrhizine were (172.18±12.38), (147.26±1.82) min; AUC of palmatine and jatrorrhizine were (2 553.14±214.91), (328.83±10.81) mg•min•L⁻¹. The oral bioavailability of palmatine was 10.98% and jatrorrhizine was 43.90%.

[Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats].

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg1, Re, Rf, Rb1, Rg2, Rc, Rb2, Rb3, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg1, Re, Rf, Rg2, Rc, Rd, Rb3 was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb1 were three-compartment model; aqueous solution of ginsenoside monomers Rb2 was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future.

[Study on early screening of high saponin ginseng lines].

The study aims at screening the specific bands by PCR, quickly and accurately evaluating the quality of ginseng seeding, accelerating the process of ginseng breeding. Based on the correlation of genetic differences and saponin content between individuals, a pair of specific primer GC1 was screened by PCR. According to the experiment by L16 (45) orthogonal test, a PCR system most suitable for GC1 was established, which came out total 25 µL reaction system containing DNA 2.60 mg•L⁻¹, Mg²âº 1.44 mmol•L⁻¹, dNTP 0.19 mmol•L⁻¹, primer 0.32 µmol•L⁻¹ and Taq enzyme concentration 0.076 U•µL⁻¹. By comparing the saponin content and the GC1 PCR electrophoretogram of samples, the ginseng, with 1 200 bp specific band by PCR of GC1, the contents of 9 monosodium saponins and their additions were higher than others, which provided a reliable method for accelerating the process of ginseng breeding. The sequence was sequenced and 99% homologous to glycerol-3-phosphate dehydrogenase.

Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.

G protein-coupled kinase (GRK) 6 is a member of the GRK family that mediates agonist-induced desensitization and signaling of G protein-coupled receptors (GPCRs), thus involving in a wide variety of processes including inflammation and nociception. Recent studies have indicated that chemokines play an important role in chronic pain via increased expression of respective GPCRs. This study was designed to investigate the role of GRK6 and its interaction with substrate chemokine receptors in dorsal root ganglion (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Following induction of CCI, GRK6 expression was significantly downregulated in rat DRGs at L4-L6 segments. Overexpression of GRK6 using lentiviral-mediated production strategy via sciatic nerve injection markedly attenuated mechanical allodynia and thermal hyperalgesia in CCI rats. Overexpression of GRK6 also drastically reversed the hyperexcitability of DRG neurons innervating the hind paw and suppressed the enhanced expression of CXCR2 in DRGs of CCI rats. In addition, co-immunoprecipitation, immunofluorescence, and correlation analysis supported the interaction between GRK6 and CXCR2. These results suggest that GRK6 might be a key molecular involved in peripheral mechanism of neuropathic pain and that overexpression of GRK6 might be a potential strategy for treatment for neuropathic pain through inhibition of CXCR2 signal pathway.

Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation.

PURPOSE: Low back pain and sciatica are the most common symptoms of patients with lumbar disc herniation (LDH). The pathophysiology of lumbocrural pain and sciatica is not fully understood. The aim of the present study was to define the membrane properties and activities of voltage-gated sodium channels of dorsal root ganglion (DRG) neurons in a rat model of LDH. METHODS: LDH was established by transplantation of autologous nucleus pulposus (NP) to lumbar 5 and 6 spinal nerves (L5-L6 DRG) of adult male rats. Mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) were measured 1 day before and through 35 days after transplantation of NP. Changes in expression of VGSCs were determined by western blotting. L5-L6 DRGs neurons innervating the hindpaw were labeled with DiI and acutely dissociated for measuring excitability and sodium channel currents under whole-cell patch clamp configurations. RESULTS: NP transplantation significantly reduced the PWT and PWL in association with a significant reduction in rheobase and an increase in numbers of action potentials evoked by 2X and 3X rheobase current stimulation. Voltage-gated sodium current density was significantly enhanced in L5-L6 DRG neurons from LDH rats. The inactivation curve showed a leftward shift in LDH rats while activation curve did not significantly alter. However, NP transplantation remarkably enhanced expression of NaV1.7 and NaV1.8 in L5-L6 DRGs but not in T10-12 DRGs. CONCLUSION: These data suggest that NP application produces pain-related behavior and potentiates sodium current density of DRG neurons, which is most likely mediated by enhanced expression of NaV1.7 and NaV1.8.

Upregulation of cystathionine ß-synthetase in the arcuate nucleus produces pain hypersensitivity via PKC upregulation and GluN2B phosphorylation in rats with chronic pancreatitis.

Hydrogen sulfide (H2S) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of H2S and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Western blot analysis was performed to detect protein expression in the ARC. CP markedly upregulated cystathionine ß-synthetase (CBS) expression but did not alter cystathionine-γ-lyase level in the ARC at 4 weeks after TNBS injection. Although the expression of total GluN2B was not altered, CP greatly enhanced the phosphorylation level of GluN2B in the ARC when compared with age- and sex-matched control rats. CP also significantly increased expression of protein kinase Cγ (PKCγ) in the ARC. Arcuate microinjection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA, an inhibitor of CBS) significantly attenuated abdominal pain in CP rats in a dose-dependent manner and reversed the CP-induced upregulation of p-GluN2B and PKCγ in the ARC. Furthermore, the GluN2B inhibitor or specific PKC inhibitor chelerythrine significantly attenuated abdominal hyperalgesia in CP rats. The p-GluN2B expression was also suppressed by PKC inhibitor. Taken together, our results suggest that the upregulation of CBS in the ARC leads to an activation of GluN2B via PKCγ, which may play an important role in generation of pain hypersensitivity of CP.

[Identification of Strawberry Ripeness Based on Multispectral Indexes Extracted from Hyperspectral Images].

In order to establish new multispectral indexes for automatic identification of strawberry ripeness, hyperspectral imaging technology was applied in this paper. Eight indexes: Ind1=R730+R640-2×R680, Ind2=R680/(R640+R730), Ind3=R675/R800, IAD=log10(R720/R670), I1=R650/R550, I2=R650/R450, I3=R650/(R450+R550), I4=2×R650-(R550+R450) were calculated by extracting average spectral of strawberry samples and their identification effects of strawberry samples in three ripening stages(mature, nearly mature and immature) were judged with Fisher linear discriminant(FLD). The result showed that the identification effects of linear discriminant analysis model based on index I4 was the best among 8 indexes and the identification accuracy of modeling and prediction set was 90% and 91. 67% respectively. Three wavelengths (535, 675, 980 nm) related to strawberry ripeness were extracted based on average spectral of strawberry samples and 4 new indexes were established based on these three wavelengths: i1=2×R675- (R980+R535), i2=R675/(R980+R535), i3= (R675-R535)/(R675+R535), i4=[R675- (R535+R980)]/[R675+(R535+R980)]. The identification effects was judged with FLD and the results showed that the effects of linear discriminant analysis models based on i1, i2, i4 were better than index I4 and the identification accuracy of modeling and prediction set was 95.83%，95.83%，95.83% and 95%，95%，96.67% respectively. In conclusion, new established indexes i1, i2, i4 could be used in automatic identification of strawberry ripeness.

[Identification of Microalgae Species Using Visible/Near Infrared Transmission Spectroscopy].

At present, the identification and classification of the microalgae and its biochemical analysis have become one of the hot spots on marine biology research. Four microalgae species, including Chlorella vulgaris, Chlorella pyrenoidosa, Nannochloropsis oculata, Chlamydomonas reinhardtii, were chosen as the experimental materials. Using an established spectral acquisition system, which consists of a portable USB 4000 spectrometer having transmitting and receiving fiber bundles connected by a fiber optic probe, a halogen light source, and a computer, the Vis/NIR transmission spectral data of 120 different samples of the microalgae with different concentration gradients were collected, and the spectral curves of fourmicroalgae species were pre-processed by different pre-treatment methods (baseline filtering, convolution smoothing, etc. ). Based on the pre-treated effects, SPA was applied to select effective wavelengths (EWs), and the selected EWs were introduced as inputs to develop and compare PLS, Least Square Support Vector Machines (LS-SVM), Extreme Learning Machine (ELM)models, so as to explore the feasibility of using Vis/NIR transmission spectroscopy technology for the rapid identification of four microalgae species in situ. The results showed that: the effect of Savitzky-Golay smoothing was much better than the other pre-treatment methods. Six EWs selected in the spectraby SPA were possibly relevant to the content of carotenoids, chlorophyll in the microalgae. Moreover, the SPA-PLS model obtained better performance than the Full-Spectral-PLS model. The average prediction accuracy of three methods including SPA-LV-SVM, SPA-ELM, and SPA-PLS were 80%, 85% and 65%. The established method in this study may identify four microalgae species effectively, which provides a new way for the identification and classification of the microalgae species. The methodology using Vis/NIR spectroscopy with a portable optic probe would be applicable to a diverse range of microalgae species and proves to be a rapid, real-time, non-destructive, precise method for the physiological and biochemical detection for microalgae.

Adrenergic signaling mediates mechanical hyperalgesia through activation of P2X3 receptors in primary sensory neurons of rats with chronic pancreatitis.

The mechanism of pain in chronic pancreatitis (CP) is poorly understood. The aim of this study was designed to investigate roles of norepinephrine (NE) and P2X receptor (P2XR) signaling pathway in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Mechanical hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. P2XR-mediated responses of pancreatic dorsal root ganglion (DRG) neurons were measured utilizing calcium imaging and whole cell patch-clamp-recording techniques. Western blot analysis and immunofluorescence were performed to examine protein expression. TNBS injection produced a significant upregulation of P2X3R expression and an increase in ATP-evoked responses of pancreatic DRG neurons. The sensitization of P2X3Rs was reversed by administration of ß-adrenergic receptor antagonist propranolol. Incubation of DRG neurons with NE significantly enhanced ATP-induced intracellular calcium signals, which were abolished by propranolol, and partially blocked by protein kinase A inhibitor H-89. Interestingly, TNBS injection led to a significant elevation of NE concentration in DRGs and the pancreas, an upregulation of ß2-adrenergic receptor expression in DRGs, and amplification of the NE-induced potentiation of ATP responses. Importantly, pancreatic hyperalgesia was markedly attenuated by administration of purinergic receptor antagonist suramin or A317491 or ß2-adrenergic receptor antagonist butoxamine. Sensitization of P2X3Rs, which was likely mediated by adrenergic signaling in primary sensory neurons, contributes to pancreatic pain, thus identifying a potential target for treating pancreatic pain caused by inflammation.

[Preparation and characterization of tumor targeted CdTe quantum dots modified with functional polymer].

N-acetyl-L-cysteine (NAC) capped quantum dots (QDs) were synthesized by a hydrothermal method and coated with 2-amino-2-deoxy-D-glucose (DG), polyethylene glycol (PEG), and 9-D-arginine (9R). The optical properties, morphology and structure of 9R/DG-coated CdTe QDs were characterized by ultraviolet-visible spectrometry, fluorescence spectrum, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometer (LC-MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transmission electron micrographs (TEM). Furthermore, the biocompatibility, tumor targeted ability and transmembrane action of 9R/DG-coated CdTe QDs were studied. Results indicated that 9R/DG-coated CdTe QDs was constructed successfully by ligand exchange. The 9R/DG-coated CdTe QDs with the size of 8-10 nm had good dispersity and the absorbance and fluorescence peaks of CdTe QDs after modification were red shifted from 480 nm to 510 nm and 627 nm to 659 nm, respectively. In addition, the CdTe QDs modified by PEG, DG and 9R displayed good biocompatibility, high targeted ability to the cancer cells with glucose transporter type 1 (GLUT1) receptor high expression and obvious transmembrane ability.

[Chemical constituents from supercritical CO2 extraction of Schisandra chinensis].

OBJECTIVE: To study the chemical constituents from the supercritical CO2 extraction of Schisandra chinensis. METHODS: The compounds were separated and purified by conventional column chromatography and their structures were identified by spectroscopic methods. RESULTS: Nine compounds were isolated from the supercritical CO2 extraction of Schisandra chinensis, and their structures were identified as chrysophanol(1),schisandrin B(2), ß-sitosterol(3), schisandrin C(4),schisandrol A(5), angeloylgomisin H(6), daucosterol(7) 1, 5-dimethyl citrate (8), and shikimic acid (9). CONCLUSION: Compounds 1, 8 and 9 are isolated from Schisandra chinensis for the first time,and compound 1 as an anthraquinone is isolated from this genus for the first time.

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway.

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 µM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

[Synchrotron radiation-based FTIR microspectroscopy study of 6-hydroxydopamine induced Parkinson's disease cell model].

SH-SY5Y cell line treated with 6-hydroxydopamine (6-OHDA) is a classical Parkinson's disease (PD). In the present study, synchrotron-based Fourier transform infrared (FTIR) microspectroscopy was used to analyze the biochemical composition of SH-SY5Y cell line treated with 6-OHDA. The detailed spectral analyses show the significant changes in cellular compositions such as lipids, proteins and nucleic acids in SH-SY5Y cells treated with 6-OHDA compared to control SH-SY5Y cells. As a result, the unsaturation levels of phospholipids decrease in SH-SY5Y cells treated with 6-OHDA compared to control cells, the analysis of protein secondary structure shows the significantly higher ratio of beta-sheet in PD cells compared to that of control cells, and the content of nuclear acid is highly decreased compared to that of control cells, suggesting that 6-OHDA induces the serious oxidative damage in SH-SY5Y cells. These findings suggest that SR-FTIR is an effective and precise technical tool to probe the biochemical changes of cells and then evaluate the pathological damage in cells.