Objective To explore the functional activation cerebral areas evoked by mechanical stimulation induced pruritus perception imitating physiological process.Methods Scratching the planta gently to induce pruritus with brush pen wool in a group of 16 healthy volunteers,scanning BOLD-fMRI serials with a block design on a 3.0 T MR machine,and identifying the functional cerebral areas evoked by pruritus with SPM8 software for analysis.Student's t test was used to compare the difference of incidences with P＜0.05 for statistical significance.Results Several brain regions were activated by pruritus stimulus.The strongest activation evoked by pruritus was found at the contralateral thalamus and paracentral lobule(t=5.26,5.23),the most activation volumes were found at the contralateral paracentral lobule,postcentral gyrus and prefrontal lobule(146,151 and 326 volumes).Different degrees of activation were discovered at bilateral insula,preeentral and postcentral gyrus,thalamus,lentiform nucleus and cingulated gyrus.Conclusion The postcentral gyrus,paracentral lobule,insula,precentral gyrus and frontal lobe were the functional activation cerebral areas of pruritus perception evoked by mechanical stimulation.

This article focuses on the research of molecular mechanism of brain tumor treatment using the Jinlong capsule via system biology technology. Methods:Human Genome U133 Plus 2.0 gene chip was used to detect the genes of samples, in-cluding the brain tumor tissues of nude mice after Jinlong capsule intervention and those of blank control group mice. Differentially ex-pressed genes were identified based on fold change between the two groups. To identify the upstream regulators of the response signa-tures, the differentially expressed genes were subjected to interactome analysis by one-step overconnectivity test and multi-step hidden node algorithm. A set of genes preferentially connected to differentially expressed genes via direct interactions and pathways (called to-pologically significant genes) was generated. Concurrent pathway enrichment analysis on key pathways, processes, and functional units of both differentially expressed genes and topologically significant genes was performed to identify the most likely signaling pathways connecting regulators and effector genes. Finally, condition-specific networks (called causal network) were built to model molecular events by using a set of manually annotated protein interactions, pathways, and proteins and a toolkit of algorithms and filters on Meta-Core platform. Results:A total of 37 differentially expressed genes have been identified between Jinlong capsule-treated sample and ve-hicle sample with fold change of 2. Connection analysis identified 106 topologically significant genes. The main feature of the causal network is stimulation of neural cell specific genes that regulate normal cell physiology, particularly developmental processes and apop-tosis. Another important effect of the Jinlong capsule is its inhibition of the gene markers of interferon response, suggesting signaling in-hibition, followed by de-activation of immune response. Conclusion:Jinlong capsule exerts an anti-neoplastic effect by inducing stimu-lation of neural cell and by inhibiting interferon signal transduction.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.

Objective:To assess the clinical result of repeated combined detrusor-trigone botulinum toxin A(BTX-A)injection and intermittent catheterization(IC) for male adults with neurogenic detrusor overactivity (NDO) and urinary incontinence(UI) secondary to spinal cord injury(SCI).Methods:From January to August 2021, the data of 43 adult male patients with NDO and UI secondary to SCI who received repeated trigone-including intradetrusor BTX-A injection in Guangdong Provincial Work Injury Rehabilitation Hospital were retrospectively analyzed. The mean age of the patients was (29.1±10.7) years. The mean incontinence specific quality of life (I-QOL) was (39±4.8). The UI episodes was (11.9±2.6), mean voiding volume was (170.7±20.1)ml, mean maximum detrusor pressure at first NDO was (81.4±19.6) cmH 2O and mean volume at first NDO was (169.1±40.0)ml.All patients received trigone-including intradetrusor BTX-A (300 U, 30 sites) injection for four times and IC. Clinical data including I-QOL, bladder diary, video-urodynamic test and adverse events were recorded at baseline and 12 weeks after each injection. Results:Mean interval between four injections were (220.6±27.4), (222.8±24.1) and (224.4±39.0) d ( P=0.13). Compared with baseline data before first injection, mean I-QOL after the first, second, third and fourth injection increased to (54.9±9.1), (56.1±7.9), (61.7±9.1) and (68.8±8.9) (all P<0.001). The number of urinary incontinence cases decreased to 36, 35, 35 and 33 (all P<0.05). The mean urinary incontinence episodes per day decreased to (4.4±0.6), (3.8±0.4), (2.2±0.5) and (2.1±0.3)(all P<0.001). Mean voiding volume increased to (288.3±40.2), (300.0±38.6), (316.9±46.8) and (319.5±36.7) ml (all P<0.001). Mean maximum detrusor pressure at first NDO decreased to (29.4± 11.0), (26.1±8.7), (20.3±5.9) and (18.5±6.0) cmH 2O (all P<0.001) and mean volume at first NDO increased to (270.0±48.7), (284.9±51.3), (287.7±47.9) and (303.0±46.2) ml (all P<0.001), respectively. Compared with four injections, no difference in response was found in the mean I-QOL, the number of urinary incontinence cases, mean urinary incontinence episodes mean voiding volume, mean maximum detrusor pressure at first NDO and mean volume at first NDO (all P>0.05). No de novo VUR occurred and 2 cases of grade Ⅱ VUR at baseline had resolved after the first injection. 9 patients experienced serious gross hematuria within first week after injection, but the urine returned to clear by prolonging the catheter indwelling time or bladder irrigation. 12 patients with active urinary tract infection were treated with indwelling catheter and sensitive antibiotics. Patients continued IC when the symptoms, signs and laboratory examination were normal. Conclusions:Combined detrusor-trigone BTX-A injection and IC could help decrease detrusor pressure, restore some of the lower urinary tract function and improve the quality of life for male patients with NDO and UI secondary to SCI. Repeated injection is as effective and safe as the first injection.

AIM: To investigate the possible use of anti-FGF-2 nanobody for the treatment of pathological neovascularization. METHODS: SD rats were divided into a sham operation group, a control group (3 mm diameter circular filter paper soaked with 1 mol/L NaOH solution was applied to the central part of the cornea of rats for 30 s to prepare the rat model of alkali-burn angiogenesis) and a treatment group (treated with a drop of 3 mg/mL anti-FGF-2 nanobody 7 days after the operation. Repeat application 3x/day for 14 days). Corneal angiogenesis was measured by stereoscopic microscopy and CD31 immunohistochemical staining. The mRNA and protein expression levels of VEGF and FGF-2 were detected by quantitative fluorescence PCR (qPCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.RESULTS: (1) Blood vessel: The area of the treatment group was significantly reduced compared with the model group, and the vascular lumen was narrower (P<0.05). The difference was the most significant after 14 days of drug intervention; (2) Expression level of FGF-2 mRNA and protein: the model group had similar results to the treatment group (P>0.05); (3) Expression levels of VEGF mRNA and protein: The treatment group was significantly higher than the model group (P<0.05). In addition, the expression of VEGF also increased significantly in the continuous administration of the sham operation group. CONCLUSION: Anti-FGF-2 nanobody can be used for the treatment of angiogenesis. However, the expressions of VEGF will compensatorily increase after blocking FGF-2 in normal or pathological rats.

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (

Objective: To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity(DU). Methods: A prospective and self-controlled trail was conducted from August 2012 to October 2017. Male patients with nerve injury, dysuria more than 6 months, DU(bladder contractility index less than 100) were enrolled in this study. Exclusion criteria included patients with acute urinary tract infection, bladder stone, benign prostate hyperplasia, urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline, and the solution of BTX- A was injected into 4 different points(3-o’clock, 6-o’clock, 9-o’clock, and 12-o’clock) in external urinary sphincter with each point of 1ml solution. Patients were evaluated at baseline and 12 weeks after injection. The outcomes included post void residual (PVR), maximum flow rate (Q_max), maximum detrusor pressure during voiding phases (P_det.max), maximum urethral closure pressure (MUCP), the case number of intermittent catheterization (IC)and the score of quality of life (QOL score). Adverse events were also recorded. Results: A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital)with mean age 28.6 years suffered from cerebral palsy (n=2), cerebrovascular accident(n=19)and spinal cord injury(n=37) were included into the study. Compared to baseline data, significant difference were observed at week 12 in PVR (56.68 ml vs. 280.11 ml, P<0.001), P_det.max(23.95 cmH₂O vs. 30.01 cmH₂O, P=0.019), Q_max(6.74 ml/s vs. 3.28 ml/s, P=0.042), MUCP(48.25 cmH₂O vs. 79.34 cmH₂O, P<0.001), the case number of IC(40 vs. 58, P<0.001) and QOL score(3.63 vs.5.22, P<0.001) respectively. 5 cases developed perineal pain and 16 cases developed mild transient haematuria. These adverse events were disappeared by medical symptomatic treatment during 3-5 days. Conclusions BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.

Squamosa promoter binding protein-like (SPL) family is a group of important transcription factors involved in the regulation of plant growth and development and the response to environmental stress, but there are few studies in perennial fruit trees such as citrus. In this study, Ziyang Xiangcheng (Citrus junos Sib.ex Tanaka), an important rootstock of Citrus, was used as the material for analysis. Based on plantTFDB transcription factor database and sweet orange genome database, 15 SPL family members were genome-widely identified and cloned from Ziyang Xiangcheng, and named CjSPL1-CjSPL15. Sequence analysis showed that the open reading frame (ORF) length of CjSPLs ranged from 393 bp to 2 865 bp, encoding 130-954 amino acids. Phylogenetic tree divided 15 CjSPLs into 9 subfamilies. Gene structure and conserved domain analysis predicted 20 different conserved motifs and SBP basic domains. Analysis of cis-acting promoter elements predicted 20 different promoter elements, including those related to plant growth and development, abiotic stress and secondary metabolites. The expression patterns of CjSPLs under drought, salt and low temperature stresses were analyzed by real-time fluorescence quantitative PCR (qRT-PCR), and many CjSPLs were significantly up-regulated after stress treatment. This study provides a reference for further study on the function of SPL family transcription factors in citrus and other fruit trees.
Phylogeny ; Transcription Factors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Multigene Family ; Stress, Physiological

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.