Therapeutic Effect of Canagliflozin on Nephrotic Syndrome and Its Ultrasonic Evaluation / 中山大学学报(医学科学版)

ObjectiveTo investigate the therapeutic effect of antidiabetic drug canagliflozin （CGLZ） on adriamycin-induced nephrotic syndrome （NS） in rats， and the evaluation of contrast-enhanced ultrasound （CEUS） combined with color Doppler flow imaging （CDFI） during the treatment. MethodsA total of 56 male SD rats were randomly divided into normal group （NG）， model group （MG）， prednisone （PAT） group （PG）， low-dose single CGLZ group （LSCG）， high-dose single CGLZ group （HSCG）， low-dose CGLZ + PAT group （LUCG） and high-dose CGLZ + PAT group （HUCG）， with 8 rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein， and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein （24 h-UTP） was assessed one day before the start of oral administration and at the end of 2， 4 and 6 weeks after oral administration， respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration， and the blood of abdominal aorta was taken for serological test the next day. ResultsCompared with those detection index of NG rats， the 24-hour UTP of MG rats increased （P＜0.01）， the serum ALB decreased and TG， TC， LDL increased （P＜0.01）， and CDFI shows that RRCT was thinner （P＜0.01） and the renal artery blood flow indicators RA-PI， RA-RI， RA-S/D all increased （P＜0.05）， and CEUS image shows that the TIC curve parameters TTP， AT， AUC all increased and DPI decrease in MG rats （P＜0.01）. After drug treatment， compared with those detection index of MG rats， 24 h-UTP decrease in LSCG after 2 weeks （P＜0.01）， and decrease significantly in all drug groups after 6 weeks （P＜0.01）； the serological test results show that the serum ALB in all CGLZ groups increased （P＜0.05）， TG decrease in LSCG （P＜0.01）， TC and LDL also decrease in LUCG after 6 weeks （P＜0.05）； CDFI shows that the RRCT thinning degree in all CGLZ is reduced （P＜0.01）， and the RA-PI in LSCG， RA-RI in PG， and RA-S/D in PG， LSCG， HSCG and LUCG rats all decreased （P＜0.05）； CEUS shows that the TTP， AT and AUC of renal TIC curve in drug treatment groups all decreased （P＜0.01）， and the DPI in PG， HSCG， LUCG and HUCG rats increased （P＜0.01）. ConclusionsCGLZ has the effect of treating NS， and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment， which is helpful to guide clinical application.

Correlation between postoperative decentration and tilt of aspherical intraocular lens implantation and visual quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the correlation between postoperative lens decentration and tilt and visual quality in eyes implanted with aspherical intraocular lens(IOL)by using a new anterior segment swept-source optical coherence tomography(OCT)CASIA2.METHODS: An observational study. A total of 90 eyes of 62 participants who underwent age-related cataract surgery at 1mo were included. Using CASIA2 by an experienced examiner, IOL tilt and decentration were obtained three consecutive times after mydriasis and the vector mean values were calculated. Double-pass optical quality analysis system(OQAS)and wavefront aberration instrument KR-1W were used for the visual quality measurements, including the total high-order aberration(tHOA), spherical aberration(SA), Coma, objective scatter index(OSI), modulation transfer function cut off frequency(MTF cut off)and Strehl ratio(SR)at 4 and 6mm pupil diameter.RESULTS: IOL decentration was positively correlated with SA(r=0.347, P=0.001)and OSI(r=0.343, P=0.002)at 4mm pupil diameter, and it was negatively correlated with MTF cut off(r=-0.244, P=0.032). There was no significant correlation between IOL decentration and tHOA, Coma and SR. IOL tilt was negatively correlated with MTF cut off(r=0.-345, P=0.002)and SR(r=-0.256, P=0.023)at 4mm pupil diameter, but it was not correlated with tHOA, SA, Coma and OSI. There were no significant correlations between the IOL decentration and tilt and tHOA, SA, Coma, MTF cut off and SR at 6mm pupil diameter.CONCLUSION: After aspherical IOL implantation in age-related cataract patients, IOL decentration was weakly correlated with SA at 4mm pupil diameter, while decentration and tilt were not significantly correlated with other higher-order aberrations. The decentration and tilt were weakly correlated with OSI value and MTF cut off value of the visual quality parameters. The results suggest that clinicians should pay more attention to higher-order aberrations and visual quality during precise cataract surgery.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease / 中西医结合学报

OBJECTIVE@#To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD).@*METHODS@#Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice.@*RESULTS@#Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01) in APP/PS1 mice.@*CONCLUSION@#Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain / 国际口腔科学杂志·英文版

Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund's adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.

Surgical plane positioning with a disposable circumcision suture device for the treatment of phimosis and redundant prepuce / 中华男科学杂志

<p><b>Objective</b>To investigate the clinical effects of circumcision by surgical plane positioning with a disposable circumcision suture device in the treatment of phimosis and redundant prepuce.</p><p><b>METHODS</b>From September 2016 to June 2017, we treated 250 patients with phimosis or redundant prepuce, 127 by conventional circumcision (the control group) and the other 123 by surgical plane positioning with a disposable circumcision suture device (the observation group). We compared the operation time, intra-operative bleeding, preputial frenulum alignment, postoperative ecchymosis, and postoperative penile appearance between the two groups of patients.</p><p><b>RESULTS</b>Compared with the controls, the patients in the observation group showed significantly longer operation time (［4.48 ± 1.18］ vs ［7.17 ± 1.42］ min, P<0.05), lower rates of intra-operative frenulum bleeding (15.0% ［19/127］ vs 4.1% ［5/123］, P<0.05) and frenulum misalignment (26.8% ［34/127］ vs 0.8% ［1/123］, P<0.05), higher incidence of postoperative ecchymosis (41.7% ［53/127］ vs 21.1% ［26/123］, P<0.05), and higher satisfaction of the patients with the postoperative penile appearance (92.9% ［18/127］ vs 98.4% ［121/123］, P<0.05). However, no statistically significant difference was found between the control and observation groups in intra-operative non-frenulum bleeding (4.7% ［6/127］ vs 1.6% ［2/123］, P = 0.164).</p><p><b>CONCLUSIONS</b>Circumcision by surgical plane positioning with a disposable circumcision suture device can effectively avoid preputial frenulum misalignment, reduce intra-operative bleeding, and improve postoperative penile appearance.</p>

Lipoxin A4 Ameliorates Lipopolysaccharide-Induced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1 / 中华医学杂志(英文版)

<p><b>Background</b>Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4.</p><p><b>Methods</b>A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression.</p><p><b>Results</b>The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4.</p><p><b>Conclusion</b>Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.</p>

The structure and function of habenula / 生理学报

The habenula (Hb) is an evolutionarily conserved diencephalic structure in vertebrates. It is considered as an emotion center and plays critical roles in regulating diverse types of emotion-related behaviors, including anxiety, fear, reward, depression, and nicotine withdrawal. On the one hand, action selection- and emotion-relevant inputs are transferred to the Hb through the basal ganglia and limbic system, respectively. At the same time, sensory inputs of multiple modalities also converge on the Hb. Among them, the visual input of the Hb from the retina ganglion cells ‒ thalamus pathway has been found to play a critical role in light-preference behavior of zebrafish. On the other hand, the Hb projects to two main neuromodulatory systems, the dopaminergic system and the serotoninergic system. As the Hb receives both internal emotion inputs and external sensory inputs and regulates the function of neuromodulatory systems, its functions are quite diverse and complex. In this review, we summarize the progress in both the structure and connection of the Hb and propose future study direction.

Establishment of an anesthesia model induced by etomidate in larval zebrafish / 生理学报

Despite the wide application of general anesthetic drugs in clinic, it is still unclear how these drugs induce the state of general anesthesia. Larval zebrafish has emerged as an ideal model for dissecting the mechanism of neural systems due to the conserved and simple brain structure. In the present study, we established an anesthesia model from behavioral to electrophysiological levels using larval zebrafish for the first time. Bath application of etomidate, as a kind of intravenous anesthetic drugs, suppressed the spontaneous locomotion of zebrafish in a concentration-dependent manner. Consistently, in vivo fictive motor patterns of spinal motoneurons recorded extracellularly were significantly inhibited as well. Furthermore, using in vivo extracellular recording and whole-cell recording, we found that etomidate application suppressed local field potentials (LFP) of the brain and blocked visually evoked responses of optic tectal neurons. The study indicates that larval zebrafish can serve as an ideal vertebrate animal model for studying neural mechanisms underlying general anesthesia.

Progress in the study of the blood-brain barrier / 生理学报

Blood-brain barrier (BBB) precisely controls the material exchange between the blood and brain tissue, and plays a critical role in the maintenance of brain microenvironment homeostasis. Brain microvascular endothelial cells connect tightly with each other and intertwine with surrounding pericytes and astrocytes to form the BBB. These cells regulate the development and function of the BBB through expressing tight and adherens junction proteins, transporters, and relevant signal molecules. Neurons and microglia can also regulate the function of BBB in physiological and pathological conditions. Recent studies indicate that the occurrence and progress of various neurological diseases are accompanied with structural and functional impairment of the BBB. Therefore, elucidation of the mechanisms underlying BBB development and function will further benefit our understanding of neurovascular interaction and provide an important theoretical basis for the treatment of neurological diseases. In this review, we briefly summarize the progress of BBB research.

Influence of prenylation at C-8 of ring A of flavonoid on bioactivity of parent compound / 中草药

The flavonoids with the prenylation on site 8 are a unique class of natural flavonoids. The existence of prenyl-moiety could dramatically increase the lipophilicity and the relevant bioactivities of flavonoids. This review discussed the influences of the prenylation at C-8 of ring A in flavonoids on the activities of antioxidant, anti-bone resorption, antimicrobial activity, anti-tumor activity, and tyrosinase inhibition of the backbone flavonoids.

Physiological properties and functions of microglia / 生理学报

Microglia, the resident immune effective cells of the central nervous system, play crucial roles in mediating immune-related process. It becomes activated quickly in response to even minor pathological insults and participates in series of immune responses. Under physiological conditions, most microglia stay in a typical resting state, with ramified processes continuously extending and retracting from surrounding neural tissues, suggesting an important function of resting microglia. Recent studies indicate that resting microglia can regulate many physiological processes, including neural development, neural circuit formation, neuronal activity and plasticity, and animal grooming behavior. Here, we review the properties of resting microglia and further discuss how microglia participate in the above-mentioned functional regulation under physiological conditions.

Androgen deprivation therapy for prostate cancer: a follow-up study of the patients' survival time / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the long-term survival and prognosis of prostate cancer patients after treated by androgen deprivation therapy.</p><p><b>METHODS</b>We conducted a follow-up study of 124 patients with prostate cancer treated by androgen deprivation therapy, and compared the survival times of the patients with different pathological grades and clinical characteristics using Kaplan-Meiers survival curves.</p><p><b>RESULTS</b>The mean survival time of the 124 patients after androgen deprivation therapy was 5. 912 years, with the median survival time of 7.81 years. The patients with bone metastases showed a shorter survival time than those with non-bone metastasis (P = 0.04). Pathological grades and PSA levels were not prognostic factors. No significant differences were found in the mean survival time between those died of prostate cancer (n = 35) and those from other factors (n = 23) (P = 0.50).</p><p><b>CONCLUSION</b>Bone metastasis is an important prognostic factor in advanced prostate cancer following androgen deprivation therapy, which is more significantly correlated with the survival time of the patients than tumor grades and clinical classification.</p>

The value of 18F-FDG PET/CT in the diagnosis of secondary malignant peripheral nerve lesion / 中华核医学杂志

Objective To investigate the characteristics and diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/CT in patients with secondary malignant peripheral nerve lesions. Methods 18F-FDG PET/CT studies of 8 cases of secondary malignant peripheral nerve lesions confirmed by histopathology or follow-up were analyzed retrospectively. The maximum standardized uptake value ( SUVmax ) of infiltrating peripheral nerves and contralateral normal peripheral nerves was measured and compared with their morphological appearances on CT. Paired student t-test was performed by SPSS 10.0. Results Twelve secondary malignant peripheral nerve lesions with high 18F-FDG metabolism were found in 8 cases. On PET imaging,the lesions distributed along the neurovascular tissues or intervertebral foramina with appearances resembling those of fibre bundles,radices or nodes on PET but no density differences with the surrounding soft tissue or fat planes on CT. The SUVmax was 6.86 ± 3.87. The contralateral normal peripheral nerves showed no abnormal 18F-FDG uptake with a SUVmax of 1.10 ±0.46,which was significantly different from that of the secondary malignant peripheral nerve lesions (t = 9.231,P ＜ 0.001 ). Conclusion 18 F-FDG PET/CT may be useful in locating the secondary malignant peripheral nerve lesions and in assessing its regional infiltration.