The effect of pH transition points of ultra-pH sensitive fluorescent nanoprobes on tumor imaging efficiency / 药学学报

During fluorescence-guided cancer surgery, ultra-pH sensitive (UPS) fluorescent nanoprobes has multiple advantages such as real-time imaging procedures, ultra-high imaging sensitivity as well as broad tumor detection specificity. UPS nanoprobes stay at "OFF" state at higher pH and turn into "ON" state at lower pH with emission of strong fluorescence. Moreover, the transition pH points (transition pH point, pHt) can be precisely controlled by structural-based strategy. One of the previously-reported UPS nanoprobes showed good imaging effect. However, it is still not clear about the effect of pHt on cancer imaging efficiency of UPS nanoprobes and to further identify the optimal UPS. In this study, we synthesized a series of UPS nanoprobes with pHt at 4.5, 6.2, 6.6, 7.8 by adjusting the hydrophobic blocks of UPS polymers. Each nanoprobe showed excellent stability in "OFF" state by dynamic light scattering and uniform morphology observed by transmission electron microscopy. In vitro imaging characterized the ultra-pH sensitive fluorescence transition of each probe. In vivo imaging results identified two UPS nanoprobes (NP-6.2 and NP-6.6) with superior tumor imaging effect. All animal experiments in this study were approved by the Animal Ethics Committee of Peking University Health Science Center and were strictly followed by the welfare regulations of laboratory animals of Peking University Health Science Center. Therefore, this study has explored the effect of pHt on the cancer imaging efficiency of UPS nanoprobes and provides a new idea for design of the other cancer microenvironment-responsive polymers.

Emodin ameliorates diabetic neuropathic pain through inhibiting up-regulation of TRPV1 and pro-inflammatory cytokines in dorsal root ganglions in rats

@#Background & Objective: Peripheral neuropathy is one of the most common complications of diabetes and leads to sensory symptoms, including diabetic neuropathic pain (DNP). Emodin has potential analgesic effect for the treatment of pain-related diseases. However, the analgesic effect of emodin on DNP and its possible mechanism remains unknown. The aim of the present study is to investigate the effect of emodin on STZ-induced DNP in rats and its potential molecular mechanism. Methods: To determine the analgesic effect of emodin on DNP, a mouse model of STZ-induced DNP was established. The pain-related behaviors were evaluated by von Frey test, and hot plate test. The mRNA and protein expression of several TRP channels was detected by qRT-PCR and western blot methods, and the level of inflammatory cytokines was determined by ELISA. Results: The mechanical and thermal pain thresholds were significantly decreased in DNP rats. A single injection of emodin treatment significantly reduced DNP. Further results demonstrated that emodin inhibited the up-regulation of Trpv1 mRNA in the DRG of DNP rats. Our data also indicated that emodin significantly reduced the levels of TNF-α, IL-1β and IL-6 in the DRG of DNP rats. Conclusions: Emodin ameliorates mechanical allodynia and thermal hyperalgesia in DNP rats by down-regulating the expression of TRPV1 in DRG and the expression of TNF-α, IL-1β and IL-6. Emodin serves as a potent analgesic reagent for treatment and prevention of DNP.

Obstructive sleep apnea affects the sexual function of the male patient / 中华男科学杂志

Objective@#To explore the factors influencing the sexual function of the male patients with obstructive sleep apnea (OSA).@*METHODS@#Using Arizona Sexual Experience Scale (ASEX) and Epworth Sleepiness Scale (ESS), we conducted a questionnaire investigation among 81 male patients with OSA aged 40.5 ± 8.6 years and 35 healthy volunteers aged 38.8 ± 10 years. According to the sex drive (SD) score in ASEX, we divided the OSA patients into an SD reduction group (SD score = 4, n = 32) and a non-SD reduction group (SD score <4, n = 49), compared the clinical data and polysomnographic (PSG) indexes, and analyzed the factors influencing SD by evaluating the association of the PSG indexes with the SD score.@*RESULTS@#The OSA patients scored significantly higher than the healthy controls in ESS (8 ± 5 vs 5 ± 4, P <0.05) and ASEX (15 ± 4 vs 10 ± 2, P <0.05), and so did the patients of the SD reduction group than those of the non-SD reduction group in ESS (9 ± 5 vs 6 ± 5, P <0.05) and saturation impair time below 90% (SIT90) (41.01 ± 26.95 vs 21.87 ± 19.03, P <0.05). Multivariate regression analysis revealed that the SD score was significantly correlated with age (β = 0.25, P <0.001) and SIT90 (β = 0.4, P <0.001) in the OSA patients.@*CONCLUSIONS@#OSA affects various aspects of the sexual function, particularly SD, of the patient. The duration of hypoxia and age of the patient are independent risk factors for SD reduction, which can be considered as a main clinical symptom of OSA.

Effects of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-induced chronic atrophic gastritis / 中国中药杂志

To explore the effects and mechanism of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-related gastritis, sixty SD rats were randomly divided into control group, model group, high concentration of Xiangsha Liujunzi decoction group, moderate concentration of Xiangsha Liujunzi decoction group, low concentrations of Xiangsha Liujunzi decoction group and SB203580-treated group, with 10 rats in each group. SD rats of Hp-associated chronic atrophic gastritis models were established by intragastric gavage of Helicobacter pylori (HP) suspension. Changes in the gastric mucosa of rats were assessed by histopathology. ELISA was applied to detect the expressions of TNF-α and IL-6 in the serum, and the activity of iNOS in gastric mucosa. The content of NO in the gastric mucosa was tested by nitrate reductive enzymatic. The expressions of TLR2, TLR4, P38MAPK, NF-κB were detected by QPCR and Western-blot. The results indicated that the clinical symptoms of rats and pathological changes of gastric mucosa were improved in Xiangsha Liujunzi decoction group. Compared with normal control group, the protein expressions of TLR2, TLR4, p-P38MAPK and NF-κB in gastric mucosa of model group rats increased (P<0.01) with the levels of TNF-α and IL-6 in the serum, and the activity of iNOS and the content of NO in gastric mucosa increased. Compared with model group, the expressions decreased in Xiangsha Liujunzi decoction group, especially in the high concentration of Xiangsha Liujunzi decoction group(P<0.01), with gradually increased rate of HP eradication and decreased pathological grades of chronic atrophic gastritis. The serum level of TNF-α and IL-6 decreased from (24.313±2.261) μg•L ⁻¹ to (15.195±1.235) μg•L-1(P<0.01) and from (77.416±8.095) μg•L ⁻¹ to (33.150±2.532) μg•L ⁻¹ (P<0.01), and the activity of iNOS and the content of NO in gastric mucosa decreased from (1.530±0.206) U•mg ⁻¹ to (0.802±0.091) U•mg ⁻¹ (P<0.01) and from (0.907±0.032) mmol•g ⁻¹ to (0.335±0.026) mmol•g ⁻¹ (P<0.01) after the treatment of high concentration of Xiangsha Liujunzi decoction. All the effects increased with the increasing dosage of Xiangsha Liujunzi decoction from 0.324 g•mg ⁻¹ to 1.296 g•mg ⁻¹. The protein expressions of NF-κB decreased in the gastric mucosa after treated with P38MAPK specific inhibitor-SB203580. In the rats model, HP infection results in chronic atrophic gastritis through the activation of TLR2, TLR4/MAPK/NF-κB/iNOS/NO signal pathway. Xiangsha Liujunzi decoction can eradicate H. pylori and alleviate chronic atrophic gastric mucosal inflammation. The treatment is effective and safe to cure HP-induced chronic atrophic gastritis.

Prediction of the pharmacokinetic drug-drug interaction of pravastatin and pitavastatin with cyclosporine by a digital liver model based on metabolism and transporter / 药学学报

Information of metabolic enzymes and transporters, physiological parameters of animals and demography of Chinese people were integrated to establish a digital liver model (DLM) based on metabolism and transporter and coded with VBA. Clearance and drug-drug interaction (DDI) of candidate drugs in animal and human could be predicted based on the pharmacokinetic data obtained from in vitro and in vivo experiments. Pravastatin and pitavastatin were selected as the samples to examine this model, where their clearance and their DDI with cyclosporine were predicted. The results showed that the predicted values of median parameters in same species were within twofold of observed values for 83.3% (5/6). The program's successful prediction in DDI tendency might indicate its application in optimizing the dosage regimen and reducing the risk of clinical trial.

CD34+ antigen expression relating to prognosis in acute myeloid leukemia / 中国实验血液学杂志

To explore CD34(+) antigen expression in new diagnosed acute myeloid leukemia (AML) and analyze the prognosis for CD34(+) AML patients, the expression of antigen CD34 in 238 AML patients was detected by indirect immunofluorescence assay. The results showed that CD34 in 92 out of the 238 patients (38.7%) were positive, there was relationship between the CD34(+) expression and FAB subtypes (M(0), M(1)), and no CD34(+) expression was observed in M(3) subtypes. The complete remission rate of CD34(+) AML patients was 32%, which was lower than that of CD34(-) AML (61%). The lymphoid-associated antigen (CD7) was significantly increased in CD34(+) AML patients, compared with CD34(-) patients (P < 0.05). It is concluded that CD34(+) AML patients show poor prognosis and lower CR rate. The detection of CD34 expression is of some value in predicting prognosis in AML.