Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.

OBJECTIVE: To explore the mechanism of acupuncture plus medication on treatment of Alzheimer's disease (AD). METHODS: Sixty adult SD rats were randomly divided into a normal group, a sham operation group, a model group, an electroacupuncture (EA) group, a gastrodin group and an EA+gastrodin group, 10 rats in each one. The rat model of AD was established by intraperitoneal injection of D-galactose and bilateral hippocampal injection of Aβ1-40. Two weeks after modeling, the rats in the EA group and EA+gastrodin group were treated with EA at "Baihui" (GV 20) "Dazhui" (GV 14) and bilateral "Zusanli" (ST 36), 30 min per treatment, once a day for consecutive 4 weeks. The rats in the gastrodin group and EA+gastrodin group were treated with intraperitoneal injection of gastrodin, once a day for consecutive 4 weeks. The rats in the normal group, model group and sham operation group were not treated. The morphology of hippocampal neurons was observed by using HE staining. The expression of Bcl-2 and Bax in the hippocampal CA1 area was detected by using immunohistochemical method. The expression of Bcl-2 and Bax protein in hippocampus was detected by using Western blot. RESULTS: The HE staining results showed the arrangement of neurons in the hippocampal CA1 area was regular in the normal group and the sham operation group, and the cytoplasm and nucleus were clearly visible. The neurons in the model group were severely damaged; the cell arrangement was not close, and the cell morphology was incomplete. Compared with the model group, the cell morphology of each intervention group was significantly improved. The immunohistochemistry results showed that, compared with the normal group and the sham operation group, the expression of Bcl-2 in the hippocampal CA1 region in the model group was decreased (<0.05), but the expression of Bax was enhanced (<0.05); compared with the model group, the expression of Bcl-2 was increased (all <0.05) and the expression of Bax was decreased (all <0.05) in all intervention group; compared with the EA group or the gastrodin group, the expression of Bcl-2 was enhanced (<0.05) and the expression of Bax was decreased (<0.05) in the EA+gastrodin group. The result of Western blot method was consistent with that of immunohistochemistry method. CONCLUSION EA and gastrodin could significantly inhibit the expression of Bax and up-regulate the expression of Bcl-2, and the combination of EA and gastrodin has the most significant effect. This indicates that EA combined with gastrodin has synergistic effect on inhibiting the apoptosis of neurons in hippocampus in AD rats, which may be one of the mechanisms of EA plus medication on AD lesions.
Alzheimer Disease ; Animals ; Electroacupuncture ; Hippocampus ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein

OBJECTIVE: To evaluate the effects of Xiaojin Pill () in the treatment of Peyronie's disease (PD) in a rat model. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea (TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor (TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution (107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9 (MMP2/9), nitric oxidesynthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. RESULTS: Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum (CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group (all P<0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated (both P<0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group (all P<0.01). After Xiaojin Pill treatment, the levels of MDA, NOS and SOD appeared to be corrected (all P<0.01). CONCLUSIONS Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.

As a rare endangered medical plant that newly cultivated,little experimental information is available for growth and metabolites of Tetrastigma hemsleyanum in response to nitrogen( N). The effects of different levels of N on growth of T. hemsleyanum and the content of phytochemicals( polysaccharide,total flavonoids and phenolics) and antioxidant activity( ABTS and FRAP) in stems and leaves were investigated in this study. A certain amount of N had positive effects on most of biological traits,and excessive dose of N went against growth of T. hemsleyanum. With N levels decreased,the polysaccharide content in stems and leaves had no significant change,while the total flavonoid and phenolic content,and antioxidant activities increased steadily. Antioxidant activities and total flavonoid and phenolic content had significant positive correlation. Excessive N fertilizer should be avoided by cultivation.
Antioxidants ; Flavonoids ; Nitrogen ; Phenols ; Phytochemicals ; Plant Extracts ; Plant Leaves ; Vitaceae

Background: Due to advances in high-frequency ultrasound technology, it is easier to detect fine structures of skin lesions. The aim of this study was to examine the ultrasonographic features and use recurrence risk stratification to assess the diagnostic performance of pre-operative ultrasound examination of basal cell carcinoma (BCC). Methods: This was a retrospective study. Forty-six BCC lesions underwent pre-operative ultrasound examination using 50- and 20- MHz probes. Ultrasonographic shape, margin, internal echoes, hyper-echoic spots, posterior echoes, and depth of the lesion were evaluated and correlated with the risk of recurrence based on histological features. Results: Forty-two patients had 46 skin lesions in total. The high-risk (n = 6) and low-risk (n = 40) groups exhibited considerable overlap in the ultrasonographic manifestations and no significant difference in margin (χ² = 3.231, P = 0.072), internal echo (χ² = 1.592, P = 0.207), or posterior echo (P = 0.169). However, high-risk BCCs tended to be irregular in shape than low-risk lesions (χ² = 4.313, P = 0.038). Both types presented hyper-echoic spots (χ² = 1.850, P = 0.174). Additionally, 78% of low-risk lesions were confined to the dermis (31/40), and 100% of high-risk lesions infiltrated into the sub-cutaneous tissue, resulting in a significant difference between the two groups (χ² = 10.951, P = 0.001). Ultrasound detected sub-clinical lesions in five patients. Conclusions High-frequency ultrasound can provide important information for pre-operative evaluation of risk in BCC foci and reveal hidden lesions. The technique may play a crucial role in guiding therapeutic options for BCC.

Background: Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age. Methods: Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women’s data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 μg/L and iron overload (IO) was defined as ferritin >150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders. Results: The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ² = 10.264, P = 0.002; 6.25% vs. 3.70%, χ² = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011–3.282, P = 0.046, respectively). Conclusion: ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive. Clinical trial registration ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.

Through the traditional Chinese medicine inheritance platform system, with the help of medical records, Ye Tianshi and Wu Jutong's medication characteristics for summer heat sickness were analyzed, the laws of the two people's medication were summarized, and the similarities and differences between the two were explored to explore the relationship. As a result, it was found that both of them recognized the relationship between summer heat and wetness, and Wu Jutong believed that "wind" was also an important pathogenic factor. Both of the patients were treated with cold medicine and warm medicine. They used mostly bitter, sweet, pungent taste and lungs, spleen, stomach, and heart meridian are the main components; two are commonly used Armeniacae Semen Amarum, Talcum, Rehmanniae Radix, Ophiopogonis Radix, Pinelliae Rhizoma and other drugs, Ye Tianshi use Scrophulariae Radix, Tetrapanacis Medulla, Coicis Semen and other drugs more, Wu Jutong use Gypsum Fibrosum, Sojae Semen Praeparatum, Menthae Haplocalycis Herba and other drugs more; at the same time, a combination of two high-frequency medicines used by two people has been excavated, and a new prescription has been deduced to provide a reference for further understanding and treatment of summer diseases.

To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, >0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Mass Spectrometry ; Meridians ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Tandem Mass Spectrometry

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.
Animals ; Disease Models, Animal ; Fluorescein Angiography ; Hemodynamics ; physiology ; Humans ; Male ; Optic Disk ; pathology ; physiopathology ; Optic Neuropathy, Ischemic ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells ; physiology