Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Predictive model of curative effect of mite subcutaneous immunotherapy in 5-18 years of age patients with allergic asthma / 中华儿科杂志

Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.

Inhibitory Effect of Cinnamaldehyde on Proliferation, Migration and Tube Formation of VEGF-induced Endothelial Cells via JAK2/STAT3 Pathway / 中国实验方剂学杂志

Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), VEGF+AG490 group (50 μmol·L-1), VEGF+cinnamaldehyde group (90 μmol·L-1), VEGF+cinnamaldehyde group (150 μmol·L-1), and VEGF+cinnamaldehyde group (150 μmol·L-1)+AG490 group (50 μmol·L-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (PPPP-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (PPConclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.

Epimedium alleviates chemotherapy-induced damage to the ultrastructure and function of rat epididymides / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the protective action of Epimedium against chemotherapy-induced damage to rat epididymides.</p><p><b>METHODS</b>Fifty 60-day-old male rats were divided into a control, a model and a treatment group. Procarbazine was injected into the abdominal cavity of the model rats at the dose of 30 mg/(kg x d). In addition to procarbazine, Epimedium was given intragastrically to the treatment group. The changes in the ultrastructure of the epididymis were observed after 10 and 20 days.</p><p><b>RESULTS</b>Electron microscopy showed that the chemotherapy-induced damages to the epididymal epithelia mainly included cell swelling, local cavitation of mitochondria, tumor-like change in nucleoli, agglutination of marginal translocation of heterochromatin and cell apoptosis. The damage to the epithelial ultrastructure was slight in the treatment group as compared with the model rats. Chemotherapy significantly affected sperm concentration, sperm viability and sialic acid (SA), which were (15.59 +/- 4.01) x 10(6)/ml, (76.71 +/- 10.11)% and (19.38 +/- 9.34) g/mg prot in the model group in comparison with (10.63 +/- 3.82) x 10(6)/ml (P < 0.01), (60.03 +/- 7.54)% (P < 0.01) and (13.62 +/- 7.81) g/g prot (P < 0.05) in the control. Epimedium significantly increased sperm viability in the treatment group (60.03 +/- 7.54)% as compared with the model rats (69.90 +/- 12.58)% (P < 0.05).</p><p><b>CONCLUSION</b>Epimedium can lessen chemotherapy-induced damage to the epididymis and protect the reproductive function of rats.</p>

Promoting mechanism of enhancers and transport pathway of large hydrophilic molecular across nasal epithelium studied by ESR and CLSM technologies / 药学学报

The aim of this study is to investigate absorption-promoting mechanism of enhancers and the transport pathway of large hydrophilous molecular across rat nasal epithelium by electron spin resonance (ESR) and confocal laser scanning microscopy (CLSM) technologies. In the experiment, recombinant hirudin-2 (rHV2) was chosen as a large hydrophilic molecular model drug. After nasal administration in rats the bioavailability of rHV2 with or without various enhancers was compared. The effects of enhancers on membrane lipid fluidity and protein conformation were measured with 5-deoxyl-stearic acid (5-DSA), 16-deoxyl-stearic acid (16-DSA) and 3-maleidoproxyl (MSL) labeling ESR. The effects of enhancers on cytoskeletal F-actin of rat nasal epithelium and FITC-rHV2 transport pathway across rat nasal epithelium were performed by CLSM combined with fluorescence labeling. 0.5% Chitosan (CS), 5% hydroxyl-propyl-beta-cyclodextrin ( HP-beta-CD) and 1% ammonium glycyrrhizinate (AMGZ) were all able to significantly increase the nasal absorption of rHV2. CS could result in the paracellular pathway transport of FITC-rHV2 which seemed related to a transient effect on tight junctions. HP-beta-CD could cause paracellular and transcellular route transport of FITC-rHV2 by influencing upon membrane protein as well as lipid fluidity. AMGZ seemed to enhance the transcellular route transport of FITC-rHV2, and could exert some influence on membrane protein but not on lipid fluidity. So how it brought out this result needs further research. Present experiment may become a useful reference for promoting mechanism of enhancers and the transport pathway of large hydrophilic molecular across nasal epithelium research.

Changes in tight junction of intestinal mucosa in patients with irritable bowel syndrome: a study with tracing electron microscope / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the presence of tight junction (TJ) changes of the intestinal mucosa, and elucidate the possible mechanism for changes in bowel evacuation in patients with irritable bowel syndrome (IBS).</p><p><b>METHODS</b>In 10 normal control subjects, 10 patients with constipation predominant IBS (C-IBS) and 10 with diarrhea predominant IBS (D-IBS), biopsies were taken from the terminal ileum and ascending colon. Lanthanum nitrate tracing electron microscope and cytochemical technique were employed to observe TJ changes in the intestinal mucosa.</p><p><b>RESULTS</b>Like the control subjects, C-IBS patients had normal TJ structure in the intestinal mucosa, whereas D-IBS patients exhibited some abnormalities in TJ structure either in their terminal ileum (7 in 10) or ascending colon (8 in 10), revealed by TJ gap widening with lanthanum nitrate extravasation into the surrounding tissue. Such changes were also observed in 3 of the 4 patients with a history of acute infectious diarrhea.</p><p><b>CONCLUSION</b>The changes in the intestinal mucosal TJ structure and function might contribute to altered bowel evacuation in patients with irritable bowel syndrome.</p>

The pharmacokinetics and pharmacodynamics of recombinant hirudin-2 nasal spray / 药学学报

<p><b>AIM</b>To investigate the pharmacokinetics and the anticoagulation action of recombinant hirudin-2 (rHV2) nasal spray after administration of the preparation.</p><p><b>METHODS</b>rHV2 concentration in plasma was determined by chromogenic substrate method and the relative bioavailability was calculated. The anticoagulation action of rHV2 spray after intranasal administration in normal rats and DIC model rabbits after intranasal administration of rHV2 spary were studied.</p><p><b>RESULTS</b>The in vivo course of rHV2 in rats fitted to the one-compartment model after intranasal administration of rHV2 spray and the relative bioavailability was 28.53%. Coagulating times of APTT and TT were significantly prolonged in normal rats, and APTT in DIC model rabbits was significantly shortened and was close to the normal values after administration of rHV2 nasal spray.</p><p><b>CONCLUSION</b>rHV2 spray could be an effective nasal preparation of rHV2.</p>

Degradation of recombinant hirudin-2 in nasal mucosa of rabbits in vitro / 药学学报

<p><b>AIM</b>To investigate the degradation of recombinant hirudin-2 (rHV2) in nasal mucosa of rabbit.</p><p><b>METHODS</b>The specific and accurate HPLC method was developed for analyzing rHV2; The degrading ratios of rHV2 at different concentrations and at pH conditions in rabbit nasal mucosa homogenate were determined; The results in nasal mucosa homogenate were compared with that in small intestinal mucosa homogenate of rabbits. The stability of rHV2 in the enzyme extract of nasal mucosa surface and the effect of proteolysis inhibitor bacitracin on the degradation of rHV2 in nasal mucosa homogenate were also estimated.</p><p><b>RESULTS</b>The degradation of rHV2 in rabbit nasal mucosa homogenate showed concentration- and pH-dependence; rHV2 in nasal mucosa homogenate was more stable than that in intestinal mucosa homogenate. Also rHV2 was more stable in the enzyme extracts of nasal serosal surface than that of mucosa surface. Addition of bacitracin was able to inhibit the degradation to some degree.</p><p><b>CONCLUSION</b>Comparing with oral administration, rHV2 nasal delivery was a more tolerant route.</p>

Optimization study on extraction technology of the seed of Ziziphus jujuba var. spinosa by orthogonal design with multi-targets / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize extraction technology of the seed of Ziziphus jujuba var. spinosa with the targets of the total saponin, total jujuboside A and B and total flavonoids.</p><p><b>METHOD</b>In the method of one-way and orthogonal tests, ethanol concentration, amount of ethanol, extraction time and extraction times were the factors in orthogonal test, and each factor with three levels.</p><p><b>RESULT</b>Ethanol concentration and extraction times had significant effect on all the targets, other factors should be selected in accordance with production practice.</p><p><b>CONCLUSION</b>The best extraction technology is to extract for three times with 8 fold ethanol solution (60%), and 1.5 h each time.</p>

Studies on the nasal epithelium toxicity of adjuvants and recombination hirudin (rHV2) nasal spary / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the nasal epithelium toxicity of adjuvants and rHV2 nasal spary(HVS).</p><p><b>METHOD</b>Ciliary movement were evaluated with in situ toad palate model; The histology assessment of nasal epithelium were carried out after long-lasting and repeated use of HVS.</p><p><b>RESULT AND CONCLUSION</b>Adjuvants included SDS, Brij 35, azone, lecithin, EDTA, menthol, nipagin and thiomersal were able to significantly inhibited the ciliary movement, while tween80, glycyrrhizic acid monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials investigated had less influence on it. HVS was able to damaged the nasal epithelium, but this effect recovered soon after stopping administration. It was demonstrated that SDS, Brij 35, azone,lecithin, EDTA, menthol, nipagin and thiomersal. It had significant cilitoxity, while tween80, glycyrrhizic acid monoammonium salt, benzalkonium bromide, sodium benzoate and adhensive materials investigated had no significance; Chitosan co-administration with some adjuvants may make the cillitoxity severer; It is available that rHV2 be administered by nasal spary.</p>

Morphological alteration of the hippocampal synapses in rats prenatally exposed to magnetic resonance imaging magnetic fields / 生理学报

The present study investigated the effects of prenatal exposure to the magnetic resonance imaging (MRI) magnetic fields on the synaptic ultrastructure of hippocampal formation of rats at different postnatal development stages. Pregnant rats with gestation of 12-18 days were exposed to the magnetic fields used for MRI clinical applications. When the offspring were 1, 2, or 5-month-old, the synaptic morphologic parameters were measured in female offspring. In the 2-month-old MRI group, the curvature of synaptic interface, the length of active zone and the surface density per unit volume (S(v)) of active zone in the dentate gyrus (DG) decreased significantly, and the width of synaptic cleft increased in the CA1 area. In the 5-month-old MRI group, the width of synaptic cleft increased, the thickness of postsynaptic density and the curvature of synaptic interface decreased significantly in the CA1 region, and the width of synaptic cleft increased in the DG. No significant change was observed in the 1-month-old group. These results suggest that prenatal exposure to the medical magnetic fields causes synaptic ultrastructural changes. The relationship of these changes with behavioral impairments was discussed.

Effects of malnutrition on child survival in China as estimated by PROFILES / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To estimate the benefits of reductions in underweight and Vitamin A deficiency for child survival in China that might be expected as a result of lowering the prevalence of these conditions.</p><p><b>METHODS</b>Profiles, a process of nutrition policy analysis was used to quantify the functional consequences of malnutrition in terms of child survival.</p><p><b>RESULTS</b>Underweight: The actual reduction in underweight between 1992 and 2001 (from 15.7% to the current 10.1%) resulted in saving of 176,000 child lives. As estimated, without improvements, 612,000 children will die due to underweight between 2001 and 2010, 281,000 (46%) of them living in western provinces. Reducing underweight prevalence from 10.1% to 8% could overall save 62,000 lives. The reduction of underweight prevalence in the west alone might save 56,000 lives. Vitamin A in China as a whole, vitamin A deficiency accounts, as estimated, for 7.5% of deaths of children 6-59 months old, representing 206,000 deaths over the past ten years. Halving the prevalence over the period would save 49,000 child lives. The higher prevalence and higher mortality rates in western provinces mean that even with only 28% of the Chinese population, over half of child deaths there are related to vitamin A.</p>

Effects of malnutrition on economic productivity in China as estimated by PROFILES / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To calculate the effects of malnutrition on economic productivity in China.</p><p><b>METHODS</b>PROFILES was used to quantify the function consequences of malnutrition in term of protein energy malnutrition, iron deficiency and iodine deficiency.</p><p><b>RESULTS</b>Productivity gained due to improved iodine nutrition. The reduction in the TGR in 1992 to 2001 increased the net present value of further economic productivity by yen 142 billion. Reduction of the TGR rate to 5% over next 10 years would result in future productivity gains with value of yen 40 billion. Productivity gain due to reductions in child stunting would result in future economic productivity gains with the value of yen 101 billion. Reducing stunting further over the next 10 years would gain yen 20 billion. Productivity gain due to reduction of iron deficiency anemia reduced by 30% over the next 10 years would gain worth yen 107 billion and if childhood anemia reduced by 30% over next 10 years would gain yen 348 billion.</p><p><b>CONCLUSION</b>These interventions have huge economic payoff. That is likely to exceed their costs many times over.</p>

Transdermal delivery of diclofenac sodium gel after iontophoresis / 浙江大学学报·医学版

OBJECTIVE: To observe the in vivo effect of combined iontophoresis and laurocapram pretreatment on transdermal delivery of diclofenac sodium gel. METHODS: Diclofenac sodium gel was prepared using polyvinyl alcohol, carboxymethylcellulose sodium and hydroxypropylmethyl cellulose. The diclofenac blood level in rabbits was measured in four groups: passive diffusion, laurocapram pretreatment, iontophoresis (current density controlled at 0.3 mA/cm(2)) and combined laurocapram pretreatment and iontophoresis. Rabbit stratum corneum of each of the four groups was examined using a scanning electron microscope. RESULTS: Diclofenac blood concentration in the passive diffusion group was undetectable. The diclofenac blood concentration area under the curve compared with time was 8.4 &mgr;l ml(-1) h(-1) in the laurocapram pretreatment group, 2.7 &mgr;l ml(-1) h(-1) in the iontophoresis group and 15.4 &mgr;l ml(-1) h(-1) in the combination group. There was no detectable damage observed by scanning electron microscopyto the stratum corneum after iontophoresis or laurocapram pretreatment. CONCLUSION: The combination of iontophoresis and laurocapram pretreatment appears to enhance transdermal delivery of diclofenac sodium gel wi thout significant skin damage.