Effect of Xiaoyaosan on JNK Pathway in LPS-induced Depressive-like Behavior in Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Xiaoyaosan in alleviating lipopolysaccharide （LPS）-induced depressive-like behavior in mice based on the c-Jun N-terminal kinase （JNK） pathway. MethodAfter adaptive feeding， C57BL/6J mice were randomly divided into normal group， model group， minocycline group （intrabitoneal injection， 50 mg·kg-1）， fluoxetine group （intragastric administration， 2.6 mg·kg-1）， and low-， medium-， and high-dose Xiaoyaosan groups （intragastric administration，6.012 5， 12.025， and 24.050 g·kg-1）. After 14 days of administration， the model group and each administration group were intraperitoneally injected with 2 mg·kg-1 LPS， and the normal group was intraperitoneally injected with equal volume of normal saline. Depressive-like behavior in mice was assessed using the open field test and the elevated zero maze test. High-performance liquid chromatography （HPLC） was used to measure the levels of norepinephrine （NE） and epinephrine （E） in the mouse hippocampus. Enzyme-linked immunosorbent assay （ELISA） was performed to determine serum interleukin-1β （IL-1β） levels. Immunohistochemistry was used to measure the protein expression levels of ionized calcium-binding adapter molecule-1 （Iba-1）， c-Fos， and c-Jun. Real-time polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of IL-1β， c-Jun， c-Fos， and JNK3 in the mouse hippocampus. Protein expression levels of JNK and phosphorylated （p）-JNK in the mouse hippocampus were measured using capillary protein automated protein expression analysis system （Western）. ResultCompared with the normal group， the model group exhibited significantly reduced central area residence time， crossing times， and travel distance in the open field （P<0.01）， significantly increased serum IL-1β levels （P<0.01）， significantly decreased NE and E levels （P<0.05）， upregulated mRNA expression of IL-1β， JNK3， and c-Fos， and increased protein expression of Iba-1， c-Fos， and c-Jun （P<0.05， P<0.01）. Compared with the model group， the Xiaoyaosan groups showed increased central area residence time and open arm residence time （P<0.05）， increased NE and E levels （P<0.01）， decreased mRNA expression of IL-1β， JNK3， c-Jun， and c-Fos， and decreased protein expression of Iba-1， c-Fos， JNK， and p-JNK （P<0.05， P<0.01）. The minocycline group and the fluoxetine group showed decreased mRNA expression of JNK3， c-Jun， and c-Fos （P<0.05， P<0.01）. The minocycline group showed decreased serum IL-1β and p-JNK protein expression （P<0.01）. The fluoxetine group exhibited increased NE and E levels and decreased c-Fos protein expression （P<0.01）. ConclusionXiaoyaosan can improve depressive-like behavior induced by LPS in mice， and its mechanism may be related to the inhibition of neuroinflammatory responses and the JNK pathway.

Feasibility of Erxian Decoction and Wenshen Prescription in Treatment of Depression Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the molecular mechanism of Erxian decoction and Wenshen prescription （modified Erxian decoction） in the treatment of depression based on network pharmacology and explore the feasibility of Wenshen prescription in the treatment of depression by comparing the efficacy and mechanism of the two decoctions based on a depression model induced by maternal separation combined with chronic restraint stress. MethodActive components and targets of Erxian decoction and Wenshen prescription were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Targets related to depression were screened out from databases such as GeneCards， Online Mendelian Inheritance in Man database （OMIM）， and DrugBank. Common targets of drugs and disease were obtained and imported to Cytoscape 3.8.2 to plot the drug-active component-target-disease network. STRING platform was used to construct a protein-protein interaction （PPI） network and core targets and related core components were screened out. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analysis were performed on common targets through Metascape platform. The depression model was induced in mice by maternal separation combined with chronic restraint stress. From the 21st day of maternal separation （PD21） to the 111th day of restraint stress completion （PD111）， mice were fed with the diet mixed with Erxian decoction or Wenshen prescription for intervention. The depressive state of mice was evaluated according to the sucrose preference test， tail suspension test， open field test， and elevated O-maze test. The expression of ionized calcium-binding adapter molecule 1 （Iba1） in the microglia was observed by immunohistochemistry （IHC）. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of protein kinase B1（Akt1）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin （Syn）. ResultA total of 126 and 118 targets of Erxian decoction and Wenshen prescription in the treatment of depression were screened out， with only eight more targets of Erxian decoction than Wenshen prescription. The two decoctions shared the same core targets， mainly including Akt1， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）. KEGG pathway enrichment analysis predicted that Erxian decoction and Wenshen prescription mainly treated depression through the phosphatidylinositol-3 kinase （PI3K）/Akt signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and neuroactive ligand-receptor interaction pathway. Animal experiments showed that compared with the results in the model group， Erxian decoction and Wenshen prescription could up-regulate the sucrose preference index， prolong the time spent in the central zone， increase the number of crossings， prolong the time spent in opened arm， increase the number of crossings in the opened arm， elevate the expression levels of p-Akt1， BDNF， PSD95， and Syn （P<0.05， P<0.01）， shorten the immobility time of tail suspension， and reduce the expression level of Iba-1 in the hippocampal microglia （P<0.05， P<0.01）. No significant difference between the two decoctions was found. ConclusionUnder the pathogenesis and syndrome law of depression dominated by kidney yang deficiency， Wenshen prescription modified from Erxian decoction is feasible in the treatment of depression. The mechanism may be attributed to the fact that both decoctions can improve neuroinflammation and synaptic plasticity in the hippocampus by affecting Akt1， IL-1β， IL-6， TNF-α， and other core targets and regulating the PI3K/Akt， MAPK， and neuroactive ligand-receptor interaction signaling pathways.

Molecular Mechanism of Erxian Decoction in Treatment of Anxiety Disorder Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology， and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards， therapeutic target database （TTD）， online mendelian inheritance in man database （OMIM）， and DrugBank， and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction （PPI） network was constructed by the STRING database， and the core targets were screened out based on topological parameter analysis. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day （PD21） to the completion of restraint stress on the 97th postnatal day （PD97）， the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone （CORT） in mice was detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of protein kinase B （Akt1）， mammalian target of rapamycin （mTOR）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder， with 161 drug-disease intersection targets. Among these intersection targets， core targets such as Akt1， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase （PI3K）/Akt， mitogen-activated protein kinase （MAPK）， and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group， the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times， with significantly increased expression levels of p-Akt1， p-mTOR， BDNF， PSD95， and synaptophysin （Syp）. ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder， and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1， IL-1β， IL-6， TNF， mTOR， and other core targets and modulating PI3K/Akt， MAPK， as well as neuroactive ligand-receptor interaction signal pathways.

Molecular Mechanism of Erxian Decoction in Treatment of Anxiety Disorder Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology， and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards， therapeutic target database （TTD）， online mendelian inheritance in man database （OMIM）， and DrugBank， and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction （PPI） network was constructed by the STRING database， and the core targets were screened out based on topological parameter analysis. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day （PD21） to the completion of restraint stress on the 97th postnatal day （PD97）， the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone （CORT） in mice was detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of protein kinase B （Akt1）， mammalian target of rapamycin （mTOR）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder， with 161 drug-disease intersection targets. Among these intersection targets， core targets such as Akt1， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase （PI3K）/Akt， mitogen-activated protein kinase （MAPK）， and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group， the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times， with significantly increased expression levels of p-Akt1， p-mTOR， BDNF， PSD95， and synaptophysin （Syp）. ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder， and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1， IL-1β， IL-6， TNF， mTOR， and other core targets and modulating PI3K/Akt， MAPK， as well as neuroactive ligand-receptor interaction signal pathways.

Regulation and mechanism of mannose-binding lectin on autophagy during the differentiation of 3T3-L1 adipocytes / 中华微生物学和免疫学杂志

Objective:To investigate the regulatory effects and mechanism of mannose-binding lectin(MBL) on autophagy during the differentiation of 3T3-L1 adipocytes, and provide the feasibility for targeting autophagy to prevent obesity and related pathological conditions in natural immunity.Methods:3T3-L1 preadipocytes were cultured in vitro and induced to differentiation. Cell differentiation and lipid accumulation were analyzed by oil red O staining and CCK-8 was used to detect the effect of different concentrations of MBL (0, 1, 5, 10 μg/ml) on cell proliferation ability at different differentiation stages. Western blot was used to analyze the expression of MBL(10 μg/ml) on the key autophagy factors LC3B, Beclin1 and p62 protein at different stages of differentiation, and the changes of lipid droplet accumulation under the intervention of MBL were observed by oil red O staining. The protein and mRNA expression of autophagy key factors under the intervention of different concentrations of MBL were detected by Western blot and qRT-PCR. And autophagy flow analysis based on autophagic degradation was used to further illustrate the autophagic activity. The expression and phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling molecules were analyzed by Western blot. Results:The results of oil red O staining showed that 3T3-L1 preadipocytes could achieve complete differentiation after 10 days of induction. CCK-8 showed that the concentration of MBL (1-10 μg/ml) in the experimental group had no effect on cell proliferation at different differentiation stages. During the differentiation of 3T3-L1 preadipocytes, Western blot and qRT-PCR showed that the expression of autophagy-related proteins and mRNA levels was enhanced in the MBL treated group, and presented a concentration-dependent relationship. Oil red O staining showed that the lipid droplets in adipocytes at different stages of differentiation are reduced to varying degrees under the intervention of MBL. Fluorescence microscopy results further confirmed that MBL enhanced the autophagy activity of adipocytes by increasing the synthesis of autophagosomes. Moreover, under the intervention of MBL, the phosphorylation level of AMPK was significantly up-regulated, while the phosphorylation level of mTOR was significantly down-regulated, also showing a concentration-dependent relationship.Conclusions:MBL accelerates the autophagy process during the differentiation of 3T3-L1 adipocytes through AMPK/mTOR signaling pathway, reduces lipid accumulation, providing a possible functional pathway for the treatment of obesity and related metabolic diseases.

Effect of Infection on Autonomic Nervous Function and Calcitonin Gene-related Peptide in Patients with Functional Dyspepsia / 中国医学科学院学报

To investigate the effects of ()infection on autonomic nervous function and calcitonin gene-related peptide in patients with functional dyspepsia(FD). Thirty-one patients with FD matching Rome Ⅳ criteria were included and divided into -positive group and -negative group.All patients were evaluated by Symptom Index of Dyspepsia(SID),Nepean Dyspepsia Index(NDI),and Hospital Anxiety and Depression Scale(HADS).Their heart rate variability(HRV)and calcitonin gene-related peptide(CGRP)level were also measured. There were no significant differences in SID(=-0.858, =0.858),NDI(=-1.464, =0.143),and Hospital Depression Scale score(=0.699, =0.485).However,the Hospital Anxiety Scale score was significantly higher in -positive group than the -negative group(=-2.470, =0.014).The level of CGRP in -positive group[(0.999±0.274)ng/ml]was significantly higher than that in the -negative group[(0.812±0.172)ng/ml;=2.238, =0.033].HRV data showed no significant difference between these two groups at very low frequency(=-1.210, =0.236),low frequency(LF)(=0.419, =0.678),high frequency(HF)(=0.612, =0.546),LF/HF(=-0.882, =0.399),and total power(=-0.963, =0.344). In FD patients,patients with -positive FD patients have higher depression and CGRP levels than those without infection,although their dyspepsia symptoms and HRV show no notable changes.

Regulation and mechanism of mannan-binding lectin (MBL) on adipogenic differentiation of 3T3-L1 preadipocytes / 中华微生物学和免疫学杂志

Objective:To investigate the regulatory effects and mechanism of mannan-binding lectin (MBL) on adipogenic differentiation of 3T3-L1 preadipocytes.Methods:3T3-L1 preadipocytes were induced to differentiate into adipocytes in vitro, and stimulated with different concentrations of MBL (0, 1, 10, 20 μg/ml). Firstly, changes in cell proliferation ability were detected by CCK-8. Then lipid accumulation was analyzed by Oil red O staining and intracellular triglyceride content determination. Further, the expression of adipogenic differentiation-related factors PPARγ and C/EBPα at protein and mRNA levels were detected by Western blot and qRT-PCR, respectively. Finally, Western blot was used to analyze the expression and phosphorylation of Akt, a signal molecule related to adipogenic differentiation. Results:MBL at the concentrations of 0, 1, 10 and 20 μg/ml had no effect on the proliferation of 3T3-L1 preadipocytes. The level of triglyceride in MBL treatment groups decreased in a dose-dependent manner on 3 d after 3T3-L1 preadipocyte differentiation. Results of Oil red O staining showed that the number of lipid droplets in MBL treatment groups reduced significantly, and the absorbance values also decreased significantly in a concentration-dependent manner. Western blot and qRT-PCR results showed that the expression of PPARγ and C/EBPα at both protein and mRNA levels in MBL treatment groups decreased significantly in a dose-dependent manner, and the phosphorylation level of Akt was significantly down-regulated as well.Conclusions:MBL regulates the adipogenic differentiation of 3T3-L1 preadipocytes via Akt signaling pathway.

Application of ATR-FTIR spectroscopy in analysis of stratum corneum components in sensitive facial skin / 中华皮肤科杂志

Objective:To investigate differences in stratum corneum components between sensitive skin and normal skin by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and to evaluate the value of ATR-FTIR spectroscopy in the study of pathogenesis of sensitive skin.Methods:From December 2018 to February 2019, 148 volunteers were recruited, who had lived in Shanghai for ≥ 6 years. Through questionnaire survey, lactic acid sting test and capsaicin test, the subjects were divided into normal skin group and sensitive skin group; meanwhile, total sting score and total burning score of the subjects were recorded in the lactic acid sting test and capsaicin test respectively. ATR-FTIR spectroscopy was performed to detect stratum corneum components, including natural moisturizing factor (NMF), stratum corneum lipids, free fatty acids (FFA) and β-sheet/α-helix (β/α) ratio; moreover, other non-invasive techniques were used to measure skin physiological parameters, including transepidermal water loss (TEWL), stratum corneum hydration (SCH) levels, stratum corneum lipids, skin pH, current perception thresholds of 3 peripheral sensory nerve fibers, and superficial skin blood flow perfusion. Spearman correlation coefficients between stratum corneum components and the total sting score as well as total burning pain score were analyzed, so were Pearson correlation coefficients between the stratum corneum components and skin physiological parameters.Results:A total of 73 volunteers completed all tests, including 15 males and 19 females aged 41.8 ± 8.9 years in the sensitive skin group, and 19 males and 20 females aged 42.8 ± 9.4 years in the normal skin group. Compared with the normal skin group, the sensitive skin group showed significantly decreased levels of stratum corneum NMF (30.90 ± 7.38 vs. 37.01 ± 8.77, t = 3.193, P < 0.01) and FFA (14.90 ± 6.75 vs. 20.45 ± 11.76, t = 2.422, P < 0.05), but significantly increased β/α ratio (3.17 ± 1.03 vs. 2.67 ± 0.56, t = -2.595, P < 0.05) ; there was no significant difference in stratum corneum lipid content between the two groups ( t = 1.458, P > 0.05). As far as the skin physiological parameters were concerned, the sensitive skin group showed significantly increased TEWL ( t = -3.496, P < 0.001), but significantly decreased current perception thresholds at a frequency of 5 Hz and epidermal density (both P < 0.05) compared with the normal skin group; no significant difference in stratum corneum lipid content was observed between the two groups ( P > 0.05). Correlation analysis revealed that NMF, FFA and β/α ratio were significantly correlated with TEWL ( r = -0.405, -0.562, 0.503, respectively, all P < 0.01) and total sting score ( rs = -0.401, -0.285, 0.316, respectively, P < 0.01 or 0.05) ; meanwhile, epidermal density was also significantly correlated with NMF ( r = 0.402, P < 0.01) and β/α ratio ( r = -0.369, P < 0.05). However, none of NMF, FFA and β/α ratio was correlated with stratum corneum lipid content, current perception thresholds of the 3 sensory nerve fibers, superficial skin blood flow perfusion or epidermal thickness (all P > 0.05) . Conclusions:NMF, FFA and β/α ratio in the stratum corneum significantly differed between the sensitive skin and normal skin, and were significantly correlated with some physiological parameters related to stratum corneum barrier function. ATR-FTIR spectroscopy is an effective method for evaluating barrier function of sensitive skin.

Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy / 医学前沿

Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.

Mannan-binding lectin regulates Treg/Th17 cell balance in mice with Candida albicans infection / 中华微生物学和免疫学杂志

Objective To investigate the regulation of Treg/Th17 axis by mannan-binding lectin (MBL) in mice with Candida albicans ( C. albicans ) infection. -ethods MBL gene-knockdown (MBL-/-) C57BL/6 mice and wild-type (WT) C57BL/6 mice were divided into four groups. C. albicans strains (2×107 CFU) were injected intraperitoneally into the mice of infection groups. Paraffin sections of mouse liver and kidney tissues were prepared on 3 d. Histopathological changes were observed with hematox-ylin and eosin ( HE) and Periodic acid-Schiff ( PAS) staining. Flow cytometry was performed to analyze Th17 and Treg cells in mice on 7 d. The levels of IL-10 and IL-17A were measured by ELISA. CD4+T cells were obtained from spleen cells by magnetic sorting. Expression of Foxp3 and RORγt at mRNA and protein levels were detected by qRT-PCR and Western blot, respectively. Results The mouse model of C. albicans infection was established successfully. After infection, the MBL-/- mice had higher percentages of Th17 cells, but lower percentages of Treg cells than the WT mice. ELISA results showed that compared with the WT mice with C. albicans infection, the MBL-/- mice had significantly increased IL-17A and decreased IL-10 after infection. Moreover, the expression of RORγt at both mRNA and protein levels was up-regula-ted, while that of Foxp3 was down-regulated in the MBL-/- mice than in the WT mice following infection. Conclusions MBL regulates the immune balance of Treg/Th17 cells in mice infected with C. albicans through promoting the differentiation of CD4+ T cells into Treg cell subsets and inhibiting the differentiation into Th17 cell subsets.

Increased Expression of MIF in Peripheral Blood Mononuclear Cells from Patients with Crytococcal Meningitis and Its Clinical Significance / 现代检验医学杂志

Objective To test the expression of MIF in peripheral blood mononuclear cells (PBMCs)from patients with Cry-tococcal Meningitis and further discuss its clinical significance.Methods Peripheral blood from 42 patients with Crytococcal Meningitis diagnosed in Changhai Hospital,Shanghai and 42 healthy individuals examined at the same time was collected from August,2012 to November,2015.PBMCs were separated by density gradient centrifugation method,mRNA relative expression of MIF in PBMCs was measured by PCR,the level of MIF,IL-17,IL-1β,TNF-α,IFN-γand IL-4 in plasma was tested by Enzyme-linked immunosorbent assay (ELISA).The comparison for expression level of cytokines between the two groups was by two-independent samples t test.Pearson correlation coefficient was used to measure the relation between MIF and other cytokines.Results The protein levels of MIF in experimental and controlled groups were 34.17±7.88 ng/ml vs 10.89±2.76 ng/ml(t=18.07,P<0.0001),while relative expression of RNA was 2.87±0.94 vs 1.95±0.89(t=4.606,P<0.0001),and there was statistical significance (P<0.005).Pearson correlation analysis showed that MIF was positively related with IL-1β,IL-17 (r=0.467,0.401,P<0.01),with statisticaldifference.Conclusion MIF may involve in the im-mune regulation for Crytococcal Meningitis by affecting the secretion and function of cytokines as IL-1β,IL-17,and it was potential target and monitored biomarker for this disease.

Safty research of intraoperative intraperitoneal chemotherapy with raltitrexed for advanced colorectal cancer / 国际肿瘤学杂志

Objective To investigate the intraoperative intraperitoneal chemotherapy security with raltitrexed in advanced colorectal cancer surgical operation.Methods Sixty patients with colorectal cancer undergone surgery were randomly divided into trial group (n =30) and control group (n =30) according to the random number table method.The trial group was given surgical operation plus with intraperitoneal chemotherapy with raltitrexed.The control group was given surgical operation plus with intraperitoneal saline perfusion.Theroutine blood test,liver and kidney functions,toxic side effects and complications in two groups before and after surgery were investigated.Results The white blood cells in trial group before and after surgery was (6.36 ± 2.63) × 109/L vs.(8.20 ± 2.08) × 109/L,with statistically significant difference (t =3.06,P ＜0.05).The ratio of absolute neutrophil count in trial group before and after surgery was 65.17％ ± 10.36％ vs.72.21％ ± 10.53％ (t =3.22,P ＜ 0.05).The platelets in trial group before and after surgery was (261.03 ±84.74) × 109/L vs.(228.47 ± 58.69) × 109/L (t =2.07,P ＜ 0.05).The white blood cells,the ratio of absolute neutrophil count and the platelets after surgery had no statistically significant differeuces between the two groups (P ＞0.05).The trial group had higher 1,2 level vomiting (60.00％ vs.23.33％;x2 =8.30,P ＜ 0.05),and nausea (30.00％ vs.6.67％;x2 =5.46,P ＜ 0.05) incidence rates,but there was no statistically significant difference in other toxic side effects (P ＞ 0.05).The major complications post operation included intestinal obstruction,incision infection,abdominal cavity bleeding,and anastomotic fistula.There were equivalent complications in two groups (6.67％ vs.3.33％,x2 =0.35,P ＞0.05;10.00％ vs.6.67％,x2 =0.22,P＞0.05;0 vs.0;3.33％ vs.0,P＞0.05).Conclusion For patients with advanced colorectal cancer,intraoperative intraperitoneal chemotherapy with raltitrexed is safe and feasible,and the adverse reactions can be tolerated without increasing postoperative complications.

Effects of Acupuncture on Hippocampal Synaptic Transmission Signal Molecules in Rats with Vascular Dementia / 中国中医药信息杂志

Objective To observe the effects of acupuncture on synaptic transmission signal molecules in rats with vascular dementia (VD), such as PKC, CaMKⅡ and NR2B, and discuss the molecular mechanism of acupuncture treatment for VD.Methods The multi-infarct dementia model was established by injection of emboli into the internal carotid artery. Experimental rats were randomly divided into normal group, model group, acupuncture group and non-acupoint group. For acupuncture group, acupuncture needles were penetrated into bilateral Zusanli. Non-acupoint group was given acupuncture treatment at the bilateral hypochondrium (10 mm above iliac crest). The rats in normal group and model group were performed to the same amount of capture stimulation as the acupuncture and non-acupoint groups. After treatment, the hippocampal PKC activity was detected by ELISA. Western blot was used to detect CaMKⅡ expression, and the protein expression of NR2B in CA1, CA3 and DG zones was assayed by immunohistochemical staining.Results Compared with normal group, PKC activity and NR2B expression in the hippocampus significantly decreased in the model group (P<0.01). After the acupuncture treatment, PKC activity increased significantly (P<0.05), and the protein expression of NR2B showed a trend to increase. There was no obvious difference in CaMKⅡ expression among all groups.Conclusion Acupuncture at Zusanli can enhance the activity of hippocampal PKC, a synaptic transmission signal molecule, which maybe one of the important molecular targets for the treatment of VD.

Establishing a finite element model of the mandible containing the temporomandibular joint after bilateral-sagitta-split-ramus-osteotomy with internal fixation / 中国组织工程研究

BACKGROUND:Bilateral-sagitta-split-ramus-osteotomy (BSSRO) has become a conventional method to correct facial deformities, and the finite element method is a significant way to study biomechanics of the mandible and temporomandibular joint (TMJ) after BSSRO. OBJECTIVE: To establish a precise and high simulation model of mandible containing TMJ after BSSRO with internal fixation, which is the base to study the biomechanics of the mandible and TMJ after BSSRO. METHODS: Spiral CT scan was used to get the data of DICOM that were input into MIMICS to establish the three-dimensional model of the mandible. The three-dimensional model was wrapped into a single closed shel for mesh generation and conversion in ANSYS. Then, the model was input into the ANSYS software for temporomandibular joint reconstruction and simulation of BSSRO and internal fixation. RESULTS AND CONCLUSION: The three-dimensional finite element model of mandible containing TMJ after BSSRO was established using MIMICS and ANSYS. This model had biological similarity and geometric similarity in comparison with the human tissues. The model could undergo various internal fixations through antedisplacement, retroposition and rotational movement of the distal end. Based on different experimental purposes, the established model can apply a load to al parts to study changes in stress and displacement of different tissues after BSSRO and internal fixation, and it also can be used to study the effect of different fixation materials on the rear stability after internal fixation.

The research of SurgiCase CMF software in surgical simulation and prediction for mandibular asymmetry / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate the predictive accuracy of the SurgiCase CMF software in surgical simulation and prediction for mandibular asymmetry with 3-dimensional simulation and measurement.</p><p><b>METHODS</b>CBCT data of 27 patients with mandibular asymmetry were observed in CMF, and postoperative soft tissue physiognomy were predicted by simulating sagittal ramus osteotomy with or without genioplasty. The measurement parameters representing the symmetry of soft tissue were selected and the horizontal, coronal and sagittal planes were established. The results were analyzed by SPSS 19. 0. The overlap compared color grading charts were observed.</p><p><b>RESULTS</b>Angles between cheilions and the horizonta plane (Ch-Ch-FH) in the simulation and postoperative soft tissues are (2. 35 ± 1. 81)° and (1. 44 ± 1. 13)°. The angles constructed among subnasale, upper lip and lower lip (Sn-UL-LL) are (4. 02 ± 3. 05)° and (2. 59 ± 1. 64)°, showing statistically different (P < 0. 01, P < 0. 05), which means that predictive accuracy of the lip canting and lip vertical deviation is relatively low. Distance between gonioi and sagittal plane (Go'-MS), distance between gonion and pogonion (Go'-Pog') and angle betweer subnasale to menton and the horizontal plane (Sn-Me'-MS) are not statistically different, which mean! high predictive accuracy of mandibular angle and chin. By observing the overlap compared color gradin-) charts, the predictive accuracy is not good in the cheek, especially in the deviate side.</p><p><b>CONCLUSIONS</b>The predictive accuracy of CMF system for patients with mandibular asymmetry is relatively high, but it is not good in the lip and cheek. The software improvement is still necessary.</p>

Hypnotic interaction between midazolam and emulsified isoflurane in rats / 中华麻醉学杂志

Objective To examine the effects of different doses of midazelam on ED50 of emulsified isoflurane and to determine the type of interaction between them for hypnosis by isobelographic analysis in rats. Methods One hundred and twenty-five adult male SD rats weighing 240-300 g were randomized into 5 groups (n=25 each): group Ⅰmidazolam (M); group Ⅱ emulsified isnflurane (Ⅰ); group Ⅲ ,Ⅳ ,Ⅴ, 1/4, 1/2 and 3/4 ED50 of midazelam for hypnosis + emulsified isoflurane (MI1 , MI2, MI3). Up-and-down sequential experiment was used to determine ED50of midazolam and emulsified isoflurane for loss of righting reflex in group Ⅰ -Ⅴ . The intial dose of midazolm was 17.3 mg/kg in group M. The initial doses of emulsified isoflurane (120 mg/ml) were 0.55 (in group Ⅰ, 0.22 (MI1), 0.19 (MI2) and 0.12 ml/kg (MI3) respectively. In group MI1-3 midazolam was injected over 15 seconds and after an interval of 2.5 min emulsified isoflurane was injected over 10 s. ED50 was calculated using Dixon-Mood method. Isebolographic and algebraic analyses were used to determine the type of interaction between midazolam and emulsified isoflurane. Results The five groups were comparable with respect to M/F sex ratio and body weight. The Edso of midazolam was 26.0 mg/kg in group M. Midazolam 6.5, 13.0 and 19.5 mg/kg were given in group MI1 , MI2 and MI3 respectively. The ED50 of emulsified isoflurane was 0.67 (ingroup Ⅰ), 0.30 (MI1), 0.22 (MI2) and 0.18 ml/kg (MI3) respectively. The isobolographic analysis indicated that with increasing doses of midazolam, the Edw of emulsified isoflurane decreased progressively in a non-linear fashion. The isobolographic and algebraic analyses demonstrated that the interaction between midazolam and emulsified isoflurane was synergistic for hypnosis. Conclusion The hypnosis is synergistic when midazolam 6.5,13 mg/kg are combined with emulsified isoflurane and additive when midazolam 19.5 mg/kg is combined with emulsified isoflurane.