Data mining of medical rule in Lingnan TCM masters for treating Allergic rhinitis / 国际中医中药杂志

Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.

Hemolysin Sph2 from Leptospira interrogans amplified inflammatory response in murine macrophages J774A.1 through HMGB1 / 中华微生物学和免疫学杂志

Objective:To investigate the possible mechanism of high mobility group box-1 (HMGB1) in amplifing inflammatory responses in Leptospira interrogans hemolysin Sph2-treated J774A.1 macrophages. Methods:Recombinant Sph2 was incubated with J774A.1 macrophages. The damage of cell membrane was detected by lactate dehydrogenase(LDH) determination; the changes of cell structure were observed by cryo-electron microscope; ELISA was used to determine the expression of HMGB1. After the commercial recombinant HMGB1 was incubated with mouse J774A.1 macrophages, the phosphorylation of NF-κB, p38-MAPK and JNK signaling pathway wsa detected by Western blot, and the expression of IL-1β, IL-6, and KC (IL-8) was detected by ELISA.Results:Recombinant hemolysin rSph2 induced significant changes in the structures of J774A.1 cells, including nucleus disappearance, cell membrane structure damage, cell lysis and membrane swelling. The yields of LDH and HMGB1 also increased significantly. Phosphorylated-NF-κB, -p38-MAPK and -JNK were increased by HMGB1. The expression of IL-1β, IL-6 and KC in J774A.1 cells was up-regulated by HMGB1 and inhibited via inhibitors of NF-κB, p38-MAPK and JNK signal pathways.Conclusions:Hemolysin rSph2 damaged the membrane of J774A.1 cells, and induced the secretion of HMGB1. Secreted-HMGB1 might induce the expression of IL-1β, IL-6 and KC in J774A.1 cells via NF-κB, p38-MAPK and JNK signal pathways, thus amplifying the inflammatory responses caused by Sph2.

Construction and verification of a new nomogram for predicting stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy at high altitude / 临床肝胆病杂志

ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio ［OR］= 3.245, 95% confidence interval ［CI］: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

Identification of a novel CHS1/LYST variant in a Chinese pedigree affected with Chediak-Higashi syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.@*METHODS@#Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.@*RESULTS@#The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.@*CONCLUSION@#Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.

Lead sulfide quantum dots for the near-infrared IIb window fluorescence imaging of colon cancer / 药学学报

The near-infrared-IIb (NIR-IIb, 1 500-1 700 nm) window fluorescence with long emission wavelength has reduced light scattering and tissue auto-fluorescent background, achieving deep tissue imaging with high spatial resolution. Herein, we prepared an NIR-IIb fluorescent quantum dots (QDs) composed of lead sulfide (PbS). The fluorescence spectrum of PbS QDs were adjusted by controlling the size of the PbS core. Cadmium sulfide (CdS) shell was synthesized by the cation exchange method to form the core/shelled lead sulfide/cadmium sulfide quantum dots (CSQDs). The surface of CSQDs was modified with polyethylene glycol (PEG) to increase their stability in aqueous solution. The resulting PEG-modified CSQDs (PEG-CSQDs) had the emission peak at ~1 550 nm with quantum yield of 7.2%. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. At 2 h postinjection, PEG-CSQDs clearly delineated the tumor region of mice bearing orthotopic CT26-Luc colon cancer model in the NIR-IIb fluorescence imaging. The fluorescent intensity ratio of primary tumor and adjacent normal tissue was 42.3, and that of metastatic tumor and adjacent normal tissue was 22.3, which allowed to detect the primary tumor of 3.4 mm×2.5 mm in dimension and the metastatic tumor of 1.2 mm×0.9 mm in dimension, and accurately guided the excision of tumors. The PEG-CSQDs prepared in this study provided a new approach for the early diagnosis and guidance of surgical resection of colon cancer.

Identification of Sigma N signaling system target genes in Leptospira interrogans / 中华微生物学和免疫学杂志

Objective:To confirm the Sigma N transcription factor activity of a gene product encoded by LA2404 gene of Leptospira interrogans ( L. interrogans) and to identify the target genes of Sigma N signaling system. Methods:L. interrogans LA2404 gene and its regulated target genes were predicted using bioinformatic analysis according to the promoter sequence signature in Sigma N-regulated genes. A LA2404 gene-knockout (ΔLA2404) strain of L. interrogans was constructed based on homologous sequence recombinant of suicide plasmid. Real-time fluorescent quantitative RT-PCR (qRT-PCR) was used to detect the changes in the expression of target genes at mRNA level in the ΔLA2404 mutant. A prokaryotic expression system for LA2404 gene was established and the target recombinant protein rSigma N was extracted by Ni-NTA affinity chromatography. Gel electrophoresis mobility shift assay (EMSA) was used to screen out the target genes regulated by rSigma N. Results:Pathogenic L. interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai carried one Sigma N gene and 22 Sigma N promoter sequence-containing target genes. Qualitative examination of the ΔLA2404 mutant by microscopy revealed no defect in motility and appearance. Expression of LA1188, LA2306, LA3426, LA1968, LA1313, LA3806 and LA0773 genes at mRNA level in the ΔLA2404 mutant was significantly down-regulated ( P<0.05), but no significant changes in the expression of other target genes at mRNA level were detected. EMSA results confirmed that rSigma N could bind to the promotor sequences of the target genes mentioned above. Conclusions:Sigma N transcription factor was encoded by LA2404 gene. LA1188, LA2306, LA3426, LA1968, LA1313, LA3806 and LA0773 genes contained Sigma N promoter sequence and the expression of them was regulated by Sigma N signaling system.

Comparisons of the resting-state fMRI functional connectivity of the habenula in the first-episode current depression and remitted depression / 中华行为医学与脑科学杂志

Objective:To investigate the difference of functional connectivity(FC) between the habenula and other brain regions in the patients with first-episode current depression (fMDD) and remitted depression (rMDD).Methods:Thirty-five patients with first-episode current depression (fMDD), 35 patients with remitted depression (rMDD) and 30 healthy controls (HC) matched with gender, age and education years were scanned by resting-state fMRI. Hamilton Depression Scale (HAMD 17) was used to assess the severity of the patients. After preprocessing, seed-based FC analysis was performed on the habenula. Pearson correlation analysis was performed between the FC values and HAMD 17 and duration of disease. Results:(1) Compared with the HC group, FC decreased between the habenula and left middle occipital gyrus(l-MOG) in fMDD group (x, y, z=-48, -84, 3, t=-4.335, P<0.05), while FC increased between the habenula and left supramarginal gyrus (x, y, z=-66, -30, 36, t=4.876, P<0.05), left superior frontal gyrus(l-SFG) (x, y, z=-6, -33, 51, t=4.402, P<0.05), left inferior parietal lobe(l-IPL)( t=3.300, P<0.05) and right inferior parietal lobe(r-IPL) ( t=3.557, P<0.05) in fMDD group. Compared with the HC, FC decreased between the habenula and l-MOG (x, y, z=-48, -84, 3, t=-4.321, P<0.05) and left thalamus (x, y, z=-9, 3, 3, t=-3.971, P<0.05) in rMDD group, while FC increased between the habenula and left middle temporal gyrus(l-MTG)( x, y, z=-48, -39, 9, t=4.062, P<0.05), left supramarginal gyrus (x, y, z=-51, -15, 45, t=2.906, P<0.05), l-SFG (x, y, z=-24, -21, 39, t=3.044, P<0.05), l-IPL ( t=2.880, P<0.05) and r-IPL ( t=3.512, P<0.05) in rMDD group. (2) FC decreased in fMDD group between the habenula and right orbitofrontal cortex(r-OFC) ( t=-3.899, P<0.05) and l-MTG ( t=-4.023, P<0.05) than rMDD group, while FC increased between the habenula and left supramarginal gyrus ( t=4.157, P<0.05), l-SFG( t=3.327, P<0.05), left thalamus ( t=3.316, P<0.05) and l-IPL ( t=3.909, P<0.05) than rMDD group. (3)There was no significantly correlation between the HAMD 17 and the FC value changes among the different regions, and was marginal significantly correlation between duration of disease and the FC values from the habenula and l-MOG( r=0.328, P=0.063). Conclusion:Both fMDD and rMDD show abnormal FC between the habenula and default mode network, visual network and reward network, which may be related to the pathogenesis of depression. The FC of the habenula in rMDD still had not recovered to normal.

Characterization of myelin oligodendrocyte glycoprotein (MOG)35-55-specific CD8+ T cells in experimental autoimmune encephalomyelitis / 中华医学杂志(英文版)

BACKGROUND@#The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.@*METHODS@#Female C57BL/6 mice (n = 20) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4 and CD8 T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 and CD8 T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55-specific CD8 or CD4 T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.@*RESULTS@#CD8CD3 and CD4CD3 cells were 86% and 94% pure of total CD3 cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. Although the CD8 T cells had a generally lower response to MOG35-55 than CD4 T cells, the response of CD8 T cells was not always dependent on CD4. CD8 T cell secreted less IFN-γ and IL-4 compared with CD4 T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG35-55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 T cells from immunized B6 mice compared with transfer of CD4 T cells.@*CONCLUSION@#Our data suggest that CD8 autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4 counterparts.

Methylation of forkhead box protein 3 gene promoter in CD4+ T cells in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

Objective@#To investigate the methylation status and expression of FOXP3 in CD4+ T cells of patients with chronic hepatitis B (CHB).@*Methods@#Peripheral blood mononuclear cells (PBMCs) from 59 CHB patients and 22 healthy controls (HC) were collected. The percentage of CD4+ CD25+ Foxp3+ Tregs in CD4+ T cells was estimated by flow cytometry. FOXP3 expression was measured by quantitative real time-polymerase chain reaction (RT-qPCR) and Western blotting. The methylation status of FOXP3 was determined by methylation-specific polymerase chain reaction.@*Results@#The percentage of CD4+ CD25+ pFoxp3+ Tregs in CD4+ T cells, FOXP3 mRNA and protein expression levels were significantly higher in patients with CHB than HCs (P<0.05). Meanwhile, the methylation frequency of FOXP3 was significantly lower in CHB patients than HCs (P<0.05). FOXP3 mRNA levels and the percentage of CD4+ CD25+ Foxp3+ Tregs were significantly lower (P<0.05) in patients with gene methylation than those without.@*Conclusions@#Aberrant demethylation of FOXP3 gene existed in CD4+ T cells of CHB, which contributed to an elevation in FOXP3 expression and percentage of CD4+ CD25+ Foxp3+ Tregs. It might provide a new target for prevention and treatment of CHB.

Quantitative evaluation of blood-brain barrier permeability in patients with ischemic white matter lesions with dynamic contrast-enhanced MRI / 中国医学影像技术

Objective To investigate the changes of blood-brain barrier (BBB) permeability and the correlation with cognitive function in patients with ischemic white matter disease with dynamic contrast-enhanced MRI (DCE-MRI).Methods Totally 71 subjects underwent routine MRI,DCE-MRI,mini-mental state examination (MMSE) and Fazekas scoring,and then were divided into patient group and control group according to the Fazekas scores.The leakage rate (K),area under the leakage curve (AUC) and fractional blood plasma volume (Vp) in cerebral white matter hyperintensities area and normal appearing white matter area were measured and compared between the two groups.The correlation between these parameters and MMSE scores were analyzed.Results K and AUC value of white matter hyperintensities area and normal appearing white matter area in patient group were significantly higher than those in control group (all P＜0.001).Vp value of normal appearing white matter area in patient group was lower than that in control group (P=0.015).K and AUC value of white matter hyperintensities area in patient group had significant negative correlation with MMSE scores (r=-0.440,--0.540,both P＜0.001).Conclusion BBB permeability increased in cerebral white matter hyperintensities and normal appearing white matter area in patients with ischemic white matter lesions,which correlated with cognitive function.

Three-dimensional Speckle Tracking Imaging for the Assessment of Left Ventricular Systolic Function of Mild Systemic Lupus Erythematosus / 中国医学影像学杂志

Purpose Heart damage occurs frequently in patients with systemic lupus erythematosus(SLE), and most of the patients have no obvious symptoms. In this study, three-dimensional speckle tracking imaging (3D-STI) was used to assess the systolic function of left ventricle, for early diagnosis of cardiac function changes in patients with mild SLE. Materials and Methods Thirty-six patients with clinical diagnosed mild SLE were enrolled and 40 healthy volunteers were selected as control group. All the participants underwent both conventional echocardiographic and 3D-STI examinations, left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), interventricular septal depth (IVSd), left ventricular posterior wall depth (LVPWd), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (GLS), left ventricular global circumferential strain (GCS), left ventricular global radial strain (GRS) and left ventricular global area strain (GAS) were compared between the two groups. Results The GLS, GCS, GRS and GAS of the study group were all lower than the control group, and the difference was statistically significant (P0.05). Conclusion 3D-STI is able to make an objective evaluation of the left ventricular systolic function for patients with mild SLE, and provide help for clinical cardiac function monitoring.

Flocculation and purification of the total saponins of Lysimachia capillipes Hemsl. with chitosan / 中国药学杂志

CONCLUSION: Compared with traditional tannin removing process, chitosan flocculation purification process can effectively retain the active ingredients in the solution and has good process stability, which is suitable for industrial production.

The influences upon the passive tensile of the masticatory muscles and ligaments by twin-block appliance under various bite reconstruction / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the regularity of the passive tensile of the masticatory muscles and ligaments by Twin-Block appliance under various bite reconstruction, and to provide some biomechanical references for the clinical use and improvement of Twin-Block appliance.</p><p><b>METHODS</b>"Temporomandibular joint, mandible and Twin-Block appliance" model was set up by the three dimensional finite element method, and the related masticatory muscles and ligaments were added on it. Seven experimental groups were designed according to the clinical and research, the occlusal inclined plate's angles of Twin-Block appliance were 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees and 70 degrees. The passive tensile in the masticatory muscles and ligaments were analyzed by the computer.</p><p><b>RESULTS</b>Under various experimental groups, the passive tensile in the anterior deep masseter (AM), the posterior deep masseter (PM), the anterior temporalis (AT), the posterior temporalis (PT), the stylomandibular ligament and sphenomandibular ligament improved with the increased slant angles of occlusal guide. The maximum value of the passive tensile was 82.57 N, the minimum value was 0.07 N.</p><p><b>CONCLUSION</b>1) In various experimental groups, AT, AM, PM, PT, stylomandibular ligament and sphenomandibular ligament are subject to passive tension force in the process of Twin-Block appliance guiding the mandibular forward and play the important role on the remodeling of the mandible. 2)All groups of occlusal inclined plate's angle are in physiologically tolerable range and can be used in clinic.</p>