Pharmacological mechanisms of Taohe Chengqi decoction in diabetic cardiovascular complications: A systematic review, network pharmacology and molecular docking.

Background: Diabetic cardiovascular complications are the leading cause of diabetes-related deaths. These complications place an enormous and growing burden on global health systems and economies. The objective of this study was to conduct a systematic review on the therapeutic mechanisms of Taohe Chengqi Decoction (THCQD) in the treatment of diabetic cardiovascular complications. To predict the potential mechanisms of action of THCQD on diabetic cardiovascular complications using network pharmacology, and to validate these predictions through molecular docking analysis. Methods: To collect relevant animal experiments, we searched a total of 6 databases. Eligibility for the study was determined based on inclusion and exclusion criteria. Data extraction was then performed on the literature. Methodological quality of animal studies was assessed using SYRCLE criteria. Based on network pharmacology, intersecting genes for THCQD and diabetic cardiovascular complications were obtained using Venny, PPI analysis and topology analysis of intersecting genes were performed; GO and KEGG were used for enrichment analysis and prediction of new targets of action. Molecular docking techniques were employed to model the interactions between drug components and target genes, thereby validating the results of network pharmacology predictions. Results: A total of 16 studies were finally identified that fit the direction of this review. Included 6 studies of the myocardium, 1 study of the aortic arch, 5 studies of the femoral artery, 4 studies of the thoracic aorta. THCQD exhibited anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects on cardiovascular complications in diabetic rats. Network pharmacology results showed that C0363 (Resveratrol), C0041 (Emodin), and C1114 (Baicalein) were the key components in the treatment of diabetic cardiovascular complications by THCQD. PPI results showed that INS, AKT1, TNF, ALB, IL6, IL1B as the genes that interact with the top 6. KEGG enrichment analysis identified the AGE-RAGE signaling pathway in diabetic complications as the most prominent pathway enriched by THCQD for diabetic cardiovascular complications genes. The results of molecular docking showed that the key active components demonstrated favorable interactions with their corresponding target genes. Conclusion: In conclusion, the results of both basic and web-based pharmacological studies support the beneficial effects of the natural herbal formulation THCQD on diabetic cardiovascular complications. This decoction has anti-inflammatory and antifibrotic properties and is effective in ameliorating diabetic cardiovascular disease. The network pharmacology results further support these ideas and identify the AGE-RAGE signaling pathway in diabetic complications as possibly the most relevant pathway for THCQD in the treatment of diabetic cardiovascular complications. The extent of the therapeutic potential of all-natural herbal components in the treatment of diabetic cardiovascular disease merits further investigation.

The expression of CD86 in CD3+CD56+ NKT cells is associated with the occurrence and prognosis of sepsis-associated encephalopathy in sepsis patients: a prospective observational cohort study.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.

Expression of MicroRNAs in Peripheral Blood of Patients with Primary Immune Thrombocytopenia and Its Correlation with the Imbalance of Th1/Th2 Cell / 中国实验血液学杂志

OBJECTIVE@#To investigate the expressions of microRNAs in peripheral blood of patients with primary immune thrombocytopenia(ITP) and its correlation with the imbalance of Th1/Th2 cells.@*METHODS@#Thirty patients with ITP (ITP group) and 15 healthy people (control group) were enrolled．Real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of six miRNAs (miR-107,miR-205-5p,miR-138-5p,miR-326,miR-1827,miR-185-5p) and Th1-specific transcription factor T-bet mRNA and Th2-specific transcription factor GATA-3 mRNA in the peripheral blood of the two groups. Th1 and Th2 cells were detected by flow cytometry. The expressions of Th1-cytokines TNF-α and IFN-γ and Th2-cytokines IL-4 and IL-10 were detected by AimPlex multiple immunoassays for Flow. The expression difference of miRNAs, mRNA, Th1, Th2 cells and cytokines of the two groups were compared, and the correlations of miRNAs to mRNA, Th1, Th2 cells and cytokines were analyzed in ITP group.@*RESULTS@#The expressions of miRNAs（miR-107, miR-205-5p, miR-138-5p, miR-326, miR-1827, miR-185-5p）and Th2-specific transcription factor GATA-3 mRNA of the patients in ITP group were significantly decreased (P<0.05) as compared with those in control, while the expressions of Th1 cells and Th1-specific transcription factor T-bet mRNA and Th1-cytokines TNF-α were significantly increased (P<0.05), also for the ratios of T-bet mRNA/GATA-3 mRNA and Th1/Th2 cells were significantly increased (P<0.05). The relative expressions of miR-107, miR-205-5p, miR-138-5p in ITP patients were negatively correlated with Th2 cells (r=-0.411, r=-0.593, r=-0.403,P<0.05) and the relative expression of miR-1827 was negatively correlated with TNF-α (r=-0.390).@*CONCLUSION@#The relative expressions of the six miRNAs in peripheral blood of patients with ITP are significantly decreased, which result in the increasing ratio of T-bet mRNA/GATA-3 mRNA, then lead to the imbalance of Th1/Th2.

Influence of ox-LDL on migration function of THP-1 macrophages and microRNA21 expression and MAPK pathway phosphorylation / 心血管康复医学杂志

Objective :To explore influence of oxidized low density lipoprotein (ox-LDL ) on migration function of THP-1 macrophages ,expression of microRNA 21 (miR-21) and mitogen-activated protein kinase (MAPK) path-way.Methods :Phorbol myristate acetate (PMA) of 160nmol/L was used to induce THP-1 cells to differentiate into macrophages.According to application of ox-LDL treatment and liposomes-mediated miR-21 inhibitor transfecting THP-1 macrophages (transfection for short) or not ,THP-1 macrophages were divided into blank control group (re-ceived neither ox-LDL treatment nor transfection ) ,ox-LDL group (received 50mg/L ox-LDL treatment without transfection) ,miR-21 inhibitor group (received 50mg/L ox-LDL treatment after transfection ) and miR-21 inhibitor negative-control group (received 50mg/L ox-LDL treatment after negative-control transfection ).THP-1 macro-phage migration number was measured by transwell method ,miR-21 expression was measured by real-time quantita-tive PCR ,and expression of dual specific phosphate 8 (DUSP-8) and phosphorylation level of MAPK pathway were measured by Western-blot method .Results :Compared with blank control group ,there were significant rise in mi-gration number of THP-1 macrophages [(74.10 ± 15.10) vs.(184.10 ± 26.28)] ,miR-21 expression [(1.00 ± 0.21) vs.(2.02 ± 0.27)] and phosphorylation levels of JNK and P38 protein ,and significant reduction in expression of DUSP-8 protein in ox-LDL group ,P＜0.01 all.Compared with ox-LDL group ,there were significant reductions in migration number of THP-1 macrophages [ (184.10 ± 26.28) vs.(58.50 ± 10.24)] ,miR-21 expression [ (2.02 ± 0.27) vs.(0.66 ± 0.16)] and phosphorylation levels of JNK and P38 protein ,and significant rise in expression of DUSP-8 protein in ox-LDL group , P＜0. 01 all .Conclusion : Ox-LDL enhances migration function of macrophages , which may be related to its effects of upregulating miR-21 expression ,enhancing phosphorylation of JNK and P38 protein of MAPK pathway and reducing DUSP-8 expression .

Combination of periodontal, orthodontic and endodontic therapy in upper anterior teeth with hopeless prognosis and long-time follow-up:a case report / 北京大学学报(医学版)

It is complicated to decide the treatment plan of hopeless anterior teeth in esthetic zone due to severe periodontitis, periodontal-endodontic combined lesion or teeth trauma.The optional treatment plan for this kind of teeth includes retention after periodontal treatment, extraction and implant treatment, extraction and prosthodontic treatment and so on.To make an appropriate treatment plan, patients'' periodontal conditions, periodontal biotype, local anatomy, esthetic demand, economic condition and social psychological status should be comprehensively considered.A combine of periodontal, endodontic and orthodontic therapy may achieve a good treatment effect in hopeless anterior teeth with severe periodontal destruction, tooth extrusion and occlusal trauma.In this case, a 20-year-old female who presented with symptoms of bleeding on brushing and upper incisors loosening for 1 month came to the Department of Periodontology, Peking University School and Hospital of Stomatology.The clinical examinations revealed that the patient''s right upper incisor had signs of mobility (Ⅲ°), intrusion of 1-2 mm, and probing depth (PD) of 9-10 mm.The periapical radiograph showed that the alveolar bone of right upper incisor absorbed horizontally to the apex.And the patients showed Angle Ⅱ° malocclusion with Ⅱ° overbite in anterior teeth and maxillary protrusion.A diagnosis of aggressive periodontitis and Angle Ⅱ° malocclusion was made.The treatment of this patient lasts for 5 years which include periodontal initial therapy, orthodontic therapy, guided tissue regeneration (GTR) of right upper incisor and supportive periodontal therapy and the clinical result is fine.A hopeless upper incisor was successfully retained and the longtime clinical condition was stable.The strategy of retention of hopeless upper anterior teeth, the relationship of periodontal treatment and orthodontic treatment, and the indications of periodontal and orthodontic combined therapy were also discussed on the basis of this case.Generally, the positive factors in retention of hopeless teeth includes young age, absence of systemic conditions, strong motivation for maintaining the tooth, single root anatomy, integrated dentition, good response to cause-related therapy, intrabony alveolar bone defect, thick periodontal biotype, and regular supportive periodontal therapy.And in the progress of orthodontic therapy, regular supportive periodontal therapy and good plaque control is extremely important.

Analysis of the plaster casts of Class II division 1 non-extraction patients treated with Alexander technique / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of arch width and arch length in Class II division 1 non-extraction patients treated with Alexander technique.</p><p><b>METHODS</b>Dental casts of 21 Class II division 1 non-extraction patients treated with Alexander appliance were taken before (T1) and after treatment (T2). All the casts were laser scanned. The arch width and arch length were digitally measured. The differences of arch width and arch length between T1 and T2 were recorded and analyzed.</p><p><b>RESULTS</b>The upper arch length decreased from (32.82 ± 2.51) mm to (31.97 ± 2.17) mm (P < 0.05). The lower arch length increased from (27.53 ± 2.61) mm to (28.80 ± 1.81) mm (P < 0.05). The intercanine width in the upper arch changed significantly from T1 to T2. The intermolar width in the upper and lower arches increased significantly from T1 to T2.</p><p><b>CONCLUSIONS</b>Class II division 1 non-extraction patients could be treated successfully by increasing the upper arch width.</p>

Evaluation of myelin basic protein levels with receiver operating characteristic curves for diagnosis of multiple sclerosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of cerebral spinal fluid (CSF) and serum myelin basic protein (MBP) levels in the diagnosis of multiple sclerosis (MS).</p><p><b>METHODS</b>Enzyme-linked immunosorbent assay was used to detect the CSF and serum levels of MBP in patients with MS (n=45), patients with Guillain-Barre syndrome (GBS) (n=36) and control subjects (control) (n=33). The sensitivity and specificity of MBP in CSF and serum in the diagnosis of MS were evaluated using the receiver-operating characteristic (ROC) curves.</p><p><b>RESULTS</b>The MBP levels in CSF and serum both increased significantly in MS group as compared with those in GBS (P<0.01) and control groups (P<0.01). The area under the curve (AUC) of the ROC curve of MBP in CSF was 0.853-/+0.037 for MS diagnosis, and with the optimal cut-off value of 0.87 pg/ml, CSF MBP showed a diagnostic sensitivity of 83.7% and specificity of 78.3%. The AUC of the ROC curve of serum MBP was 0.761-/+0.046, and the optimal cut-off value of 0.25 pg/ml resulted in a diagnostic sensitivity of 62.8% and specificity of 73.9%. No statistically significant difference was found between the two AUCs (P>0.05).</p><p><b>CONCLUSION</b>Evaluation of CSF and serum MBP levels allows accurate diagnosis of MS, and MBP level in the CSF has greater diagnostic sensitivity than serum MBP. The combination of both CSF and serum MBP levels may serve as a sensitive index for the diagnosis of MS.</p>

Influence of Hearing Disorder on Newborns with Hyperbilirubinemia / 实用儿科临床杂志

Objective To investigate the incidence of hearing disorder and analyse the high-risk factors with hearing injury in newborns with hyperbilirubinemia.Methods The newborns with hyperbilirubinemia who admitted to the department of neonate,were received the distortion product otoacoustic emission(DPOAE)test when they recovered from hyperbilirubinemia;those babies who didn′t pass the first test received screening again in 42 days after birth.Those babies who didn′t pass the second test received auditory brain stem response(ABR)test.Results Fifty-eight(33.2%)newborns didn′t pass the first DPOAE test among 235 newborns with hyperbilirubinemia;11(18.9%)infants didn′t pass the second DPOAE test among 58 infants;5 infants failed to pass the ABR test,the ratio of hea-ring disorder in newborns with hyperbilirubinemia was 2.13%;18(9.9%)newborns didn′t pass the first DPOAE test among 182 normal newborns,and those infants all passed the second DPOAE test.Conclusions Hyperbilirubinemia is high-risk population of hearing disorder.The congenital cytomegalovirus infection,neonatal septicemia and hemolytic disease of newborn are the high risk factors responsible for hearing disorder.All high risk newborns should recieve hearing examination regularly.

Clinicopathologic and prognostic significance of MMP-7 (matrilysin) expression in human rectal cancer.

OBJECTIVE: There is increasing evidence to indicate that MMP-7 plays a more important role in tumor progression than other MMPs. The aim of this study was to detect MMP-7 expression in human rectal cancer and normal rectal tissue and to determine whether it is correlated with invasion and metastasis of human rectal cancer. METHODS: Eighty-six paired samples of rectal cancer and distant normal rectal tissue obtained from 100 inpatients were allocated into two groups (cancer group and control group). MMP-7 mRNA was detected by relative quantitative real-time RT-PCR and MMP-7 protein was examined by immunohistochemical staining and computerized image analysis. RESULTS: MMP-7 mRNA expression in cancer group was higher than that in control group (P = 0.006), the expression ratios of 31 samples (37.35%) were <1 and 52 (62.65%) were >1. The mRNA expression level was correlated with Dukes Staging, histological differentiation grade and CEA level. The MMP-7 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in cancer group (1.82 +/- 0.03) was different from that in control group (1.17 +/- 0.13, P = 0.002). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (2.04 +/- 0.18, n = 52) was higher than that in low-level mRNA ones (1.58 +/- 0.23, n = 31, P = 0.008). CONCLUSIONS: Our results suggest that MMP-7 plays an important role in the progression of human rectal cancer. MMP-7 may be selected as a clinical diagnosis and prognosis index in rectal cancer.

Ultrastructural characteristics of SARS associated virus in infected cells / 中华病理学杂志

<p><b>OBJECTIVE</b>Electron microscopical study of infected cells to identify the pathogenic agent of SARS.</p><p><b>METHODS</b>Vero E6 cells infected with lung autopsy samples or nasopharyngeal swabs from SARS patients of Beijing and Guangzhou were inoculated. The supernatant and cultured cells exhibiting identifiable cytopathic effect (CPE) were prepared for electron microscopic study.</p><p><b>RESULTS</b>Examination of CPE cells on thin-section revealed characteristic coronavirus particles within the cisternae of endoplasmic reticulum, Golgi apparatus, vesicles and extracellular space. They were mainly spherical or oval in shape, annular or dense, about 80 nm in diameter. Negative-stain electron microscopy identified coronavirus particles in culture supernatant, 80 - 120 nm in diameter, with club-shaped surface projections. Elongated, rod-, kidney- or other irregular shaped virons with the size of 100 - 200 nm by 60 - 90 nm were also found in the cultured cells infected with the lung samples from the Guangdong patients. Infectious virons entered cells by endocytosis or membrane fusion and released through a budding process.</p><p><b>CONCLUSION</b>These data indicate a novel coronavirus as the causative agent of SARS. Most viral particles showed typical characteristics of coronavirus. The potential role of special shape viruses is expected to be further investigated.</p>