Combining metabolomics and network pharmacology to investigate the protective effect of Jiawei Xinglou Chengqi Granules in ischemic stroke.

Jiawei Xinglou Chengqi Granule (JXCG) is an effective herbal medicine for the treatment of ischemic stroke (IS). JXCG has been shown to effectively ameliorate cerebral ischemic symptoms in clinical practice, but the underlying mechanisms are unclear. In this study, we investigated the mechanisms of action of JXCG in the treatment of IS by combining metabolomics with network pharmacology. The chemical composition of JXCG was analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UHPLC-Q-TOF MS) untargeted metabolomics were used to identify differential metabolites within metabolic pathways. Network pharmacology was applied to mine potential targets of JXCG in the treatment of IS. The identified key targets were validated by constructing an integrated network of metabolomics and network pharmacology and by molecular docking using Cytoscape. The effect of JXCG on IS was evaluated in vivo, and the predicted targets and pathways of JXCG in IS therapy were assessed using immunoblotting. Combining metabolomics and network pharmacology, we identified the therapeutic targets of JXCG for IS. Notably, JXCG lessened neuronal damage and reduced cerebral infarct size in rats with IS. Western blot analysis showed that JXCG upregulated PRKCH and downregulated PRKCE and PRKCQ proteins. Our combined network pharmacology and metabolomics findings showed that JXCG may have therapeutic potential in the treatment of IS by targeting multiple factors and pathways.

[Computed tomographic images analysis of frontal recess anatomy based on three-dimension reconstruction].

OBJECTIVE: To observe the CT three-dimensional imaging features of the frontal recess region with advanced three-dimensional reconstruction, and develop the real image of the important anatomical structures around the region to conduct surgery. METHOD: Thirty patients were undergone spiral CT by 16 line high speed spiral CT, and multiplanar reconstruction images using standard three-dimensional reconstruction protocol on a computer workstation. The structure of the frontal recess, the agger nasi cell and adhere style of the uncinate process were observed. The parameter of the important anatomic structure of frontal recess was measured precisely. RESULT: After the reconstruction, we get the three-dimensional model very close to the true state of the nasal cavity-sinuses cell, in which parts of the frontal recess can clearly identify the agger nasi cell, frontal cell and other important structures. In these patients, the height, width and depth of the agger nasi and frontal sinus were (9.45 ± 3.60)mm, (8.08 ± 3.37)mm, (26.98 ± 6.82)mm and (26.86 ± 9.45)mm, respectively. CONCLUSION: This study tried to develop the standardized techniques and measurements from three-dimensional reconstructed images of the frontal sinus and to ascertain the usefulness of the frontal sinus in identification of patients. The project results in better preoperative patient counselling and in predicting postoperative improvement in clinical status.

[3D computed tomographic analysis of frontal recess region].

OBJECTIVE: The purpose of the study was to observe the three-dimensional (3D) CT imaging features of the frontal recess region with 3D reconstruction, and obtain the real image of the important anatomical structures of the region to conduct surgery. METHOD: Five patients were undergone spiral CT by 16 line high speed spiral CT, and multiplanar reconstruction images using standard 3D reconstruction protocol on a computer workstation. The structure of the frontal recess, the agger nasi cell and adhere style of the uncinate process were observed. The parameter of the important anatomic structure of frontal recess was measured precisely. RESULT: After the reconstruction, we get the 3D model very close to the true state of the nasal cavity--sinuses cell, in which parts of the frontal recess can clearly identify the agger nasi cell, frontal cell and other important structures. In this patient, the height, width and depth of the agger nasi and frontal sinus were 12.3 mm, 12.1 mm, 38.5 mm, respectively. CONCLUSION: This study tried to develop the standardized techniques and measurements from 3D reconstructed images of the frontal sinus and to ascertain the usefulness of the frontal sinus in identification of patients. The results in better preoperative patient counselling and in predicting postoperative improvement in clinical status.

[A case of malignant melanoma on the left side of the maxillary sinus].

The clinical manifestations of the disease lacked specificity,and the clinical symptoms were nasal obstruction, any blood in snively and slightly swelling pain on face. The neoplasm with unsmooth surface looked taupe and maroon, and was brittle and easy blooding. Paranasal sinus CT:crumbly mass lesion within the shadow filled in the left side of the maxillary sinus,and the sinus stopped up,sinus wall bone was absorpt and thinned, front and rear wall and inner wall bone were boundedness broken off, knuckle partly to the nasal cavity. Direct reinforcement MRI:in addition to the result of paranasal sinus CT,enhance examination found obviously asymmetrical intensify of the focus. The pathological diagnosis of postoperation was malignant melanoma on the left side of the maxillary sinus.

[The expression of IL-23 in nasal mucosa of allergic rhinitis patients and its significance].

OBJECTIVE: To investigate the expression of interleukin (IL)-23 in the nasal mucosa of allergic rhinitis patients and its significance. METHOD: mRNA and protein expression of IL-23 in inferior turbinate mucosa from 12 allergic rhinitis patients and 11 control patients was measured by means of real-time RT-PCR and immunohistochemistry, respectively. RESULT: IL-23p19 mRNA relative expression level in nasal mucosa was significantly increased in allergic rhinitis patients compared with normal controls (P < 0.01). Immunohistochemical staining demonstrated that IL-23 protein was mainly expressed by infiltrating inflammatory cells in lamina propria and there was increased number of IL-23 positive cells in allergic rhinitis patients in comparison with normal controls. Correlation analysis showed that the mRNA and protein expression level of IL-23 was significantly positively correlated with the number of the inflammatory cells (r = 0.678 and 0.644, respectively; both P < 0.01) and the degree of subepithelial collagen deposition (r = 0.834 and 0.721, respectively; both P < 0.01). IL-23p19 mRNA relative expression level in nasal mucosa was significantly decreased in allergic rhinitis patients who used glucocorticoids compared with controls (P < 0.01). CONCLUSION: IL-23 may contribute to the chronic inflammation and airway remodelling in allergic rhinitis.

Increased serum complement component 3 and mannose-binding lectin levels in adult Chinese patients with chronic rhinosinusitis.

OBJECTIVE: To study the immune function of adult Chinese patients with chronic rhinosinusitis (CRS) to elucidate its potential role in the pathogenesis of CRS. METHODS: A prospective three-arm case-control study. The study population comprised 72 CRS patients without nasal polyps (NPs), 95 CRS patients with NPs, and 110 healthy controls. The concentrations of serum immunoglobulin A (IgA), M (IgM), G (IgG), IgG subclasses (IgG1-4), complement component 3 (C3), and complement component 4 (C4) were measured by nephelometry. Serum mannose-binding lectin (MBL) levels were analyzed by enzyme-linked immunosorbent assay. All CRS patients had a complete blood count with differential, atopic status evaluation, coronal computed tomographic (CT) scan of the sinuses, and nasal endoscopy. RESULTS: Frequency of immunoglobulin, C3, C4, or MBL deficiency showed no difference among groups. The prevalence of coexistence of MBL and immunoglobulin or complement component deficiency did not differ significantly among groups either. However, compared with controls, decreased IgG3 levels were found in CRS patients without NPs, and increased C3 and MBL levels was found in both CRS patients with and without NPs. Moreover, MBL levels were significantly higher in CRS patients with NPs than in CRS patients without NPs, which positively correlated with extent of disease seen on CT scan and endoscopy, and peripheral eosinophil count. CONCLUSIONS: Immunoglobulin, C3, C4, and MBL deficiency is not the main cause of CRS in adult Chinese patients. However, on the contrary, increased C3 and MBL levels in serum might play a modulatory role in CRS development.

[Computed tomographic analysis of frontal recess region].

OBJECTIVE: The purpose of the study was to observe the CT imaging features of the frontal recess regional. METHOD: Eighty-two patients were undergone spiral computed tomography (CT). Then multiplanar reconstruction images were made using standard triplanar reconstruction protocol on a computer workstation. RESULT: The prevalence of agger nasi cell was 87.8% (144/164). One hundred and forty-five (89%, 145/164) uncinate processes had one superior attachment for each uncinate process. The others had two superior attachments for each uncinate process. The uncinate process' single superior attachment of into the surrounding structures was identified to have the following distribution: 90/164 (54.9%): to the lamina papyracea, 50/164 (30.5%) to the middle turbinate, and 5/164 (3.0%) to the skull base. Of all the frontal cells were identified in 144 (87.8%) sides of frontal recesses, the prevalence of type I II, type III IV, were 30.5% and 9.8% respectively. CONCLUSION: T Agger nasi cell and uncinate process play an important role in endoscopic frontal sinus surgery.

[Prevalence of sensitization to allergens in patients with allergic rhinitis and respiratory disease in Qingshan of Wuhan].

OBJECTIVE: The purpose of this study was to determine which allergens were prevalent in patients with allergic rhinitis and respiratory disease in Qingshan Wuhan. METHOD: A total of 700 cases, which were diagnosed as allergic rhinitis and respiratory disease by history and clinical presentation, underwent ELISA test with 7 standardized allergens, and the most important sensitizing allergens were assessed. The samples were stratified on two age groups: AR and respiratory disease group and the positive rate of two main allergens in two groups were contrast analyzed. RESULT: For patients with allergic rhinitis, the positive rate of the top seven aeroallergen were dermatophagoides (47%), herbs (19.7%), tree (18%), animal dander (8.9%), house dust (6.5%), mold (4.9%) and wormwood (3%). There was no significant difference in higher sensitivity to dust mite and ragweed between allergic rhinitis and respiratory disease group (P > 0.05). CONCLUSION: Dust mite, Tree and Herbs are the most important three aeroallergens in Qingshan region of Wuhan.

Lack of association of Clara cell 10-kDa protein gene variant with chronic rhinosinusitis in a Chinese Han population.

BACKGROUND: Clara cell 10-kDa protein (CC10) is an anti-inflammatory molecule and has been implicated in the involvement of the pathogenesis of asthma and chronic rhinosinusitis (CRS). A single nucleotide polymorphism (SNP) in CC10 gene (A + 38G) was previously shown to be associated with asthma and plasma CC10 levels. The purpose of this study is to examine whether there is an association between the CC10 A + 38G SNP, plasma CC10 levels, and CRS in a central Chinese population of Han nationality. METHODS: The CC10 A + 38G SNP was analyzed by means of polymerase chain reaction with restriction fragment length polymorphism and plasma CC10 levels were measured using enzyme-linked immunosorbent assay in 220 patients with CRS (90 patients with nasal polyps [NPs] and 130 patients without NPs) and 180 healthy control subjects. Among 220 patients with CRS, 108 patients were atopic subjects. Severity of disease was determined by coronal computed tomography (CT) scan in CRS patients, which was graded according to Lund and Mackay. RESULTS: The frequency of the A allele was 0.394, which was not significantly higher than the frequencies of other reported ethnic groups except for German. No association between the CC10 A + 38G SNP and CRS, any subgroup of CRS, or CRS severity could be found. Although subjects carrying the AA genotype had a significantly lower plasma CC10 concentration than those carrying the GG and GA genotypes in both CRS and control groups (p = 0.00 for all), no association was found between the plasma CC10 levels and CRS phenotype. CONCLUSION: The CC10 A + 38G SNP may not exert a substantial influence on the development of CRS in the Chinese Han population.

[The investigation of efficacy and safety of Aerius to seasonal allergic rhinitis].

OBJECTIVE: To evaluate the efficacy and safety of Aerius to seasonal allergic rhinitis. METHOD: Using randomized, controlled method, treatment group 40 cases, oral administration Aerius 5 mg/d for 12 days; control group 35 cases, oral administration Aerius 5 mg/d for 12 days, investigating their efficacy and safety. RESULT: The total effective rate of treatment group was 92.50%, while control group was 85.71%, there was significant difference between them (P<0.05). Significant improvements of seasonal allergic rhinitis nasal obstruction were seen in treatment group after using Aerius (P<0.05). The incidence of side effect of treatment group was 2.50%. CONCLUSION: Aerius is safe and can effectively reduction in nasal and nonnasal symptoms in patients with seasonal allergic rhinitis.

[Endoscopic removal of ethmoid osteoma: report of 13 cases].

OBJECTIVE: To report 13 cases of ethmoid osteoma removed through an endoscopic approach and discuss the operative technique and clinical value. METHOD: Thirteen cases with ethmoid osteoma were retrospectively reviewed in the study. All procedures were performed with CT image guidance-according to the site of attachment. The anterior ethmoid cell was resected, and the whitish osteoma found. A double blunt elevator was used to separate the osteoma from ethmoid cell, and to push the osteoma medially toward the nasal septum, and (or) inferiorly toward the middle meatus. This method was performed in 7 patients (8 sides), whose CT scan showed the osteoma bases were not attached to lamina papyracea, and (or) anterior skull base. The others were drilled out with a intranasal powered drill for its attached to lamina papyracea in 4 patients and to anterior skull base in 2 patients. RESULT: Thirteen cases of ethmoid osteoma were removed completely through an endoscopic approach and there were no intraorbital or intracranial complication. Endoscopy showed normal epithelization at around 6 to 8 weeks after surgery. CONCLUSION: Preoperative CT scans, including coronal and axial images, is very helpful to determine the sites of the osteoma attachment and plan the operation. Endoscopic removal of ethmoid osteoma is not only an ideal, less invasive surgical approach, but also no cosmetic alteration.

[Correlation between rhinosinusitis symptoms and objective sinus examinations].

OBJECTIVE: To explore the relationship between rhinosinusitis symptoms and objective sinus examinations. METHOD: Prospective data of 75 patients with CRS scheduled for surgery were collected and analyzed retrospectively. The preoperative computed tomography (CT) scans were graded according to Lund and Mackay. The preoperative nasal endoscopy was graded by assigning an endoscopy score according to Lanza and Kennedy. A visual analog scale (VAS) symptom score was completed. RESULT: (1) There was a significant correlation between preoperative CT and endoscopy scores (r = 0.88, P < 0.01); (2) The severity of smell function disturbance correlated with severity of disease on CT scan and endoscopy (r value was 0.57 and 0.53 respectively, P < 0.01). However, other symptoms and overall sinonasal symptom severity had no correlation (P > 0.05). Furthermore, a statistically significant but weak correlation was found between the VAS score based on the sum of five sinonasal symptoms and the Lund-Mackay CT scan score (r = 0.26, P < 0.05), while no correlation between VAS score based on the sum of five sinonasal symptoms and endoscopy score was found ( P > 0.05). CONCLUSION: There is no good correlation between CRS symptoms and objective examinations. In order to evaluate CRS patients' severity and select treatment properly, both symptoms and objective examinations must be considered.

[Expression difference of toll-like receptors among chronic rhinosinusitis and nasal polyps].

OBJECTIVE: To compare the expression difference of Toll-like receptor-2 (TLR-2) and Toll-like receptor-4 (TLR-4) protein and mRNA among the chronic rhinosinusitis tissues, nasal polyps tissues, and normal mucosa tissues. METHODS: The mRNA expression of TLR-2 and TLR-4 in chronic rhinosinusitis tissues from 10 patients, in nasal polyp tissues from 10 patients, and in inferior turbinate tissues from 10 patients underwent nasal septum operation was detected by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to detected the expression of TLR-2 and TLR-4 protein in a different set of 20 chronic rhinosinusitis tissues, 20 nasal polyp tissues, and 20 normal inferior turbinate tissues. RESULTS: (1) The mRNA and protein expression of TLR-2 and TLR-4 was detected on epithelial and glandular cells membrane in all chronic rhinosinusitis, nasal polyps and control tissues . (2) The mRNA and protein expression of TLR-2 and the mRNA expression of TLR-4 in chronic rhinosinusitis tissues was significantly increased compared with that in nasal polyps and control tissues (P < 0.05). (3) The expression intensity of TLR-2 and TLR-4 mRNA and protein between nasal polyps and control tissues was found no significant difference (P > 0.05). CONCLUSIONS: Different TLR-2 and TLR-4 protein and mRNA level in chronic rhinosinusitis and nasal polyp tissues might imply that TLR-2 and TLR-4 play different role in the pathogenesis of chronic rhinosinusitis and nasal polyps.

[The perioperative glycemic control in chronic rhinosinusitis coexisting diabetes].

OBJECTIVE: To evaluate the method of the perioperative blood glucose control in chronic rhinosinusitis coexisting diabetes. METHOD: Twenty-two cases of chronic rhinosinusitis coexisting diabetes were investigated retrospectively, including one case of type 1 diabetes and 21 cases of type 2 diabetes. The study cohort was divided into two groups, the one was complication group and the other was non-complication group. The patients in complication group were injected insulin to control blood glucose level, and the patients in non-complication group were prescribed oral medicine. RESULT: Blood glucose levels below 9.0 mmol/L in complication group and below 7.0 mmol/L in non-complication group were both the surgical indication for the patients in this research cohort. Twenty-one cases were completely recovered and one case made progress significantly. CONCLUSION: The detection of blood and urine glucose levels must be the routine item before the nasal endoscopic surgery. To control blood glucose levels in type 2 diabetes with non-complication, oral medicine is the first choice, in type 1 diabetes and type 2 diabetes with complication, insulin should be first considered.

[Three dimensional reconstruction study of multi-slice helical CT imaging on optic canal area].

OBJECTIVE: To investigate the accuracy and clinical application of multi-slice spiral CT imaging on optic canal area. METHOD: Forty intact specimens of human corpse head were tested with three dimensional reconstruction of multi-slice spiral CT imaging. The results of radiology and anatomy were compared on adjacent structures of optic canal interior wall and its developmental relationship with sphenoid sinus. RESULT: (1) The high spatial resolution of integrity could be obtained with dimensional processing technique. The anatomical structure of optic canal and its surrounding area could be demonstrated clearly. (2) With the technique of virtual endoscopy, the interior reconstruction of optic canal could demonstrate the inner topography of optic canal, the reconstruction image of which was identical to that of the control subjects. (3) There was no significant difference between the data of multi-slice spiral CT imaging and that of anatomy (P > 0.05). CONCLUSION: Associated application of dimensional processing technique and virtual endoscopy, not only can the subtle structures of optic canal be demonstrated and measured, but also the detailed information on spatial relationships of optic canal area can be provided for operation.

[The difference in some clinical and pathological characteristics between chronic sinusitis patients with and without nasal polyps].

OBJECTIVE: To explore the difference in some subjective symptoms, objective examination results, and pathological characteristics between chronic sinusitis patients with and without nasal polyps (CRSwNP and CRSsNP). METHOD: Prospective data of 42 CRSsNP patients and 33 CRSwNP patients scheduled for surgery were collected and analyzed retrospectively. A visual analog scale (VAS) symptom score was completed. The preoperative computed tomography (CT) scans were graded according to Lund and Mackay. The preoperative nasal endoscopy was graded by assigning an endoscopy score according to Lanza and Kennedy. Blood was drawn to determine the number of peripheral eosinophils (EOS) by means of automated analysis. Surgical specimen was examined pathologically for the number of EOS per high-powered field. Interleukin (IL)-5 was determined by means of quantitative enzyme-linked immunosorbent assay. RESULT: (1) As to the single VAS symptom score relating to overall symptom severity and the VAS score based on the sum of five sinonasal symptoms, there was no difference between CRSsNP and CRSwNP patients (P > 0.05). However, compared with CRSwNP patients, CRSsNP patients had higher VAS score of nasal discharge (P < 0.05) and lower score of hyposmia (P < 0.01); (2) Compared with CRSsNP patients, CRSwNP patients had higher CT and endoscopy scores, peripheral and mucosal EOS counts, and mucosal IL-5 level (P < 0.05); (3) The preoperative CT and endoscopy scores were positively correlated with peripheral and mucosal EOS counts and mucosal IL-5 level (P < 0.01). CONCLUSION: There is no significant difference in overall symptom between CRSsNP and CRSwNP patients. However, CRSwNP patients have more severe inflammation in nasal and sinus cavity, which is related to eosinophilic inflammation in local mucosa.

[Clinical observation on inhalation of pulmicort in patients with chronic rhinosinusitis after surgery].

OBJECTIVE: Whether inhalation of pulmicort into the sinus of chronic rhinosinusitis patients could improve reepithelization after endoscopic sinus surgery was assessed. METHOD: Prospective study 60 patients with chronic rhinosinusitis after endoscopic sinus surgery were divided into 2 groups randomized, the one was treatment group, and the other was control group. The patients in treatment group received inhalation of pulmicort 2 ml plus 0.5% Aeuromycin solution 10 ml by oxygen driving force, once a day, persisting for 3 weeks. The patients in control group received Rhinocort. Besides the different therapies above mentioned above therapy was different, two groups received the same conventional route therapy. To observe the time of reepithelization under nasal endoscope, was observed, respectively. RESULT: The average time of reepithelization in treatment group was (5.3333 +/- 0.9942) weeks. The other group was (6.6667 +/- 1.3476) weeks, the statistical difference between the two groups was very significant. CONCLUSION: Inhalation of pulmicort into the sinus can promote reepithelization and shorten the time of treatment.

The up-regulated expression of tenascin C in human nasal polyp tissues is related to eosinophil-derived transforming growth factor beta1.

BACKGROUND: Tissue remodeling is an important characteristic of nasal polyps (NPs). However, the mechanisms underlying the remodeling processes are poorly defined. This study investigated the role of transforming growth factor (TGF) beta1 and eosinophils in the expression of tenascin C (Tn-C), an extracellular matrix glycoprotein, in NPs. METHODS: The protein expression of Tn-C and TGF-beta1 was examined by means of immunohistochemistry in NPs and normal control inferior turbinate tissues. Furthermore, cell culture, quantitative RT-PCR, and in situ immunocytofluorescence techniques were used to investigate the direct effect of TGF-beta1 and eosinophils on Tn-C production in primary nasal epithelial cells. RESULTS: Tn-C protein expression was significantly up-regulated in NP tissues and correlated with TGF-beta1+ eosinophils. TGF-beta1 and eosinophils dramatically induced Tn-C mRNA and protein expression in nasal epithelial cells. The effect of eosinophils could be inhibited partly by a neutralizing antibody to TGF-beta1. CONCLUSION: Eosinophil-derived TGF-beta1 may contribute, at least in part, to the tissue remodeling in NPs.

[Clinical evaluation of the styloid process by plain radiographs and three-dimensional computed tomography].

OBJECTIVE: To investigate the relation between radiological and clinical diagnosis for Eagle's syndrome and to evaluate the value of plain radiograph (PR) and three-dimensional CT reconstructional image (3-DCT) of styloid process (SP). METHOD: The length of the 144 SPs from the PR was recorded and the palpation of the SP in tonsillar fossa was carried out in 113 patients with suspective Eagles syndrome. Twenty-three of 113 patients also underwent 3-DCT, so that the length and angulation of the 30 SPs were measured. RESULT: Seventy-eight of 113 patients (31 men and 47 women) were diagnosed as having Eagles syndrome. The age ranged from 32 to 68 years (average age: Forty-two years). A good agreement between the PR and the palpation was determinated, Kappa coefficient was 0.58. The difference value of the length of 30 SPs between the PR and the 3-DCT was (1.59 +/- 1.32) mm, and there were statistically significant difference of the length (t = 6.64, P < 0.01) on the length of SP between the PR and the 3-DCT. Positive correlation between the PR and the 3-DCT was found to be statistically significant (r = 0.982 4 +/- 95% confidence interval: 0.9631, 0.9917). The mean of medial angle of SPs was (25.60 +/- 2.56) degrees in patients with positive palpation and (15.42 +/- 2.79) degrees in those with negative palpation, respectively (P < 0.01) and the mean of anterior angle of SPs was (16.86 +/- 4.83) degrees in patients with positive palpation and (12.71 +/- 3.39) degrees in those with negative palpation, respectively (P < 0.01). The abnormal medial and anterior angles of unilateral SP without more than 30mm long was also objectively diagnostic of SPS in 8 patients with positive palpation. Four patients, whose elongated SP is too tenuous to be palpated preoperatively, underwent intraoral styloidectomy because of the fact that 3-DCT showed the tip of SPs medial and anterior deflexion. CONCLUSION: Despite magnifying image, the PR of SP is enough to diagnose Eagle's syndrome for the majority of cases. 3-DCT allows precise measurement of the length and the angulation of SPs, it is the best for the complementary purpose to the PR and to the selection of surgical approach in some cases.