A comprehensive clinical evaluation of HER2-TKIs in patients with previously treated HER2-positive metastatic breast cancer.

Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.

[The technique and application of individualized tympanic membrane flap in the repair of tympanic membrane under endoscopy ear surgery].

Objective:To investigate the technique of personalized flap making under otoscopy and its clinical application. Methods:The clinical data of patients who underwent 301 Military Hospital myringoplasty in the Department of otoendoscopic surgery, Department of Otorhinolaryngology, head and neck surgery, Department of Otorhinolaryngology, from October 2022 to 2023 August were analyzed retrospectively, all enrolled patients were performed independently by the same skilled otoendoscopic surgeon. The patients' general condition, medical history, tympanic membrane perforation scope, perforation size, need for tympanic cavity exploration, thickness of skin flap, tympanic cavity lesion scope, skin flap making method and postoperative rehabilitation were collected. Results:Many factors such as the location of tympanic membrane perforation, the thickness of the skin flap, the degree of curvature or stricture of the ear canal and the extent of the lesion in the tympanic cavity should be considered in the manufacture of the individualized tympanic membrane skin flap, the way of skin flap making does not affect the long-term postoperative rehabilitation, but it can effectively avoid unnecessary ear canal skin flap injury and improve the operation efficiency. Conclusion:Scientific flap fabrication is important for improving surgical efficiency and enhancing surgical confidence.

Research Progress of PI3K/PTEN/AKT Signaling Pathway Associated with Renal Cell Carcinoma.

Renal cell carcinoma is a common renal malignancy of the urinary system and the most malignant type of kidney cancer. Phosphatidylinositol 3-kinase (PI3K) is an intracellular phosphatidylinositol kinase associated with oncogene products such as v-src and with serine/threonine kinase activity, and its increased activity correlates with the development of several cancers. Protein kinase B (AKT) is a cyclic guanosine phosphate-dependent protein kinase that plays an important role in cell survival and apoptosis. Phosphatase and tensin homolog (PTEN), a newly discovered oncogene in recent years, participates in tumorigenesis and development by competing with tyrosine kinases for common substrates. The product encoded by PTEN was found to negatively regulate the PI3K/Akt signaling pathway, thereby inhibiting cell proliferation and promoting apoptosis. The PI3K/PTEN/AKT signaling pathway has also been identified in several studies as being involved in the development of several malignancies, including renal cell carcinoma. Radiotherapy is currently one of the most effective means of treatment for renal cell carcinoma, whereas it is predisposed to significant tolerance during the course of radiotherapy, thereby leading to treatment failure. Therefore, new treatment options may potentiate the efficiency of renal cell carcinoma treatment. With the development of tumor molecular biology, targeted biological therapy for malignant tumors has gradually become a research hotspot. Given the above research background, this study reviews the application of the PI3K/PTEN/AKT signaling pathway in renal cell carcinoma, aiming to provide more references for the treatment of clinical renal cell carcinoma.

Case Report: Primary Aldosteronism and Subclinical Cushing Syndrome in a 49-Year-Old Woman With Hypertension Plus Hypokalaemia.

Background: Coexisting primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) caused by bilateral adrenocortical adenomas have occasionally been reported. Precise diagnosis and treatment of the disease pose a challenge to clinicians due to its atypical clinical manifestations and laboratory findings. Case Summary: A 49-year-old woman was admitted to our hospital due to fatigue, increased nocturia and refractory hypertension. The patient had a history of severe left hydronephrosis 6 months prior. Laboratory examinations showed hypokalaemia (2.58 mmol/L) and high urine potassium (71 mmol/24 h). Adrenal computed tomography (CT) showed bilateral adrenal masses. Undetectable ACTH and unsuppressed plasma cortisol levels by dexamethasone indicated ACTH-independent Cushing's syndrome. Although the upright aldosterone-to-renin ratio (ARR) was 3.06 which did not exceed 3.7, elevated plasma aldosterone concentrations (PAC) with unsuppressed PAC after the captopril test still suggested PA. Adrenal venous sampling (AVS) without adrenocorticotropic hormone further revealed hypersecretion of aldosterone from the right side and no dominant side of cortisol secretion. A laparoscopic right adrenal tumor resection was performed. The pathological diagnosis was adrenocortical adenoma. After the operation, the supine and standing PAC were normalized; while the plasma cortisol levels postoperatively were still high and plasma renin was activated. The patient's postoperative serum potassium and 24-h urine potassium returned to normal without any pharmacological treatment. In addition, the patient's blood pressure was controlled normally with irbesartan alone. Conclusion: Patients with refractory hypertension should be screened for the cause of secondary hypertension. AVS should be performed in patients in which PA is highly suspected to determine whether there is the option of surgical treatment. Moreover, patients with PA should be screened for hypercortisolism, which can contribute to a proper understanding of the AVS result.

Increased expression of interleukin-22 and its receptor is relevant to poor prognosis in laryngeal squamous cell carcinoma: A case control trial.

ABSTRACT: To detect the expression of interlerukin-22 (IL-22) and associated genes and to evaluate their relationship with clinicopathological features and prognosis in laryngeal squamous cell carcinoma (LSCC).The expression of IL-22 and associated genes were evaluated by immunohistochemistry and real time polymerase chain reaction in LSCC tissues from 30 patients and adjacent non-tumor tissues. A statistical analysis was implemented to assess the relationship among levels of expression, clinicopathological factors, and overall survival.The expression of IL-22 and interleukin 22 receptor 1 (IL-22R1) was mainly located in the cytoplasm, and the expression of LSCC was significantly higher than in controls. The expression of aryl hydrocarbon receptor and signal transducer and activator of transcription 3 distributed in the cell nucleus, which was significantly higher in LSCC than in controls. The expression of IL-22 and IL-22R1 was associated with metastasis of lymph node and clinical stage of LSCC. Overall survival of LSCC was significantly poorer with higher expression of IL-22 and IL-22R1 than in those with lower expression.The present research indicated that the increased level of IL-22 and IL-22R1 may be related to the pathogenesis and prognosis of LSCC. IL-22 may be the important biomarker, which need further research.

Clinical effect of a novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation for thoracolumbar burst fractures.

BACKGROUND: Short-segment transpedicular screw fixation is a common method for the treatment of thoracolumbar burst fractures (TBFs),but this technique has many problems. Therefore,the purpose of this article is to observe and evaluate the clinical efficacy of a novel transpedicular reducer that we designed for fractured vertebral body reduction and bone grafting in the treatment of TBFs. METHODS: From July 2018 to November 2020, 70 cases of TBFs were included. Thirty-five patients were treated with the novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation (observation group), and 35 patients were treated with short-segment transpedicular screw fixation (control group). Before the operation, after reduction, and 3 days, 3 months,and 12 months after the operation, the two groups were assessed, and compared with respect to the anterior and middle heights of the injured vertebrae, the ratios of the anterior and middle heights of the injured vertebral body to the respective heights of the adjacent uninjured vertebral bodies (AVBHr and MVBHr, respectively), and the Cobb angle of the patients. We compared the pain VAS score and quality of life GQOL-74 score at the last follow-up. Finally,we evaluated the distribution of bone grafts and bone healing 12 months after the operation. RESULTS: The anterior height, middle height, AVBHr, MVBHr, and Cobb angle of the injured vertebral body in the observation after reduction, and 3 days, 3 months and 12 months post-operatively were compared with those of the injured vertebral body before operation. All of these parameters were improved, and the difference was statistically significant (p < 0.05). These parameters in the observation group at the above time points were significantly better than thoes in the control group at the corresponding time points (p < 0.05). The VAS scores at the last follow-up were significantly better than those of the control group (p < 0.05), but the GQOL-74 score differences were not statistically significant (p > 0.05). The observation group showed no obvious defects on CT at 12 months after the operation, and the bone healing was good. CONCLUSION: The novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation for TBFs has good clinical efficacy.

[Percutaneous full-endoscopic bilateral decompression via unilateral posterior approach for lumbar spinal stenosis].

OBJECTIVE: To design the surgical strategy of percutaneous full-endoscopic bilateral decompression via unilateral posterior approach for bilateral lumbar spinal stenosis (LSS) and to evaluate the effectiveness. METHODS: The percutaneous full-endoscopic bilateral decompression via unilateral posterior approach for bilateral LSS was designed according to the pathological features of LSS. The technique was used to treat 42 patients with LSS between January 2016 and January 2018. There were 18 males and 24 females with an average age of 61.7 years (range, 46-81 years). The duration of symptoms was 1-20 years, with an average of 9.7 years. The surgical segment at L 4, 5 were 27 cases, at L 5, S 1 were 15 cases. The operation time and perioperative complications were recorded. Lumbar X-ray, CT, and MRI examinations were performed at 1 week, 3 months, and 1 year after operation. Visual analogue scale (VAS) score was used to evaluate the low back pain and leg pain, Oswestry disability index (ODI) was used to evaluate the lumbar function, and single continuous walking distance (SCWD) was used to evaluate lower extremity nerve function. The clinical efficacy was evaluated by MacNab criteria at 1 year after operation. RESULTS: All patients underwent surgery successfully. The operation time was 68-141 minutes with an average of 98.2 minutes. All 42 patients were followed up 12-24 months with an average of 18.8 months. There were 2 cases of dural tears during operation, and 1 case of transient dysfunction of the lower limbs of the decompression channel after operation. All of them were cured after corresponding treatment. No serious complications such as death, major bleeding, or irreversible nerve injury occurred during follow-up. No segmental instability was found according to postoperative lumbar hyperextension and flexion X-ray films, and postoperative CT and MRI imaging showed that the stenotic lumbar spinal canal was significantly enlarged, and the compression of the nerve root was sufficient. The VAS score of low back pain and leg pain, ODI score, and SCWD at each time point after operation were significantly improved when compared with those before operation ( P<0.05); the indexes were significantly improved over time after operation, and the differences were significantly ( P<0.05). The clinical efficacy was evaluated by MacNab standard at 1 year after operation, and the results were excellent in 18 cases, good in 20 cases, fair in 3 cases, and poor in 1 case. The excellent and good rate was 90.5%. CONCLUSION: The percutaneous full-endoscopic bilateral decompression via unilateral posterior approach for LSS is a safe and effective procedure. A well-designed surgical strategy and mastery of its technical points are important guarantees for successful operation and satisfactory results.

[Retrospective analysis on clinical data and genetic variations of patients with beta-ketothiolase deficiency].

OBJECTIVE: To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD). METHODS: Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed. RESULTS: Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C5:1) were 0.43 (0.20-0.89) µmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) µmol/L. Both were significantly higher than those of healthy controls (P<0.01). Urinary 2-methyl-3-hydroxybutyric acid was 56.04 (7.69-182.20) and methylcrotonyl glycine was 42.83 (9.20-127.01), both were higher than normal levels. In 5 patients urinary 2-methyl-3-hydroxybutyric acid level was remarkably decreased (P<0.05) after treatment. Analysis of ACAT1 gene mutation was performed in six families. Missense variations were detected in 78.6% of the cases. 42.8% of the 7 BKD patients have carried c.1124A>G (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing. CONCLUSION: Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.

Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: A meta-analysis of 40 studies.

Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor progression, mainly through immune suppression. Inverse correlations have been observed between MDSC levels and patient survival for various malignancies. The purpose of this meta-analysis was to evaluate the prognostic value of pretreatment circulating MDSCs. We searched MEDLINE and EMBASE from their inceptions to September 2017 to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). A total of 40 studies comprising 2721 were included. For solid tumors, high levels of pretreatment circulating MDSCs were significantly associated with worse OS (HR = 1.796, 95% CI = 1.587-2.032) and DFS/PFS/RFS (HR = 2.459, 95% CI = 2.018-2.997). Breast cancer showed the largest association between high MDSC levels and worse OS (pooled HR = 3.053). Elevated MDSCs were also associated with worse OS for mixed-stage tumors (pooled HR = 1.659) and advanced-stage tumors (pooled HR = 2.337). Furthermore, both monocytic-MDSCs (M-MDSCs) and granulocytic or polymorphonuclear (PMN-MDSCs) showed negative associations with survival outcomes. Overall, high levels of pretreatment circulating MDSCs negatively influenced survival in most cancers. Pretreatment circulating MDSCs should be taken into account to further improve prognostic evaluation and develop novel therapeutic strategies.

Categorising bone defect hematomas - Enhance early bone healing.

Fracture hematoma formation describes a transitional phase that involves a dynamic and tightly choreographed interaction between the fibrin matrix, cells, and cytokines that guides the ensuing bone repair. Here we propose a novel hypothesis to explain why hematomas in conjunction with critical sized bone defects are prone to differentiate into fibrous tissues, which eventually results in non-unions of the bone. We postulate that certain hematoma qualities are triggers that influence cell biological behaviours and that the release of certain growth factors determines what pattern of remodelling will prevail: intramembranous or endochondral ossification. A detailed characterization of the structural parameters of hematomas will allow researchers to create a microenvironment that aids the migration of mesenchymal stromal cells into the hematoma where, once established, they accelerate the bone healing process. Such a strategy would be particularly useful when faced with the complications arising from large recalcitrant bone defects that often fail to heal naturally.

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis.

Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73-32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85-7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%. Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

Allergy reduces the risk of meningioma: a meta-analysis.

Meningiomas are the most common brain tumours; however, little is known regarding their aetiology. The data are inconsistent concerning atopic disease and the risk of developing meningioma. Thus, we conducted a meta-analysis to investigate the association between allergic conditions and the risk of developing meningioma. A systematic literature search was conducted using PubMed and Web of SCI from Jan 1979 to Feb 2016. Two investigators independently selected the relevant articles according to the inclusion criteria. Eight case-control studies and 2 cohort studies were included in the final analysis, comprising 5,679 meningioma cases and 55,621 control subjects. Compared with no history of allergy, the pooled odds ratio (OR) for allergic conditions was 0.81 (0.70-0.94) for meningioma in a random-effects meta-analysis. Inverse correlations of meningioma occurrence were also identified for asthma and eczema, in which the pooled ORs were 0.78 (0.70-0.86) and 0.78 (0.69-0.87), respectively. A reduced risk of meningioma occurrence was identified in hay fever; however, the association was weak (0.88, 95% CI = 0.78-0.99). The source of this heterogeneity could be the various confounding variables in individual studies. Overall, the current meta-analysis indicated that allergy reduced the risk of developing meningiomas. Large cohort studies are required to investigate this relationship.

Cathepsin L is involved in X-ray-induced invasion and migration of human glioma U251 cells.

An important therapeutic method of glioblastoma, the most common primary brain tumor, is radiotherapy. However, several studies reported recently that radiation could also promote the invasion and migration of malignant tumor. Herein, we have identified that a significant increase of migration and invasiveness of human glioma U251 cells undergoing X-ray was observed compared to controls, accompanied by the increase of cathepsin L (CTSL), which is a lysosomal cysteine protease overexpressed and secreted by tumor cells. To verify if there was a relationship between CTSL and the X-ray-induced glioma invasion, a CTSL specific inhibitor Z-FY-CHO or a short hairpin RNA interference was used to pretreat U251 cells. As a result, the cell invasion and migration was impaired via down-regulation of CTSL. Additionally, a marked reduction of the cell-signaling molecules Rho kinase was also detected compared with controls. We also found that CTSL is involved in EMT progress: both in vitro and in clinical specimens. Overall, our findings show that CTSL is an important protein which mediates cell invasion and migration of human glioma U251 cells induced by X-ray, and the inhibition of CTSL expression might diminish the invasion of U251 cells by reducing the activity of RhoA and CDC42 as well as EMT positive markers.

Bifurcation Location Is Significantly Associated with Rupture of Small Intracranial Aneurysms (<5 mm).

BACKGROUND AND OBJECTIVE: Patients with small (<5 mm) unruptured intracranial aneurysms (UIAs) are at risk of subarachnoid hemorrhage, but risk assessment of these patients remains controversial in daily clinical practice. We aimed to identify the risk factors of aneurysmal rupture in these patients. METHODS: We retrospectively analyzed consecutive patients with small UIAs who were admitted to our center between February 2009 and December 2014. The enrolled patients were divided into ruptured and unruptured groups. The risk factors for aneurysmal rupture were determined using multivariate logistic regression analysis. RESULTS: A total of 548 patients with 618 small intracranial aneurysms (267 ruptured and 351 unruptured) were included. Univariate analysis showed that rupture of small aneurysms was related to sex, age, smoking, hypertension, aspect ratio, size ratio, irregular shape, aneurysm width, height, and neck diameter, and location at bifurcation or posterior circulation. Multivariate logistic regression showed that rupture was associated with bifurcation location (odds ratio [OR], 5.409; 95% confidence interval [CI], 3.656-8.001; P < 0.001), size ratio (OR, 3.092; 95% CI, 2.002-4.774; P < 0.001), location (OR, 2.624; 95% CI, 1.428-4.824; P = 0.002), hypertension (OR, 1.698; 95% CI, 1.1140-2.527; P = 0.009), and age at diagnosis of UIA (OR, 1.826; 95% CI, 1.225-2.723; P = 0.003). CONCLUSIONS: This study showed that 70.4% of small ruptured intracranial aneurysms (<5 mm) were located at parent artery bifurcations and that bifurcation location was a significant independent factor for the risk of rupture of small UIAs (<5 mm). Prophylactic treatment should be recommended for small UIAs in this location.

Erythropoietin improves glucose metabolism and pancreatic ß-cell damage in experimental diabetic rats.

Previous studies have implicated erythropoietin (EPO) signaling in the regulation of glucose metabolism. Whether EPO can be used treat diabetes and the underlying mechanism remain to be elucidated. The present study aimed to investigate whether EPO affects glucose metabolism, and the underlying mechanisms, in experimental diabetic rats. The effects of EPO (300 U/kg three times a week for 4 weeks) on glucose metabolism, hematopoietic function, blood selenium content and the ultrastructure of pancreatic ß­cells were investigated in low dose (25 mg/kg body weight) streptozotocin­induced experimental diabetic rats provided with a high­fat diet. The results demonstrated that EPO significantly decreased the fasting blood glucose, the area under the curve of the oral glucose tolerance and insulin tolerance tests and L­alanine gluconeogenesis. Ultrastructural examination of the pancreatic islets revealed that EPO prevented the dysfunction of pancreatic ß­cells in experimental diabetic rats, ameliorated cytoplasmic vacuolation and fragmentation of mitochondria, and increased the number of secretory granules. EPO administration increased the activities of superoxide dismutase and glutathione peroxidase, and decreased the level of malondialdehyde. Additionally, EPO increased blood selenium in the diabetic rats and produced a hematopoietic effect. These results indicated that EPO modulated glucose metabolism and improved pancreatic ß­cells damage by increasing anti­oxidation. The detailed mechanisms underlying these effects require further investigation.

Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis.

In order to explore the role of innate immunity in the remodeling of CRS (chronic rhinosinusitis), we investigated the correlation between TLR2, TLR4 and remodeling involved cytokines and histopathological features. Immunohistochemical staining was applied to detect the expression of TLR2, TLR4 and TGF-ß1. Masson staining was used for observing the collagen deposition. The other histopathologic features of remodeling were observed by hemotoxylin and eosin (HE) staining. Nasal epithelial cell culture was used to elucidate the effect of TLR2, TLR4 agonists and inhibitors on the expression of TGF-ß1 and MMP-9. The association study showed that the significantly higher expression of TLR2, TLR4, TGF-ß1 and collagen appeared in CRSsNP (chronic rhinosinusitis without nasal polyps) patients compared with CRSwNP (chronic rhinosinusitis with nasal polyps) patients. In CRSsNP, patients with a severe epithelial damage (score 3) had a significantly higher expression of TLR2 than patients with mild epithelial damage (score ≤ 2) (P < 0.05). Moreover the expression of TLR2 correlated negatively with squamous hyperplasia in CRSsNP, and positively with gland hyperplasia in CRSwNP. The expression of TLR2 and TLR4 was closely related to neutrophil infiltration in CRSsNP (P < 0.01). TGF-ß1 was downregulated by TLR2 agonist in CRSwNP and upregulated by TLR4 agonist in CRSsNP (P < 0.05). MMP-9 was upregulated by TLR4 agonist in CRSwNP (P < 0.05). TLR2 and TLR4 had close relationship with TGF-ß1 and the histologic features of remodeling, especially collagen deposition and neutrophil infiltration in CRSsNP. The innate immunity could influence the histologic characteristics and involved cytokines through TLR2 and TLR4 in the remodeling of CRS.

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect.

BACKGROUND: In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. METHODS: The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. RESULTS: The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05-2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06-2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29-4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11-2.72) and smoking (OR, 1.86; 95% CI, 1.05-3.29) independently. CONCLUSIONS: Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently.

[Expression and significance of Toll like receptor 2 and Toll like receptor 4 in chronic rhinosinusitis].

OBJECTIVE: To explore the role of the innate immune factors TLR2 and TLR4 in the pathogenesis of chronic rhinosinusitis (CRS) by detecting their expression in different clinical types of CRS and the normal control group. METHOD: Immunohistochemistry was used to detect the expression of TLR2 and TLR4 respectively in 21 cases (chronic rhinosinusitis with nasal polyps, CRSwNP) group, 15 cases (chronic rhinosinusitis without nasal polyos, CRSsNP) group, 11 cases recurrent CRSwNP group and 13 cases control group. Positive cells were counted under the microscope artificially, Mann-Whitney U analysis was applied for the ranked data, and one-way anova analysis was adopted to analyze the experimental group and control group. RESULT: (1) TLR2 and TLR4 expression had the same characteristics. Expression mainly concentrated in parts of the whole layer of epithelial basement membrane, cytoplasm of glandular cells, very few inflammatory cells such as monocytes and plasma cells in the cytoplasm, sometimes unknown cell nuclei positive expression. (2) The glandular cells were stained manual counting and color grading. TLR2 and TLR4 packet application Wilcoxon rank test Mann-Whitney U test analysis was not statistically significant (P > 0.05), measurement data within the group variance statistical difference between the groups (P < 0.05). CONCLUSION: The Nasal mucosa can produce the innate immune factors TLR2 and TLR4. The different expression of TLR2 and TLR4 in the various clinical types of CRS suggests that they play the certain role in the pathogenesis of CRS.

[Expression of TGF-beta1 and collagen fibers in chronic nasal-sinusitis nasal mucosa of patients].

OBJECTIVE: Explore the TGF-beta1 and collagen fibers in chronic nasal sinusitis each type and degree of expression of the normal control group and in the nasal mucosa epithelial tissue remodeling and the role of TGF-beta1 and collagen deposition relationship. METHOD: Sixty-two patients experimental group (CRSwNP of 21 cases. CRSs NP group of 15 cases. 11 cases of recurrent nasal polyps; control group 15 cases specimens for immunohistochemistry and masson collagen staining. Manual counting the number of positive cells by the Mann-Whitney U test to analyze the expression in experimental group and the control group. Experimental group and control group between the single-factor analysis of variance with a One-Way ANOVA analysis. RESULT: Experimental group and control group were expressed TGF-beta1 with collagen deposition. Which, TGF-beta1 in CRSsNP group was significantly lower than the control group (P < 0.05), CRSwNP group was significantly increased compared with CRSsNP group (P < 0.05); masson collagen staining, CRSsNP group was significantly lower than the control group (P < 0.01), recurrent nasal polyps group than in the control group was significantly increased (P < 0.05). TGF-beta1 and collagen staining masson positive correlation between (P < 0.01 ). CONCLUSION: TGF-beta1 and collagen deposi tion and chronic nasal-sinusitis tissue remodeling has its relevance. Furthermore. TGF-beta1 expression increased with excessive deposition of collagen fibers also positively correlated.