Drug-induced hypersensitivity syndrome related to piperacillin-tazobactam: a case report and review of the literature.

Allergic reactions to drugs caused by piperacillin-tazobactam are common in clinical practice. However, we also found a few cases of drug-induced hypersensitivity syndrome (DiHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by piperacillin-tazobactam in our clinical work. We report a case of a 60-year-old female patient who was treated with piperacillin-tazobactam anti-infective therapy after the diagnosis of hematogenous lung abscess, developed fever, rash, and blood abnormalities after 26 days of application, and was later diagnosed as DIHS, which was improved after the administration of glucocorticoid and anti-allergic drugs. In addition, we also retrospectively analyzed 17 cases of DiHS caused by piperacillin-tazobactam from the PubMed databases between March 1980 and September 2023. The majority of the patients had an incubation period of more than 14 days, and the common clinical features included elevated eosinophil count/percentage, fever, rash, liver damage, and lymph node enlargement. After treatment with topical or systemic glucocorticoids, 16 of the 17 patients improved and one died because of the underlying condition. The clinical features of DiHS were diverse and included a long incubation period, skin rash, elevated eosinophils, and impaired organ function. Since some patients have atypical clinical features, clinicians should raise awareness of the disease, recognize these features early, and treat them promptly.

Acute pneumonia due to Tropheryma whipplei diagnosed by metagenomic next-generation sequencing and pathology: A case report.

Tropheryma whipplei (TW) is a rod-shaped, gram-positive bacterium that, when chronically infects humans, can lead to multi-system pathologies, including joint pain, abdominal pain with diarrhea and weight loss, myocarditis, pericarditis, and neurologic inflammation. Moreover, acute infections can lead to bronchopulmonary infections, bacteraemia, and acute diarrhea. However, fewer cases of acute pneumonia due to TW have been reported, and this diagnosis is not well founded. Herein, we report a case of acute pneumonia caused by a TW infection. The patient, a middle-aged man, underwent bronchoscopic alveolar lavage, and the metagenomic next-generation sequencing of the lavage fluid suggested TW infection. A lung puncture biopsy tissue specimen was also positive based on periodic acid-Schiff staining. After confirming the diagnosis, the patient was administered ceftriaxone for anti-infection treatment, improving clinical symptoms and lung imaging results. Therefore, in cases where conventional anti-infective treatment is ineffective for patients with acute pneumonia, we should consider the possibility of TW infection, conduct prompt pathogenetic examination, and provide timely treatment after diagnosis to improve overall patient prognosis.

Paraneoplastic focal segmental glomerulosclerosis associated with gastrointestinal stromal tumor with cutaneous metastasis: A case report.

BACKGROUND: Gastrointestinal stromal tumor (GIST) with cutaneous metastasis is very rare. As a result, cutaneous GISTs have not been well characterized. Focal segmental glomerulosclerosis (FSGS) is also a rare symptom among paraneoplastic nephritic syndromes (PNS). CASE SUMMARY: In this case report, we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS, for whom symptomatic treatment was ineffective, but clinical remission was achieved after surgery. Moreover, the patient has a missense mutation in NPHP4, which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random. CONCLUSION: This is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.

Hepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss.

Patients with Alzheimer's disease (AD) often have lower bone mass than healthy individuals. However, the mechanisms underlying this change remain elusive. Previously, we found that Tg2576 mice, an AD animal model that ubiquitously expresses Swedish mutant amyloid precursor protein (APPswe), shows osteoporotic changes, reduced bone formation, and increased bone resorption. To understand how bone deficits develop in Tg2576 mice, we used a multiplex antibody array to screen for serum proteins that are altered in Tg2576 mice and identified hepcidin, a master regulator of iron homeostasis. We further investigated hepcidin's function in bone homeostasis and found that hepcidin levels were increased not only in the serum but also in the liver, muscle, and osteoblast (OB) lineage cells in Tg2576 mice at both the mRNA and protein levels. We then generated mice selectively expressing hepcidin in hepatocytes or OB lineage cells, which showed trabecular bone loss and increased osteoclast (OC)-mediated bone resorption. Further cell studies suggested that hepcidin increased OC precursor proliferation and differentiation by downregulating ferroportin (FPN) expression and increasing intracellular iron levels. In OB lineage cells, APPswe enhanced hepcidin expression by inducing ER stress and increasing OC formation, in part through hepcidin. Together, these results suggest that increased hepcidin expression in hepatocytes and OB lineage cells in Tg2576 mice contributes to enhanced osteoclastogenesis and trabecular bone loss, identifying the hepcidin-FPN-iron axis as a potential therapeutic target to prevent AD-associated bone loss.

Comparison of airflow characteristics after Draf â ¢ frontal sinus surgery and normal person by numerical simulation.

Draf III frontal sinus surgery is confirmed as an effective surgical treatment for refractory sinusitis and frontal sinus tumors, etc. Although it has been reported to improve symptoms and reduce the recurrence rate of polyps significantly, the study of airflow characteristics in frontal sinus after Draf III is still rare, especially compared with normal person. This study was designed to describe the airflow characteristics of frontal sinus after Draf III procedure and differences compared with normal subject. One patient with refractory sinusitis received Draf III procedure15 months ago, and one normal person were selected retrospectively. The two subjects reported no discomfort and no abnormalities in their paranasal sinus within computed tomography scans. Computational fluid dynamics and numerical simulation calculation was performed with the finite volume method. The quantitative indexes of airflow in the frontal sinus of Draf III and normal subjects were achieved. Areas of relatively high-pressure and high wall shear stress located in a posterior part of frontal sinus ostium in both models. Inside frontal sinus, pressure and velocity of flow between Draf III and normal models were statistically significant differences (p < 0.01) after analyzed by Mann-Whitney U test. But airflow pattern of each section in frontal sinus was basically the same. Draf III sinus surgery is able to achieve nasal airflow patterns similar to those of normal person. Although values of airflow pressure and velocity were different from normal person, patients could have no subjective discomfort after surgery. "Frontal T" structure is a key anatomical site interacted with airflow to be an important cause of postoperative edema after Draf III procedure.

The role of RORα in salivary gland lesions in patients with primary Sjögren's syndrome.

BACKGROUND: The orphan nuclear receptors retinoic acid-related receptor α and γt (RORα and RORγt) are critical in the development of T helper 17 (Th17) cells, and ROR-specific synthetic ligands have proven efficacy in several mouse models of autoimmunity. However, the pathological significance of RORα in primary Sjögren's syndrome (pSS) remains to be elucidated. The present study was designed to clarify the significance of RORα in the pathogenesis of pSS. METHODS: RORα expression in the labial salivary gland (LSG) was determined by immunohistochemical analysis using a quantitative scoring system in 34 patients with pSS. The correlation between RORα expression in LSGs and the focus score (FS) was determined, and Th17 and IL-17 receptor A (1L-17RA) levels in LSGs were determined. To investigate the effect of RORs and the therapeutic potential of targeting RORs in pSS, we administered SR1001, a selective RORα/γt inverse agonist, to non-obese diabetic (NOD) mice. RESULTS: The expression of RORα was significantly increased in LSGs of patients with pSS and intensified with disease stage/FS, showing a similar increasing trend with IL-17A and IL-17RA. SR1001 significantly improved salivary gland secretory function and relieved sialadenitis in treated mice. CONCLUSION: Our data reveal the importance of RORα in controlling pathologic lymphocytic infiltration of the salivary glands and suggest that RORα may be a druggable target in treating pSS.

YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating ß-catenin signaling.

YAP (yes-associated protein) is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP's function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis. YAP is selectively expressed in osteoblast (OB)-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with ß-catenin and is necessary for maintenance of nuclear ß-catenin level and Wnt/ß-catenin signaling. Expression of ß-catenin in YAP-deficient BMSCs (bone marrow stromal cells) diminishes the osteogenesis deficit. These results thus identify YAP-ß-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.

The intranasal endoscopic removal of schwannoma of the pterygopalatine and infratemporal fossae via the prelacrimal recess approach.

OBJECTIVE: This study was undertaken to analyze the results of a novel surgical method-the endoscopic prelacrimal recess approach (PLRA)-in patients with tumors involving the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). The surgical technique and indications for this approach are also discussed. METHODS: The authors analyzed data from 7 cases involving patients who underwent resection of PPF and ITF tumors by means of the endoscopic PLRA from 2004 to 2013. Preoperative and postoperative imaging studies were available in all cases and were reviewed. The surgical specimens were all confirmed to be schwannomas. RESULTS: All tumors were completely resected via endoscopic PLRA. There were no recurrences noted over a 28-month follow-up period. In 4 cases, the patients experienced postoperative facial numbness during the first two weeks after surgery, which gradually lessened thereafter. One patient continued to have mild facial numbness at most recent follow-up. The numbness had fully resolved in the other 3 cases. CONCLUSIONS: The intranasal endoscopic removal of schwannoma from PPF and ITF via PLRA can spare the whole lateral nasal wall, resulting in a reduction in morbidity. This is a novel minimally invasive surgical method for PPF and ITF tumors.

[Ecological adaptability evaluation of peanut cultivars based on biomass and nutrient accumulation].

To identify the good peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability, 19 selected peanut cultivars were planted in the low champaign area and piedmont plain area of Hebei Province. By using principal component analysis, the adaptability of these 19 cultivars was evaluated for different ecological regions through comparing their 16 main traits including biomass and nutrient parameters. According to the critical value of principal component (>1.0), the 16 biomass and nutrient characteristics were integrated into 4 principal components which accounted for 85% of the original information. The results indicated that there were obvious differences in yield and nutrient use efficiency for the peanut cultivars in different ecological regions. The 19 peanut cultivars were classified into 2 groups according to their ecological adaptability, and the cultivars from the group with wide adaptability could further be divided into 3 categories according to their yield and nutrient use efficiency. Among these cultivars, Yuhua 9719, Jihua 0212-4, Weihua 10, Yuhua 15, Puhua 28 and Jihua 10 were selected as the better peanut cultivars with the properties of high yield, high nutrient use efficiency and wide adaptability.

Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

Patients of Alzheimer's disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis: A Preliminary Report.

BACKGROUND: Adenoid hypertrophy (AH) is associated with pediatric chronic rhinosinusitis (pCRS), but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis (CRS), including antimicrobial peptides and pattern recognition receptors (PRRs). The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. METHODS: Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS: Human ß-defensin (HBD) 2 and 3, surfactant protein (SP)-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain (NOD)-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-κB (NF-κB). RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. RESULTS: The relative expression of SP-D in adenoidal epithelium of pCRS group was significantly lower than that in AH group (pCRS 0.73 ± 0.10 vs. AH 1.21 ± 0.15; P = 0.0173, t = 2.654). The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. CONCLUSIONS: Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process of pCRS.

[Clinical implication of global osteitis score system and its role in evaluation of osteitis of chronic rhinosinusitis].

OBJECTIVE: To investigate the clinical application of Global Osteitis Score System (GOSS). To determine the association between GOSS, Lund-Mackay scores and Lund-Kennedy scores and to investigate the incidence of osteitis in patients with chronic rhinosinusitis (CRS). METHODS: Three hundreds and thirty-four patients with CRS were enrolled prospectively in a large tertiary referral center. The paranasal sinus bone Hounsfield unit (HU), thickness, scope were measured by PHILIPS MxLiteView software. Nasal endoscopy Lund-Kennedy score was analyzed in all patients. Sinus CT scans of all patients were analyzed for Lund-Mackay score and for osteitis using the GOSS. Association between GOSS and Lund-Mackay, Lund-Kennedy was examined. RESULTS: The incidence of osteitis in patients with chronic rhinosinusitis was from 33.83% to 53.89%. Average GOSS score of osteitis was 7.51 ± 7.27. The highest incidences of osteitis were in the maxillary and anterior ethmoid sinuses. The left anterior ethmoid sinuses was 37.2%. The right anterior ethmoid sinuses was 32.8%. The left maxillary sinuses was 46.1%. The right maxillary sinuses was 42.2%. Global osteitis score were significantly correlated with Lund-Mackay and Lund-Kennedy scores (r value were 0.497 and 0.409 respectively, all P < 0.001). CONCLUSIONS: GOSS can define and evaluate the extent and the severity of osteitis in patients with CRS by using CT, and can also reflect the extent and the severity of CRS.

Intranasal endoscopic prelacrimal recess approach to maxillary sinus.

BACKGROUND: The inferior turbinate (IT) and nasolacrimal duct (NLD) are often sacrificed while managing the diffuse lesion of maxillary sinus (MS). We report a new approach to MS without ablation of NLD and IT. METHODS: This retrospective study enrolled 19 hospitalized patients (aged from 42 to 68 years) who underwent endoscopic sinus surgery between 2003 and 2008. Twelve patients had inverted papilloma (IP), two had nasal polyps, two had Kubo's postoperative cyst of MS, one had recurrent bone cyst of maxilla, one had dentigerous cyst and one had bleeding of internal maxillary artery secondary to Caldwell-Luc operation respectively. Two IP patients were excluded from this group since the follow-up time was less than 12 months. The NLD was dissected after removing the anterior bony portion of nasal lateral wall. The prelacrimal recess approach (PLRA) to MS was established when IT-NLD flap was raised medially. The flap was repositioned when MS lesion was removed. RESULTS: All the 17 patients had unilateral lesions. Ten MS IP patients were at the T3 Krouse stage. The follow-up ranged from 7 to 60 months. No recurrence was seen in 16 patients. Only one IP patient had a local recurrence in MS. All of them had no any complications. CONCLUSION: The diffuse or severe diseases of MS may be the potential indications for PLRA.

[Removal of Schwannoma in the pterygopalatine and infratemporal fossa via endoscopic prelacrimal recess approach].

OBJECTIVE: To sum up and analyze the results of surgical removal of Schwannoma in the pterygopalatine and infratemporal fossa (PPF and ITF) through postero-lateral wall via prelacrimal recess approach (PLRA). The surgical technique and indications were presented and discussed. METHODS: Six patients aged from 29-59 year-old with Schwannoma in the PPF and ITF, who received the tumor resection via PLRA under endoscope, were enrolled in this paper. Three were female and 3 were male. All of them received preoperative CT and MRI. The PPF and ITF were approached via prelacrimal recess endoscopically under general anesthesia. Schwannoma was histopathologically confirmed after surgery. The postoperative periodical CT and MRI follow up was conducted. RESULTS: The tumors were removed completely in these 6 patients. No recurrence was found during 19.3 months follow up on the average. Three patients had obvious numbness in the V2 innervation area 1 or 2 weeks after operation and disappeared afterwards. Only 1 patient had mild altercation numbness at the end of follow up. CONCLUSIONS: Schwannoma involved PPF and ITF can be removed endoscopically via PLRA. The lateral wall of nasal cavity might be kept intact. It is a novel minimally transnasal invasive approach to PPF and ITF with less damage and complications.

[CT and MRI diagnosis of lesions in unilateral maxillary sinus].

OBJECTIVE: To study the CT and MRI findings of lesions in unilateral maxillary sinus, and to compare the effect of CT and MRI in the differential diagnosis of lesions in unilateral maxillary sinus. METHODS: Retrospective analysis of CT and contract-enhanced MRI imaging data from 34 patients with lesions in unilateral maxillary sinus which were diagnosed by endoscopic sinus surgery and postoperative pathology. The CT and contract-enhanced MRI's value in the differential diagnosis in lesions in unilateral maxillary sinus was analysed. RESULTS: All 34 patients had unilateral maxillary sinus lesions. On CT: soft tissue density shadow in the unilateral maxillary sinus was found in all 34 cases. Five cases showed spot high density with thickening bone in the maxillary sinus wall. Eleven cases showed expansion of the opening of maxillary sinuses. Two cases showed broken lateral wall of nasal cavity . One case showed soft tissue density shadow in the maxillary sinus with curve edge with high density shadow which had a tooth shadow in it. Other 14 cases showed only soft density shadow in the maxillary sinuses. On MRI: all 34 cases revealed lower signals on T1WI compared to gray matter. Little loss signal were found in the inner of the maxillary sinus fungal balls on T1WI. Enhanced MR imaging showed no enhanced in nasal sinusitis, sinus cysts and polyp of posterior naris. In homogenous enhancing and "the cerebral convolution sign" were found in the hemorrhagic and necrotic nasal polyp, the nasal inverted papilloma and the malignant tumor cases. Higher signals were seen in the nasal sinusitis, fungal balls and the polyp of posterior naris cases on T2WI. In homogenous signal with different levels were found in the hemorrhagic and necrotic nasal polyp, the nasal inverted papilloma and the malignant tumor cases on T2WI. CONCLUSIONS: CT and MRI examination are important in the diagnosis of the unilateral maxillary sinus lesions. Both CT and MRI had more differential diagnostic value in the unilateral maxillary sinus lesions than only CT used.

[Analysis of follow-up outcomes of endoscopic modified Lothrop procedure].

OBJECTIVE: To sum up the follow-up outcomes of endoscopic modified Lothrop procedure (EMLP) and retrospectively analyze the indications, methods and prognostic factors of EMLP. METHODS: The collected data of 73 cases who received EMLP with frontal sinus diseases were analyzed in this paper. The mean age was 45.6 (ranging from 14 to 72 years). There were 52 males and 21 females. Only patients with follow-up time greater or equal to 6 months were included. Paranasal sinus CT scan was adopted for all cases and MRI for tumor patients. All patients were followed under endoscope. RESULTS: There were 21 inverted papilloma in the frontal sinus, 16 chronic sinusitis with asthma, 12 frontal sinusitis, 9 chronic sinusitis with or without polyps, 7 osteoma of the frontal sinus, 4 frontal mucocele, 3 allergic fungal sinusitis and 1 congenital encephalocele. Sixty-one cases had prior surgical history (1.8 times on the average). Their mean follow-up was 25.0 months, (ranging from 6 to 122 months). At the end of follow-up, 44 cases (60.3%) had well opened frontal drainage pathway. Twenty-five (34.2%) was re-stenosed and 4 (5.5%) closed. Seven cases (9.6%) underwent revision surgeries. There were no surgical complications. CONCLUSIONS: EMLP is an effective and salvage procedure in dealing with tumor of frontal sinus and recurrent frontal sinusitis. Combined with medical treatment, EMLP will have a better results for chronic sinusitis with or without polyps and asthma. The degree of diseases, mucosal loss, anatomic variability and prior surgeries are important prognostic factors.

[Clinical application of Draf IIb frontal sinusotomy and it's modified procedures].

OBJECTIVE: To summarize the follow-up outcomes of Draf IIb frontal sinusotomy and it's modified procedures, and to discuss the surgical indications and prognostic factors. METHODS: Thirty-two patients treated between 2004 and 2010 were enrolled in this study. There were 15 patients for recurrent frontal inverted papilloma (IP), 6 for mucocele, 4 for recurrent frontal sinusitis, 3 for osteoma, 2 for meningoencephalocele with cerebrospinal fluid rhinorrhea, 1 for meningoencephalocele alone and 1 for acute frontal sinusitis. All patients underwent preoperative paranasal sinus computed tomography (CT) scans. Patients with tumor accepted magnetic resonance imaging (MRI). The patients with meningoencephalocele and cerebrospinal fluid rhinorrhea received magnetic resonance cisternography (MRC). The Draf IIb frontal sinusotomy and it's modified Draf IIb-1-3 procedures were applied endoscopically under general anesthesia mainly by high speed bur and power system. The postoperative CT scan was obtained as a base line for follow-up 1 week after the operation. Postoperative follow-up was performed under endoscope. RESULTS: Among 19 cases of Draf IIb, 12 were recurrent IP of frontal sinus, 4 were mucocele, 2 were recurrent frontal sinusitis and 1 were osteoma. Five cases received Draf IIb-1, 2 for each recurrent IP of frontal sinus and recurrent frontal sinusitis and 1 for osteoma. Six cases received Draf IIb-2, 3 for meningoencephalocele, 1 for each IP, acute frontal sinusitis and osteoma. Two cases received Draf IIb-3 were mucocele. The follow-up ranged from 8 to 73 months. Twenty-two cases of the frontal nepostium were widely opened, 7 were stenosis and 3 were closed. Revision surgery was seen in 2 cases with IP. All of them had no complications. CONCLUSIONS: The Draf IIb frontal sinusotomy and it's modified procedures are suitable for complex frontal sinus disease, which can be selected according to pathological and anatomical features, and have a good prospect for clinical application.

Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins.

Respiratory syncytial virus (RSV) infection is associated with serious lung disease in infants and immunocompromised individuals and is linked to development of asthma. In mice, acute RSV infection causes airway hyperresponsiveness (AHR), inflammation, and mucus hypersecretion. Infected cells induce complement activation, producing the anaphylatoxin C3a. In this paper, we show RSV-infected wild-type mice produce Th17 cytokines, a response not previously associated with viral infections. Mice deficient in the C3aR fail to develop AHR following acute RSV infection, and production of Th17 cytokines was significantly attenuated. Tachykinin production also has been implicated in RSV pathophysiology, and tachykinin receptor-null mice were similarly protected from developing AHR. These animals were also deficient in production of Th17 cytokines. Tachykinin release was absent in mice deficient in C3aR, whereas C3a levels were unchanged in tachykinin receptor-null animals. Thus, our data reveal a crucial sequence following acute RSV infection where initial C3a production causes tachykinin release, followed by activation of the IL-17A pathway. Deficiency of either receptor affords protection from AHR, identifying two potential therapeutic targets.

APPswe/Aß regulation of osteoclast activation and RAGE expression in an age-dependent manner.

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid ß peptide (Aß) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aß in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter, exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aß oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL-induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aß, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aß and RAGE as common denominators for both AD and osteoporosis.

[Juvenile nasopharyngeal angiofibroma: endoscopic surgery and follow-up results].

OBJECTIVE: To present the changes of surgical approaches for the resection of juvenile nasopharyngeal angiofibromas (JNA) and the follow-up results. METHODS: The clinical records of 59 patients with JNA treated under endoscope between 2002 and 2009 were reviewed retrospectively. The patients were divided into two groups: Group A (Radkowski I a-II b) and Group B (Radkowsik II c-III b). The tumor stages, feeding vessels, operating time, complications and recurrence were observed and recorded. RESULTS: There were 7 patients with stage I a, 3 patients with stage I b, 5 patients with stage II a, 6 patients with stage II b, 4 patients with stage II c, 23 patients with stage III a, 11 patients with stage III b. The average age at diagnosis in Group A (21 cases) was 23.9 years old. The average operating time was (106.0 +/- 43.7) min. The follow-up ranged from 3 months to 74 months (median 36 months) except for 3 missing cases. The average age at diagnosis in Group B (38 cases) was 16.2 years old and the average operating time was (152.9 +/- 58.0) min. The follow-up ranged from 3 months to 87 months (median 25 months) except for 5 missing cases. During follow-up, 6 patients in group B recurred. Infarction of thalamencephalon happened in 1 patient in group B who recovered totally afterwards. The difference in operating time between two groups was statistically significant (t = -3.232, P = 0.002). The life table was used to evaluate the survival curves and Log-rank test showed that the difference of recurrent time between two groups was statistically significant (P = 0.03). CONCLUSIONS: The key techniques to remove tumor are bleeding control, drilling-out the bone that tumor invaded. Transpterygoid or posterolateral wall of maxillary sinus approach are recommended for tumors that extend to infratemporal fossa. Small and intermediate-sized JNA which have no deep invasion of skull base (RadkowskiIa-II b) have a low morbidity. JNA at Radkowski stage IIc and above have residual and recurrent risk.