Background: Primary Sjögren’s syndrome (PSS) is associated with various histological patterns of interstitial lung disease. Although chest images and lung function studies showed that lung involvement predominantly occurs in small airways, pathological findings were not consistent with the results of high-resolution CT (HRCT) and lung function tests. Objectives: To investigate the pathological characteristics of PSS-associated interstitial lung disease (PSS-ILD) and their relationship with HRCT lung function tests. Methods: Fourteen patients diagnosed as PSS who underwent surgical lung biopsy in Peking Union Medical College Hospital from October 2000 to October 2006 were reviewed. Histopathologic findings, radiologic findings and lung function tests were analyzed. Results:The study included 13 women. The median age was 46 years. Most patients presented with dyspnea and cough. CT scans revealed bilateral ground-glass, consolidative, reticular and nodular opacities and cyst lesions. The histological patterns included nonspecific interstitial pneumonia (NSIP) cellular pattern associated with organizing pneumonia (OP), NSIP mixed pattern associated with OP, noncaseating granulomas, chronic bronchiolitis, follicular bronchiolitis, constrictive bronchiolitis, lymphocytic interstitial pneumonia associated with follicular bronchiolitis, NSIP mixed pattern associated with follicular bronchiolitis, NSIP mixed pattern coexisting with chronic bronchiolitis, OP associated with chronic bronchiolitis, and noncaseating granulomas coexisting with OP. Treatment included prednisone and cyclophosphamide. During the follow-up period (median 38 months), most patients improved or remained stable. The patient with constrictive bronchiolitis died from progression of primary disease. Conclusions: The histopathologic patterns of PSS-ILD included lung interstitial involvement and small airway involvement or both. Corticosteroid therapy combined with cyclophosphamide was administered with a favorable response in the majority of patients.

Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases.

To screen for ribosomal RNA mutants defective in peptide chain termination, we have been looking for rRNA mutants that exhibit different patterns of suppression of nonsense mutations and that do not suppress missense mutations at the same positions in the same reporter gene. The rRNA mutations were induced by segment-directed randomly mutagenic PCR treatment of a cloned rrnB operon, followed by subcloning of the mutagenesis products and transformation of strains containing different nonsense mutations in the Escherichia coli trpA gene. To date, we have repeatedly obtained only two small sets of mutations, one in the 3' domain of 16S rRNA, at five nucleotides out of the 610 mutagenized (two in helix 34 and three in helix 44), and the other in 23S rRNA at only four neighboring nucleotide positions (in a highly conserved hexanucleotide loop) within the 1.4 kb mutagenized segment. There is variety, however, in the suppression patterns of the mutants, ranging from suppression of UAG or UGA, through suppression of UAG and UGA, but not UAA, to suppression of all three termination codons. The two helices in 16S rRNA have previously been associated both physically and functionally with the decoding center of the ribosome. The 23S region is part of the binding site for the large subunit protein L11 and the antibiotic thiostrepton, both of which have been shown to affect peptide chain termination. Finally, we have demonstrated that the 23S mutant A1093, which suppresses trpA UGA mutations very efficiently, is lethal at temperatures above 36 degrees C (when highly expressed). This lethality is overcome by secondary 23S rRNA mutations in domain V. Our results suggest that specific regions of 16S and 23S rRNA are involved in peptide chain termination, that the lethality of A1093 is caused by high-level UGA suppression, and that intramolecular interaction between domains II and V of 23S rRNA may play a role in peptide chain termination at the UGA stop codon.

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Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α expression levels were examined in 81 human degenerated NP samples using real-time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1α siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by~30-fold in response to hypoxia. The expression of HIF-1α, but not HIF-2α, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1α knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1α and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression. Low back pain (LBP) is one of the most common clinical complaints. Approximately 80% of people experience LBP during their lifespan, 1 and this condition causes severe pain, disability, and heavy economic burden. Among the various causes of LBP, intervertebral disc degeneration is thought to be one of the most central causes. 2,3 The intervertebral disc consists of the central proteoglycan-rich nucleus pulposus (NP) and the surrounding fibrocartilaginous annulus fibrosis (AF) with good restoration of strength, ROM, and function. The highly absorptive proteoglycans in the NP absorb stress and maintain the structural and functional integrity of the spine. 4,5 An imbalance between NP extracellular matrix (ECM) anabolism and catabolism leads to degenerative disc disease. 6 NP cell aging or changes to the microenvironment can lead to decreased normal ECM protein synthesis (mainly type II collagen and aggrecan) and increased synthesis of ECM proteins related to fibrosis, such as type I collagen. 6 Inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, stimulate the expression of ECM catabolic enzymes, such as matrix metallopr...

BackgroundDecompression illness (DCI) is a major concern in pressure-related activities. Due to its specific prerequisite conditions, DCI is rare in comparison with other illnesses and most physicians are inexperienced in treatment. In a fishery area in northern China, during the past decade, tens of thousands of divers engaged in seafood harvesting and thousands suffered from DCI. We established a hyperbaric facility there and treated the majority of the cases.Methods and ResultsA total of 5,278 DCI cases were admitted in our facility from February 2000 through December 2010 and treated using our recompression schedules. Cutaneous abnormalities, joint and muscular pain and neurological manifestations were three most common symptoms. The initial symptom occurred within 6 h after surfacing in 98.9% of cases, with an overall median latency of 62 min. The shorter the latent time, the more serious the symptoms would be (P<0.0001). Nine cases died before recompression and 5,269 were treated using four recompression schedules, with an overall effectiveness rate of 99.3%. The full recovery rate decreased with the increase of the delay from the onset of symptoms to the treatment (P<0.0001).ConclusionsDCI presents specific occurrence rules. Recompression should be administered as soon as possible and should never be abandoned irrespective of the delay. The recompression schedules used were effective and flexible for variety conditions of DCI.

Mutations in the GTPase center of Escherichia coli 23S rRNA were characterized in vivo as UGA-specific nonsense suppressors. Some site-directed mutations did not exhibit suppressor activity and were interspersed among suppressor mutations. Our results demonstrate the involvement of the two adjacent loops of this conserved rRNA structure in UGA-dependent translation termination and, taken with previous in vitro analyses and with consideration of the crystal structure of the GTPase center RNA, indicate that nucleotides 1067, 1093, 1094, and 1095 are sites of interaction with release factor 2.

Objective: The aim of this study was to investigate the magnetic resonance (MR) features of alveolar soft-part sarcoma (ASPS). Methods: We studied 12 patients with ASPS confirmed by pathology in this retrospective study. MR features were analyzed, especially for the location, morphology, signals, and related enhanced features of the tumor vessels. Results: Flow voids were shown in the central part of the tumor on T2-weighted imaging (T2WI) in all patients; they were arrayed in a radiating mode gathered toward the center (8 cases), designated by us as vascular center-gathered syndrome (VCGS), or scattered like twigs (4 cases). The flow voids were accompanied by high signals in all patients, including tubular (6 cases) and platy (6 cases) signals. Slightly higher signals were shown in the peripheral part of the tumor in all patients. Flow voids in the peripheral part were shown in all patients, and the majority of the flow voids surrounded the tumor (8 cases). The vessels around the tumor in 9 patients showed high signals, and the majority of the vessels were located at the superior and inferior poles (8 cases). 6 patients underwent enhanced scanning, including moderate (5 cases) and significant enhancement (1 case). Conclusion: Low signals of radiating flow voids accompanied by high signals of slow blood flow or blood sinuses in the center part have high significance for the diagnosis of ASPS.