Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Association between Dietary Inflammatory Index and Risk of Colorectal Adenomatous Polyps in Kashgar Prefecture of Xinjiang, China.

Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.

Is the pelvic incidence a determinant factor for kyphosis curve patterns of ankylosing spondylitis patients?

To investigate the influence of pelvic incidence (PI) on the kyphosis curve patterns and clinical outcomes in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis and to construct a classification of AS according to the PI value for surgical decision-making. 107 AS patients underwent single-level lumbar pedicle subtraction osteotomy (PSO) and finished a minimal of 2-year follow-up. All patients were divided into three groups: low PI (PI ≤ 40°), moderate PI (40° < PI ≤ 60°), and high PI (PI > 60°). Standing lateral radiographs were taken to evaluate the location of kyphotic apex, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (SVA), spino-sacral angle (SSA), global kyphosis (GK), PI, sacral slope (SS), and pelvic tilt (PT). Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate quality of life. Before surgery, a significant difference was shown in the average LL and the mean GK in high PI group was the largest among the three groups. Correction of SVA, GK and LL in high PI group was the smallest among the three group. No significant difference in clinical outcomes was found among the three groups before surgery and at the final follow-up. Regarding the preoperative sagittal profile, the kyphosis curve pattern of moderate PI group is similar to that of low PI group. For AS patients in these two groups, harmonious sagittal alignment can be restored by a single-level PSO. However, the sagittal imbalance is insufficiently realigned by a single-level PSO in a patient with high PI.

Surgical Navigation System for Hypertensive Intracerebral Hemorrhage Based on Mixed Reality.

Hypertensive intracerebral hemorrhage (HICH) is an intracerebral bleeding disease that affects 2.5 per 10,000 people worldwide each year. An effective way to cure this disease is puncture through the dura with a brain puncture drill and tube; the accuracy of the insertion determines the quality of the surgery. In recent decades, surgical navigation systems have been widely used to improve the accuracy of surgery and minimize risks. Augmented reality- and mixed reality-based surgical navigation is a promising new technology for surgical navigation in the clinic, aiming to improve the safety and accuracy of the operation. In this study, we present a novel multimodel mixed reality navigation system for HICH surgery in which medical images and virtual anatomical structures can be aligned intraoperatively with the actual structures of the patient in a head-mounted device and adjusted when the patient moves in real time while under local anesthesia; this approach can help the surgeon intuitively perform intraoperative navigation. A novel registration method is used to register the holographic space and serves as an intraoperative optical tracker, and a method for calibrating the HICH surgical tools is used to track the tools in real time. The results of phantom experiments revealed a mean registration error of 1.03 mm and an average time consumption of 12.9 min. In clinical usage, the registration error was 1.94 mm, and the time consumption was 14.2 min, showing that this system is sufficiently accurate and effective for clinical application.

Augmented reality surgical navigation system based on the spatial drift compensation method for glioma resection surgery.

BACKGROUND: The number of patients who suffer from glioma has been increasing, and this malignancy is a serious threat to human health. The mainstream treatment for glioma is surgical resection; therefore, accurate resection can improve postoperative patient recovery. PURPOSE: Many studies have investigated surgical navigation guided by mixed reality, with good outcomes. However, the limitations of mixed reality, such as spatial drift caused by environmental changes, limit its clinical application. Therefore, we present a mixed reality surgical navigation system for glioma resection. Preoperative information can be fused precisely with the real patient with the spatial compensation method to achieve clinically suitable accuracy. METHODS: A head-mounted device was used to display virtual information, and a markerless spatial registration method was applied to precisely align the virtual anatomy with the real patient preoperatively. High-accuracy preoperative and intraoperative movement and spatial drift compensation methods were used to increase the positional accuracy of the mixed reality-guided glioma resection system when the patient's head is fixed to the bed frame. Several experiments were designed to validate the accuracy and efficacy of this system. RESULTS: Phantom experiments were performed to test the efficacy and accuracy of this system under ideal conditions, and clinical tests were conducted to assess the performance of this system in clinical application. The accuracy of spatial registration was 1.18 mm in the phantom experiments and 1.86 mm in the clinical application. CONCLUSIONS: Herein, we present a mixed reality-based multimodality-fused surgical navigation system for assisting surgeons in intuitively identifying the glioma boundary intraoperatively. The experimental results indicate that this system has suitable accuracy and efficacy for clinical usage.

Does the Level of Pedicle Subtraction Osteotomy Affect the Surgical Outcomes in Ankylosing Spondylitis-Related Thoracolumbar Kyphosis With the Same Curve Pattern?

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effect of pedicle subtraction osteotomy (PSO) level on the surgical outcomes in ankylosing spondylitis-related thoracolumbar kyphosis with the same curve pattern. METHODS: ankylosing spondylitis (AS) patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO between March 2006 and June 2017, were retrospectively reviewed. Criteria for curve-matched thoracolumbar kyphosis were: (1) have same level of preoperative apex (pre-apex); (2) have similar global kyphosis (GK, the angle between the superior/inferior endplate of the maximally tilted upper and lower end vertebra) (the difference of GK less than 15˚). The radiographic parameters measured were sagittal vertical axis (SVA, the horizontal distance between the C7 plumb line and the posterosuperior corner of the S1), GK, thoracic kyphosis (TK, the angle between the T5 superior endplate and the T12 inferior endplate), lumbar lordosis (LL, the angle between the L1 and S1 superior endplate), sacral slope (SS, the angle between the sacral endplate and the horizontal line), pelvic tilt (PT, the angle between the vertical and the line joining the midpoint of the sacral plate and hip axis), and pelvic incidence (PI, the angle between the line vertical to the superior margin of S1 and the line connecting the sacral plate midpoint with the hip joint axis). All of these parameters and health-related quality of life (HRQoL, evaluated by preoperative and the last follow-up questionnaires including ODI and VAS) scores were collected before surgery and at the last follow-up. According to their osteotomy level, patients were devided into 2 sub-groups (L1 group and L2 group), and differences of these mentioned parameters between 2 groups were compared. RESULTS: 26 curve-matched patients were recruited with a mean follow-up of 37.2 months. All patients improved significantly after surgery in HRQoL scores (VAS 1.6 vs 5.4, P < 0.001; ODI 11.9 vs 26.4, P < 0.001). Except for TK and PI, those radiographic parameters were also observed to be significantly changed after surgery. Compared to L2 group, PSO at L1 may have larger correction of TK (ΔTK -6.8 vs -0.3°, P = 0.164), PI (ΔPI -7.4 vs -0.7°, P = 0.364) and smaller correction of SVA (ΔSVA -105.3 vs -128.5 mm, P = 0.096), LL (ΔLL -31.1 vs -43.0°, P = 0.307) and SS (ΔSS 6.9 vs 12.2°, P = 0.279) but had no statistical significance. CONCLUSION: The results of this investigation showed that in AS-related thoracolumbar kyphosis patients with the same curve pattern, the different levels of osteotomy had little effect on the improvement of surgical outcomes. However, osteotomy at L2 is more likely to obtain a larger correction of SVA compared to osteotomy at L1.

A neuroendoscopic navigation system based on dual-mode augmented reality for minimally invasive surgical treatment of hypertensive intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Hypertensive intracerebral hemorrhage is characterized by a high rate of morbidity, mortality, disability and recurrence. Neuroendoscopy has been utilized for treatment as an advanced technology. However, traditional neuroendoscopy allows professionals to see only tissue surfaces, and the field of vision is limited, which cannot provide spatial guidance. In this study, an AR-based neuroendoscopic navigation system is proposed to assist surgeons in locating and clearing hematoma. METHODS: The neuroendoscope can be registered through the vector closed loop algorithm. The single-shot method is designed to register medical images with patients precisely. Real-time AR is realized based on video stream fusion. Dual-mode AR navigation is proposed to provide comprehensive guidance from catheter implantation to hematoma removal. A series of experiments is designed to validate the accuracy and significance of this system. RESULTS: The average root mean square error of the registration between medical images and patients is 0.784 mm, and the variance is 0.1426 mm. The pixel mismatching degrees are less than 1% in different AR modes. In catheter implantation experiments, the average error of distance is 1.28 mm, and the variance is 0.43 mm, while the average error of angles is 1.34°, and the variance is 0.45°. Comparative experiments are also conducted to evaluate the feasibility of this system. CONCLUSION: This system can provide stereo images with depth information fused with patients to guide surgeons to locate targets and remove hematoma. It has been validated to have high accuracy and feasibility.

Expression and Tumor-Promoting Effect of Tyrosine Phosphatase Receptor Type N (PTPRN) in Human Glioma.

Tyrosine phosphatase receptor type N (PTPRN) plays an important role in the regulation of the secretion pathways of various neuroendocrine cells. Moreover, PTPRN was demonstrated to play a crucial role in the initiation and progression of the signalling cascade regulating cell function. In this study, fifty-seven glioma patients were enrolled for clinical and prognostic analyses. The cell phenotype was determined by cell proliferation and migration assays. RNA-seq, co-IP and mass spectrometry were used to study the molecular mechanism of the effects of PTPRN on cell proliferation and metastasis. The result showed that High expression of PTPRN indicated a poor prognosis of high-grade glioma. PTPRN downregulation reduced the proliferation and migration of glioma cells, and PTPRN overexpression induced the proliferation and migration of glioma cells. PTPRN knockdown decreased tumor growth in a mouse xenograft model. Effect of PTPRN knockdown on the transcriptome was studied in U87 glioma cells. PTPRN activated the PI3K/AKT pathway by interacting with HSP90AA1. In conclusion, PTPRN is an important proliferation- and metastasis-promoting factor. Reducing the expression of PTPRN in glioma cells can be used as a potential therapeutic strategy.

[Detection of respiratory pathogens and clinical features in 225 children with acute exacerbation of bronchial asthma].

OBJECTIVE: To investigate the respiratory pathogens and clinical features in children with acute exacerbation of bronchial asthma. METHODS: Nasopharyngeal swabs were collected from 225 children with acute exacerbation of bronchial asthma, aged <14 years, who attended the outpatient service or were hospitalized from August 2017 to August 2019. Quantitative real-time PCR was used to detect 12 pathogens, i.e., respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus A (IFVA), influenza virus B (IFVB), parainfluenza virus types 1-3 (PIV1-3), human metapneumovirus (HMPV), adenovirus (ADV), Bordetella pertussis (BP), Chlamydia pneumoniae (CP), and Mycoplasma pneumoniae (MP). RESULTS: The overall detection rate of virus was 46.2% (104/225), and 7 kinds of viruses were detected, i.e., HRV (19.6%, 44/225), ADV (16.0%, 36/225), IFVB (5.8%, 13/225), RSV (4.9%, 11/225), IFVA (3.6%, 8/225), PIV3 (1.8%, 4/225), and HMPV (0.4%, 1/225). Of all pathogens, BP had the highest detection rate of 28.4% (64/225), and the detection rates of MP and CP were 16.4% (37/225) and 0.4% (1/225), respectively. The mild exacerbation group had a higher detection rate of BP than the severe exacerbation group (P<0.05), while the severe exacerbation group had significantly higher detection rates of RSV and MP than the mild exacerbation group (P<0.05). There were significant differences in the proportion of children with paroxysmal cough, spasmodic cough, fever, lung rales and abnormal lung imaging findings among the simple BP infection, simple virus infection and simple MP infection groups (P<0.05). CONCLUSIONS: BP, HRV, and MP are common respiratory pathogens detected in children with acute exacerbation of bronchial asthma, and respiratory virus infection is an important pathogen of acute exacerbation of asthma in children. Acute exacerbation of asthma caused by different pathogens has different clinical features and severities.

Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer.

PURPOSE: The recent emergence of radioligand therapies for cancer treatment has increased enthusiasm for developing new theranostic strategies coupling both imaging and cytotoxicity in the same entity. In this study, we evaluated whether CUB domain containing protein 1 (CDCP1), a single-pass transmembrane protein highly overexpressed in diverse human cancers, might be a target for cancer theranostics. EXPERIMENTAL DESIGN: The ectodomain of CDCP1 was targeted using radiolabeled forms of 4A06, a potent and specific recombinant human antibody that we developed. Imaging and antitumor assessment studies were performed in animal models of pancreatic cancer, including two patient-derived xenograft models we developed for this study. For antitumor assessment studies, the endpoints were death due to tumor volume >3,000 mm3 or ≥20% loss in body weight. Specific tracer binding or antitumor effects were assessed with an unpaired, two-tailed Student t test and survival advantages were assessed with a log rank (Mantel-Cox) test. Differences at the 95% confidence level were interpreted to be significant. RESULTS: 89Zr-4A06 detected a broad dynamic range of full length or cleaved CDCP1 expression on seven human pancreatic cancer tumors (n = 4/tumor). Treating mice with single or fractionated doses of 177Lu-4A06 significantly reduced pancreatic cancer tumor volume compared with mice receiving vehicle or unlabeled 4A06 (n = 8; P < 0.01). A single dose of 225Ac-4A06 also inhibited tumor growth, although the effect was less profound compared with 177Lu-4A06 (n = 8; P < 0.01). A significant survival advantage was imparted by 225Ac-4A06 (HR = 2.56; P < 0.05). CONCLUSIONS: These data establish that CDCP1 can be exploited for theranostics, a finding with widespread implications given its breadth of overexpression in cancer.

Does relocation of the apex after osteotomy affect surgical and clinical outcomes in patients with ankylosing spondylitis and thoracolumbar kyphosis?

OBJECTIVE: Relocation of the apex is often found in patients with ankylosing spondylitis (AS)-associated thoracolumbar/lumbar kyphosis after corrective surgery. This study evaluates the influence of different postoperative apex locations on surgical and clinical outcomes of osteotomy for patients with AS and thoracolumbar kyphosis. METHODS: Sixty-two patients with a mean age of 34.6 ± 9.7 years (range 17-59 years) and a minimum of 2 years of follow-up, who underwent 1-level lumbar pedicle subtraction osteotomy for AS-related thoracolumbar kyphosis, were enrolled in the study, as well as 62 age-matched healthy individuals. Patients were divided into 2 groups according to the postoperative location of the apex (group 1, T8 or above; group 2, T9 or below). Demographic data, radiographic measurements (including 3 postoperative apex-related parameters), and clinical outcomes were compared between the 2 groups preoperatively, postoperatively, and at the last follow-up. Furthermore, a subgroup analysis was performed among patients with a postoperative apex located at T6-11 and postoperatively the entire AS cohort was compared with normal controls regarding the apex location of the thoracic spine. RESULTS: In the majority of the enrolled patients, the apex location changed from T12-L2 preoperatively to T6-9 postoperatively. The sagittal vertical axis (SVA) differed significantly both postoperatively (25.7 vs 59.0 mm, p = 0.001) and at the last follow-up (34.6 vs 59.9 mm, p = 0.003) between the 2 groups, and the patients in group 1 had significantly smaller horizontal distance between the C7-vertical line and the apex (DCA) than the patients in group 2 (67.5 vs 103.7 mm, p = 0.001). Subgroup analysis demonstrated similar results, showing that the patients with a postoperative apex located at T8 or above had an average SVA < 47 mm. Notably, a significant correlation was found between postoperative SVA and DCA (r = 0.642, p = 0.001). Patients who underwent an osteotomy at L3 had limited apex relocation but larger SVA correction than those at L1 or L2. However, no significant difference was found in health-related quality of life between the 2 groups. CONCLUSIONS: AS patients with an apex located at T8 or above after surgery tended to have better SVA correction (within 47 mm) than those who had a more caudally located apical vertebra. For ideal postoperative apex relocation, a higher (closer to or at the preoperative apex) level of osteotomy is more likely to obtain the surgical goal.

The relationship between global spinal alignment and pelvic orientation from standing to sitting following pedicle subtraction osteotomy in ankylosing spondylitis patients with thoracolumbar kyphosis.

INTRODUCTION: To investigate the relationship between the spinal sagittal alignment and arc of pelvic motion from standing to sitting in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis following pedicle subtraction osteotomy (PSO). MATERIALS AND METHODS: AS patients who underwent PSO for thoracolumbar kyphosis from January 2016 to July 2018 were recruited. EOS standing and sitting images were obtained pre- and postoperatively. Radiographic parameters were measured on the sagittal radiographs, including lumbar lordosis, thoracic kyphosis, pelvic incidence, pelvic tilt, sacral slope, sagittal vertical axis (SVA), spinosacral angle, anterior pelvic plane angle (APPA) and knee flexion angle. RESULTS: Thirty-six patients were enrolled. From standing to sitting, APPA was increased by a mean of 14.7° (P < 0.001) and 3.0° (P = 0.083) before and after surgery, respectively. The increase in APPA from standing to sitting was correlated with the standing SVA (R = 0.592, P < 0.001) preoperatively. After PSO, the change in APPA was correlated with the change in SSA in both the standing and sitting position (R = 0.381, P = 0.022 and R = 0.667, P < 0.001, respectively). The APPA from standing to sitting was decreased in 11 patients with standing C7 plumb line posterior to the femoral head postoperatively. CONCLUSIONS: In AS patients, pelvic orientation was adjusted by the global spinal alignment. When planning total hip arthroplasty for AS patients, global spinal alignment should be considered to improve the joint stability.

Does postoperative PI-LL mismatching affect surgical outcomes in thoracolumbar kyphosis associated with ankylosing spondylitis patients?

OBJECTIVE: To investigate if pelvic incidence (PI) and lumbar lordosis (LL) mismatching affects surgical outcomes for ankylosing spondylitis (AS) related kyphosis following 1-level lumbar pedicle subtraction osteotomy (PSO). PATIENTS AND METHODS: AS patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO from March 2006 and February 2014 in our institution, were retrospectively reviewed. The radiographic measurements and health-related quality of life (HRQoL) scores, including Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) for pain, were recorded at baseline and the last follow-up. Patients were divided into 2 groups according to PI-LL matching or not postoperatively (Match Group, Mismatch Group), and comparison of the aforementioned parameters between the two groups was performed. RESULTS: Seventy patients were enrolled with a mean age of 34.60 ±â€¯9.45 years (range, 17 yrs.-59 yrs.). Among them, 44 were included in the Match Group and 26 in the Mismatch Group. At baseline, patients in the Match Group had larger LL (p = 0.014) and smaller pelvic tilt (PT, p < 0.001) than patients in the Mismatch Group. At the last follow-up, along with larger LL (p = 0.004) and smaller PT (p = 0.001), Match Group patients also had significantly smaller sagittal vertical axis (SVA, 3.31 cm vs 6.27 cm, p = 0.001) than those in the Mismatch Group. Seventy-five percent (33/44) of the patients in the Match Group had a SVA < 5 cm at the last follow-up, while in the Mismatch Group, only 35% (9/26) of the patients did. However, no significant difference was found between the two groups regarding HRQoL scores. CONCLUSION: Patients with postoperative PI-LL matching were more likely to have a better correction of SVA; they also tended to have a smaller preoperative PT. However, PI-LL mismatching didn't affect HRQoL scores at the last follow-up, which was different from the results of previous studies in the settings of ASD.

Tetramethylpyrazine Protects Against Glucocorticoid-Induced Apoptosis by Promoting Autophagy in Mesenchymal Stem Cells and Improves Bone Mass in Glucocorticoid-Induced Osteoporosis Rats.

Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated BMSCs with different concentrations of TMP (50, 100, or 200 µM) and exposed them to 10-6 M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein fluorescence double labeling and microcomputed tomography scanning indicated that 12 weeks of TMP administration augmented bone formation and protected trabecular bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first time that TMP can protect BMSCs from exposure to excess glucocorticoids by promoting autophagy through AMPK/mTOR pathway and might be an effective agent for the prevention and treatment of GIOP.

[Candidemia combined with bacterial bloodstream infection: analysis of clinical features and associated risk factors].

OBJECTIVE: To investigate the clinical characteristics of and risk factors for candidemia combined with bacterial bloodstream infection(BSI) by retrospective analysis of cases. METHOD: The clinical data of cases diagnosed as candidemia combined with BSI confirmed by blood culture were compared with those of cases with mono-candidemia in Beiing Tongren Hospital from January 2009 to December 2011. A logistic regression analysis was performed to investigate the independent risk factors. RESULTS: Forty-two cases diagnosed as candidemia were analyzed including 14 cases of candidemia combined with BSI and 28 cases of mono-candidemia. Ten strains of gram-positive cocci and 4 strains of gram-negative bacilli were isolated from candidemia combined with BSI group.Six strains of C.albicans, 4 strains of C.glabrata, 3 strains of C.tropicalis and 1 strain of C.krosei were isolated. There was no C.parapsilosis isolated from candidemia combined with BSI group but 9 strains in the mono-candidemia group. The septic shock rate of the candidemia combined with BSI group was higher than that of the mono-candidemia group (12/14 vs 7/28, P = 0.000). The mortality rate of the candidemia combined with BSI group was higher than that of the mono-candidemia group (10/14 vs 15/28), but the difference did not reach statistical significance (P = 0.266).Four factors were found statistically different by univariate analysis, including hospitalization more than 4 weeks (P = 0.001), bacteremia before candidemia(P = 0.005), hematological tumor (P = 0.01) and abdominal infection (P = 0.001). Multivariate analysis showed that hospitalization more than 4 weeks was the independent risk factor. CONCLUSION: Gram-positive cocci were the predominant species and septic shock was more common in candidemia combined with BSI. Hospitalization more than 4 weeks was the independent risk factor for candidemia combined with BSI.

Imbalance between subpopulations of regulatory T cells in COPD.

BACKGROUND: Recent evidence indicates that human regulatory T cells (Tregs) are composed of three distinct subpopulations: CD25(++) CD45RA(+) resting Tregs (rTregs), CD25(+++) CD45RA(-) activated Tregs (aTregs), which are suppressive, and CD25(++) CD45RA(-) cytokine-secreting (Fr III) cells with pro-inflammatory capacity. OBJECTIVES: To evaluate the dynamic changes in circulating and pulmonary Treg subpopulations in smokers and patients with chronic obstructive pulmonary disease (COPD), and to explore their potential roles in COPD pathogenesis. METHODS: Blood samples were obtained from 57 never-smokers, 32 smokers with normal lung function and 66 patients with COPD. Bronchoalveolar lavage (BAL) samples were taken from 12 never-smokers, 12 smokers and 18 patients with COPD. The proportions of Treg subpopulations and activated CD8 T cells were evaluated using flow cytometry. RESULTS: In peripheral blood, increased proportions of rTregs, aTregs and Fr III cells were found in smokers compared with never-smokers, whereas patients with COPD showed decreased rTregs and aTregs, and significantly increased Fr III cells compared with smokers. The changes in Treg subpopulations, with an overall decrease in the (aTreg+rTreg):(Fr III) ratio, indicated that immune homeostasis favoured inflammation and correlated with enhanced CD8 T-cell activation (r=-0.399, p<0.001) and forced expiratory volume in 1 s (FEV1) % predicted value (r=0.435, p<0.001).The BAL (aTreg+rTreg):(Fr III) ratios displayed more robust correlations with FEV1% predicted value (r=0.741, p<0.01) and activation of effector T cells (r=-0.763, p<0.001). CONCLUSIONS: The imbalance between the anti-inflammatory subsets (aTreg+rTreg) and the pro-inflammatory subset (Fr III) of Tregs may play an important role in COPD progression.

[Idiopathic diffuse pulmonary ossification: a case report and review of the literature].

OBJECTIVE: To describe the clinical features and diagnosis of idiopathic diffuse pulmonary ossification (DPO). METHODS: A case of DPO confirmed by video-assisted thoracoscopic (VATS) lung biopsy was reported, and the literature was reviewed. RESULTS: A 32 year-old male was admitted to this hospital because of increased lung markings on chest X-ray for 7 years, and diffuse micro-nodular and reticular lesions on chest CT for 2 years. There were no significant symptoms, such as cough, sputum production and shortness of breath. Routine examinations and transbronchial lung biopsy failed to give a definite diagnosis, and therefore VATS lung biopsy was performed. The pathological study confirmed the presence of bone tissue in the lung, and the diagnosis of idiopathic DPD was made after careful exclusion of underlying diseases. Eleven cases of DPO diagnosed by lung biopsy in living patients were collected by review of the literature. The patients were all males, with a mean age of (48 +/- 17) years. No clinical symptoms were present in 4 cases, while spontaneous pneumothorax was the initial presentation in 3 cases. Other complaints included cough and shortness of breath. No case was reported in the Chinese literature. CONCLUSION: DPO is a rare disease, often without significant symptoms despite radiologically diffuse pulmonary lesions, which are easily misdiagnosed as other interstitial lung diseases.