Concurrent fabry disease and immunoglobulin a nephropathy: a case report.

BACKGROUND: Fabry disease (FD) is an X-linked, hereditary dysfunction of glycosphingolipid storage caused by mutations in the GLA gene encoding alpha-galactosidase A enzyme. In rare cases, FD may coexist with immunoglobulin A nephropathy (IgAN). We describe a case of concurrent FD, IgAN, and dilated cardiomyopathy-causing mutations in the TTN and BAG3 genes, which has not been reported previously. CASE PRESENTATION: A 60-year-old female patient was admitted with a one-week history of facial and lower-limb edema, two-year history of left ventricular hypertrophy and sinus bradycardia, and recurring numbness and pain in three lateral digits with bilateral thenar muscle atrophy. Renal biopsy revealed concurrent FD (confirmed via an alpha-galactosidase A enzyme assay, Lyso-GL-3 quantification, and GLA gene sequencing) and IgAN. Heterozygous mutations in the TTN (c.30,484 C > A;p.P10162T) and BAG3 (c.88 A > G;p.I30V) genes were observed. The patient reported that two of her brothers had undergone kidney transplantation; one died suddenly at 60 years of age, and the other required a cardiac pacemaker. The 35-year-old son of the patient was screened for the GLA gene mutation and found to be positive for the same mutation as the patient. The patient was administered oral losartan (50 mg/day). Enzyme replacement therapy was refused due to financial reasons. Her renal and cardiac functions were stable yet worth closely monitoring during follow-up. CONCLUSION: The family history of patients with concurrent heart and renal diseases should be assessed in detail. Genetic testing and histological examinations are essential for diagnosing FD with IgAN.

[A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis]. / Tç»†èƒžæ´»åŒ–å ç–«çƒè›‹ç™½æŠ‘åˆ¶Våž‹ç»“æž„åŸŸåœ¨å¹¼å¹´ç‰¹å‘æ€§å ³èŠ‚ç‚Žä¸­ä½œç”¨çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA. METHODS: In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14+ mononuclear cells, CD4+ T lymphocytes, and CD8+ T lymphocytes. RESULTS: The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4+ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8+ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14+ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05). CONCLUSIONS: The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.

Comparison of Radiation Dose and Image Quality Between Split-Filter Twin Beam Dual-Energy Images and Single-Energy Images in Single-Source Contrast-Enhanced Chest Computed Tomography.

OBJECTIVE: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT). METHODS: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate. RESULTS: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001). CONCLUSIONS: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.

Predicting the Prognosis of Gastric Cancer by Albumin/Globulin Ratio and the Prognostic Nutritional Index.

Background: Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are used to assess the nutritional status and severity of disease for a cancer patient. However, the clinical significance of combining these two predictors in gastric cancer (GC) remains unclear. This study evaluated the prognostic value of pretreatment serum AGR and the PNI for GC.Methods: A total of 273 patients with GC, diagnosed between January 2010 and January 2014, were enrolled. The association of AGR, PNI with clinicopathological characters and prognosis were assessed by Cox regression and Kaplan-Meier methods.Results: Both low AGR group and low PNI group had poor overall survival (OS) and progression-free survival (PFS) (all p < 0.001), while patients with low AGR and PNI had the lowest OS rate. Multivariate analyses revealed that AGR (for OS HR = 0.657, 95%CI: 0.449-0.962, p = 0.031; for PFS HR = 0.684, 95%CI: 0.528-0.895, p = 0.035) was an independent prognostic factor for OS and PFS in patients with GC, and PNI was verified as a predictor for OS (HR = 0.782, 95%CI: 0.503 -0.997, p = 0.048).Conclusions: Low level of pretreatment AGR and PNI may be independent prognostic factors for patients with GC, and patients with both factors indicated the worst OS.

Long-term follow-up of persistent pulmonary pure ground-glass nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning-assisted nodule segmentation. METHODS: Between January 2007 and October 2018, 110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth. RESULTS: The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8 months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339-8640) days, and their median MDT was 1332 (range, 290-38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p < 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (p = 0.044), initial mean diameter (p < 0.001), volume (p = 0.003), and mass (p = 0.023) predicted pGGN growth. CONCLUSIONS: Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow. KEY POINTS: • The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594). • The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448 days (range, 339-8640 days), and their median mass doubling time (MDT) was 1332 days (range, 290-38,912 days). The mean time to growth in volume was 854 ± 675 days (range, 116-2856 days). • The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.

Dual PI3K-BRD4 Inhibitor SF1126 Inhibits Colorectal Cancer Cell Growth in Vitro and in Vivo.

BACKGROUND/AIMS: Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are key oncogenic cascades in colorectal cancer (CRC). SF1126 is a novel and potent PI3K-BRD4 dual inhibitor. METHODS: CRC cells and human colon epithelial cells were treated with SF1126. Cell survival was tested by MTT and soft agar colony formation assays. Cell proliferation was tested by BrdU ELISA method. Cell apoptosis was tested by a TUNEL staining method and Histone DNA ELISA. Western blotting was utilized to test the signaling proteins. A HT-29 xenograft mice model was established to study the anti-tumor activity of SF1126 in vivo. RESULTS: SF1126 potently inhibited the survival, proliferation, and progression of the cell cycle in an established CRC cell line (HT-29) and primary human colon cancer cells. Significant activation of apoptosis was detected in SF1126-treated CRC cells. In CRC cells, SF1126 blocked Akt-mammalian target of rapamycin (mTOR) complex1/2 signaling and downregulated BRD4 target proteins (Myc and cyclin D1). Further studies showed that SF1126 activated p38 signaling in CRC cells. In contrast, the p38 inhibitors or p38 short hairpin RNA inhibited SF1126-induced cytotoxicity and apoptosis in CRC cells. In vivo, subcutaneous administration of SF1126 significantly inhibited HT-29 xenograft tumor growth in nude mice. CONCLUSION: SF1126 inhibits CRC cell growth possibly by targeting PI3K-Akt-mTOR, BRD4, and p38 signaling.

IL-22 suppresses HSV-2 replication in human cervical epithelial cells.

Interleukin (IL)-22, a member of the IL-10 family, plays a role in antiviral immune responses to a number of viral infections. However, it is unclear whether IL-22 is involved in the mucosal immunity against herpes simplex virus 2 (HSV-2) infection in the female reproductive tract (FRT). In this study, we studied whether IL-22 could inhibit HSV-2 infection of human cervical epithelial cells (End1/E6E7 cells). We showed that End1/E6E7 cells express the functional IL-22 receptor complex (IL-22R1 and IL-10R2). When treated with IL-22, End1/E6E7 cells expressed the higher levels of IFN-stimulated genes (ISGs: ISG15, ISG56, OAS-1, OAS-2, and Mx2) than untreated cells. In addition, IL-22-treated cells produced higher levels of the tight junction proteins (ZO-1 and Occludin) than untreated cells. Mechanistically, IL-22 could activate the JAK/STAT signaling pathway by inducing the phosphorylation of STAT1 and STAT3. These observations indicate the potential of IL-22 as an anti-HSV-2 agent in the FRT mucosal innate immunity against HSV-2 infection.

Macrophage polarization in human gingival tissue in response to periodontal disease.

OBJECTIVE: Although accumulating evidence indicates that macrophages are central players in the destructive and reparative phases of periodontal disease, their polarization states at different stages of periodontal inflammation remain unclear. METHODS: We collected gingival biopsies from patients with chronic periodontitis (P group), gingivitis (G group), or periodontally healthy individuals (H group). Polarized macrophages were identified through immunofluorescence. M1- and M2-related cytokines were detected by immunohistochemistry. RESULTS: Compared with the H group, the P group had more M1 cells (higher M1/M2 ratio) and significantly higher TNF-α, IFN-γ, IL-6, and IL-12 levels. Although the G group also exhibited higher TNF-α and IL-12 levels than the H group, they had similar M1/M2 ratios. The M1/M2 ratio and IFN-γ and IL-6 levels were significantly higher in the P than the G group. Among M2-related cytokines, IL-4 levels were significantly higher in the G than the H group. The M1/M2 ratio was positively correlated with clinical probing depth (PD), and both were positively correlated with IFN-γ and IL-6. PD was negatively correlated with IL-4. CONCLUSION: Macrophage polarization in gingival tissue may be responsible for the development and progression of inflammation-induced tissue destruction, and modulating macrophage function may be a potential strategy for periodontal disease management.

Elevated serum levels of interleukin-37 correlate with poor prognosis in gastric cancer.

BACKGROUND: interleukin-37 (IL-37) is as a natural suppressor of the innate inflammatory and immune responses. It has also been reported to be involved in carcinogenesis and metastasis. The present case-control study was designed to investigate the role of serum levels of IL-37 in patients with gastric cancer. METHODS: serum IL-37 levels were determined using the enzyme-linked immunosorbent assay in 180 patients diagnosed with gastric cancer and 100 healthy controls. The association between IL-37 levels and clinical factors was assessed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters in gastric cancer. RESULTS: serum IL-37 levels in gastric cancer patients (5.606 ± 0.837 pg/ml) were significantly higher than those in healthy controls (2.364 ± 0.210 pg/ml, p < 0.001). High serum IL-37 levels were related to a poorly differentiated histologic type (p = 0.046) and advanced T stage (p = 0.003). The Kaplan-Meier survival analysis indicated that the high-IL-37 group had a poorer overall survival and progression-free survival (overall survival [OS]: 39.0 months vs 13.0 months, p < 0.001, progression-free survival [PFS]: 25.0 months vs 10.0 months, p < 0.001). Multivariate analyses showed serum IL-37 to be an independent prognostic factor for gastric cancer patients (OS: hazard ratios [HR] = 1.842, 95% CI: 1.190-2.854, p = 0.006; PFS: HR = 1.547, 95% CI: 1.014-2.359, p = 0.043). CONCLUSIONS: in conclusion, serum IL-37 levels were associated with poor overall survival and progression-free survival in gastric cancer patients. IL-37 may be a potential predictor of prognosis in gastric cancer.

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner.

BACKGROUND/AIMS: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH) on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK) contributed to metabolic responses to IH in liver cells. METHODS: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour) or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. RESULTS: IH decreased insulin-stimulated protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1) expression and phosphoenolpyruvate carboxykinase (PEPCK) transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3ß phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. CONCLUSION: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3ß phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

Novel compound heterozygous mutations in ZAP70 in a Chinese patient with leaky severe combined immunodeficiency disorder.

In humans, the complete lack of tyrosine kinase ZAP70 function results in combined immunodeficiency (CID), with abnormal thymic development and defective T cell receptor (TCR) signaling of peripheral T cells, characterized by the selective absence of CD8+ T cells. So far, 15 unique ZAP70 mutations have been identified in approximately 20 patients with CID, with variable clinical presentations. Herein, we report the first case from China of novel compound heterozygous mutations in ZAP70 (c.598-599delCT, p.L200fsX28; c.847 C>T, R283H). The patient suffered from early-onset and recurrent infections, but showed normal growth and development without signs of failure to thrive, thus presenting as leaky SCID. The patient also had clinical manifestations of autoimmunity, such as eczematous skin lesion, inflammatory bowel disease (IBD), and intractable diarrhea, suggesting compromised T cell tolerogenic functions. Residual ZAP70 expression was identified. Immunological analysis revealed the selective absence of CD8+ T cells in the periphery and the presence of CD4+ T cells that failed to respond to phytohemagglutinin. Stimulation with lectin from pokeweed mitogen also failed to stimulate B cell proliferation in the patient. The frequency of Tfhs and Tregs in the patient was lower compared with the normal reference. Compared with the age-matched healthy control, the level of IL-17 was higher and the levels of IFN-γ, IL-4, and IL-21 were lower. Infants with selected CD8 deficiency and severe autoimmune disorders or exaggerated inflammation should be screened for ZAP70 deficiency.

Effects of Tripterygium wilfordii Induction Therapy to IgA Nephropathy Patients with Heavy Proteinuria.

Although some new drugs have been developed, Tripterygium wilfordii HOOK F. (TWHF) has the merits of relatively lower price and fewer side effects. Unfortunately, the efficacy and safety of the TWHF (especially dosage 120 mg/d) in the immunoglobulin A (IgA) nephropathy (IgAN) are still lacking. A cohort study including 49 IgAN patients with heavy proteinuria who received induction therapy was undertaken. Patients were divided into three groups: Prednisone (PRE), conventional-dose TWHF (CTW) and double-dose TWHF (DTW). The clinical features, laboratory data, histological manifestations and outcomes of the groups were compared. We found that urinary protein excretion and rates of elevated n-acetyl-ß-D-glucosaminidase (NAG) and retinol binding protein (RBP) were prominent in all groups. Neither histopathological changes nor the rates of renal insufficiency were significantly different among groups. Patients in the PRE (69.2%) and DTW groups (87.5%) achieved complete remission; none of the CTW group did. Furthermore, the total remission rate of the DTW group was substantially higher than that of the CTW group. The degree of hypoproteinemia, improved considerably in the PRE and DTW groups. Treatment was well tolerated in all patients, and no serious adverse events were observed. Our findings suggested that induction therapy with double dose TWHF significantly improved response rates in IgAN patients with heavy proteinuria, and did not considerably increase side effects.

Effect of Asymptomatic Visible Third Molars on Periodontal Health of Adjacent Second Molars: A Cross-Sectional Study.

PURPOSE: Evidence that asymptomatic third molars (M3s) negatively affect their adjacent second molars (A-M2s) is limited. The present study evaluated the association between visible M3s (V-M3s) of various clinical status with the periodontal pathologic features of their A-M2s. PATIENTS AND METHODS: Subjects with at least 1 quadrant having intact first and second molars, either with V-M3s and symptom free or without adjacent V-M3s, were enrolled in the present cross-sectional investigation. Periodontal parameters, including plaque index (PLI), bleeding on probing (BOP), probing pocket depth (PPD), and at least 1 site with a PPD of 5 mm or more (PPD5+), obtained from M2s were analyzed according to the presence or absence of V-M3s or the status of the M3s. The χ2 test or t test was used to compare the mean PLI, PPD, BOP percentage, and PPD5+ percentage. The association of PPD5+ with V-M3 status was assessed using a multivariable logistic regression model (quadrant-based analysis), and variances were adjusted for clustered observations within subjects. RESULTS: In total, 572 subjects were enrolled in the study, and 423 had at least 1 V-M3. At the in-quadrant level, the presence of a V-M3 significantly increased M2 pathologic parameters, including PLI, PPD, BOP, and PPD5+. When analyzed using a multivariate logistic regression model, impacted M3s and normally erupted M3s significantly elevated the risk of PPD5+ on their A-M2s (odds ratio 3.20 and 1.67, respectively). Other factors associated with an increased odds of PPD5+ were mandibular region and older age. Finally, the patient-matched comparison showed that the percentage of BOP and PPD5+ on M2s increased when V-M3s were present. CONCLUSIONS: Irrespective of their status, the presence of V-M3s is a risk factor for the development of periodontal pathologic features in their A-M2s. Although the prophylactic removal of asymptomatic V-M3s remains controversial, medical decisions should be made as early as possible, because, ideally, extraction should be performed before symptom onset.

Nonimpacted Third Molars Affect the Periodontal Status of Adjacent Teeth: A Cross-Sectional Study.

PURPOSE: Most previous studies of the effect of third molars (M3s) on the health of adjacent second molars (A-M2s) have focused on impacted M3s (I-M3s). The purpose of this study was to investigate whether nonimpacted M3 (N-M3s) could affect the periodontal status of A-M2s. PATIENTS AND METHODS: In this cross-sectional study, patients (≥18 years) who had at least 1 quadrant with intact first and second molars and a nonimpacted or absent M3 were enrolled in this study. The periodontal measurements of M2 (6 sites) in the examined quadrants included the gingival index (GI), plaque index (PLI), probing pocket depth (PPD), clinical attachment level (CAL), gingival recession, and bleeding on probing (BOP). The mean GI, PLI, PPD, CAL, and BOP proportion and the proportion with at least 1 site with a PPD of at least 5 mm (PPD5+) were compared using the t test or χ2 test. The association of PPD5+ (percentage) or BOP (percentage) with the presence of N-M3s was assessed using a 2-level logistic regression model (quadrant-based analysis). RESULTS: One hundred thirty-five patients (43.7% men; 40.6 ± 11.5 yr old) were enrolled in this study. Patients who had at least 1 quadrant with 3 intact molars and an N-M3 were enrolled in group A (105 patients), and patients who had at least 1 quadrant with intact first and second molars without an M3 were enrolled in group B (30 patients). The periodontal parameters (ie, GI, PLI, PPD, CAL, BOP, and PPD5+) were markedly greater in group A. When other factors associated with periodontal disease were controlled, N-M3s were associated with the PPD5+ (odds ratio = 6.7) and BOP (odds ratio = 4.0) of the A-M2s. Other factors positively associated with A-M2 PPD5+ were location on the mandible, age older than 35 years, and smoking. CONCLUSIONS: The presence of N-M3s is a potential risk factor for the development of periodontitis in A-M2s.

Long-term efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma: a systemic review and meta-analysis.

OBJECTIVE: To evaluate the long-term efficacy and safety of bronchial thermoplasty (BT) in the treatment of patients with moderate-to-severe persistent asthma. METHODS: We therefore performed a systematic literature review of peer-reviewed studies focusing on BT intervention in asthma control published between January 2000 and June 2014. Three randomized controlled studies and extension studies met the inclusion criteria (n = 6). Outcomes assessed after BT included spirometric data, adverse respiratory events, emergency room (ER) visits and hospitalization for respiratory illness. One-year and 5-year follow-up data were defined as V1 and V5, respectively. RESULTS: There were 249 BT-treated subjects in total who had a 1-year follow-up (V1), whereas 216 of them finished a 5-year follow-up (V5). No evidence of significant decline was found in pre-bronchodilator FEV1 (% predicted) (WMD = 0.75; 95% CI: 3.36 to 1.85; p = 0.57), or in post-bronchodilator FEV1 (% predicted) (WMD = 0.62; 95% CI: 3.32 to 2.08; p = 0.65) between V1 and V5. In addition, the frequency of respiratory adverse events was reduced significantly during the follow-up (RR = 3.41, 95% CI: 2.96-3.93, p < 0.00001). The number of ER visits for adverse respiratory events remained unchanged (RR = 1.06, 95% CI: 0.77-1.46, p = 0.71) after BT treatment. There was no statistically significant increase in the incidence of hospitalization for respiratory adverse events (V5 vs. V1, RR = 1.47, 95% CI: 0.69-3.12, p = 0.32). CONCLUSIONS: These data demonstrate long-term benefits of BT with regard to both asthma control and safety for moderate-to-severe asthmatic patients.

Combined effect of obstructive sleep apnea and chronic smoking on cognitive impairment.

OBJECTIVES: Little is known about combined effect of obstructive sleep apnea (OSA) and chronic smoking on cognitive impairment. We aimed to determine whether smoking synergizes with OSA in deteriorating cognitive function and whether smoking cessation contributes to cognitive benefits. METHODS: One hundred and eighteen male patients were enrolled in the study and asked to complete neurocognitive function tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), clock drawing test (CDT), and verbal fluency test (VFT). Variables of those neurocognitive function tests were analyzed with two factors: OSA and smoking. RESULTS: After adjustment of potential confounding factors, an OSA-by-smoking interaction was found in CDT-C scores and a main smoking effect were showed in MoCA scores. Smoking patients with OSA had the worst performance in the four tests compared with the other three groups (smoking patients without OSA, non-smoking patients with and without OSA). Ex-smokers with OSA tended to perform better than current smokers, but still worse than never-smokers with OSA in those tests. CONCLUSION: The results suggested that the coexistence of OSA and chronic smoking resulted in more pronounced cognitive deficits than either factor along. Smoking cessation may benefit cognitive function to some extents in patients with OSA.

Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China.

PURPOSE: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. METHODS: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. RESULTS: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. CONCLUSIONS: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.

Factors affecting blood pressure profile in pre and postmenopausal women with obstructive sleep apnea hypopnea syndrome.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for development of hypertension. Epidemiological surveys have found that risk of cardiovascular diseases increased in postmenopausal women. However, it is not well known about the profiles of hypertension of women with OSAHS in their different reproductive stages. This study aimed to investigate the difference of blood pressure profile between pre and postmenopausal women with OSAHS. METHODS: Women who were tested by polysomnography (PSG) (n = 207) in Ruijin Hospital were recruited in the study. The subjects were divided into two groups of premenopausal women (24 with and 30 without OSAHS), and two groups of postmenopausal women (116 with and 37 without OSAHS). Among the groups, the differences of demographic and PSG variables were compared. The factors influencing blood pressure were further studied. RESULTS: The prevalence of hypertension (56.9 %) in postmenopausal OSAHS patients was higher than the other three groups. Among OSAHS patients, both average systolic blood pressure (SBP) and diastolic blood pressure (DBP) of postmenopausal women were higher than those of premenopausal ones [(129.9 ± 16.16 mmHg vs. 123.7 ± 18.89), (84.96 ± 9.88 mmHg vs. 78.81 ± 10.34), P = 0.05, P < 0.01, respectively], with the elevation of DBP being more pronounced. For premenopausal women, body mass index (BMI) was the only factor affecting blood pressure (p < 0.05); in postmenopausal women, BMI was a factor affecting SBP, while BMI and apnea hypopnea index (AHI) affecting DBP (P < 0.05). CONCLUSION: Blood pressure profile of postmenopausal women with OSAHS was affected by both BMI and AHI. But those of premenopausal ones were predominantly related to BMI.

Co-Graft of Bone Marrow Stromal Cells and Schwann Cells Into Acellular Nerve Scaffold for Sciatic Nerve Regeneration in Rats.

PURPOSE: The conventional strategy for bridging large nerve defects, namely nerve autograft transplantation, results in donor-site morbidity. This detrimental consequence currently drives the search for alternatives. The authors used an acellular nerve scaffold filled with bone marrow stromal cells (BMSCs) and Schwann cells (SCs) to enhance regeneration. MATERIALS AND METHODS: In 60 adult rats, a 10-mm sciatic nerve defect was bridged with a nerve autograft (positive control), an acellular nerve scaffold (negative control), an acellular nerve scaffold with BMSCs (group I), an acellular nerve scaffold with SCs (group II), or an acellular nerve scaffold with BMSCs plus SCs (group III). After regenerating for 4 and 16 weeks after surgery, nerve regeneration was functionally assessed by a walking track analysis. The compound muscle action potential (CMAP), nerve conduction velocity (NCV) along regenerated sciatic nerves, and gastrocnemius muscle index (GMI) were recorded to assess the conduction properties and extent of denervation atrophy. The number of retrograde-labeled lumbar motor neurons identified by fluorescent dyes in the ipsilateral ventral horn and spinal ganglia were counted to assess the regeneration of axons. RESULTS: After 4 and 16 weeks, improvement of the sciatic function index of the sciatic nerve in group III was statistically greater than that of the negative control group, group I, and group II. At 16 weeks after grafting, obvious differences in the GMI were found among groups. Group III had a statistical increase in GMI compared with the negative control group, group I, and group II. The CMAP and NCV measurements showed comparable results at 16 weeks after reconstruction: group III had statistically better results compared with the negative control group, group I, and group II. Fluorescent dye analysis of the retrograde-labeled lumbar motoneurons in the ipsilateral ventral horn and spinal ganglia showed that more motor neurons in the ipsilateral ventral horns and spinal ganglia were labeled in group III than in the negative control group, group I, and group II at 16 weeks after the operation. All results consistently showed that when BMSCs and SCs were loaded together in an acellular nerve scaffold, functional recovery of the sciatic nerve was enhanced to the greatest degree among the 3 cell-treated groups; furthermore, its beneficial effect on sciatic injury regeneration was similar to the autograft group, although it never exceeded it. CONCLUSIONS: This study is a step forward in the search for an alternative to the nerve autograft because it showed that co-grafting of BMSCs and SCs into an acellular nerve scaffold enhanced sciatic nerve functional recovery in rats. Its beneficial effect on sciatic injury regeneration was similar to the autograft group, although it did not exceed it.

Monitoring response to gefitinib in nude mouse tumor xenografts by (18)F-FDG microPET-CT: correlation between (18)F-FDG uptake and pathological response.

BACKGROUND: The purpose of this study is to investigate whether (18)F-fluorodeoxyglucose (FDG) micro-positron emission tomography-computed tomography (microPET-CT) can be used to monitor a metabolic response to gefitinib in nude mouse tumor xenografts. METHODS: Sixteen nude mice were implanted with human A431 epidermoid carcinoma cells and ten with human A549 lung adenocarcinoma cells, and the tumors were allowed to grow to an approximate size of 150 mm(3). Ten and five of these mice, respectively, received intragastric gefitinib (100 mg/kg) once daily for 14 days, whereas six and five, respectively, received sterile water. Tumor metabolic activity was assessed by (18)F-FDG microPET imaging before treatment (day 0) and on days 2, 7, and 14. Tumor uptake of (18)F-FDG was determined from a region-of-interest drawn around the tumor, and the maximum percentage injected dose per gram (%ID/gmax) was calculated. Tumor volume measured on day 14 by microCT was used to categorize tumors as sensitive, stable, or resistant to gefitinib, and pathologic changes in these tumors were analyzed. RESULTS: On day 2, the average changes in (18)F-FDG uptake by A431 tumors sensitive, stable, and resistant to gefitinib were -30.92% ± 6.66%, -5.68% ± 6.95%, and 7.72% ± 3.85%, respectively (P < 0.05 each), with no significant differences in the sizes of tumors sensitive and stable to gefitinib (P = 0.169). On day 7, sensitive tumors were significantly smaller than stable tumors (P = 0.034). On day 14, areas of necrosis were observed in gefitinib-sensitive tumors, with tumor necrosis ratios differing significantly among the sensitive, stable, and control groups (P < 0.05 each). In mice implanted with A549 cells, however, tumor (18)F-FDG uptake, volume, and percent necrosis did not differ significantly between gefitinib-treated and untreated mice on days 0, 2, 7, and 14 (P > 0.05 each). CONCLUSIONS: F-FDG uptake is a sensitive method of detecting metabolic changes in tumors associated with therapy in vivo.