Association of blood heavy metal concentrations with hearing loss: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to assess the associations between blood heavy metal concentrations and hearing loss. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: A comprehensive literature search was performed using Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, Wanfang and Weipu databases. Ten studies were included, and a random or fixed-effects model was used for the meta-analysis. Review Manager 5.4 software was used for data synthesis, and Stata 15.1 software was used for the publication bias and sensitivity analyses. RESULTS: Blood lead concentrations were significantly and substantially associated with hearing loss (mean difference (MD) = 1.14; 95% confidence interval [CI] = 0.03, 2.26; P = 0.04; I2 = 81%), and iron deficiency was significantly related to hearing loss (MD = -0.42; 95% CI = -0.66, -0.18; P = 0.12; I2 = 60%). CONCLUSIONS: These results suggest an association between blood heavy metal concentrations and hearing loss. However, there were limitations: confounding factors, lack of description for the specific methods of blinding and independent verification of case definition, limited sample size, Chinese publications comprising half of the primary data and the lack of assessment of the relationship between different blood heavy metal concentrations and the severity of hearing loss. Therefore, larger and well-designed prospective cohort studies are required for further exploration.

[Discussion on two common problems in renal transplantation donor-specificity discrimination of anti-human leukocyte antigen antibody].

Antibody-mediated rejection (AMR) is a key factor affecting the long-term survival of renal allografts. Donor-specific antibody (DSA) is the etiology of AMR. So it is very important to accurately detect DSA. The single antigen bead (SAB) method, which is widely used in clinical practice, is prone to miss DSA detection and underestimate its mean fluorescence intensity (MFI). In this paper, the probability of missed detection of two SAB reagents was calculated by comparing common HLA alleles in China population, and the in vitro effect of antibody cross reaction on MFI value of DSA was revealed. The authors emphasized the clinical significance of the above two problems, tried to manage them by using functional epitope (eplet) analysis and give some clinical examples. Finally, the limitations of this correction method were analyzed.

[Safety and efficacy of a new domestic distal perforated stent graft in the treatment of Stanford type B aortic dissection].

Objective: To evaluate the safety and efficacy of a new domestic distal perforated stent graft (Talos stent) in the treatment of Stanford type B aortic dissection (TBAD). Methods: Twenty-five patients with TBAD treated with Talos stent in Yan'an Hospital Affiliated to Kunming Medical University from February 2018 to December 2019 were selected as the research subjects. Intraoperative angiography was performed to determine the number of branch arteries that remained after stent release. On postoperative day 5 (POD5), the pain intensity of the patients was evaluated by visual analog scale (VAS). The computed tomography angiography (CTA) of the patients before operation, 6 months and 12 months after operation were compared including aortic diameter, true lumen diameter, and false lumen diameter at the level of tracheal bifurcation. Follow-up was performed 1 month, 6 months, 12 months, and 24 months after surgery, and the occurrence of stent-related adverse events, reoperation and survival rate were recorded. Results: The enrolled patients included 19 males and 6 females, aged (52.6±11.1) years. Intraoperative angiography showed that 4 (1, 7) branch arteries were preserved, and the VAS score was 1 (0, 1) on POD5. The aortic diameters at the level of the tracheal bifurcation were (34.9±1.1) mm, (34.6±0.9) mm and (34.8±1.0) mm before surgery, 6 months and 12 months after surgery, and there was no significant difference (P=0.926); the diameters of the main true lumen at the level of the tracheal bifurcation were (13.3±1.6) mm, (21.8±1.0) mm and (22.3±1.1) mm before surgery, 6 months and 12 months postoperatively, while the diameters of the main false lumen at the level of the tracheal bifurcation were (20.8±2.2) mm, (4.5±1.5) mm, and (4.6±1.7) mm, respectively. Compared with before surgery, the diameter of true lumen increased significantly 6 months and 12 months after surgery (both P<0.001), while the diameter of false lumen decreased (both P<0.001). No stent-related adverse events occurred within 30 days after surgery, no secondary operations occurred within 12 months after surgery, no type Ⅰ and type Ⅲ endoleaks, no deaths or cases of paraplegia were reported, and the stent structure and position remained good. There were no deaths or paraplegia cases 24 months postoperatively, and no stent-related adverse events occurred. Conclusion: Using Talos stent in the treatment of TBAD can effectively help remodel the aorta, while preserve the intercostal artery and spinal artery, with good clinical effect and safety.

[Altered dynamics of brain spontaneous activity in betel quid dependence chewers].

Objective: To investigate the dynamic characteristics of brain spontaneous activity in betel quid dependence (BQD) chewers and its relationship with clinical indexes. Method: This study was conducted in Hainan General Hospital from April to December 2019 and the data of 53 BQD chewers (37 males and 16 females, aged 20 to 58(38±11) years) and 37 healthy controls (HC) (24 males and 13 females, aged 23-57(42±12) years) were collected. All these subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The dynamic characteristics of resting fMRI indexes, including dynamic amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC) of these subjects were calculated using the sliding time window method, parameters such as age and dynamic local consistency were analyzed and compared between the two groups. Pearson correlation was used to analyze the relationship between dynamic indexes, betel quid dependence score (BQDS) and disease duration in BQD group. Results: BQD chewers showed decreased dynamic ALFF in the left orbital prefrontal cortex (0.138±0.041 vs 0.171±0.070), the right temporal pole superior temporal gyrus (0.277±0.070 vs 0.319±0.086) and the right inferior parietal lobule (0.223±0.052 vs 0.259±0.088) than HC (all P<0.05). For regional homogeneity, BQD chewers showed a decrease dynamic ReHo in the right inferior temporal gyrus (0.055±0.008 vs 0.061±0.009), the orbital prefrontal cortex (0.058±0.005 vs 0.063±0.008), the right inferior frontal gyrus (0.081±0.006 vs 0.087±0.011), the right superior occipital gyrus (0.056±0.007 vs 0.062±0.008), the left precentral gyrus (0.068±0.008 vs 0.074±0.008), and the left superior frontal gyrus (0.058±0.008 vs 0.064±0.009) than HC (all P<0.05). BQD chewers showed an increase dynamic ReHo in the right precuneus (0.095±0.009 vs 0.089±0.008) (P<0.05). There was no significant difference in DC between the two groups (all P>0.05). The relationships between three dynamic ALFF and BQDS (r=-0.104, -0.015, -0.119), seven dynamic ReHo and BQDS (r=-0.099, -0.141, -0.055, -0.078, -0.027, -0.111, -0.090), three dynamic ALFF and disease duration (r=-0.122, -0.095, -0.171), and seven dynamic ReHo and disease duration (r=0.242, -0.252, 0.035, 0.056, 0.047, 0.081, 0.169) were not statistically significant (all P>0.05). Conclusions: BQD chewers showed a decrease dynamic ReHo and/or ALFF in multiple brain regions dominated by prefrontal cortex, and an increase dynamic ReHo in the right precuneus.

[Spindle cell hemangioma: a clinicopathological and molecular analysis of eight cases].

Objective: To investigate the clinicopathological and genetic characteristics of spindle cell hemangioma (SCH). Methods: The clinical, morphological and immunohistochemical features of 8 SCHs diagnosed from January 2013 to September 2021 in West China Hospital, Sichuan University, Chengdu, China were retrospectively analyzed. Hotspot mutations for IDH1 codon 132 and IDH2 codon 172 were tested in 4 SCHs and 29 other non-SCH lesions using Sanger sequencing. Results: The 8 cases occurred in patients with a wide age range, from neonate to 46 years (mean 28 years, median 32 years). Both genders were equally affected. The course of the disease spanned from half a year to 31 years. Two SCHs were recurrent tumors. All tumors involved the distal extremities (4 of foot, 2 of ankle and 2 of hand). Six cases were presented as a single lesion and 2 cases as multiple lesions. The tumor diameters were 1-5 cm. All the 8 SCHs were typically composed of cavernous vascular space and solid components consisting of slit-like vessels, spindle cells and epithelioid endothelial cells which often exhibited cytoplasmic vacuolation. These two alternating components and the vacuolated epithelioid endothelial cells were the distinctive diagnostic clues for SCH. Vascular endothelial cells including epithelioid cells in the solid areas expressed CD31 (8/8), ERG (4/4), CD34 (5/8) and D2-40 (2/3). The spindle cells expressed SMA (8/8). Neither endothelial cells nor spindle cells expressed HHV8 (0/7), Desmin (0/5) or S-100 (0/3). Mutations were revealed in 2 SCHs, with IDH1 mutation (p.R132C) and IDH2 mutation (p.R172G), respectively. The IDH1/2 gene hotspot mutations were not found in the remaining 2 SCHs or the other 29 non-SCH lesions. Simple excisions were performed for 7 cases, and partial resection for 1 case. Follow-up information was obtained in 6 cases, with follow-up time ranging from 5 to 90 months (average, 46 months). No metastasis occurred in the 6 cases. No recurrence occurred in cases treated with simple excision. The residual lesions of the patient who received partial resection were stable. Conclusions: SCH is rare and should be differentiated from a variety of benign and malignant vascular lesions. An accurate diagnosis of SCH is clinically important and can be achieved by combining clinical information and typical pathological presentation. IDH1/2 gene hotspot mutations are specific to SCH in vascular lesions. Genetic detection is helpful in the diagnosis of challenging cases.

[Diagnostic value of MDM2 RNA in situ hybridization in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma].

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.

[Nodular fasciitis of the breast: a clinicopathological and genetic analysis of seven cases].

Objective: To investigate the clinicopathological and genetic features of nodular fasciitis of the breast (NFB). Methods: The clinical and histologic features of seven NFBs were retrospectively reviewed. Immunohistochemistry, fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) were performed. Results: All the seven patients were female, with a mean age of 36 years (range from 15 to 51 years). The duration of the lesion ranged from 10 days to 2 years. There was no history of trauma for all patients. The lesions occurred in the upper quadrant (4 cases), the lower quadrant (2 cases) and the axillary tail region (1 case). The maximum diameter was 1.0-3.5 cm. All cases showed similar morphology as nodular fasciitis occurring elsewhere in the body. They were composed of plump spindle cells arranged in short bundles or fascicles within a loose collagenous/myxoid stroma. Erythrocyte extravasation, mixed chronic inflammatory cells infiltration and microcystic changes were typically seen. Mitoses were present, with no atypical mitoses observed. The spindle cells were positive for smooth muscleactin(SMA, 6/6), CD10(2/3), and negative for desmin, ß-catenin, CD34, CKpan, EMA, S-100, p63 and ALK-1.The Ki-67 index were 5%-15%. USP6 gene rearrangement was found in six cases and MYH9-USP6 gene fusion in two cases. Local resection was performed in six cases. Spontaneous regression was observed in one case. Follow-up of all seven cases revealed no recurrence or metastasis. Conclusions: Although rare, NFB can mimic breast cancer clinically, radiologically and histologically. It should be always considered in the differential diagnosis for the spindle cell proliferations of the breast. A diagnosis of NFB can be achieved basing on the typical clinicopathological presentation. FISH detection of USP6 gene rearrangement in challenging cases is of great value.

Depth-Resolved Magnetization Dynamics Revealed by X-Ray Reflectometry Ferromagnetic Resonance.

Magnetic multilayers offer diverse opportunities for the development of ultrafast functional devices through advanced interface and layer engineering. Nevertheless, a method for determining their dynamic properties as a function of depth throughout such stacks has remained elusive. By probing the ferromagnetic resonance modes with element-selective soft x-ray resonant reflectivity, we gain access to the magnetization dynamics as a function of depth. Most notably, using reflectometry ferromagnetic resonance, we find a phase lag between the coupled ferromagnetic layers in [CoFeB/MgO/Ta]_{4} multilayers that is invisible to other techniques. The use of reflectometry ferromagnetic resonance enables the time-resolved and depth-resolved probing of the complex magnetization dynamics of a wide range of functional magnetic heterostructures with absorption edges in the soft x-ray wavelength regime.

[Multicenter performance of the different classification criteria for rheumatoid arthritis].

OBJECTIVE: To evaluate the classification criteria of early rheumatoid arthritis (ERA) and compare the sensitivity and specificity with the criteria of 1987 American College of Rheumatology (ACR) criteria and 2010 ACR/European League Against Rheumatism (EULAR). METHODS: Patients from 4 hospitals, aged more than 16 years, with arthritis, whose disease duration was ≤1 year, and with ≥1 joint pain and swelling were enrolled in the study. The indicators including clinical manifestations, laboratory tests and imaging examinations were observed. The ERA patients were dignosed by two experienced rheumatologists based on the clinical features, drug therapy information and radiography features. RESULTS: (1) A total of 325 patients with arthritis were enrolled, including 98 males (30.15%) and 227 females (69.85%), The average age was (47.53±14.44) years, and the median disease duration was 5 (2, 8) months. Finally, 236 patients were dignosed with ERA, and 89 patients were dignosed with other diseases (Non-ERA, including osteoarthritis, reactive arthritis, undifferentiated arthritis, spondyloarthritis, etc). (2) The sensitivity of ERA criteria was 87.29%, and the specificity was 84.37%. The sensitivity was higher than that of 1987 ACR criteria (χ2=43.641, P < 0.001), and had no significant difference compared with 2010 ACR/EULAR criteria (χ2=0.446, P=0.593). But the specificity of ERA criteria was lower than that of 1987 ACR criteria (χ2=4.891, P=0.027), which was not statistically significant compared with 2010 ACR/EULAR criteria (χ2=0.044, P=1.000). (3) In the patients with arthritis whose disease duration was ≤3 months and ≤6 months, the sensitivity of ERA criteria was 81.71% and 86.79%, respectively, both were higher than the 1987 ACR criteria (χ2=7.131, P=0.008; χ2=22.015, P < 0.001) and had no statistically difference compared with the 2010 ACR/EULAR criteria (χ2=0.220, P=0.755; χ2=0.473, P=0.491). The differences of the three criteria in specificity were not statistically significant. (4) The three different classification criteria were consistent with the clinical diagnosis, among which the ERA criteria and 2010 ACR/EULAR criteria were slightly higher (Kappa>0.6). The results of the consistency comparison between the three criteria showed that the ERA criteria and 2010 ACR/EULAR criteria had a better consistency (Kappa=0.836). CONCLUSION: The sensitivity of ERA classification criteria in the diagnosis of ERA was higher than that of 1987 ACR criteria, and was equivalent to that of 2010 ACR/EULAR criteria. There is no significant difference in specificity between these three criteria. The ERA criteria can also identify patients with RA at a very early stage in arthritis with disease duration ≤3 months.

[A long-term follow-up study on the occurrence of heterotopic ossification after artificial cervical disc replacement with Discover disc].

Objective: To analyze the incidence of heterotopic ossification after artificial cervical disc replacement with Discover disc, and to explore the effect of heterotopic ossification on postoperative radiological and clinical efficacy. Methods: From January 2010 to January 2015, 45 patients with cervical spondylosis underwent single-level artificial cervical disc replacement in Shanghai Changzheng Hospital, including 29 cases of cervical spondylotic myelopathy, 11 cases of cervical spondylotic radiculopathy and 5 cases of mixed cervical spondylosis. At the last follow-up, Mehren grading method was used for classification of heterotopic ossification, among which, grade 0-Ⅱ was defined as low grade ossification group, and 26 patients (16 male, 10 female) were enrolled in this group; grade Ⅲ-Ⅳ was defined as high grade ossification group, and 19 patients (12 males, 7 females) were included in this group. C(2-7) Cobb angle, cervical total range of motion and range of motion at index level were used to evaluate the radiological outcomes of the two groups. Japanese Orthopaedic Association (JOA) score, neck disability index (NDI) score and visual analogue scale (VAS) were used to evaluate the clinical outcomes of the two groups. The adjacent segment intervertebral disc height and range of motion were used to evaluate the effects of heterotopic ossification on adjacent segment. Results: All patients were followed up regularly for (98±18) months. There were no statistical differences between the two groups regarding to demographic data (all P>0.05). There was no significant differences in C(2-7) Cobb angle and total range of motion between the two groups at the last follow-up (all P>0.05), but range of motion at index level in the group with low grades was significantly higher than that in the group with high grades (7.8°±6.2° vs 2.6°±1.2°, t=3.60, P<0.05). There was no significant differences in JOA score, recovery rate and NDI score between the two groups (all P>0.05). There was no significant differences in the adjacent segment intervertebral disc height before operation and at the last follow-up (both P>0.05). There was no significant differences in range of motion at adjacent segment before operation (P>0.05), while range of motion at adjacent segment in the group with low grades was significantly lower than that in the group with high grades (9.5°±1.1° vs 10.6°±1.8° and 9.4°±1.4° vs 10.5°±1.7°, repectively, t=2.54, 2.31, both P<0.05). Conclusions: Heterotopic ossification does not affect the clinical outcomes, cervical curvature and cervical total range of motion after artificial cervical disc replacement with Discover disc. However, the higher grade of heterotopic ossification, the lower range of motion at index level and the higher range of motion at adjacent segment.

[Clinical study of psychological changes and post traumatic stress disorder in elderly patients with hip fracture].

Objective: To explore the psychological state and affected factors of elderly patients with hip fractures. Methods: A retrospective analysis of 156 elderly hip fracture patients(>65 years) admitted to the Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University from January 2016 to August 2019 was performed. General and psychological information were collected by questionnaire.General information included age, gender, education, whether surgery, length of stay.SCL-90, a self-assessment scale, was chosen as the psychological test to analyzed the elderly hip fracture patients' psychological status during hospitalization and the norms of SCL-90 in Chinese which were established in 1986 were used as the control group. The prognostic factors were examined by univariate and multivariate analysis. Results: Somatization, interpersonal sensitivity, depression, anxiety, paranoid factor scores, and total scores of the elderly hip fracture patients were significantly higher than control group(all P=0.00).Univariate analysis and logistic regression analysis showed that non-surgery treatment and more than 10 days of hospitalization were independent prognostic factors that affected the psychological state of elderly hip fracture patients (all P=0.00). Conclusion: Elderly patients hospitalized with osteoporosis and hip fractures are prone to have negative emotional and psychological changes.The length of hospitalization and the choice of treatment can affect patients' psychological state, suggesting that effective psychological intervention is necessary.

Energy intake at different times of the day: Its association with elevated total and LDL cholesterol levels.

BACKGROUND AND AIMS: This study examined the association between macronutrient intake at different times of the day and blood lipid levels. METHODS AND RESULTS: The study was based on the Nutrition and Health Survey in Taiwan, a cross-sectional study of non-institutionalized and non-pregnant healthy adults (≥19-years-old). A one-day (24 h) dietary recall assessed participants' food intake. Fasting plasma triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol were determined. Low-density lipoprotein (LDL) cholesterol was estimated based on the Friedewald formula. According to the data of eligible subjects (n = 1283), the time of energy intake was categorized into three meal times 0500-0929 (morning), 1130-1329 (noon), and 1730-2029 (evening), along with three snack times 0930-1129 (mid-morning), 1330-1729 (afternoon), and 2030-0459 (night). Energy and macronutrient intake were calculated for the 6 time periods, based on 24 h recall data. An adjusted regression model showed that by transferring 100 kcal intake at night to the morning or noon, LDL cholesterol would be lower by 1.46 (95% CI: 2.42-0.50) and 1.27 mg/dL (95% CI: 2.24-0.30), respectively. Transferring 100 kcal of fat intake at night to earlier periods was associated with a lower LDL cholesterol level, especially transferring to noontime (significantly lower by 5.21 mg/dL, 95% CI: [7.42-2.99]) and evening (significantly lower by 3.19 mg/dL, 95% CI: [6.29-0.08]). CONCLUSIONS: Total cholesterol and LDL cholesterol had the same pattern of association with the timing of energy intake. The study showed that elevated total and LDL cholesterol were positively associated with nighttime energy and fat intake.

[Surgery treatment of neurofibromatosis associated severe cervical kyphotic deformity: mid- and long-term follow-up and efficacy analysis].

Objective: To investigate the surgical strategy and mid-and long-term outcomes of neurofibromatosis associated cervical kyphotic deformity. Methods: Thirteen patients with neurofibromatosis associated cervical kyphotic deformity operated in Shanghai Changzheng Hospital from January 1998 to December 2015 were analyzed retrospectively. There were 7 males and 6 females in this group, aged from 12 to 61 years, with an average age of (28±15) years. Eight patients were treated with anterior surgery (Group A) and 5 patients were treated with combined anterior and posterior surgery (Group A+P). Cobb angle correction of cervical kyphosis and improvement of clinical symptoms were followed up. Clinical efficacy between the two groups was compared and analyzed. Chi-square test, Fisher exact test and independent sample t test were used for comparative analysis between the two groups. Results: All patients were operated successfully and finished follow up. The follow-up period was from 42 to 128 months ((80±22) months). After the surgery, neurological symptoms and pain were significantly improved in all patients. Compared with preoperative values, Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) score for pain at the last follow-up were significantly improved (t=7.63, -5.19, 8.63, -4.75, all P<0.01). Cervical kyphosis was significantly improved in all patients after surgery. In group A, the Cobb angle was improved from 64°±24° preoperatively to 12°±11° at the last follow-up, and the average correction rate of Cobb angle was 82.6%. In group A+P, the Cobb angle was improved from 55°±10° preoperatively to 7°±9° at the last follow-up, and the average correction rate of Cobb angle was 88.3%. The operation time, intraoperative blood loss and length of stay in group A were all significantly lower than those in group A+P (t=-6.32, -11.92, -6.52, all P<0.01). At the last follow-up, there was no significant difference in Cobb angle, JOA score and VAS score between the two groups (t=0.89, 0.94, 1.02, all P>0.05). Conclusions: Mid-and long-term results of anterior and combined anterior and posterior surgery for neurofibromatosis associated severe cervical kyphosis are satisfactory. Moderate correction strategy for cervical kyphosis is safe and effective. The incidence of complications of nerve injury can be reduced.

[Expression of RAGE in asthmatic rats and the intervention of Roxithromycin].

Objective: To observe the expression of the Receptor of Advanced glycation end products (RAGE) in asthmatic rats, and explore the intervention of Roxithromycin. Methods: A total of 18 Specific Pathogen Free-class Brown Norway male rats were randomly divided into control group, asthma model group and Roxithromycin group, with 6 rats in each group. The asthmatic model was sensitized by intraperitoneal injection of Ovalbumin (OVA)+Al(OH)(3), and challenged with OVA. Rats in Roxithromycin group were given Roxithromycin 30 mg/kg 30 minutes before each challenge. Rats in control group and asthma model group were treated with equal volume of saline. The concentrations of RAGE and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELISA); the pathological changes of lung tissues were observed by HE-staining; the thickness of airway wall and airway smooth muscle were measured by Image-Pro Plus; the relative expression of RAGE in lung tissues were detected by Western blot. Results: In asthma model group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously higher than those in control group [(494±32) vs (327±45) ng/L; (32.4±5.8) vs (13.1±2.9) ng/L; (553±38) vs (399±56) ng/L; (37.8±3.4) vs (19.4±2.5) ng/L] (all P<0.01); in Roxithromycin group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously lower than those in asthma model group [(438±18) vs (494±32) ng/L; (22.8±6.0) vs (32.4±5.8) ng/L; (444±42) vs (553±38) ng/L; (25.6±4.5) vs (37.8±3.4) ng/L] (all P<0.05). In asthma model group, the bronchial wall was thickened, the lumen was narrow, the mucosal wrinkles were significantly increased, edema appeared under the mucosa, and a large number of inflammatory cells infiltrated and aggregated in the bronchi, perivascular and alveolar spaces; the thickness of airway wall and airway smooth muscle were significantly increased than those in control group (P<0.01); in Roxithromycin group, airway inflammation and remodeling were alleviated compared with those in asthma model group (P<0.05). In asthma model group, the expression of RAGE in lung tissues were significantly increased than those in control group (P<0.01); in Roxithromycin group, the expression of RAGE were significantly decreased than those in asthma model group (P<0.01). There were positive correlations between the expression of RAGE and IL-4 in BALF and serum (r=0.782, 0.804, all P<0.01); there were positive correlations between RAGE and total white cell counts, eosinophil counts, smooth muscle thickness (r=0.897, 0.927, 0.860, all P<0.01). Conclusions: The increasing of RAGE in asthmatic rats are positively correlated with airway inflammation and airway remodeling. Roxithromycin may inhibit the development of asthma by reducing the expression of RAGE.

[Overexpression of protein phosphatase 2 regulatory subunit B''α gene effect on proliferation and invasion of hepatoma cells].

Objective: To study the overexpression of protein phosphatase 2 regulatory subunit B''α gene effects on the proliferation and invasion of hepatoma cells. Methods: Immunohistochemistry method was used to analyze the expression of PPP2R3A in cancerous and paracancerous tissues. Hepatocellular carcinoma cell lines (Huh-7 and HepG2) with stably overexpressing PPP2R3A were constructed by lentiviral vector. Biological behavioral transition in hepatocellular carcinoma cell proliferation, cell cycle, apoptosis, invasion and metastasis were detected by cell counting kit-8 assay (CCK-8), flow cytometry, and transwell assay. A subcutaneous nude tumor mice model was constructed to validate the growth of hepatoma cells. Two independent sample t-tests were used to compare the groups. Results: The expression of PPP2R3A gene in human hepatocarcinoma tissues was higher than paracancerous tissues. The absorbance (A value) of hepatoma cells was increased (P < 0.05) after overexpression of PPP2R3A gene. The transition from G1-to-S phase was significantly increased i.e., the G1 phase of the cell cycle was reduced (Huh-7: t = 3.04, P = 0.0384; HepG2: t = 4.06, P = 0.0153), while the S phase was increased (Huh-7: t = 3.47, P = 0.0255; HepG2: t = 4.46, P = 0.0112). Early apoptotic rate was decreased (Huh-7: t = 7.34, P = 0.0018; HepG2: t = 4.06, P = 0.0153). The number of Huh-7 cells migrating to the lower chamber was increased (t = 3.18, P = 0.0334), and after the use of matrigel the number of cells reaching to the lower chamber was also increased (t = 2.84, P = 0.0464). The results of animal experiments showed that the subcutaneous tumor growth (t = 4.31, P = 0.0035) was significantly overexpressed in nude mice group. The results of Western blot showed that the expression of PARP and P53 protein in the spliced ​​forms decreased, while the accumulation of ß-catenin protein in the liver cancer cells was increased. Conclusion: Overexpressed PPP2R3A gene may promote proliferation, migration and invasion ability, inhibit apoptosis, induce G1/S phase transition, and participate in the biological behavior of hepatoma cells.

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

[Comparison of three different posterior cervical approaches for treating cervical spine trauma with ossification of posterior longitudinal ligament].

Objective: To investigate the clinical application value of using laminoplasty combine with short-segment pedicle screw fixation in the treatment of cervical spine trauma patients with ossification of posterior longitudinal ligament (OPLL). Methods: Fifty-four cervical spine trauma patients with OPLL from June 2014 to June 2016 were retrospectively analyzed of Department of Spine Surgery, Changzheng Hospital, Naval Military Medical University. There were 31 males and 23 females, aging (68.4±4.3) years (rang: 46 to 82 years). All patients had a history of cervical spine trauma, confirmed by imaging examination of OPLL, and there are signs and symptoms related to cervical spinal cord compression. Eighteen patients underwent one-stage laminoplasty combine with short-segment pedicle screw fixation(group A), and 15 patients underwent posterior cervical laminectomy and pedicle screw fixation (group B). Twenty-one patients underwent posterior laminoplasty (C group). According to the range of OPLL and the compression of the spinal cord, the range of laminoplasty was selected. MRI scan was used to evaluated the compression condition of cervical spine and the injury condition of anterior longitudinal ligament injury and other factors that can cause local instability of the cervical spine. Posterior unilateral pedicle screw fixation (two pedicles) were performed in the instability segment. The neurological function of the patients was assessed by the Japanese Orthopedic Association (JOA) Score before surgery, the second day after surgery, 3 months, 1 year and the last follow-up. The cervical spine X-ray films were used to evaluate cervical curvature, cervical spine activity and internal fixation-related complications. Results: The average follow-up time was 18 months (6-30 months). Satisfactory neurological improvement was achieved in all three groups, and no internal fixation-related complications occurred during follow-up. The range of laminoplasty was 22 cases in 4 segments (C(3)-C(6), C(4)-C(7)) and 17 cases in 5 segments (C(3)-C(7)). Unilateral pedicle screw fixation was performed in 11 patients with C(3-4) fixation and 7 patients with C(4-5) fixation. Cervical curvature was basically the same in the three groups after operation and at the last follow-up. No significant changes in cervical curvature and kyphosis were observed during the follow-up period. The overall cervical mobility (C(2)-C(7)) in group A and group C had no significant difference compared with preoperative (P=0.077). The overall mobility of cervical vertebrae in group B was significantly lower than that before surgery (P=0.013). Conclusions: For cervical spine trauma patients with OPLL, laminoplasty combined short-segment pedicle screw fixation can increase cervical segmental stability while extensive decompression of cervical spinal cord compression. At the same time, to some extent, the complications of postoperative axial symptoms caused by posterior cervical laminectomy and pedicle screw fixation were avoided.

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

Risk of developing pressure sore in amyotrophic lateral sclerosis patients - a nationwide cohort study.

BACKGROUND: Prior investigations with few cases have disclosed lack of pressure sore (PrS) formation was characteristic in amyotrophic lateral sclerosis (ALS) patients. However, studies with larger samples are lacking to ascertain this concept. OBJECTIVE: To investigate whether patients with ALS have higher risk of PrS. METHODS: Utilizing a Taiwan National Insurance claims data set with 23 million participants, we extracted 514 patients with ALS and 2056 controls from 1 January 2000 to 31 December 2008. Both groups were followed up until PrS occurrence during study period (2000-2011). The PrS risk was calculated with Cox proportional regression model. RESULTS: The patients with ALS had a greater PrS risk (adjusted hazard ratio [aHR] = 8.82, 95% confidence interval [CI] = 4.90-15.9, P < 0.001) than the controls did. PrS risk was much higher in ALS women (aHR = 26.6, 95% CI = 9.05-78.2, P < 0.001) than in ALS men (aHR = 4.38, 95% CI = 1.99-9.68, P < 0.001). Besides, in people aged 20-54, ALS was linked with a much greater PrS risk (aHR = 27.7, 95% CI = 5.79-132, P < 0.001) than in those aged ≥55 (aHR = 6.10, 95% CI = 3.10-12.0, P < 0.001). CONCLUSIONS: Amyotrophic lateral sclerosis is discovered to be correlated with an enhanced PrS risk. For PrS prevention, it is needed to pay more attention to the management of the patients with ALS, particularly in women and those with relatively younger age. Further investigations are needed to confirm the findings in this study.

Impact of weight-related advice from healthcare professionals on body mass index of patients in the USA.

OBJECTIVES: Healthcare professionals (HCPs) can help promote healthy eating and active living in patients. This study assessed the effects of weight-related advice from HCPs on change in body mass index (BMI) of patients in the USA. STUDY DESIGN: A 1-year follow-up study of 20,002 adults who participated in a nationally representative survey between 2004 and 2008. METHODS: Using the 2004-2008 Medical Expenditure Panel Survey data, 1-year BMI and weight status changes were compared between patients who did and did not report receiving advice on exercise or on restricted intake of fat and cholesterol from their HCPs. RESULTS: Patients who received weight-related advice had a greater increase in BMI compared with those who did not receive weight-related advice. Stratified by the baseline weight status of patients (i.e. normal weight, overweight or obese), adverse direction of BMI change was only significantly associated with advice on exercise. Patients who received advice to exercise more were more likely to move to a higher weight status than remaining at the same weight status, compared with patients who did not receive advice to exercise more. CONCLUSION: This study did not find that weight-related advice from HCPs had a positive impact on BMI loss in patients. On the contrary, patients who reported receiving weight-related advice from HCPs had worse weight outcomes 1 year later than patients who did not report receiving weight-related advice. Further research is warranted to elucidate the role of weight-related advice from HCPs on lifestyle change and obesity prevention and control.