[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

Characterizing kinase intergenic-breakpoint rearrangements in a large-scale lung cancer population and real-world clinical outcomes.

BACKGROUND: Kinase gene fusions are strong driver mutations in neoplasia; however, kinase intergenic-breakpoint rearrangements (IGRs) confound the detection of such fusions and of targeted treatments. We aim to provide an overview of kinase IGRs in a large lung cancer cohort and examine real-world survival outcomes of patients with such fusions. METHODS: Mutational profiles analyzed using targeted next-generation sequencing of 425 cancer-related genes between June 2016 and July 2019 were retrospectively reviewed. Patients' demographic data, clinical characteristics, and survivals were analyzed. RNA sequencing or immunohistochemical assays were carried out to verify chimeric fusion products. RESULTS: We identified 3411 patients with kinase fusions from a cohort of 30 450 patients with lung cancer, and 624 kinase IGR events were identified in 538 of the 3411 patients. The most frequently identified kinase genes included anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), ROS proto-oncogene 1 (ROS1), Erb-B2 receptor tyrosine kinase 2/3 (ERBB2/3), and epidermal growth factor receptor (EGFR). Our data showed that most (67%) kinase IGRs occurred on the same chromosome and kinase domains remained intact at the 3'-end. Approximately 3% (19/624) of the kinase IGRs had one genomic breakpoint located in gene promoter regions, including nine fusion events involving ALK, RET, ROS1, EGFR, ERBB2, or fibroblast growth factor receptor 3 (FGFR3). Among the 538 patients with kinase IGRs, 167 (31%) lacked oncogenic driver mutations, among which 28 received targeted therapies in real-world practice. Notably, three ALK IGR patients who harbored no canonical oncogenic aberrations were confirmed with an EML4-ALK chimeric fusion product by RNA sequencing and/or ALK immunohistochemical assays. One patient demonstrated a favorable clinical outcome after 14 months on crizotinib. An additional two patients who had ROS1 IGRs demonstrated a clinical benefit after 13 and 19 months on crizotinib, respectively. CONCLUSION: A large real-world lung cancer cohort with kinase IGRs was comprehensively analyzed for their molecular characteristics. The data indicated the potential oncogenic function of kinase IGRs and their outcomes following the administration of targeted therapies.

[Clinical application of serum Golgi protein 73 in patients with chronic liver diseases].

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

[Effect of extracorporeal membrane oxygenation on pharmacokinetics of antimicrobial drugs: recent progress and recommendations].

Extracorporeal membrane oxygenation (ECMO) is an effective means to provide life support for patients with severe respiratory or heart failure. Existing studies have shown that ECMO may affect the metabolic process of some drugs by drug adsorption, increasing the apparent distribution volume and changing the clearance rate of the drugs. This review summarizes the recent progress in the studies of the effect of ECMO on the pharmacokinetics of antibacterial and antifungal drugs. For the antibacterial drugs, it is recommended that the dose of teicoplanin, imipenem, and linezolid should be increased during ECMO support, while the dose of azithromycin, ciprofloxacin, and tigecycline should not be modified for the time being. Currently studies on pharmacokinetic changes of antifungal drugs during ECMO support remain limited. Voriconazole can be absorbed substantially by ECMO due to its high lipophilicity, and higher doses are therefore recommended. The dose of micafungin also needs to be increased in children undergoing ECMO. However, current evidence concerning the dose of caspofungin and fluconazole are limited, and it is not clear whether the routine dose should be adjusted during ECMO support.

[Relationship between platelet/lymphocyte ratio and cognitive impairment in diabetic patients treated with maintenance hemodialysis].

Objective: To explore the relationship between platelet/lymphocyte ratio (PLR) and cognitive impairment (CI) in diabetic patients treated with maintenance hemodialysis (MHD). Methods: The data of age, gender, underlying diseases, medication history, mini-mental state examination (MMSE) and biochemical indexes of diabetic MHD patients who were treated in 18 hemodialysis center in Guizhou Province between May and August 2019 were collected. According to whether they had CI or not, the patients were divided into CI group and control group, and the clinical characteristics between the two groups were compared. In addition, the patients were divided into four groups according to the quartile of PLR (PLR Q1, Q2, Q3 and Q4 group). Multivariate logistic regression models were used to analyze the relationship between PLR level and CI in diabetic MHD patients. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of PLR in detecting CI in diabetic MHD patients. Results: Totally, 586 diabetic MHD patients (389 males) were included, with a mean age of (63±11) years. Multivariate logistic regression analysis showed that PLR was associated with the risk of CI in diabetic MHD patients, and the risk of CI in PLR Q4 group was 3.022 times of that of PLR Q1 Group (95%CI: 1.866-4.895, P<0.001). After adjusting for gender, age, dialysis age and education level, the risk of CI in PLR Q4 group was 2.529 times of that in PLR Q1 Group (95%CI: 1.536-4.164, P<0.001). After further adjusting for hemoglobin, albumin, creatinine, leukocyte and blood glucose, the risk of CI in PLR Q4 group was 2.281 times of that in PLR Q1 group (95%CI: 1.203-4.326, P=0.012). ROC curve analysis showed that the optimal threshold for PLR to predict CI in diabetic MHD patients was 155.3, with a sensitivity of 57.2% and a specificity of 60.8%, and the area under the curve was 0.608 (95%CI: 0.561-0.644, P<0.001). Conclusion: PLR is associated with CI in diabetic MHD patients.

[Investigation on the awareness of snoring hazard and prevalence of obstructive sleep apnea among civil servants].

Objective: To investigate the awareness of snoring hazard and prevalence of obstructive sleep apnea (OSA) among civil servants. Methods: A cross-sectional survey was conducted to investigate the awareness of snoring hazards among in-service civil servants who had annual medical examination in a Guangdong provincial institution from September to November 2017. The high-risk group for OSA was screened and diagnosed by sleep monitoring. Results: 1 036 of 1 241 civil servants were enrolled in the study for integral data. 60.1% (623/1 036) of the subjects realized that snoring was harmful to health. The most common source to develop OSA awareness was network (59.6%, 371/623), followed by television (48.0%), relatives and friends (46.6%), newspaper (44.5%) and radio (18.9%). The awareness rate of snoring consequences was as follows: decreased sleep quality (71.9%, 448/623), sudden death (52.2%), daytime sleepiness (44.3%), cardiovascular and cerebrovascular diseases (42.9%), hypertension (24.4%) and sexual dysfunction (16.7%). 22.0% (228 / 1 036) of the cases were classified into high-risk OSA. The prevalence of OSA among high-risk group was 46.05%(105/228)and only 0.9% (2/228) of them had been diagnosed with OSA. Conclusion: Civil servants had awareness of snoring hazard to a certain extent. Among civil servants classified into high-risk OSA, the OSA perveance was high but the rate of diagnosis and treatment was very low.

[The expressions of CTLA-4 and PD-1 on CD(4)(+) T cells and the level of plasma VEGF in patients with obstructive sleep apnea hypopnea syndrome].

Objective: CD(4)(+)T cells, cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF) are associated with cancer development. The aim of the present study was to investigate the expression of CTLA-4, PD-1 and VEGF in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From January 2017 to January 2018, a total of 47 first-visit outpatients were recruited in the Sleep and Respiratory Disorder Center of Guangdong Provincial People's Hospital, and were divided into control group (N=17, mean age 54±12 years), mild-to-moderate OSAHS group (N=15, mean age 54±12 years) and severe OSAHS group (N=15, mean age 56±13 years). Venous blood was collected, plasma and cells were isolated, the expressions of PD-1 and CTLA-4 on the surface of CD(4)(+)T cells were detected by flow cytometry, and plasma VEGF was measured by enzyme linked immunosorbent assay. Results: The proportion of CD(4)(+)T cells in control group, mild-to-moderate OSAHS group and severe OSAHS group were respectively(38±8)%, (35±8)% and (38±6)% (F=1.228, P>0.05). The expression of CTLA-4 on CD(4)(+)T cells were respectively [1.13 (0.59~1.78)]%, [0.45 (0.16~1.43)]% and [0.87(0.47~1.46)]% (H=2.205, P>0.05). The expression of PD-1 on CD(4)(+)T cells were respectively [4.24 (2.12~6.03)]%, [3.54(2.69~5.09)]% and [3.31(1.67~8.25)]% (H=0.541, P>0.05). The concentrations of VEGF in control group, mild-to-moderate OSAHS group and severe OSAHS group were statistically different [(395.16±87.78) ng/L vs (452.85±107.97) ng/L vs (546.42±199.27) ng/L, F=4.827, P=0.013]. Compared with the control group, VEGF concentration was significantly increased in the severe OSAHS group(P<0.01). VEGF concentration was correlated negatively with the lowest SpO(2) (r (s)=-0.480,P=0.001), but positively with apnea-hypopnea index(r (s)=0.403, P=0.005), oxygen desaturation index (r (s)=0.378, P=0.010) and proportion of SpO(2) less than or equal to 90% of total sleep time(r (s)=0.547, P=0.000 3). Conclusion: There was no significant difference of PD-1 and CTLA-4 expression on CD(4)(+)T cells in patients with and without OSAHS. The expression of VEGF was elevated in OSAHS patients, and increased with the severity of OSAHS and hypoxia.

Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via the PI3K-Akt-mTOR signaling pathway in rheumatoid arthritis.

Our previous study revealed that Yin Yang 1(YY1) played an important part in promoting interleukin (IL)-6 production in rheumatoid arthritis (RA). However, whether YY1 has any role in regulation of IL-8 in RA remains unclear. YY1 and IL-8 expression in RA patients were analyzed by real-time polymerase chain reaction (PCR). Ingenuity pathway analysis (IPA) was used to analyze the signaling pathway involved in YY1-induced IL-8 production. The expression of YY1 and proteins involved in the pathway were detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Migration of neutrophils was performed by chemotaxis assay. In this study, we found that high expression of IL-8 was positively associated with YY1 expression in RA. Blocking YY1 expression by YY1-short hairpin (sh)RNA lentivirus reduced IL-8 production. Mechanistically, we showed YY1 activated IL-8 production via the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Further, using a co-culture system consisting of peripheral blood mononuclear cells (PBMC) and neutrophils, we found that migration of neutrophils would be inhibited by YY1 RNA interference. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the YY1-shRNA lentivirus led to reduction of IL-8 levels and attenuation of inflammation and neutrophil infiltration in vivo. Our results reveal a role of YY1 involved in neutrophil infiltration in RA via the PI3K/Akt/mTOR/IL-8 signaling pathway. YY1 may be a new therapeutic target for treatment of RA.

[Performance of matrix assisted laser desorption ionization time of flight biotyper system in clinical bacteria identification].

Objective: To evaluate the performance of MALDI Biotyper system in identification of clinically isolated pathogens so as to provide a new rapid identification method. Methods: Total 21 270 pathogens strains, isolated from the First Affiliated Hospital of Fujian Medical Universityduring Nov. 2015 to Dec. 2016, were identified by VITEK-Ⅱ, API and MALDI Biotyper system, respectively.The isolated strains were confirmed by DNA sequencing. Results: The identification of common bacteria with MALDI Biotyper and phenotypic system is highly consistent (>95% and >90%). Among 43 strains of anaerobic bacteria, MALDI Biotyper could identify 90.7% bacteria to species level and 97.7% bacteria to genus level with the statistical significance(χ(2)=6.76, P<0.01), while phenotypic system only identified 65.1% bacteria to species and 69.8% bacteria to genus. Also, no statistical significance was shown for Trichosporon and Candida(P>0.05). MALDI Biotyper could identify 76% filamentous fungi and all of Actinomycetes, Nocardia, Mycobacterium and Legionella to genus level. Conclusions: MALDI Biotyper is an easy-performed, sensitive method for the identification of clinically isolated pathogens. Additionally, the pretreatment and reference database has the effect on identification.

[A cross-sectional survey of treatment acceptance and influence factors in patients with obstructive sleep apnea].

Objective: To investigate the treatment acceptance in patients with obstructive sleep apnea (OSA) and its influence factors. Methods: This cross-sectional survey recruited OSA patients diagnosed at sleep center in Guangdong General Hospital from January 2014 to December 2015. By phone follow-up, a pre-designed questionnaire was performed for all adults, which composed of the following sections: treatment or none, treatment method, reason for non-treatment, revisit or none. Results: From 524 OSA patients with completed contact information, 480 (91.6%) valid questionnaires were collected. The apnea hypopnea index was (36.1±21.4) /h. The mild, moderate, severe OSA patients accounted for 12.5%(60 cases), 33.1%(159 cases), 54.4%(261 cases) respectively. For all 480 included subjects, 200 (41.7%) received treatment and among them 184 (92.0%) were treated by continuous positive airway pressure. The treatment rate was lower in mild OSA, non-obesity, female, and patients without daytime sleepiness. Receiving treatment was negative correlated to difficult falling asleep. The first reason of non-treatment was self-determined behavioral intervention and the second was self-concept of no requirement for treatment. The specialist revisit rate was 3.8%, which was slightly higher in treated patients and those with sudden awakening when feeling asphyxia. Conclusion: A majority of OSA patients do not receive treatment, primarily as a result of their self-determined behavior intervention and self-concept of no requirement for treatment.

Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). OBJECTIVE: To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. METHODS: Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. RESULTS: Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. CONCLUSION: The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD.

[Long-term outcome and prognostic factors in pregnant women with pulmonary arterial hypertension associated with congenital heart disease].

Objective: To investigate the perinatal outcome, risk factors and long-term outcome of pregnancy complicated with pulmonary arterial hypertension(PAH) and congenital heart diseases (CHD). Methods: Clinical data of 110 pregnant women who were diagnosed as PAH-CHD were retrospectively analyzed in the Department of Obstetrics and Gynecology and Surgical Intensive Care Unit at Beijing Anzhen Hospital from 2004 to 2013. The survival and treatment status were followed up. Results: 110 subjects consisted of 11 mild PAH, 33 moderate and 66 severe ones. The incidences of deterioration in New York Heart Association (NYHA) classes (≥2) during pregnancy, respiratory failure, pulmonary hypertension crisis and arrhythmia were 25.5% (28/110), 7.3% (8/110), 10.0% (11/110), 10.0% (11/110) respectively. Among them, the difference of deterioration in NYHA classes (≥2) during pregnancy among the three groups was statistically significant. A total of 8 (7.3%) maternal deaths occurred during hospitalization, all of whom were severe PAH cases. Multivariate analysis showed that pulmonary artery systolic pressure was a risk factor of perioperative death (OR=1.042, P=0.005). There were 55 cases (50.0%) of term delivery, and 35 cases (31.8%) of iatrogenic abortion. The proportion of term delivery in the severe PAH group was significantly lower. The proportion of iatrogenic abortion and small for gestational age infant (SGA) were higher in severe group. The incidence of neonatal malformations was 8.0% (6/75). The follow-up rate was 61.8% (63/102). Sudden death was reported in a parturient a few days after discharge. The remaining 62 patients survived during follow-up, while 53 patients (85.5%) were functional class (FC) Ⅰ-Ⅱ, 9 (14.5%) were FC Ⅲ-Ⅳ at follow-up. The cardiac function deterioration during pregnancy was not significantly correlated with long-term deterioration (P=0.767). Conclusions: Perinatal mortality and the incidence of maternal and fetal adverse events were high in pregnancy with PAH-CHD. Pulmonary artery systolic pressure is a major risk factor for perioperative mortality in pregnant women. PAH-CHD woman had good overall outcome after puerperium.

A molecular epidemiological study of methicillin-resistant Staphylococci environmental contamination in railway stations and coach stations in Guangzhou of China.

Methicillin-resistant Staphylococcus aureus (MRSA) has caused a series of public health problems since it was first found in 1961. However, there are few research studies on the MRSA environmental contamination in railway stations and coach stations. Therefore, the aim of this study was to determine MRSA environmental contamination in public transport stations. Between December 2013 and January 2014, 380 surface samples from three railway stations (180) and four coach stations (200) in Guangzhou were collected to isolate and determine the prevalence and characteristics of Staphylococci strains. 39·21% of all samples were Staphylococci isolates, 1·58% of Staphylococci isolates were MRSA isolates, and 6·05% were methicillin-susceptible S. aureus. The proportion of multidrug resistant among 149 Staphylococci isolates was 75·84%. None of MRSA isolates was identified with the Panton-Valentine Leukocidin (PVL) genes, and one of them was identified with the qac gene. Four MRSA isolates were Staphylococcal Cassette Chromosome mec IVa, and the other two were nontypeable. Staphylococcus aureus isolates were classified into several sequence types (STs), and STs showed possible cross-transmissions of isolates from various sources. Methicillin-resistant Staphylococci contamination prevalence was high, and the environment of stations may be the vectors transmitting the Staphylococci to passengers. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to comprehensively report the prevalence, antibiotic resistance, and molecular characteristics of contamination of Staphylococci isolates in railway stations and coach stations of China. It will have great public health implications on infection control in community settings because of the serious hazard of Staphylococci, especially methicillin-resistant Staphylococci. Our findings have provided evidence for relevant departments to reduce the contamination of Staphylococci in environment of public transport stations.

[The expression of macrophage migration inhibitory factor in obstructive sleep apnea hypopnea syndrome and its injury to endothelial cells].

Objective: To study the expression of macrophage migration inhibitory factor (MIF) in obstructive sleep apnea hypopnea syndrome (OSAHS) and its injury to endothelial cells. Methods: According to the PSG test results, subjects who were the first time to take PSG examination without treatment (n=71) were divided into a control group (n=20), a mild OSAHS group (n=19), a moderate OSAHS group (n=15) and severe OSAHS group (n=17). For each patients, 4 ml fasting peripheral blood was obtained when PSG was finished around 6: 30 in the next morning, and the MIF level in plasma was detected with the ELISA method. Peripheral blood mononuclear cells (PBMC) from the control group and the severe OSAHS patients were cocultured with umbilical vein endothelial cells (HUVEC) for 72 hours. The apoptosis of HUVEC was detected by flow cytometry, while ET-1, NO, sICAM-1 and IL-6 in the supernatants were measured with the ELISA method. Results: The plasma level of MIF in the control group and the mild, the moderate, and the severe OSAHS patients was (26±8), (28±9), (31±14), (39±15) ng/ml, respectively (F=15.65, P<0.001), and it was higher in the severe OSAHS group as compared to the control group(P<0.01). The level of MIF was associated positively with the apnea hypoventilation index (AHI, r=0.365, P=0.008) and the oxygen index reduction (ODI, r=0.308, P=0.308) n but negatively with the lowest blood oxygen (r=0.323, P=0.323). Endothelial cell apoptosis rate in the control group and the severe OSAHS group was (2.94±1.02) %, (8.23± 3.01) %, respectively, t=5.97, P<0.001. ET-1 in the control group and the severe OSAHS group was (6.71±5.52), (9.88±4.79) pg/ml, respectively, t=3.018, P=0.141. sICAM-1 in the control group and the severe OSAHS group was (11±8), (20±7) ng/ml, respectively, t=7.58, P=0.014. NO in the control group and the severe OSAHS group was (35±16), (25±5) mol/L, respectively, t=2.01, P=0.067. IL-6 in the control group and the severe OSAHS group was (220±42), (436±178) mol/L, respectively, t=2.77, P<0.05. Conclusion: MIF is closely related to the degree of OSAHS severity, and it may be involved in the development and endothelial injury in OSAHS.

[Analysis of long-term compliance to continuous positive airway pressure in patients with obstructive sleep apnea].

OBJECTIVE: To explore the continuous positive airway pressure (CPAP) therapy compliance in patients with obstructive sleep apnea (OSA). METHODS: This prospective study recruited a group of subjects from May 2009 to December 2013 who were diagnosed and had accepted CPAP treatment in Sleep Center of Guangdong General Hospital, and the patients were followed-up regularly for long-term and assessed the CPAP treatment compliance. The patients were diagnosed, had pressure titration and CPAP treatment through out of center sleep test. The subjects were followed-up for 1 st, 3rd, 6th, 12th month, and each year regularly after accepting the CPAP treatment in Sleep Center by face to face follow-up with specialist physicians. Physicians followed-up the patients' subjective symptoms, CPAP adherence, patient education and side effect solutions. The patients were classified into good and poor compliance groups, and statistical analysis was done between the two groups. RESULTS: There were 77 cases enrolled until December 2015, only 73 patients completed the study. The patients were followed-up about 2-6 years, the average was (3.93±1.29) years, the compliance accounted for 54.8% (40/73), and the average compliance was (4.02±1.87) hours/night. The trend of the long-term compliance showed that there was a gradual increase within the first 3 months of CPAP treatment and then the compliance decreased; it then increased gradually after the first two years. The good compliance group showed that the compliance increased gradually in the initial 3 months, and then fell; from the first year to the 3rd year, the compliance was stable; after the 3rd year there was a drop and the compliance tended to increase again after the 4th year. The poor compliance group showed the compliance had a downward trend from the beginning of the first two years, then after a brief rise, the compliance decreased linearly. Multivariate analysis showed that long-term compliance was not associated with age, daytime sleepiness (ESS), oxygen desaturation index (ODI), anxiety, depression (P>0.05), etc. However, it was associated with the time of the titration treatment (P<0.001), the time of the flow monitored (P<0.01) and the number of the pressure titration within one week (P<0.05). CONCLUSIONS: Long-term compliance shows a curve change, the increased compliance is related with the regular follow-up. Long-term compliance can be predicted by the degree of cooperation with the initial diagnosis and treatment.

Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration.

Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.

Hybrid biofilm-membrane bioreactor (Bf-MBR) for minimization of bulk liquid-phase organic substances and its positive effect on membrane permeability.

Four biofilm membrane bioreactors (Bf-MBRs) with various fixed carrier volumes (C:M) were operated in parallel to investigate the effect of attached-growth mode biomass involvement to the change of liquid-phase organics characteristics and membrane permeability, by comparing with conventional MBR. The experiments displayed that C:M and co-existence of biofilm with suspended solids in Bf-MBRs resulted in slight difference in pollutants removal effectiveness, and in rather distinct biomass properties and bacterial activities. The membrane permeability and specific resistance of bulk suspension of Bf-MBRs related closely with the liquid-phase organic substance, including soluble microbial products (SMP) and biopolymer cluster (BPC). Compared with conventional MBR, Bf-MBR with proper C:M had a low total biomass content and food-chain, where biofilm formation and its dominance affected liquid-phase organics, especially through reducing their content and minimizing strongly and weakly hydrophobic components with small molecular weight, and thus to mitigate membrane fouling significantly.

Interleukin-10 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.

It has been reported that interleukin-10 (IL-10) promoter genes (1082 A/G, 819 T/C, 592 A/C) are associated with nasopharyngeal carcinoma (NPC). However, the results remain controversial and ambiguous. To resolve inconsistencies in published data, we performed a meta-analysis to ascertain the association between IL-10 polymorphisms and NPC risk. Two case-control studies and two cohort studies were quantitatively analyzed to evaluate IL-10 promoter gene polymorphisms and NPC risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for each genetic model and allelic comparison. A random-effect model or a fixed-effect model was used to calculate the overall combined risk estimates. Overall, the variant genotypes (AA and AG) of the IL-10-1082 A/G polymorphism were associated with elevated risk of NPC compared with the GG homozygote (AG vs GG: OR = 1.77; 95%CI = 1.39-2.26; AG + GG vs AA: OR = 1.78; 95%CI = 1.42-2.22); no significant associations were observed in allelic contrast and the recessive model. Strong positive association was seen in the cohort studies but not in the case-control studies. No statistically significant association was detected between IL-10-819 T/C and IL-10-592 A/C polymorphisms and NPC. Additionally, publication bias was not found. Based on the current evidence, this meta-analysis suggests that IL-1082 A/G polymorphism may increase the risk of NPC, but IL-10-819 T/C and IL-10-592 A/C polymorphisms do not. Further multicenter studies that are better controlled are required to confirm these findings.