Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

[Role and mechanism of IL-6/STAT3/Th17 signaling pathway in the intervention of forsythia in acute lung injury of septic rats].

Objective: To investigate the mechanism of interleukin-6 (IL-6) /signal transducers and activators of transcriptional 3 (STAT3) /helper T cell 17 (Th17) signaling pathway in lung injury of rats with sepsis intervened by forsythia, with a view to provide experimental basis for the role and mechanism of forsythia in the treatment of sepsis. Methods: In July 2021, 30 healthy Wistar male rats were selected and randomly divided into sham operation group, model group and treatment group, with 10 rats in each group. The rat model of sepsis was established by cecal ligation and puncture. 2 h after recovery, the rats were given traditional Chinese medicine forsythia orally, twice a day at an interval of 12 h. The wet/dry mass ratio (W/D) of lung tissue was detected 24 h after surgery. The morphological changes of lung tissue were detected by HE staining. Flow cytometry was used to detect Th17 population in peripheral blood. The expression levels of IL-6 and interleukin-17A (IL-17A) in serum were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of IL-17A and IL-6 in lung tissues were detected by reverse transcription-polymerase chain reaction. The expression levels of STAT3 and IL-17A in lung tissue were determined by Western blotting. Results: Compared with model group, the W/D of lung tissue in treatment group was decreased, and the difference was statistically significant (P<0.05). HE staining of lung tissue showed that compared with the model group, the degree of lung lesion and injury was reduced in the treatment group. Compared with sham operation group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in model group was significantly increased (P<0.05). Compared with model group, the proportion of Th17 cells in CD4 lymphocytes in peripheral blood of rats in treatment group was significantly decreased (P<0.05). Compared with sham operation group, peripheral blood serum IL-6 and IL-17 of rats in model group were significantly increased (P<0.05). Compared with model group, IL-6 and IL-17 in peripheral blood serum of rats in treatment group were decreased (P<0.05). Compared with sham operation group, the expressions of IL-17A and IL-6 mRNA in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the expressions of IL-17A and IL-6 mRNA in lung tissue of rats in treatment group were significantly decreased (P<0.05). Compared with sham operation group, the protein expressions of STAT3 and IL-17A in lung tissue in model group were significantly increased (P<0.05). Compared with model group, the pritein expressions of STAT3 and IL-17A in lung tissue in treatment group were significantly decreased (P<0.05) . Conclusion: Forsythia plays a role in alleviating lung injury by down-regulating the expressions of the signaling pathway IL-6/STAT3/Th17, which providing a new target for the treatment of sepsis induced lung injury.

[Exploring the treatment of sepsis-associated acute lung injury with Liangge Powder via ERK1/2 and PI3K/AKT pathways: based on network pharmacology and whole animal experimentation].

Objective: To investigate the therapeutic effect and mechanism of Liangge Powder against sepsis-induced acute lung injury (ALI) . Methods: From April to December 2021, the key components of Liangge Powder and its targets against sepsis-induced ALI were analyzed by network pharmacology, and to enrich for relevant signaling pathways. A total of 90 male Sprague-Dawley rats were randomly assigned to sham-operated group, sepsis-induced ALI model group (model group), Liangge Powder low, medium and high dose group, ten rats in the sham-operated group and 20 rats in each of the remaining four groups. Sepsis-induced ALI model was established by cecal ligation and puncture. Sham-operated group: gavage with 2 ml saline and no surgical treatment. Model group: surgery was performed and 2 ml saline was gavaged. Liangge Powder low, medium and high dose groups: surgery and gavage of Liangge Powder 3.9, 7.8 and 15.6 g/kg, respectively. To measure the wet/dry mass ratio of rats lung tissue and evaluate the permeability of alveolar capillary barrier. Lung tissue were stained with hematoxylin and eosin for histomorphological analysis. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1ß in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The relative protein expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-protein kinase B (AKT), and p-ertracellular regulated protein kinases (ERK) were detected via Western blot analysis. Results: Network pharmacology analysis indicated that 177 active compounds of Liangge Powder were selected. A total of 88 potential targets of Liangge Powder on sepsis-induced ALI were identified. 354 GO terms of Liangge Powder on sepsis-induced ALI and 108 pathways were identified using GO and KEGG analysis. PI3K/AKT signaling pathway was recognized to play an important role for Liangge Powder against sepsis-induced ALI. Compared with the sham-operated group, the lung tissue wet/dry weight ratio of rats in the model group (6.35±0.95) was increased (P<0.001). HE staining showed the destruction of normal structure of lung tissue. The levels of IL-6 [ (392.36±66.83) pg/ml], IL-1ß [ (137.11±26.83) pg/ml] and TNF-α [ (238.34±59.36) pg/ml] were increased in the BALF (P<0.001, =0.001, <0.001), and the expression levels of p-PI3K, p-AKT and p-ERK1/2 proteins (1.04±0.15, 0.51±0.04, 2.31±0.41) were increased in lung tissue (P=0.002, 0.003, 0.005). The lung histopathological changes were reduced in each dose group of Liangge Powder compared with the model group. Compared with the model group, the wet/dry weight ratio of lung tissue (4.29±1.26) was reduced in the Liangge Powder medium dose group (P=0.019). TNF-α level [ (147.85±39.05) pg/ml] was reduced (P=0.022), and the relative protein expression levels of p-PI3K (0.37±0.18) and p-ERK1/2 (1.36±0.07) were reduced (P=0.008, 0.017). The wet/dry weight ratio of lung tissue (4.16±0.66) was reduced in the high-dose group (P=0.003). Levels of IL-6, IL-1ß and TNF-α[ (187.98±53.28) pg/ml, (92.45±25.39) pg/ml, (129.77±55.94) pg/ml] were reduced (P=0.001, 0.027, 0.018), and relative protein expression levels of p-PI3K, p-AKT and p-ERK1/2 (0.65±0.05, 0.31±0.08, 1.30±0.12) were reduced (P=0.013, 0.018, 0.015) . Conclusion: Liangge Powder has therapeutic effects in rats with sepsis-induced ALI, and the mechanism may be related to the inhibition of ERK1/2 and PI3K/AKT pathway activation in lung tissue.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3, 2021 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); The total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[Advances in immunotherapy for neuroendocrine neoplasms].

Neuroendocrine neoplasms (NEN) is a rare and heterogeneous tumor. Different pathologic morphology, differentiation, grade and clinical stages of the tumors had various treatment and prognosis. Patients with recurrent or metastatic NEN have limited treatment options and poor prognosis. In recent years, PD-1 pathway blockade has become integral components of disease management for many cancers. Immunotherapy is being explored in NEN. Studies have shown that the efficacy of immune monotherapy in NEN is limited, and it can be considered for selected patients. Biomarkers for predicting efficacy of immunotherapy include PD-L1 expression, TMB-H, MSI-H/dMMR, etc. Combined regimens of anti-CTLA-4 and anti-PD-1/PD-L1 inhibitors, and immune checkpoint inhibitor combined with anti-angiogenic drugs or chemotherapy are promising in patients with NEN, and it is worthwhile to further explore of the responding populations.

[Adrenocortical oncocytic tumors: a clinicopathological analysis of 44 cases].

Objective: To study the clinicopathological features of adrenocortical oncocytic tumors (ACOT) and to compare the diagnostic values of Lin-Weiss-Bisceglia (LWB) score and Helsinki score. Methods: Forty-four cases of ACOT diagnosed at Beijing Friendship Hospital, China from March 2008 to July 2019 were histologically analyzed to evaluate their malignant potential (benign versus malignant) according to two scoring criteria. Immunohistochemical studies (EnVision method) were also used. Results: There were 23 males and 21 females with an average age of 46 years. Histologically, the tumor cells were arranged in trabecular, chrysanthemum-shaped, glandular and microcapsule structures, while clear cells were rare or absent. Most of the tumor cells were moderately atypical, and intranuclear inclusion bodies were conspicuous. Immunohistochemical staining showed that tumor cells were positive for Melan A, inhibin, Syn and calretinin. The average proliferation index was 3% in benign ACOT, about 5% in ACOT of malignant potential, and>20% in malignant ACOT. According to the LWB score, 61.4% (27/44) of the tumors were on the left side and had multiple lesions. The percentage of benign ACOT was 59.1% (26/44), malignant potential 6.8% (3/44), malignant 34.1% (15/44), respectively. Among the 15 malignant ACOT, the mitotic figures>5/50 HPF were found in 13 cases, necrosis in 11 cases and capsule invasion in 10 cases. According to the Helsinki score, 65.9% (29/44) of the tumors were benign, and 34.1% (15/44) were malignant. There was no significant difference between the two scoring standards (P>0.05). During the follow-up of 9 to 144 months, 31 patients survived without disease and 13 patients relapsed or had metastasis. Conclusions: ACOT more likely be benign than malignant. The left side is more common. Malignant tumors are prone to recurrence and metastasis. The morphological parameters (high mitotic index, necrosis, and capsular invasion) in the LWB scoring standards combined with immunohistochemical parameters (Ki-67) in the Helsinki score are helpful for the diagnosis of malignant ACOT and are important predictors of poor prognosis.

[Clinical and genetic characteristics of children with STXBP1 encephalopathy].

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

Reduced serum exosomal miR-874 expression predicts poor prognosis in colorectal cancer.

OBJECTIVE: Emerging evidence has indicated that serum exosomal microRNAs (miRNAs) have promising diagnostic and prognostic value for colorectal cancer (CRC). This study aimed to detect serum exosomal miR-874 expression in CRC patients and assess its potential clinical significance. PATIENTS AND METHODS: Blood samples were collected from 125 CRC patients, 45 cases with benign adenomas (AD) and 70 healthy individuals. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to examine serum exosomal miR-874 levels. RESULTS: The results showed that serum exosomal miR-874 levels were significantly downregulated in CRC patients compared to AD cases and healthy controls. Receiver operating characteristic (ROC) curve analysis revealed that serum exosomal miR-874 expression could discriminate CRC patients from healthy controls, as well as patients with AD. In addition, low serum exosomal miR-874 expression was associated with positive distant metastasis, positive lymph node metastasis, poor differentiation, and advanced TNM stage. Moreover, serum exosomal miR-874 expression was identified as a statistically significant independent prognostic factor for overall survival of CRC patients. CONCLUSIONS: Collectively, serum exosomal miR-874 expression might serve as a reliable marker for CRC diagnosis and prognosis prediction.

[Effects of rhodiola rosea on oxidative stress and negative emotional states in patients with obstructive sleep apnea].

Objective:The aim of this study is to investigate the effects of rhodiola rosea on oxidative stress, anxiety and depression in patients with OSA. Method:Ninety patients with moderate and severe OSA patients with negative emotions diagnosed by PSG, self-rating depression scale （SDS） and self-rating anxiety scale （SAS） were selected from the respiratory department of our hospital from February 2015 to February 2018. According to the random number table method, the patients were randomly divided into non-invasive ventilator group, rhodiola rosea+non-invasive ventilator group and rhodiola rosea group, with 30 cases in each group. Patients in the non-invasive ventilator group were treated with continuous positive airway pressure （CPAP） for 3 months, and those in the rhodiola rosea+non-invasive ventilator group were treated with oral rhodiola capsules for 3 months on the basis of CPAP, and those in the rhodiola rosea treatment group were treated with pure oral rhodiola capsules for 3 months. The changes of SDS and SAS before and after the three groups were compared, and the changes of serum SOD and MDA were detected by immunoenzyme-linked adsorption for comparative analysis. Result:There were no significant differences in SDS and SAS scores between the three groups （P>0.05）. SDS and SAS scores of patients in the rhodiola rosea+non-invasive ventilator group decreased after treatment （P<0.05） compared with those in the non-invasive ventilator group. SDS and SAS scores of patients in the rhodiola treatment group increased after treatment （P<0.05）. Compared with those in the rhodiola treatment group, SDS and SAS scores of patients in the rhodiola+non-invasive breathing group decreased after treatment （P<0.05）. Three group patients were no significant difference in serum SOD and malondialdehyde （MDA） before treatment （P>0.05）. Compared with before treatment, serum SOD level were all increased and MDA level were all decreased in the three groups after treatment （P<0.05）. Compared with noninvasive breathing unit after treatment, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）, and for the treatment group after treatment in patients with serum SOD levels drop, the MDA levels （P<0.05）, and the after rhodiola rosea treatment group compared, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）. Conclusion:Rhodiola may improve the negative emotions such as anxiety and depression by inhibiting oxygen free radicals and lipid peroxidation in patients with OSA.

[The importance of occupational history in clinical thinking from the diagnosis and treatment of a case of Tsutsugamushi disease].

A farm worker in Baodi District of Tianjin was diagnosed with Tsutsugamushi disease due to fever and intermittent cough for more than 3 months.The patient's diagnosis and treatment process was complicated, and the diagnosis was delayed in the early stage of the disease because the clinician neglected the occupational history and lacked knowledge about the prevention and control of tsutsugamushi disease. As an important part of the epidemiological history, occupational history is crucial for the diagnosis of occupational related diseases. Clinical thinking runs through the whole process of clinical diagnosis and disease treatment, and correct clinical thinking can effectively reduce the occurrence of misdiagnosis.Clinicians should ask and record career history in detail to improve the quality of health care.

[Effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea complicated with metabolic syndrome].

Objective:The aim of this study is to analyze the effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea（OSA） complicated with metabolic syndrome. Method:One hundred and fifty-nine patients with OSA and MS were enrolled in the group A according to the exclusion criteria. One hundred and fifty-nine patients with MS group were not included in the OSA group, and 159 patients were included in the control group. Before and after treatment, the levels of serum malondialdehyde （MDA）, superoxide dismutase （SOD）, Leptin and ADP were respectively detected, and the clinical effects of the three groups were compared. Result:Compared with the control group, the contents of MDA and Leptin in the case A and B groups were significantly higher than that of the control group, and the contents of SOD and ADP were significantly lower than that of the control group, and the difference was statistically significant, especially in case group A. The level of SOD and ADP was significantly higher in the group after treatment than before treatment, and the level of MDA and Leptin was significantly lower than before treatment. The difference was statistically significant, especially in case group A, too. Conclusion:Patients with OSA and MS are associated with oxidative stress. Glutathione can effectively improve the body's ability to resist oxidative stress, reduce oxidative damage, reduce leptin, and increase ADP levels.

[Effects of butylphthalide on plasma nitric oxide and endothelin-1 in severe elderly OSAHS patients].

Objective:To investigate the effect of butylphthalide on plasma nitric oxide(NO) and endothelin-1(ET-1) in severe elderly OSAHS patients. Method:A total of 120 severe elderly OSAHS patients were chosen by PSG measurement. According to random number table method, OSAHS patients were randomly divided into non-invasive ventilation control group(n=40), butylphthalide treatment group(n=40) and butylphthalide combined with non-invasive ventilation group (n=40). Non-invasive ventilation control group was given double level airway positive pressure ventilation treatment for six months, butylphthalide treatment group accepted oral butylphthalide therapy for six months, butylphthalide combined with non-invasive ventilation group was given double level airway positive pressure ventilation treatment and accepted oral butylphthalide therapy for six months. The changes of plasma NO and ET-1 were detected by immunoenzyme adsorption before treatment and three and six months after treatment. Result:The difference of plasma NO and ET-1 before treatment in the three groups was not statistically significant (P>0.05). Compared with before treatment, the level of plasma NO decreased and the level of plasma ET-1 increased in the three groups after three and six months treatment (P<0.01). Compared with butylphthalide treatment group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in both non-invasive ventilation control group and butylphthalide combined with non-invasive ventilation group (P<0.05). Compared with non-invasive ventilation control group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in butylphthalide combined with non-invasive ventilation group (P<0.05). Conclusion:Butylphthalide may improve the vascular endothelial function of severe elderly OSAHS patients by increasing the level of NO and decreasing the level of ET-1 in plasma.

[Progress in studies on obstructive sleep apnea and intestinal microecological balance].

SummaryObstructive sleep apnea （OSA） is closely related to the development of various diseases. Hypoxic perfusion caused by OSA can mediate the occurrence of inflammatory reactions or aggravate metabolic disorders to affect intestinal microecological balance. Intestinal bacteria can participate in the development of inflammatory reaction or metabolic disorder by itself or its components, and the oxidative stress reaction of the body develops in a vicious circle. The mechanism has not yet been fully elucidated, so we reviewed the research progress on OSA and intestinal microecological balance.

[Effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome patients].

Objective:To explore the effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome (OSAHS)patients.Method:A total of 90 old OSAHS patients with cognitive impairment were choosed with Polysomnography（PSG）. By random number table method OSAHS patients were randomly divided into non-invasive ventilator group (n=30), butylphthalide with non-invasive ventilator group(n=30) and treatment group of butylphthalide(n=30). Non-invasive ventilator group was given continuous positive airway pressure treatment for three months, butylphthalide with non-invasive ventilator group accepted oral butylphthalide therapy and continuous positive airway pressure treatment for three months, treatment group of butylphthalide only accepted oral butylphthalide therapy for three months. Cognitive function of three groups wered observed by the Montreal cognitive assessment scale (MoCA) before and after treatment, at the same time, the changes of serum superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by immunoenzyme-linked adsorption.Result:The differences of serum SOD and MDA before treatment among the three groups were not statistically significant (P＞0.05). Compared with before treatment, the level of serum SOD increased and the level of MDA decreased in the three groups (P<0.05). Compared with non-invasive ventilator group after treatment，the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05)， the level of SOD decreased and the level of MDA increased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05); The scores of MoCA on cognitive function before treatment in the three groups was not statistically significant (P＞0.05). After treatment the scores of MoCA on cognitive function in the three groups were higher than those before treatment (P<0.05). Compared with non-invasive ventilator group after treatment， the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05),the the scores of MoCA decreased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05).Conclution: Butylphthalide can improve the activity of antioxidant enzymes in the serum of old patients with OSAHS, inhibit the oxygen free radical and lipid peroxidation and to a certain extent improve the cognitive function.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

[The effect of monrustet on the exhalation of nitric oxide and inflammatory cytokines in patients with asthma combined with OSAHS].

Objective:To study the effect of monrustet on fractional exhaled nitric oxide and inflammatory cytokines in the elderly with bronchial asthma combined obstructive sleep apnea hypopnea syndrome.Method:150 cases diagnosed as asthma were enrolled in this study. The patients were divided into bronchial asthma combined with OSAHS (n=72)and bronchial asthma (n=78). According to the different treatment methods , patients were divided into observation group and control group. Two groups were given common treatment with inhaled corticosteroids, and the observation group was taken orally montrast 10mg/night additionally. The fractional exhaled nitric oxide was detected before and after treatment. Serum were collected for detection of tumor necrosis factor alpha (TNR-α), Creactive protein (CRP) and interleukin 6 (IL-6), according to the sleep monitoring results, the sleep apnea low ventilation index (AHI) was calculated, and the changes of FeNO level,CRP,TNR-α,IL-6 and AHI were analyzed in the two groups.Result:Before treatment, the gender, age, degree of disease, FeNO level,TNR-α, CRP,IL-6 and AHI differences were not statistically significant in the two groups (P>0.05).After treatment, both groups of FeNO, TNR-α,CRP,IL-6 and AHI decreased before treatment (P < 0.05).The observation group was lower than the control group, and the difference was statistically significant (FeNO level, AHIP< 0.01,TNR-α, CRP,IL-6 P< 0.05).Conclusion::Montelukast can reduce the FeNO level, the expression of TNR-α, CRP, and IL-6 of patients of bronchial asthma combined with OSAHS. Further improvement of the patient's condition, and provide reference value for the clinical medicine of patients with asthma.

[Effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome].

Objective:To study effects of ketotifen on fractional exhaled nitric oxide in patients with combined allergic rhinitis and asthma syndrome.Method:One hundred and twelve patients with asthma were selected from department of respiration, Affiliated Hospital of North China University of science and technology from January 2016 to 2017 in March. Eighty-four patients with allergic rhinitis were selected as the subjects, Randomly divided into two groups,including observed group(n=42) and control group(n=42).The control group was treated with antitussive,expectorant and inhaled corticosteroids, while the observed group in the control group combined with ketotifen 1 mg 2/ day oral treatment,the changes of FeNO and IL-17 in the two groups were compared after one month treament.Result:Before treatment, two groups of patients in general IL-17 and fractional exhaled nitric oxide ware no significant difference(P> 0.05).After treatment, compared to the control group, the observed group was significantly more effective,the difference was statistically significant(P <0.05);fractional exhaled nitric oxide in treatment group were lower than those in control group, the difference was statistically significant(P<0.05,P< 0.01).And the observed group was lower than the control group, and the differences were statistically significant,t(P<0.05).Conclusion:Ketotifen significantly reduce the FeNO of allergic rhinitis and asthma syndrome, reduce airway inflammation.