More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective To investigate the expression and clinical significance of S100A14 and LOXL2 in papillary thyroid carcinoma tissues. Methods Paraffin blocks from 90 cases of thyroid lesion were collected to make tissue microarray. The expression of S100A14 and LOXL2 in 30 cases of nodular goiter (NG), 30 cases of classic papillary thyroid carcinoma (CPTC) and 30 cases of high invasion papillary thyroid carcinoma were detected by immunohistochemistry. The correlation of S100A14 and LOXL2 expression with the clinicopathological characteristics of papillary thyroid carcinoma patients was investigated. Results S100A4 and LOXL2 were highly expressed in papillary thyroid carcinoma. There was a gradually increasing trend from the expression in NG group, CPTC group to high invasive group. The positive rate of S100A14 in papillary thyroid carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.05). There was significant difference of S100A14 and LOXL2 expression between CPTC group and high invasion group (P < 0.05). S100A14 expression was positively correlated with LOXL2 expression (r=0.332). Conclusion The high expression of S100A14 and LOXL2 may be related to the malignant biological behavior and invasiveness of papillary thyroid carcinoma, and S100A14 may promote lymph node metastasis.

OBJECTIVETo detect the presence of p15 antisense RNA(p15AS) in acute myeloid leukemia(AML).

METHODSp15AS and p15 mRNA in two leukemia cell lines was detected with strand-specific primer RT-qPCR. To explore the connection between p15AS and AML, 43 patients with newly diagnosed AML and 21 patients with benign diseases (Iron deficiency anemia) as controls were enrolled. The expression level of p15AS in bone marrow cells derived from the patients and the controls were determined by strand-specific primer RT-qPCR, and its relationship with clinical features was analyzed.

RESULTSThe two AML lines displayed high p15AS and low p15 expression. Samples derived from the AML patients showed relatively increased expression of p15AS and down-regulated p15 expression in their bone cells. In contrast, the 21 controls showed high expression of p15 but relatively low expression of the p15AS. Compared with the normal controls, the expression levels of p15 protein were significantly lower among the AML patients (P<0.01). No relationships were detected between the level of p15AS and the patient's age, gender, FAB subtype, total white blood cell count, platelet count, proliferative degree of bone marrow cell and karyotype classification (P>0.05 for all comparisons).

CONCLUSIONHigh expression of p15 antisense RNA was frequently found among AML patients, and may play an important role in epigenetic silencing of p15.

Adult ; Aged ; Bone Marrow Cells ; metabolism ; Cyclin-Dependent Kinase Inhibitor p15 ; genetics ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; RNA, Antisense ; genetics ; metabolism ; Up-Regulation ; Young Adult

Objective To investigate the correlation of serum lipoprotein(a)[Lp(a)]level and coronary artery lesion degree in elderly coronary heart disease (CAD) patients with type 2 diabetes mellitus.Methods 163 elderly patients with CAD in accordance with the control fasting glucose(FPG)levels on admission were divided into A,B,C three groups:FPG <6.1 mmol/L for group A(50 cases);6.1 mmol/L≤FPG <7.0 mmol/L for group B (69 cases);FPG >7.1 mmol/L for group C (44 cases).The clinical data,count in patients with coronary artery lesions and lesion severity index(Gensini score),blood lipid and lipoprotein(a)[Lp(a)],etc were recorded.Results There was significant difference in serum Lp(a)among three groups(F =21.577,P <0.001),the Lp(a)of group C [(413.5 ±63.1)mmol/L]was higher than group B[(376.3 ±58.3)mmol/L],group B was higher than group C [(335.3 ±52.5 )mmol/L].The differences of serum Lp (a)between coronary lesion groups were statistically significant(F =69.447,P <0.001),three lesion group Lp(a)[(436.6 ±60.2)mmol/L]was higher than the double branch lesions[(362.5 ±55.7 )mmol/L],double branch lesion group was higher than the single lesion group [(315.4 ±49.9)mmol/L];Gensini score between different coronary lesions group had significant differences (F =179.969,P <0.001),three lesion group Gensini score[(61.9 ±15.4)points]was higher than double branch lesion group[(34.3 ±12.5 )points],double branch lesion group was higher than the single lesion group [(17.2 ± 9.1)points];Lp(a)≥372.3 mmol/L group Gensini score[(58.4 ±12.5)points]was significantly higher than the Lp(a)<372.3 mmol/L group[(19.2 ±10.3)points](t =21.836,P <0.01);Lp(a)≥372.3 mmol/L group three lesions proportion(57.3%)was significantly higher than 18.5% of Lp(a)<372.3 mmol/L group(χ2 =37.142, P <0.001);Pearson correlation analysis showed that the serum level of Lp(a)was positively related with Gensini score(r =0.439,P <0.001 );Multiple linear regression analysis showed that the Lp(a)was the independent risk factors affecting the Gensini score(β=4.210,P <0.001).Conclusion In elderly patients with CAD 2 diabetes significantly higher serum levels of Lp(a),the higher level is closely related to the severity of coronary lesions,and can be used as an independent predictor of coronary artery lesion severity.

BACKGROUNDCardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming.

METHODSTwenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n = 10) and control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. The volume of the priming solution, composed of 6% HES 130/0.4 and 125 IU heparin, was less than 12 ml. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rat of 100-120 ml × kg (-1)× min(-1) in CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg.

RESULTSAll CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable.

CONCLUSIONSThe establishment of CPB without blood priming in rats can be achieved successfully. The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

Animals ; Cardiopulmonary Bypass ; methods ; Lung Injury ; surgery ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDLarge animal cardiopulmonary bypass (CPB) models are expensive, and prevent assessment of neurocognitive function, and difficulties with long-term recovery. The purpose of this study was to establish a novel rat model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.

METHODSTwenty adult male Sprague-Dawley rats weighing 450-560 g were randomized to CPB with deep hypothermic circulatory arrest (DHCA) and control groups, with 10 rats each. The experimental protocols, including blood and crystalloid fluid administration, anesthesia, orotracheal intubation, ventilation, cannulation, and heparinization were identical in both groups. After inducing cardiac arrest, the circuit was turned off and rats were left in a DHCA state for 15 minutes. Rats were rewarmed to 34°C to 35°C over a period of 36 to 42 minutes using CPB-assisted rewarming, a heating blanket, and a heating lamp along with administration of 0.1 mEq of sodium bicarbonate and 0.14 mEq of calcium chloride. The remaining priming volume was reinfused and animals were weaned from CPB.

RESULTSAll CPB with DHCA processes were successfully achieved. Blood gas analysis and hemodynamic parameters were in the normal range. The vital signs of all rats were stable.

CONCLUSIONSOur CPB circuit has several novel features, including a small priming volume, active cooling/rewarming processes, vacuum-assisted venous drainage, peripheral cannulation without thoracotomy or sternotomy, and an accurate means of monitoring peripheral tissue oxygenation.

Animals ; Cardiopulmonary Bypass ; methods ; Circulatory Arrest, Deep Hypothermia Induced ; methods ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVE: To investigate the ubiquitin expression in laryngeal squamous cell carcinoma (LSCC) whether along with local lymph node metastasis, and further study its correlation with local lymph node metastasis and other clinicopathological parameters in laryngeal squamous cell carcinoma. METHOD: We detected the different expression level of ubiquitin in paraffin specimens between 19 cases of LSCC associated with cervical lymph node metastasis LSCC(N+) and 20 cases of LSCC not associated with cervical lymph node metastasis LSCC(N-) by immunohistochemical staining combined with stereology image analysis system. Statistics were analyzed by student test, variance analysis and ROC curve. RESULT: Ubiquitin expression in LSCC(N+) was significantly higher than LSCC(N-) (P < 0.01); their expression level was not correlated with age,history of tobacco, alcohol addiction, clinical stage and primary site,etc. CONCLUSION Ubiquitin was significantly up-expressed in LSCC(N+) than ILSCC (N-), which may imply that it is one of the important elements in mechanism of lymph node metastasis in LSCC.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Squamous Cell Carcinoma of Head and Neck ; Ubiquitin ; metabolism

Objective To evaluate the application value of BODE and the relationship between BODE index and life quality in patients with chronic obstructive pulmonary disease (COPD) in rural China. Methods A total of 26 rural patients with stable COPD were enrolled. BODE index and it's four components including body mass index ( BMI ), airflow obstruction ( FEV1 % ), dyspnea ( MMRC ) and exercise capacity ( 6MWD ) were calculated. St. Georgeps Respiratory Questionnaire (SGRQ) were used to evaluate health-related quality of life of these patients. Results The BODE index was significantly correlated with the SGRQ total score , symptom ,activity and impact score ( r = 0. 674,0. 430,0. 460,0. 495 respectively, Ps ＜ 0. 05 ). GOLD grade was only significantly correlated with the SGRQ total score and active score( r =0. 447,0. 418 ,Ps ＜0. 05 ). Stepwise liner multiple regression analysis showed that activity score of SGRRQ was an influence factor of BODE index. 6MWD of BODE index( t = - 2. 397, P = 0. 025 ) and MMRC ( t = 2. 257, P = 0. 034 ) were independently correlated with activity scores of SGRQ . Conclusion BODE index and life quality had significant relationship. 6MWD and MMRC of BODE index were the most powerful influence factors of life quality in rural COPD patients.