To explore the clinical significance of changes in maximal expiratory flow in 50％ and 25％ vital capacity (Vmax50％ & Vmax25％) before and after bronchodilator reversibility testing in patients with asthma.Forced expiratory volume in one second (FEV1),Vmax50％ and Vmax25％ were measured before and after bronchodilator reversibility testing in 118 patients with asthma and 82 with chronic obstructive pulmonary disease (COPD).The rate of positive reversibility in Vmax50％ was significantly higher than that in FEV1 in 118 asthmatics (x2 =7.995,P =0.007).The rates of positive reversibility in Vmax50％ and Vmax25％ were significantly higher in asthmatics than those in COPD patients (x2 =9.335,P =0.009).

Plasma level of N-terminal pro brain natriuretic peptide (NT-proBNP) was measured for 362 elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), including 97 of AECOPD complicated with left-heart failure and 265 of isolated AECOPD.Results indicated that there was significant difference in plasma level of NT-proBNP between the two groups ( P = 0.000).With a cut-off value of 1643.5 ng/L NT-proBNP, its sensitivity, specificity and accuracy for identifying AECOPD complicated with left-heart failure in the elderly were 84.4%, 85.3% and 85.1%, respectively.It is suggested that assay for plasma NT-proBNP may be helpful to identify left-heart failure in elderly patients with AECOPD.

Objective To investigate clinical significance of small airway function and eosinophil (Eos) percentage,levels of eosinophil cationic protein (ECP) and IL-5 in induced sputum among patients with clinically controlled asthma. Methods Sixty-two patients with clinically controlled asthma were selected for the study. Lung function was performed and percentage of Eos, levels of ECP and IL-5 in induced sputum were measured by Wrights' stain, fluorescence immuno-CAP system and ELISA,respectively. Thirty patients of asthma at acute exacerbation period and 20 healthy subjects were selected as controls. Results In 62 patients with clinically controlled asthma, 43 (69. 4% ) showed abnormal small airway function and 19(30. 6% ) normal one. Percentage of Eos [(5. 6 ±2. 9)%], levels of ECP [( 129 ±100) μg/L] and IL-5 [(21± 12) μg/L] in induced sputum were significantly lower in patients with clinically controlled asthma than those of asthma at acute exacerbation period [( 16. 2 ± 9. 7 ) %, ( 362 ±182) μg/L and IL-5(51 ±26) μg/L, respectively] (all P ＜0. 01 ), but significantly higher than those in healthy controls ( all P ＜ 0. 01 ). Percentage of Eos, levels of ECP and IL-5 in induced sputum were significantly higher in patients with clinically controlled asthma with abnormal small airway function than those with normal ane [(6.9±3.1)% vs. (2.0±1.1)%, (148±90) μg/Lvs. (54±29) μg/L and (24 ±12) μg/L vs. ( 13 ± 5 ) μg/L, respectively] ( all P ＜ 0. 01 ). Conclusions Abnormal small airway function and airway inflammation persistently exist in patients with clinically controlled asthma and it may be helpful to guild treatment during clinical control to determine small airway function and inflammatory markers in their induced sputum.

Objective To explore the effects of theophylline plus salmeterol/fluticasone propionate combination product (SFC) on clinical control,lung function and airway inflammation in asthmatics.Methods A total of 146 asthmatics received 200 mg theophylline plus 50/250 μg SFC twice daily for 24 weeks.The level of asthma control was assessed by the asthma control test.Testing of lung function and inflammatory markers in induced sputum were performed.And 142 asthmatics received 50/250 μg SFC twice daily for 24 weeks as control.Results Asthma was completely controlled in 61 and 59 in the theophylline plus SFC and SFC groups respectively after a 24-week treatment period (P ＞ 0.05).Theophylline plus SFC improved the FEF25％ 75％ value,indicating small airway function,to a greater extent than SFC [(66.7 ± 18.2) ％ & (56.6 ± 17.4) ％,P ＜ 0.01].Percentage of eosinophil and concentration of eosinophil cationic protein in induced sputum were significantly lower in the theophylline plus SFC group than those in the SFC group [(4.1 ±2.3)％ vs.(6.2±2.7)％ & (63.9±39.4) vs.(90.3 ±46.2) μg/Lrespeetively] (all P ＜ 0.01).Conclusion The therapy of theophylline plus SFC may provide greater improvements in small airway function and airway inflammation.

Objective:To investigate the effect of type ⅡNKT cells activated by sulfatide on airway inflammation in a murine model of asthma.Methods:Thirty-two BALB/c mice were randomly divided into four groups:normal control group ( n=8 ) , asthma group (n=8),sulfatide treatment group (n=8) and adoptive transfer group (n=8).The murine model of asthma was established by sensitization with intraperitoneal injection of ovalbumin ( OVA) and intranasal challenge in all animals except for the normal control group where PBS was used instead.Intraperitoneal injection of sulfatide in a sulfatide treatment group, adoptive transfer of sulfatide-activated typeⅡNKT cells in adoptive transfer group and PBS in asthma group were carried out 1 hour before the first challenge.PBS was used for intraperitoneal administration in the normal control group.Lung histology and goblet cell hyperplasia were analyzed by HE or PAS staining.Differential cell count in bronchial alveolar lavage ( BALF) was measured by May-Gruenwald Giemsa;levels of OVA-specific IgE in serum and L-4,IL-5 in BALF were measured by ELISA.The percentages of lung type Ⅱ NKT cells,IL-4+and IFN-γ+typeⅡNKT cells were detected by flow cytometry.Results:Inflammatory cell infiltration in lung tissue and goblet cell hyperplasia in the airway were decreased in sulfatide treatment group and adoptive transfer group.Percentages of eosinophil in BALF,level of OVA-specific IgE in serum,and levels of IL-4,IL-5 in BALF in sulfatide treatment group and adoptive transfer group were significantly lower than those in asthma group (all P<0.05).The percentages of lung IL-4+and IFN-γ+typeⅡNKT cells in sulfatide treatment group was significantly higher than those in asthma group ( P<0.01 ).Conclusion: Type Ⅱ NKT cells activated by sulfatide may inhibit airway inflammation in a murine model of asthma.

Objective:To observe the antibacterial effect of Ag +-loaded TiO 2 (Ag -TiO 2) and Ag -TiO 2 coated endotracheal tube (ETT) on the bacterial biofilm (BF) of Staphylococcus aureus. Methods:2, 3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric method was used to detect minimal inhibitory concertation (MIC) of Ag-TiO 2 for inhibition of BF of Staphylococcus aureus. The Ag -TiO 2 coated ETT were prepared, and divided into 11 mg/L, 8 mg/L, 5 mg/L, 2 mg/L and 0 mg/L ETT group, according to the concentration gradient, then impregnated in the liquid with Staphylococcus aureus at a concentration of 1.0×10 9cfu/L. The influence of antibacterial coated ETT on the formation of Staphylococcus aureus BF was determined by detecting the colonies of bacteria and BF on the ETT. Results:Ag-TiO 2 had a significant inhibitory effect on Staphylococcus aureus BF in a concentration -dependent manner, and its MIC was 10 mg/L. Ag -TiO 2 coated ETT has significant anti -Staphylococcus aureus BF effect, and the higher the concentration, the stronger the effect. The absorbance ( A) values of Ag -TiO 2 5 mg/L, 8 mg/L, 11 mg/L ETT groups were significantly lower than that in control group (0.176±0.004, 0.147±0.002, 0.094±0.002 vs. 0.267±0.045, all P < 0.05). The inhibitory rates of Ag -TiO 2 2 mg/L, 5 mg/L, 8 mg/L ETT groups were increased gradually, and 11 mg/L Ag -TiO 2 coated ETT group had the highest inhibitory rate for BF, the inhibitory rates were 6.4%, 34.1%, 44.9% and 64.8%, respectively. Conclusion:Both Ag-TiO 2 and Ag-TiO 2 coated ETT have significant inhibitory effects on Staphylococcus aureus BF.

Objective To describe and analyze the disease burden and its changing trend of liver cancer caused by nonalcoholic steatohepatitis (NASH) in China from 1990 to 2019, and to provide reference for reducing the morbidity and mortality of liver cancer in China. Methods Based on data from the Global Burden of Disease (GBD2019) study, different gender and age groups were selected. The morbidity, mortality, and disability adjusted life year (DALY) rate were used to analyze the disease burden of liver cancer caused by NASH in China from 1990 to 2019. The time trend was analyzed by using the Joinpoint regression model, and the annual percent of change (APC) and annual average percentage change (AAPC) of morbidity, mortality and DALY rate were calculated. Results Compared with 1990, the incidence rate, mortality rate and DALY rate of liver cancer caused by NASH in 2019 decreased by 4.05%, 12% and 25.79%, respectively. Age-standardized morbidity, standardized mortality and standardized DALY rates decreased by 49.50%, 54.72% and 58.45%, respectively. In 2019, the incidence rate, mortality data and DALY rate of liver cancer caused by NASH increased with age, and the highest mortality rate was among people over 85 years old. The average annual change percentage (AAPC) of age-standardized incidence rate, standardized mortality rate and standardized DALY rate of liver cancer caused by NASH from 1990 to 2019 were -2.65% ［95% CI（-3.09%，-2.21 %），P<0.001］, -2.86%［95% CI（-3.34%，-2.38 %），P<0.001］, and -2.91%［95% CI（-3.23%，-2.58%），P<0.001］，respectively. The AAPC of all indexes in males was higher than that in females. Conclusion From 1990 to 2019, the disease burden of liver cancer caused by NASH in China showed an overall downward trend. The AAPC of all indexes in males is higher than that in females, and the elderly population is a high-risk group.

This paper elaborates the specific implementation process of the "research-based learning" teaching reform of genetic experiment in medical undergraduate education, including the change of teaching philosophy among teachers, the integration and expansion of experimental contents, the innovation of classroom-teaching model, the compilation of proper textbook, the update of assessment methods and the establishment of evaluation mechanism for teaching and so on. Preliminary research shows that RBL teaching reform can stimulate medical students' interest and potential in learning, and improve their practical and scientific research innovation ability.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Objective:To explore the safety and efficacy of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma with PD-L1 negativity in transplanted liver tissue.Methods:From May 2020 to December 2020, retrospective analysis was performed for 3 cases of camrelizumab salvage therapy for extrahepatic recurrent hepatocellular carcinoma recipients with PD-L1 negative in transplanted liver tissue.Three recipients with extrahepatic recurrence progressed after first/second-line targeted drug therapy.Camrelizumab was given as salvage therapy after normal tissue of ransplanted liver was confirmed as negative for PD-L1 by immunohistochemistry.The safety and efficacy of treatment were observed by monitoring the changes in the levels of alanine aminotransferase, aspartate aminotransferase and bilirubin, the occurrence of complications and the outcome of treatment before and after dosing.Results:During a follow-up period of 1.5 to 15.5 months, no recipients showed acute rejection symptoms such as sharp elevations of transaminase and bilirubin.Headache ( n=1), vomiting ( n=1) and fatigue & hypertension ( n=1) became relieved after treatment.As of February 28, 2022, there were one survivor and two deaths.The fatal causes were tumor progression ( n=1) and thoracic aortic rupture due to esophageal perforation ( n=1). The survival time of recipients was (11-15.5) months and the progression-free survival time (4-6) months. Conclusions:For extrahepatic recurrent hepatocellular carcinoma with PD-L1-negative liver transplantation in normal liver tissue, camrelizumab salvage therapy can control tumor progression to a certain extent and prolong the survival time of recipients.