[Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year].

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

[Impact of transcatheter aortic valve replacement on renal function in patients with severe aortic stenosis].

Objective: To explore the impact of transcatheter aortic valve replacement (TAVR) on renal function in patients with severe aortic stenosis. Methods: This is a single-center retrospective study. Consecutive patients with severe aortic valve stenosis and received TAVR in Zhongshan Hospital from December 2014 to December 2019 were included. The patients were divided into four groups according to the estimate glomerular filtration rate (eGFR) measured at one day before TAVR, namely eGFR>90 ml·min-1·1.73m-2 group, 6090 ml·min-1·1.73m-2 group, 60

[Relationship of TLR2 and TLR4 expressions on the surface of peripheral blood mononuclear cells to small intestinal bacteria overgrowth in patients with hepatocellular carcinoma].

Objective: To investigate TLR2 and TLR4 expressional situation on the surface of peripheral blood mononuclear cells (PBMC) in patients with hepatocellular carcinoma (HCC) and their relationship with small intestinal bacterial overgrowth (SIBO). Methods: Flow cytometry was used to detect TLR2 and TLR4 expressional situation on the surface of PBMC in 78 cases with HCC, 56 cases with cirrhosis and 33 healthy controls. Furthermore, lactose hydrogen breath test (LHBT) was used to detect small intestinal bacterial overgrowth. Results: Of the 78 cases with HCC, 56 cases (71.8%) were SIBO-positive, 23 cases (41.1%) were SIBO- positive in 56 cases with cirrhosis, and 1 (3.0%) was SIBO-positive in 33 healthy controls. The incidence of SIBO in HCC patients was higher than cirrhosis patients (χ(2) = 12.72, P < 0.05) and healthy controls (χ(2) = 41.18, P < 0.05). The expression levels of TLR2 and TLR4 in HCC patients (100.55 ± 24.22, 42.76 ± 15.96) were significantly higher than cirrhosis (67.42 ± 18.36, 24.38 ± 8.68)and healthy control group (33.06 ± 11.72, 12.52 ± 4.46) (P < 0.05). Furthermore, the expression levels of TLR2 and TLR4 in SIBO-positive patients (108.75 ± 20.40, 48.1 ± 14.98) were higher than SIBO-negative patients (79.67 ± 20.60, 28.62 ± 7.36) (P < 0.05). Conclusion: The expression of TLR2 and TLR4 and the incidence of SIBO in HCC patients are significantly higher than cirrhosis and healthy control group. Moreover, the high expressions of TLR2 and TLR4 in SIBO-positive HCC patients may promote the development of HCC.

[Effects of transcatheter aortic valve replacement in patients with severe aortic valve stenosis].

Objective: To investigate the effects of transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis. Methods: The clinical data of 130 patients with severe aortic valve stenosis, who underwent TAVR in our hospital with self-expanding valve between January 1,2010 and October 30, 2016, were analyzed retrospectively. The patients were divided into calcific aortic valve stenosis (CAS) group (112 cases) and non-calcific aortic valve stenosis (NCAS) group (18 cases) according to 3D volume-rendering reconstruction under multiple detector computed tomography before TAVR. The baseline clinical features, imageology results, procedural details, and clinical prognosis were compared between the 2 groups. Results: (1) Compared with CAS group, the patients in NCAS group were younger, had higher proportion of rheumatic heart disease, and less proportion of bicuspid aortic valve morphology (P<0.01 or 0.05). Except for minimum value of sinotubular junction (P=0.017), there were no significant differences in multiple detector computed tomography measurements of aortic valve annulus and aortic root structure between the 2 groups (all P>0.05). (2) Compared with CAS group, the proportions of valve release under rapid pacing and oversized valve release were larger than pre-procedural evaluation, and the proportion of post-dilation was lower in NCAS group (P<0.01 or 0.05). (3) Post-procedural transthoracic echocardiography revealed that left ventricular ejection fraction was higher than baseline level in CAS group (P<0.001), while which was similar in NCAS group (P=0.552). Compared with before TAVR, mean pressure gradient and maximum transvalvular velocity were significantly reduced, aortic valve orifice area was significantly increased, and proportion of moderate to severe aortic regurgitation was significantly reduced after the procedure in both groups (all P<0.01). There were no significant differences in left ventricular ejection fraction, mean pressure gradient, maximum transvalvular velocity, aortic valve orifice area, and proportion of moderate to severe aortic regurgitation after TAVR between the 2 groups (all P>0.05). (4) There were no significant differences in successful rate of device placement and cardiovascular related death within 30 days after TAVR between the 2 groups (105/112 vs. 17/18, P=0.909; 3/112 vs. 1/18, P=0.453, respectively). Conclusion: TAVR is safe and effective for patients with severe aortic valve stenosis.

[Safety and efficacy of transcatheter aortic valve replacement through transcarotid approach for patients with severe aortic valve stenosis].

Objective: To investigate the safety and efficacy of transcatheter aortic valve replacement(TAVR) through transcarotid approach for patients with severe aortic valve stenosis. Methods: The clinical data of 9 symptomatic severe aortic valve stenosis patients who had high or prohibitive risk for surgery and not suitable for TAVR through femoral artery access,and thus received TAVR through transcarotid approach in our hospital from November 2015 to February 2017 were retrospectively analyzed.The patients were followed up to observe the safety and efficacy of the procedure. Results: There were 4 male and 5 female patients in this cohort, and age was (75.7±8.7) years old. The Society of Thoracic Surgery (STS) scores were (7.9±1.6)%. All patients were treated by left carotid artery approach. One patient experienced valve dislodgement during the procedure and received surgery, and TAVR procedure was successful in the rest 8 patients. Two patients were implanted with permanent pacemaker because of third degree atrioventricular block during the procedure.One patient had cardiac arrest during the procedure and recovered after external chest compression.One patient developed severe carotid stenosis,and there was no clinical manifestation of nerve function deficit after the procedure. All patients were followed up at (30±3) days after the procedure, and there were no adverse events. The modified Rankin scale score was 0. Echocardiography examination showed that the tranvalvular mean gradient was reduced from (63.0±19.2)mmHg(1 mmHg=0.133 kPa) on baseline to (18.1±4.9)mmHg(P<0.001), 4 cases had mild paravalvular leakage, and there was no moderate or severe paravalvular leakage.The NYHA classes was significantly improved at 30 days when compared with before the procedure(2 cases class Ⅱ, 4 cases class Ⅲ,3 cases class Ⅳ before the procedure,and 5 cases classⅠ, 4 cases class Ⅱ after the procedure, P=0.006) , and left ventricular ejection fraction increased from (55.9±13.1)% to (60.4±10.0)% (P=0.030). Conclusion: Our initial experience indicates that transcarotid TAVR is safe and effective for patients with severe aortic valve stenosis.

Inhibition of JMJD6 expression reduces the proliferation, migration and invasion of neuroglioma stem cells.

Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now. Hence, to explore the effects of JMJD6 expression on neuroglioma, we firstly isolated glioma stem cells by using CD133 MicroBead Kit, and identified via neurosphere-forming assay and Immunofluorescence staining. At the same time, we investigated the effects and mechanism of JMJD6 on the proliferation, migration and invasion of glioma stem cells through MTT, transwell assays and the Cignal finder cancer 10-pathway reporter array. The results demonstrated that the glioma neurosphere cells positively expressed stem cell marker SOX2, neuroectodermal stem cell marker Nestin, and also expressed astrocytes marker GFAP and neurons marker ß-tubulin III fter FBS-induced differentiation for a week, which proved the glioma neurosphere cells have the self-renewal and multipotential differentiation capacity. Moreover, shRNA lentiviral vector mediated knockdown of JMJD6 in glioma stem cells led to decreased proliferation, migration and invasion, the underlying molecular mechanism is related to the weaken of Wnt signaling pathway and strengthen of p53 signaling pathway.

[Analysis of pulmonary valve function in patients with tetralogy of Fallot after radical surgery].

Objective: To analyze the pulmonary valve function in patients with tetralogy of Fallot after radical surgery. Methods: Clinical data of 263 patients (119 male, mean age (33.2±11.5) years old) with tetralogy of Fallot underwent radical surgery in our hospital from January 2010 to June 2016 were retrospectively analyzed. According to age, patients were divided into 14-17 years old group (14 cases), 18-29 years old group (100 cases), 30-39 years old group (61 cases) and above 40 years old group (87 cases). The patients were divided into pulmonary regurgitation group (87 cases) and control group (176 cases) according to weather they have moderate or severe pulmonary regurgitation. Echocardiographic data were compared among groups. Results: A total of 83 patients received re-operation. The median age of the primary radical operation was 9 (5, 13) years, and the median time from the primary radical operation to echocardiographic follow-up was 5 (1, 13) years. Among the 263 enrolled patients, prevalence of pulmonary regurgitation was 36.1% (95/263), and pulmonary stenosis was evidenced in 28 patients (10.6%). The ratio of moderate to severe tricuspid regurgitation was 14.3% (2/14), 27.0% (27/100), 32.8% (20/61) and 37.9% (33/87) in 14-17 years old group, 18-29 years old group, 30-39 years old group and above 40 years old group, respectively (P=0.029), while prevalence of moderate and severe pulmonary regurgitation, moderate and severe pulmonary valve stenosis, pulmonary valve transvalvular pressure >40 mmHg (1 mmHg=0.133 kPa), right atrial and right ventricular enlargement ratio were similar among groups (all P>0.05). The ratio of moderate and severe tricuspid regurgitation and right ventricular enlargement in the pulmonary regurgitation group was significantly higher than in the control group (40.2% (35/87) vs. 27.3% (48/176) and 96.6% (84/87) vs. 87.5% (154/176), all P<0.05), while left ventricular ejection fraction, right atrial enlargement, and right ventricular wall thickness were similar between the two groups (all P>0.05). Conclusion: Pulmonary regurgitation is a common clinical feature among survivors of tetralogy of Fallot patients after radical surgery, and moderate to severe pulmonary regurgitation increases the risk of tricuspid regurgitation and enlargement of the right ventricle.

Late gestational liver dysfunction and its impact on pregnancy outcomes.

OBJECTIVE: The aim of this study was to investigate the impacts of late gestational liver dysfunction and its impact on pregnancy outcomes. MATERIALS AND METHODS: The patients hospitalized for liver dysfunction in their late pregnancy between 2010-2012 were set as the observation group, and the pregnant women with normal liver function at the same period were randomly selected and set as the control group. The impacts towards the pregnancy outcomes were compared between these two groups and the impacts of different-degree transaminase increasing towards the pregnancy outcome were analyzed. RESULTS: The incidence rates of cesarean section, post-partum hemorrhage, fetal distress, premature birth, premature rupture of membranes (PROM) of the observation group and the transaminase-severely-increased group (the severe group) were higher, and the differences were statistically significant (p < 0.01 or < 0.05); while only the cesarean rate of the mild and moderate group was significantly different from the control group (p < 0.01 or < 0.05). The ratios of intrahepatic cholestasis in pregnancy (ICP), gestational hypertension + HELLP syndrome, acute fatty liver in pregnancy (AFLP) of the severe group were higher than the mild and moderate group, and the differences were statistically significant; the non-alcoholic fatty liver disease (NAFLD) group and the unknown cause group mainly showed a mildly increased transaminase; the distributions of viral hepatitis in pregnancy (VHP), post-viral-hepatitis-B cirrhosis, biliary tract disease, and infected toxic liver dysfunction in different-degree increased transaminase groups had no significant difference. CONCLUSIONS: Liver dysfunction in later pregnancy, especially with severe transaminase increase, might significantly increase the risk of adverse maternal events. The major causes of severe liver dysfunction in late pregnancy were ICP, gestational hypertensive disorders, and AFLP.

[Risk factors of lung cancer complicated with symptomatic venous thromboembolism].

OBJECTIVE: To seek risk factors of VTE in patients with lung cancer through analysis of clinical features of patients with lung cancer complicated with venous thromboembolism (VTE). METHODS: Retrospective investigation was performed on patients diagnosed with lung cancer and with complete clinical data who were hospitalized in Peking University People's Hospital from January 1, 2010 to December 31, 2014. According to the presence of symptomatic VTE, patients were distributed into two groups, VTE group and control group. Patients' clinical data and laboratory parameters were collected. Single factor analysis was applied to compare the differences between the two groups. t test or nonparametric test was applied for intragroup comparison of measurement data, and chi-square test was applied for the comparison of counting information. Logistic regression analysis was applied to explore risk factors of venous thromboembolism. For VTE patients with this diagnosis when they were hospitalized, D-dimer and PT were obtained after the occurrence of VTE, so D-dimer and PT were eliminated in the multiple factors analysis. SPSS 13.0 statistical software was applied for statistical management and analysis. RESULTS: 548 patients with lung cancer were include in the investigation, with male 357, female 191, average age of (63.8±10.9) years old, 46 patients in VTE group and 502 patinets in control group. According to the results of single factor analysis in gender, age, tumor pathologic type, tumor stage, WBC, Hb, PLT, CEA, ALT, FIB, D-dimer, PT, APTT, PT-INR, the tumor stage (χ(2)=14.177), CEA (t=2.129) and Hb (t=-2.424) were risk factors for lung cancer patients complicated with venous thromboembolism. Logistic regression analysis showed that tumor stage was the independent risk factor of lung cancer complicated with venous thromboembolism (OR 2.058, 95%CI 1.307-3.238, P=0.002) , and CEA (r=0.395, P<0.001) and Hb (r=-0.144, P=0.001) were associated with lung cancer stage. The area under the curve formed by D-dimer predicting VTE was 0.825 (95%CI 0.751-0.900, P<0.001). CONCLUSION: Tumor stage is the only risk factor for lung cancer patients complicated with venous thromboembolism in the study. However, because this study is a retrospective study, other potential high risk factors causing VTE cannot be excluded.

HLA-A gene polymorphisms contribute to osteoporosis susceptibility in postmenopausal Han Chinese women.

Osteoporosis is a common disease characterized by low bone mineral density, deterioration in bone microarchitecture, and increased fracture risk and is more prevalent in postmenopausal women. HLA is a complex gene family; previous studies have shown that it plays an important role in the pathogenesis of osteoporosis among Japanese and Greek populations. Prompted by these findings, this study was designed to explore the associations between HLA-A gene polymorphisms and postmenopausal osteoporosis in the Han Chinese population. The polymerase chain reaction-sequence-based typing method was used for DNA genotyping at the HLA-A locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls. We identified 17 HLA-A alleles in patients with postmenopausal osteoporosis and 20 HLA-A alleles in control subjects. Furthermore, we found that the frequency of the HLA-A* 02:07 allele was significantly higher in patients with postmenopausal osteoporosis than in control subjects (P = 0.023), and the relative risk was 4.065 (95% confidence interval = 1.109-14.893). Our study provides supportive evidence for the contribution of HLA-A gene polymorphisms to the susceptibility to postmenopausal osteoporosis and suggests that HLA-A* 02:07 is likely an important genetic risk factor for postmenopausal osteoporosis in the Han Chinese population.

Associations between polymorphisms of HLA-B gene and postmenopausal osteoporosis in Chinese Han population.

Osteoporosis is a systemic skeletal disease, which is more prevalent in postmenopausal women. Osteoporosis likely develops beginning with genetic risk. This study explored the relationships between polymorphisms of HLA-B gene and postmenopausal osteoporosis in a Chinese Han population. Polymerase chain reaction sequence-based typing (PCR-SBT) method was used for DNA typing at HLA-B locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls in female Han population of Shaanxi Province, situated in north-western China. We found that 40 HLA-B alleles in postmenopausal osteoporosis patients and control subjects, respectively. Furthermore, the frequency of HLA-B* 3501 allele was significantly higher in postmenopausal osteoporosis patients than in the control group (P = 0.033), and the relative risk was 7.632 (95% CI: 0.927-62.850). Our results suggest that HLA-B* 3501 was likely an important risk factor for postmenopausal osteoporosis. As different populations have different HLA polymorphisms, further investigation of the relationship of various HLA genes and osteoporosis with larger sample size is still necessary in the future.

Association study of human leucocyte antigen-A gene with idiopathic male infertility in Han population of China.

Human leucocyte antigen (HLA) is a complex gene family that contains several highly polymorphic genes. Some studies have reported HLA-A gene to have a strong role in idiopathic male infertility in Japanese and Yugoslavia populations. Prompted by these findings, we investigated the distributions of HLA-A gene to ascertain their associations with idiopathic male infertility in Chinese population. Polymerase chain reaction-sequence-based typing (PCR-SBT) method was used for DNA typing at HLA-A locus in 109 patients with idiopathic male infertility and 152 healthy controls in Han male population of Shaanxi Province, situated in north-western China. In total, we detected 23 HLA-A alleles in all infertile patients, 22 HLA-A alleles in control subjects. However, no significant differences of these allelic frequencies were found between the patients and the control subjects, suggesting that the HLA-A gene was unlikely a major risk factor of idiopathic male infertility in this sample population. As different populations have different HLA polymorphisms, investigation into the relationship of other HLA genes and idiopathic male infertility in our population is needed in the future.