Objective To investigate the relationship between transforming growth factor gene (TGF) single nucleotide poly‐morphism (SNP) and multiple myeloma (MM) .Methods The case control study was performed ,55 patients with MM and 55 healthy controls were selected .The genotype and allele detections were performed by adopting the polymerase chain reaction (PCR) and the ligase detection reaction (LDR) respectively .Then the sequencing based typing was further conducted .Results There were no statistically significant differences in the two loci genotype frequencies ,allele frequencies and genotype frequencies in joint hap‐loid typing between the MM group and the control group(P>0 .05) .Conclusion SNP of TGF gene has no obvious correlation with the occurrence of MM and subtypes.

Objective: To evaluate the short-term effect of thrombus aspiration catheters combining tiroifban medication for myocardial tissue reperfusion recovery in patients with acute ST-elevation myocardial infarction (STEMI).
Methods: A total of 105 STEMI patients with percutaneous coronary intervention (PCI) in our hospital from 2011-05 to 2013-05 were studied, there were 73 male and 32 female with the mean age of (58.39 ± 10.37) years. The patients were randomly divided into 2 groups, Group A, the patients received thrombus aspiration catheters with intravenous tiroifban, n=53 and Group B, the patients received tiroifban and PCI, n=52. The basic clinical features, myocardial tissue perfusion level, major adverse cardiovascular events (MACE) at post operative and in-hospital period were recorded, the cardiac function was examined by echocardiography at 6 months after PCI in both groups.
Results: The basic clinical features were similar between 2 groups. The thrombolysis in myocardial infarction trial (TIMI) 3 lfow rate was higher in Group A than that in Group B (92.45% vs 55.77%), P=0.000. TIMI 2 and TIMI 0~1 lfow rates were lower in Group A than that in Group B (7.55%vs 26.92%), P=0.008 and (0%vs 17.31%), P=0.002. The adjusted TIMI frame was lower in Group A (27.26±5.50) vs (38.98±5.42), P<0.001. The echocardiography at 6 months after PCI indicated that Group A had higher LVEF than that in Group B (0.55±0.06) vs (0.47±0.06), P<0.001;lower left ventricular end diastolic diameter (50.77±5.45) vs (54.76±5.34), P<0.001;less angina and target vessel revascularization (16.98%vs 40.38%), P=0.008 and (9.43%vs 17.31%), P=0.008. The incidence of MI, acute heart failure, cardiac death and non-target vessel revascularization were similar between 2 groups, P>0.05.
Conclusion:Thrombus aspiration catheters combining tiroifban medication may obviously improve the myocardial tissue reperfusion and the short-term cardiac function in STEMI patients after PCI, it could reduce the incidence of no-relfow without increasing MACE.

Objective: To explore the clinical response on cardiac resynchronization therapy (CRT) in patients of chronic heart failure (CHF) with different QRS wave morphology. Methods: A total of 52 CHF patients received CRT in our hospital and the Seventh People's Hospital of Zhengzhou City from 2010-03 to 2013-07 were retrospectively studied. The patients were divided into 3 groups: True-complete left bundle branch block (t-CLBBB) group,n=20, Classic LBBB (CLBBB) group,n=15 and IVCD group,n=17. The general clinical condition, the indexes of echocardiography at 6 months of follow-up study including left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), NYHA classiifcation and 6-MWT were examined and compared among different groups. Results: In general clinical condition, the ratio of non-ischemic heart disease patients in t-CLBBB group was higher than those in CLBBB group and IVCD group, allP<0.05. By 6 months follow-up study, LVEDD in t-CLBBB group (62.6 ± 8.9) mm was lower than those in CLBBB group (70.0 ± 8.9) mm and IVCD group (72.8 ± 8.0) mm, LVEF was higher in t-CLBBB group (38.5 ± 6.2) % than those in CLBBB group (31.7 ± 6.7) % and IVCD group (30.1 ± 6.7) %. NYHA classiifcation in t-CLBBB group (2.00 ± 0.45) grade was lower than those in CLBBB group (2.73 ± 0.80) grade and IVCD group (3.12 ± 0.78) grade . 6-MWT in t-CLBBB group (302.0 ± 57.9) m was longer than those in CLBBB group (257.3 ± 59.0) m and IVCD group (220.2 ± 57.9) m, allP<0.05. Conclusion: CRT is an effective method for treating CHD patients, different QRS morphology may have different response, the patients with t-CLBBB would make better response.

Objective:To study the protective effects of sea buckthorn polysaccharide extracts on lipopolysaccharide( LPS)/D-galactosa mine ( D-GalN )-induced liver injury in mice and investigate the regulation on hepatic TLR4 and SOCS3 expression.Methods:C57BL/6 male mice were randomly divided into six groups:control group,model group,dexamethasone positive control group, low, medium and high dose group of sea buckthorn polysaccharide.Mice in the sea buckthorn polysaccharides low, medium and high dose group were gavaged with 50, 100 and 200 mg/kg sea buckthorn polysaccharide extracts for 14 days respectively.Acute liver injury model were established by intraperitoneal injection of LPS(10 μg/kg) and D-GalN (700 mg/kg).The mice in the dexamethasone positive control group were intraperitoneally injected with dexamethasone (10 mg/kg) before model estab-lishment.Serum and liver samples were collected after model establishment for 4 h .Serum levels of ALT and AST were detected.Histological changes of liver tissue were observed by HE staining.Hepatic expression of TLR4 and SOCS3 was detected by Western blot.Results:Sea buckthorn polysaccharide significantly inhibited LPS/D-GalN-induced elevation in serum levels of ALT and AST.It also alleviated liver cell injury and inflammatory infiltration.Western blot results showed that sea buckthorn polysaccharide inhibited LPS/D-GalN-induced TLR4 expression.SOCS3 expression was not dramatically influenced by sea buckthorn polysaccharide supplementation.Conclusion:Sea buckthorn polysaccharide protects against LPS/D-GalN-induced liver injury.This protective effects may be achieved by inhibiting the expression of TLR4 but not associated with modulation on SOCS3 expression.

Objective:Using the macrophage cell lines RAW264.7 stably expressing Rab5a and its dominant negative mutant Rab5aN133I as models to analyze the effect and the mechanism of Rab 5a,Rab5aN133I on CpG-induced production of pro-inflammatory cytokines and type Ⅰ IFN.Methods: The eukaryotic expression vectors of Rab5a and Rab5aN133I were transfected into RAW264.7 cells by liposome,and screened with G418.The G418-resistant colonies were obtained and amplified.The transformed cell lines were i-dentified by RT-PCR,Real time-PCR and Western blot.The production of cytokines were measured after transformed cell lines of Rab5a and Rab5aN133I was stimulation with CpG for 8 h.Results: Rab5a expression in transfected cells was significantly higher than the control cell group (P<0.05).Overexpression of Rab5a significantly promoted the production of TNF -α,IL1-β(P<0.01) and IFN-β( P<0.05) in CpG stimulated RAW264.7.The production of cytokines was restored in Rab 5aN133I transfected cell line.Conclusion:Rab 5a promotes CpG-induced pro-inflammatory cytokines and typeⅠIFN in macrophages,it may be act as a positive regulator in TLR9 signaling pathway.

In order to investigate the application of proton magnetic resonance spectroscopy (1H-MRS) and computerized tomography (CT) in the quantitative diagnosis of nonalcoholic fatty liver disease (NAFLD) and evaluation of therapeutic effects, 22 patients with NAFLD were selected according to the Chinese Medical Association's (CMA) standard of the NAFLD in comparison with 20 healthy volunteers (as control group). Blood samples for biochemistry were collected. The severity of hepatosteatosis was evaluated by 1H-MRS scan and CT scan of liver. The intrahepatic content of lipid (IHCL) and CT value ratio of liver to spleen were calculated. The patients in NAFLD group were treated with Ganzhixiao Capsule for 8 weeks. The changes in IHCL and CT value ratio of liver to spleen were observed before and after treatment. In NAFLD group serum ALT, TG, IHCL calculated by 1HMRS were increased and CT value ratio of liver to spleen decreased significantly as compared with control group. After treatment for 8 weeks serum ALT, TG, IHCL were decreased significantly, while CT value ratio of liver to spleen increased significantly in NAFLD group. It was suggested that IHCL could be measured precisely by 1HMRS. NAFLD was treated effectively by Ganzhixiao capsule.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

OBJECTIVE To mine and analyze the risk signal of glucagon- like peptide -1 receptor agonists （GLP-1RA）related adverse drug reaction （ADR）. METHODS ADR data related to GLP- 1RA from April 1，2005 to October 16，2021 in the openFDA database were collected ，and the Bayesian confidence propagation neoral network （BCPNN）method was used for data mining. ADR were classified and described by using systematic organ classification （SOC）of drug ADR terminology set in 24.0 edition of MedDRA. RESULTS & CONCLUSIONS A total of 175 719 ADR reports related to GLP- 1RA were retrieved ，with 140 ADR positive signals ，involving five drugs such as exenatide （77 027 cases of ADR and 31 ADR positive signals ），dulaglutide （45 329 cases of ADR and 26 ADR positive signals ），liraglutide （42 748 cases of ADR and 32 ADR positive signals ）， semaglutide（8 844 cases of ADR and 27 ADR positive signals ）and lixisenatide （1 771 cases of ADR and 24 ADR positive signals）. According to SOC classification ，GLP-1RA-induced ADR involved gastrointestinal system ，hepatobiliary system ，nervous system，urinary and renal system ，endocrine system ，immune system and administration site. In the gastrointestinal system ，the risk of （acute）pancreatitis was higher ，and the order of risk was liraglutide ＞exenatide＞semaglutide＞dulaglutide＞lixisenatide； ADR signal of hepatobiliary system was stronger for cholelithiasis ，and the order of risk was liraglutide ＞semaglutide＞exenatide＞ lixisenatide＞dulaglutide. In the nervous system ，the risk of taste disorder was higher ；compared with dulaglutide and lixisenatide ， liraglutide，exenatide and semaglutide were more likely to cause headache and dizziness. In urinary and renal system ， compared with exena tide，dulaglutide and lixisenatide ，liraglutide and semaglutide were more likely to cause acute renal injury. In the endocrine system ，the risk of hypoglycemia was higher ，and the order of risk was exenatide ＞liraglutide＞lixisenatide＞ semaglutide＞dulaglutide. In the immune system ，lixisenatide was more likely to develop urticaria than other drugs ，dulaglutide and liraglutide did not caused ADR signal. Among the administration sites ，the risk of ADR caused by exenatide and dulaglutide was higher，while the risk of related ADR caused by semaglutide was lower. When using GLP- 1RA clinically ，we should closely monitor the renal function and blood glucose of patients ，and pay attention to patients with sudden upper abdominal pain ；in case of relevant ADR ，timely intervention measures should be taken to ensure the safety and effectiveness of medication.

Objective:To summarize the clinical and genetic features of children with intellectual developmental disorder with seizures and language delay (IDDSELD) due to 12q24.31 deletion and SETD1B locus variants. Methods:The clinical data of a child with 12q24.31 deletion diagnosed in the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in September 2022 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) and copy number variations sequencing (CNV-seq) were used for genetic analysis. The relevant literatures were reviewed to summarize the clinical features of the disease.Results:The proband was a 7 years and 9 month old girl who had clinical features of global developmental delay, epilepsy, hyperactivity, hypertonia, gait disorder, special facial features (high eyebrow arch, big ears, upper lip protrusion), funnel chest, lumbar lordosis. Karyotypic analysis showed 46XX in the proband. CNV-seq showed 12q24.31 (chr12: 121895654-122449092) position had a deletion of about 553.44 kb which contained the SETD1B gene. Trio-WES showed deletion of all exons 1-16 of the SETD1B gene. CNV-seq results of her parents were normal: the SETD1B gene was wild-type. This type has not been reported in China. Four children with IDDSELD caused by 12q24.31 deletion (including the SETD1B gene) were retrieved (totally 5 cases including this case), with male to female ratio of 1∶4, all with de novo mutations, and all with mental retardation, cephalo-facial and skeletal malformations. Three cases had seizures, 2 cases still had developmental backwardness after treatment, and 1 case was seizure controlled. Forty-seven cases of IDDSELD due to point mutation in the SETD1B gene were retrieved: male to female ratio was 31∶16, missense mutations (38/47) were predominant, most were de novo mutations (36/47), and a few were inherited from their fathers/mothers (6/47) or of unknown origin (5/47), with clinical manifestations of speech delay (43/47), growth retardation (43/47), intellectual disability (37/41), behavioral problems (37/47), facial malformations (34/47), skeletal malformations (23/47), obesity (16/47), skin abnormalities (11/47), etc. Thirty-nine cases were combined with seizures, 23 of whom were under control after treatment, and 8 cases were recorded as still having developmental backwardness after treatment. Conclusions:IDDSELD patients are rare at home and abroad, with diverse clinical phenotypes and difficult diagnosis. Symptomatic treatment is the main approach. And the patients can leave behind seizures and varying degrees of developmental backwardness. Among them, patients with 12q24.31 deletion are relatively rare and have not been reported in China, and this type is more common in females, all of whom have de novo mutations, and genetic testing is helpful for the early diagnosis of IDDSELD.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of dupilumab in the treatment of severe asthma with rapid health technology assessment （HTA）， and to provide evidence-based evidence for clinical treatment. METHODS Retrieved from PubMed，Cochrane Library，CNKI，Wanfang， VIP database， and other related websites of HTA. HTA reports， systematic review/meta-analysis， and economic studies of dupilumab in the treatment of severe asthma were collected. Researchers independently identified literature， extracted data， and assessed the quality of included studies. Qualitative description was performed. RESULTS A total of 15 pieces of literature were included， involving 9 systematic reviews/meta-analyses and 6 economic studies. In terms of effectiveness， dupilumab was significantly better than placebo. Compared with other biological drugs， in the patients with severe asthma aged 12 years and above， for those with eosinophil （EOS） ≥300 cells/μL， dupilumab ranked first in improving forced expiratory volume in one second （FEV1）， outperforming tezepelumab， benralizumab， and mepolizumab. It ranked second in reducing acute exacerbations， surpassed only by tezepelumab， while its effect on improving asthma control questionnaire score was relatively lower， being better only than benralizumab. For those with 150 cells/μL ≤EOS＜300 cells/μL， dupilumab was superior to mepolizumab in reducing asthma exacerbation， while the effect on FEV1 was weaker than benralizumab and mepolizumab. In terms of safety， there was no significant difference in the incidence of adverse events and serious adverse events between dupilumab and placebo or other biological drugs， while the incidence of injection site reactions of dupilumab was significantly higher than placebo. In terms of cost-effectiveness， the research results of different countries were not consistent， and there was a lack of research data from China. CONCLUSIONS Dupilumab is an effective and safe choice in the treatment of severe asthma， and its cost-effectiveness requires further research based on China’s medical environment to be determined.