OBJECTIVE: To study the impacts of RelA antisense oligonucleotides on proliferation in laryngeal carcinoma Hep-2 cell. METHOD: RelA antisense oligonucleotides was designed, which was transferred into laryngeal carcinoma Hep-2 cell. MTT was used to detect the growth-inhibiting ratio at different transferred timepoints. Hep-2 cell which was transferred 48 h was used to do colony assay, and expression of RelA was detected by Reverse Transcription PCR and Western blot. RESULT: MTT results showed that RelA antisense oligonucleotides could significantly suppress the proliferation of Hep-2 cell, and the suppression-ratio elevated with time. There were statistical difference compared with control groups. The number of cells colony was reduced in RelA antisense oligonucleotides group compared with control groups, which had statistic significance. RT-PCR and Western blot results demonstrated that RelA antisense oligonucleotides could significantly inhibit the expression of messenger RNA and protein in Hep-2 cell. CONCLUSION RelA antisense oligonucleotides can inhibit the expression of messenger RNA and protein, and induce the cell proliferation and increase the number of cells colony in Hep-2 cell.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Laryngeal Neoplasms ; genetics ; pathology ; Oligonucleotides, Antisense ; genetics ; pharmacology ; Transcription Factor RelA ; genetics

OBJECTIVETo study the association of single nucleotide polymorphisms (SNP) (rs2393903 and rs10995251) in ZNF365 gene with bronchial asthma and its clinical characteristics in Han Chinese children in Hubei, China.

METHODSA total of 221 children with bronchial asthma and 243 normal children, all of whom were from Hubei, were recruited to carry out a case-control study. The genotype and allele frequencies of two SNPs in ZNF365 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism technique.

RESULTSThere were no significant differences in the distribution of three genotypes (GG, GA, AA) and allele frequency in SNP rs2393903 between the asthma and control groups (P>0.05). However, there were significant differences in the distribution of three genotypes (CC, CT, TT) and allele frequency in SNP rs10995251 between the asthma and control groups (P<0.05); C allele was a risk factor (OR=1.380). The asthmatic children with CC genotype of SNP rs10995251 had a significantly higher serum level of total immunoglobulin E (IgE) than those with TT genotype (P<0.05).

CONCLUSIONSThe SNP rs10995251 in ZNF365 gene is associated with the susceptibility to bronchial asthma in children in Hubei, China, and the SNP may affect the level of serum IgE in these children.

Asthma ; genetics ; Child ; Child, Preschool ; DNA-Binding Proteins ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Polymorphism, Single Nucleotide ; Transcription Factors ; genetics

OBJECTIVE：To unscramble the Notice on Standardizing the Allocation and Use of Licensed Pharmacists in Drug Retail Enterprises （called Notice for short ）and related document ，and to give some suggestions to provide reference for the industry and policy decision departments. METHODS ：The background and content of Notice were described briefly ；the problemsexisting in the corresponding provincial differentiated allocation policy and the difficulties existing in the implementation were analyzed to give some relevant suggestions. RESULTS & CONCLUSIONS ：The main contents of Notice contained adhering to the policy of licensed pharmacists ，steadily improving the allocation level of licensed pharmacists ，refining and implementing the allocation requirements ，and strengthening the implementation of supervision and inspection responsibilities ；giving full play to the role of licensed pharmacists and continuously strengthening the team building. At present ，drug administrations of many provinces in China have issued specific policies on the differentiated allocation of licensed pharmacists and pharmaceutical technicians ，which are mainly divided into four schemes. The author believes that the classification method of drug retail enterprises implemented in Shandong and Guangdong provinces are the most scientific. The implementation of differentiated allocation of pharmacists with health（pharmacy）professional title in drug retail enterprises can alleviate the problem of insufficient licensed pharmacists to a certain extent ，but the disadvantage is that it can not achieve accurate registration and control as well as the management of licensed pharmacists ，which is easy to produce policy gaps ；after the “affiliation licensed pharmacist ’s certificate ”phenomenon， the“certificate affiliation of pharmacist with health （pharmacy）professional title ”phenomenon appeared. It is suggested that the provincial drug supervision and administration departments should try the differentiated allocation scheme of hierarchical management；learn from the management experience of licensed pharmacists and pharmaceutical technicians in Guangdong province， develop relevant platforms to manage the information of pharmaceutical technicians uniformly ； strengthen the communication and interaction with the health and human resource security department as well as the mutual promotion mechanism of personnel information screening ，so as to solve the core bottleneck of licensed pharmacists ’quality.

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

OBJECTIVE: To investigate the inhibitory effect of ANA-12 that blocks brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling on inflammatory pain in rats and explore the underlying mechanism. METHODS: Forty-two adult SD rats were randomized into BDNF-induced acute pain group (n=24) and CFA-induced chronic pain group. The former group were randomly divided into 4 subgroups, including a control group, ANA-12 treatment group, BDNF treatment group, and BDNF+ANA-12 treatment group; the latter group were subgrouped into control group, CFA treatment group (CFA) and CFA + ANA-12 treatment group. The effects of ANA-12 treatment on pain behaviors of the rats with BDNF-induced acute pain and CFA-induced chronic inflammatory pain were observed. Western blotting was used to examine TrkB signaling and expressions of microglia marker protein Iba1 and TNF-α in the spinal cord of the rats. RESULTS: BDNF injection into the subarachnoid space significantly increased the number of spontaneous paw withdrawal of the rats (P < 0.05), which was obviously reduced by ANA-12 treatment (P < 0.05). The rats with intraplantar injection of CFA, showed significantly increased ipsilateral mechanical stimulation sensitivity (P < 0.05), and ANA-12 treatment obviously increased the ipsilateral foot withdrawal threshold (P < 0.05). Treatment with either BDNF or CFA significantly increased the phosphorylation level of TrkB (Y705) in the spinal cord of the rats (P < 0.05), which was significantly lowered by ANA-12 treatment (P < 0.05). Treatment with BDNF and CFA both significantly up-regulated the expressions of Iba1 and TNF-α in the spinal cord (P < 0.05), but ANA-12 significantly reduced their expression levels (P < 0.05). CONCLUSION ANA-12 can reduce spinal cord inflammation and relieve acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Chronic Pain/drug therapy* ; Inflammation ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism*

Objective To retrospectively evaluate the safety ,technical success rate and long‐term efficacy of the hepatic mul‐tiple cavernous hemangioma with super selective arterial cheoembolization .Methods 6 cases multiple hepatic cavernous hemangio‐ma by clinical diagnosed between 2004-2011 years in our hospital ,Through arterial super selective and completely filling cheoem‐bolization by Pingyang mycin lipiodol emulsion(PYM‐Lip) ,To assess the long‐term efficacy .by multi slice spiral CT enhanced scan‐ning and carry on relevant statistics processing in postoperative 6 ,12 ,36months .Results 26 lesions were embolismed in 6 cases multiple hepatic cavernous hemangioma ,Among the number of successful embolization were 15 of 1 cases ,2 of 4 cases ,3 of 1 cases , respectively .26 lesions was decreased with different degrees ,which the diameter of lesions were reduced with embolismed by CT enhanced scanning in postoperative 6 ,12 ,36months and diameter reduced> 50% ,diameter reduced≤50% ,lesions disappear was 38% (10/26) ,54% (14/26) ,8% (2/26) ,62% (16/26) ,23% (6/26) ,15% (4/26) ,69% (18/26) ,12% (3/26) ,19% (5/26) .Technical operation success rate 100% ,not serious complications occurred .There are statistically significant differences in the size of lesions before and after operation(P<0 .01) .Conclusion The technique success rate was high ,minimally invasive ,the complications was less ,the curative efficacy was obvious by transcatheter arterial super selective cheoembolizaton with hepatic multiple cavernous he ‐mangioma .

OBJECTIVE: To delineate the clinical feature and genetic basis of four patients with congenital neutropenia. METHODS: All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. RESULTS: The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically. CONCLUSION The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.
Congenital Bone Marrow Failure Syndromes/genetics* ; Female ; Genetic Testing ; Humans ; Infant ; Leukocyte Elastase/genetics* ; Male ; Mutation ; Neutropenia/genetics*

OBJECTIVE: To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome. METHODS: Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Copy number variations (CNV) were detected by CNV-seq and validated by real-time PCR. RESULTS: Proband 1 was found to carry a de novo heterogeneous variant (c.823+1G>T) of the EHMT1 gene, which may affect its expression. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS2+PM2). Proband 2 was found to carry a de novo missense variant c.439C>G (p.L147V) of the EHMT1 gene, which was predicted to be likely pathogenic (PS2+PM1+PM2+PP3). Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq. The deletion has encompassed the whole of the EHMT1 gene. Real-time PCR has detected no CNV of this region in her parents. CONCLUSION Variants of the EHMT1 gene probably underlay the disease in these patients. Genetic testing has provided a basis for their clinical diagnosis.
Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities ; DNA Copy Number Variations ; Female ; Genetic Testing ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics* ; Mutation

Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A(MEN 2A)family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma ( MTC).Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members(p.C634R), which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years(ranging from 19 years to 65 years) and the mean maximum diameter of MTC was 2.3 cm(ranging from 0.7 cm to 5.2 cm). Among them 3 members had palpable neck masses (1 case with diarrhea).Right total thyroidectomy +right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy +bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy +bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom ( PHEO) underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient( T3N 1bM 0-1) underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively (T1N 1bM0 and T2N 1bM0), and the other one patient was closely monitored and followed up for 22 months(T2N 1b M0).Moreover, The calcitonin levels dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.