Objective: : To observe whether cytokines rIL 2,TNF ?,I FN ? and anti CD3/anti glioma bispecific antibody(BsAb) can work coordinately, and to investigate how to further enhance cytotoxicity of T lymphocyte against human glioma cells by BsAb. Methods: There were 12 groups,contr ast method were used to analyze the effect of cytokines rIL 2,TNF ?,IFN ? to cytoxicity directed by BsAb by single and combined experiments. Cytotoxicity was assayed by standard 18 h 3H TdR incorporation release. Resul ts: rIL 2,TNF ?,IFN ? and BsAb could cooperatively enhance the cy totoxicity of effect cells( P

[Abstract ] Objective Numerous studies had shown that synaptic-associated proteins (SNAPs) were closely related to the occurrence and development of tumors .The aim of this study was to investigate the expression of synaptosomal-associated protein 47 (SNAP47) and its correlation with the clinicopathological features in non-small cell lung cancer(NSCLC). Methods The expres-sions of SNAP family (SNAP23, SNAP25, SNAP29 and SNAP47) were extracted and analyzed through the gene expression microarray and the cancer genome atlas ( TCGA) data-base.SNAP47 mRNA expression in 52 cases of lung adenocarcinoma and their correspond-ing normal tissues were detected by quantitative real-time PCR ( qRT-PCR) . Results Among 52 cases of lung adenocarcinoma , SNAP47 mRNA expression levels of 41 cases(78.9%) were significantly higher than the adjacent lung tissue (P<0.05).The mRNA level of SNAP47 was associated with lymph node invasion and advanced clinical patho-logical stage .The mRNA levels of SNAP47 of patients in II/III stage were significantly higher than those of I stage patients ( 6.558 ± 4.730 vs 2.718 ±2.370, P<0.05).The mRNA levels of N1+N2 were higher than those of N0 (6.609 ±4.942 vs 3.360 ±2.987,P<0.05). Conclusion The high specificity of SNAP47 expression in lung cancer tissues might be associated with the invasion and lymph node metastasis of NSCLC , which is the potential therapeutic target of lung cancer .

Sepsis is frequently associated with multi-system organ dysfunction and refractory hypotension,leading to a high mortality and poor prognosis.As an antioxidant,ascorbic acid (vitamin C) is an important auxiliary factor for many enzymes in the organism.Numerous studies have revealed that vitamin C can attenuate the inflammatory response,improve microcirculatory and hypotension in sepsis,and also can enhance the role of catecholamine in central nervous system,to prevent sepsis-induced organ failure and improve prognosis of patients.

OBJECTIVETo analyze the karyotypes and SRD5A2 gene mutations in 25 patients with sporadic or familial hypospadias.

METHODSThe patients included 10 adults and 15 children, whose chromosomes were analyzed by G-banded karyotyping, and the SRD5A2 genes were sequenced.

RESULTSTwo patients were found to have an abnormal karyotype, while eight have carried compound heterozygous mutations of the SRD5A2 gene, which included 5 genotypes formed by 6 types of mutations, i.e., p.G203S/p.R227Q, p.R227Q/p.R246Q, p.Q6X/p.Q71X, p.L20P/p.G203S, and p.Q71X/p.R227Q. Mutations of the SRD5A2 gene were present in 32% (8/25) of all patients, 35% (8/23) in those with a normal karyotype, and 44.4% (8/18) in those with proximal type hypospadia. Bioinformatic analysis, literature review and pedigree analysis confirmed that all such mutations are pathogenic.

CONCLUSIONChromosomal anomalies and mutations of the SRD5A2 gene are the main cause of hypospadias. Sequencing of the SRD5A2 gene may explain the etiology of nearly half of the patients with proximal type of hypospadas but a normal karyotype, which can facilitate genetic consulting.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; genetics ; metabolism ; Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; Female ; Humans ; Hypospadias ; enzymology ; genetics ; Infant ; Infant, Newborn ; Karyotyping ; Male ; Membrane Proteins ; genetics ; metabolism ; Mutation ; Young Adult

OBJECTIVE: To evaluate the expressions of chemokine receptor 6 (CCR6), chemokine receptor 7 (CCR7) and their ligands (CCL20, CCL19/CCL21) in laryngeal squamous cell carcinoma (LSCC), and then explore their correlation with the clinicopathological features of LSCC. METHOD: Blood samples, fresh specimens of LSCC and paired adjacent tissues were collected. The expressions of CCR6, CCR7 and their ligands CCL20, CCL19/ CCL21 mRNA as well as the protein CCR6, CCR7 were detected by real-time qRT-PCR and IHC respectively. Flow cytometry was also used to investigate CCR6, CCR7 expressed on PBMC. RESULT: The relative expression levels of CCR6, CCR7, CCL19 and CCL21 mRNA in tumor tissue was significantly higher than that of adjacent tissues (P < 0.05), while the relative expression level of CCL20 mRNA in tumor tissue were significantly lower than that of adjacent tissues (P < 0.05). IHC confirmed the expression of protein CCR6 and CCR7 in both tumor tissue and metastatic ILN and the expression levels of protein CCR6, CCR7 were higher in the cases with lymphatic metastasis than that of those without lymphatic metastasis (P < 0.05). FCM showed the percentage of CD4+ CCR6+ T cells of LSCC was significantly higher than that of normal control (P < 0.05), while that of CD4+ CCR7+ T cells was significantly lower (P < 0.05). CONCLUSION CCR6 and CCR7 are expressed in tumor situ, metastatic LN and PBMC,and might exert a potential role in LSCC development.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Chemokine CCL19 ; metabolism ; Chemokine CCL20 ; metabolism ; Chemokine CCL21 ; metabolism ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Middle Aged ; Receptors, CCR6 ; metabolism ; Receptors, CCR7 ; metabolism

Objective:To investigate the correlation between the annual professional proficiency test results and the theoretical examination score of completion assessment in standardized residency training, as well as the value of the annual professional proficiency test results in predicting whether a resident passes the theoretical examination of completion assessment.Methods:The residents who participated in the annual professional proficiency test of residency training in Affiliated Hospital 2 of Nantong University in 2019-2021 and the completion assessment of residency training in 2020-2022 were selected as subjects, and related data were collected, including sex, education background, personnel type, training specialty, the results of annual professional proficiency test, and the theoretical examination score of completion assessment. According to whether the resident passed the theoretical examination of completion assessment, they were divided into passed group and failed group. SPSS 19.0 was used to perform the chi-square test, the independent samples t-test, and the binary logistic regression analysis; the Pearson correlation coefficient was used for correlation analysis; the sensitivity analysis was represented by ROC curve. Results:Compared with the residents who passed the theoretical examination of completion assessment, the residents who did not pass the examination had a significant reduction in the proportion of the residents from our hospital and a significant increase in the proportion of the residents commissioned by foreign institutions ( χ 2=7.00, P=0.008). The passed group had a significantly higher national percentile of annual professional proficiency test score than the failed group (43.46%±26.61% vs. 23.40%±18.71%, t=6.02, P<0.001). The national percentile of annual professional proficiency test score was positively correlated with the theoretical examination score of completion assessment ( r=0.43, P<0.05). The source of residents commissioned by foreign institutions and the low percentile of annual professional proficiency test score were independent risk factors for failing the theoretical examination of completion assessment ( P=0.020 and P<0.001). The national percentile of annual professional proficiency test score had an area under the ROC curve of 0.73 (95% CI: 0.65-0.80) in predicting the outcome of theoretical examination and had a certain predictive value with a cut-off value of 15.1%. Conclusions:In addition to strengthening homogenization and professional base management for residency training, it is necessary to make full use of the results of annual professional proficiency test in standardized residency training and timely check the professional knowledge of the residents whose a national percentile of <15.1%, so as to effectively improve the pass rate of theoretical examination and the quality of training.

Objective:To survey the cognition of general practice residency training and the willingness of teaching among specialists.Methods:A questionnaire survey was conducted among 221 specialists from 24 departments in Nantong First People's Hospital from May 2021 to June 2021 to investigate the their cognition of general practice residency training program and the teaching willingness.Results:Total 221 questionnaires were distributed and 185 valid ones were retrieved with a response rate of 83.70%. The results showed that 49 specialists (26.49%) well knew the national general practice training policy, 70 (37.84%) knew the most, 52 (28.11%) knew basically, 11 (5.95%) knew little, and 3 (1.62%) did not know at all. Meanwhile, 44 specialists (23.78%) well knew the hospital incentive policies about general practice education, 62 (33.51%) knew the most, 57 (30.81%) knew basically, 18 (9.73%) knew little, and 4 (2.16%) did not know at all. Whether they holding the teaching certificate of general practice was significantly associated with the cognition of national general practice training policy (χ2=14.28, P=0.003) and with their knowledge of residency training program (χ2=16.79, P=0.001), but not associated with knowing the hospital-level incentive policy (χ2=8.18, P=0.075). A total of 170 (91.89%) participants were willing to be clinical teachers of general practice. The reasons for the willingness of teaching were as following: learning more from the teaching in 161 participants (94.71%), expanding sources of patients from rural areas in 102 (60.00%), facilitating promotion in 77 (45.29%), and others in 30 (17.60%). Among 62 specialists holding teaching certificate, 60 (96.77%) were willing to teach general practice residents; while among 123 specialists without teaching certificate, 110 (89.43%) were willing to teach (χ2=4.92, P=0.027). In all hospital incentive policies, promotion of professional titles was most attractive one (82, 44.32%), followed by performance appraisal (63, 34.05%), priority for in-service training (25, 13.51%), and appraisal for excellence award (15, 8.11%). Conclusions:Strengthening trainings for general practice the faculty is helpful to improve their cognition of the general practice residency training programs. And rational hospital incentive policies can enhance the willingness of specialists to teach general practice residency.

OBJECTIVETo screen for FOXL2 gene mutations in 6 patients with blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlation.

METHODSPeripheral venous blood samples were collected from the patients for the extraction of genomic DNA. PCR and Sanger sequencing were employed to analyze the coding region and flanking sequences of the FOXL2 gene. Pathogenicity of the identified mutations was verified through literature review and bioinformatic analysis.

RESULTSA heterozygous c.672_701dup30 mutation was found in the probands from the two familial cases, while three heterozygous mutations (two were novel), namely c.462_468del (p.Pro156Argfs*113), c.251T to A (p.Ile84Asn) and c.988_989insG (p.Ala330Glyfs*204) were detected in the three sporadic cases. Literature review and bioinformatic analysis indicated that all these mutations are pathogenic.

CONCLUSIONIdentification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blepharophimosis ; diagnosis ; genetics ; China ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Genetic Association Studies ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Skin Abnormalities ; diagnosis ; genetics ; Urogenital Abnormalities ; diagnosis ; genetics ; Young Adult

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.