Objective:To analyze the mutations of globin genes among patients suspected for thalassemia from the Shanghai area.Methods:A total of 4 644 patients diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between June 2016 and December 2019 were selected as the study subjects. The patients were tested for common mutations associated with thalassemia gene by Gap-PCR and reverse dot blotting (RDB). Patients were suspected to harbor rare mutations based on the inconsistency between hematological phenotypes and results of common mutation detection, and were further analyzed by Gap-PCR and Sanger sequencing.Results:Among the 4 644 patients, 2 194 (47.24%) were found to carry common thalassemia mutations, among which 701 (15.09%) were α-thalassemia, 1 448 (31.18%) were β-thalassemia, and 45 (0.97%) were both α- and β-thalassemia. Forty six samples were found to harbor rare mutations, which included 17 α-globin gene and 29 β-globin gene mutations. CD77(CCC>ACC) ( HBA2: c. 232C>A) of the α-globin gene, NG_000007.3: g. 70567_71015del449, codon 102(-A) ( HBB: c. 308_308delA) and IVS-Ⅱ-636 (A>G) ( HBB: c. 316-215A>G) of the β-globin gene were previously unreported new types of globin gene mutations. Conclusion:Among the 4 644 patients, the detection rate for common thalassemia mutations was 47.24%, whilst 46 samples were detected with rare gene mutations. The type of gene mutation types were diverse in the Shanghai area. The study has provided more accurate results for genetic diagnosis and counseling.

NUT carcinoma is a rare, high lethal cancer which feature as the rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, and its pathogenesis and treatment is not yet clear, the prognosis is poor. Due to NUT carcinoma often occurred on the middle position of the body, such as eyes, nose and palate, mediastinum, so it is also called NUT midline carcinoma (NMC). In this case, we report a 70 years old man who was diagnosed as primary pulmonary NUT carcinoma in the Department of Thoracic Oncology, West China Hospital of Sichuan University. A tumor was found at the left hilus pulmonis when his physical examination without any symptom. Postoperative pathological showed poorly differentiated carcinoma, confirmed by fluorescence in situ hybridization technique for the NUT carcinoma. After operation, chemotherapy, antiangiogenesis therapy, and radiotherapy were given, and he got a long lifetime. Combined with the literature review, we report the clinical and pathological features, and treatment strategies of the rare pulmonary NUT carcinoma case.
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Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

OBJECTIVES: To investigate the distribution of serum calcium and the relationship between serum calcium and serum metabolic parameters in endometrial carcinoma (EC) patients. METHODS: Retrospective assessment of patients diagnosed with endometrial cancer from Peking University People's Hospital from 2004 to 2009. Clinical characteristics as well as pretreatment serum calcium, albumin, fasting plasma glucose (FPG), serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) value were extracted from patient records. Serum calcium was corrected for albumin. Unpaired t test and analysis of covariance were used to compare serum calcium among categorical variables. Simple correlation analyses and partial correlation analyses were used to assess the associations between serum calcium and continuous variables. RESULTS: Two-hundred twenty patients were included in this study. After adjusting for confounders, postmenopausal patients had higher total serum calcium (p=0.002) and albumin-corrected serum calcium (p=0.012) than premenopausal patients, endometrioid endometrial carcinoma (EEC) patients had higher total serum calcium than non-endometrioid endometrial carcinoma (NEEC) patients (p=0.037). Significant positive correlations were found between total serum calcium and FPG (p=0.017), TG (p=0.043), HDL (p=0.042), LDL (p < 0.001), and TC (p < 0.001) after adjusting for multiple variables, and the corrected serum calcium showed no significant correlation with metabolic parameters. CONCLUSION: Total serum calcium might be a more sensitive parameter for metabolic syndrome in endometrioid endometrial cancer patients than lipids.
Beijing ; Blood Glucose ; Calcium* ; Cholesterol ; Endometrial Neoplasms* ; Fasting ; Female ; Humans ; Lipoproteins ; Retrospective Studies ; Triglycerides

Objective To explore the effect of low-level laser therapy (LLLT)applied to the quadriceps muscle on the recovery of exhausting-cycling-exercise-induced fatigue.Methods According to a randomised,double-blind and crossover design,16 healthy male students were randomly assigned to an LLLT-1,LLLT-3,LLLT-5 and a placebo group,and received LLLT for 300 s at the dosage of 0.06 J· cm-2,0.18 J·cm-2,0.3 J·cm-2 and 0 to the bilateral rectus femoris after the exhausting-cycling-exercise-induced fatigue.The blood lactate(BL),heart rate(HR),rated perceived exertion(RPE)and visual analogue scale(VAS)were assessed before the exercise,immediately after exercise,10 and 20 min after exercise,as well as immediately after the first Wingate(WG)test,5 and 30 min after the WG test.Meanwhile,the second WG test was performed 40 min after the first WG test.Results The average HR value of LLLT-1 group was significantly lower than the placebo group at 10 min after exercise(P＜ 0.05)and immediately after the WG test(P＜0.01),while that of LLLT-3 and LLLT-5 groups was significantly lower than the placebo group immediately and 5 min after the WG test(P＜0.01).Compared to the placebo group,the average BL of LLLT-1,LLLT-3 and LLLT-5 groups was significantly lower 10 min after exercise(P＜0.05 for all)and that of LLLT-5 group was also significantly lower 30 min after the first WG test(P＜0.05).However,the average blood glucose of LLLT-5 group was significantly higher than the placebo group right after the first WG test(P＜0.05).Moreover,significant increase was observed in the mean(P=0.002)and peak power(P=0.006)at the second WG test and the mean(P=0.048) power at the first WG test of LLLT-3 group,compared to the placebo group.Conclusion LLLT applied to quadriceps muscles after exhausting exercise may enhance recovery,and LLLT at the dose of 0.18 J·cm-2 is of the best effect.

Objective To investigate the phenotypic and functional properties of in vitro-induced He-lios+regulatory T cells(Helios+iTreg) and to analyze the differences between Helios+iTreg and Helios+thymic-derived natural Treg (Helios+nTreg). Methods CD4+CD25- effector T cells (CD4+CD25- Teff) that were separated from healthy subjects were cultured with anti-CD3 and anti-CD28 antibodies and stimulated with IL-2 and TGF-β to induce the generation of Helios+iTreg. Flow cytometry and real-time PCR were respectively used to analyze the differences in phenotype and CpG methylation in Treg-specific demethylated region (TSDR) be-tween Helios+iTreg and Helios+nTreg derived from the same donor. Results CD45RA was highly expressed on Helios+iTreg, but not on Helios+nTreg. Additionally, Helios+iTreg expressed significantly higher levels of CD127,ICOS and PD-1,but lower levels of CXCR3,CCR4 and CD25 than Helios+nTreg did. IFN-γ and IL-2 that expressed by Helios+iTreg were more than those by Helios+nTreg. It was also found that the level of CpG methylation in TSDR was much higher in Helios+iTreg than in Helios+nTreg. Conclusion Both nTreg and iTreg expressed Helios,but the phenotypic and functional properties of the two Treg subsets were different. It was suggested that Helios+iTreg and Helios+nTreg might play different roles in the immune system.

Objective To evaluate the role of combined detections of routine blood test,serum iron and hemoglobin electrophoresis in screening thalassemia in non-high incidence area.Methods Peripheral blood and serum samples of 1 000 outpatients from the department of hematology and the department of gynecology and obstetrics were obtained.Common mutations of thalassemia were detected by using GAP-PCR and reverse dot blotting,and Sanger sequencing was performed to discover rare mutations of ct-and β-thalassemia.Routine blood test,serum iron and hemoglobin electrophoresis were also performed for every patient.Results Among 1 000 samples,225 (22.5％) are detected as α-thalassemia,403 (40.3％) β-thalassemia and 15 (1.5％) composite thalassemia.Among 225 α-thalassemia patients,28 were silent,138 were intermedia,and 59 were HbH disease.Of 403 β-thalassemia,390 were carriers,7 were double heterozygote,and 6 were homozygote.In all samples,there were 357 patients detected with no common mutations,38 patients had higher result values for both MCV and MCH and none detected with thalassemia gene.There were 48 patients who had higher serum iron but normal or lower MCV,42 of them (87.5％) had thalassemia gene.Furthermore,38 patients showed abnormal hemoglobin electrophoresis,35 of them were HbH disease,while the other 3 were HbF-related thalassemia.Five patients showed abnormal hemoglobin electrophoresis,lower MCV and MCH,as well as higher serum iron,had no frequent mutation but rare ones.Conclusion Patients with higher MCV and MCH can mostly be excluded to have thalassemia,while higher serum iron represents thalassemia possibility and can provide a preliminary indication of thalassemia type,and last but not least abnormal hemoglobin electrophoresis indicates the disease.It is recommended to further carry out sequencing of rare mutations for those who had abnormal results in the combined screening,and detected with no frequent mutation.Combination of these three examinations can improve the detection efficiency of patients with thalassemia.

There are many discussions and researches on the positive role of security and negative role of insecurity. However, from the view of biology and evolution, insecurity should be exist when people were born. It makes human to think, then produce relevant behaviors. Just these thinking and behaviors produce culture, maintain psychological individual balance and realize personal value.

OBJECTIVETo assess the association of genetic polymorphisms of mitogen-activated protein kinase activated protein kinase 2 gene (MK2) and zinc finger protein 36 gene (ZFP36) with high density lipoprotein cholesterol (HDL-C) in Xinjiang Urgur population.

METHODSNine hundred thirty Uygur individuals were randomly recruited from Hetian area. Single nucleotide polymorphisms (SNP) in MK2 gene (rs44890 and rs45514798) and ZFP36 gene (rs251864 and rs3746083) were determined with Taqman-PCR. All subjects were investigated with questionnaire, physical examination and measurement of lipid levels and plasma tumor necrosis factor-alpha.

RESULTS(1)In Uygur men younger than 50 years old, SNP rs45514798 was associated with HDL-C [dominant model P=0.054, OR(95%CI)0.261(0.082-0.833) after age, smoking, drinking, abdominal circumference, waist/hip ratio and body mass index and tumor necrosis factor were controlled]. (2) For males younger than 50 years old, the concentration of total cholesterol, HDL-C, low density lipoprotein cholesterol were different in dominant model of rs45514798(P< 0.05). Female: total cholesterol, low density lipoprotein cholesterol were different in dominant model of rs45514798(P< 0.05). (3) The distribution of genotype of ZFP36 gene did not differ significantly between the low HDL-C groups and the control group.

CONCLUSIONMK2 gene rs45514798 polymorphisms may be associated with HDL-C in Uygur men younger than 50 years old from Hetian area of Xinjiang. ZFP36 gene is not associated with HDL-C in Uygur people from Xinjiang.

Adult ; Age Factors ; Aged ; Base Sequence ; China ; ethnology ; Cholesterol, HDL ; blood ; Female ; Genetic Association Studies ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics ; Sex Factors ; Tristetraprolin ; genetics