Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder characterized by high heterogeneity. This study aimed to further understand the correlation between clinical phenotypes and genotypes in GD patients through a retrospective analysis of 20 cases in Shanxi Bethune Hospital, including their clinical manifestations, laboratory tests, enzyme studies, and genetic results. Among the 20 GD patients, 16 were classified as Type Ⅰ GD with a median age of diagnosis of 24 years, and 4 were classified as Type Ⅲ GD with a median age of diagnosis of 19 years. All patients exhibited splenomegaly and thrombocytopenia, with 16 patients showing skeletal imaging changes, and 5 of them presenting with bone pain symptoms. Genetic analysis revealed 15 distinct mutations, predominantly missense mutations, with L483P being the most prevalent (35.7%), followed by V414L, L303I, and F252I. Mutation sites were predominantly located in exon 7. Noteworthy findings included the first report of the S310G mutation by our research group and the first occurrence of the K196R mutation in the Chinese population. Additionally, the N227S mutation was implicated in a potential association with neuropathy. Despite advancements, Uncertainties still exist in the correlation between clinical phenotypes and genotypes in GD patients.

Myeloid sarcoma (MS) is a solid tumor formed by extramedullary infiltration of primitive or immature cells of the myeloid lineage. Pathology is the gold standard for diagnosis, but the misdiagnosis rate is high. Immunohistochemical staining can reduce misdiagnosis. Molecular biology and cytogenetics are important complementary diagnostic indicators. Imaging techniques, especially fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT), are important for the diagnosis of MS. Acute myeloid leukemia (AML) chemotherapy regimen combined with hematopoietic stem cell transplantation is currently the main treatment for MS.

OBJECTIVE: To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models. RESULTS: The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C. CONCLUSION Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.
Humans ; Factor XII/genetics* ; Pedigree ; Mutation ; Mutation, Missense ; Heterozygote ; Factor XII Deficiency/genetics*

Objective:To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.

Objective To investigate the clinical efficacy of video-assisted thoracic surgery (VATS) in the treatment of elderly non-small cell lung cancer (NSCLC). Methods A total of 92 elderly patients with NSCLC admitted to our hospital were randomly divided into control group and observation group, with 46 cases in each group. The control group was treated with classical treatment of thoracotomy plus mediastinal lymph node dissection, while the observation group was treated with VATS. The operation-related indexes, cardiac function [heart rate, (HR), pulse oxygen saturation (SpO2) ]and respiratory function indexes[forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximal voluntary ventilation (MVV) ]were compared between the two groups. The incidence of complications, hospital stay and expenses were compared. Results The operation was successfully completed in both groups, and no patients conversed to thoracotomy in the observation group. There were no significant differences in operation time and number of lymph node dissection between the two groups (P＞ 0. 05). Incision length, intraoperative bleeding volume and indwelling drainage time of the observation group were shorter than that of the control group (P ＜0. 01); but no differences were observed in HR, SpO2, FVC, FEV1, MVV of the two groups (P＞0. 05). The above indexes (except for SpO2) at 1 week after treatment of the two groups showed significant differences compared with treatment before (P ＜ 0. 05), and showed significant between-group differences (P ＜ 0. 05). The complication rate of the observation group was lower than that of the control group (6. 52％ vs. 21. 74％, P ＜ 0. 05), and the hospitalization time and medical expenses were (11. 93 ± 2. 57) d, (3. 06 ± 0. 58) ten thousand RMB, which were significantly lower than (13. 62 ± 3. 14) d, (3. 43 ± 0. 75) ten thousand RMB (P ＜ 0. 05). Conclusion Video-assisted thoracoscopic lobectomy (VATS) for elderly patients with NSCLC can not only achieve the same effect as thoracotomy for resection of tumors, but also have the advantages of less impact on cardiac function and pulmonary respiratory function, rapid recovery and less complication, and lower medical costs.

Objective To investigate the clinical efficacy of video-assisted thoracic surgery (VATS) in the treatment of elderly non-small cell lung cancer (NSCLC). Methods A total of 92 elderly patients with NSCLC admitted to our hospital were randomly divided into control group and observation group, with 46 cases in each group. The control group was treated with classical treatment of thoracotomy plus mediastinal lymph node dissection, while the observation group was treated with VATS. The operation-related indexes, cardiac function [heart rate, (HR), pulse oxygen saturation (SpO2) ]and respiratory function indexes[forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximal voluntary ventilation (MVV) ]were compared between the two groups. The incidence of complications, hospital stay and expenses were compared. Results The operation was successfully completed in both groups, and no patients conversed to thoracotomy in the observation group. There were no significant differences in operation time and number of lymph node dissection between the two groups (P＞ 0. 05). Incision length, intraoperative bleeding volume and indwelling drainage time of the observation group were shorter than that of the control group (P ＜0. 01); but no differences were observed in HR, SpO2, FVC, FEV1, MVV of the two groups (P＞0. 05). The above indexes (except for SpO2) at 1 week after treatment of the two groups showed significant differences compared with treatment before (P ＜ 0. 05), and showed significant between-group differences (P ＜ 0. 05). The complication rate of the observation group was lower than that of the control group (6. 52％ vs. 21. 74％, P ＜ 0. 05), and the hospitalization time and medical expenses were (11. 93 ± 2. 57) d, (3. 06 ± 0. 58) ten thousand RMB, which were significantly lower than (13. 62 ± 3. 14) d, (3. 43 ± 0. 75) ten thousand RMB (P ＜ 0. 05). Conclusion Video-assisted thoracoscopic lobectomy (VATS) for elderly patients with NSCLC can not only achieve the same effect as thoracotomy for resection of tumors, but also have the advantages of less impact on cardiac function and pulmonary respiratory function, rapid recovery and less complication, and lower medical costs.

Objective To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. Methods The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. Results The frequencies of HLA-A*0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4％vs 0.6％,χ2=10.788, P=0.001, Pc=0.016;7.5％vs 0％,χ2=69.850, P<0.0001);the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4％vs 16.1％,χ2=9.845, P=0.002, Pc=0.044;0％vs 3.1％,χ2=18.520, P<0.001). Conclusion The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.

Objective To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. Methods The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. Results The frequencies of HLA-A*0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4％vs 0.6％,χ2=10.788, P=0.001, Pc=0.016;7.5％vs 0％,χ2=69.850, P<0.0001);the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4％vs 16.1％,χ2=9.845, P=0.002, Pc=0.044;0％vs 3.1％,χ2=18.520, P<0.001). Conclusion The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.

Objective To investigate the radiosensitizing effects of artemisinin on CNE human nasopharyngeal carcinoma cells in vitro.Methods CNE human nasopharyngeal carcinoma cell line was used in this study.Cell growth kinetics was determined by MTT assay.Effect of the drug on radiosensitivity of CNE cells was analyzed by clonogenic assay.The change of cell cycle was measured by flow cytometry.Results The inhibition of CNE cells growth by artemisinin was increased with concentrations.Artemisinin (1 μmol/L)could enhance the radiosensitizing effects on CNE cell line,and the sensitizing enhancement ratio(SER)was 1.26.Artemisinin abrogated radiation-induced G2/M arrest of the tested CNE cells.Compared with the radiation alone group,the proportion of G2/M phase cells increased in radiation combined with drug group.Conclusions Artemisinin could reduce radiation-induced G2/M arrest and enhance the cytotoxicity of γ-irradiation on the CNE ceils.

Objective To investigate the radiosensitizing effects of artesunate on human HeLa cells of cervical cancer in vitro.Methods Hela cells were irradiated with 60Co γ-rays.The dose rate was 0.635 Gy/min and the radiation dose was 0,1,2,4,6 Gy,respectively.The anti-proliferation activities of artesunate on HeLa cells were evaluated with MTT assay,to determine the most appropriate drug concentration.The effect of radiosensitivity was observed by using clonogenic assay.The single-hit multitarget model was used to plot the HeLa cell's dose-survival curve,to calculate mean lethal dose,quasithreshold dose and sensitization enhancement rate,and to evaluate its radiosensitization effect.The apoptosis was analyzed with flow cytometry (FCM) to further test the radiation senseitization of artesunate on HeLa cells.Results The inhibition of artesunate on HeLa cells increased with concentration.In radiation group,the cell cloning efficiency were 91.67% ,82.02% ,58.60% ,25.01%,respectively,and in artesunate (2.0 μ mol/L) + radiation group,the cell cloning efficiency were 74.93% ,60.53% ,22.38% ,5.05%.In radiation group and artesunate (2.0 μmol/L) + radiation group,the mean lethal dose(D0) was 2.95 and 2.07 Gy,respectively,while the qusai-threshold dose (Dq) were 2.01 and 1.24 Gy,respectively,and SER was 1.43.Compared with 2 and 6 Gy radiation group,the apoptosis rate of drug + radiation group increased from 12.26% ,40.08% to 22.71% ,59.92%.Conclusions The inhibiting effect of artesunate on HeLa cells is concentration-dependent.Artesunate has radiosensitizing effect on HeLa cells in vitro.