Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma / 医学前沿

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

OShnscc: a novel user-friendly online survival analysis tool for head and neck squamous cell carcinoma based on RNA expression profiles and long-term survival information / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 ‍ 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.

Analysis on the relationship between pulmonary tuberculosis and vitamin D in Qinghai Province / 中华传染病杂志

Objective:To investigate the vitamin D level of pulmonary tuberculosis patients in Qinghai Province, and to explore the correlation between vitamin D level and pulmonary tuberculosis.Methods:From May to September 2020, 208 bacterial confirmed pulmonary tuberculosis patients who were admitted to The 4th People′s Hospital of Qinghai Province were enrolled as the pulmonary tuberculosis group, and 129 healthy people who underwent physical examination during the same period were enrolled as the healthy control group. Independent sample t test and chi-square test were used for statistical analysis. Results:The deficiency rate of vitamin D was 11.06%(23/208) in the pulmonary tuberculosis group, which was higher than that (3.10%(4/129)) in the healthy control group, and the difference was statistically significant ( χ2=6.840, P=0.009). The vitamin D level was (56.84±20.03) μg/L in the pulmonary tuberculosis group, which was lower than that ((67.39±17.07) μg/L) in the healthy control group, and the difference was statistically significant ( t=5.154, P<0.01). The vitamin D levels were not different between the newly treated ((56.66±20.02) μg/L)) and retreated pulmonary tuberculosis patients ((59.11±20.81) μg/L) ( t=0.468, P=0.650). The vitamin D level of simple pulmonary tuberculosis patients ((57.82±20.01) μg/L) was higher than that of pulmonary tuberculosis patients combined with other diseases ((48.08±18.46) μg/L), and the difference was statistically significant ( t=2.132, P=0.034). Conclusion:Pulmonary tuberculosis is associated with decreased vitamin D levels, and patients with pulmonary tuberculosis are more likely to suffer from decreased or deficient vitamin D, which suggests clinicians considering the vitamin D status when treating pulmonary tuberculosis patients.

Study on VNTR diversity of clinical Mycobacterium tuberculosis isolates from Qinghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the variable number tandem repeats (VNTR) genetic polymorphisms, genotyping and distribution pattern of clinical Mycobacterium (M.) tuberculosis isolates from Qinghai province.</p><p><b>METHODS</b>The clinical M. tuberculosis strains isolated from the patients with tuberculosis and related background data were collected from Qinghai Provincial Center for Disease Control and Prevention from 2009 to 2012. Genotyping was conducted by using multiple locus VNTR analysis (MLVA). Genomic DNA was extracted and 15 VNTR loci were amplified with PCR and the PCR products were detected with gel electrophoresis. The VNTR diversity and clusters of genotyping were analyzed with BioNumerics (Version 5.0).</p><p><b>RESULTS</b>A total of 251 clinical M. tuberculosis isolates were analyzed with 15 VNTR loci showing that there were great genetic diversity in these isolates. Six of the 15 VNTR loci, showed that the Hunter-Gaston index (HGI) were higher than 0.6, in which the highest resolution was MIRU26. The clusters of genotyping showed that these isolates could be categorized into four gene clusters and 238 genotypes. The four gene clusters accounted for 4.9%, 91.9%, 1.6% and 1.6% of the clinical isolates, respectively.</p><p><b>CONCLUSION</b>The results showed that there is great variety of VNTR genetic polymorphisms in clinical M. tuberculosis isolates in Qinghai province.</p>

Surgical approach and outcomes for treatment of pulmonary metastases

To investigate the surgical approach and outcomes, as well as prognostic factors for pulmonary metastasectomy. Clinical data of 201 patients treated by pulmonary metastasectomy between January 1990 and December 2009 were retrospectively reviewed. One hundred thirty three patients were received an approach of thoracotomy while 68 with video-assisted thoracoscopic surgery [VATS]. There were 54 lobectomies, 139 wedge resections and 8 pneumonectomies. Hilar or mediastinal lymph nodes dissection or sampling was carried out in 38 patients with lobectomy. The Kaplan-Meier method was used for the survival analysis. Cox proportional hazards model was used for multivariate analysis. The 5 years survival rate of patients after metastasectomy was 50.5%, and the median survival time was 65.9 months. The median survival time of patients with hilar or mediastinal lymph nodes metastasis was 23 months. By univariate analysis, significant prognostic factors included disease-free interval [DFI], number of metastases, number of affected lobe, surgical approach [open vs. VATS] and pathology types. DFI, number of metastases, and pathology types were revealed by Cox multivariate analysis as independent prognostic factors. Surgical resection of pulmonary metastases is safe and effective. Palpation of the lung is still seen as necessary to detect the occult nodule. More accurate and sensitive pre-operative mediastinal staging are required

Survival analysis of patients with pathologic T2-3N0 squamous cell carcinoma of thoracic esophagus after esophagectomy / 肿瘤研究与临床

Objective To analyze the clinicopathologic features of patients with pathologic T2-3N0 thoracic esophageal squamous cell carcinoma (ESCC) and correlation to their prognosis.Methods The clinicopathologic data of 422 patients with pathologic T2-3N0 thoracic ESCC,who were treated with surgery were analyzed.Cumulative survival rate was analyzed by the Kaplan-Meier method and compared by Log-rank test.Cox regression model was used for multivariate prognostic analysis.Results The overall 1-,3-and 5-year survival rates were 89.3 ％,63.5 ％ and 52.5 ％,respectively.Univariate analysis revealed that the factors affecting the prognosis included gender (x2 =7.45,P ＜ 0.01),depth of invasion (x2 =7.79,P ＜ 0.01) andtissues differentiation (x2 =15.81,P ＜ 0.01).They were also independent prognostic factors according Cox regression multivariate survival analysis.Conclusion The gender,depth of invasion and differentiation should be independent prognostic factors of pathologic T2-3N0 ESCC.Surgery is still the standard treatment for pathologic T2-3N0 esophageal cancer.

Features of lymph node metastasis and its effects on the prognosis of patients after radical operation for thoracic esophageal squamous cell cancer / 中华消化外科杂志

Objective To investigate the features of lymph node metastasis and its effects on the prognosis of patients after radical operation for thoracic esophageal squamous cell cancer, and investigate the reasonable postoperative adjuvant protocol. Methods Multivariate analysis of the clinical data of 204 patients was carried out by Spearman correlation analysis, Cox model and Kaplan-Meier method. Results The lymph node metastasis rate was 40.2% (82/204), and 166 out of 2193 dissected lymph nodes had metastasis with the rate of 7.57%. The analysis of related factors revealed that the invasion depth, tumor length and differentiation grade were significantly associated with the postoperative lymph node metastasis (χ2 = 17.466, 11.494, 6.767, P <0.05), while age, tumor site were not significantly correlated with the postoperative lymph node metastasis (χ2=1.086, 3.897, P > 0.05). Kaplan-Meier analysis showed that the 1-, 3-, 5-year survival rates of patients with < 4 lymph nodes metastasis were significantly higher than those with ≥4 lymph nodes metastasis (χ2=4.493, 4.494, 4.450, P < 0.05). The recurrence and metastasis were more often occurred in patients with lymph node metastasis compared with those without lymph node metastasis (r=-2.060, -4.296, P <0.05). Multivariate analysis confirmed that the pathological stage, tumor differentiation grade, and the postoperative adjuvant treatment were the independent prognostic factors. Conclusions The invasion depth, tumor length and differentiation grade are significantly associated with the postoperative lymph node metastasis. The lymph node metastasis state and the number of involved lymph nodes affect the prognosis of patients. Oral administration of 5-FU is benefit to the patients without lymph node metastasis.

Protein Preparation, Crystallization and Preliminary X-ray Crystallographic Analysis of Smu_195c From Caries Pathogen Streptococcus mutans / 生物化学与生物物理进展

Smu_195c is a protein with 86 amino acids in Streptococcus mutans, a primary pathogen for human dental caries. The specific function of Smu_195c is still unknown and there are no conserved domains in it. In order to find out its function, the gene encodes Smu_195c was cloned and expressed in E. coli as N-terminally 6*His tagged recombinant protein. Two crystal forms were obtained by the hanging drop method. Form Ⅰ belongs to space group P6122 or P6522 with the unit cell parameters a = b = 62.93 (A), c= 90.63 (A), γ=120° and form Ⅱ belongs to the space group P41212 or P43212 with the unit cell parameters a =b=57.97 (A), c = 103.51 (A).Crystals from the protein with His-tag belong to form Ⅰ, however, crystals from the protein without His-tag belong to both.

Preparation, Crystallization and Preliminary X-ray Crystallographic Analysis of Smu.776 From Caries Pathogen Streptococcus mutans / 生物化学与生物物理进展

The gene smu. 776 encodes a possible S-adenosylmethionine-dependent methyltransferase of 385 residues in Streptococcus mutans, a primary pathogen for human dental caries. The DNA fragment of smu.776 was cloned into pET28a and expressed in good amount from the E. coli strain BL21 (DE3). Smu.776 protein was purified to homogeneity in a two-step procedure ofNi2+ chelating and size exclusion chromatography. Crystals were obtained by hanging-drop vapor diffusion method and diffracted to 2.0 (A) resolution.The crystal belongs to orthorhombic space group C2 with cell dimension of a=168.47 (A), b= 50.66 (A), c=53.96 (A), β=104.22°. The asymmetric unit is expected to contain one molecule with solvent content of 51.3%.

Expression,Purification,Crystallization and Preliminary X-ray Studies of a Deoxycytidylate Deaminase From Streptococcus mutans / 生物化学与生物物理进展

Deoxycytidylate (dCMP) deaminase is an enzyme belonged to dCMP cyt deam family. The dCMP deaminase from Streptococcus mutans UA159 was cloned and expressed in E. coli, and purified to homogeneity. The FPLC size exclusion chromatography analysis reveals that the S. mutans dCMP deaminase forms hexamer in solution. The protein was crystallized using hanging drop vapour-diffusion method and diffracted to a resolution of 3.1 ?. The diffraction data were collected at BSRF beamline 3W1A. The crystals belong to P213 space group, with unit cell parameters a = b = c = 113.2 ?, ? = ? = ? = 90?. Assuming there are two subunits per asymmetric unit, the Matthews coefficient is 3.6 ?3?Da-1. This is the first crystallization report of the wild-type deoxycytidylate deaminase.

Progress in Structural and Functional Study of Ubiquitin Ligases / 生物化学与生物物理进展

Ubiquitination on target proteins is the signal of cellular protein degradation.Ubiquitin ligase E3 is one of the key enzymes in ubiquitination,it recognizes a specific substrate protein and recruits an ubiquitin conjugating enzyme E2,mediating the ubquitin transfer from the E2 to the substrate protein.Ubiquitin ligase E3 can be divided into two subfamilies according to their different structure characters and function mechanisms,the HECT(homologous to E6AP C terminus) family and the RING-finger family.Members of the HECT E3 share the common HECT catalytic domain,which can bind to an E2 and load the ubiquitin on themselves before catalyzing the transfer of ubiquitin to the target proteins.While the RING-finger E3 all contain an similar E2 binding domain and a unique substrate binding part,mediating direct ubiquitin transfer from the E2 to the substrate.The most recent progresses in the stuctural and functional studies of these two E3 famlies were summarized.

Expression, Purification, Crystallization and Preliminary X-ray Studies of a Deoxycytidylate Deaminase From Streptococcus mutans / 生物化学与生物物理进展

Deoxycytidylate (dCMP) deaminase is an enzyme belonged to dCMP cyt deam family. The dCMP deaminase from Streptococcus mutans UA159 was cloned and expressed in E. coli, and purified to homogeneity. The FPLC size exclusion chromatography analysis reveals that the S. mutans dCMP deaminase forms hexamer in solution. The protein was crystallized using hanging drop vapour-diffusion method and diffracted to a resolution of 3.1 (A). The diffraction data were collected at BSRF beamline3W1A. The crystals belong to P213 space group, with unit cell parameters a = b = c = 113.2(A), α =β = γ = 90°. Assuming there are two subunits per asymmetric unit, the Matthews coefficient is 3.6 (A)3 ·Da-1. This is the first crystallization report of the wild-type deoxycytidylate deaminase.

Protein Preparation, Crystallization and Preliminary X-ray Crystallographic Analysis of Smu.260 From Streptococcus mutans--a Cariogenic Dental Pathogen / 生物化学与生物物理进展

Smu. 260 encodes a putative protein of 200 residues in Streptococcus mutans, a primary pathogen for human dental caries. Smu. 260 was cloned into expression vector pET28a and expressed in good amount trom the E. coli strain BL21 (DE3). Smu.260 protein was purified to homogeneity in a two-step procedure of Ni2+ chelating and size exclusion chromatography. The purified protein exists in two forms, a dimer form about 46 ku with yellow color and a tetramer form without apparent color. Crystals were obtained from the dimer protein by hanging-drop vapor-diffusion method. The crystals diffracted to about 2.3 A resolution and belong to orthorhombic space group P212121 with cell dimensions of a = 89.88A, b = 90.91 A, c = 105.17 A. The asymmetric unit is expected to contain two dimers with solvent content of 53%.