Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. @*Materials and Methods@#A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. @*Results@#TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. @*Conclusion@#This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Analysis of disease free survival based on CT imaging features in patients with cN0 gastric cancer / 中华放射学杂志

Objective:To explore CT imaging features related to disease-free survival (DFS) for gastric cancer (GC) patients with no clinical lymph node metastasis (cN0).Methods:From January 2005 to December 2018, 298 patients with GC were collected retrospectively in Peking University People′s Hospital. All the patients performed CT scanning before operation, and cT1-4N0M0 was defined by CT images. The clinical tumor stage (cT), extramural vessel invasion (EMVI), tumor morphological type, location and size were defined and recorded based on preoperative contrast-enhanced CT images. According to the pathological results, the patients were divided into pT1-2, pT3-4, pN0, and pN1-3 subgroups, with 148, 150, 135, and 163 cases, respectively. Progressive events and corresponding time were recorded during follow-up. DFS was defined as the time from radical operation to progressive events; if no progressive events occurred, DFS was defined as the time from radical operation to the last follow-up. The Kaplan-Meier curve and log-rank test were used to analyze the differences in cumulative DFS among patients with different CT imaging features, and Cox survival analysis was used to explore the independent CT imaging risk factors affecting DFS of cN0 patients. The log-rank test was used to test the effect of independent risk factors on cumulative DFS in different subgroups.Results:The follow-up time of enrolled patients was 36.0 (14.9, 59.3) months. The 3-year cumulative DFS rates of cT3-4 and cT1-2 GC patients were 61.2% and 85.6%, respectively, and the difference of DFS was statistically significant (χ 2=22.72, P<0.001). The 3-year cumulative DFS rate of EMVI-positive patients was 46.3%, which was lower than that of EMVI-negative patients (77.1%), and the difference was statistically significant (χ 2=21.34, P<0.001). There was no significant difference in 3-year cumulative DFS between different tumor locations and morphological types (χ 2=1.75, 1.73, P=0.189, 0.196). The difference in 3-year cumulative DFS between the tumor maximal diameter ≥3.4 cm and <3.4 cm groups was statistically significant (χ 2=17.58, P<0.001). On Cox survival analysis, cT (HR=5.203, P=0.001) and EMVI (HR=1.971, P=0.025) were independent risk factors for 3-year DFS in patients with cN0 GC. The results of subgroup analysis showed that the effect of EMVI on the 3-year DFS in pN0, pN1-3, pT1-2 and pT3-4 subgroups was statistically significant ( P<0.05). The effect of cT on the 3-year DFS was statistically significant in pN0, pN1-3, and pT1-2 subgroups ( P<0.05), but not in pT3-4 group (χ 2=2.58, P=0.108). Conclusion:cT and EMVI defined on preoperative CT examination are independently prognostic factors of 3-year DFS for patients with cN0 GC.

Multicentric Castleman disease with high IgG4 level: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the diagnosis and treatment of multicentric Castleman disease (MCD).Methods:The diagnosis and treatment of one MCD patient admitted in Hangzhou First People's Hospital in July 2020 was analyzed and related literatures were reviewed.Results:The patient was a 55-year-old male with anemia, elevated globulin levels and IgG4 > 10 g/L, and enlarged lymph nodes. He was undiagnosed for 7 years. Lymph node biopsy revealed a large number of polyclonal plasma cell hyperplasia, and the ratio of IgG4/IgG was less than 0.40; the serum interleukin (IL)-6 was more than 6 000 pg/ml and then he was eventually diagnosed as MCD (plasma cell type). Rituximab + cyclophosphamide + dexamethasone (RCD) regimen was not effective, and it was changed to anti-IL-6 receptor antibody tocilizumab for 2 courses and then the patient obtained good results.Conclusions:Castleman disease is a rare disease with a poor prognosis. It has high heterogeneity and is easy to be misdiagnosed clinically. The diagnosis requires pathological examination. IL-6 is considered to be closely related to the onset of Castleman disease and has become an effective target for treatment.

Clinicopathological characteristics of solid pseudopapillary neoplasm of the pancreas, an analysis of 23 cases / 中华普通外科杂志

Objective To study the clinicopathological characteristics and immunophenotype of solid pseudopapillary neoplasm (SPN) of the pancreas.Methods Retrospective analysis was performed for the clinical materials,pathological features and immunohistochemical phenotype characteristics of the 23 SPN cases.Results Ratio of male to female was 1:10;the average age was 32 years.10(43％) patients had no clinical symptoms,12 (52％) patients had abdominal pain,abdominal distention or diarrhea;1 patient had jaundice.Tumors were in the head of pancreas in 10(43％) cases,and were in the tail or body of pancreas in 13 cases.Grossly,tumors were solid-cystic or solid;the maximum diameter were from 1.3 cm to 17 cm,with the average of 5.9 cm;12 (52％) cases appeared encapsulated.Histopathologically,21 (91％) cases appeared to exhibit a fibrous capsule surrounding the tumors,and the fibrous capsule invasion were observed in all these cases;Pancreas tissues were involved in 8(35％) cases.Tumor cells arranged in sheets,nests and pseudopapillary patterns.Hemorrhage,necrosis and cystic degeneration were often seen.Tumor cells were positive for vimentin,β-catenin,CK,CD10,PR,CD56 and Syn.Tumor were mostly negative for CgA and Ki-67.23 cases were followed up for 2 to 44 months,and all were alive.Conclusion SPN is a low degree malignant tumor often seen in young women with various histological patterns and multiple immunophenotypes.Definite diagnosis of SPN can be made by combining clinicopathological characteristics with a panel of immunohistochemicat marks.SPN grows slowly,often responds to surgical resection and rarely recur.

Discussion on the Ethical Issues of Hepatic Encephalopathy Complicated with Liver Cirrhosis / 中国医学伦理学

Objective:To explore the ethical issues in liver cirrhosis and hepatic encephalopathy and integratet-hem into health education. Methods:36 patients with hepatic encephalopathy and their family members were car-ried out medical ethics education and adopted relevant nursing care. Results:It was proved that integrating medi-cal ethical knowledge into health education could greatly relieve patients′pressure and emotion swing, so as to ob-tain better treatment effect. Conclusion:Through carrying out effective ethics education for the patients with liver cirrhosis and hepatic encephalopathy, strictly complying with the principle of medical ethics that keeping secret for patients, protecting the subjects maximally, holding the issues between ethics and medical moral and cooperating with comprehensive treatment and nursing care, the death rate of hepatic encephalopathy can be largely reduced and relationship between doctors, nurses and patients can be improved.

The research of myosin-binding protein C in duced autoimmune myositis model / 中华风湿病学杂志

Objective To establish a new murine model of experimental autoimmune myositis by immunizing with MYBPC2 protein. Methods The purified Myosin-binding protein C, fast type (MYBPC2) was emulsified with complete Freundˊs adjuvant, then C57BL/6 mice were immunized by multi-point subcutaneous injection (0, 7 days), and intraperitoneal injection of pertussis toxin 2 μg simultaneously. The pathological changes of mice with different immunizing dose at the preconceived time were ex-plored. Mean-while, mice were immunized with 600 μg each time, and the muscle endurance was tested on the 21th day. The expression of major histocompatibility complex (MHC) class-Ⅰ and the surface biomarkers of the inflammatory cells in muscle tissues were observed. Mann-Whitney U test was used for statistical analysis. Results ① With the increase of immunizing dosage, muscle damage and inflammation tended to be more serious. On the 21th and 28th day, muscle lesions were most significant. Muscle fiber degeneration and necrosis and inflammatory cell infiltration could be seen in the experimental group. ② Compared with the control group, muscle endurance of mice in the experimental group decreased significantly [(6.1 ±1.3) min versus (9.2±1.6) min, U=2.00, P=0.017]. The MHC class-Ⅰ on the muscle fiber surface of the experimental group was positive, scattered infiltration of CD4 +, CD8+ T ly-mphocytes and CD68 + macrophages between muscle fibers and around the vascular areas could be observed, and CD20+B lymphocytes mainly distributed in the area around the blood vessels, nevertheless rarely seen between muscle fibers. Conclusion Exper-imental autoimmune myositis models of mice have been successfully induced by immunizing with MYBPC2 in China for the first time, and similar clinical and pathological features of human polymyositis could be observed. This new model can be used for studying the pathogenesis of autoimmune myositis.

Study of association between neutrophil extracellular trap and interstitial lung disease in dermatomyositis patients / 中华风湿病学杂志

Objective This study was focused on the association between neutrophil extracellular traps (NETs) and interstitial lung disease (ILD) in patients with dermatomyositis (DM).Methods Thirty six patients who satisfied the Bohan & Peter criteria for DM were recruited to this study,among whom 19 were complicated with ILD.Forty seven age and sex matched healthy Chinese volunteers were selected to be control subjects.The plasma samples of these patients were tested for the formation and degradation of NETs.Results DM plasma induced more NETs formation than control plasma did [(246±93) RFUs vs (192±53) RFUs,P=0.002].Compared to control,DM plasma exhibited a signficantry decreased ability to degrade NETs.Further mere,compared with DM patients without ILD (DMNL),DM patients with ILD (DML) could not degrade NETs completely [(83±13)％ vs (59±21)％,P＜0.01].All four DM patients with subacute ILD exhibited a significantly lower ability to degrade NETs than patients with chronic or asymptomatic ILD [(36±14)％ vs (65±19)％,P=0.0139].Conclusion These data show that more NETs formation is induced by plasma and DML fails to completely degrade NETs.These suggest that NETs may play a role in the pathogenesis of DM and DM-associated ILD.

Prokaryotic expression of recombinant mouse histidyl-tRNA synthetase-maltose binding protein fusion gene and identification of its antigen specificity / 中华风湿病学杂志

Objective To express the recombinant mouse histidyl-tRNA synthetase (HARS) and maltose binding protein (MBP) gene in Escherichia coli and obtain the purified protein which possesses antigen specificity.Methods Total RNA was extracted from the myocytes of C57BL/6 mouse and reversely transcripted to cDNA.The gene of N-terminal origin of 591 base pairs was amplified,then cloned into pMALc-5e vector.The recombinant plasmid was transformed into Rosetta-gami B,then IPTG was used to induce the expression of HARS-MBP.Fusion protein was purified by affinity chromatograph.The molecular weight (MW) of HARS-MBP was roughly determined by SDS-PAGE.The antigen specificity was identified by Western blotting using anti-Jo-1 serum from patients,commercial anti-HARS and anti-MBP antibodies.Results The recombinant HARS-MBP protein gene was efficiently expressed in Escherichia coli,and the MW was consistent with predicted MW of 66 000.The fusion protein was specifically combined with its antibody.Conclusion The HARS-MBP fusion protein could be efficiently and steadily synthesized in Escherichia coli,which shows satisfactory antigen specificity and provides the key requirement for making a deep study of HARS in the pathogenesis of idiopathic inflammatory myopathy(IIM) and animal modeling of IIM.