Comprehensive analysis of the immune and prognostic implication of MASP1 in stomach adenocarcinoma.

OBJECTIVE: Stomach adenocarcinoma (STAD) is the major cancer worldwide with high morbidity and mortality rate. Late diagnosis and limited treatment options of STAD lead to disease progression, spread, and metastasis. Therefore, finding a new biomarker to diagnosis and treatment is very important for STAD in clinical practice. MATERIALS AND METHODS: The clinical data, transcriptome data and CCLE data were downloaded from TCGA database and CCLE database, respectively. TIMER website, TISIDB website and CIBERSORT methodology were used to analyse immune infiltration. R software and R package were used to analyse gene difference expression, determine co-expression genes, conduct gene enrichment analyses, construct a prognostic signature and establish nomogram. RESULTS: MASP1 was decreased in STAD compared with normal tissue at the mRNA level (p < 0.001). The enrichment analysis showed that mismatch repair (MMR) was related to the MASP1 gene. Up-regulation of MAPS1 expression was positively associated with dendritic cells (p < 0.01), neutrophils (p < 0.05), macrophages (p < 0.001), CD4+ T cells (p < 0.001) and B cells (p < 0.05). A four-gene prognostic signature was determined based on MASP1-related immunomodulators. The prognostic signature was an independent prognostic predictor in STAD. Finally, we established a nomogram to forecast survival and the nomogram has a good prediction accuracy. CONCLUSIONS: In STAD, MASP1 is closely related to immunity. MASP1 has the potential to positively regulate the abundance of immune cells. The MASP1-related prognosis signature and nomogram can accurately predict the survival of patients with STAD. Therefore, MASP1 is likely to be a diagnosis and promising immunotherapy target spot in STAD clinical practice.

[Study on the etiological characteristics and prevention and control of adult community-acquired pneumonia in hospitalized patients in a hospital in Beijing from 2015 to 2019].

Objective: To explore the distribution characteristics of pathogens in adult patients with community-acquired pneumonia (CAP) and to provide basis for the diagnosis, treatment, prevention of CAP. Methods: 1 446 inpatients with CAP were prospectively enrolled in a third-class hospital in Beijing in recent 5 years (from January 2015 to December 2019). Respiratory tract samples were collected for smear, culture, nucleic acid, antigen and antibody detection to identify the pathogen of CAP. Mann-Whitney U test was used for continuous variables and χ2 test or Fisher's exact test was used for categorical data for statistical analysis. Results: Among the 1 446 patients, 822 (56.85%) patients were infected with a single pathogen, 231 (15.98%) patients were infected with multiple pathogens, and 393 (27.18%) patients were not clear about the pathogen. Influenza virus is the first pathogen of CAP (20.95%, 303/1 446), mainly H1N1 (8.51%, 123/1 446), followed by mycoplasma pneumoniae (7.19%, 104/1 446), Mycobacterium tuberculosis (5.33%, 77/1 446) and Streptococcus pneumoniae (5.05%, 73/1 446). The outbreak of H1N1 occurred from December 2018 to February 2019, and the epidemic of mycoplasma pneumoniae pneumonia was monitored from August to November 2019. Patients under 65 years old had high detection rates of Mycoplasma pneumoniae (14.41% vs. 2.41%, χ²=74.712,P<0.001), Streptococcus pneumoniae (8.16% vs. 2.99%, χ²=18.156, P<0.001), rhinovirus (6.08% vs. 3.56%, χ²=5.025, P<0.025), Chlamydia pneumoniae (5.90% vs. 1.15%, χ²=26.542, P<0.001) and adenovirus (3.13% vs. 0.92%, χ²=9.547, P=0.002). The severe disease rate of CAP was 14.66% (212/1 446), and the average mortality rate was 3.66% (53/1 446). The severe illness rate and mortality rate of bacterial-viral co-infection were 28.97% (31/107) and 19.63% (21/107), respectively. Conclusions: Influenza virus is the primary pathogen of adult CAP. Outbreaks of Mycoplasma pneumoniae and H1N1 were detected in 2018 and 2019, respectively. The remission rate and mortality rate of virus-bacteria co-infection were significantly higher than those of single pathogen infection. Accurate etiological basis not only plays a role in clinical diagnosis and treatment, but also provides important data support for prevention and early warning.

[Clinical high risk factors and prognosis of 25 pulmonary mucormycosis cases].

Objective: To analyze high risk factors, therapeutic regimen and prognosis of patients with pulmonary mucormycosis. Methods: A retrospective analysis was performed on the clinical data of 25 patients who were diagnosed as pulmonary mucormycosis in the First Affiliated Hospital, School of Medicine, Zhejiang University, between January 2009 and December 2017. Results: Univariate analysis revealed that no risk factor had significant effect on prognosis of these 25 cases, while multivariate logistic regression analysis confirmed that the exposure to antifungal drugs was correlated to worse prognosis(P=0.046). All 4 patients who had received surgical lesionectomy were cured, and 8 patients who had not received any therapy targeted to mucormycosis were all dead. Seven of 13 patients received antifungal drug to mucormycosis were effective, with an effective rate of 54.0%. The mortality rate of the operative group was lower than that of the non-operative group (P=0.026), and the prognosis of the patients received drug treatment was better than patients without treatment(P=0.022). There was no significant difference in the prognosis between groups of single drug or combination of amphotericin B and posaconazole. Conclusions: Pulmonary mucormycosis is more likely to occur in patients with tumor of the hematopoietic and lymphoid tissues, immunosuppression after solid organ transplantation, long-term glucocorticoid usage and diabetes. Surgical lesionectomy can improve the survival rate, and the treatment with amphotericin B and /or posaconazole can also improve the prognosis of the patients.

[Clinical features and prognosis of pulmonary sarcomatoid carcinoma].

Objective: To investigate the clinical features and prognosis of patients with pulmonary sarcomatoid carcinoma (PSC). Methods: The study retrospectively reviewed the clinical, radiological, pathological characteristics and prognosis of 76 patients with PSC who were treated in the First Affiliated Hospital of Medical School of Zhejiang University from January 2011 to December 2016. Gender, age, smoking history, tumor location, tumor size, lymph node metastasis, distant metastasis, TNM staging and treatment methods were analyzed to determine the factors affecting the prognosis of PSC patients. Results: The 76 patients with PSC consisted of 61 men and 15 women, the average age was (62.9±9.8) years old. Cough (31 cases, 40.8%), hemoptysis (29 cases, 38.2%) and chest pain (15 cases, 19.7%) were the main clinical manifestations; the average diameter of tumor was (4.7±2.3) cm; the peripheral type (48 cases, 63.2%), right lung (51 cases, 67.1%) and upper lobe of the lung (46 cases, 60.5%) were the common locations. The tumors usually were with a smooth margin, showing an irregular annular enhancement around the area, but the central part of the tumors were not enhanced obviously. The main pathologic type was pleomorphic carcinoma, and immunohistochemistry showed that vimentin and cytokeratin were usually expressed.Tumor size, lymph node metastasis, distant metastasis, TNM staging and early surgical treatment (P<0.05) were prognostic factors for survival, and distant metastasis and TNM staging (P<0.001) were independent prognostic factors affecting the prognosis of patients. Conclusions: There are no specificity in the clinical and radiological features of PSC patients in our study, and the diagnosis of PSC depends mainly on pathological analysis. Distant metastasis and TNM staging are independent prognostic factors.

[Correlation of liver stiffness measured by FibroTouch and FibroScan with Ishak fibrosis score in patients with chronic hepatitis B].

Objective: To investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B. Methods: A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis. Results: There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P < 0.01); serum ALT and AST levels and liver inflammatory activity were correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and FS and fibrosis stage (r = 0.501 and 0.526, both P < 0.001), and APRI and FIB-4 were also positively correlated with fibrosis stage (r = 0.236 and 0.218, both P < 0.001). Based on the Ishak fibrosis score, in the diagnosis of fibrosis stages F3, F4, F5, and F6, the areas under the ROC curve were 0.915/0.856/0.839/0.816 for FT, 0.933/0.883/0.849/0.856 for FS, 0.618/0.630/0.608/0.638 for APRI, and 0.614/0.624/0.595/0.649 for FIB-4, and FT and FS had a significantly larger areas under the ROC curve than APRI and FIB-4. Conclusion: LSM determined by FT or FS has a good correlation with the Ishak fibrosis score, so FT and FS have a significantly better diagnostic performance for liver fibrosis than APRI and FIB-4.

Abnormal expression of PTEN and PIK3CA in pemetrexed-resistant human pancreatic cancer cell line Patu8988.

The aim of this study was to investigate the expression of PTEN and PIK3CA in the pemetrexed-resistant human pancreatic cancer cell line Patu8988, and to evaluate their effects on the biological behavior of pancreatic cancer cells. PTEN and PIK3CA gene and protein expressions were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively, in a pemetrexed-resistant pancreatic cancer cell line and in the parent strain of the pancreatic cancer cells. The discrepancies between the two types of cell lines were detected by a transwell test. RT-PCR and western blot analyses revealed that PTEN and PIK3CA were overexpressed in the pemetrexed-resistant pancreatic cancer cell line. PTEN and PIK3CA were shown to be upregulated by 89 and 76% (western blot), respectively, in the pemetrexed-resistant cell line, compared to the normal pancreatic cancer cell line. The migratory and invasive abilities of the pemetrexed-resistant pancreatic cancer cell were significantly reduced compared to those of the parent strain (P < 0.05; transwell assay). Both PTEN and PIK3CA expression was abnormally enhanced in the pemetrexed-resistant cell line Patu8988; the co-existence of high levels of PTEN and PIK3CA in the pemetrexed-resistant pancreatic cancer line cells induced a significant decrease in their migratory and invasive capacities. This suggested that the mechanism of pemetrexed resistant may be affected by PTEN and PIK3CA, and that these may alter the biological behavior of cancer cells.

[Clinical analysis of the character and prognostic factors of 23 cases of mantle cell lymphoma].

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of mantle cell lymphoma (MCL) patients. METHODS: The clinical data of 23 MCL patients were retrospectively analyzed. Immunohistochemical stain was performed to detect the protein expressions of Mcl-1, pNF-κB p65 and 14-3-3ζ of MCL patients to analyze its prognostic factors. RESULTS: Among 23 MCL patients, there were 17(73.9%) patients with IPI 0-2 (low risk group) and 6(26.1%) patients with IPI 3-4. Only the rate of 2y-progression-free survival (PFS) of group IPI 0-2 was superior to that of group IPI 3-4 patients (47.1% vs 0, P=0.049); There were 16 (69.5%) patients with MIPI < 5.7, whose rates of overall response rate (ORR), 2y overall survival (OS) and PFS were better than those of the ones with MIPI ≥ 5.7(ORR: 81.3% vs 33.3% P=0.032; OS: 68.8% vs 16.7% P=0.041; PFS: 50% vs 0, P=0.040 respectively). The rates of ORR, 2y-OS and 2y-PFS (100.0%, 80.0% and 70.0%) of patienets received regimen R+CHOP(E) were all superior to those (38.5%, 30.8% and 7.7%) of ones received regimen CHOP(E) (P=0.002, P= 0.024, P=0.003, respectively). Among 12 patients, 2 out of 6 cases with Mcl-1 positive expression achieved good response (CR+PR) and 2y-OS, 1 case 2y-PFS; All 6 cases with Mcl-1 negative expression achieved good response (CR+PR) and 2y-OS, 5 cases 2y-PFS. 3 out of 6 cases with pNF-κB p65 positive expression achieved good response (CR+PR) and 2y-OS, 1 case 2y-PFS; 5 out of 6 cases with pNF-κB p65 negative expression achieved good response (CR+ PR) and 2y-OS/PFS. 5 out of 8 cases with 14-3-3ζ positive expression achieved good response (CR+PR), 4 cases 2y-OS, and 3 cases 2y-PFS. 3 out of 4 cases with 14-3-3ζ negative expression achieved CR, 4 cases 2y-OS, and 3 cases 2y-PFS. CONCLUSION: MCL patients had high heterogeneity. MIPI has better prognostic significance than IPI. R+CHOP(E) as first line treatment improved the rates of OS/PFS. The expressions of Mcl-1, pNF-κB p65 and 14-3-3ζ proteins in MCL might be related to prognosis.