m 6A RNA Methylation Decreases Atherosclerotic Vulnerable Plaque Through Inducing T Cells

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques.

Papillary renal neoplasm with reverse polarity: a clinicopathological analysis / 中华病理学杂志

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.

Expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone and its diagnostic value / 中华病理学杂志

To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.

Multi-Detector Row Computed Tomographic Evaluation of a Rare Type of Complete Vascular Ring: Double Aortic Arch with Atretic Left Arch Distal to the Origin of Left Subclavian Artery

Double aortic arch with an atretic left arch distal to the origin of left subclavian artery was diagnosed with multi-detector row computed tomography (MDCT) in two children with dysphagia. This rare type of complete vascular ring is clinically important because it may be confused with right aortic arch in mirror imaging. Anatomic details of this rare type of complete vascular ring demonstrated on MDCT facilitated appropriate surgical treatment.

The indication and time of treatment of thoracic endovascular aortic repair in acute Stanford B dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To study the indication of thoracic endovascular aortic repair (TEVAR) in acute Stanford B dissection.</p><p><b>METHODS</b>From February 2004 to June 2008, 464 cases of Stanford B dissection (391 males and 73 females, age from 26 to 88 with a mean of 56.6 years) underwent TEVAR. Patients were divided into group A (acute, n=298) and group B (chronic, n=166). Risk factors of rupture were evaluated and results were compared between the two groups.</p><p><b>RESULTS</b>The incidence of persistent or recurrent pain and hemothorax in ruptured patients was 83.3% and 94.4%, greater than 10.4% and 14.1% in the non-ruptured patients (P<0.01). The mean maximal diameter of the descending thoracic aorta in the rupture group was 49.4 mm, greater than 35.1 mm in the non-rupture group (P<0.01). Aortic branch vessel ischemia was greatly alleviated after TEVAR. Resolution of the proximal false lumen was 51.7% in group A, 19.5% in group B, and the rate of patent distal false lumen was 59.2% in group A, 79.3% in group B (P<0.01). Four out of 24 cases of intramural hematoma had recurrent dissection.</p><p><b>CONCLUSIONS</b>Acute dissection with a patent proximal false lumen is an indication for TEVAR. Intramural hematoma could be given medical treatment under close follow-up. Persistent or recurrent pain, hemothorax, descending thoracic aorta greater than 4.5 cm, or aortic branch vessels ischemia warrant prompt TEVAR.</p>

Comparative study on gemcitabine plus cisplatin and vinorelbine plus ifosfamide plus cisplatin combined chemotherapy in the treatment of advanced non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To compare the effect and toxicity between gemcitabine and cisplatin (GP) with vinorelbine, ifosfamide and cisplatin (NIP) combined chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Eighty patients received either gemcitabine 1 000 mg/m² on days 1, 8, or 15 plus cisplatin 70-80 mg/m² on day 1, or vinorelbine 25 mg/m² on days 1, 8, ifosfamide 1.2 g/m² on days 1-4 plus cisplatin 70-80 mg/m² on day 1, every 28 days as a cycle.</p><p><b>RESULTS</b>The objective response rate was 40.0% in GP goup, compared with 52.5% in NIP group (P > 0.05). Median survival time of GP and NIP groups was 13.68 and 15.34 months respectively, and 1-year survival rates were 54.29% and 59.46% respectively (P > 0.05). Leukopenia at grade III+IV was significantly lower in GP arm (27.5%) than that in NIP arm (55.0%) (P < 0.05). Non-hematological toxicities were less frequent in GP group than those in NIP group (P < 0.05).</p><p><b>CONCLUSIONS</b>Although the response rate tends to be higher in three-drug than in two-drug combined chemotherapy, but no significant difference is observed. Three-drug combinations often result in more toxicities. Two-drug combination GP may be the standard protocol for chemotherapy of advanced NSCLC. Three-drug combination NIP should be given to young patients with good performance status.</p>

Analysis of prognostic factors in patients with non-small cell lung cancer treated by surgery and chemotherapy / 中国癌症杂志

Background and Purpose:Lung cancer is the most malignant tumour in the world.Its incidence is growing and NSCLC is predominent(80%) in lung cancer.Most patients with lung cancer were diagnosed in late stages.The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following,operation could be improved,micrometastasis could be annihilated and survival could be extended.Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC.Methods:98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC,stageⅠ~Ⅲ,were collected retrospectively in our hospital from 1995 to 1997.35 cases were stageⅠ.21 cases were stage Ⅱ.42 cases were stage Ⅲ.83 cases had 1 cycle of chemotherapy pre-operatively.15 cases had 2 cycles chemotherapy pre-operatively.Regimes of chemotherapy were MVP,MOP and MAP et al.Response rate(RR) of chemotherapy was:45 cases had partial response(PR) and 53 cases were stable disease(SD).Operative mode was lobectomy and pneumectomy with lymph nodes dissection.Pathologic type was squamous,adeno,adeno-squamous and others.All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stageⅠin 1996~1997.After being followed-up for more than 5 years,data were examined using life table,KaplanMeier method,Log Rank statistic and Cox-mantel test.The possible factors affecting survival were tested with univariate and multivariate analysis.Results:The median followed-up time of 98 cases for NSCLC was 41.2 months.36 cases were alive.62 cases were dead.The 1-,3-,5-year survival rate of 98 cases for NSCLC was 88.78%、49.63% and 18.46%.The 5-year survival rates of stageⅠ、ⅡandⅢ were 33.23%、20.26% and 5.52% respectively(P=0.0002).The 5-year survival rates of N_(0)、N_(1)、N_(2) were 35.49%、19.08% and 4.90% respectively(P=0.0004).In the 98 cases of NSCLC,better prognosis was correlated with earlier stage.The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy,lung hila activity,thorax lymph nodes negativity and squamous cancer was better.The prognosis was poorer if the tumor had invaded big vessels,viscera,chest wall,pericardium and quantity bleeding during≥400ml.The prognosis was better if the tumor was fibrotic.The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle.The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better.Conclusions:The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage,the period from last chemotherapy before operation to operation,operation mode,lung hila activity,thorax lymph nodes,site of tumor invasion,bleeding quantity,pathologic type,tumor fibrosis and necrotis,cycles chemotherapy pro-operation and chemotherapy post-operation.

Influence of some factors on the prognosis of the postoperative stage ⅢA-N2 non-small cell lung cancer / 中国癌症杂志

Purpose:To identify clinical predictors of stage ⅢA-N2 in patients with non-small cell lung cancer. Methods:From March 1995 to February 1998, 118 patients with pathological stage ⅢA-N2 non-small cell lung cancer who underwent a resection by Shanghai Chest Hospital were analysed. Prognostic factors were estimated from the date of operation using the Kaplan-Meier and log-rank analysis. The Cox regression model evaluated the influence of factors on the survival. Results:The overall of 3-year and 5-year survivals of the 118 patients were 40.5% and 18.4%. Margin, the number of N2 lymph nodes and stations, the cycles of adjuvant chemotherapy were associated with survival. In a multivariate analysis, the number of N2 lymph nodes and the cycles of adjuvant chemotherapy significantly influenced survival. Conclusions:The number of N2 lymph nodes and the cycles of adjuvant chemotherapy were important prognostic factors of stage ⅢA-N2 non-small cell lung cancer.

Randomized study of low molecular weight heparin (LMWH) plus chemtherapy in advanced non-small cell lung cancer / 中国癌症杂志

Purpose: To evaluate the efficacy, safety and survival of low molecular weight heparin ( LMWH) plus chemotherapy in patients with advanced non-small cell lung cancer. Methods: 46 patients with NSCLC were randomized into chemotherapy plus LMWH. (study group) and chemotherapy only( control group). Both groups received two cycles of MVP regimen (MMC 6 mg/m2, YDS 3 mg/m2 x 2, DDP 90 mg/m2). Patients in the study group were treated with LMWH 5000u twice daily from the third day before chemtherapy up to 7 days. Results: The response rate was 56. 5% (13/23) for the study group and 39. l%(9/23) for the control group. Median survival time( MST) and 1-year survival rate were 12, 1 months(95%CI:8.52~14.64) and 52.2% for the study group compare 8.4 months(95%CI:6.15 ~ 10. 85) and 34. 8% for the control group. There were significant differences for MST( 12. 1 vs 8. 4) and 1 year survival rate(52. 2% vs 34. 8%) in the study group as compared to the control group. No difference in response rate and toxicities were found between the two groups. Conclusions: Chemotherapy( MVP regimen) plus LMWH is effective and safe. Prolonged survival was observed in patients who received MVP regimen plus LMWH.