[Overexpression of Nei endonuclease VIII-like protein 3 in hepatocellular carcinoma indicates increased levels of immune infiltration and an unfavorable prognosis].

Objective: To evaluate the role and molecular mechanism of Nei endonuclease VIII-like protein 3 (NEIL3) in hepatocellular carcinoma (HCC) through The Cancer Genome Atlas database. Methods: RNA sequencing of HCC samples was the first step in determining the level of gene NEIL3 expression in normal tissues and tumors. Then, NEIL3 was used for the Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, gene enrichment analysis, immune cell infiltration analysis. The samples were divided into high and low expression groups according to the median expression level of NEIL3 in liver cancer tissues. Logistic regression analysis, Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, and a nomogram prognostic model were used to explore the clinical and prognostic significance of NEIL3 in HCC. Results: Compared with normal samples, NEIL3 was highly expressed in most malignant tumors, including HCC (P < 0.05). High expression of NEIL3 was related to cell cycle, DNA replication, and cell receptor pathways. In addition, the high expression of NEIL3 was significantly positively correlated with T-helper 2 lymphocytes and infiltration levels (R = 0.670, P < 0.001). Compared with the NEIL3 low expression group, the NEIL3 high expression group had a higher level of Th2 cell infiltration in tumor tissues (P < 0.001). Logistic regression analysis showed that NEIL3 overexpression was associated with high T stage, high pathological stage, high tissue grade, AFP > 400 µg/L and vascular invasion of HCC. The Kaplan-Meier analysis results showed that overall survival [hazard ratio (HR) = 2.53, P < 0.001)], disease-specific survival (HR = 2.52, P < 0.001), and progression-free interval (HR = 1.82, P < 0.001) in patients with HCC with high NEIL3 expression were unfavorable. Cox regression analysis results showed that high NEIL3 expression was an independent risk factor for an unfavorable prognosis in HCC patients (P = 0.002). The nomogram and calibration chart further demonstrated that high NEIL3 expression was one of the risk factors for an unfavorable prognosis in HCC patients. Conclusion: Elevated expression of NEIL3 is associated with an unfavorable prognosis and an increased proportion of immune cells in HCC, and it is likely to be used as a potential biomarker for evaluating the prognosis and immune infiltration level.

[Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study].

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

[Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases].

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

[Clinicopathological and molecular genetic features of cyclin D1-negative mantle cell lymphoma].

Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.

[Clinicopathological characteristics of natural killer cell enteropathy: report of two cases and review of literature].

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.

[Nodal lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia: a clinicopathological and prognostical study].

Objective: To study the clinicopathological features and prognosis of nodal lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (n-LPL/WM). Methods: A total of 19 cases of n-LPL/WM were collected from May 2009 to January 2020 at First Affiliated Hospital of Zhengzhou University. The clinicopathologic features, immunophenotype, Ig gene rearrangement (BIOMED-2), MYD88 L265P mutation status (by Sanger sequencing) and follow-up data (by telephone) were analyzed. Results: There were 15 males and 4 females with a median age of 61 years (range 43 to 82 years). There were 14 WM and five LPL. The most common symptoms were weakness, fatigue (9/19) and B symptoms (11/19). Majority of the patients (16/18) presented with systemic multiple lymphadenopathies. Eighteen patients presented at advanced stages (Ⅲ/Ⅳ stage). Serum M protein status was IgM (15 cases), IgG (1 case), IgA (1 case) and no-secretory type (2 cases). Seventeen patients had bone marrow involvement. Morphologically, all 19 cases were divided into two groups: typical group (9 cases) or atypical group (10 cases). In the typical group, the structures of the lymph nodes were preserved; the neoplastic cells were predominantly plasmacytoid lymphocytes or mixed small lymphocytes, plasmacytoid lymphocytes and plasma cells, without proliferation of FDC network and follicular implantation. In the atypical group, the tumor showed effaced nodal architecture (5 cases), mainly proliferation of small lymphocytes (6 cases), FDC proliferation and/or follicular implantation (6 cases), marginal zone B cell differentiation (4 cases) and diffuse amyloidosis (1 case). Hemosiderin deposition (19 cases), infiltration of fatty tissue (19 cases) and interstitial sclerosis (9 cases) were commonly seen in both groups. Immunohistochemically, the neoplastic B cells expressed CD20 and CD79α, and the neoplastic plasma cells were positive for CD38, CD138 and MUM-1; eight cases showed light chain restriction; of the seven detected cases, five expressed IgM and the other two expressed IgG and IgA respectively; four cases expressed CD23 weakly, Ki-67 index was 10%-30%. MYD88 L265P mutation was seen in 18/18 cases. There was no significant difference in clinicopathologic features and prognosis between the two groups (P>0.05). The median follow-up time was 61 months, 11 patients were alive, while eight died; the 5-year survival rate was 21.1%. Conclusions: n-LPL/WM is rare, but patients usually present in advanced stages. It is easily confused with other small B-cell lymphomas with plasma cell differentiation, especially basing on morphologic features alone; thus the accurate diagnosis of n-LPL/WM requires a combination of clinical features, serum M protein, immunohistochemistry, bone marrow morphology,flow cytometry and MYD88 L265P mutation status etc. The prognosis of n-LPL/WM may be not very good, and further studies with more cases are needed.

[Clinicopathological and molecular genetic features of Burkitt-like lymphoma with 11q aberration].

Objective: To investigate the clinicopathological features, molecular genetics, treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q). Methods: Six cases of BLL-11q diagnosed at the First Affiliated Hospital of Zhengzhou University, from January 2016 to January 2020 were reviewed and analyzed using hematoxylin-eosin staining, immunohistochemistry, EBER in situ hybridization and fluorescence in situ hybridization. Clinical information including follow-up data was collected and analyzed. Results: The median age of the six immunocompetent patients was 29 years (range 20-38 years) and the male to female ratio was 5∶1. All patients had nodal disease in the head and neck region. Five patients had Ann Arbor stage Ⅰ-Ⅱ disease, while one patient had stage Ⅳ disease. Lymph nodes showed partial or total architectural effacement by a diffuse proliferation of monomorphic lymphocytes. Four cases were morphologically similar to Burkitt lymphoma, and two cases were unclassified with histological features between Burkitt lymphoma and diffuse large B-cell lymphoma. Mitotic figures, apoptosis and necrosis were conspicuous. Five cases exhibited the"starry sky"pattern. CD20, CD10 and bcl-6 were diffusely and strongly positive. The Ki-67 index was more than 95%. The follicular-dendritic-cell meshwork was noted in one case using CD21 stain. C-MYC was expressed variably. CD3, bcl-2, MUM-1, CD30 and TDT were negative in all cases. EBER in situ hybridization was also all negative. FISH analyses using C-MYC, bcl-2 and bcl-6 break-apart probes were all negative. All cases had the 11q23.3 gain/11q24.3 loss pattern, and 11q23.3 amplification was found in one case. IgH and IRF4 break-apart probes analysis was also negative. All patients were alive with no disease after a follow-up of 4 to 19 months. Conclusion: BLL-11q is a rare lymphoma that resembles Burkitt lymphoma morphologically and phenotypically, but lacks C-MYC gene rearrangements. Instead, it has a chromosome-11q alteration characterized by proximal gains and telomeric losses. It's necessary to improve our understanding of BLL-11q to avoid misdiagnosis and missed diagnosis.

[Characteristics of primary cutaneous rare nasal extranodal NK/T cell lymphoma: a clinicopathological study of 15 cases].

Objective: To investigate the clinicopathological features and differential diagnosis of primary cutaneous nasal extranodal NK/T cell lymphoma (pcENKTCL-NT). Methods: Fifteen cases of pcENKTCL-NT were collected at the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019. The clinical characteristics, morphological features, immunophenotypes, and results of in situ hybridization and gene detection were analyzed. Results: Among the 15 patients, 7 were male and 8 were female, with a male to female ratio of 1.0∶1.1. Their ages ranged from 29 to 86 years, and the median age was 59.3 years. All patients were hospitalized for skin lesions, including skin ulcers, scattered patchy red papules, and local blisters. The skin lesion might be a hard nodular mass, and part of it was a confluent patchy erythema; it could be manifested as multiple scattered nodules of different sizes, and some lesions were like round ulceration. There were 8 cases of lower limbs, 4 cases of chest (1 case with upper limb lesions), 2 cases of trunk and 1 case of neck. Most of the patients were sensitive to GGDP regimen (cisplatin, dexamethasone, gemcitabine and pemostatin). Histologically, most lesions showed tumor cells invading the epidermis and skin appendages, dermal infiltration, diffuse distribution, vascular and peritubular destruction, and some subcutaneous adipose tissue involvement. Morphologically, most of the tumor cells were mixed with small-to medium-size lymphocytes, and some were large cells, mixed cells or small cells. Immunohistochemistry showed that CD3, CD3 ε and TIA-1 were expressed in all cases, but not CD20 and CD8. CD56 and granzyme B were expressed in most of the cases, and CD5 was not expressed. Ki-67 positive index was about 50%-90%. EBV in situ hybridization was positive in all cases. The clonal rearrangement of T cell receptor gene was found in some CD56 negative cases. The 15 patients were followed up for 5-45 months, and one of them was lost to follow-up. Five patients died within 5-13 months after the diagnosis, accounting for 35.7% (5/14) of the 14 patients. The average survival time of the deceased patients was 8.6 months. Conclusions: The incidence rate of pcENKTCL-NT is relatively low, but its biological behavior is aggressive and its prognosis is overall poor. Its skin lesions and histopathological features are relatively diverse. The diagnosis should be determined with using clinical data, histological morphology, immunophenotype and EB virus in situ hybridization. At the same time, attention should be paid to differential diagnosis from other cutaneous lymphoma with cytotoxic phenotype to avoid missed diagnosis and misdiagnosis.

[Clinicopathological features and MYD88 L265P mutation status of intravascular large B cell lymphoma].

Objective: To study the clinicopathologic features and MYD88 L265P mutation status of intravascular large B cell lymphoma (IVLBCL). Methods: Fourteen cases of IVLBCLs were diagnosed from March 2014 to December 2019 at the First Affiliated Hospital of Zhengzhou University. The clinicopathologic features and prognosis were analyzed. Epstein-Barr virus encoded RNAs and MYD88 L265P mutation status were detected using in situ hybridization and Sanger sequencing, respectively. The follow-up data were obtained by telephone interview. Results: There were 6 males and 8 females with a median age of 62 years (range: 48-73 years). The involved anatomic locations were demonstrated by positron emission tomography-computed tomography, including adrenal gland (7/14), bone (6/14), central nerve system (4/14), skin (3/14), female reproductive system (3/14), local lymph nodes (3/14), prostate (2/14), liver and spleen (2/14), sphenoid sinus (1/14), penis (1/14), bladder (1/14), and right lung (1/14). Fever was the most common symptom (7/14), followed by neurologic symptoms and lower abdominal pain (2/14 each). The reminder symptoms included rash with edema, legs weakness and numbness, or postmenopausal bleeding (1/14 each). Eleven cases were at Lugano stage Ⅳ. Four cases were associated with the hemophagocytic syndrome, while 6 cases with bone marrow involved. Microscopically, the tumor cells were generally concentrated within the small-to-medium vascular lumens or sinusoids; they had centroblast-like appearance and showed large round or oval nuclei with slightly irregularities, coarse chromatin and 1-3 distinct nucleoli. One exception was the one case with an embryoid nuclei, reminiscent of anaplastic large cell lymphoma. The mitosis was not uncommon. Extravascular neoplastic cells were seen in two cases. The neutrophils could be appreciable in most of the cases (10/14). Immunophenotyping showed that CD20 and CD79α were diffusely and strongly positive in 14 cases; 12 cases were classified as the non-GCB subtype; 6 out of the 11 cases were double expressor lymphoma; 7 out of the 12 cases were CD5-positive. Twelve cases were EBER negative. The MYD88 L265P mutation was detected in 1 case (1/10). The duration of the follow-up ranged from 0.5 to 24.0 months, and 11 patients survived and 3 died. Conclusions: IVLBCL is rare. The most common type of IVLBCL in China is Asian type with scant tumor cells. Combination of clinical and immunohistochemical features can avoid most, if not all, misdiagnoses and missed diagnoses. Some IVLBCL cases may harbor the MYD88 L265P mutation, but the prevalence of MYD88 L265P mutation in the population still warrants additional studies.

[Clinicopathological features of primary EB virus positive nodal T/NK cell lymphoma].

Objective: To investigate the clinicopathological features of primary Epstein-Barrvirus (EBV) positive nodal T/NK-cell lymphomas (EBV+nodal TNKL). Methods: The clinicopathological features of 7 cases of EBV+nodal TNKL diagnosed between November 2015 and May 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry, PCR gene rearrangement and in situ hybridization.Follow-up data were also collected. Results: There were 5 males and 2 females with a median age of 54 years (ranged from 41 to 75 years). All patients presented with multiple lymphadenopathies and common B symptoms (5/7) and at an advanced Ann Arbor stage Ⅲ/Ⅳ(6/7). Bone marrow involvementwas detected in 1 patient.Six cases of T-cell origin had monomorphic patterns, and the tumor cells showed CD56 negativity and TCRαß+/TCRγδ－ with T-cell clonality. One case of NK-cell origin had polymorphic pattern, and the tumor cells showed CD56 positivity and TCRαß-/TCRγδ-without T-cell clonality. All cases were positive for the cytotoxic markers, but showed various CD4/CD8 expression. All 7 cases were diffusely positive for EBV (>100 cell/high power field). Six of the patients received chemotherapy, and 1 patient declined the treatments. During the follow-up period ranging from 3 to 48 months, 5 of the 7 patients died of the disease. Conclusions: EBV+nodal TNKL is a rare entity and is characterized by cytotoxic molecule expression, T/NK-cell derivation, and a predominance of nodal involvement at an advanced stage. It should be differentiated from other EBV+T/NK cell lymphoproliferative disorders, especially extranodal NK/T cell lymphoma.

[Peripheral T-cell lymphoma with follicular helper of T cell phenotype of Waldeyer's ring: a clinicopathological and genetic study of eight cases].

Objective: To study the clinicopathologic and genetic features of Waldeyer's ring peripheral T-cell lymphoma with follicular helper T cell immunophenotypes (wPTCL-TFH), with comparison to the nodal peripheral T-cell lymphoma with TFH immunophenotypes (nPTCL-TFH) and angioimmunoblastic T-cell lymphoma (AITL), as to know this rare tumor better. Methods: The clinical data, histopathology features, EBV positivity, T cell clonality and IDH2(R172) gene mutation in 8 cases of wPTCL-TFH were collected at the First Affiliated Hospital of Zhengzhou University from December 2015 to April 2019, and analyzed by immunohistochemistry, in situ hybridization, TCR gene rearrangement (BIOMED-2) and Sanger sequencing.Follow-up data were obtained by telephone. Results: There were 6 males and 2 females with a median age of 62.5 years (age ranging from 30 to 75 years). All patients had neither fever nor skin manifestations, but were all found mucosa thickened or mass of waldeyer's ring with multiple lymph nodes enlarged by PET-CT/CT scans. Five of the 7 patients were at advanced stages (Ⅲ/Ⅳ stage). Microscopically, the mucosa was infiltrated diffusely and characteristically by numerous small-medium sized lymphocytes, lacking polymorphous inflammatory background and extra-follicular expansion of follicular dendritic cell networks (FDC networks). The clear T cells presented in 5 cases. Ulcers on mucosal surfaces (6 cases) and local-extensive loss of intramucosal glands (7 cases) were commonly noted. Granulomas composed of epithelioid histiocytes were observed in 2 cases. Immunohistochemically, all the tumor cells expressed CD4 and at least 2 types of follicular helper of T cell (TFH) markers: PD-1 (8/8), bcl-6 (8/8), CXCL13 (7/8) and CD10 (1/8). Most of the cases (6 cases) expressed CD30. EBV positive appeared in 4 cases. All 8 cases were T cell monoclonal. IDH2(R172) were wild-type in 6 cases. One patient died at the follow-up time on 18 months; the other 7 survived (the follow-up time varied from 3 to 10 months). Conclusions: wPTCL-TFH is rare, and its clinicopathological features are similar to nPTCL-TFH which may be the manifestation of the same disease at different stage, and partly overlapped with AITL. The differential diagnosis from PTCL-NOS is necessary and comprehensive analyses of clinical, morphological, immunohistochemical and genetic features can help make a correct diagnosis.

[Mediastinal T lymphoblastic lymphoma/leukemia: clinicopathological and prognostic analyses of 61 cases].

Objective: To investigate the clinicopathologic features and prognosis of mediastinal T lymphoblastic lymphoma/leukemia (T-LBL/ALL). Methods: Sixty-one patients with mediastinal T-LBL/ALL diagnosed at First Affiliated Hospital of Zhengzhou University from August 1, 2011 to December 31, 2018 were enrolled. Their clinical, pathological, imaging features and prognosis were retrospectively analyzed. Results: Of the 61 patients with mediastinal T-LBL/ALL, 46 were male and 15 were female, with a male to female ratio of approximately 3∶1, aged 5 to 71 years (median 24 years, average of 24.5 years). Radiological findings were mediastinal soft tissue masses (58 cases) or mediastinal multiple enlarged lymph nodes (1 case). The tumor had a diameter of 4.9 to 18.3 cm in size, and data of 2 cases was unavailable. The patient's main symptoms were superior vena cava syndrome (cough, dyspnea, facial or neck edema), shortness of breath and chest pain, while about 1/3 of patients developed B symptoms (high fever, night sweats or significant weight loss). All 61 cases were biopsy specimens, and 2 of the tumors were later resected. Histopathologic examination showed that the thymic tissue epithelial network structure was destroyed or completely disappeared. A large number of lymphocytoid tumor cells were diffusely infiltrative, with infiltration into adipose tissue, starry sky phenomenon, linear-like arrangement, interstitial collagen hyperplasia and tumor cell extrusion. Focal tumor necrosis was present in some cases. Tumor cells were overall small to medium in size. They had little cytoplasm, slightly distorted, round or oval-shaped nuclei, fine chromatin, and innocuous/small nucleoli. Immunohistochemical studies showed that the tumor cells expressed CD7 (100%, 33/33), TDT (93.4%, 57/61), CD99 (83.3%, 25/30), CD1a (4/7), CD10 (8/18), CD34 (13.2%, 5/38), but did not express B cell markers (CD20 and PAX5) or granulocyte monocyte marker (MPO). The Ki-67 proliferation index was usually greater than 50%. One case was tested for TCR clonal rearrangement, which was positive. Several hemotherapy regiments were used. Hyper-CVAD (cyclophosphamide, vindesine, dexamethasone, and epirubicin) were most frequently administrated (60.4%, 32/53), followed by BFM-90 (50.9%, 27/53). Some patients were treated with the above two and other treatment options. Follow-up data were available in 55 of the 61 patients, and 26 patients (47.3%) survived. The average five-year survival rate was 50.6%. The patient's prognosis was not significantly related to the International Prognostic Index, age of onset, gender, or tumor size. Conclusions: The mediastinal T-LBL/ALL is rare, and most of its specimens are needle biopsies. The histological morphology is often difficult to interpret, while the addition of clinical features and immunohistochemistry may help. The combination of CKpan, TDT, CD99, CD7, CD3, PAX5, CD34, CD10, and Ki-67 immunohistochemicl studies may assist in diagnosis of the most cases.

[Effect of orthodontic tooth movement on keratinized gingival width].

OBJECTIVE: The relationship between the orthodontic tooth movement and the change of keratinized gingival width was analyzed by measuring the keratinized gingival width and position of the teeth before and after 28 orthodontic treatments. METHODS: The photos were matched to the model and the width of the keratinized gingival was obtained by measuring the length of the crown, and the keratinized gingiva. The pre- and post-treatment models were overlapped on rapidform 2006 and the change of tooth position before and after orthodontic movement could be accurately measured, and the relationship between tooth intrusion and extrusion, retraction and forward movement, torque variation and keratinized gingival width was statistically investigated. RESULTS: Analysis of the correlation between data before and after treatments for 213 teeth in 28 patients revealed a strong correlation between changes in tooth torque angle and changes in keratinized gingiva width (r=-0.47, P<0.001). In the multi-level linear regression analysis, the correlation between them was verified (regression coefficient<0, P<0.001), and there was no significant correlation between the intrusion and retraction of the teeth and the change of the width of keratinized gingiva (P>0.05). Regression coefficient was negatively relative to the reference incisor between the teeth for the canines and premolars (canine regression coefficient=-0.35, premolar regression coefficient=-0.38, P<0.05). Therefore, the study found that there was a strong negative correlation between the changes in tooth torque angle and width of keratinized gingival (r=-0.41, P<0.001), that is, an increase in positive torque led to the reduction of width of keratinized gingiva, and on the contrary the increase of negative torque would cause the width of keratinized gingiva increase. There was no significant correlation between the intrusion and extrusion of the teeth for the width of keratinized gingiva. The sensitivity of different teeth for the width of keratinized gingiva differed, with incisor compared with canines and premolars that were more prone to keratinized gingiva width changes. CONCLUSION: Tooth movement during orthodontics affected the width of the keratinized gingiva width, and the increase in positive torque was more likely to cause a reduction in the width of keratinized gingiva. There was no significant correlation between the intrusion and retraction of the teeth and the change in the width of keratinized gingiva. Incisors were more prone to changes in the width of keratinized gingiva relative to the cuspids and premolars during tooth movement. In the orthodontic process, it is possible to predict the effect of changes in the position of the teeth on the keratinized gingiva width, and attention shoud be to the changes in the keratinized gingiva width.

Effects of dexmedetomidine on myocardial ischemia-reperfusion injury through PI3K-Akt-mTOR signaling pathway.

OBJECTIVE: To explore the role of dexmedetomidine (DEX) in myocardial ischemia-reperfusion (I/R) injury model and investigate its specific molecular mechanism. MATERIALS AND METHODS: The I/R rat model was established by ligating the anterior descending coronary artery for 30 min and reperfusion for 120 min. In this experiment, all rats were divided into sham operation (SH) group, I/R group, DEX group and I/R + rapamycin (RAP) group. After 120 min of I/R treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rise and fall of left ventricular pressure (±dp/dtmax) and ischemic area were detected. Serum samples of rats in each group were collected. The levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), superoxide dismutase (SOD), creatine kinase (CK), CK-muscle/brain (CK-MB), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR), protein kinase B (Akt) and p-Akt in myocardial tissues were detected via Western blotting. Moreover, the messenger ribonucleic acid (mRNA) expression level of mTOR in each group was detected using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with SH group, LVSP and ±dp/dtmax in I/R group were significantly decreased, whereas LVEDP was remarkably increased in I/R group (p<0.01). After DEX administration, LVSP and ±dp/dtmax were remarkably increased, while LVEDP and infarction area were markedly decreased (p<0.01). After treatment with mTOR inhibitor rapamycin (RAP), LVSP and ±dp/dtmax were evidently decreased, while LVEDP and infarction area were increased when compared with those of DEX group (p<0.01). Compared with SH group, the levels of CK, CK-MB, TNF-α and IL-6 in I/R group were significantly increased. However, the levels of these molecules were significantly decreased after DEX treatment in I/R rats. After the combination of DEX and RAP, the expression levels of these indexes were significantly increased. No significant differences were found between DEX + RAP group and model group, and between I/R + RAP group and model group. MDA level in I/R group was significantly higher than that of SH group, while the levels of SOD, CAT and GSH-PX were notably lower (p<0.01). Compared with I/R group, the level of MDA in DEX group was significantly reduced, but the levels of SOD, CAT and GSH-PX were markedly increased (p<0.05, p<0.01). Meanwhile, compared with DEX group, MDA level in I/R group was significantly increased. However, the levels of SOD, CAT and GSH-PX were remarkably decreased after the application of combined DEX and mTOR inhibitor (p<0.01). After the addition of RAP, no significant changes were found in each index compared with I/R group. DEX could alleviate myocardial cell apoptosis caused by I/R treatment (p<0.01). The levels of p-mTOR and p-Akt in I/R group were significantly increased when compared with those of SH group. However, the levels of these indexes in DEX group were evidently higher than those of I/R group after DEX administration based on myocardial I/R model (p<0.01). After combination of DEX and RAP, the latter canceled the effect of the former on enhancing the expression of p-mTOR and the phosphorylation level of mTOR. Furthermore, there was no significant change in mTOR and its mRNA expression in each group. CONCLUSIONS: DEX can play a protective role in myocardial I/R rats, improve the cardiac function of I/R rats, eliminate oxygen free radicals, relieve oxidative stress injury, inhibit inflammatory responses and reduce the release of CK and other substances. The myocardial protection effects of DEX are mainly achieved through the phosphatidylin-ositol-3-kinase (PI3K)-Akt-mTOR pathway.

[Role of probiotics in treatment of nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in China and manifests as simple fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies have shown that intestinal flora can affect the development and progression of NAFLD via the "gut-liver axis" . Probiotics are active microorganisms with beneficial effects on the host, and more and more studies have found that probiotics play a positive role in improving NAFLD. They are cheaper, less harmful, and safer compared with antibiotics and surgery, and therefore, it may become a new method for the prevention and treatment of NAFLD. This article reviews the research advances in probiotics in the treatment of NAFLD, in order to provide a basis for the treatment of NAFLD using probiotics.

[The application of the three-step approach based on the regional distribution of hepatic vessel in laparoscopic hemihepatectomy].

OBJECTIVE: To investigate the clinical significance of the three-step approach in laparoscopic hemihepatectomy. METHODS: A total of 32 patients received laparoscopic hemihepatectomy with the three-step approach in Yijishan Hospital affiliated to Wannan Medical College between Aug 2013 and Oct 2015. All patients underwent thin slice CT scan and hemihepatectomy was imitated with the imagic explorer, preoperatively. The vessel distribution was observed at the section and the three-step approach was used in the hemihepatectomy. Pre- and post-operative data were collected and analyzed retrospectively. RESULTS: The length of middle hepatic vein (MHV) was (59.1±12.9) mm and the number of branchs to the left and right lobe were 3.07±0.78 and 3.11±0.64 respectively. The distance between the first branch of MHV and the diaphragmatic surface was (28.07±3.74) mm and the distance between MHV and the visceral surface was (14.4±4.3) mm. The laparoscopic surgeries (left hemihepatectomy in 28 and right hemihepatectomy in 4) were performed successfully in all cases with the three-step approach, without any conversion to the open surgeries. The operation time was (165±42) min in left hemihepatectomy and (305±50) min in right hemihepatectomy. The intraoperative blood loss was (242±65) ml in left hemihepatectomy and (695±122)ml in right hemihepatectomy. All the patients recovered well without severe complications except for bile leakage in 3 patients who were cured with drainage. The postoperative hospital stay was (7.96±1.8) d. CONCLUSIONS: the distribution of vessel is regional at the section of hemihepatectomy and the three-step approach based on this feature is safe and effective in laparoscopic hemihepatectomy, which can shorten the operation time and reduce the difficulty of operation.

Effects of two different anesthetic methods on cellular immunity of patients after liver cancer resection.

This study aims to investigate the effects of epidural block in combination with general anesthesia and general anesthesia alone on the immune function of patients undergoing primary liver cancer resection. Twenty-four patients with liver cancer who received treatment in the Third Hospital of Harbin Medical University, Heilongjiang, China, were enrolled and randomly allocated into group A and group B, with 12 in each group. The data on the T lymphocyte subpopulation, pro-inflammatory cytokines and antiinflammatory cytokines were recorded before, immediately after and 24 h after liver cancer resection to compare differences and changes. It was found that CD4+ of patients who underwent combined anesthesia decreased after surgery and CD8+ of those patients was lower than that of the general anesthesia group. The content of interleukin (IL)-10 of patients who underwent general anesthesia combined with epidural block showed a decreasing tendency immediately after surgery, but increased 24 h after surgery, and the increase was greater than that of the general anesthesia group; furthermore, those patients had lower levels of IL-1ß and interferon (IFN)-γ. In addition, patients who underwent epidural block and general anesthesia had a higher ratio of IFN-γ to IL-4 (Th1/Th2). These findings suggest that general anesthesia combined with epidural block has little passive influence on the cellular immunity of the body and can be selected as an anesthetic approach for patients with liver cancer.

Comparative Evaluation of Intrathecal Bupivacaine Alone, Bupivacaine-fentanyl, and Bupivacaine-dexmedetomidine in Caesarean Section.

PURPOSE: In this study, we aimed to compare the effects of bupivacaine alone, bupivacaine plus fentanyl, and bupivacaine plus dexmedetomidine for postoperative analgesia in women undergoing cesarean section under spinal anesthesia. MATERIAL AND METHODS: 90 term parturients scheduled to have elective cesarean section and ASA physical status I or II were allocated randomly into 3 groups to receive either bupivacaine (Bv group) or bupivacaine plus fentanyl (BvF group) or bupivacaine plus dexmedetomidine (BvD group). The onset time of sensory block, maximum sensory block level, duration of motor and sensory block, onset of post-operative pain, sedation scores, Apgar scores and side effects were recorded and statistically compared across 3 groups. RESULTS: Regression time to T10 was significantly longer in BvD group, sensory block was also prolonged in BvD group without any difference in duration of motor block. Onset of post-operative pain was delayed in BvD group. Sedation scores (VAS) were improved in case of BvD with least values of 0-3 followed by BvF (1-4). There was no significant difference in Apgar scores and neonatal arterial gas pressures across 3 groups. CONCLUSION: The use of dexmedtomidine as an adjuvant to bupivacaine in cesarean surgeries provides better intra-operative and post-operative analgesia without having significant impact on Apgar scores or incidence of side effects.