Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice / 国际口腔科学杂志·英文版

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

The clinicopathological characteristics and prognosis of 30 patients with hepatoid ade-nocarcinoma of stomach / 中国肿瘤临床

Objective:To review the clinicopathological characteristics and analyze the prognostic factors of hepatoid adenocarcinoma of stomach(HAS).Methods:From August 2012 to June 2017,30 patients with HAS were diagnosed in Daycare of Peking University Cancer Hospital.Clinicopathological data and follow-up information of these patients were retrospectively collected and analyzed.Re-sults:The median age of these 30 patients was 58 years at diagnosis,with a male-to-female ratio of 2.75:1.Twenty-nine patients were confirmed to have lymph node metastases and 7 patients had distant metastases.Ten patients died because of the cancer within the follow-up period.The 1-and 3-year survival rates were 60% and 52%,respectively.Cox multivariate regression revealed that elevated serum CA199 levels,higher lymph node staging,not having undergone radical surgery,and stronger immunohistochemical(IHC)stain-ing intensity of alpha fetoprotein(AFP)were independent poor prognostic factors.Conclusions:Elevated serum CA199 levels,lymph node staging,and IHC staining intensity of AFP are verified in this study as independent risk factors of poor outcome in HAS patients. Early detection and diagnosis of the disease may improve the clinical prognosis.Multidisciplinary team discussions are important in making therapy decisions and radical surgery should be performed whenever possible.

Adult-onset generalized autoimmune enteropathy involving small intestine and colon: report of a case and review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of adult-onset autoimmune enteropathy (AIE).</p><p><b>METHODS</b>A case of adult-onset AIE was described along with a literature review.</p><p><b>RESULTS</b>A 41-year-old male patient was admitted for intractable diarrhea for more than three months despite of any dietary restriction or anti-inflammatory therapy. Fat globule was observed by stool examination and Sudan III staining of the stool was positive. Enteroclysis showed weak movement and few plica of small intestine, while colonoscopy appeared normal. Small bowel biopsies revealed villus atrophy and increased crypt apoptotic bodies and lymphocytic infiltration in deep crypt. Although without significant surface intro-epithelial lymphocytosis, there were a large number of monocytes, lymphocytes, plasmacytes and neutrophilic granulocytes infiltrating in the lamina propria. Morphologically, the colonic mucous was similar to the small intestine although cryptitis and crypt abscess were significant in the former. Serum IgG anti-goblet cell antibody was demonstrated by indirect immunofluorescence. Other causes of diarrhea were excluded on the base of medical history, histopathology and other accessory examinations before the diagnosis of AIE was made. The patient had a complete remission after steroid treatment without recurrence for eight months during the follow-up even after steroid withdrawal for five months.</p><p><b>CONCLUSIONS</b>AIE is exceedingly rare and timely diagnosis is important for successful therapy. Histological differential diagnoses should include ulcerative colitis, celiac disease, lymphocytic colitis, etc. The final diagnosis should be based on histological examination combined with the patient history, clinical manifestation, endoscopy finding and serological testing.</p>

Expression and prognostic value of COX- 2, p16(INK4A) and p53 in patients with classical Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of COX-2, p16(INK4A) and p53 in patients with classic Hodgkin's lymphoma (cHL), and to evaluate their correlation with prognosis.</p><p><b>METHODS</b>The clinical data and samples of 52 cHL cases were collected. Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state. Correlation between the protein expression and prognosis of patients was analyzed.</p><p><b>RESULTS</b>Of 52 cases, the male and female ratio was 1.6∶1, the age was from 22 to 68 years old. All lesions located primarily in lymph nodes. All samples from 52 cases were stained with COX-2, p16(INK4A) and p53, and the positive expression of COX-2 was found in 28 cases (53.8%）, that of p16(INK4A) in 25 cases (48.1%)and p53 in 42 cases (80.8%）. All patients were divided into two groups according to differences in age (<40 years/ ≥ 40 years), gender (male/female), EBV infection (yes/no), B symptoms (yes/no), and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ), the correlation with COX-2, p16(INK4A) and p53 expression were analyzed, and only p53 expression was correlated with Ann Arbor staging (P=0.027). The statistical analysis of correlations between COX- 2, p16(INK4A) and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008), and p16 (INK4A) was not related to either COX-2 or p53 (P=0.246 and 0.958). Kaplan- Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients'event free survival (EFS) (P=0.003). Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091, 95% CI 0.017-0.505, P=0.006).</p><p><b>CONCLUSION</b>The expression rate of COX-2, p16 (INK4A) and p53 in the cHL were relatively high; and they were not statistically correlated with tumor EBV infection status; the COX-2 positive group had poor prognosis, but only event free survival time becomes statistically significant shorter. COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.</p>

Clinicopathologic features and prognosis of primary bone anaplastic large cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL).</p><p><b>METHODS</b>Twelve patients diagnosed with primary bone ALCL were retrospectively reviewed. The clinicopathologic features, immunohistochemic findings and results of in situ hybridization for EB virus were analyzed.</p><p><b>RESULTS</b>Of the 12 patients, the male-to-female was 7: 5 with a median age of 17.5 years (range from 9 to 64 years). Bone pain was the presenting symptom in all patients. Radiographic examination demonstrated solitary osteolytic lesion in 8 patients and multiple lesions in the rest 4 patients. Spine (7 cases) was the most common site to be involved, followed by ilium (5 cases), sacrum (2 cases), humerus (1 case) and collarbone (1 case). Ten patients were available with the follow-up data including 5 ALK-positive and 5 ALK-negative patients, and the follow-up time was 2 to 47 months. Interestingly, the 3 dead patients were ALK-negative whereas 5 of 7 ALK-positive patients achieved remission.</p><p><b>CONCLUSIONS</b>Primary bone ALCL is a rare type of non-Hodgkin lymphoma and it more frequently involves the axial skeleton. Boys and young males are more commonly affected. Patients usually present at an early stage and have a relatively favorable prognosis. Expression of ALK protein may be associated with a favorable prognosis in primary bone ALCL.</p>

Analysis of clinicopthologic features and prognosis of 4 cases primary gastric anaplastic large cell lymphomas / 白血病·淋巴瘤

Objective To evaluate clinicopathologic features and prognosis of primary gastric anaplastic large cell lymphomas (ALCL).Methods Clinical data and parafiin blocks of 4 patients diagnosed with primary gastric ALCL were obtained. The diagnosis of all cases was based on the criteria of WHO classification of hematolymphoid neoplasm.Furthermore,chromosomal rearrangement involving ALK gene was detected by interphase fluorescence in situ hybridization (FISH) and Epstein-Barr virus (EBV) status was determined by in situ hybridization(ISH) for EBV-encoded small RNAs (EBERs).Results The patients (3 males and 1 female) were from 27 to 87 years old, with a median age of 58.5 years. All the four cases presented with a solitary ulcerative mass in stomach. Morphologically, the normal architecture of gastric wall was effaced by the diffuse infiltration of tumor cells in which the characteristic hallmark cells were easily identified.The tumor cells of all cases showed a consistently strong expression of LCA and CD30,and CD3e was expressed in 3 of the 4 cases.Both ALK expression and ALK gene rearrangements were negative in all cases.Two cases underwent total or partial gastrectomy followed by CHOP chemotherapy. Another one patient was treated with chemotherapy and autologous stem cell transplantation. None of these 3 patients developed a relapse or progression till the last follow-up on Nov 30,2011. While the rest one patient refused to take any treatment and died 20 months after diagnosis. Conclusions Primary gastric ALCL is very rare and usually ALK negative. Its pathologic features as well as the clinical outcome are quite similar to the ALK negative ALCL from other sites, except the more frequently positive CD3e Early diagnosis and proper therapy are of great significance to the prognosis.

Analysis of prognostic factors of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue / 白血病·淋巴瘤

Objective To study the clinicopathologic features and explore the potential prognostic factors of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).Methods 86 patients diagnosed with MALT lymphoma were retrieved and divided into 2 subgroups according to the location of tumor,namely gastric (32 cases) and non-gastric (54 cases) subgroup.Histological characteristics were reassessed on hematoxylin-eosin staining slides,and immunophenotypic features were determined by immunohistochemical staining.Interphase fluorescence in-situ hybridization (FISH) was carried out to detect the cytogenetic abnormalities.Results There were no significant difference of clinical behavior,histology,and immunophenotype between gastric and non-gastric subgroups.In addition,FISH detected t(14;18) in 9 ％ (4/45) and t(11;18) in 12 ％ cases (6/50) respectively.Among the 20 cases treated with H pylori (HP) eradication,a significantly lower remission rate was observed in cases with bcl-10 (20 ％) nuclear expression or those harboring t(11;18) (33 ％) compared with those in the negative group (73 ％,91％)(x2 =3.842 and 4.639,P =0.035 and 0.031,respectively).For the 35 non-gastric patients with follow-up data,males (35 ％) and patients older than 60 yrs (25 ％) tended to have a lower remission rate as compared to females (60 ％) and those younger than 60 yrs (63 ％) (x2 =3.905 and 7.373,P =0.048 and 0.007,respectively).Moreover,progression-free survival rate was significantly lower in patients with higher stage (ⅢⅣ) (25 ％) and without t(14;18) (50 ％) than that in patients with stage Ⅰ-Ⅱ (52 ％) and with t(14;18)(75 ％).The differences had statistical significance (x2 =4.207 and 4.363,P =0.040 and 0.037,respectively).Conclusion MALT lymphoma in general is an indolent B-cell non-Hodgkin’ s lymphoma which more frequently occurs in the elderly people.Differences in the response to treatment or the prognosis are observed between gastric and non-gastric MALT lymphoma patients.

Analysis of transvaginal ultrasound examination to diagnose 156 cases of extranterine pregnancy / 中国基层医药

Objective To improve the accuracy rate of diagnosis by discussing the ultrasonographic features of extrauterine pregnancy by the transvagiual ultrasonography. Methods To analyze the characteristic of 156 cases which were examined by transvaginal ultrasonography,the features as well as distinguish main point,throuth the ret- rospective method. Results The accuracy rate is 94.3 % in this group. Conclusion There are many styles of ultra- sonographic .features,which examined by transvaginal ultrasonography in the extrauterine pregnancy. And different from one to another. Itis in evidence to improve the accuracy rate of diagnosis by using transvaginal ultrasono- graphy. The differentiate diagnosis are related to the history of sickness and the mutuality test and check.