The trend of accurate pathology diagnosis of breast cancer / 中华病理学杂志

Accurate pathology diagnosis of breast cancer is the premise of personalized treatment. In recent years, the pathology diagnosis of breast cancer have been updated and optimized to provide better guidance and basis for clinical treatment. In this paper, we provide an overview on the advances in histological classification of breast cancer, the progress of biomarker detection related to novel antibody-drug conjugates and immunotherapy in breast cancer, the pathology evaluation of breast cancer specimen after neoadjuvant therapy and sentinel lymph nodes, the progress of genetic testing in breast cancer, and the application of artificial intelligence in breast pathology.

Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

Current Situation and Reconsideration on the Study of Integrated Chinese and Western Medicine Andrology / 中国结合医学杂志

The development of Chinese medicine and Western medicine andrology is based on different social background and academic systems, either Chinese medicine or Western medicine andrology has their limitations, therefore, integration of Chinese and Western medicine (ICWM) andrology is in a great need. After more than 30 years of development, andrology has made great achievements in the construction of specialized academic association, holding academic conferences and publication of academic monographs, and the research progress on this field is mainly in the combination of disease and syndrome, microdifferentiation of symptoms and signs and basic research development. However, the comprehensive theoretic system of ICWM andrology has not yet established, and the related studies are still on the primary stage. In the future studies, great efforts still need to be made to expand the methods for the investigation of ICWM, and make innovations in the field of andrology.

Analysis of gene expression of Tetrahymena thermophila treated with Panax japonicas / 中国中药杂志

Panax japonicus is a traditional Chinese medicine,and its principle components have shown certain pharmacological activities for cell damage,aging and cell apoptosis. In order to clarify the pharmacological mechanism and involved metabolic pathways of P. japonicas,the gene expression of Tetrahymena thermophila under P. japonicus treatment was analyzed through high-throughput transcriptome sequencing in this study. Based on the transcriptome analysis,3 544 differentially expressed genes were identified in control group,of which 1 945 genes showed up-regulated expression and 1 599 genes showed down-regulated expression. Under P. japonicas treatment in the experiment group,3 312 differentially expressed genes were screened,of which 1 `493 genes showed up-regulated expression and 1 819 genes showed down-regulated expression. GO enrichment analysis indicated that in control group,the genes in the cells in a series of fundamental biological process were down-regulated,such as DNA replication and protein synthesis; while the signal transduction process and fatty acids oxidizing process were enriched. Whereas in the experiment group,down-regulated genes were mainly enriched in oxidation-reduction,cofactor metabolic process and vitamin metabolic process; up-regulated genes were enriched in signal transduction process and protein modification process. In the analysis using KEGG database,cell cycle pathway was enhanced and autophagy pathway was inhibited under the condition of P. japonicas treatment. Real-time quantitative polymerase chain reaction( RT-qPCR) was used to detect the expression differences between 6 up-regulated and 4 down-regulated genes in related metabolic pathways. The RT-q PCR results and RNA-Seq data were highly correlated and consistent with each other. This study could provide important direction and basis for further study on the mechanism of cell growth regulation with the treatment of P. japonica.

Immunogenicity of recombinant Lactobacillus plantarum NC8 expressing goose parvovirus VP2 gene in BALB/c mice

Goose parvovirus (GPV) continues to be a threat to goose farms and has significant economic effects on the production of geese. Current commercially available vaccines only rarely prevent GPV infection. In our study, Lactobacillus (L.) plantarum NC8 was selected as a vector to express the VP2 gene of GPV, and recombinant L. plantarum pSIP409-VP2/NC8 was successfully constructed. The molecular weight of the expressed recombinant protein was approximately 70 kDa. Mice were immunized with a 2 × 109 colony-forming unit/200 µL dose of the recombinant L. plantarum strain, and the ratios and numbers of CD11c⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, and interferon gamma- and tumor necrosis factor alpha-expressing spleen lymphocytes in the pSIP409-VP2/NC8 group were higher than those in the control groups. In addition, we assessed the capacity of L. plantarum SIP409-VP2/NC8 to induce secretory IgA production. We conclude that administered pSIP409-VP2/NC8 leads to relatively extensive cellular responses. This study provides information on GPV infection and offers a clear framework of options available for GPV control strategies.

Bushen Daozhuo Granules for type Ⅲ prostatitis: A multicenter randomized controlled clinical trial / 中华男科学杂志

Objective@#To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in the treatment of type Ⅲ prostatitis.@*METHODS@#This multicenter randomized controlled clinical trial included 478 patients with type Ⅲ prostatitis, 290 in the trial group and 188 as controls, the former treated with BDG at 200 ml bid and the latter with tamsulosin hydrochloride sustainedrelease capsules at 0.2 mg qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom Index (NIHCPSI) scores and compared the safety and effectiveness rate between the two groups of patients.@*RESULTS@#Compared with the baseline, the NIHCPSI score was markedly decreased in the control group after 4 weeks of medication (21.42 ± 4.02 vs 15.67 ± 3.65, P 0.05), while the NIHCPSI score in the trial group was remarkably lower than the baseline both after 4 weeks of medication and at 4 weeks after drug withdrawal (10.92 ± 2.06 and 12.91 ± 2.64 vs 21.58 ± 3.67, P < 0.05). The trial group exhibited both a higher rate of total effectiveness and safety than the control (P < 0.05).@*CONCLUSIONS@#BDG is safe and effective for the treatment of type Ⅲ prostatitis.

Mitotically active cellular fibroma of ovary: a clinicopathologic analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of mitotically active cellular fibroma (MACF) of the ovary.</p><p><b>METHODS</b>The clinicopathologic features of 11 cases of MACF from 2008 to 2012 years were retrospectively reviewed and immunohistochemic EnVision method was performed.</p><p><b>RESULTS</b>The age of patients ranged from 21 to 65 years (mean = 46 years). The maximum tumor diameter varied from 6 to 16 cm (mean = 9.8 cm). The tumors were densely cellular and composed of intersecting bundles of spindle cells, sometimes associated with storiform pattern. The mitotic count ranged from 4 to 20 per 10 high-power field (mean = 8.4). Atypical mitotic figures were not identified and coagulative tumor necrosis was not found. There was at most mild to moderate degree of nuclear atypia. Immunohistochemically, 8 cases showed positive stain for vimentin and 5 cases expressed diffusely or focally WT-1. In 6 cases, Ki-67 positive index ranged from 5%-30%, including 1 case (10%), and 1 case (30%) in which mitotic figures were 20/10 HPF. CK,AE1/AE3, CD117, CD34, CD99 and desmin were negative in the detected 5 cases. Reticular fiber staining in 2 cases showed dense reticular fibers enveloping individual tumor cells. Ten patients who followed-up range from 4 to 38 months were alive without evidence of recurrence or disease progression. One patient was alive with local recurrence 94 months after surgery.</p><p><b>CONCLUSIONS</b>Cellular fibromatous neoplasm with mitotic count of ≥ 4/10 HPF but relatively bland nuclear features should be considered as MACF rather than ovarian fibrosarcoma. MACF is a group of ovarian tumor which carries a low malignant potential and occasional chance of recurrence.</p>

Value of cytopathology in endobronchial ultrasound-guided transbronchial needle aspiration / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the role of cytopathology in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lung tumor diagnosis and staging.</p><p><b>METHODS</b>Two-hundred consecutive cases of lung tumor with EBUS-TBNA performed during the period from April, 2009 to September, 2010 in Shanghai Cancer Hospital were retrospectively reviewed. The cytologic diagnoses were categorized as non-diagnostic, negative, suspicious and malignant. When available, cell block preparation and immunohistochemistry were performed. On the 22 positive cases diagnosed by on-site evaluation, epidermal growth factor receptor (EGFR) mutation study was carried out.</p><p><b>RESULTS</b>In the 200 cases of cytology specimens, 122 cases (69.3%) were diagnosed as malignant, 42 cases (23.9%) as benign and 12 cases (6.8%) as suspicious for malignancy. The non-diagnostic rate was 12.0% (24/200). Amongst the 200 cases studied, 140 cases (70.0%) had histologic correlation available (via core biopsy, mediastinoscopic biopsy or surgical excision). The sensitivity and specificity of EBUS-TBNA cytologic diagnoses were 94.4% and 100%, when using histopathologic findings and clinical follow-up data as gold standard. The cell block preparation and immunohistochemistry were useful in subtyping and diagnosis of extrathoracic malignancy. EGFR mutations were detected in 8 cytology samples (36.4%).</p><p><b>CONCLUSIONS</b>EBUS-TBNA is a sensitive and specific tool for diagnosis and staging of lung cancer. The cytology samples can be used for further ancillary investigations including cell block preparation, immunohistochemistry and molecular studies.</p>

Neuroendocrine carcinoma of the breast: mammographic features correlated with sonography and histopathological findings / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to describe the X-ray features of the neuroendocrine carcinoma (NEC) of breast to raise the awareness for the disease.</p><p><b>METHODS</b>The mammography, sonography and clinicopathologic features in a total of 16 cases of pathologically proven breast neuroendocrine carcinoma in Fudan University Cancer Hospital were analyzed retrospectively.</p><p><b>RESULTS</b>All the 16 patients were women with a mean age of 67.3 years old (ranged from 45 to 75 years old). Twelve patients had palpable masses and the other four patients had outflow from the nipple. Pathological diagnosis included endocrine ductal carcinoma in situ (E-DCIS) in 4 cases, E-DCIS with microinvasion in 5, and invasive solid neuroendocrine carcinoma in 7. On mammography, 9 of 16 cases exhibited round or slightly lobulated masses. Five of the 16 cases exhibited irregular or asymmetric opacities. Two of the 16 cases had negative findings. The borders of the 14 masses detected on mammography were vague in 7, partly unclear in 3 and clear-cut in 4 cases. Malignant microcalcification was not found in all cases. The accuracy rates of preoperative qualitative diagnosis for NEC with mammography and sonography were 68.8% (11/16) and 81.3% (13/16), respectively. Given the application of combined mammography and sonography, the accuracy rates could be improved to 87.5% (14/16).</p><p><b>CONCLUSIONS</b>A round mass and irregular or asymmetric opacities without malignant calcification are the most frequent appearances of mammography in neuroendocrine carcinoma of the breast. Combination of mammography and sonography may be useful to improve the accuracy of diagnosis and early detection of neuroendocrine carcinoma of the breast.</p>

Meta-analysis of randomized trials comparing the effectiveness of on-pump and off-pump coronary artery bypass / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The growing enthusiasm for coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is emerging, but the role of off-pump coronary artery bypass (OPCAB) in clinical practice remains controversial. The purpose of this study was to assess differences in the incidences of stroke, atrial fibrillation (AF), and myocardial infarction (MI) between OPCAB and conventional coronary artery bypass grafting (CCABG) by meta-analyses of randomized clinical trials.</p><p><b>METHODS</b>A literature search for the period before March 2010 supplemented with manual bibliographic review was performed for all Chinese or English publications in Medline, the Science Citation Index Expanded, the Cochrane Central Register of Controlled Trials (CENTRAL) and CBMdisc. A systematic overview (meta-analyses) of randomized clinical trials was conducted to evaluate the differences between OPCAB and CCABG in the incidences of stroke, AF, and MI. The meta-analysis was performed using RevMan 5 software.</p><p><b>RESULTS</b>Forty-three randomized clinical trials were selected for meta-analysis after screening a total of 356 references, with 8104 patients in the OPCAB group and 8724 cases in the CCABG group. The meta-analyses of these trials showed no significant difference between OPCAB and CCABG in the incidences of stroke (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.52 - 1.22, P = 0.30) and MI (OR = 0.73, 95%CI = 0.52 - 1.02, P = 0.06). However, we found a significantly reduced risk of AF (OR = 0.65, 95%CI = 0.52 - 0.82, P = 0.0002) in off-pump patients.</p><p><b>CONCLUSIONS</b>Our meta-analyses suggest that OPCAB reduces the risk of postoperative AF compared with CCABG, but there is no significant difference in the incidences of stroke and MI between OPCAB and CCABG.</p>

Solid variant of mammary adenoid cystic carcinoma with basaloid features: a clinicopathologic and immunohistochemical study / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features.</p><p><b>METHODS</b>Clinical and pathological data were collected in four cases of the solid variant of mammary adenoid cystic carcinoma with basaloid features, and microscopic pathological examination and immunohistochemistry EnVision method were performed. The relevant literature was also reviewed.</p><p><b>RESULTS</b>The four patients were female, with age ranged from 46 - 65 years old (average 56 years) and the maximum tumor diameter ranged from 1.5 to 2.5 cm. Microscopically, the tumors exhibited a predominantly solid architecture with a myxoid or hyalinized stroma. The tumor cells showed moderate to marked nuclear atypia, and a basaloid appearance with scanty cytoplasm and inconspicuous nucleoli, and ≥ 5 mitotic figures per 10 high power fields. Glandular space embedded within tumor islands could be noticed. These spaces were genuine glandular structures and the cells lining these true glandular lumens had more abundant and eosinophilic cytoplasm. Pseudoglandular spaces of cribriform pattern or variable shape were also occasionally seen, and these cysts contained homogenous eosinophilic material. Focal necrosis was found. All cases were negative for ER, PR and HER2. Immunohistochemical staining for CK5/6, CK7 and CK14 was positive in the genuine glandular structures. All cases were positive for CD10, but also positive with varying intensity from weak to strong for vimentin and CD117. Staining for Ki-67 in three patients showed 10% - 50% positive.</p><p><b>CONCLUSIONS</b>The solid variant of mammary adenoid cystic carcinoma with basaloid features is a histologically distinctive and also a rare subset of the mammary adenoid cystic carcinoma. Awareness of its pathological features can help with the diagnosis as well as differential diagnosis. More cases are still needed for accurately assessing the prognosis of this particular tumor.</p>

Clinical observation of physiological and psychological reactions to electric stimulation of the amygdaloid nucleus and the nucleus accumbens in heroin addicts after detoxification / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stereotactic surgery has been used to treat heroin abstinence in China since 2000 by ablating the amygdaloid nucleus (AMY) and the nucleus accumbens (NAc), which also provides opportunity to identify the relationship between these nuclei and addiction. Our study aimed to explore the physiological and psychological effects of electrically stimulating the AMY and the NAc in heroin addicts after detoxification by observing changes of heart rate, arterial pressure and occurrence of euphoria similar to heroin induced euphoria.</p><p><b>METHODS</b>A total of 70 heroin addicts after detoxification were recruited, and 61 of them were eligible to be given stereotactic surgery for heroin abstinence. The operation was carried out after determining the coordinates of all target nucleuses, and stimulation was performed at the AMY and the NAc solely or jointly. Heart rate, arterial pressure and occurrence of euphoria similar to heroin induced euphoria were recorded and analyzed.</p><p><b>RESULTS</b>The average heat rate was (66 ± 10) beats/min before electric stimulation, and significantly increased to (84 ± 14) beats/min during stimulation, and changed to (73 ± 12) beats/min 10 minutes after stimulation. There was a significant elevation of the average arterial pressure from 83 mmHg before stimulation to 98 mmHg during the stimulation, and it then decreased to 90 mmHg after stimulation. Forty-three of the 61 patients showed intense euphoria similar to heroin induced euphoria. The largest number (118/186) of euphoric responses occurred when the AMY and the NAc were stimulated at the same time. Odds ratio was 5.4 (95%CI: 2.4 - 11.9, P < 0.0001) to quantify the association. Results from a Logistic regression model showed a positive correlation between unilateral stimulation of either the AMY or NAC and induction of euphoria (OR > 1), especially when the left AMY or left NAc was stimulated (P < 0.05).</p><p><b>CONCLUSIONS</b>Our data are consistent with existing results that the AMY and the NAc are related to addiction. Different roles in drug dependence would be suggested according to the location of the AMY and NAc.</p>

Rhabdomyosarcoma of the breast: a clinicopathologic study and review of the literature / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rhabdomyosarcoma (RMS) is an uncommon malignancy of the breast. The aim of this study was to summarize its clinicopathologic features and biological behavior.</p><p><b>METHODS</b>Five primary or secondary breast RMSs were collected. Their clinicopathological characteristics and all published literature about breast RMS were reviewed. Immunohistochemical study of desmin, myogenic differentiation 1 (MyoD1), myogenin, leukocyte common antigen (LCA), vimentin, cytokeratin (AE1/AE3), E-cadherin, neuron specific enolase (NSE), CD99, chorioallantoic membrane 5.2 (CAM5.2) and epithelial membrane antigen (EMA) expression were performed.</p><p><b>RESULTS</b>The five patients were all female with ages ranging from 16 to 46 years old (mean, 30 years). Three were metastatic breast RMSs, two embryonal and one solid variant alveolar, with the primary tumor sites the right labium majus, left nasal meatus and nasopharynx, respectively. The other two, one embryonal and one alveolar, were primaries. Grossly, the surgical specimens revealed round or oval, well-demarcated but nonencapsulated masses. Their cut surfaces consisted of homogeneous grayish yellow or white tissue. Microscopically, most tumor cells were poorly differentiated small round, oval or small polygons with eosinophilic cytoplasm. All cases were positive for vimentin, desmin, MyoD1 and myogenin. One embryonal RMS also had a few cells with perinuclear staining of AE1/AE3. The other markers were negative.</p><p><b>CONCLUSIONS</b>Although primary or metastatic RMS in breast was almost confined to young adolescent females, our cases suggested that it can also happen to the middle-aged women. Embryonal RMS has a certain metastatic potential. MyoD1 and myogenin are two useful markers when making differential diagnosis. Axillary lymph node status and age may play a role in the prognosis of primary breast RMS patients.</p>

A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastases enables the selection of patients for axillary lymph node dissections during the same operation, reducing the need for a second operation. The present study aimed to prospectively compare the GeneSearch(TM) Breast Lymph Node (BLN) Assay with touch imprint cytology (TIC) for intraoperative evaluation of SLNs.</p><p><b>METHODS</b>SLNs were sectioned in 1.5 - 3.0 mm pieces. TIC was performed on all pieces and the BLN Assay and postoperative histology evaluations were performed on different alternating node pieces. Overall performance of the BLN Assay was compared with that of TIC relative to the postoperative histology results.</p><p><b>RESULTS</b>A total of 90 patients enrolled in the study. Complete intraoperative data for both the BLN Assay and TIC were collected in 86 patients. The sensitivity, specificity, and overall accuracy of the BLN Assay were 82%, 97%, and 92%, respectively on a per patient basis compared with those of TIC which were 67%, 100%, and 90%.</p><p><b>CONCLUSIONS</b>Performance of the BLN Assay was superior to that of TIC and the additional application of TIC did not help improve the total sensitivity and accuracy of the intraoperative assessment. The existence of ectopic breast tissue might be a possible cause of false positive for the BLN assay. In addition, the BLN Assay complements histopathology assessment and can minimize sampling error without increasing pathologists' workload.</p>

Invasive carcinoma arising in breast microglandular adenosis: a clinicopathologic study of three cases and review of the literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotypes and differential diagnoses of invasive carcinoma arising in breast microglandular adenosis (MGACA).</p><p><b>METHODS</b>Clinical and pathologic findings of 3 cases of MGACA were analyzed by histomorphology and immunohistochemical staining of CK7, S-100 protein, ER, PR, HER2, SMA, MSA, p63 and PAS. Literatures were reviewed.</p><p><b>RESULTS</b>(1) Histologically, 3 tumors all showed a spectrum of glandular proliferations ranging from microglandular adenosis (MGA) to atypical microglandular adenosis (AMGA) to in situ carcinoma (DCIS) to invasive carcinoma. The invasive carcinoma component was ductal in case 1, and matrix-producing in case 2 and case 3. (2) All epithelial cells in MGA, AMGA, DCIS and MGACA were positive for CK7 and S-100 protein, but were negative for ER and HER2. PR was negative in case 1 and case 2 but was low positive in case 3. Myoepithelial cell differentiation was not demonstrated in MGA, AMGA, DCIS and MGACA by immunohistochemical staining for SMA, MSA or p63. PAS staining showed the presence of basement membrane in MGA, AMGA and DCIS, except MGACA.</p><p><b>CONCLUSIONS</b>MGACA is an extremely rare tumor of the breast and has distinct morphological and immunohistochemical features. Further studies are needed to evaluate the clinical behavior of this rare neoplasm.</p>

Transcriptional regulation of BHLHB2 induced by PML-RARα / 中国实验血液学杂志

Objective of this study was to investigate the transcriptional regulation of BHLHB2 gene by the PML-RARα fusion protein in APL cells and reveal the pathogenesis of APL. RT-PCR was performed to detect the expression change of BHLHB2 before and after the induction of PML-RARα in PR9 cells, and its expression level after the treatment of ATRA in PR9 and APL patient derived NB4 cells. Chromatin immunoprecipitation (ChIP)-based PCR was used to analyze whether the BHLHB2 promoter could be bound by PML-RARα in vivo. A large-scale gene expression profile dataset was used to observe the expression pattern of BHLHB2 in AML. The results showed that the expression level of BHLHB2 was significantly reduced with the induction of PML-RARα and ATRA could reverse this inhibition in both PR9 and NB4 cells and increase the expression of BHLHB2. However, the expression of BHLHB2 could not be induced by ATRA in U937 cells which do not express PML-RARα. Mechanism study revealed that PML-RARα could bound to the promoter of BHLHB2 in vivo to regulate the the expression of BHLHB2. It was found that the expression of BHLHB2 was relatively lower in APL as compared with other subtypes of AML and normal bone marrow cells. It is concluded that BHLHB2 is the target of PML-RARα, and the expression of BHLHB2 is inhibited by PML-RARα through binding to its promoter in APL.

Comparison of compensatory sweating and quality of life following thoracic sympathetic block for palmar hyperhidrosis: electrocautery hook versus titanium clip / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Video-assisted thoracic sympathetic block is an effective, safe, and minimally invasive method for treatment of primary hyperhidrosis. The purpose of this study was to decide which one of using electrocautery hook and titanium clip is the appropriate procedure for primary palmar hyperhidrosis by assessing the compensatory sweating (CS) and quality of life (QOL) of patients after sympathetic block.</p><p><b>METHODS</b>Between October 2007 to August 2010, 120 patients with primary palmar hyperhidrosis were randomly divided into two groups, electrocautery hook group (60 patients) and titanium clip group (60 patients). All patients were treated by sympathetic block at T4 level. The CS was graded based on severity and location; the QOL was classified to 5 different levels based upon the summed total scores (range from 20 to 100) before and after surgery. The variables were compared.</p><p><b>RESULTS</b>The postoperative follow-up period was 2 months. All patients were cured. Three patients in electrocautery hook group and 1 patient in titanium clip group had a unilateral pneumothorax on chest X-ray, but none of them was necessary to have chest drainage. Neither perioperative mortality nor serious complications such as cardiac arrhythmia or arrest were observed during the operation. No bradycardia or Horner's syndrome occured. CS was not more common in patients in titanium clip group than in those in electrocautery hook group (P = 0.001). Moderate and severe CS was few in all patients, and there was no significant difference between two groups (P = 0.193). Most of the patients feel a notable improvement of the the QOL; nevertheless, there was no significant difference between the groups (P = 0.588).</p><p><b>CONCLUSIONS</b>Both electrocautery hook and titanium clip used for sympathetic block at the T4 level are effective, safe, and minimally invasive for palmar hyperhidrosis. Because of the lower severity of CS and the similar improvements in the QOL after operation, we prefer to use of titanium clip for treating palmar hyperhidrosis.</p>

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer.</p><p><b>METHODS</b>Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS), respectively.</p><p><b>RESULTS</b>The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P < 0.05). The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner.</p><p><b>CONCLUSION</b>XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.</p>

Clinicopathologic study and immunohistochemistry comparison of Pax2, p53 and Ki-67 in low- and high-grade ovarian serous carcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the two-tier system for the grading of ovarian serous carcinomas, and to analyze Pax2, p53, Ki-67 protein expression and their prognostic values for low- and high-grade ovarian serous carcinomas.</p><p><b>METHODS</b>A total of 38 cases of low-grade and 100 cases of high-grade ovarian serous carcinomas were selected based on the two-tier grading system. Immunohistochemistry was used to detect Pax2, p53 and Ki-67 protein expression in all cases. Correlation of the two-tier system with immunohistochemical results and prognostic parameters were performed.</p><p><b>RESULTS</b>(1) The overall survival, disease-free survival and 5-year survival rates were significantly higher in the low-grade serous carcinoma cases than in the high-grade cases (P < 0.05). (2) Significant differences in protein expressions were found between the low- and high-grade serous carcinomas. The high-grade serous carcinomas had a significantly higher expression level of p53 (55.0% vs 13.2%, P < 0.05) and Ki-67 (42.1% vs 13.7%, P < 0.05), while low-grade carcinomas had a significantly higher expression level of Pax2 (65.8% vs 13.0%, P < 0.05). (3) Pax2 positive cases had a significantly better overall survival and 5-year survival rates than Pax2 negative cases (P < 0.05). The expressions of p53 and Ki-67 were found to have little correlation with overall survival and disease-free survival (P > 0.05).</p><p><b>CONCLUSIONS</b>The two-tier system for the grading of ovarian serous carcinomas has a good prognostic value. There are significantly differences in expressions of Pax2, p53 and Ki-67 between low- and high-grade ovarian serous carcinomas. Compared with p53 and Ki-67, Pax2 is likely a better prognostic indicator for ovarian serous carcinoma.</p>

Retrospective analysis of trastuzumab treatment in 141 patients with Her-2 positive breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.</p><p><b>METHODS</b>From January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.</p><p><b>RESULTS</b>In the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.</p><p><b>CONCLUSION</b>The regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.</p>