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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion., (© 2023 Wiley Periodicals LLC.)

Introduction: Northeast China has always been an area with severe brucellosis prevalence. This study will identify Brucella in Northeast China and test its resistance to antibiotics, in order to clarify its resistance mechanism. Brucella is a widespread and highly pathogenic bacteria that poses serious threats to public health and animal husbandry., Methods: In this study, 61 Brucella isolates were identified by abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR) for biotypes and epidemic potential was clarified by multi-locus sequence analysis. Whole-genome sequencing (WGS) was performed and the antibiotic susceptibility of the Brucella strains against 13 antibiotics was detected with the use of E-test strips., Results: The results showed that all of the isolates were Brucella melitensis ST8, group CC4 with little genetic variation and obvious geographical characteristics. All 61 Brucella isolates were sensitive to doxycycline, tetracycline, minocycline, levofloxacin, ciprofloxacin, gentamicin, and streptomycin, while 24.6%, 86.9%, 65.6%, 27.9%, 3.3%, and 1.6% were resistant to rifampin, azithromycin, cefepime, cefoperazone/sulbactam, cefotaxime, and meperidine/sulfamethoxazole, respectively. This is the first report of cephalosporin-resistant B. melitensis in China. The WGS results indicated that about 60% of the antibiotic resistance genes were associated with efflux pumps (mainly the resistance nodulation division family)., Discussion: Brucellosis is usually treated with antibiotics for several months, which can easily lead to the emergence of antibiotic resistance. To ensure the effectiveness and safety of antibiotics for treatment of brucellosis, continuous surveillance of antibiotic susceptibility is especially important., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Xu, Wang, Bu, Yao, Zheng, Sun, Ji and Liu.)

Background: Adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) is the main strategy in treatment of children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC). Yet, an optimal number of NAC cycles remains unknown. We aimed to optimize the NAC cycle and potentially contribute to clinical decision making for the individual treatment of CA-LANPC., Patients and Methods: Utilizing an NPC-specific database through an acknowledged big-data information system at our center, we identified 143 CA-LANPC treated with NAC followed by CCRT between September 2007 through April 2018. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict disease-free survival (DFS). The clinical benefits of NAC cycles (two cycles vs three cycles) were assessed in each risk group., Results: Independent factors derived from multivariable analysis to predict DFS were T stage (T1-3 vs T4) and plasma Epstein-Barr virus (EBV) DNA (< 4000 vs ≥ 4000 copies/mL) for risk stratification. Consequently, 87 (61%) participants were classified as low-risk group (T1-3 with low or high EBV DNA, and T4 with low EBV DNA) and the other 56 patients (39%) were classified as a high-risk group (T4 with high EBV DNA) through RPA, and corresponding 5-year DFS rates of 91.9% and 71.2%, respectively (p = 0.001). Among the high-risk group, patients receiving three cycles of NAC had statistically significant improvement in 5-year DFS over those who received two cycles of NAC (86.7% vs 59.1%; p = 0.020), while the survival benefit of three cycles NAC for low-risk groups were not observed (94.7% vs 89.7%; p = 0.652)., Conclusions: We found three cycles of NAC with CCRT was a positive prognostic indicator for improved DFS for the high-risk group among CA-LANPC. However, whether low-risk patients could benefit from three cycles NAC needs further study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Bacteria translocation and systemic inflammatory response caused by intestinal barrier injury play a significant role in sepsis occurrence and deterioration, while hyperglycemia is linked to adverse outcomes in sepsis. Previous studies have shown that hyperglycemia is an independent risk factor for intestinal barrier injury. Concurrently, increasing evidence has indicated that some anti-hyperglycemic agents not only improve intestinal barrier function but are also beneficial in managing sepsis-induced organ dysfunction. Therefore, we assume that these agents can block or reduce the severity of sepsis by improving intestinal barrier function. Accordingly, we explicated the connection between sepsis, intestinal barrier, and hyperglycemia, overviewed the evidence on improving intestinal barrier function and alleviating sepsis-induced organ dysfunction by anti-hyperglycemic agents (eg, metformin, peroxisome proliferators activated receptor-γ agonists, berberine, and curcumin), and summarized some common characteristics of these agents to provide a new perspective in the adjuvant treatment of sepsis., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Wang et al.)

Background: To determine whether preoperative computed tomography (CT) features can be used for the prediction of gastrointestinal stromal tumors (GISTs) with a high Ki-67 proliferation index (Ki-67 PI)., Methods: A total of 198 patients with surgically and pathologically proven GISTs were retrospectively included. All GISTs were divided into a low Ki-67 PI group (<10%) and a high Ki-67 PI group (≥10%). All imaging features were blindly interpreted by two radiologists. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the predictive performance of the imaging features., Results: Imaging features were found to be significantly different between the low and the high Ki-67 PI groups (P<0.05). Wall thickness of necrosis showed the highest predictive ability, with an area under the curve (AUC) of 0.838 [95% confidence interval (CI): 0.627-0.957], followed by necrosis, necrosis degree, hyperenhancement of the overlying mucosa (HYOM), and long diameter (LD) (AUC >0.7, P<0.05). HYOM was the strongest predictive feature for the high Ki-67 PI GISTs group, with an odds ratio (OR) value of 30.037 (95% CI: 5.707-158.106)., Conclusions: Imaging features, including the presence of necrosis, high necrosis degree, thick wall of necrosis, and HYOM were significant predictive indicators for the high Ki-67 PI GISTs group., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4669). Dr. BS serves as an unpaid Associate Editor-in-chief of Annals of Translational Medicine from Sept 2020 to Aug 2022. The other authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT)., Methods: The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected., Results: Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT., Conclusion: Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background: Repeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage., Aim: To explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis., Methods: The difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level., Results: The diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation ( P < 0.05). The diameter (R2) increased after dilation ( P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations ( P < 0.05). The total symptom distress score significantly increased with the number of dilations ( P < 0.05). The symptom distress scores of the patients were negatively correlated ( P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1 st to 4 th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation ( P > 0.05) with the other dilations., Conclusion: In patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

BACKGROUND Osteosarcoma is a common malignant tumor of musculoskeletal stromal cells. Osteosarcoma clinical behavior depends mostly on the histologic grade, the site of primary tumor, the response to chemotherapy, and the presence of pulmonary metastases. The aim of this study was to knockout SHOX CNE9/10 in U2OS osteosarcoma cells and to analyze the effects on cell growth and apoptosis. MATERIAL AND METHODS U2OS cells with CNE9 knockout and U2OS cells with CNE10 knockout were established via the CRISPR/Cas9 system. Sanger sequencing was used to detect the success of the knockdown experiment. Western blotting and quantitative polymerase chain reaction were used to detect the expression levels of short stature homeobox-containing gene (SHOX) protein and messenger RNA (mRNA) after knockdown of CNE9 and CNE10. The cell viability and apoptotic rate were detected by the Cell Counting Kit-8 method and by flow cytometry. RESULTS The Sanger sequencing results showed that the knockdown experiment was successful. The levels of SHOX mRNA and protein were significantly reduced after knocking down CNE9 and CNE10. Knockdown of CNE9 and CNE10 significantly increased the growth and inhibited the apoptosis of U2OS osteosarcoma cells. CNE9/CNE10 knockdown U2OS cells were successfully constructed. CONCLUSIONS Knockdown of CNE9 and CNE10 promoted U2OS cell growth and inhibited apoptosis by decreasing SHOX expression. This CNE9/CNE10 knockout U2OS cell model could provide a bridge for the research on SHOX and CNEs in osteosarcoma.

Type 2 diabetes (T2DM) is characterized by hyperglycemia resulting from insulin resistance. Jiao-Tai-Wan (JTW), a traditional Chinese medicine consisting of a 10:1 formulation of Rhizoma Coptidis (RC) and Cortex Cinnamomi (cinnamon) was shown to have hypoglycemic efficacy in a type 2 diabetic mouse model. Here we investigated whether glucose consumption by insulin-resistant adipocytes could be modulated by serum from JTW-treated rats, and if so, through what mechanism. JTW-medicated serum was prepared from rats following oral administration of JTW decoction twice a day for 4 days. Fully differentiated 3T3-L1 adipocytes - rendered insulin resistance by dexamethasone treatment - were cultured in medium containing JTW-medicated rat serum. JTW-medicated serum treatment increased glucose uptake, up-regulated levels of phosphorylated adenosine 5'-monophoshate-activated protein kinase (p-AMPK), and stimulated expression and translocation of glucose transporter 4 (GLUT4). JTW-medicated serum induced significantly greater up-regulation of p-AMPK and GLUT4 than either RC or cinnamon-medicated serum. JTW-medicated serum induced effects on 3T3-L1 adipocytes could be partially inhibited by treatment with the AMPK inhibitor compound C. In conclusion, JTW-medicated serum increased glucose consumption by IR adipocytes partially through the activation of the AMPK pathway, and JTW was more effective on glucose consumption than either RC or cinnamon alone., (© 2019 The Author(s).)

Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1β (IL-1β)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1β-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.

Aim: The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI-NENs) patients., Methods: Patients diagnosed with GI-NENs were retrospectively indentified from existing databases of the pathological institute at our institution from January 2009 to November 2015., Results: We identified 414 patients with GI-NENs, 250 cases were diagnosed as neuroendocrine tumor G1 (NET G1), 25 as neuroendocrine tumor G2 (NET G2), 53 as neuroendocrine tumor G3 (NET G3), 55 as neuroendocrine carcinoma G3 (NEC G3), and 31 as mixed adenoneuroendocrine carcinoma (MANEC); the overall survival (OS) rate at three years were 94.9%, 91.7%, 74.3%, 62.7% and 38.1%, respectively. The difference in progression-free survival (PFS) duration among the patients with NET G1, NET G2, NET G3, NEC G3, and MANEC was statistically significant (P < 0.001). However, the PFS of NEC G3 and MANEC was low and similar (P = 0.090). In multivariate analysis of patients with GI-NENs, surgical margin, comorbidity, proposed new classification and tumor location were useful predictors of OS (P < 0.05)., Conclusion: Our findings suggest that the proposed new classification can accurately reflect the clinical outcome, together with surgical margin, comorbidity, and tumor location may be meaningful prognostic factors for the OS of GI-NENs., (© 2017 John Wiley & Sons Australia, Ltd.)

Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.

Objective: To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST)., Methods: The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively., Results: The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively. C-kit and PDGFRα mutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all the c-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502&#95;Y503dup (n = 6) and Y403&#95;F504ins (n = 14), while the mutation type were K642Q in exon 13 (n = 1) and N822K in 17 (n = 2). There were 6 patients with the mutation types of PDGFRα in exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRα mutation patients were significantly lower than that in c-kit mutation and wild type patients (P = 0.007). In the various type of c-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types (P < 0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients (P = 0.006)., Conclusion: The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST is c-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types.

The herbs used as the material for traditional Chinese medicine are mostly planted at mountain areas where there is appropriate weather condition. Due to the complex terrain condition in mountain area, the planting at such places is always associated with a scattered pattern, which inevitably bring difficulty to the work of accurate measurement for the planting area. Advanced research about monitoring the planting area for medicine-herb under complex environmental condition is so critical and meaningful for developing the medicine-herb planting to a large scale and an industry. Therefore, this research, taking the planting of Herpetospermum pedunculosum in Luding county as an example, utilizes RS&GIS: using the image data from TM and ETM datum as the remote sensing information source, integrating GPS data from quadrat survey on the spots, and analyzing on a GIS platform, to extract the planting area of H. pedunculosum in Luding county. The results indicate that: (1) the method and technology used to estimate the planting area of H. pedunculosum are feasible and can be applied to monitoring the planting area of medicine-herb at mountain area under complex environmental conditions: (2) the planting area of H. pedunculosum in Luding county is estimated to be 857. 246 acres by the methods utilized in this research, which is closed to the value from local statistical data with an error range less than 5%; (3) in consideration of those inevitable errorrs generating from the procedures such as remote sensing data acquisition, data preprocessing, data interpretation, and so on, and the fact that the classification of remote sensing data, which must be implemented by those above procedures, was used directly to extract the herb type, the accuracy of area estimation for the herb is significantly influenced by the accuracy of classification for herb type, and the estimated area is inevitably associated with some error.

Objective: To investigate the effect of coenzyme Q10 on the levels of tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10) in gingival tissue of experimental periodontitis in rats., Methods: A total of 48 healthy Wistar rats were divided into 3 groups of 16 randomly, normal group, coenzyme Q10 treatment group (Q10 group) and periodontitis group.Normal group was fed with normal diet and water. Periodontitis models were established in other two groups.Q10 group received coenzyme Q10 for 12 weeks and periodontitis group was fed with the same dose of normal saline.Four rats in each group were sacrified before administration and 4, 8 and 12 weeks after administration. Gingival tissue samples from mandiblar first permanent molar were taken. The levels of TNF-α and IL-10 were detected by immunohistochemistry., Results: The expression of TNF-α in periodontitis group [54.9% (52.9%, 57.3%)] was significantly higher than that in Q10 group [15.1% (12.7%, 17.5%)] at 12 weeks (P < 0.0167) . The expression of IL-10 in periodontitis group [8.9% (7.9%, 10.0%)]was significantly lower than that in the Q10 group [38.9% (38.0%, 40.4%)] (P < 0.0167) . The expression of TNF-α in periodontitis group was significantly higher than that in Q10 group at 12th weeks (P < 0.0167) . The expression of IL-10 in periodontitis group was significantly lower than that in the Q10 group (P < 0.0167)., Conclusions: Coenzyme Q10 inhibits the expression of TNF-α and promotes the expression of IL-10 in periodontal tissues of experimental periodontitis rats. Coenzyme Q10 may play a role in treating periodontitis.

Objective: To explore anatomical material basis of the lung meridian and its three-dimensional position in vivo., Methods: Continuous thin-section CT image sets were collected from a normal adult female volunteer's left upper extremity after she was acupunctured at 8 acupoints in Lung Meridian of Hand-Taiyin (LU). The connective tissue around the needle-tip of LU acupoints in continuous thin-section CT image sets was observed. The LU acupoints and part of the meridian were three-dimensional reconstructed in vivo and displayed with digital medical technology based on the CT-scan data. Then, the images were compared with traditional meridian records., Results: The connective tissue structure around the needle-tip of the eight LU acupoints was observed as follows: 5 acupoints were closely related to periosteum and 3 of them were closely related to blood vessels and nerve sheath. Three-dimensional reconstruction of anatomical position of the Lung Meridian of Hand-Taiyin was successfully completed in vivo, and the traveling course of meridian was similar to classical meridian illustration in traditional Chinese medicine., Conclusion: There is no specific entity of anatomical structure of LU acupoints and the meridian. The fascia and connective tissue may be the anatomical basis of meridian.

Objective: To investigate the prognosis and influencing factors of patients with adrenocortical carcinoma., Methods: Thirty-five patients (20 males and 15 females) with biopsy-diagnosed adrenocortical carcinoma were followed retrospectively. Cox proportional hazards regression analysis was performed to identify factors that influenced the prognosis of the patients., Results: Three patients were classified as stage I, 15 as stage II, 12 as stage III, and 5 as stage IV. Fourteen patients were still alive and 21 died at the end of the follow-up. The patients had a median survival time of 33 months, with a survival rate of 77.1%, 62.5%, and 38.3% for the first year, second year, and fifth year respectively. The univariate analysis found no significant differences in survival rates with gender, tumor location (left or right adrenal), diameter (> or = 10 cm or <10 cm) of tumor, functionality of tumor, smoking, hypertension and hypokalemia (P > 0.05). The multivariate analysis revealed that being male, younger than 50 years, non-smoking and early-stage of tumor were significant protective factors for the survival of patients with adrenocarcinoma. Patients at stage III and stage II had 52 and 3 times higher mortality than those at stage I, respectively., Conclusion: Clinical stage and age are the main factors that influence the survival of patients with adrenocortical carcinoma. Patients younger than 50 years and those with an earlier stage of tumor would have a better prognosis.

Background: The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson (NSBR) histological grading system for invasive breast cancer (IBC) adopted by the World Health Organization (WHO) has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system., Methods: Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index (Ki-67LI) was determined by immunohistochemistry, and its correlations with histological grade and survival were determined., Results: With respect to interobserver reproducibility, NSBR grading was fairly reproducible (kappa = 0.34); as for the components of NSBR grading, agreement was best for tubule formation (kappa = 0.46), intermediate for nuclear pleomorphism (kappa = 0.42), and poorest for mitotic count (kappa = 0.28). In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading (kappa = 0.30 - 0.69) and nuclear pleomorphism (kappa = 0.28 - 0.69), moderate to substantial for tubule formation (kappa = 0.51 - 0.78), and slight to substantial for mitotic count (kappa = 0.19 - 0.71). There were characteristic Ki-67LI ranges for grades 1, 2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival., Conclusions: The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate grading and treatment for IBC. Ki-67, with proven prognostic significance, adds complementary value to the NSBR system.

Objective: To investigate the association between distribution of protein gene product (PGP) 9.5-immunoactive nerve fibers in peritoneal endometriotic lesions and disease-associated pain symptoms., Methods: Thirty two peritoneal endometriotic lesions from patients with endometriosis (16 cases with pain and 16 cases without pain) and matched with 20 peritoneal tissues from patients with uterine leiomyoma without endometriosis were stained immunohistochemically for PGP9.5-immunoactive nerve fibers., Results: The positive rate and density of PGP9.5-immunoreactive nerve fibers in peritoneal endometriotic leision were 62% (10/16) and (3.8+/-1.7)/mm2 in endometriosis patients with pain, which were significantly higher than 19% (3/16) and (1.7+/-0.5)/mm2 in endometriosis patients without pain (P<0.05) and 25% (5/20) and (1.3+/-0.6)/mm2 in peritoneal tissues in women without endometriosis (P<0.05). However, no differences were found between endometriosis patients without pain and women without endometriosis (P>0.05). Moreover, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions in endometriosis patients with pain was positively correlated with the severity of pain (r=0.855, P<0.05). In addition, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions was statistically higher in endometriosis patients with chronic pelvic pain and (or) dysmenorrhea than those in endometriosis patients with other type of pain (P<0.05), which was not associated with active lesion, site and staging (P>0.05)., Conclusion: It suggested that PGP9.5-immunoreactive nerve fibers might confer the mechanism of pelvic pain with endometriosis.

Objective: To detect the expression of beta-catenin and Estrogen Receptor in desmoid-type fibromatosis., Methods: Nuclear beta-catenin expression was detected by immunohistochemistry in 77 lesions with desmoid-type fibromatosis and 171 other spindle cell lesions, including superficial fibromatosis (n = 18), nodular fasciitis (n = 36), keloid (n = 16), scar (n = 10), granulation tissue (n = 9), synovial sarcoma (n = 38), neufibroma (n = 13), solitary fibrous tumor (n =12), gastrointestinal stromal tumor (n = 10), low-grade myxofibrosarcoma (n = 3), low-grade fibromyxoid sarcoma (n = 3), and smooth muscle tumor (n = 10). In addition, the immunohistochemical expressions of ER-alpha, ER-beta and Ki-67 were examined in all of the lesions with desmoid-type fibromatosis. The nuclear immunohistochemical staining for nuclear beta-catenin and ER-beta was graded as high level ( > or = 25% of cells), low level (5%-25%) or none., Results: High-level nuclear beta-catenin staining was detected in a very limited subset of tissue types, which included 70.1% of lesions with desmoid-type fibromatosis (54/77) and 6.3% of lesions with keloid (1/16). No high-level nuclear beta-catenin staining was seen in any of the other lesions. None of the lesions with desmoid-type fibromatosis expressed ER-alpha. However, 62 (80.5%) of the lesions with desmoids-type fibromatosis were positive in ER-beta, which included 52 (67.5%) with high-level expression, and 10 (13%) with low-level expression. The Spearman correlation analysis suggested that the expression of beta-catenin was positively correlated (r = 0.867, P < 0.05) with the expression of ER-beta. The lesions with desmoid-type fibromatosis had very low Ki-67 positive rate. The recurrence of desmoids-type fibromatosis was not correlated independently with beta-catenin, ER-beta or Ki-67., Conclusion: High-level nuclear beta-catenin staining serves as a useful diagnostic tool for desmoid-type fibromatosis. The high expression of ER-beta in desmoid-type fibromatosis provides a biological mechanism for the antiestrogenic compounds to treat fibromatosis. There might exists an interaction between beta-catenin and ER-beta. Beta-catenin, ER-beta or Ki-67 can not predict the prognosis of desmoid-type fibromatosis.

Background: Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is a rare soft tissue tumor, which is generally considered low-grade. To distinguish the tumor from other soft tissue lesions, we analyzed the clinicopathologic and ultrastructural features, immunophenotypes, and flow cytometric DNA ploidy of PHAT in 9 cases., Methods: PHAT specimens were collected from 9 patients with PHAT from 1990 to 2004. Each specimen was cut into pieces and stained with hematoxylin-eosin, phosphotungstic acid-hematoxylin, Prussian blue, and Masson trichrome, respectively. Immunohistochemical stains for vimentin, S-100 protein, CD34, CD31, CD99, VEGF, desmin, CD117, alpha-SMA, and MIB-1 were performed with the Envision system. Flow cytometry was used in four specimens, two of which were observed by electron microscopy., Results: In the 9 cases, the PHAT occurred at the lower extremity in 2 patients, inguinal in 2, waist in 1, forearm in 1, buttock in 1, foot in 1, and the chest wall in 1. All the lesions presented in the superficial subcutaneous tissues. Follow-up data were available in 7 of the patients, among whom 2 (28.6%) had recurrence after primary therapy. Microscopically, typical PHAT was characterized by sheet-like proliferation of spindle or pleomorphic cells and clusters of thin-walled hyalinized cstatic vessels. In some areas of the tumor, hemosiderin-laden spindle cells, numerous small single vessels, and myxoid extracellular matrix could be identified, indicating an "atypical PHAT". Mitotic figures were rare in all the cases. In 5 of the 9 patients (55.6%), the tumor was typical PHAT; and in the other 4 (44.4%), typical and atypical PHAT coexisted. Immunohistochemically, the neoplastic cells were positive for vimentin, CD34, CD99, and VEGF, but negative for S-100 protein, desmin, SMA, and CD31. In all the cases, the MIB-1 proliferative activity of the neoplastic cells was lower than 2%. Ultrastructural analysis did not reveal any evidence of specific differentiation. Aneuploidy was not detected by flow cytometry., Conclusions: Histologically, typical PHAT is characterized by spindle and pleomorphic cells associated with an angiectatic vasculature. The neoplastic cells often express vimentin and CD34, and may be positive for CD99 and VEGF. Ultrastructurally, the tumor usually has no specific differentiation. The low MIB-1 index and the absence of aneuploidy in PHAT indicate a non-malignancy. However, we consider the tumor as a borderline neoplasm because of its aggressive behaviour, and suggest wide local resection with tumor-free margin for the treatment of the disease.

Objective: To study the clinicopathologic features and immunophenotype of solid papillary carcinoma (SPC) of breast., Methods: Clinical and pathologic features of 21 cases of SPC, with or without stromal invasion, were analyzed. Immunohistochemical study (LSAB method, for cytokeratins, myoepithelial markers, chromogranin A, synaptophysin, Ki-67, estrogen receptor, progesterone receptor, c-erbB-2 and pS2) and alcian blue staining were performed., Results: All the patients were females with a mean age of 66.1 years. The clinical features were similar to those of classic papillary tumor. Metastasis was not observed in patients who had undergone axillary lymph node dissection. Histologically, the tumor displayed solid papillary growth pattern, with mucin production demonstrated in 19 cases. The tumor cells were oval, polygonal, spindled or signet ring-like and contained mildly to moderately pleomorphic nuclei. The mitotic count measured less than 5 per 10 high-power fields in 15 cases. Seven cases contained foci of invasive carcinoma which showed similar cytologic features as those of the in-situ component. Immunohistochemical study showed that the tumor cells expressed CK8 but not basal cell cytokeratin. Positivity for smooth muscle actin-alpha, calponin and p63 was demonstrated in the myoepithelial layers of fibrovascular cores, as well as around the expanded ductolobular units. Most cases also showed cytoplasmic positivity for chromogranin A (88.2%) and synaptophysin (82.4%). The proliferation index, as highlighted by Ki-67 immunostain, was 8.1%. The tumor expressed estrogen receptor, progesterone receptor and pS2. The staining for c-erbB-2 oncoprotein was negative. Follow up of 16 patients showed no evidence of recurrence or metastasis., Conclusions: SPC predominantly affects elderly females and has distinctive pathologic features and immunophenotype. Some cases of SPC are associated with mucinous and neuroendocrine components. Follow-up data suggest that SPC often carries an indolent clinical behavior and favorable prognosis.

Objective: To investigate the clinicopathologic and immunohistochemical features of secretory meningiomas., Methods: Nine secretory meningiomas were examined. From each specimen, sections were cut and stained with hematoxylin-eosin, periodic acid-Schiff (PAS) stain, and periodic acid-Schiff stain with diatase(PAS-D ). Immunohistochemical markers including oestrogen receptor (ER), progesterone receptor (PR), carcinoembryonic antigen (CEA), cytokeratin (CK), epithelial membrane antigen (EMA), and MIB-1 were detected with streptavidin peroxidase (SP) immunohistochemical staining methods. One case was observed by electron microscopy (EM)., Results: The 9 secretory meningiomas were located at sphenoid ridge, left parietal lobe or frontal lobe. Severe peritumoral edema was observed in 5 cases. Seven cases were followed up for 6 to 88 months; none of them showed evidence of recurrence. Histologically, the conspicuous feature was the eosinophilic inclusions. The finding of pericytic proliferation on examination was helpful to making a diagnosis. In all 9 cases, the tumor cells were positive for PR, but in 6 cases the inclusions were negative. ER was negative in 8 cases. CEA,CK, EMA expressed in the inclusions and the surrounding cells in 7 cases. In 1 case the positive rate for MIB-1 was 5%, but in the other 8 cases the positive rates were not more than 2%. The intercellular lumens and intracellular mucosa were observed under EM., Conclusion: Secretory meningioma is a rare subtype of meningioma that shows glandular epithelium differentiation. It is a meningioma of the low-risk type in terms of incidence, recurrence and prognosis.

Background: Melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. The description of the course of the tumors differs somewhat, but it is generally considered as a benign lesion. We investigated the clinicopathologic features, immunophenotypes, and ultrastructural features of 13 patients with nonpsammomatous melanotic schwannoma (NPMS)., Methods: Tumor specimens of each patient were sectioned and stained with hematoxylin-eosin, Fontana-Masson, Prussian blue, and periodic acid-Schiff (PAS). Immunohistochemical markers such as S-100, Leu-7, HMB-45, Melan-A, CK, EMA, vimentin, GFAP, laminin, collagen IV and MIB-1 were detected with the Envision immunohistochemical staining method. Four of the cases were observed by electron microscopy., Results: Of the 13 patients, 8 were male and 5 female, aged from 11 to 92 years (mean, 38.6 years). The tumor sites included the spinal nerve root (5 patients), cranial nerve (1), greater omentum (1), subcutaneous tissue (3), mesentery (1), bone (1) and mediastinum (1). Eleven patients were followed up for over 2 years, with a mean of 5.9 years. One patient (9.1%) with a primary tumor in the greater omentum developed another primary tumor of the same type in the subcutaneous tissue of the abdominal wall after the first operation. Local recurrence of the tumor was seen in 2 patients (18.2%). One patient (9.1%) showed the local recurrence and metastasis. Seven patients (63.6%) showed no evidence of the recurrence or metastasis. Grossly, all tumors were well-circumscribed and the gross findings were suggestive of melanin-containing tumors. The tumor was composed of spindled and epithelioid cells with abundant intracytoplasmic melanin pigments. Nuclei were round and contained delicate, evenly distributed chromatins as well as small, distinct nucleoli. In some areas, the nucleoli were large and prominent. Rare mitoses were seen in most lesions except the larger omentum lesion. The pigment was shown to be positive for the Fontana-Masson and negative for Prussian blue and PAS. Immunohistochemical staining for S-100, Leu-7, HMB-45, Melan-A, and vimentin were strongly positive. Linear immunoreactions of both laminin and collagen IV was detected in all patients. Ultrastructurally, numerous elongated tumor-cell processes, duplicated basement membrane and melanosomes were observed in all developmental stages., Conclusions: Histologically, melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. Distinguishing between this tumor and malignant melanoma is of paramount importance in planning of management. Immunohistochemically, combined use of laminin and collagen IV is valuable in distinguishing melanotic schwannoma from malignant melanoma. Wide local resection and additional radiotherapy should be advocated. Further studies including cytogenetic or molecular biology are still required to better delineate melanotic schwannoma from malignant melanoma. Appropriate long-term follow-up is needed for all melanotic schwannomas.

Objective: To investigate the pulmonary protective effects of short-term leukocyte depletion with a modified filter located at the CPB venous line in canine., Methods: Sixteen healthy hybrid canines were randomly allocated to the LD-1 group, with an LD-1 filter installed in the CPB venous-line for a 5-minute leukocyte depletion at the beginning of the CPB, and to the control group. Blood samples were taken for routine test respectively at 9 time-points, namely pre-CPB, at 5, 10, 40, 70 min of the CPB, 5 min after aortic cross-clamp being off, at the discontinuation of the CPB, 5 min after protamine being administered, and 2 h after the CPB. Oxygen index (OI), pulmonary pathology and levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in plasma were measured at pre-CPB, 5 min after protamine being administered and 2 h after the CPB respectively. The levels of IL-6 and IL-8 in the bronchial alveolar lavage fluid (BALF) were measured at 2 h after the CPB. RESULTS; In LD-1 group, white blood cell (WBC) counts were significantly less than those in control group at 5 min of the CPB (P < 0.05), the filtration rate of WBC was (65.72 +/- 9.36)%. The WBC counts showed no significant difference in either group from 40 min of the CPB to 2 h after the CPB. OI was higher in LD-1 group than that in control group (P < 0.05) at 5 min after protamine being administered and 2 h after the CPB. There was significantly less WBC infiltration and alveolar edema of the lung in LD-1 group than that in control group at 5 min after protamine being administered and 2 h after the CPB. There were no significant differences of IL-6 and IL-8 in plasma between the two groups at 5 min after protamine being administered (P > 0.05), but the levels of IL-6 and IL-8 were much lower in the LD-1 group than those in the control group at 2 h after CPB. At 2 h after the CPB, IL-6 level in the BALF showed no significant difference in each group (P > 0.05); however, the level of IL-8 was lower in LD-1 group than that in control group (P < 0.05)., Conclusion: The LD-1 filter in the CPB venous-line in canine model used for short-term leukocyte depletion filtration could reduce WBC counts significantly, decrease the levels of IL-6 and IL-8 in plasma, attenuate inflammatory response in the lung after CPB, so it has protective effect on canine lung.

Objective: To evaluate the clinical value of HER2 overexpression in breast cancer and its prognostic implication in patients with lymph node negative breast carcinoma., Methods: The following electronic database were extracted using appropriate inclusive and exclusive standards: Cochrane library, PUBMED, Embase (1984 - 2003), OVID, CMCC and CNKI. Excel and RevMan 4.2 were used for statistical analysis., Results: Fifty-six articles were extracted to calculate the positive rate of HER2 overexpression. The pooled positive rate was 23.14% [19.54%, 26.73%], with positive immunohistochemistry (IHC) rate of 23.13% [19.49%, 26.77%] and positive FISH rate of 20.90% [15.54%, 26.25%]. Seven articles were used to evaluate prognostic predication of HER2 expression. It was concluded that in patients with lymph node negative breast carcinoma, HER2 overexpression (both IHC and FISH) independently predicted a poor prognosis based on disease-free survival (DFS) and overall survival (OS) with a P < 0.05. For DFS, the pooled RR was 1.38 [1.07, 1.80] with 1.16 [1.02, 1.31] for IHC and 1.98 [1.56, 2.52] for FISH. For OS, the pooled RR was 1.58 [1.16, 2.14] with 1.37 [1.14 to 1.64] for IHC and 2.33 [1.45 to 3.75] for FISH. HER2 overexpression effectively predicted DFS/OS of patients without adjuvant therapy and OS of patients with the therapy, but not for DFS, with the pooled RR of 1.46 [1.02, 2.09] and 1.11 [0.95, 1.31] for DFS, respectively and the pooled RR of 1.93 [1.44 to 2.58] and 1.25 [1.01, 1.56] for OS, respectively., Conclusions: In patients with lymph node negative breast carcinoma, the positive rate of HER2 overexpression is 23.14%. HER2 overexpression indicates a poor prognosis and adjuvant therapy after surgery should be recommended.

Objective: The aim of this study involving general pathologists was to assess interobserver reproducibility in the pathologic diagnosis of borderline ductal proliferative breast diseases., Methods: Ten general pathologists independently reviewed 43 specimens chosen to represent the spectrum of borderline ductal proliferative breast lesions. All slides were blindly reviewed without given standardized criteria, and were classified as either mild usual hyperplasia, moderate-severe usual hyperplasia, mild atypical hyperplasia, moderate-severe atypical hyperplasia, ductal carcinoma in situ, or ductal carcinoma in situ with invasion. According to the years of training, these 10 general pathologists were divided into the experienced group and the less trained group. Interobserver agreement was statistically analyzed using Kappa statistic. Then, by comparing all the diagnoses of individual pathologist with the consensus opinion confirmed by two breast pathologists in terms of Page standard, we acquired the diagnostic accuracy and ascertained the undue diagnosis., Results: The ten general pathologists' interobserver reproducibility in the diagnosis of borderline ductal proliferative breast diseases was rather low, especially that in their diagnosis of atypical hyperplasia. The reproducibility and accuracy were slightly higher in the experienced pathologists than in the less trained pathologists. Some pathologists made over-diagnosis or under-diagnosis of the lesions to different degrees. However, when the categories of diagnostic terms were simplified, the interobserver reproducibility increased., Conclusion: The use of standardized criteria is an important approach to increasing the diagnostic reproducibility and accuracy.

Objective: To study the clinicopathologic and immunohistochemical features of solitary fibrous tumor (SFT) and its biologic behaviour., Methods: Clinicopathologic data of 26 cases were collected and analyzed. Among them, immunohistochemical staining (Envision method) for CD34, vimentin, CD99, bcl-2, S-100, SMA, HBME-1, EMA and Ki67 were performed in 23 cases., Results: The 17 male and 9 female patients were between 15 and 66 years of age (mean, 44). Their SFTs were located in nose and nasopharynx, cranial cavity, soft tissue, mediastinum, and parietal and visceral pleura. The main clinical manifestations were local mass and pressure symptom. The characteristic microscopic features included patternless growth pattern, alternating hyper- and hypo-cellular areas, blunt spindle cells within keloid-like hyalinization, and hemangiopericytoma-like regions. Positive immunohistochemical staining: vimentin 100%(23/23), CD34 82%(19/23), bcl-2 87%(20/23), CD99 100%(23/23), SMA 30%(7/23). All cases were negative for S-100, HBME-1 and EMA. Follow-up information on 13 cases revealed that 3 patients had had relapse and died, the other 10 patients were alive without evidence of recurrence., Conclusion: SFT is a rare mesenchymal spindle cell tumor which may be found in various parts of human body and needs to be distinguished from other spindle cell tumors by differential diagnosis. The immunophenotype can be of help in this connexion. About 10% to 23% SFTs have malignant behaviour, manifesting as local recurrence or metastasis. The behavior of SFT is unpredictable, which requires careful, longterm follow-up.