Association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with major depressive disorder.

BACKGROUND: Sarcopenia is a skeletal muscle disorder. Recent studies have shown an association between muscle health and suicide. However, there have been no previous studies on the relationship between suicide risk severity and sarcopenia in major depressive disorder (MDD). This study aimed to explore the association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with MDD. METHODS: The first-episode drug-naïve MDD inpatients aged 20-59 years with the 24-item Hamilton Rating Scale for Depression (HAMD-24) scores of >20 were included, who were then classified into low, intermediate, high and very high suicide risk groups according to the Nurses' Global Assessment of Suicide Risk (NGASR). The HAMD-24, the Hamilton Rating Scale for Anxiety (HAMA) and the SARC-F questionnaire were used to assess depression severity, anxiety severity and sarcopenia, respectively. The plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured. RESULTS: A total of 192 MDD inpatients (122 females, 70 males; aged 39.3 ± 11.7 years) were included, with 12.5% meeting criteria for sarcopenia. There were significant differences in gender, HAMD score and prevalence of sarcopenia among the suicide risk groups. Adjusted ordinal regression analysis showed that sarcopenia was significantly associated with more severe suicide risk (OR = 2.39, 95%CI 1.02-5.58, p = 0.044) independent of depression severity. CONCLUSIONS: This study revealed that sarcopenia was significantly associated with higher suicide risk in non-elderly Chinese MDD inpatients after adjustment for depression severity. Intervention of sarcopenia might be effective in reducing the risk of suicide in non-elderly MDD patients.

[Analysis of the Spatiotemporal Distribution of Algal Blooms and Its Driving Factors in Chaohu Lake Based on Multi-source Datasets].

Eutrophication and harmful algae blooms are one of the common ecological and environmental problems faced by freshwater lakes all over the world. As a typical inland freshwater lake, Chaohu Lake exhibits a high level of eutrophication and algae blooms year-round and shows a spatiotemporal difference in different regions of the lake. In order to understand the basic regularity of the development and outbreak of algal blooms in Chaohu Lake, the data from the comprehensive water observation platform and remote sensing were integrated to obtain the spatiotemporal distribution of algal blooms from 2015 to 2020. Then, an evaluation model based on Boosted Regression Trees (BRT) was constructed to quantitatively assess the importance and interactions of various environmental factors on algal blooms at different stages. The results indicated that:① The occurrence of algal blooms in Chaohu Lake exhibited significant seasonal variations, with the cyanobacteria beginning to recover in spring and bring about a light degree of algal blooms in the western and coastal areas of Chaohu Lake. The density of cyanobacteria reached its maximum in summer and autumn, accompanied by moderate and severe degrees of algal bloom outbreaks. ② During the non-outbreak period, the variation in the cyanobacteria density was greatly affected by physical and chemical factors, which explained 80.3% of the variance in the change in cyanobacteria density. The high concentrations of dissolved oxygen content in the water column and the weak alkalinity (7.2-7.6) and appropriate water temperature (about 3℃) provided a favorable environmental condition for the breeding and growth of cyanobacteria. In addition, the onset of algal blooms was closely related to the air temperature steadily passing through the threshold. According to the statistics, the date of first outbreak of algal blooms in Chaohu Lake was 11 days or so after the air temperature steadily remained above 7℃. ③ During the outbreak period, the occurrence of algal blooms was influenced by the combination of cyanobacterial biomass and meteorological conditions such as temperature, wind speed, and sunshine duration. The cumulative contribution ratio of the four factors was as high as 95%, and each factor had an optimal interval conductive to the outbreak of algal blooms. Furthermore, the results of multi-factor interaction analysis indicated a larger probability of the outbreak of algal blooms in Chaohu Lake under the combined effect of high cyanobacteria density, suitable temperature, and the breeze. This study analyzed and revealed the spatiotemporal characteristics and the dominant influencing factors of algal blooms in Chaohu Lake at different stages, which could provide the scientific basis for the prediction, early warning, and disposal of algal blooms under the context of climate change.

[MRI outstands mammogram in sensitivity of breast ductal carcinoma in situ:an analysis of 122 cases].

OBJECTIVES: To compare the sensitivity of mammogram and breast dedicated MRI in detecting ductal carcinoma in situ with microinvaion (DCIS-MI) and ductal carcinoma in situ (DCIS) lesions, and to further investigate the independent predictive factors of mammogram and MRI sensitivity. METHODS: From August 2009 to November 2011, 122 consecutive confirmed breast cancer patients who had received operations were recruited for this clinical research. These patients were divided into two groups including DCIS (72 cases) and DCIS-MI (50 cases) based on pathologic reports. All the patients were female, with mean ages of 52.6 years and 54.4 years. Preoperative bilateral breast mammogram, breast dedicated MRI depictions and reports as well as histopathological reports were collected. RESULTS: Sensitivity of MRI outstood mammogram in each subgroups: 84.7% vs. 42.4% in DCIS (χ(2) = 27.028, P = 0.000), 94.0% vs. 80.0% in DCIS-MI group (χ(2) = 4.540, P = 0.040). And further analysis showed that MRI was more sensitive to high nuclear grade DCIS and DCIS-MI lesions than low nuclear grade ones (OR = 3.471, P = 0.031). RESULTS: of logistic regression analysis proved microcalcification was an independent predictive factor of mammogram sensitivity (OR = 11.287, P = 0.001). CONCLUSIONS: Sensitivity of breast dedicated MRI is superior to mammogram in detecting DCIS and DCIS-MI groups. Lesions with microcalcifiation is an independent predictive marker which meant that mammogram would achieve high detection rate in cancers presented calcification on mammogram image when compared with non-calcification. Diagnostic performance of breast MRI is less affected by clinical and pathological characteristics of the early stage breast cancer patients but further increased detection rate is observed in DCIS and DCIS-MI with high nuclear grade lesions which indicated that MRI could detect more early stage cancers with relative more aggression biological behaviour and provide these patients with early surgical interventions before possible progression to invasive breast cancers.

Expression of deleted in malignant brain tumours 1 (DMBT1) relates to the proliferation and malignant transformation of hepatic progenitor cells in hepatitis B virus-related liver diseases.

AIMS: The molecular mechanisms underlying proliferation and malignant transformation of hepatic progenitor cells (HPCs) remain largely unknown. The purpose of this study was to evaluate the correlation between the expression of deleted in malignant brain tumours 1 (DMBT1) and the biological behaviour of HPCs in different hepatitis B virus (HBV)-related human liver diseases. METHODS AND RESULTS: Expression of DMBT1 in HPCs was investigated by double immunofluorescence labelling in control-group and HBV-related liver diseases, including hepatitis, hepatocellular carcinoma (HCC), non-tumoral liver tissue away from HCC, non-tumoral cirrhotic tissue adjacent to HCC, and non-HCC cirrhosis. DMBT1-positive HPCs were isolated by laser capture microdissection and subjected to duplex polymerase chain reaction in order to detect homozygous deletion of DMBT1. The number of DMBT1-positive HPCs increased in direct proportion to inflammation severity. Loss of heterozygosity for DMBT1 was more frequent in HCC tumour area and non-tumoral cirrhotic tissue adjacent to HCC, compared with other HBV-related liver diseases (P < 0.05). CONCLUSIONS: DMBT1 may play an important role in the proliferation of HPCs in HBV-related liver diseases. Moreover, down-expression of DMBT1 might enhance the risk of malignant transformation of HPCs.

DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.

DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive. Here, we show that Dhtkd1-/- mice mimic the major aspects of CMT2 phenotypes, characterized by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity. Moreover, DHTKD1 deficiency causes severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies revealed that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion. Subsequently, elevated insulin regulates myelin protein zero (Mpz) transcription in Schwann cells via upregulating the expression of early growth response 2 (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2-AAA-fed mice do reproduce phenotypes similar to CMT2Q phenotypes. In conclusion, we have demonstrated that loss of DHTKD1 causes CMT2Q-like phenotypes through dysregulation of Mpz mRNA and protein zero (P0) which are closely associated with elevated DHTKD1 substrate and insulin levels. These findings further indicate an important role of metabolic disorders in addition to mitochondrial insufficiency in the pathogenesis of peripheral neuropathies.

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma.

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

Pulmonary enteric adenocarcinoma with pancreatic metastasis: A case report.

Pulmonary enteric adenocarcinoma is a markedly rare pathological type of lung adenocarcinoma. As the pancreas is a relatively uncommon site for metastasis, the present case is even more unusual. A 62-year-old male was admitted to hospital following the identification of masses in the left chest wall, right abdominal wall and right upper limb, but with no respiratory symptoms. Computed tomography (CT) of the chest revealed a lump in the lung and a mass in the left chest wall, and 18F-fluorodeoxyglucose (18F-FDG) uptake by the lumps was increased. An enhanced abdominal CT revealed a hypodense and homogeneous mass on the head of the pancreas, which was slightly enhanced compared with normal pancreatic tissue. In addition, the 18F-FDG uptake of the lesion was increased and the standardized uptake value (SUV) delayed was not evidently decreased compared with SUVearly. A number of other abnormal metabolic lesions were also identified using positron emission tomography/CT, whereas no abnormal 18F-FDG uptake was identified in the gastrointestinal organ. Furthermore, rectocolonoscopy was performed to exclude diagnosis of metastatic colorectal adenocarcinoma. The hematoxylin- and eosin-stained smears of the masses in the right lung and left chest demonstrated an enteric pattern, which shared morphological and immunohistochemical (IHC) features with those of colorectal adenocarcinoma. The IHC detection revealed that the lesions in the right lung were positive for cytokeratin 7 (CK7), and negative for CK20 and thyroid transcription factor 1 (TTF-1), and the expression of caudal type homeobox 2 (CDX2) was weakly positive; the masses in the left chest wall were positive for CK7, negative for TTF-1, and CK20 and CDX2 were weakly expressed.

[Gene expression profiling of diffuse-type gastric cancer by cDNA microarray].

OBJECTIVE: To identify cancer-related genes in diffuse-type gastric cancer and to explore its molecular mechanism by cDNA microarray analysis. METHODS: A total of 22 pairs of diffuse-type gastric cancer tissue and the corresponding normal mucosa were taken and freshly frozen. cDNA microarray with 14,592 genes/ESTs was used. Genes were considered to be up- or down-regulated when the fluorescent intensity ratio between tumor and normal mucosa was over 2-fold in over 50% of the samples (P < 0.05). Hierarchical clustering of regulated genes was performed as a measure to study expressional similarity. Validation of array results was carried out by real time quantitative PCR (QPCR). RESULTS: Compared with those of corresponding normal mucosa, there were a total of 153 genes/ESTs up-regulated and 204 down-regulated in diffuse-type gastric cancer. Hierarchical clustering demonstrated that the genes belonging to the same subgroup displayed similar function. Most of the overexpressed genes were those related to cell adhesion, cell motility, matrix reconstruction, cell proliferation and/or signal transduction; while genes related to defense response, toxicoid metabolism, DNA repairing, nuclear-cytoplasmic transport and/or anti-apoptosis made up the main list of the underexpressed genes. Seven genes showed higher expression in TNM (T I + T II) group than in (T III + T IV) group. QPCR confirmed the array analysis results. CONCLUSION: Gene expression profiling by cDNA microarray analysis provides not only molecular understanding of biological properties of cancer, but may also be helpful in discovering new diagnostic markers and therapeutic targets in gastric adenocarcinoma.

The molecular cytogenetic aberration analyzed by comparative genomic hybridization and its significance in diffuse large B-cell lymphoma.

OBJECTIVE: To identify genetic alterations in diffuse large B-cell lymphoma (DLBCL) and to analyse the relationship between the genetic aberrations and the clinical characteristics. METHODS: Using comparative genomic hybridization (CGH) to investigate the genomic changes in 24 cases of DLBCL and to analyse the relationship between these aberrations and clinical parameters including Ann arbor stage, systemic symptoms, chemotherapy efficacy and survival. RESULTS: Aberrations were detected in 62.5% patients of 24 cases; the most common chromosomal alterations included loss of 6q15-21 as well as gain of 18q11-ter, of which the incidences were 20.8% and 16.7%, respectively; with comparing clinical parameters between patients with normal CGH and abnormal CGH, we found that patients with abnormal CGH suffered more from stage III-IV and had higher incidence of systemic symptoms, poor chemotherapy efficacy and poor survival (P<0.05), but there was no difference observed in the incidence of extranodal involvement between two groups. CONCLUSION: The gains and/or losses of genomic DNA from DLBCL patients are the common molecular cytogenetic aberrations; loss of 6q15-21 and gain of 18q11-ter are nonrandom event to DLBCL patients; abnormal CGH is a clinical parameter reflecting malignant progressive course and poor survival to DLBCL patients.

[Clinicopathologic characteristics of myopericytoma].

OBJECTIVE: To investigate the clinicopathologic characteristics and differential diagnosis of myopericytoma. METHODS: Six cases of myopericytomas were analyzed by light microscopy and immunohistochemistry (LSAB detection method). RESULTS: Tumors from 3 females and 3 males were found on the extremities and chest wall. The ages of these 6 patients ranged from 16 to 58 years. Histologically, all tumors were unencapsulated. The neoplastic cells were oval to spindle shaped with eosinophilic cytoplasm, had a myoid appearance and showd areas of concentric perivascular proliferation around lesional blood vessels which were present with focal myxoid stroma. Morphologically in some cases the tumor overlap myofibroma, hemangiopericytoma or glomus tumor. One tumor was located entirely within the lumen of a vein. In another case, the tumor displayed cellular pleomorphism, mitotic activity, necrosis should be diagnosed as malignant myopericytoma. The neoplastic cells were positive for SMA and negative for CD31, CD34, S-100, and CK. CONCLUSIONS: Myopericytoma is composed of oval to spindle shaped myoid cells with a striking tendeny for concentric perivascular growth. These cells differentiate towards perivascular myoid cells or myopericytes. Extremely rare malignant myopericytoma exist.

[The surgical treatment of the solid-pseudopapillary tumor of pancreas: report of 21 cases].

OBJECTIVE: The surgical therapies and prognoses on 21 solid-pseudopapillary tumors (SPT) of pancreas were summarized in our center. METHODS: Twenty-one SPTs were retrospectively studied and divided into two groups, the complete capsular group and the incomplete one. The analyses were performed by SAS6.12 Stat. software. RESULTS: There are no tumor recurrences in all patients. There are significant difference between operative types in radical resection and the tumor position of the pancreas (P = 0.038). There are also significant differences between the capsular integrity and the course of the diseases (P = 0.029), and the possible malignant cells by the frozen section examination (P = 0.001), and the size of the tumor (P = 0.0004). The judgement on the capsular integrity of the tumor could directly effect the adoptable operative types (P = 0.001). CONCLUSIONS: The surgical resection is good treatment for the SPT, which has satisfying prognosis.

Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G â†’ A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.

Hepatic progenitor cells in human liver cirrhosis: immunohistochemical, electron microscopic and immunofluorencence confocal microscopic findings.

AIM: To investigate whether hepatic progenitor cells (HPC), that reveal the features of oval cells in rodents and small epithelial cells (SEC) in certain human liver disease, were also found in human liver cirrhosis (HLC). METHODS: Surgical liver specimens from 20 cases of hepatitis B virus-positive HLC (15 cases containing hepatocellular carcinoma) were investigated by light microscopic immunohistochemistry (LM-IHC). Among them specimens from 15 cases were investigated by electron microscopy (EM) and those from 5 cases by immunofluorencence confocal laser scanning microscopy (ICLSM). Antibodies against cytokeratin 7 and albumin were used and single and/or double labelling were performed respectively. RESULTS: LM-IHC showed that at the margins of regenerating nodules and in the fibrous septae, a small number of cells in the proliferating bile ductules were positive for CK7 and albumin. At the EM level these HPC were morphologically similar to the SEC described previously, and also similar to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, a high nucleus/cytoplasm ratio, a low organelle content in cytoplasm, and existence of tonofilaments and intercellular junctions. ICLSM revealed that HPC expressed both cytokeratin 7 and albumin. CONCLUSION: HPC with ultrastructural and immunophenotypical features of oval cells, i.e., hepatic stem cell-like cells as noted in other liver diseases, were found in HLC. These findings further support the hypothesis that bipotent hepatic stem cells, that may give rise to biliary epithelial cells and hepatocytes, exist in human livers.

[Pathologic diagnosis and subtyping of lymphoma in bone marrow biopsies using histologic examination, immunohistochemistry and gene rearrangement studies].

OBJECTIVE: To assess the value of histologic examination, immunohistochemistry and gene rearrangement studies in the diagnosis and subtyping of lymphoma with bone marrow involvement (BMI). METHODS: Sixty-two formalin fixed, paraffin embedded bone marrow biopsy specimens were studied. Immunohistochemical and immunoglobulin heavy chain (IgH) and T-cell receptor gene rearrangement studies were performed in each case. RESULTS: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated mainly and interstitial infiltration by dysplastic lymphocytes, with intertrabecular nodular arrangement or in dispersion. Sometimes, pseudofollicles may be noted. A predominantly para- or intertrabecular infiltration by nodules of lymphoma cells was characteristic of follicle center cell lymphoma (FCL) cases. In most lymphoplasmacytoid lymphoma (LPL) cases, there was infiltration by small lymphocytes and plasma cells between bony trabeculae. In marginal zone cell lymphoma (MZL), vague inter- or para-trabecular nodules of polymorphic lymphoma cells with clear cytoplasm might be noted. Small to medium-sized dysplastic lymphocytes, with absence of paraimmunoblasts or pseudofollicles, were the most frequent findings in mantle cell lymphoma (MCL). Hairy cell leukemia (HCL) might be identified by the presence of distinct cell membrane and abundant clear cytoplasm, resulting in a "fried-egg" appearance. Tumor cells with large nuclei and eosinophilic nucleoli were characteristically seen in lymphomatosis diffusa (Hodgkin's disease, HD). In T-cell non-Hodgkin lymphoma with BMI, dispersed or clusters of intertrabecular neoplastic lymphoid cells with clear cytoplasm and gyriform nuclei were often observed. In diffuse large B-cell lymphoma (DLBL), the tumor cells were large and isolated or arranged in diffuse pattern. Immunohistochemically, a panel of markers, including CD3 CD20, and CD79 are valuable for the differential diagnosis of T- and B-cell lymphomas. The neoplastic cells in MCL were cyclin D1- and CD5-positive, while BCL2- and CD10-positivity was characteristic for FCL. CLL/SLL cells might be stained with CD5 and CD23, in addition to CD20 and CD79. CD25 expression might be noted in HCL: the positivity for CD15, CD30 and fascin suggests HD. There was a higher positivity rate for IgH gene rearrangement in CLL/SLL, LPL MZL and DLBL (80%, 60%, 66.7%, 70% respectively) and for T- cell receptor gamma gene rearrangement in T-cell lymphoma (66.7%). CONCLUSION: A combination of histopathology, immunohistochemistry and IgH / T-cell receptor gamma gene rearrangement studies may be of aid to the diagnosis and subtyping of lymphoma with BMI, especially if there is only a small number of tumor cells present in the specimen.

[The diagnosis and differential diagnosis of histiocytic necrotizing lymphadenitis. A study of histology, immunohistochemistry and electron microscopy].

OBJECTIVE: To study the diagnosis and differential diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi disease, KD). METHODS: Histologic analysis and immunohistochemical study (EnVision method) was carried out in 46 cases of KD, 5 cases of nonspecific lymphadenitis (NLD), 5 cases of non-Hodgkin's lymphoma (NHL), 5 cases of Hodgkin's lymphoma (HD), 5 cases of cat-scratch disease (CSD) and 5 cases of tuberculous lymphadenitis (TBL). Electron microscopy was also performed in 6 cases of KD and 2 cases of NHL. RESULTS: Three histologic (proliferative, necrotizing and xanthomatous) patterns were noted in KD. In any of these patterns, there were some basic histologic findings: a wedge-shaped pale area at the edge of the lymph node or paracortical nodules associated with an increase in apoptotic cells or karyorrhectic debris, crescentic histiocytes, proliferative mononuclear histiocytes and absence of or very scanty neutrophils. Immunohistochemical study demonstrated focal occurrence of histiocytes expressing both CD68 and MPO. Electron microscopy confirmed the presence of apoptotic bodies, proliferative mononuclear histiocytes, crescentic histiocytes and dispersed T cells in the lesional areas. CONCLUSIONS: In general, there should not be much difficulty in differentiating KD from other types of lymphadenopathy. Sometimes, problems arise mainly because of the diversity of KD histology. Correct diagnosis can be made if one pays attention to the described characteristic morphology, peculiar immunophenotype of the histiocytes and possibly ultrastructural features.

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10-50 ng ml(-1).

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the 'grey zone' (2.0-10.0 ng ml(-1)). However, the PSA 'grey zone' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10-50 ng ml(-1). Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10-19.9 ng ml(-1) PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20-50 ng ml(-1) were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10-50 ng ml(-1). In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10-50 ng ml(-1) regarding their PCa risks.

Development of a survival prediction model for gastric cancer using serine proteases and their inhibitors.

Proteolytic enzymes play a key role in the metastatic stage of gastric cancer (GC). In this study, we aimed to identify the serine proteases (SPs) and their inhibitors (serpins) as related to GC. The gene expression profiles of 40 cases of GC were initially detected by cDNA microarray. The results of the differentially expressed SPs and their inhibitor genes from the microarrays were confirmed by real-time PCR. The status of the immunohistochemical staining of the confirmed genes in patients with complete data was used to develop a survival prediction model. Finally, the prediction model was tested in different groups of GC patients. As a result, seven genes, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8, were considered as GC progression-related genes. A survival prediction model including the immunohistochemical scores of three genes and the tumor node metastasis (TNM) score was developed: Survival time (months) = 88.8607 + 2.6395 SERPINB5 - 12.0772 KLK10 + 13.7562 KLK11 - 7.0318 TNM. In conclusion, SERPINB5, KLK10, KLK11, HPN, SPINK1, SERPINA5 and PRSS8 were GC progression-related SPs or serpin genes. The model consisting of the expression profiles of three genes extracted from the microarray study accompanied by the TNM score accurately predicts surgery-related survival of GC patients.

Prognostic value of nuclear maspin expression for adjuvant 5-fluorouracil-based chemotherapy in advanced gastric cancer.

To assess the prognostic and predictive value of maspin expression for the clinical response to 5-fluorouracil (5-FU)-based chemotherapy in advanced gastric cancer (GC) patients, the expression of maspin in primary tumors from 127 patients with advanced GC was examined using immunohistochemistry. Of the 127 patients, 74 were treated with surgery alone and 53 received additional adjuvant 5-FU-based chemotherapy. Nuclear and cytoplasmic maspin expression was observed in 46.5 (59/127) and 68.5% (87/127) of patients, respectively. Nuclear maspin immunoreactivity was significantly associated with larger tumor size (p=0.036), the depth of tumor invasion (p=0.02) and lymph node metastasis (p=0.002). Cytoplasmic maspin immunoreactivity was associated with tumor cell differentiation but not with the other clinicopathological variables. Nuclear maspin immunoreactivity had a significant association with overall survival (OS). Among the nuclear maspin-expressing patients, those who were treated with 5-FU-based adjuvant chemotherapy showed significantly longer OS than those without chemotherapy (p=0.0004). In conclusion, nuclear maspin expression is associated with adverse clinical outcomes in patients with advanced GC. Patients with positive nuclear maspin expression may be more responsive to adjuvant 5-FU chemotherapy.

Accuracy of physical examination, ultrasonography, and magnetic resonance imaging in predicting response to neo-adjuvant chemotherapy for breast cancer.

BACKGROUND: Accurate evaluation of response following chemotherapy treatment is essential for surgical decision making in patients with breast cancer. Modalities that have been used to monitor response to neo-adjuvant chemotherapy (NAC) include physical examination (PE), ultrasound (US), and magnetic resonance imaging (MRI). The purpose of this study was to evaluate the accuracy of PE, US, and MRI in predicting the response to NAC in patients with breast cancer. METHODS: According to the response evaluation criteria in solid tumors guidelines, the largest unidimensional measurement of the tumor diameter evaluated by PE, US, and MRI before and after NAC was classified into four grades, including clinical complete response, clinical partial response, clinical progressive disease, clinical stable disease, and compared with the final histopathological examination. RESULTS: Of the 64 patients who received NAC, the pathologic complete response (pCR) was shown in 13 of 64 patients (20%). The sensitivity of PE, US, and MRI in predicting the major pathologic response was 73%, 75%, and 80%, respectively, and the specificity was 45%, 50%, and 50% respectively. For predicting a pCR, the sensitivity of PE, US, and MRI was 46%, 46%, and 39%, respectively, and the specificity was 65%, 98%, and 92% respectively. CONCLUSIONS: Compared with final pathologic findings, all these three clinical and imaging modalities tended to obviously underestimate the pCR rate. A more appropriate, universal, and practical standard by clinical and imaging modalities in predicting the response to neo-adjuvant chemotherapy in vivo is essential.

Hepatic progenitor cell represents a transitioning cell population between liver epithelium and stroma.

Following an acute injury, the liver may maintain its structure and function through mitotic division of mature hepatocytes (i.e. hepatic regeneration). However, the regeneration ability of hepatocytes can be impaired in chronic liver diseases including chronic viral infection and alcohol abuse. Hepatic progenitor cells/oval cells (HPCs/OCs), capable of differentiation into both hepatocytes and cholangiocytes, occur and proliferate during chronic injury. Unfortunately, a use of HPCs for clinical therapy is blocked by the difficulty of exact identity of HPCs in liver. Focusing on the links between phenotype of HPCs and real stem cells originating from fetal liver or bone marrow (BM), the recent studies of HPCs neglect functional analysis and the close relationship between activation of HPCs and extracellular matrix (ECM) remodeling. It is currently widely accepted that mesenchymal-epithelial transition (EMT) and epithelial-mesenchymal transition (MET) play important roles not only in liver development but also in healing of chronic injured adult liver. Co-expression of epithelial/mesenchymal and HPCs markers has been demonstrated in cells undergoing EMT/MET. These cells led to hepatic regeneration after transplanted into rats with chronic liver injury. Notably, there is an increased expression of mesenchymal markers in HPCs after exposure to transforming growth factor-beta1 (TGF-ß1). Based on these evidences, we hypothesize that HPCs represent a transitioning cell population undergoing EMT/MET, both parenchymal and mesenchymal cells of liver may be the direct sources of HPCs.