Can adding personalized rule-based feedback improve the therapeutic effect of self-help digital cognitive behavioral therapy for insomnia in young adults?

INTRODUCTION: Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but low accessibility and relatively high cost limits the dissemination of the treatment. Several forms of digital CBT-I have been developed to increase the accessibility and shown to be effective; however, the treatment effect may be restricted by the lack of interaction within the treatment. The current study examines whether the therapeutic effects of self-help digital CBT-I could be enhanced by adding simple rule-based personalized feedback. METHOD: Ninety-two young adults with self-reported insomnia were randomly assigned to three groups: a self-help group (SH, n = 31), who received an eight-session email-delivered CBT-I program; a feedback group (FB, n = 31), who went through the same CBT-I program with personalized feedback; and a waitlist group (WL, n = 30). The Insomnia Severity Index (ISI) was used as the primary outcome measure, and the 16-item version of the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), Sleep Hygiene Practice Scale (SHPS), and sleep diary were used as the secondary outcome measures. Treatment satisfaction and adherence were also compared between the treatment groups. RESULTS: Both the SH and FB groups showed significantly more improvements in insomnia severity, sleep-related beliefs, and sleep hygiene behaviors than the WL group. Sleep onset latency and sleep efficiency in the sleep diary were also significantly improved after treatment. None of these effects significantly differed between the two treatment groups. Nonetheless, participants in the FB group reported higher treatment satisfaction than those in the SH group. CONCLUSION: This study supports the effectiveness of email-delivered self-help CBT-I for young adults with insomnia. Furthermore, while adding simple personalized feedback may not have an additional effect on sleep per se, it can enhance treatment satisfaction. This simple intervention shows promise in addressing sleep disturbance in young adults.

Effects of Anesthetic Technique on Postoperative Pulmonary Metastasis in Patients Undergoing Laryngectomy.

BACKGROUND: Whether laryngeal cancer is directly implanted into the lungs during orotracheal intubation is still unclear. Therefore, this study aimed to find whether orotracheal intubation is an independent risk factor for postoperative pulmonary metastasis in patients undergoing laryngectomy. PATIENTS AND METHODS: Medical records from January 1, 2006, to December 31, 2016, were reviewed. According to similar propensity scores, patients who received orotracheal intubation (tracheal intubation group, n = 515) were matched 1:1 with those who received tracheotomy (tracheotomy group, n = 326) in the induction of general anesthesia. The primary outcome was postoperative pulmonary metastasis. Secondary outcomes included local recurrence, lymphatic metastasis, tracheostomal recurrence and overall survival. RESULTS: Between the two groups, there was no significant difference in postoperative pulmonary metastasis (P = 0.688), local recurrence (P = 0.215), lymphatic metastasis (P = 0.480), tracheostomal recurrence (P = 0.246) or all-cause death (P = 0.299). The primary site of cancer was an independent risk factor for pulmonary metastasis [HR 0.29, 95% CI 0.13-0.68; P = 0.013] and local recurrence (HR 2.69, 95% CI 1.39-5.21; P = 0.003). Type of surgery (HR 3.13, 95% CI 2.03-4.84; P < 0.001) and N classification of TNM (HR 0.27, 95% CI 0.10-0.75; P = 0.012) were risk factors for local recurrence. Postoperative chemotherapy was an independent risk factor for lung metastasis (HR 7.58, 95% CI 3.11-18.47; P < 0.001) and lymphatic metastasis (HR 5.18, 95% CI 2.57-11.91; P < 0.001), and 5-year overall survival was associated with age (P = 0.028), clinical stage (P < 0.001) and postoperative chemotherapy (P = 0.003) but not with anesthetic technique (P = 0.473). CONCLUSION: This retrospective study suggests that orotracheal intubation in laryngectomy is not a risk factor for postoperative pulmonary metastasis, local recurrence, lymphatic metastasis or overall survival.

Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A.

CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40°C or within a broad pH range (pH 5.0-7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics.

Anti-candidal activity of a novel peptide derived from human chromogranin A and its mechanism of action against Candida krusei.

Candida species (Candida spp.) are important fungal pathogens, which cause numerous clinical diseases associated with significant mortality and morbidity in healthcare settings. In our previous study, we identified a recombinant peptide, chromogranin A (CGA)-N46, corresponding to the N-terminal Pro31-Gln76 sequence of human CGA, that exhibited antifungal activity against Candida albicans. The present study investigated the antifungal activity of CGA-N46, and its underlying mechanism, against numerous Candida spp. CGA-N46 inhibited the growth of all of the tested Candida spp., of which Candida krusei exhibited the greatest sensitivity. CGA-N46 was able to disrupt the stability of the phospholipid monolayer without damaging the integrity and permeability of the outer membrane of C. krusei cells, and induced cytoplasm vacuolization and mitochondrial damage. In addition, treatment of C. krusei with CGA-N46 was associated with decreased levels of intracellular reactive oxygen species, a reduction in the mitochondrial membrane potential, and DNA synthesis inhibition. The results of the present study suggested that CGA-N46 was able to pass through the cell membrane of Candida spp. by temporarily destabilizing the phospholipid membrane, which in turn led to mitochondrial dysfunction and inhibition of DNA synthesis. Therefore, CGA-N46 may be considered a novel antifungal compound for the treatment of patients with C. krusei infections.

[Correlation of KRAS gene mutations and clinicopathologic parameters in colorectal carcinoma].

OBJECTIVE: To investigate the relationship between KRAS gene mutations and clinicopathological parameters in patients with colorectal carcinoma (CRC). METHODS: PCR-based direct sequencing was used to detect the mutations of KRAS gene and to correlate between clinicopathological characteristics and the presence of various KRAS mutations in 244 cases of CRC. RESULTS: KRAS mutations were identified in 92 cases (37.7%) of CRC. Five types of mutation were detected at codon 12, including G12D (40 cases, 16.4%), G12V (16 cases, 6.6%), G12A (7 cases, 2.9%), G12S (5 cases, 2.0%) and G12C (4 cases, 1.6%). Two types of mutation were detected at codon 13, including G13D (17 cases, 7.0%) and G13C (2 cases, 0.8%). One type of mutation was detected in codon 61, i.e. Q61K (1 case, 0.4%). KRAS mutation rate was higher in females (45.6%, 36/79) than in males (32.1%, 53/165; P < 0.05), but not related to another clinicopathological characteristics. CONCLUSIONS: Female CRC patients have a higher KRAS mutation rate than the male patients. KRAS mutation has no significant correlation with patient's age, tumor site, tumor gross appearance, degree of differentiation, depth of invasion, TNM stages, lymphatic invasion, abdominal or distant metastases and prognosis in this study.

Gene silencing of ß-catenin by RNAi inhibits proliferation of human esophageal cancer cells by inducing G0/G1 cell cycle arrest.

OBJECTIVES: The aim of the present study was to explore mechanisms underlying the effects of down-regulating ß-catenin expression on esophageal carcinoma (EC) cells. METHODS: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1/2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. RESULTS: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating ß-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). CONCLUSION: Inhibition of EC Eca-109 cellproliferation by down-regulating ß-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

[The changes of peripheral blood lymphocyte subsets in patients with acute hydrogen chloride gas poisoning].

OBJECTIVE: To explore the changes of peripheral blood lymphocyte subsets in patients with acute hydrogen chloride gas poisoning. METHODS: When the patients were admitted or on the secondary day, the percentages of total T-cell lymphocyte subsets (CD(3)(+)CD(19)(-)), CD(4)(+)T cells (CD(3)(+)CD(4)(+)), CD(8)(+)T cells (CD(3)(+)CD(8)(+)), B cells (CD(3)(-)CD(19)(+)) and NK cells (CD(3)(-)CD(16)(+)CD(56)(+)), and the ration of CD(4)(+)/CD(8)(+) in 37 cases with acute hydrogen chloride gas poisoning and 49 healthy controls were detected with flow cytometer. RESULTS: The total T-cell percentage and total CD(4)(+)T cell percentage in 37 cases were significantly lower than those in 47 controls (P < 0.05). The percentages of NK cells and B lymphocytes in 37 cases significantly increased, as compared with controls (P < 0.05). The ration of CD(4)(+)/CD(8)(+) in 37 cases significantly decreased, as compared with controls (P < 0.05). CONCLUSION: The lymphocyte subsets in the patients with acute hydrogen chloride gas poisoning changed, which could influence the immune function of patients.

[Expression and predictive role of excision repair cross complementation group 1, ribonucleotide reductase subunit M1, and ß-tubulin 3 in postoperative patients with non-small cell lung cancer receiving adjuvant chemotherapy].

OBJECTIVE: To determine the predictive value of excision repair cross complementation group 1 (ERCC1),ribonucleotide reductase subunit M1 (RRM1), and ß-tubulin 3 expressions in postoperative patients with stage 1- 3 non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy. METHODS: All NSCLC patients received surgery therapy followed by at least one cycle of adjuvant chemotherapy in our hospital from January 2004 to December 2007. The expressions of ERCC1, RRM1, and ß-tubulin 3 were detected by immunohistochemical methods. The relationships among clinicopathologic characteristics, chemotherapy regimens,biomarkers' expressions and disease-free survival (DFS) were analyzed. RESULTS: The high-expression rates of ERCC1, RRM1, and ß-tubulin 3 were 36.4%,43.7%,and 38.4%,respectively. The expressions of these three biomarkers were not correlated. After a median follow-up of 35.8 months, 80 patients experienced metastatic or recurrent tumors and 40 patients died. The median overall survival was not reached and the median DFS was 24.1 months. Univariate survival analysis showed that sex, clinical stage,and adenocarcinoma or not were related to DFS, while age, smoke history, chemotherapy regimens, and expression levels of ERCC1, RRM1, and ß-tubulin 3 has no prognostic significance in these surgically resected NSCLC patients who were receiving adjuvant chemotherapy. Male (P=0.036), earlier clinical stage (P=0.001), and non-adenocarcinoma (P=0.004) predicted better DFS. Stratified analysis indicated that in RRM1 high-expression strata,the regimens with gemcitabine had curtailed DFS compared with other regimens (P=0.054); in ß-tubulin 3 high-expression strata,the regimens containing taxane (including paclitaxel and docetaxel subgroups) had curtailed DFS compared with other regimens (P=0.076), although there was no statistical significance. However,there were no similar predictive significance in RRM1 and ß-tubulin 3 low-expression strata or in ERCC1 strata with different expression levels. COX proportional regression analysis showed that adenocarcinoma or not and clinical stage were independent risk factors of DFS in this population. CONCLUSIONS: In postoperative NSCLC patients who are receiving adjuvant chemotherapy, patients with high expression of RRM1 tends to be resistant to gemcitabine and patients with high expression of ß-tubulin 3 tends to be resistant to taxane drugs. ERCC1, RRM1, and ß-tubulin 3 detected by immunohistochemistry can be biomarkers to help to choose better chemotherapy regimen and predict the effectiveness of adjuvant chemotherapy.

[Application of a narcotrend-assisted anesthesia in-depth monitor in the microwave coagulation for liver cancer during total intravenous anesthesia with propofol and fentanyl].

BACKGROUND AND OBJECTIVE: CT-guided microwave coagulation is a minimally invasive surgery for patients with liver cancer. Total intravenous anesthesia with propofol and fentanyl is commonly used. The depth of anesthesia during microwave coagulation for liver cancer is still monitored by clinical signs. There are few subjective and effective indicators. This study explored the application of Narcotrend-assisted "depth of anesthesia" monitoring on microwave coagulation for patients with liver cancer during total intravenous anesthesia with propofol and fentanyl. METHODS: Forty liver cancer patients underwent CT-guided microwave coagulation were randomly assigned to receive Narcotrend index monitoring or standard clinical monitoring for depth of anesthesia with 20 patients in each group. All patients received total intravenous anesthesia with propofol and fentanyl. The depth of anesthesia for patients in the Narcotrend group was measured according to a Narcotrend index, which was maintained between D2 and E0. The depth of anesthesia for those in the standard clinical practice group was measured according to heart rate, mean arterial pressure, and patient movement. Changes of hemodynamics, the duration of the emergence from anesthesia, and the recovery of orientation were recorded. The doses of propofol and fentanyl, postoperative visual analogue scores (VAS), and the incidence of postoperative nausea and vomiting were also recorded. RESULTS: There was no significant alteration in heart rate or mean arterial pressure between the two groups. Compared with other anesthetic stages, both heart rate and mean arterial pressure decreased during the induction of the anesthesia in the two groups(P<0.05). The doses of propofol were higher in the standard clinical practice group than in the Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P<0.01]. The duration of emergence and orientation were longer in the standard clinical practice group than in the Narcotrend group [(9.5+/-2.9) min vs. (4.9+/-2.2) min, P<0.01; (12.2+/-3.5) min vs. (6.6+/-3.2) min, P<0.01, respectively]. There was no difference in the dosage of fentanyl, VAS, or the incidence of postoperative nausea or vomiting between the two groups (P>0.05). CONCLUSION: For patients with liver cancer, monitoring the depth of anesthesia with Narcotrend on microwave coagulation can contribute to lower dosage of propofol and shorten duration of recovery during total intravenous anesthesia with propofol and fentanyl.

[Effects of neuraxial block and general anesthesia on tumor metastasis in rats].

OBJECTIVE: To investigate the effects of different anesthesia methods on immune surveillance and tumor metastasis in tumor-bearing rats. METHODS: Seventy-two Fischer 344 rats were randomly assigned into 3 equal groups and anesthetized for 1 h with ketamine (group K), propofol (group P), or neuraxial block (group B). All the rats were subjected to laparotomy followed by intravenous injection of MADB106 tumor cells, and 24 h after the injection, the number and activity of circulating CD3(+), CD4(+), CD8(+), and D4(+)/CD8(+) lymphocyte subsets and NK cellèCD161a(+)éwere assessed. Three weeks later, the lung metastases were counted. RESULTS: Compared with those in group B, the numbers of CD3(+), CD4(+), CD8(+), and CD161a(+) lymphocytes and the activity of circulating NK cells were significantly reduced, and the lung metastases of MADB106 increased significantly in groups K and P (P<0.05 or 0.01 ). The activity of immune surveillance in group K was significantly lower than that in group P except for CD8(+) cells, and the tumor metastases in group K increased significantly in comparison with those in group P (P<0.05 or 0.01). CONCLUSION: Neuraxial block provides protection of the activity of immune surveillance and reduces tumor metastases in tumor-bearing rats compared with general anesthesia.

[Clinicopathologic significance of chromosome 17 polysomy in breast cancer].

OBJECTIVE: To investigate the clinicopathological significance of chromosome 17 polysomy in breast cancer. METHODS: Retrospective study of 200 cases of breast cancer including 106 cases of invasive ductal carcinoma and 94 cases of in-situ carcinoma was performed by fluorescence in-situ hybridization (FISH) to explore the relationship between chromosome 17 polysomy and age, nuclear atypia, lymphatic metastasis, HER2 gene amplification and HER2 protein expression. RESULTS: Twenty-six percent (52/200) of chromosome 17 polysomy was detected in 200 cases of breast ductal carcinoma, all of which were invasive ductal carcinoma. Overall 52. 8% (52/180) of invasive ductal carcinoma cases showed chromosome 17 polysomy, which was correlated to HER2 gene amplification (P = 0.000) and HER-2 protein expression (P=0.000), and to HER2 expression combined with HER2 gene amplification (P=0.001). Chromosome 17 polysomy with or without HER2 gene amplification was also associated with high-grade nuclear atypia (P = 0.012 or P = 0.010) and lymphatic metastasis (P = 0.002 or P = 0.009 ). However, chromosome 17 polysomy with or without HER2 gene amplification was not correlative with the age of patients (P = 1. 000 or P = 0. 415). CONCLUSION: Chromosome 17 polysomy may be related to the nuclear atypia, metastasis, HER2 gene amplification of invasive ductal carcinoma and thus a worse prognosis of the patients.

[Correlation of acute pain treatment to occurrence of chronic pain in tumor patients after thoracotomy].

BACKGROUND & OBJECTIVE: Some researches found that the intensity, property and management of acute pain are associated with chronic pain in tumor patients after thoracotomy. Chronic pain may be transformed from acute pain. However, there are no routine or standard strategies to effectively prevent or relieve chronic pain in tumor patients after thoracotomy. This study was to explore the correlation of acute and chronic pain in tumor patients after thoracotomy. METHODS: A total of 105 patients (American Society of Anesthesiologists physical status I-II) underwent thoracotomy were randomly divided into 3 groups: 36 received administration of ropivacaine and morphine through thoracic epidural preoperatively (group PE), 36 received the same treatment postoperatively (group E), and 33 received intravenous infusion of fentanyl postoperatively (group IV). VAS scores were recorded in the first 48 h after operation. The occurrence of chronic pain was observed at the first, second, third, sixth months after operation. RESULTS: VAS scores in the first 48h after operation were significantly lower in group PE and group E than that in group IV (P<0.05). VAS scores were significantly lower in group PE than in group E (P=0.004 at 4 h, P=0.013 at 8 h, P=0.035 at 24 h). The occurrence rate of pain after operation was significantly lower in group PE than in groups E and IV in the first and second months (Chi2=5.989, P=0.014; Chi2=7.603, P=0.006), and lower in groups PE and E than in group IV in the third and sixth months (Chi2=6.585, P=0.010; Chi2=8.661, P=0.003). The duration of pain was significantly shorter in group PE than in groups E and IV (P=0.027, P=0.009). CONCLUSIONS: Chronic pain after thoracotomy is associated with the intensity and management of acute pain after thoracotomy. The patients with intensive acute pain would experience intensive and long-term chronic pain. Preemptive administration with thoracic epidural ropivacaine and morphine can decrease the incidence and duration of chronic pain after operation.

[Protective effect of ketamine against acute rat lung injury induced by liopolysaccharide and its mechanism].

OBJECTIVE: To investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism. METHODS: Forty-eight male Wistar rats were randomized into 4 equal groups, namely the control group, LPS group, ketamine group I (5 mg/kg), and ketamine group II (10 mg/kg). The neutrophil count, protein contents in the bronchoalveolar lavage fluid (BALF) and the wet/dry lung weight ratio were measured 4 h after LPS injection. TNF-alpha, IL-8, NO, iNOS and NF-kappaB were also measured in the lung tissues. RESULTS: In LPS group, the neutrophil count, protein contents in BALF, the wet/dry lung weight ratio and the levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-8 (IL-8), and NO were all significantly increased compared with the control group (P<0.01). The mRNA expression of iNOS and the protein expression of NF-kappaB were also increased in LPS groups. Ketamine treatment attenuated the increase in wet/dry lung weight ratio, neutrophil count, and protein contents in BALF in a dose-dependent manner. Ketamine also dose-dependently inhibited the production of TNF-alpha, IL-8 , and NO and lowered iNOS mRNA and NF-kappaB protein expression. CONCLUSION: Ketamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-kappaB and attenuating the production of the inflammatory cytokines.

[Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumor: a study of 156 cases].

OBJECTIVE: To evaluate the prognostic significance of various clinicopathologic parameters in gastrointestinal stromal tumor (GIST), and to study the frequency of c-kit exon 11 mutations in this tumor. METHODS: One hundred and fifty-six cases of gastric or small intestinal GIST were retrieved from the archival files of the Department of Pathology, Chinese PLA General Hospital. The clinical features, site of occurrence, tumor diameter, mitotic index, coagulative tumor necrosis, and risk grade were studied and analyzed statistically. Tumor DNA was extracted and c-kit exon 11 was amplified. Upon detection by denaturing high-performance liquid chromatography, the amplified exon 11 was sequenced. RESULTS: For the 83 cases of gastric GIST studied, the mean age of patients was 55.4 years. Follow-up information was available in 62 cases, with 17 cases having local recurrence or distant metastasis. The 5-year survival rate was 66.5% +/- 17.1%. For the 73 cases of small intestinal GIST studied, the mean age of patients was 50.6 years. Follow-up information was available in 43 cases, with 22 cases having local recurrence or distant metastasis. The 5-year survival rate was 61.8% +/- 18.3%. In general, for gastric GIST, age younger than 50 years (P = 0.046), advanced clinical stage (P = 0.0001), large tumor size (P = 0.0001), high mitotic index (P = 0.0001), presence of coagulative tumor necrosis (P = 0.0001), and high risk grade (P = 0.004) were associated with lower survival rate. COX hazard proportional model revealed that advanced clinical stage (P = 0.001), large tumor size (P = 0.001), high mitotic index (P = 0.002) and high risk grade (P = 0.018) indicated worse prognosi. For small intestinal GIST, advanced clinical stage (P = 0.010) and presence of coagulative tumor necrosis (P = 0.036) were associated with lower survival rate. Advanced clinical stage was an independent prognostic factor. A total of 25 cases harbored c-kit mutations. The frequency of c-kit mutations was 32% and 22.5% for gastric and small intestinal GIST respectively. For gastric GIST, c-kit mutations occurred mainly in patients older than 50 years. In contrast, c-kit mutations in small intestinal GIST occurred in the age group of 40 to 49 years. CONCLUSIONS: For gastric GIST, advanced clinical stage, tumor diameter, mitotic index and risk grade are the main prognostic indicators. For small intestinal GIST, advanced clinical stage and presence of coagulative tumor necrosis indicate poor prognosis. In general, small intestinal GIST is more frequently associated with metastasis and tumor relapse than gastric GIST. The occurrence of c-kit mutations also correlates with age of patients.

Aberrant FHIT protein expression in classical Hodgkin's lymphoma: a potential marker.

AIMS: The fragile histidine triad (FHIT) gene is frequently inactivated in human cancers; however, the FHIT gene remains unexplored in Hodgkin's lymphoma. The aim of this study was to investigate the role of FHIT expression in classical Hodgkin's lymphoma. METHODS: Classical Hodgkin's lymphomas were analysed for FHIT gene expression by two-step non-biotin immunohistochemical method and Western blotting. RESULTS: Thirty of the 33 (91%) cases of Hodgkin's lymphoma tested were positive for FHIT protein by immuohistochemistry. The expression of FHIT was mainly located in cytoplasm of Reed-Sternberg (HRS) cells. The protein expression was also documented by Western blotting. The non-Hodgkin's lymphomas were negative for FHIT protein. CONCLUSIONS: The results indicate that abnormal FHIT expression is noted frequently in classical Hodgkin's lymphoma and the expression can give insight into the pathogenesis of the disease. The protein may serve as a marker to localise HRS cells in classical Hodgkin's lymphoma.

[Expression of fragile histidine triad (FHIT) protein and its significance in diagnosing classical Hodgkin lymphoma].

OBJECTIVE: To study the expression of FHIT protein and its potential application in diagnosing classic Hodgkin lymphoma. METHODS: Immunohistochemical study using EnVision method for FHIT tumor suppressor protein, hematopoietic stem cell markers CD133/AC133 and CD34, B-cell marker CD20, T-cell marker CD3 and oncoprotein c-erbB2 was performed on 33 cases of classic Hodgkin lymphoma. RESULTS: Thirty-three of the Hodgkin lymphoma cases (90.9%) expressed FHIT protein. The antigen was mainly located in the cytoplasm, nucleus and membrane of classic Reed-Sternberg and Reed-Sternberg-like cells. Normal B and T lymphocytes, as well as their malignant counterparts, were negative for FHIT protein; whereas monocytes, histiocytes and dendritic cells were positive. All the cases studied were negative for CD133/AC133, CD34, CD3 and c-erbB-2. Two of the 33 cases showed positive staining for CD20 in some of the Reed-Sternberg cells. CONCLUSION: The expression of FHIT protein can be used as a useful adjunct in diagnosing classic Hodgkin lymphoma.

[Diagnosis of human papillomavirus infection in paraffin-embedded cervical tissues by gene clip technology].

OBJECTIVE: To study the feasibility of diagnosing of human papillomavirus (HPV) infection in paraffin-embedded cervical tissues by high-throughput gene chip technology and its clinical significance. METHODS: Forty cases of HPV-related cervical lesions, including 18 cases of invasive squamous cell carcinoma, 12 cases of cervical intraepithelial neoplasia (CIN) III, 6 cases of CIN II and 4 cases of CIN I, were enrolled. DNA was extracted from paraffin-embedded tissues and amplified by polymerase chain reaction (PCR) using HPV DNA primers. The PCR products were then reversely hybridized with gene chip technology. The results were compared with that of in-situ hybridization (ISH). RESULTS: All of the 18 cases of cervical squamous cell carcinoma were positive for high-risk HPV genotypes (with 1 case showing a mixture with low-risk genotypes). In contrast, 11 cases (91.7%) of CIN III, 5 cases (83%) of CIN II and none of the CIN I cases were positive for high-risk HPV genotypes. On the other hand, low-risk HPV genotypes were detected only in 1 case (17%) of CIN II and 2 cases (50%) of CIN I. The difference between the two groups (CIN III/squamous cell carcinoma versus CIN I/CIN II) was statistically significant (U = 80.0, P < 0.01). Among the 10 squamous carcinoma cases positive for HPV types 16 and 18 by gene chip technology, high-risk HPV DNA was also detected in 6 of them when using in-situ hybridization. CONCLUSIONS: Gene chip technology is able to detect multiple HPV genotypes in paraffin-embedded tissues with high sensitivity and specificity. The distinction between low and high-risk HPV genotypes is seemed useful in prevention and management of cervical cancer.

Clinicopathological significance of FHIT protein expression in gastric adenocarcinoma patients.

AIM: To investigate the expression of fragile histidine triad (FHIT) protein, and the possible relationship between FHIT expression and clinicopathological indices in gastric carcinoma. METHODS: FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS: The FHIT protein expression was positive in 28/76 (36.8%) cases of adenocarcinoma tissue, 22/58 (37.9%) cases of adjacent dysplastic tissue and 76/76 (100%) cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa (P = 0.000). FHIT protein expression was found in 64.3% (18/28) of grades I and II cancers, and 20.8% (10/48) of grade III cancers (P = 0.000), in 56.3% (18/32) of stages I and II cancers and 22.7% (10/44) of stages III and IV cancers (P = 0.004), and in 63.6% (14/22) of cancers without metastasis but only 25.9% (14/54) of those with metastasis (P = 0.003). The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT (71 mo) and those without (33 mo, log rank = 20.78, P = 0.000). CONCLUSION: FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma.

[Significance of MMP2 and MMP9 expression in prostate cancer].

OBJECTIVE: To evaluate the significance of the expression of matrix metalloproteinases (MMPs) in prostate cancer (PCa) and its clinical association. METHODS: Fifty one cases of PCa and 10 cases of BPH were studied by immunohistochemical method using monoclonal antibodies to MMP2 and MMP9. RESULTS: There was significant correlation between MMP2 or MMP9 and pathological grade, Gleason score and PCa metastasis. CONCLUSION: The expression of MMP2 and MMP9 may play an important role in the development and metastasis of PCa.

[Morphology and immunohistochemical characteristics of hepatic primary and metastatic malignant spindle cell tumors].

OBJECTIVE: To investigate the morphology and immunohistochemical characteristics of hepatic primary and metastatic malignant spindle cell tumors, and to conclude the diagnostic and differential diagnostic criteria for these morphologically similar tumors. METHODS: Forty-six specimens of hepatic spindle cell tumors. 20 primary tumors (43.4%), including 3 cases of sarcomatoid carcinoma (6.5%), 11 of angiosarcoma (23.9%), 2 of epithelioid hemangioendothelioma (5%), 1 of spindle cell carcinoid (2.2%), and 3 of undifferentiated sarcoma (6.5%). and 26 metastatic malignant tumors (56.5%), including 20 cases of gastrointestinal stromal tumors (GIST, 43.4%), 3 of leiomyosarcoma (6.5%), 2 of malignant peripheral never sheath tumor (4.3%), and 1 of meningeal hemangiopericytoma (2.2%), resected during operation or collected during imaging-mediated liver puncture underwent hematoxylin-eosin staining, SP staining, and EnVision immunohistochemical staining. RESULTS: Either primary or metastatic tumors showed extensive overlapping in histopathologic appearance, and hemangiopericytoma-like structure was the predominant pattern, which could be seen in nearly every kind of hepatic spindle cell tumors. The morphology of GIST was the most complex. Two or three entirely different kinds of structure could be seen in one specimen of GIST, especially in the resected ones. Most stromal tumor cases were CD117 positive, and existed the condition that the primary tumor was positive and the metastatic tumor was negative or vice versa or one part of specimen was positive but other part was negative. Leiomyosarcoma was immunoreactive to smooth muscle specific antigen (SMA), malignant peripheral nerve sheath tumor was immunoreactive to S-100 protein and neurofilament (NF), and both were CD117 negative. Angiosarcoma and epithelioid hemangioendothelioma expressed different immunoreactivity to CD31, CD34 and factor VIII related antigen. Sarcomatoid carcinoma was positive for CK and vimentin. Spindle cell carcinoid was positive for CK and neuroendocrine markers, such as synaptophysin and chromogranin A. CONCLUSION: Primary angiosarcoma is the most common form of primary spindle cell tumor in liver, and metastatic GIST is predominant in hepatic metastatic spindle cell tumors. A penal of immunohistochemical markers is necessary for the final diagnosis of these tumors because of the complexity and similarity of different tumors of this kind.