Stereodivergent Synthesis of Alkaloid (±)-223A and (±)-6-epi-223A via Rh-Catalyzed Hydroformylation Double Cyclization.

A stereodivergent approach toward total syntheses of Dendrobatid alkaloids 223A and 6-epi-223A is described. The approach features a concise construction of an indolizidine skeleton by Rh-catalyzed domino hydroformylation double cyclization and sequential stereocontrolled transformations such as reductive alkylation or anti-selective α-alkylation of the 5-oxoindolizidine. These stereoselective reactions afford the desired stereochemistry in the targets.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Patients with oral cancer do not undergo surgery as primary treatment: A population-based study in Taiwan.

BACKGROUND: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. METHODS: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test. RESULTS: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01). CONCLUSION: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval.

CDN1163, a SERCA activator, causes intracellular Ca2+ leak, mitochondrial hyperpolarization and cell cycle arrest in mouse neuronal N2A cells.

OBJECTIVE: Activity or expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) is diminished in some disease states such as cardiac failure and diabetes mellitus. A newly developed activator of SERCA, CDN1163, reportedly rescued or alleviated pathological conditions attributed to dysfunctional SERCA. We examined whether CDN1163 could relieve mouse neuronal N2A cell growth inhibition caused by cyclopiazonic acid (CPA, SERCA inhibitor). We also examined how CDN1163 affected cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential. METHODS: Cell viability was measured by MTT assay and trypan blue exclusion test. Cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential were measured using fura 2, Rhod-2 and JC-1, respectively, as fluorescent probes. RESULTS: CDN1163 (10 µM) itself suppressed cell proliferation, and did not alleviate CPA's inhibitory effect (and vice versa). Cell cycle was arrested at the G1 phase after CDN1163 treatment. CDN1163 treatment caused a slow yet persistent cytosolic [Ca2+] elevation partly due to Ca2+ release from an internal store other than the CPA-sensitive endoplasmic reticulum (ER). Treatment with CDN1163 for 3 h raised mitochondrial Ca2+ level and such increase was suppressed by MCU-i4 (an inhibitor of mitochondria Ca2+ uniporter, MCU), suggesting Ca2+ entered the mitochondrial matrix through MCU. Treatment of cells with CDN1163 up to 2 days resulted in mitochondrial hyperpolarization. CONCLUSION: CDN1163 caused internal Ca2+ leak, cytosolic Ca2+ overload, mitochondrial Ca2+ elevation and hyperpolarization, cell cycle arrest and cell growth inhibition.

Rh-Catalyzed Hydroformylation-Initiated Bicyclization: Construction of Azabicyclic Systems.

Here, we describe the recent progress toward construction of 1-azabicyclic structures using a domino hydroformylation double cyclization strategy of an amide bearing the trisubstituted alkene functionality. The method provides a rapid and atom-economic access to alkaloid structures under mild conditions, especially for quinolizidine and pyrrolidine-fused azepane skeletons with yields up to 82% and good diastereoselectivity. Subsequent oxidative cleavage conditions are developed for the synthesis of Dendrobatid alkaloid epi-epiquinamide.

Ezrin overexpression in gastrointestinal stromal tumors: an independent adverse prognosticator associated with the non-gastric location.

Ezrin, a member of the ezrin-radixin-moesin family, acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It implicates tumor progression, metastatic dissemination, and adverse outcomes in several cancer types, including pediatric and adult sarcomas. Although ezrin upregulation was shown by cDNA expression profiling, no study has systematically evaluated the significance of ezrin expression in a large cohort of gastrointestinal stromal tumors (GISTs). Ezrin immunostaining was carried out on tissue microarrays of primary GISTs and assessable in 347 cases, 188 of which were successfully evaluated for mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes by sequencing with or without screening by denatured high-performance liquid chromatography. These GISTs with known RTK genotypes were dichotomized into two prognostically different groups. The endogenous expression and phosphorylation of ezrin in GIST cell lines were analyzed by western blotting. By immunohistochemistry, ezrin overexpression was present in 66% of GISTs and significantly associated with the non-gastric location (P=0.002) and decreased disease-free survival (P=0.032, univariately). However, it was not related to the National Institute of Health (NIH) risk category, Ki-67 labeling index, RTK genotypes, and other variables. In multivariate analyses, ezrin overexpression remained independently predictive of adverse outcome (P=0.008, risk ratio=2.363), together with Ki-67 labeling index >5% (P<0.001, risk ratio=3.581), high-risk category (P<0.001, risk ratio=2.156), and the non-gastric location (P=0.029, risk ratio=1.899). Despite the variation in the ezrin expression level, phosphorylated ezrin at threonine(567) was only detectable in GIST882 and GIST48 cells, but not in colonic smooth muscle cells. In conclusion, ezrin is frequently overexpressed in GISTs, especially those arising from the non-gastric sites. Given that its impact is independent of the NIH risk category, cell proliferation, and tumor location, ezrin immunoreactivity represents a valuable prognostic adjunct of GISTs, suggesting a causative role in conferring an aggressive phenotype.

Heat shock protein 90 overexpression independently predicts inferior disease-free survival with differential expression of the alpha and beta isoforms in gastrointestinal stromal tumors.

PURPOSE: Most gastrointestinal stromal tumors harbor a mutated KIT or PDGFRA receptor tyrosine kinase (RTK). Heat shock protein 90 (Hsp90) is a chaperone mediating the folding and stabilization of many oncoproteins, including KIT. An Hsp90 inhibitor, 17-AAG, can attenuate KIT activation and proliferation of gastrointestinal stromal tumor cell lines. We further evaluated Hsp90 immunoexpression and the difference between alpha and beta isoforms in gastrointestinal stromal tumor specimens. EXPERIMENTAL DESIGN: Hsp90 immunostain was assessable in 306 cases on tissue microarrays of primary gastrointestinal stromal tumors and correlated with various variables and disease-free survival (DFS). RTK mutation variants, confirmed in 142 cases by sequencing with or without precedent denaturing high pressure liquid chromatography screening, were dichotomized into two prognostically different groups. Differential expression of transcript and protein isoforms was measured by real-time reverse transcription-PCR and Western blotting in 16 and 6 cases, respectively. RESULTS: Hsp90 overexpression (55%) significantly correlated with larger size, nongastric location, higher mitotic count and NIH risk level, Ki-67 overexpression (all P < or = 0.001), and unfavorable RTK genotypes (P = 0.020). It strongly portended inferior DFS univariately (P < 0.0001) and remained independent in multivariate analysis (P = 0.031; risk ratio, 2.44), along with high-risk category, Ki-67 overexpression, and old age. For both mRNA and protein, Hsp90beta was more abundant than Hsp90alpha, whereas the latter was significantly higher in high-risk cases. CONCLUSIONS: Hsp90 overexpression represents a poor prognosticator that correlates with several adverse parameters, highlighting its role in disease progression and alternative therapy for high-risk, imatinib-resistant gastrointestinal stromal tumors. Hsp90alpha seems more relevant to the intrinsic aggressiveness of gastrointestinal stromal tumors, albeit less abundant than Hsp90beta.

Immunohistochemical and biogenetic features of diffuse-type tenosynovial giant cell tumors: the potential roles of cyclin A, P53, and deletion of 15q in sarcomatous transformation.

PURPOSE: Diffuse-type tenosynovial giant cell tumor (D-TSGCT) is an aggressive proliferation of synovial-like mononuclear cells with inflammatory infiltrates. Despite the COL6A3-CSF1 gene fusion discovered in benign lesions, molecular aberrations of malignant D-TSGCTs remain unidentified. EXPERIMENTAL DESIGN: We used fluorescent in situ hybridization and in situ hybridization to evaluate CSF1 translocation and mRNA expression in six malignant D-TSGCTs, which were further immunohistochemically compared with 24 benign cases for cell cycle regulators involving G(1) phase and G(1)-S transition. Comparative genomic hybridization, real-time reverse transcription-PCR, and a combination of laser microdissection and sequencing were adopted to assess chromosomal imbalances, cyclin A expression, and TP53 gene, respectively. RESULTS: Five of six malignant D-TSGCTs displayed CSF1 mRNA expression by in situ hybridization, despite only one having CSF1 translocation. Cyclin A (P = 0.008) and P53 (P < 0.001) could distinguish malignant from benign lesions without overlaps in labeling indices. Cyclin A transcripts were more abundant in malignant D-TSGCTs (P < 0.001). All malignant cases revealed a wild-type TP53 gene, which was validated by an antibody specifically against wild-type P53 protein. Chromosomal imbalances were only detected in malignant D-TSGCTs, with DNA losses predominating over gains. Notably, -15q was recurrently identified in five malignant D-TSGCTs, four of which showed a minimal overlapping deletion at 15q22-24. CONCLUSIONS: Deregulated CFS1 overexpression is frequent in malignant D-TSGCTs. The sarcomatous transformation involves aberrations of cyclin A, P53, and chromosome arm 15q. Cyclin A mRNA is up-regulated in malignant D-TSGCTs. Non-random losses at 15q22-24 suggest candidate tumor suppressor gene(s) in this region. However, P53 overexpression is likely caused by alternative mechanisms rather than mutations in hotspot exons.

Primary urothelial carcinoma of the upper tract: important clinicopathological factors predicting bladder recurrence after surgical resection.

The aim of the present study was to further characterize potential clinicopathological predictors for urinary bladder recurrence-free survival (UBRFS) in patients with primary urothelial carcinoma of the upper urinary tract (UUT-UC). The present series included 385 cases of surgically treated primary localized UUT-UC without previous or concurrent urothelial carcinoma of the urinary bladder. Among the 374 patients with follow-up information, clinicopathological features and therapeutic information including whether they received a laparoscopy-assisted nephroureterectomy (LNU) and adjuvant chemotherapy were correlated with UBRFS. After a median follow up of 69 months, 86 patients (23%) developed urinary bladder recurrence. The median time to develop urinary bladder recurrence was 12 months. At the univariate level, an increment in histological grade (P= 0.0321), a prominent papillary configuration (P= 0.0004), LNU (P= 0.0397) and male gender (P= 0.0401) significantly predicted an inferior UBRFS. At the multivariate level, increase of histological grade (P < 0.0001, relative risk (RR) = 3.776), prominent papillary configuration (P < 0.0001, RR = 3.244), and male gender (P= 0.0463, RR = 1.444) independently predicted UBRFS. In conclusion, male patients and those with high-grade and papillary UUT-UC, and who received LNU had higher risks of urinary bladder recurrence. Accordingly, for these patients, more intensive follow up coupled with postoperative intravesical adjuvant therapy to prevent urinary bladder recurrence should also be considered.

Predicting factors in the last week of survival in elderly patients with terminal cancer: a prospective study in southern Taiwan.

BACKGROUND/PURPOSE: The proportion of elderly persons among terminal cancer patients is around 60% in Taiwan. Prediction of the last week of survival can be significant in palliative care units for planning patient management, fulfilling patients' wishes at the end of life, and meeting the needs of relatives. We aimed to find out the predictive factors for the last week of survival in elderly terminal cancer patients. METHODS: We prospectively observed items based on previous research that we anticipated might influence survival among 459 consecutive elderly patients. Within 24 hours of admission, we collected data including clinical symptoms and signs, demographic information, and biochemical test results. Multivariate logistic regression analysis was performed to identify factors associated with patient mortality within 7 days. RESULTS: Multivariate analysis indicated that the following factors were predictive of death: higher score of Eastern Cooperative Oncology Group (ECOG) performance status (OR, 2.018; p < 0.001), primary liver cancer (OR, 1.968; p = 0.024), male gender (OR, 2.885; p < 0.001), lower extremity muscle power (OR, 0.722; p = 0.0266), lower systolic blood pressure (OR, 0.985; p = 0.011), higher heart rate (OR, 1.017; p = 0.016), higher hemoglobin (OR, 1.216; p = 0.003), and higher blood urea nitrogen (BUN) (OR, 1.028; p < 0.001). CONCLUSION: We propose that the probability of survival of less than a week can be predicted by our formula. This formula, which includes factors of demographic information (male gender, and presence of liver cancer), clinical signs (lower systolic blood pressure, higher heart rate, and lower mean extremity muscle power), and biochemical tests (elevated BUN, and higher hemoglobin), may help improve survival prediction in terminal elderly cancer patients.

Malignant diffuse-type tenosynovial giant cell tumors: a series of 7 cases comparing with 24 benign lesions with review of the literature.

BACKGROUND: Malignant diffuse-type tenosynovial giant cell tumor (D-TSGCT), an unusual sarcoma with concurrent or previous benign D-TSGCTs, poses challenges to diagnosis and prognostication. METHODS: We described the radiologic, clinicopathologic, and immunophenotypical findings of 5 primary and 2 metachronous malignant D-TSGCTs and reviewed published cases to better delineate their morphologic spectrum and behavior. Twenty-four benign D-TSGCTs were also statically compared to analyze the diagnostic values of various variables. RESULTS: The 7 malignant cases affected 4 females and 3 males aged 45 to 78 (mean, 60.9) years, which included 1 intraarticular and 6 extra-articular lesions. These tumors were 5 to 17 cm (mean, 9.4) and located within or near the large joints of extremities. Magnetic resonance imaging revealed expansile or infiltrative masses with frequent lobulation and heterogeneous signals. Histologically, areas of benign D-TSGCTs blended abruptly or gradually with frank sarcomas composed of pleomorphic, spindle, or enlarged oval cells, forming malignant fibrous histiocytomalike (n = 4), fibrosarcomatous (n = 1), myxosarcomatous (n = 1), or giant cell tumorlike (n = 1) patterns. One patient experienced recurrences twice, and another 3 developed metastases to the lymph nodes (n = 2), lung (n = 1), or vertebrae (n = 1), with 1 dying from disseminated diseases. An older age (P = 0.003), a larger size (P = 0.036), tumor necrosis (P < 0.001), atypical mitoses (P < 0.001), and Ki-67 overexpression (P < 0.001) appeared preferentially in malignant lesions, but these parameters had overlap between few benign and malignant tumors. CONCLUSIONS: Malignant D-TSGCTs are a distinct sarcoma with considerable morphologic variability, metastatic propensity, and lethality. Altered architecture with anaplastic cells represents an important distinguishing feature, while abnormalities of other parameters should not be directly equated with malignancy.

Flow cytometric analysis of DNA ploidy and S-phase fraction in primary localized myxofibrosarcoma: correlations with clinicopathological factors, Skp2 expression, and patient survival.

BACKGROUND: Histological assessment for prognostication of myxofibrosarcomas remains challenging. We previously reported independent prognostic value of Skp2, an oncoprotein promoting S-phase progression (Clin Cancer Res 2006;12:487-98). METHODS: We evaluated S-phase fraction (SPF) and ploidy of myxofibrosarcomas and the association between SPF and Skp2. Flow cytometric findings were analyzed for 75 cases and correlated with clinicopathological factors, Skp2 labeling index (LI), metastasis-free survival (MeFS), and overall survival (OS). RESULTS: Forty-seven and 28 cases were classified as diploid and nondiploid, respectively. High SPF (>or=20%) was detected in 32 of 61 interpretable cases. Skp2 overexpression (LI >or= 10%) was seen in 36 of 72 cases with scoring. Nondiploidy correlated with higher French Federation of Cancer Centers (FNCLCC) grades (P = .006), remarkable necrosis (P = .010), and Skp2 overexpression (P = .018). Noticeably, SPF was significantly related to Skp2 LI (P < .001, r = .458), FNCLCC grade, American Joint Committee on Cancer stage, and mitotic rate. Nondiploidy predicted shorter OS (P = .0045) and MeFS (P = .0489), whereas SPF >or= 20% was only associated with inferior MeFS (P = .0252). In multivariate analyses, nondiploidy independently correlated with both OS (P = .020, RR = 3.337) and MeFS (P = .013, RR = 5.780), together with Skp2 overexpression (P = .014 for OS; P = .017 for MeFS) and disease-positive margins (P = .004 for OS; P = .002 for MeFS). CONCLUSION: Skp2 promotes S-phase progression in myxofibrosarcomas. SPF provides no independent prognostic usefulness; it is probably overshadowed by Skp2. Nondiploidy adds another predictive value to Skp2 overexpression and disease-positive margins in prognostication.

Human herpesvirus type 8 in patients with cirrhosis: correlation with sex, alcoholism, hepatitis B virus, disease severity, and thrombocytopenia.

Immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. The association between cirrhosis and human herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; P = .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P = .003). Antibody titers in seropositive patients also significantly exceeded those in healthy control subjects (P = .008). All subjects were negative for anti-HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and patients with alcohol- or HBV-related cirrhosis.

A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome.

BACKGROUND: By reappraising the National Institutes of Health (NIH) consensus criteria, we worked on establishing a modified scheme to identify highly lethal gastrointestinal stromal tumors (GISTs), which have an imperative demand for sequencing analysis to assess the suitability of an adjuvant imatinib trial. METHODS: Clinicopathologic features, including NIH and modified schemes, were retrospectively analyzed for 289 patients with localized GISTs. We combined the very low/low-risk GISTs into a single "risk level I" group (5 cm and >10/50 HPF, with the rest of high-risk GISTs defined as "risk level III." RESULTS: The cumulative 5-year rate of disease-specific survival (DSS) for all 289 patients was 82%, and the DSS rates for patients with GISTs classified as risk levels I to IV were 100%, 96%, 67%, and 25% at 5 years, respectively. The prognostic differences were striking between the risk level II and III groups (P < .0001) and between the risk level III and IV groups (P = .0002). The higher risk level of our scheme represented the strongest independent adverse factor (risk ratio [RR] = 11.299 for risk level III; RR = 33.815 for risk level IV; P < .0001), followed by mixed/epithelioid histology (RR = 2.837, P = .003) and older age (>or=70 years, RR = 1.955, P = .044). CONCLUSIONS: Remarkable prognostic heterogeneity exists in the high-risk category of the NIH scheme, which is not as effective as the modified criteria in identifying highly lethal GISTs that we classified as risk level IV.

Diagnostic value of tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions.

BACKGROUND: Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions (LAC-CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC-CNPEs from benign PEs. METHODS: PE samples were collected from 74 patients with lung adenocarcinoma with associated cytologically positive (41 patients) and negative (33 patients) PEs, and from 99 patients with benign conditions including tuberculosis (26 patients), pneumonia (28 patients), congestive heart failure (25 patients), and cirrhosis (20 patients). The authors evaluated the diagnostic sensitivity and optimal cutoff points for the tumor markers HER2/neu, CYFRA 21-1, and carcinoembryonic antigen (CEA) to distinguish LAC-CNPEs from benign PEs. RESULTS: Mean levels of HER2/neu, CYRFA 21-1, and CEA were found to be significantly higher in LAC-CNPEs compared with benign PEs (P = .0050, P = .0039, and P < .0001, respectively). The cutoff points for HER2/neu, CYFRA 21-1, and CEA were optimally set at 3.6 ng/mL, 60 ng/mL, and 6.0 ng/mL, respectively. Their sensitivities ranged from 12.1%, to 30.3%, to 63.6%, respectively. CEA combined with CYFRA 21-1 increased diagnostic sensitivity to 66.7%. The false-positive rates of these markers in benign PEs were 6.1%, 2.0%, and 0%, respectively. CONCLUSIONS: The combination of CEA with CYFRA 21-1 appears to provide the best differentiation between LAC-CNPEs and benign PEs to date using 2 tumor markers, and allows for the early diagnosis and early treatment of approximately two-thirds of affected patients.

Is the SF-12 version 2 Health Survey a valid and equivalent substitute for the SF-36 version 2 Health Survey for the Chinese?

RATIONALE AND OBJECTIVES: The scoring algorithm of the 12-item Short-Form Health Survey (SF-12) was revised in the second version (SF-12v2), but information on its psychometric properties is lacking. This study determined whether the SF-12v2 was a valid and equivalent substitute for the SF-36v2 Health Survey (version 2) for the Chinese. METHODS: A total of 2410 Chinese adults in Hong Kong completed the SF-36 Health Survey by telephone. The SF-12v2 data were extracted from the SF-36 data. Internal consistency was assessed by Cronbach's alpha, and test-retest reliabilities were evaluated by intraclass correlation. Criterion validity and equivalence were assessed using the SF-36v2 scores as a gold standard. Construct validity and sensitivity were assessed by known-group comparison. RESULTS: Internal consistency and test-retest reliabilities were good (range 0.67-0.82) for all except three scales. The SF-12v2 summary scores explained >80% of the total variances of the SF-36v2 summary scores. Construct validity and sensitivity were confirmed by significantly lower SF-12v2 scores in people with chronic diseases than those without. Effect size differences were less than 0.3 and relative validities were greater than 0.7 between SF-12v2 and SF-36v2 scores for different groups. CONCLUSION: The SF-12v2 was valid, reliable and sensitive for the Chinese. It is an equivalent substitute for the SF-36v2 for the summary scales.

[Treatment of facial pigmentation after burns with traditional Chinese medicine mask and skin care].

OBJECTIVE: To observe the effects of traditional Chinese medicine mask combined with skin care in the treatment of facial pigmentation after burns. METHODS: Forty-one patients with facial pigmentation after burns hospitalized from January 2009 to June 2010 were enrolled and divided into treatment group (n = 26, odd number) and control group (n = 15, even number) according to the visiting order. After cleaning, massaging, and steam spraying to faces, patients in treatment and control groups were respectively treated with traditional Chinese medicine mask developed by physicians in our hospital and common commercial beauty mask. Masks were removed when they became completely dry. The treatment was repeated every other day. Ten times made up a course of treatment. Three consecutive courses were carried out on each patient. Before treatment and at the end of each course, the skin color differences were measured with Vancouver Pigmented Scar Scale; image gray scale value of pigmented skin was measured with image analysis technique. Satisfaction degree acknowledged by both patients and physicians were recorded at the end of each course; adverse effects were recorded; and the overall efficacy between two groups was compared. Data were processed with chi-square test or t test. RESULTS: Skin color differences, image gray scale value of patients in treatment group were close to those in control group before treatment (with t value respectively 0.800 and 0.694, P values all above 0.05). Skin color differences, image gray scale value, and satisfaction degree acknowledged by both patients and physicians in treatment group were better than those in control group at the end of each course. At the end of the third course of treatment, the skin color differences in treatment and control groups scored 0.5 ± 0.4 and 1.1 ± 0.6, respectively, with image gray scale value of 55 ± 5 and 66 ± 6, respectively, which were statistically different from each other (with t value respectively 3.389 and 5.102, P values all below 0.01). The overall efficacy of the treatment group was 92.3%, which was much better than that of the control group (53.3%, χ(2) = 6.31, P < 0.05). No allergy caused by the traditional Chinese medicine mask was observed during the treatment. CONCLUSIONS: The traditional Chinese medicine mask combined with skin care is effective for the treatment of facial pigmentation after burns.

Diagnostic value of Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen levels in malignant pleural effusions of lung adenocarcinoma.

AIMS: Cytology fails to detect neoplastic cells in 40-50% of cases of malignant pleural effusion, a condition that frequently accompanies lung adenocarcinoma. Published reports of diagnostic sensitivity of various tumour markers are inconsistent, and optimal cut-off points have not been determined. This study aimed to evaluate the ability of three markers to discriminate lung adenocarcinoma-associated malignant pleural effusion (LAC-MPE) from benign effusion. METHODS: Pleural effusion samples were collected from 41 patients with LAC-MPE, and from 93 with various benign conditions. The diagnostic sensitivity and specificity for Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen (CEA) were evaluated. Cut-off points for these markers are optimally set at 3.6 microg/L, 60 microg/L, and 6.0 microg/L, respectively. RESULTS: Her-2/neu, Cyfra 21-1, and CEA vary in their diagnostic accuracy to differentiate LAC-MPE from benign pleural effusion: 79.85%, 88.81%, and 94.03%, respectively. CEA combined with Cyfra 21-1 increases diagnostic sensitivity to 97.6%, with a specificity of 91.4%. CONCLUSIONS: With appropriate cut-off points, CEA currently provides the best diagnostic accuracy. Combining CEA with Cyfra 21-1 increases diagnostic sensitivity to nearly 100%. The results of the present study may help clinicians decide whether to obtain a cytological/histological specimen by invasive means to investigate a possible diagnosis of malignancy.

Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors.

PURPOSE: Chromosome 9 is frequently deleted in high-risk gastrointestinal stromal tumors (GISTs), whereas its specific tumor suppressor genes (TSGs) are less understood. We did an integrative study of MTAP gene at 9p21 to analyze its implication in GISTs. EXPERIMENTAL DESIGN: To search TSGs on chromosome 9, we used ultrahigh-resolution array comparative genomic hybridization to profile DNA copy number alterations of 22 GISTs, with special attention to MTAP gene. MTAP immunoexpression was assessable for 306 independent GISTs on tissue microarrays, with 146 cases analyzed for MTAP homozygous deletion, 181 for mutations of KIT and PDGFRA receptor tyrosine kinase genes, and 7 for MTAP hypermethylation. RESULTS: Array comparative genomic hybridization identified 11 candidate TSGs on 9p and six on 9q. MTAP and/or CDKN2A/CDKN2B at 9p21.3 were deleted in one intermediate-risk (11%) and seven high-risk (70%) GISTs with two cases homozygously codeleted at both loci. MTAP homozygous deletion, present in 25 of 146 cases, was highly associated with larger size and higher mitotic rate, Ki-67 index, and risk level (all P < 0.01) but not with receptor tyrosine kinase genotypes. Whereas MTAP homozygous deletion correlated with MTAP protein loss (P < 0.001), 7 of 30 GISTs without MTAP expression did not show homozygous deletion, including three MTAP-hypermethylated cases. MTAP homozygous deletion was univariately predictive of decreased disease-free survival (P < 0.0001) and remained multivariately independent (P = 0.0369, hazard ratio = 2.166), together with high-risk category (P < 0.0001), Ki-67 index >5% (P = 0.0106), and nongastric location (P = 0.0416). CONCLUSIONS: MTAP homozygous deletion, the predominant mechanism to deplete protein expression, is present in 17% of GISTs. It correlates with important prognosticators and independently predicts worse outcomes, highlighting the role in disease progression.

[Rescue and treatment for the mass burn casualties of yellow phosphorus explosion].

OBJECTIVE: To summarize the characteristics and treatment of burn casualties of yellow phosphorus explosion, so as to share the experiences in emergency treatment. METHODS: By analyzing the data related to this accident, the characteristics of the injury and experiences of treatment for mass burn casualties from yellow phosphorous explosion were summarized. RESULTS: Eighty-one patients, 72 males and 9 females, were injured in a yellow phosphorus explosion. The mean age of the patients was 24 +/- 13 years old (5-42 y). The mean total burn surface area was (9 +/- 11)% [(0.4% - 70.0%))] TBSA, and the mean burn surface area of III degrees/IV degrees was (7 +/- 10)% [(0.4% - 60.0%)] TBSA. Most of the patients showed the symptoms and signs of phosphorus poisoning. Among all the patients, 27 cases (33.3%) showed hepatic dysfunction, 15 cases (18.5%) had renal dysfunction, 42cases (51.9%) showed electrolytes disorders. Among the 8 patients with burn surface area over 10% TBSA and less than 20% TBSA, high levels of cardiac enzymes were found in 6 cases, anaemia in 7 cases (3 with progressive anaemia), asphyxia occurred in 1 case 48 hours after burn, and in 1 case complicated with stress ulcer. Escharectomy and skin grafting were performed within four days after burn in 72 patients. All the patients survived, some of them showed impaired hand function and hypertrophic scar, and partial finger amputation was done in 3 patients. CONCLUSION: Yellow phosphorus explosion produces deep burn injuries in surrounding people especially in exposed parts such as head, hand and so on. Adequate organization of medical resources for emergency treatment, early debridement, and accelerating excretion of phosphorus are the key points for the successful rescue of mass casualties.