Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets.

Objective: To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets. Methods: A total of 235 patients with TBM were divided into the control group (117 cases) and the observation group (118 cases). Both groups were given conventional treatment, the control group was further given isoniazid, and the observation group was further given Dex combined with isoniazid. The therapeutic effect and improvement of clinical symptoms were evaluated, peripheral blood T lymphocyte subsets and neurological function were observed, and patients' prognosis was evaluated. Results: The total effective rate of the observation group was higher. The recovery time of cerebrospinal fluid (CSF) pressure, CSF protein content, CSF cell count, and hospital stays in the observation group were shorter. The duration of cervicogenic headache, fever, vomiting, and coma in the observation group was shorter. CD3+ and CD4+/CD8+ proportions in the observation group were higher, and CD8+ proportion was lower. The NIHSS score and MRS score of the observation group were lower, as well as the incidence of adverse reactions. Conclusion: Dex combined with isoniazid alleviates clinical symptoms and neurological abnormalities and regulates peripheral blood T cell subsets in TBM.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Characteristics of plasma exosomes in drug-resistant tuberculosis patients.

BACKGROUND: Increasing prevalence of drug-resistant tuberculosis (DR-TB) poses a major challenge to the early detection and effective control of tuberculosis (TB). Exosomes carrying proteins and nucleic acid mediate intercellular communication between host and pathogen including Mycobacterium tuberculosis. However, molecular events of exosomes indicating the status and development of DR-TB remain unknown. This study determined the proteomics of exosome in DR-TB and explored the potential pathogenesis of DR-TB. METHODS: Plasma samples were collected from 17 DR-TB patients and 33 non-drug-resistant tuberculosis (NDR-TB) patients using grouped case-control study design. After exosomes of plasma were isolated and confirmed by compositional and morphological measurement for exosomal characteristics, a label-free quantitative proteomics of exosomes was performed and differential protein components were determined via bioinformatics analysis. RESULTS: Compared with the NDR-TB group, we identified 16 up-regulated proteins and 10 down-regulated proteins in the DR-TB group. The down-regulated proteins were mainly apolipoproteins and mainly enriched in cholesterol metabolism-related pathways. Apolipoproteins family including APOA1, APOB, APOC1 were key proteins in protein-protein interaction network. CONCLUSION: Differentially expressed proteins in the exosomes may indicate the status of DR-TB from NDR-TB. Apolipoproteins family including APOA1, APOB, APOC1 may be involved in the pathogenesis of DR-TB by regulating cholesterol metabolism via exosomes.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

MicroRNA-4485 ameliorates severe influenza pneumonia via inhibition of the STAT3/PI3K/AKT signaling pathway.

The present study aimed to explore the potential roles and mechanism of microRNA-4485 (miR-4485) in severe influenza pneumonia. miR-4485 expression was detected in patients with severe H1N1 pneumonia using quantitative PCR. Furthermore, the effects of aberrantly expressed miR-4485 on H1N1-infected A549 cells were investigated using Cell Counting Kit-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting and (ELISA) assays. Furthermore, the regulatory relationships between miR-4485 and the STAT3-mediated PI3K/AKT/mTOR signaling pathway were explored using a luciferase reporter and rescue assay. MiR-4485 expression was downregulated following H1N1 infection and in patients with H1N1 pneumonia. In addition, miR-4485 alleviated H1N1-induced A549 cell injury by promoting cell viability and the production of cytokines, as well as reducing apoptosis in A549 cells. Furthermore, STAT3 was revealed to be a target gene of miR-4485. Additionally, STAT3 silencing reversed the protective effects of miR-4485 knockdown on H1N1-induced cell injury via inhibition of the PI3K/AKT/mTOR signaling pathway. In conclusion, miR-4485 inhibited H1N1-induced severe pneumonia in A549 cells by targeting STAT3 via the PI3K/AKT/mTOR signaling pathway.

The epidemiology of extrapulmonary tuberculosis in China: A large-scale multi-center observational study.

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15-24 years and 25-34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803-0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989-0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.

Interactions of stimulus quality and frequency on N400 in Chinese character recognition: Evidence for cascaded processing.

Event-related brain potentials (ERPs) were recorded during a delayed character-matching (target-probe matching) task to examine the joint effects of stimulus quality (blurriness) and character frequency on the N400. The behavioral results indicated robust interactive effects of stimulus quality and character frequency on response times, suggesting the cascade of pre-lexical activation to the lexical stage. The ERP results showed an interaction between stimulus quality and character frequency on N400-like amplitude. As the N400 is basically a marker of semantic processing, these ERP findings suggested that the direct impact of stimulus blurriness on pre-lexical processing could be further cascaded to semantic processing via lexical stage. The converging behavioral and N400 evidence for the interactive effects of stimulus quality and character frequency accords well with the interactive activation (IA) model, in which stimulus quality and character frequency affect at least a common stage in a cascaded processing manner.

Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are recently identified urinary biomarkers of acute kidney injury (AKI) in critically ill patients. Because their predictive accuracies vary widely, a meta-analysis was performed to evaluate the accuracy of previously reported urinary TIMP-2 and IGFBP7 cut-offs for predicting AKI. METHODS: This meta-analysis was reported following the guideline of PRISMA. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 by 2 investigators, who independently selected studies, extracted relevant data, and evaluated study quality. A bivariate model was used to calculate the pooled estimates. RESULTS: The search identified 5 studies with 1619 critically ill patients. Urinary TIMP-2 and IGFBP7 cut-off points of 0.3 (ng/ml)/1000 had a sensitivity of 0.89 [95% confidence interval (CI) 0.85-0.93], a specificity of 0.48 (95% CI 0.45-0.51) and a diagnostic odds ratio (DOR) of 8.33 (95% CI 5.55-12.52). The area under the curve (AUC) estimated by the summary receiver operating characteristic (SROC) curve was 0.748. Based on 891 critically ill patients from 4 studies, urinary TIMP-2 and IGFBP7 cut-off points of 2.0 (ng/ml)/1000 had a sensitivity of 0.45 (95% CI 0.37-0.53), a specificity of 0.93 (95% CI 0.91-0.95) and a DOR of 11.43 (95% CI 7.43-17.57). The AUC estimated by SROC was 0.844. CONCLUSION: Cut-off values around 0.3 (ng/ml)/1000 (high sensitivity) and 2.0 (ng/ml)/1000 (high specificity) could be accurate surrogate biomarkers predicting AKI in critically ill patients. The urinary TIMP-2 and IGFBP7 cut-off point of 2.0 (ng/mL)/1000 appears to have the highest overall accuracy. TRIAL REGISTRATION: PROSPERO registration number 2018: CRD42018084457 Registered on 11 February 2018.

Clinical efficacy of nutrition support therapy combined with antibiotics in the patients of community-acquired pneumonia and its influence on serum pct and crp.

To analyze the clinical efficacy of nutrition support therapy combined with antibiotics in the treatment of patients with ICU severe community-acquired pneumonia and its effect on serum procalcitonin (PCT) and C reactive protein (CRP). A total of 90 patients with ICU severe community-acquired pneumonia treated in hospital from September 2016 to June 2017.The patients were randomly divided into A group and B group 45 cases in each group. Both groups were given antibiotic treatment of azithromycin plus cefuroxime sodium in which the A group received enteral nutrition support therapy while the B group parenteral nutritional support therapy. Levels of serum prealbumin (PA), albumin (ALB), transferrin (TF), procalcitonin (PCT) and C reactive protein (CRP) before and after treatment were compared. Before treatment there was found no significant difference in serum PA, ALB and TF levels (p>0.05) while after treatment, the serum levels of PA, ALB and TF in the A group were significantly higher than those in the B group (p<0.05). The effective rate of the A group was 88.9%, higher than that of the B group (p<0.05). In patients with ICU severe community-acquired pneumonia, the treatment of enteral nutrition support therapy combined with antibacterial drugs of azithromycin and cefuroxime sodium can effectively improve the indexes of PA, ALB and TF. The reduce levels of serum PCT and CRP with the good prognosis is important in popularization and application in clinical practices.

P2 and behavioral effects of stroke count in Chinese characters: Evidence for an analytic and attentional view.

The inconsistent stroke-count effect in Chinese character recognition has resulted in an intense debate between the analytic and holistic views of character processing. The length effects of English words on behavioral responses and event-related potentials (ERPs) are similarly inconclusive. In this study, we identified any behavioral and ERP stroke-count effects when orthographic neighborhood sizes are balanced across three stroke counts. A delayed character-matching task was conducted while ERPs were recorded. The behavioral data indicated that both response latency and error rate increased with increasing stroke count. The ERP data showed higher P2 but lower N2 amplitudes in the large count than in the median count condition. A higher P2 can reflect increased attentional load and reduced attentional resource for processing each stroke because of the additional strokes in the large count condition. The behavioral and ERP effects of stroke count provide evidence for the analytic view of character processing but also provide evidence against the holistic view.

Noise masking of S-cone increments and decrements.

S-cone increment and decrement detection thresholds were measured in the presence of bipolar, dynamic noise masks. Noise chromaticities were the L-, M-, and S-cone directions, as well as L-M, L+M, and achromatic (L+M+S) directions. Noise contrast power was varied to measure threshold Energy versus Noise (EvN) functions. S+ and S- thresholds were similarly, and weakly, raised by achromatic noise. However, S+ thresholds were much more elevated by S, L+M, L-M, L- and M-cone noises than were S- thresholds, even though the noises consisted of two symmetric chromatic polarities of equal contrast power. A linear cone combination model accounts for the overall pattern of masking of a single test polarity well. L and M cones have opposite signs in their effects upon raising S+ and S- thresholds. The results strongly indicate that the psychophysical mechanisms responsible for S+ and S- detection, presumably based on S-ON and S-OFF pathways, are distinct, unipolar mechanisms, and that they have different spatiotemporal sampling characteristics, or contrast gains, or both.

The N2- and N400-like effects of radicals on complex Chinese characters.

Participants were asked to complete a delayed character-matching task, while their event-related brain potentials (ERPs) elicited by Chinese character fragments were recorded. This task required participants to match probe characters with their preceding fragments, which were randomly assigned to be either radical or stroke-deleted. However, the same number of strokes was retained in either case. The stroke-deleted fragments, which contained fewer intact radicals, elicited larger N2- and N400-like components compared with the radical-deleted fragments. Stroke-deleted fragments displayed lower response accuracy than the radical-deleted fragments. These results indicate that simple radicals have an intermediate or sub-character function in Chinese character recognition. The processing of characters with more destroyed radicals is impeded within a multilayer interactive-activation model.

Font effects of Chinese characters and pseudo-characters on the N400: evidence for an orthographic processing view.

Event-related brain potentials (ERPs) were recorded during a Chinese character decision task to examine whether N400 amplitude is modulated by stimulus font. Results revealed large negative-going ERPs in an N400 time window of 300-500ms to stimuli presented in degraded Xing Kai Ti (XKT) font compared with more intact Song Ti (ST) font regardless of whether the stimuli were real or pseudo-characters. ERPs for the pseudo-characters were more negative than for the real characters with similar timing and scalp distribution. The N400-like font effect on amplitude is interpreted as analogous to an N400 stimulus degradation effect, an extension to Holcomb (1993); the degraded perceptual cues provided by XKT supposedly account for this degradation effect. This effect is further interpreted to reflect relative difficulty, which results from orthographic processing difficulty, in retrieving the meaning of XKT stimuli compared with ST stimuli.

N400 solution effect of Chinese character fragments: an orthographic neighborhood size effect.

In this study, event-related brain potentials (ERPs) elicited by fragments of Chinese single-character words were simultaneously recorded while participants completed a delayed character-matching task as fast as possible, wherein probe characters were matched with their prior fragments. The number of solutions for such fragments was manipulated. Results indicate that fragments completed with several characters elicited greater N400 than did fragments with a single solution. Behavioral results demonstrated that "multiple-solution" responses were slower and had lower accuracy rates than the "one-solution" responses. In this article, both behavioral and N400 solution-effects are interpreted to provide evidence that supports the interactive activation model (IAM) but counters the efficacy of serial search models.

Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma.

BACKGROUND: Several studies have suggested that fascin, cytokeratin 14 and cytokeratin 4 may have significant roles as biomarkers for the progression and survival of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: This study performed immunohistochemistry in tissue microarrays, profiling premalignant lesions and invasive tumors. RESULTS: Fascin increased across the following states as follows: normal-appearing epithelium (26%) to dysplasia (46%) to ESCC (68%), while CK4 was undetectable in ESCC (0%) compared to normal-appearing epithelium (45%) or dysplasia (41%). CK14 was elevated and invariant in expression. In regression analyses, compared to normal-appearing epithelium, higher fascin expression was associated with a 36% increased risk of dysplasia (odds ratio=1.36) and a 56% increased risk of invasive ESCC (odds ratio=1.56). CONCLUSION: Expression of fascin is up-regulated in the transformation from normal-appearing epithelium, through dysplasia, into invasive carcinoma. Expression of CK4, CK14 and fascin did not correlate with patient survival. Fascin has a potential role as an early detection biomarker and CK4 as a tumor marker in ESCC.

Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with poor prognosis. Understanding molecular changes in ESCC will enable identification of molecular subtypes and provide potential targets for early detection and therapy. EXPERIMENTAL DESIGN: We followed up a previous array study with additional discovery and confirmatory studies in new ESCC cases by using alternative methods. We profiled global gene expression for discovery and confirmation, and validated selected dysregulated genes with additional RNA and protein studies. RESULTS: A total of 159 genes showed differences with extreme statistical significance (P < E-15) and 2-fold differences or more in magnitude (tumor/normal RNA expression ratio, N = 53 cases), including 116 upregulated and 43 downregulated genes. Of 41 genes dysregulated in our prior array study, all but one showed the same fold change directional pattern in new array studies, including 29 with 2-fold changes or more. Alternative RNA expression methods validated array results: more than two thirds of 51 new cases examined by real-time PCR (RT-PCR) showed 2-fold differences or more for all seven genes assessed. Immunohistochemical protein expression results in 275 cases which were concordant with RNA for five of six genes. CONCLUSION: We identified an expanded panel of genes dysregulated in ESCC and confirmed previously identified differentially expressed genes. Microarray-based gene expression results were confirmed by RT-PCR and protein expression studies. These dysregulated genes will facilitate molecular categorization of tumor subtypes and identification of their risk factors, and serve as potential targets for early detection, outcome prediction, and therapy.

[A comparative study on the risks of esophagus-cancer patients among factors as blood relatives, paternal line, matriarchal and different sex].

OBJECTIVE: In order to provide new clues on the cause of esophagus-cancer through seeking for information among the relatives of esophagus-cancer-patients at high-risk, contrast analysis was carried out to compare the ORs between esophagus-cancer cases and the relatives of the patients. METHODS: Case-control study was adopted on 720 cases and 720 controls who were kin relatives of the patients. RESULTS: (1) Risk of the relatives to the esophagus-cancer-patient group (1.34% - 2.24%) was obviously higher than the control group (0.78% - 1.21%) (P < 0.01). In 1(st) grade relatives, the risk of parent's to the esophagus-cancer patients (6.11%) was obviously higher than the control group (2.97%) (P < 0.01). (2) According to the cascade analysis to the cases of both paternal and matriarchal, lines, results showed that the risks of both the paternal line (0.87% - 1.01%) and the matriarchal line (0.50% - 0.79%) in the group of esophagus-cancer cases were all obviously higher than the lines in the control groups (0.53% - 0.65%) and (0.38% - 0.47%). Data also showed that the risk among the male relatives of paternal line (eg: grandfathers', father's, uncles' etc.) in the group of cases was 2.68% while the matriarchal (eg: grandmother's, mother's, aunts' etc.) was 1.91%. Both figures were obviously higher than that in the control group (1.50% and 0.92%, P < 0.01). CONCLUSION: The risk factor of esophagus cancer of the next generation seemed higher if the father and his brothers or mother and her sisters having had esophagus-cancers.