Assessment of breast lesions by the Kaiser score for differential diagnosis on MRI: the added value of ADC and machine learning modeling.

OBJECTIVES: To evaluate the diagnostic performance of Kaiser score (KS) adjusted with the apparent diffusion coefficient (ADC) (KS+) and machine learning (ML) modeling. METHODS: A dataset of 402 malignant and 257 benign lesions was identified. Two radiologists assigned the KS. If a lesion with KS > 4 had ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 to become KS+. In order to consider the full spectrum of ADC as a continuous variable, the KS and ADC values were used to train diagnostic models using 5 ML algorithms. The performance was evaluated using the ROC analysis, compared by the DeLong test. The sensitivity, specificity, and accuracy achieved using the threshold of KS > 4, KS+ > 4, and ADC ≤ 1.4 × 10-3 mm2/s were obtained and compared by the McNemar test. RESULTS: The ROC curves of KS, KS+, and all ML models had comparable AUC in the range of 0.883-0.921, significantly higher than that of ADC (0.837, p < 0.0001). The KS had sensitivity = 97.3% and specificity = 59.1%; and the KS+ had sensitivity = 95.5% with significantly improved specificity to 68.5% (p < 0.0001). However, when setting at the same sensitivity of 97.3%, KS+ could not improve specificity. In ML analysis, the logistic regression model had the best performance. At sensitivity = 97.3% and specificity = 65.3%, i.e., compared to KS, 16 false-positives may be avoided without affecting true cancer diagnosis (p = 0.0015). CONCLUSION: Using dichotomized ADC to modify KS to KS+ can improve specificity, but at the price of lowered sensitivity. Machine learning algorithms may be applied to consider the ADC as a continuous variable to build more accurate diagnostic models. KEY POINTS: • When using ADC to modify the Kaiser score to KS+, the diagnostic specificity according to the results of two independent readers was improved by 9.4-9.7%, at the price of slightly degraded sensitivity by 1.5-1.8%, and overall had improved accuracy by 2.6-2.9%. • When the KS and the continuous ADC values were combined to train models by machine learning algorithms, the diagnostic specificity achieved by the logistic regression model could be significantly improved from 59.1 to 65.3% (p = 0.0015), while maintaining at the high sensitivity of KS = 97.3%, and thus, the results demonstrated the potential of ML modeling to further evaluate the contribution of ADC. • When setting the sensitivity at the same levels, the modified KS+ and the original KS have comparable specificity; therefore, KS+ with consideration of ADC may not offer much practical help, and the original KS without ADC remains as an excellent robust diagnostic method.

A novel radiomics signature based on T2-weighted imaging accurately predicts hepatic inflammation in individuals with biopsy-proven nonalcoholic fatty liver disease: a derivation and independent validation study.

Background: Currently, there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy. T2-weighted images (T2WI) are routinely obtained from liver magnetic resonance imaging (MRI) scan sequences. We aimed to establish a radiomics signature based on T2WI (T2-RS) for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study. The hepatic inflammatory activity score (IAS) was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning. One thousand and thirty-two radiomics features were extracted from the localized region of interest (ROI) in the right liver lobe of T2WI and, subsequently, selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator (LASSO) methods. The T2-RS was calculated by adding the selected features weighted by their coefficients. Results: Eighteen radiomics features from Laplacian of Gaussian, wavelet, and original images were selected for establishing T2-RS. The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation (P<0.01). The T2-RS yielded an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.80 [95% confidence interval (CI): 0.71-0.89] for predicting hepatic inflammation in the training cohort with excellent calibration. The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77 (0.61-0.93) and 0.75 (0.63-0.84), respectively. Conclusions: The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.

Radiomics based on fluoro-deoxyglucose positron emission tomography predicts liver fibrosis in biopsy-proven MAFLD: a pilot study.

Rationale: Since non-invasive tests for prediction of liver fibrosis have a poor diagnostic performance for detecting low levels of fibrosis, it is important to explore the diagnostic capabilities of other non-invasive tests to diagnose low levels of fibrosis. We aimed to evaluate the performance of radiomics based on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in predicting any liver fibrosis in individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: A total of 22 adults with biopsy-confirmed MAFLD, who underwent 18F-FDG PET/CT, were enrolled in this study. Sixty radiomics features were extracted from whole liver region of interest in 18F-FDG PET images. Subsequently, the minimum redundancy maximum relevance (mRMR) method was performed and a subset of two features mostly related to the output classes and low redundancy between them were selected according to an event per variable of 5. Logistic regression, Support Vector Machine, Naive Bayes, 5-Nearest Neighbor and linear discriminant analysis models were built based on selected features. The predictive performances were assessed by the receiver operator characteristic (ROC) curve analysis. Results: The mean (SD) age of the subjects was 38.5 (10.4) years and 17 subjects were men. 12 subjects had histological evidence of any liver fibrosis. The coarseness of neighborhood grey-level difference matrix (NGLDM) and long-run emphasis (LRE) of grey-level run length matrix (GLRLM) were selected to predict fibrosis. The logistic regression model performed best with an AUROC of 0.817 [95% confidence intervals, 0.595-0.947] for prediction of liver fibrosis. Conclusion: These preliminary data suggest that 18F-FDG PET radiomics may have clinical utility in assessing early liver fibrosis in MAFLD.

Clinical Characteristics and Factors Associated with Disease Progression of Mild to Moderate COVID-19 Patients in a Makeshift (Fangcang) Hospital: A Retrospective Cohort Study.

OBJECTIVE: Information regarding the epidemiology and clinical features of mild to moderate patients caused by COVID-19 in Fangcang Hospital is scarce. Through a retrospective cohort study, the clinical characteristics of COVID-19 patients in Dongxihu Fangcang shelter hospitals were analyzed, and the factors that affected the disease progression of COVID-19 patients were explored. METHODS: The clinical characteristics of 714 patients with COVID-19 were retrospectively analyzed at Dongxihu Fangcang Hospital between February 7 and March 8, 2020. We described the clinical characteristics and distribution of discharge or transfer times for each patient. According to the disease progression of COVID-19 patients, we divided all patients into Non-Deteriorated group and Deteriorated group. Furthermore, binary logistic regression was used for a single outcome and multiple response variables. RESULTS: We treated 789 patients with mild and moderate COVID-19, of which 714 were included in this study, which included 326 (45.66%) deteriorated patients and 388 (54.34%) non-deteriorated patients. The mean age of the study population was 48.16±12.44 years. Of all patients, 319 (44.7%) were men and 395 (55.3%) were women. The average length of the patient's stay was 16.08±5.13 days. The most common clinical feature on admission was fever (593 of 714, 83.05%). It is worth noting that 80 (11.20%) of the 714 patients were asymptomatic from exposure to admission. Multivariate logistic regression analysis showed that gender, age, diabetes, respiratory system disease, fever, dyspnea, and nasal congestion were risk factors associated with deterioration in cases with COVID-19 patients, and asymptomatic (OR: 0.058; 95% CI: 0.022-0.155; P<0.001) was the protective factor for deterioration of COVID-19 patients. CONCLUSION: Accompanied by chronic diseases, old age, fever, nasal congestion, and dyspnea were factors that influenced the aggravation of COVID-19 patients, and more attention and treatment should be given to these patients.

RT-PCR Combined with CT Examination in the Diagnosis and Prognosis Evaluation of COVID-19 Patients in Fangcang Hospital: A Case Series.

RATIONALE: Currently, the "gold standard" is real-time reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral DNA for diagnosis of COVID-19 infection. However, early reports of test performance in the Wuhan outbreak showed variable sensitivities. Therefore, the simple use of RT-PCR as a discharge standard for COVID-19 patients may be risky. Early discussions suggested that CT should be the preferred modality for the diagnosis of COVID-19. However, the use of CT for COVID-19 discharge is controversial. In the Fangcang hospital, we performed multiple nucleic acid tests and chest CT examinations in all patients. For discharged patients, we performed multiple nucleic acid tests and chest CT scans on the basis of discharge standards to minimize the incidence of false negatives in nucleic acid tests. PATIENT CONCERNS: Two 42-year-old male patients with mild to moderate COVID-19 were treated in the Fangcang Hospital According to the treatment, one patient was cured and discharged, while the other patient was sent to a higher-level hospital for further treatment. DIAGNOSES: Real-time reverse transcriptase-polymerase chain reaction amplification of the viral DNA for diagnosis of COVID-19 infection. INTERVENTIONS: The patients received Chinese medicine and antiviral treatment in the Fangcang Hospital. OUTCOMES: At follow-up, both patients were cured after treatment and returned to normal life after 2 weeks of home isolation and a negative nucleic acid test. LESSONS: The use of nucleic acid testing combined with chest CT examination can quickly diagnose patients with COVID-19 infection and evaluate their treatment in the Fangcang Hospital.

Multisystem involvement Langerhans cell histiocytosis in an adult: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare condition wherein Langerhans cells proliferate abnormally, adversely impacting organs including lymph nodes, bones, skin, lungs, and pituitary gland. The LCH disease course varies widely among patients from a self-limiting condition to one that progresses rapidly and culminates in death. It is uncommon for multisystem LCH to be observed in adults. Herein we describe a woman suffering from multi-system LCH involvement. CASE SUMMARY: A 37-year old Chinese woman was admitted to the hospital in June 2019 suffering from dyspnea that had progressed over the course of 5 years. Her medical history included: central diabetes insipidus (DI) that had been treated via radiotherapy, desmopressin acetate, and bromocriptine; bilateral pneumothorax with two surgeries having been performed to remove bullae; and autoimmune hepatitis that had been unsuccessfully treated using a combination of methylprednisolone and mycophenolate mofetil. A chest computed tomography (CT) scan revealed the presence of multiple pulmonary cysts of varying sizes. We re-analyzed right pulmonary bullae samples that had been removed in 2014, performed a systematic 18F-FDG PET/CT analysis, and convened a multidisciplinary medical team to diagnose and treat this patient. As a result, we were able to eventually diagnose this patient with LCH that was not associated with BRAF-V600E mutations. CONCLUSION: We hope to emphasize the importance of systemic evaluation and of cooperation between multidisciplinary physicians with the goal of improving awareness and detection of this orphan disease.

Correction: Associations of sexually transmitted infections and bacterial vaginosis with abnormal cervical cytology: A cross-sectional survey with 9090 community women in China.

[This corrects the article DOI: 10.1371/journal.pone.0230712.].

Associations of sexually transmitted infections and bacterial vaginosis with abnormal cervical cytology: A cross-sectional survey with 9090 community women in China.

BACKGROUND: Although it is well acknowledged that persistent infection with high-risk human papillomavirus types in genital sites plays a crucial role in the development of squamous cell cervical carcinoma, there is no unanimous consensus on the association between non-HPV sexually transmitted infections and abnormal cervical cytology. METHODS: In the present study, we evaluated cervical cytology status, sexually transmitted infections and bacterial vaginosis status, and collected social-demographic information among recruited participants to explore the association of STIs and bacterial vaginosis with abnormal cervical cytology. RESULTS: 9,090 women's specimens were successfully tested, with a total of 8,733 (96.1%) women had normal cytology and 357 (3.9%) women exhibited abnormal cytology. The prevalence of HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis was significantly higher in the ≥ASC-US group than the NILM group (P<0.05). Women with Neisseria gonorrhoeae infection (AOR = 5.30, 95% CIs = 1.30-21.51, P = 0.020) or bacterial vaginosis (AOR = 1.94, 95% CIs = 1.08-3.47, P = 0.026) exhibited an increased risk of abnormal cervical cytology after adjusted for carcinogenic HPV-positive status. CONCLUSIONS: Our results demonstrated that Neisseria gonorrhoeae infection in genital sites and/or bacterial vaginosis may independently increase the risk for cervical cytology abnormalities after adjusted for carcinogenic HPV-positive status. Besides, these results improved our understanding of the etiology of abnormal cervical cytology and may be useful for the management of women with ASC-US cytology.

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks second in terms of cancer mortality worldwide. Molecular magnetic resonance imaging (MRI) targeting HCC biomarkers such as alpha-fetoprotein (AFP) or glypican-3 (GPC3) offers new strategies to enhance specificity and help early diagnosis of HCC. However, the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3, which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors < 1 cm (MHCC). We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis. AIM: To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level. METHODS: A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3 (UAG) was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle (USPIO). At the same time, the singly labeled probes of anti-AFP-USPIO (UA) and anti-GPC3-USPIO (UG) and non-targeted USPIO (U) were also prepared for comparison. The physical characterization including morphology (transmission electron microscopy), hydrodynamic size, and zeta potential (dynamic light scattering) was conducted for each of the probes. The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3. First, AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry. Then, the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI (T2-weighted and T2-map) with a 3.0 Tesla clinical MR scanner. RESULTS: Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes. The iron Prussian blue staining and quantitative T2-map MRI analysis showed that, compared with UA, UG, and U, the uptake of double antigen-targeted UAG probe demonstrated a 23.3% (vs UA), 15.4% (vs UG), and 57.3% (vs U) increased Prussian stained cell percentage and a 14.93% (vs UA), 9.38% (vs UG), and 15.3% (vs U) reduction of T2 relaxation time, respectively. Such bi-specific probe might have the potential to overcome tumor heterogeneity. Meanwhile, the coupling of two antibodies did not influence the magnetic performance of USPIO, and the relatively small hydrodynamic size (59.60 ± 1.87 nm) of double antibody-conjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo, as they are slowly phagocytosed by macrophages. CONCLUSION: The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly- or non-targeted USPIO, paving the way for in vivo translation to further evaluate its clinical potential.

Correction: Population-based study of chlamydial and gonococcal infections among women in Shenzhen, China: Implications for programme planning.

[This corrects the article DOI: 10.1371/journal.pone.0196516.].

Population-based study of chlamydial and gonococcal infections among women in Shenzhen, China: Implications for programme planning.

This study was aimed to estimate the prevalences of chlamydia (CT) and gonococcal (NG) infections and explore risk factors associated with the CT infection among women in Shenzhen, China. We collected socio-demographic and clinical data from women (aged 20-60) and determined positivity of CT or NG by nucleic acid amplification test (NAAT) with self-collected urine specimens. We estimated prevalence of CT and NG and determined risk factors associated with CT infection. Among 9,207 participants, 4.12% (95% confidence interval [CI], 3.71%-4.53%) tested positive for CT and 0.17% (95% CIs, 0.09%-0.25%) for NG. Factors significantly associated with CT infection included being an ethnic minority (ethnicity other than Han China) (Adjusted odds ratio [AOR], 1.9; 95% CI, 1.2-3.0), using methods other than condom for contraception (AOR, 1.5; 95% CI, 1.2-1.8), having a history of adverse pregnancy outcomes (AOR, 1.4; 95% CI, 1.1-1.8), and experiencing reproductive tract symptoms in the past three months (AOR, 1.3; 95% CI, 1.0-1.7). we found that CT infection is prevalent among women in Shenzhen, China and associated with both demographic and behavioral factors. A comprehensive CT screening, surveillance and treatment programme targeting this population is warranted.

Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao.

Octopus is an important mollusk in human dietary for its nutritional value, however it also causes allergic reactions in humans. Major allergens from octopus have been identified, while the knowledge of novel allergens remains poor. In the present study, a novel allergen with molecular weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry. TIM aggregated beyond 45°C, and its IgE-binding activity was affected under extreme pH conditions due to the altered secondary structure. In simulated gastric fluid digestion, TIM can be degraded into small fragments, while retaining over 80% of the IgE-binding activity. The full-length cDNA of O. fangsiao TIM (1140bp) was cloned, which encodes 247 amino acid residues, and the entire recombinant TIM was successfully expressed in Escherichia coli BL21, which showed similar immunoreactivity to the native TIM. Different intensity of cross-reactivity among TIM from related species revealed the complexity of its epitopes. Eight linear epitopes of TIM were predicted following bioinformatic analysis. Furthermore, a conformational epitope (A71G74S69D75T73F72V67) was confirmed by the phage display technology. The results revealed the physicochemical and immunological characteristics of TIM, which is significant in the development of hyposensitivity food and allergy diagnosis.

Assessment of the sensitizing capacity and allergenicity of enzymatic cross-linked arginine kinase, the crab allergen.

SCOPE: The enzymatic cross-linking of an allergen by food processing may alter its sensitization potential. In this study, the IgE-binding activity and allergenicity of cross-linked thermal polymerized arginine kinase (CL-pAK) were investigated. METHODS AND RESULTS: The IgE-binding activity and stability of CL-pAK were analyzed by immunological and proteomics methods. The sensitization and potency to induce oral tolerance of CL-pAK were tested using in vivo assays and a cell model. According to the results of inhibition of ELISA, the half inhibitory concentration of AK after cross-linking changed from 1.13 to 228.36 µg/mL. The results of in vitro digestion demonstrated that CL-pAK showed more resistance to gastrointestinal digestion than native AK. Low allergenicity and capacity to induce oral tolerance in mice were shown by the sera levels of AK-specific antibodies and T-cell cytokine production. Exposure of RBL-2H3 cells to CL-pAK compared with AK, resulted in lower levels of mast degranulation and histamine. CONCLUSION: Enzymatic cross-linking with thermal polymerization of AK by tyrosinase and caffeic acid had high potential in mitigating IgE-binding activity and allergenicity, which were influenced by altering the molecular and immunological features of the shellfish protein.

Purification and Characterization of Protamine, the Allergen from the Milt of Large Yellow Croaker (Pseudosciaena crocea), and Its Components.

The protamine in fish milt can cause anaphylaxis in humans. To determine the allergen in the milt of large yellow croaker (Pseudosciaena crocea), crude extracts were incubated with sera from allergic patients. The results showed that a 12 kDa multicomponent protein was the major allergen in the milt of large yellow croaker. The multicomponent protein was purified, and physicochemical characterization showed that it was a glycoprotein, highly stable in acid-alkali conditions, and weakly retained immunoglobulin E (IgE)-binding activity at high temperatures. Separation and immunoreactivity analysis of the components of the multicomponent protein showed that it had six components, and component 5 had the strongest IgE-binding activity with patient sera. N-terminal sequencing confirmed the multicomponent protein was protamine. Following analysis of protamine from different fish by reversed-phase liquid chromatography and circular dichroism spectra, the protamines from different fish were found to have a similar secondary structure, although their components were different.

Association between Polymorphisms of the AKT1 Gene Promoter and Risk of the Alzheimer's Disease in a Chinese Han Population with Type 2 Diabetes.

AIMS: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v-akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D. METHODS: The association between AKT1 polymorphisms and AD risk in patients with T2D was assessed among 574 consecutive unrelated subjects including 112 AD patients with T2D, 231 patients with AD, and 231 healthy controls in a case-control study. The cognitive function of all subjects was assessed using MMSE. Six single nucleotide polymorphisms with minor allele frequency >0.2 (rs2498786, rs74090038, rs2494750, rs2494751, rs5811155, and rs2494752) in AKT1 promoter were analyzed by polymerase chain reaction (PCR), and the concentration of AKT1 protein in serum was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, there was statistically significant difference in AKT1 rs2498786 polymorphism. The CC frequency of AKT1 rs2498786 polymorphism in AD with T2D group and AD control group was significantly higher than that in healthy control group (PAD+T2D vs. health < 0.0001, PAD vs. health < 0.0001). However, the difference was not found between AD with T2D group and AD control group. Compared with healthy control group, the plasma levels of AKT1 protein in AD with T2D group (PAD+T2D vs. health < 0.0001) and AD control group (PAD vs. health = 0.0003) decreased significantly. Among genotypes of AKT1 rs2498786 polymorphism, the AKT1 protein level in GG genotype was significantly higher than that in GC genotype (PGG vs. GC < 0.0001) and CC genotype (PGG vs. CC < 0.0001). CONCLUSION: The study suggests that AKT1 rs2498786 polymorphism in insulin signaling pathway may be associated with AD risk and different genotypes may affects levels of protein expression. However, the polymorphism is not shown to be exclusive in AD patients with T2D.

Spatio-temporal analysis of female breast cancer incidence in Shenzhen, 2007-2012.

INTRODUCTION: Breast cancer is a leading tumor with a high mortality in women. This study examined the spatio-temporal distribution of the incidence of female breast cancer in Shenzhen between 2007 and 2012. METHODS: The data on breast cancer incidence were obtained from the Shenzhen Cancer Registry System. To describe the temporal trend, the average annual percentage change (AAPC) was analyzed using a joinpoint regression model. Spatial autocorrelation and a retrospective spatio-temporal scan approach were used to detect the spatio-temporal cluster distribution of breast cancer cases. RESULTS: Breast cancer ranked first among different types of cancer in women in Shenzhen between 2007 and 2012 with a crude incidence of 20.0/100,000 population. The age-standardized rate according to the world standard population was 21.1/100,000 in 2012, with an AAPC of 11.3%. The spatial autocorrelation analysis showed a spatial correlation characterized by the presence of a hotspot in south-central Shenzhen, which included the eastern part of Luohu District (Donghu and Liantang Streets) and Yantian District (Shatoujiao, Haishan, and Yantian Streets). Five spatio-temporal cluster areas were detected between 2010 and 2012, one of which was a Class 1 cluster located in southwestern Shenzhen in 2010, which included Yuehai, Nantou, Shahe, Shekou, and Nanshan Streets in Nanshan District with an incidence of 54.1/100,000 and a relative risk of 2.41; the other four were Class 2 clusters located in Yantian, Luohu, Futian, and Longhua Districts with a relative risk ranging from 1.70 to 3.25. CONCLUSIONS: This study revealed the spatio-temporal cluster pattern for the incidence of female breast cancer in Shenzhen, which will be useful for a better allocation of health resources in Shenzhen.

Elevated plasma homocysteine level is associated with ischemic stroke in Chinese hypertensive patients.

BACKGROUND: Accumulating data suggest that hyperhomocysteinemia is associated with the risk of ischemic stroke (IS) and coronary heart disease (CHD) in the general population, but the relationship remains unclear in hypertensive patients. We examined the association of total homocysteine (tHcy) with IS and CHD in hypertensive patients. METHODS: A total of 5935 Chinese hypertensive patients were recruited in a community-based cross-sectional study from 60 communities in Shenzhen, China. Plasma tHcy was quantitatively measured using the enzyme cycle method. Conventional risk factors for IS and CHD were obtained through questionnaire interviews and physical examinations. We included cerebral infarction, embolism and small-vessel disease as IS; and myocardial infarction, angina pectoris, coronary revascularization, and cardiac arrest as CHD. IS and CHD were retrospectively adjudicated by specialists via interviews, hospital records or relevant tests. RESULTS: Significantly higher values of tHcy were observed in IS patients than in non-IS controls among both men and women. Greater tHcy level was dose dependently associated with an increased risk of IS presence in women, men and them combined (p-trend: 0.002, 3.8×10(-4) and 0.001). The odds ratios (95% CI) of IS for tHcy ≥30 (vs. <15) µmol/L were 2.84 (1.73-4.34) in men, 4.41 (1.62-9.15) in women, and 2.86 (1.72-4.75) in their combination after adjusting for other main risk factors of IS. We did not find any significant association between tHcy and presence of CHD after the adjustment for covariates. CONCLUSIONS: Plasma homocysteine level is positively associated with the presence of IS, but not CHD, in Chinese hypertensive patients.

Disruption of mediator complex subunit 19 (Med19) inhibits cell growth and migration in tongue cancer.

BACKGROUND: Mediator complex subunit 19 (Med19) is a critical subunit of the mediator complex that forms a bridge between the transcription factors and RNA polymerase II. Although it has been reported that Med19 plays an important role in stabilizing the whole mediator complex, its biological importance in tongue cancer cell proliferation and migration has not been addressed. METHODS: By using MTT, BrdU incorporation, colony formation, flow cytometric, tumorigenesis and transwell assays, We tested the Med19 role on tongue cancer cell growth and migration. RESULTS: We demonstrated that lentivirus-mediated Med19 knockdown could arrest tongue cancer cells at G1 phase, inhibit tongue cancer cell proliferation and migration in vitro. The tumorigenicity of Med19 short hairpin RNA (shRNA)-expressing lentivirus infected tongue cancer cells were decreased after inoculating into nude mice. CONCLUSIONS: These results indicate that Med19 plays an important role in tongue cancer proliferation and migration, and suggest possible applications for tongue cancer therapy.

Vascular endothelial growth factor gene promoter polymorphisms and Alzheimer's disease risk: a meta-analysis.

AIM: Conclusions on the association between polymorphisms in the vascular endothelial growth factor (VEGF) gene promoter and risk of Alzheimer's disease (AD) are ambiguous, and sufficient evaluation of the association is lacking. Therefore, we performed a meta-analysis of observational studies to explore the association between polymorphisms in the VEGF gene promoter and AD risk. METHODS: Bibliographical searches were performed in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Three investigators independently assessed abstracts for relevant studies and independently reviewed all eligible studies. A meta-analysis was conducted using a fixed- or random-effects model. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association. All statistical analyses were performed using Stata 11.0 software. RESULTS: The meta-analysis of 2787 AD cases and 2841 controls from eight published case-control studies on the -2578C/A polymorphism and 1422 AD cases and 1063 controls from four studies on the -1154G/A polymorphism did not show any significant associations. However, in a subgroup analysis stratified by the presence of APOE є4, associations were observed with APOE ε4 (-) for -2578C/A (A vs. C: OR = 1.22, 95% CI = 1.04-1.43, P = 0.014; A/A vs. C/C: OR = 1.59, 95% CI = 1.11-2.27, P = 0.011 and A/A vs. A/C + C/C: OR = 1.46, 95% CI = 1.08-1.99, P = 0.015) and -1154G/A (A vs. G: OR = 0.74, 95% CI = 0.62-0.89, P = 0.001; A/A vs. G/G: OR = 0.57, 95% CI = 0.37-0.87, P = 0.009; A/G vs. G/G: OR = 0.69, 95% CI = 0.53-0.89, P = 0.004 and A/A + A/G vs. G/G: OR = 0.66, 95% CI = 0.52-0.85, P = 0.001). CONCLUSION: This meta-analysis showed the risk role of the -2578 polymorphism and the protective role of the -1154 polymorphism when the APOE є4 status was negative, suggesting that the two polymorphisms in the VEGF promoter may have opposing effects on AD risk in an APOE є4-independent manner.

Polymorphism -116C/G of human X-box-binding protein 1 promoter is associated with risk of Alzheimer's disease.

AIM: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum (ER) stress response. In the response, the regulator factor human X-box-binding protein 1 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid-beta (Aß) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the -116C/G polymorphism of XBP1 and the risk of AD. METHODS: The association between -116C/G polymorphism of XBP1 promoter and possible risk of AD was assessed among 276 patients with AD and 254 matched healthy individuals in a case-control study. RESULTS: Overall, there was a significantly statistical difference in genotype (P = 0.0354) and allele frequencies (P = 0.0150, OR = 1.3642, 95% CI = 1.0618-1.7528) between the AD subjects and control subjects, showing that the -116C/G polymorphism of XBP1 might lead to increased susceptibility for AD in a Chinese Han population. In addition, the -116CG and -116GG genotypes were significantly associated with increased AD risk in female (P = 0.0217) and in subjects with APOE є4 (-) (P = 0.0070) in stratified analyses, and the -116CC genotype was significantly associated with fast cognitive deterioration in the AD patients (P = 0.0270). CONCLUSION: The study supports a role for the -116C/G polymorphism of XBP1 gene in the pathogenesis of AD, and further studies with a larger sample size and detailed data should be performed in other populations.