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Abstract The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues.

Abstract Granulomatous lobular mastitis (GLM) is a chronic idiopathic granulomatous mastitis of the mammary gland characterized by significant pain and a high propensity for recurrence, the incidence rate has gradually increased, and has become a serious breast disease that should not be ignored. GLM is highly suspected relative to microbial infections, especially those of Corynebacterium species; however, the mechanisms involved are unclear, and prevention and treatment are difficult. In this study, we demonstrated the pathogenicity of Corynebacterium parakroppenstedtii in GLM using Koch’s postulates. Based on the drug sensitization results of C. parakroppenstedtii, and utilizing a retrospective study in conjunction with a comprehensive literature review, we suggested an efficacious, targeted antibiotic treatment strategy for GLM. Subsequently, we identified the pathogenic factor as a new type of glycolipid (named corynekropbactins) secreted by C. parakroppenstedtii. Corynekropbactins may chelate iron, cause the death of mammary cells and other mammary -gland-colonizing bacteria, and increase the levels of inflammatory cytokines. We further analyzed the prevalence of C. parakroppenstedtii infection in patients with GLM. Finally, we suggested that the lipophilicity of C. parakroppenstedtii may be associated with its infection route and proposed a possible model for the development of GLM. This research holds significant implications for the clinical diagnosis and therapeutic management of GLM, offering new insights into targeted treatment approaches.

Abstract Colorectal liver metastasis (CRLM) is challenging in the clinical treatment of colorectal cancer. Limited research has been conducted on how CRLM develops. RNA sequencing data were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Four machine learning algorithms were used to screen the hub CRLM-specific genes, including Least Absolute Shrinkage and Selection Operator (Lasso), Random forest, SVM-RFE, and XGboost. The model for identifying CRLM was developed using stepwise logistic regression and was validated using internal and independent datasets. The prognostic value of hub CRLM-specific genes was assessed using the Lasso-Cox method. The in vitro experiments were performed using SW620 cells. The CRLM identification model was developed based on four CRLM-specific genes (SPP1, ZG16, P2RY14, and PRKAR2B), and the model efficacy was validated using GSE41258 and three external cohorts. Five CRLM-specific prognostic hub genes, SPP1, ZG16, P2RY14, CYP2E1, and C5, were identified using the Lasso-Cox algorithm, and a risk score was constructed. The risk score was validated using the GSE39582 cohort. Three genes have both efficacy in identifying CRLM and prognostic value: ZG16, P2RY14, and SPP1. Immune infiltration and enrichment analyses demonstrated that SPP1 was associated with M2 macrophage polarization and extracellular matrix remodeling. In vitro experiments indicated that SPP1 may act as a cancer-promoting factor. The hub CRLM-specific gene SPP1 can help determine the diagnosis, prognosis, and immune infiltration of patients with CRLM.

Abstract Background Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. Methods The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. Results DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT. Conclusions PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Graphical Abstract Video Abstract

Abstract This systematic review and meta-analysis examined the association between race and ethnicity and fracture risk in the United States. We identified relevant studies by searching PubMed and EMBASE for studies published from the databases’ inception date to December 23, 2022. Only observational studies conducted in the US population that reported the effect size of racial-ethnic minority groups versus white people were included. Two investigators independently conducted literature searches, study selection, risk of bias assessment, and data abstraction; discrepancies were resolved by consensus or consultation of a third investigator. Twenty-five studies met the inclusion criteria, and the random-effects model was used to calculate the pooled effect size due to heterogeneity between the studies. Using white people as the reference group, we found that people of other races and ethnic groups had a significantly lower fracture risk. In Black people, the pooled relative risk (RR) was 0.46 (95% confidence interval (CI), 0.43–0.48, p

Recent studies suggest a shared genetic architecture between muscle and bone, yet the underlying molecular mechanisms remain elusive. This study aims to identify the functionally annotated genes with shared genetic architecture between muscle and bone using the most up-to-date genome-wide association study (GWAS) summary statistics from bone mineral density (BMD) and fracture-related genetic variants. We employed an advanced statistical functional mapping method to investigate shared genetic architecture between muscle and bone, focusing on genes highly expressed in muscle tissue. Our analysis identified three genes, EPDR1, PKDCC, and SPTBN1, which are highly expressed in muscle tissue and previously unlinked to bone metabolism. About 90% and 85% of filtered Single-Nucleotide Polymorphisms were in the intronic and intergenic regions for the threshold at P≤5×10-8 and P≤5×10-100, respectively. EPDR1 was highly expressed in multiple tissues, including muscles, adrenal glands, blood vessels, and the thyroid. SPTBN1 was highly expressed in all 30 tissue types except blood, while PKDCC was highly expressed in all 30 tissue types except the brain, pancreas, and skin. Our study provides a framework for using GWAS findings to highlight functional evidence of crosstalk between multiple tissues based on shared genetic architecture between muscle and bone. Further research should focus on functional validation, multi-omics data integration, gene-environment interactions, and clinical relevance in musculoskeletal disorders.

AbstractObjective To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids.Methods This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record.Results Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p

Objective To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).Methods 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level.Results A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14).Conclusion Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.

Abstract Background Osteoporosis is highly polygenic and heritable, with heritability ranging from 50 to 80%; most inherited susceptibility is associated with the cumulative effect of many common genetic variants. However, existing genetic risk scores (GRS) only provide a few percent predictive power for osteoporotic fracture. Methods We derived and validated a novel genome-wide polygenic score (GPS) comprised of 103,155 common genetic variants to quantify this susceptibility and tested this GPS prediction ability in an independent dataset (n = 15,776). Results Among postmenopausal women, we found a fivefold gradient in the risk of major osteoporotic fracture (MOF) (p

Abstract Past studies indicate that men are more likely to smoke and be at higher risk of smoking-related conditions than women. Our research aimed, through meta-analysis, to assess the association between smoking and fracture risk in men. The following databases were searched, including MEDLINE, EMBASE, Scopus, PsycINFO, ISI Web of Science, Google Scholar, WorldCat, and Open Grey, for identifying related studies. A random-effects model was used to pool the confounder-adjusted relative risk (R.R.). Frequentist and Bayesian hierarchical random-effects models were used for the analysis. The heterogeneity and publication bias were evaluated in this study. Twenty-seven studies met the inclusion criteria. Overall, smoking is associated with a significantly increased risk of fracture in both the frequentist approach (R.R., 1.37; 95% confidence interval: 1.22, 1.53) and the Bayesian approach (R.R., 1.36; 95% credible interval: 1.22, 1.54). Significant heterogeneity was observed in the meta-analysis (Higgin's I2 = 83%) and Cochran's Q statistic (p

BackgroundPrevious study has established two polygenic scores (PGSs) related to femoral neck bone mineral density (BMD) (PGS_FNBMDldpred) and total body BMD (PGS_TBBMDldpred) that are associated with fracture risk. However, these findings have not yet been externally validated in an independent cohort.ObjectivesThis study aimed to validate the predictive performance of the two established PGSs and to investigate whether adding PGSs to the Fracture Risk Assessment Tool (FRAX) improves the predictive ability of FRAX in identifying women at high risk of major osteoporotic fracture (MOF) and hip fractures (HF).MethodsThe study used the Women's Health Initiative (WHI) cohort of 9,000 postmenopausal women of European ancestry. Cox Proportional Hazard Models were used to assess the association between each PGS and MOF/HF risk. Four models were formulated to investigate the effect of adding PGSs to the FRAX risk factors: (1) Base model: FRAX risk factors; (2) Base model + PGS_FNBMDldpred; (3) Base model + PGS_TBBMDldpred; (4) Base model + metaPGS. The reclassification ability of models with PGS was further assessed using the Net Reclassification Improvement (NRI) and the Integrated discrimination improvement (IDI).ResultsThe study found that the PGSs were not significantly associated with MOF or HF after adjusting for FRAX risk factors. The FRAX base model showed moderate discrimination of MOF and HF, with a C-index of 0.623 (95% CI, 0.609 to 0.641) and 0.702 (95% CI, 0.609 to 0.718), respectively. Adding PGSs to the base FRAX model did not improve the ability to discriminate MOF or HF. Reclassification analysis showed that compared to the model without PGS, the model with PGS_TBBMDldpred (1.2%, p = 0.04) and metaPGS (1.7%, p = 0.05) improve the reclassification of HF, but not MOF.ConclusionsThe findings suggested that incorporating genetic information into the FRAX tool has minimal improvement in predicting HF risk for elderly Caucasian women. These results highlight the need for further research to identify other factors that may contribute to fracture risk in elderly Caucasian women.

IntroductionPersonalized Medicine (PM) holds great potential in healthcare. A few existing surveys have investigated awareness, understanding, and interest regarding PM in the general public; however, studies investigating college students' opinions about PM are lacking. This study aimed to evaluate the college student's awareness, understanding, and interest in PM, and their opinion was also analyzed by their gender and major.MethodsThe study samples were undergraduate students enrolled at the University of Nevada, Las Vegas (UNLV). A web-based survey with 42 questions was emailed to all UNLV undergraduate students. Overall survey results were analyzed by gender and each student's major. A chi-square test evaluated the significant association between responses to questions with regard to gender or major.ResultsAmong the participants, 1225 students completed the survey. This survey found that most college students had a neutral attitude to PM and were not entirely familiar with this field. For example, most students (57.6%) had a "neutral" attitude toward PM. In addition, 77.6% of students never received any personal genetic testing. More than 80% of students thought "interests" was the most important factor in using PM, and 50% of respondents chose "somewhat likely" to the recommendation about PM from the doctor. Also of importance was the finding that a significant association between the most important factor of using PM and gender was observed (p = 0.04), and the associations between a student's major affected his or her reaction to PM, how well informed she or he was about PM, his or her attitude toward a doctor's recommendation about using PM were all significant (all participant's pConclusionUNLV undergraduate students had a neutral attitude to PM and were not entirely familiar with this field.

Abstract Studies reporting trends and disparities of osteoarthritis (OA) in the United States are limited. We aimed to examine trends and disparities of OA prevalence among US adults, from 2005 to 2018. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2017–2018 were analyzed. Age-adjusted and self-reported OA prevalence, stratified by race/ethnicity and socioeconomic status (SES), was calculated separately for men and women. The linear trend and the association between the survey cycles and OA prevalence were assessed. Age-adjusted and self-reported OA prevalence linearly increased in the seven survey cycles (both Plinear trend ≤ 0.0002) in men and women. Non-Hispanic Caucasians (both Plinear trend ≤ 0.0001) in both genders and Non-Hispanic African Americans women (Plinear trend ≤ 0.0001) had significantly increasing linear trends in OA prevalence. In addition, people with lower SES had a lower age-adjusted prevalence of self-reported OA when compared to those with higher SES. The increasing linear trends still existed among both men and women after adjusting for multiple confounders (both Plinear trend ≤ 0.002). There were significant rising trends and disparities in self-reported OA prevalence among US men and women between 2005 and 2018.

Objective This survey study is designed to understand the impact of the COVID-19 pandemic on stress among specific subpopulations of college students.Design, settings and participants An online questionnaire was sent to the students from University of Nevada, Las Vegas, between October 2020 and December to assess the psychological impact of COVID-19. A total of 2091 respondents signed the consent form online and their responses were collected.Main outcome measures Measures of psychological stress, as prescribed by the Perceived Stress Scale (PSS-10). An explanatory factor analysis was carried out on the PSS-10 results. We subsequently analysed each factor using stepwise linear regression that focused on various sociodemographic groups.Results A two-factor model was obtained using the explanatory factor analysis. After comparing with the past studies that investigated the factor structure of the PSS-10 scale, we identified these two factors as ‘anxiety’ and ‘irritability’. The subsequent stepwise linear regression analysis suggested that gender and age (p

Abstract This study aimed to examine how bone health changed among T2DM patients in the past decade. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2013–2014 were analyzed to examine the trends of bone mineral density (BMD) and the prevalence trends of osteoporosis osteopenia among T2DM patients and non-diabetic people aged 40 years and older. The age- and BMI-adjusted mean BMD of the femur neck for the four NHANES cycles decreased linearly in both T2DM patients and non-diabetic people (both Plinear trend ≤ 0.009). Among women with T2DM, the mean BMD in 2013–2014 was significantly lower than that in 2005–2006, even after adjusting for multiple covariates. During 2005–2014, the prevalence of osteoporosis among T2DM patients and non-diabetic people increased but with no significant linear trend (both Plinear trend > 0.05), while the prevalence of osteopenia in the two populations increased linearly (both Plinear trend

Abstract The study aimed to utilize machine learning (ML) approaches and genomic data to develop a prediction model for bone mineral density (BMD) and identify the best modeling approach for BMD prediction. The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n = 5130) was analyzed. Genetic risk score (GRS) was calculated from 1103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop BMD prediction models separately. Ten-fold cross-validation was used for hyper-parameters optimization. Mean square error and mean absolute error were used to assess model performance. When using GRS and phenotypic covariates as the predictors, all ML models’ performance and linear regression in BMD prediction were similar. However, when replacing GRS with the 1103 individual SNPs in the model, ML models performed significantly better than linear regression (with lasso regularization), and the gradient boosting model performed the best. Our study suggested that ML models, especially gradient boosting, can improve BMD prediction in genomic data.

Abstract Exhausted CD8+ T (Tex) cells are caused by persistent antigenic stimulation during chronic viral infection or tumorigenesis. Tex cells upregulate and sustain the expressions of multiple immune inhibitory receptors (IRs). Blocking IRs of Tex cells, exemplified by PD‐1, can partially restore their effector functions and thus lead to viral suppression or tumor remission. Tex cells derived from chronic viral infections share the expression spectrum of IRs with Tex cells derived from tumors; however, whether any IRs are selectively expressed by tumor‐derived Tex cells or virus‐derived Tex cells remains to be learnt. In the study, we found that Tex cells upregulate IR natural killer cell lectin‐like receptor isoform A (NKG2A) specifically in the context of tumor but not chronic viral infection. Moreover, the NKG2A expression is attributed to tumor antigen recognition and thus bias expressed by tumor‐specific Tex cells in the tumor microenvironment instead of their counterparts in the periphery. Such dichotomous NKG2A expression further dictates the differential responsiveness of Tex cells to NKG2A immune checkpoint blockade. Therefore, our study highlighted NKG2A as a disease‐dependent IR and provided novel insights into the distinct regulatory mechanisms underlying T cell exhaustion between tumor and chronic viral infection.

P-nitrophenol (PNP) is a carcinogenic, teratogenic, and mutagenic compound that can cause serious harm to the environment. A strain of Pseudomonas putida DLL-E4, can efficiently degrade PNP in a complex process that is influenced by many factors. Previous studies showed that the expression level of pnpA, a key gene involved in PNP degradation, was upregulated significantly and the degradation of PNP was obviously accelerated in the presence of glucose. In addition, the expression of crc, crcY, and crcZ, key genes involved in catabolite repression, was downregulated, upregulated, and upregulated, respectively. To investigate the effect of the carbon catabolite repression (CCR) system on PNP degradation, the crc, crcY, and crcZ genes were successfully knocked out by conjugation experiments. Our results showed that the knockout of crc accelerated PNP degradation but slowed down the cell growth. However, the knockout of crcY or crcZ alone accelerated PNP degradation when PNP as the sole carbon source, but that knockout slowed down PNP degradation when glucose was added. The results indicate that the CCR system is involved in the regulation of PNP degradation, and further work is required to determine the details of the specific regulatory mechanism.

BackgroundPatients with coronary heart disease (CHD) often experience anxiety, but the current studies on anxiety mostly focused on a certain point in time. Therefore, this study aimed to investigate the dynamic changes of peri-procedure anxiety, status of post-procedure quality of life, and cardiovascular readmission rates in patients with CHD who undergoing elective percutaneous coronary intervention (PCI), and to analyze the influence of peri-procedure anxiety on quality of life and readmission rate after PCI.MethodsThis prospective study was conducted at Changshu NO.1 People's Hospital. A total of 220 patients with CHD undergoing elective PCI were selected as study subjects. The general information, clinical data, anxiety, quality of life and readmission of patients were collected. Multivariate linear regression was used to examine the effect of peri-procedure anxiety on quality of life, and multivariate logistic regression was used to analyze the influence of peri-procedure anxiety on readmission rate.ResultsThis study showed the anxiety scores at hospitalization appointment(T1), 3 days before procedure(T2), 1 day before procedure(T3), 1 day after procedure(T4) were 57(55,61),64(61,68),54(51.58), and 54(50,60), respectively. And, at 3 months and 6 months after PCI, the scores of Seattle Angina Questionnaire (SAQ) were 346.61(319.06,366.52) and 353.34(334.18,372.84) respectively. During 6 months follow-up, 54 cases were readmitted, with a readmission rate of 25.5%. Statistical analysis showed that T1 with anxiety (P = 0.002) and T2 with anxiety (P = 0.024) were independent risk factors for treatment satisfaction at 3 months after PCI. Anxiety in T4 (P = 0.005) was an independent risk factor on the angina frequency at 6 months after PCI. T2 with anxiety (B = 1.445, P = 0.010, 95%CI:1.409-12.773) and T4 without anxiety (B = -1.587, P = 0.042, 95%CI:-0.044-0.941) were risk factors affecting readmission for cardiovascular reasons within 6 months.ConclusionPatient anxiety at T1 and T2 affects the treatment satisfaction dimension of the SAQ at 3 months after PCI, and anxiety at T4 affects the angina frequency dimension of the SAQ at 6 months after PCI. Anxiety at T2 and no anxiety at T4 increase short-term readmission rates. In the future, interventions should be strengthened at various time points in the peri-procedure period to improve post-procedure rehabilitation effect.

Microsatellite (SSR) markers are the most popular markers for genetic analyses and molecular selective breeding in plants and animals. However, the currently available methods to develop SSRs are relatively time-consuming and expensive. One of the most factors is low frequency of polymorphic SSRs. In this study, we developed a software, SSREnricher, which composes of six core analysis procedures, including SSR mining, sequence clustering, sequence modification, enrichment containing polymorphic SSR sequences, false-positive removal and results output and multiple sequence alignment. After running of transcriptome sequences on this software, a mass of polymorphic SSRs can be identified. The validation experiments showed almost all markers (>90%) that were identified by the SSREnricher as putative polymorphic markers were indeed polymorphic. The frequency of polymorphic SSRs identified by SSREnricher was significantly higher (P < 0.05) than that of traditional and HTS approaches. The software package is publicly accessible on GitHub (https://github.com/byemaxx/SSREnricher).

PurposeThis study aimed to assess the effects of transitional health management on adherence and prognosis in elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention.MethodsWe conducted the trial from June 2016 to December 2016. A total of one hundred and fifty patients with acute myocardial infarction after PCI who met the inclusion criteria were randomly divided into an experimental (n = 75) group and a control (n = 75) group. The participants in the experimental group received transitional health management for three months. The two groups of patients were evaluated for treatment adherence, quality of life, clinical indicators, adverse cardiovascular events and statistics regarding readmission rates at baseline and 6 months after discharge.ResultsCompared with the controls, patients in the intervention group demonstrated better medication adherence, reexamination adherence, healthy lifestyle and clinical indicators (all PConclusionTransitional health management effectively improved adherence in elderly patients with acute myocardial infarction after PCI, ameliorated clinical indicators, and effectively reduced the incidence of adverse cardiovascular events and readmission rates. Transitional health management was an effective intervention for PCI patients after discharge.

Green tea (綠茶 Lǜ Chá), made from the leaves of the plant Camellia sinensis, has traditionally been used as a medicine in China for thousands of years. According to the classical work of Li Shizhen (李時珍 Lǐ Shí Zhēn) of the Ming Dynasty, “tea is cold and lowers the fire.” Since fire (inflammation) causes many diseases, could tea be effective in the prevention of many diseases? The possible prevention of chronic diseases such as cancer, metabolic syndrome, obesity, diabetes, and cardiovascular diseases has been studied with contemporary scientific methods, and the results are promising. The molecular mechanisms underlining these observations will be discussed in this presentation. One of the reasons for the failure to demonstrate a disease-preventive effect of tea in some epidemiological studies is the lower quantities of tea consumption in humans. Can we increase the quantity of tea consumption to harness its health benefits without causing gastrointestinal irritation? This is a topic for further research.

Community-acquired pneumonia (CAP) often results in severe illness and death. In large, geographically defined areas where Coccidioides spp. are endemic, coccidioidomycosis is a recognized cause of CAP, but its frequency has not been studied extensively. To determine the frequency of patients with coccidioidomycosis, we conducted a prospective evaluation of 59 patients with CAP in the Phoenix, Arizona, area. Of 35 for whom paired coccidioidal serologic testing was performed, 6 (17%) had evidence of acute coccidioidomycosis. Coccidioidal pneumonia was more likely than noncoccidioidal CAP to produce rash. The following were not found to be risk factors or reliable predictors of infection: demographic features, underlying medical conditions, duration of time spent in disease-endemic areas, occupational and recreational activities, initial laboratory studies, and chest radiography findings. Coccidioidomycosis is a common cause of CAP in our patient population. In the absence of distinguishing clinical features, coccidioidal pneumonia can be identified only with appropriate laboratory studies.

BACKGROUND:People encounter various moral issues that involve making decisions for others by giving advice. OBJECTIVE:This study investigated the characteristics of providing suggestions for oneself versus providing suggestions for others in ethical decision-making and the differences between them based on Construal Level Theory (CLT). METHODS:A total of 768 undergraduate students from three universities in China were randomly assigned to eight groups on the basis of a grid of two Construal Levels (self or others) by two different numbers of people saved (5 people or 15 people) by two problem situations (trolley problem vs. footbridge problem). The investigation examined participants' decisions to opt to take action or refrain from action that would have the consequence of saving more people. RESULTS:The main effects of Construal Level (F1, 752 = 6.46, p = .011), saving number (F1, 752 = 35.81, p < .001), and problem situation type (F1, 752 = 330.55, p < .001) were all significant. The interaction of the problem situation and saving number (F1, 752 = 1.01, p = .31), and social distance and saving number (F1, 752 = 0.85, p = .36), and interaction of the three independent factors (F1, 752 = 0.47, p = .49) were not significant. However, the interaction of social distance and problem situation (F1, 752 = 9.46, p = .002) was significant. Results indicated the participants utilized a component of utilitarian reasoning in the decision-making, and their behaviors appeared more utilitarian at low Construal Levels (CLs) compared to high. CONCLUSION:CLs, saving numbers, and problem situation significantly affected moral decision-making and exhibited significant interaction. Making decisions for oneself (low-construal) rather than giving advice to others (high-construal) was one important factor that determined whether the people were utilitarian or not. Utilitarian considerations are more relevant in impersonal dilemmas.

An outbreak of aseptic meningitis occurred in the northern area of Jiangsu Province in China from January to July in 2003. A total of 1,681 cases were involved in this outbreak, and 99% of patients were

multiple myeloma is a malignant neoplasm of plasma cells mainly affecting elderly patients. Despite the wealth of information available on therapeutic strategies, the etiology and pathogenesis of myeloma remain unclear. In the current study, a meta-analysis was conducted to assess the possible association between rheumatoid arthritis and myeloma.a literature search was conducted with PubMed, EMBASE and Web of Science for relevant studies published by December 25, 2013. Additionally, we searched annual meeting abstracts of the American Society of Hematology from 2004 to 2013. Only original studies that investigated the association between rheumatoid arthritis and myeloma were included. In total, 8 case-control and 10 cohort studies were identified for analysis.the meta-estimate of the association between rheumatoid arthritis and myeloma was 1.14 (95% CI, 0.97-1.33) overall, with significant heterogeneity among studies. The relationship between myeloma and other autoimmune diseases was additionally examined from available data. Our results showed that myeloma risk is increased 1.31 to 1.65-fold in pernicious anemia and 1.36 to 2.30-fold in ankylosing spondylitis patients.Rheumatoid arthritis does not appear to alter the risk of myeloma, while between-study heterogeneity analyses suggest caution in the interpretation of results. Pernicious anemia and ankylosing spondylitis may be potential risk factors for myeloma development. Future large-scale epidemiological studies with reliable exposure biomarkers are necessary to establish the possible contribution of autoimmune disorders to multiple myeloma.

Floating populations have been repeatedly characterized as "the tipping point" for the HIV epidemic in China. This study aims to systematically summarize and assess the effectiveness of HIV prevention interventions in floating populations in China over the past decade.We conducted a systematic search in three international databases for literature published between 2005 and 2012 with condom use as the primary outcome, and knowledge about HIV transmission and prevention and stigma towards HIV-infected individuals as secondary outcomes. The impact of interventions on changing the primary and secondary outcomes was calculated by risk difference (RD). We also performed subgroup analyses and meta-regression based on different study characteristics, using Stata 12.0, for the primary outcome.Sixteen studies (out of 149) involved 19 different programs and a total of 10,864 participants at entry from 11 provinces in China. The pooled effect estimate of all studies indicated that people participating in HIV-related interventions were 13% more likely to use condoms (95%CI: 0.07, 0.18), however, the effects on increasing condom use exhibited significant heterogeneity across programs (P

Knowledge of coping styles is useful in clinical diagnosis and suggesting specific therapeutic interventions. However, the latent structures and relationships between different aspects of coping styles have not been fully clarified. A full information item bifactor model will be beneficial to future research.One goal of this study is identification of the best fit statistical model of coping styles. A second goal is entails extended analyses of latent relationships among different coping styles. In general, such research should offer greater understanding of the mechanisms of coping styles and provide insights into coping with stress.Coping Styles Questionnaire (CSQ) and Generalized Self-Efficacy Scale (GSES) were administrated to officers suffering from military stress. Confirmatory Factor Analyses was performed to indentify the best fit model. A hierarchical item response model (bifactor model) was adopted to analyze the data. Additionally, correlations among coping styles and self-efficacy were compared using both original and bifactor models.Results showed a bifactor model best fit the data. Item loadings on general and specific factors varied among different coping styles. All items loaded significantly on the general factor, and most items also had moderate to large loadings on specific factors. The correlation between coping styles and self-efficacy and the correlation among different coping styles changed significantly after extracting the general factor of coping stress using bifactor analysis. This was seen in changes from positive (r = 0.714, p

To precisely control the application of methyl fluoride (CH3F) for analysis of methanogenic pathways, the influence of 0-10% CH3F on bacterial and archaeal communities in a thermophilic methanogenic sludge was investigated. The results suggested that CH3F acts specifically on acetoclastic methanogenesis. The inhibitory effect stabilized at an initial concentration of 3-5%, with around 90% of the total methanogenic activity being suppressed, and a characteristic of hydrogenotrophic pathway in isotope fractionation was demonstrated under this condition. However, extended exposure (12 days) to high concentrations of CH3F (>3%) altered the bacterial community structure significantly, resulting in increased diversity and decreased evenness, which can be related to acetate oxidation and CH3F degradation. Bacterial clone library analysis showed that syntrophic acetate oxidizing bacteria Thermacetogenium phaeum were highly enriched under the suppression of 10% CH3F. However, the methanogenic community did not change obviously. Thus, excessive usage of CH3F over the long term can change the composition of the bacterial community. Therefore, data from studies involving the use of CH3F as an acetoclast inhibitor should be interpreted with care. Conversely, CH3F has been suggested as a factor to stimulate the enrichment of syntrophic acetate oxidizing bacteria.

Defensins are small cationic peptides that could be used as the potential substitute for antibiotics. However, there is no efficient method for producing defensins. In this study, we developed a new strategy to produce defensin in nitrate reductase (NR)-deficient C. ellipsoidea (nrm-4). We constructed a plant expression vector carrying mutated NP-1 gene (mNP-1), a mature α-defensin NP-1 gene from rabbit with an additional initiator codon in the 5'-terminus, in which the selection markers were NptII and NR genes. We transferred mNP-1 into nrm-4 using electroporation and obtained many transgenic lines with high efficiency under selection chemicals G418 and NaNO(3). The mNP-1 was characterized using N-terminal sequencing after being isolated from transgenic lines. Excitingly, mNP-1 was produced at high levels (approximately 11.42 mg/l) even after 15 generations of continuous fermentation. In addition, mNP-1 had strong activity against Escherichia coli at 5 µg/ml. This research developed a new method for producing defensins using genetic engineering.

Circulating endothelial cells (CECs) are markers of vascular damage that have clinical relevance in many diseases, including acute myocardial infarction (AMI), and may be predictors of treatment responses. Herein, we investigated the diagnostic and prognostic value of CEC monitoring in AMI patients and a murine model.CECs were defined as Hoechst 33342(+)/CD45(-/)CD31(+)/CD146(+)/CD133(-) in human blood samples and Hoechst 33342(+)/CD45(-/)CD31(+)/KDR(+)/CD117(-) in murine samples. To evaluate the validity and variability of our CEC detection system, peripheral blood samples of vascular endothelial growth factor-treated athymic nude mice and AMI patients were collected and subjected to intra-assay analysis. CEC detection by flow cytometry and real-time PCR were compared. Blood samples were obtained from 61 AMI patients, 45 healthy volunteers and 19 samples of the original AMI patients accepted one month treatment, via flow cytometry and expressed as a percentage of peripheral blood mononuclear cells.Our CEC detection method was validated and had limited variability. CEC concentrations were higher in AMI patients compared to healthy controls. One month post-treatment, CECs levels decreased significantly.CEC levels may be useful as a diagnostic and prognostic biomarker in AMI patients.

Klotho (KL) expression is down-regulated in the renal tissues of chronic kidney disease (CKD) animal models and patients with end-stage renal disease. The putative role of KL promoter hypermethylation in the progression of CKD remains unclear. The present study aimed to determine renal and peripheral blood mononuclear cells (PBMC) levels of KL promoter methylation and analyze their relationship with clinical and histological severity in patients with CKD. Using bisulfite pyrosequencing, renal and PBMC levels of KL promoter methylation were quantified in 47 patients with CKD. 47 nephrectomy specimens of patients with renal cell carcinoma and 48 PBMC specimens of healthy volunteers were used as renal tissue and PBMC controls, respectively. Renal expression of KL protein was assayed by immunohistochemistry staining. Receiver operating characteristic (ROC) curve was used to identify the optimal cut-off value of PBMC KL promoter methylation level for renal KL promoter hypermethylation. Higher levels of KL promoter methylation were observed in renal tissue and PBMC in patients with CKD compared with controls (8.79±3.24 vs. 5.17±1.11%, P