Coffee consumption and periodontitis: a Mendelian Randomization study.

BACKGROUND: Coffee is one of the most consumed beverages in the world, coffee consumption has been growing in the United States over the past 20 years. Periodontitis is defined by the pathologic loss of the periodontal ligament and destruction of the connective tissue attachment and alveolar bone loss and is related to different systemic diseases and conditions. However, the causality has remained unclarified, thus we regarded discovering the causal relationship between coffee consumption and the liability to periodontitis as the objective of the study. METHODS: Coffee consumption was subdivided into binary coffee consumption and continuous coffee consumption to refine the study design. Genetic instruments were stretched from the MRC-IEU's (MRC Integrative Epidemiology Unit) output from the GWAS pipeline using phesant-derived variables based on the UK Biobank, the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) project, and the joint meta-analysis of a recent GWAS. The IVW (Inverse Variance Weighted) was regarded as the primary method to estimate the causality, a scatter plot revealed the intuitive result, and tests for stability were also carried out. RESULTS: An effect of continuous coffee consumption on the risk of periodontitis was found, with per SD of coffee consumed increases, the risk of periodontitis rises by 1.04% (Odds Ratio of IVW is 1.0104), while the effect of binary coffee consumption on periodontitis did not meet the requirement of indicating a strong causal association, neither were the reverse causality analyses. CONCLUSIONS: The study indicated the causality of continuous coffee consumption to the risk of periodontitis with a relatively small scale of effect estimate and no strong evidence for an effect of binary coffee-consuming behavior on periodontitis. There was also no intensive evidence suggesting reverse causality.

Association between red blood cell folate and Trichomonas vaginalis infection among women.

BACKGROUND: Increased folic acid has been found to be latently protective against gynecological infection, including several kinds of vaginosis. In this study, we laid emphasis on whether RBC (Red Blood Cell) folate was associated with the infectious ratio of Trichomonas vaginalis, a kind of anaerobic parasitic protozoan. METHODS: We set RBC folate as the exposure variable and Trichomonas vaginalis as the outcome variable. Other subsidiary variables were regarded as covariates that may work as potential effect modifiers. The cross-sectional study was conducted with two merged waves of the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004, and a sample of 1274 eligible women (1212 negative and 62 positive in Trichomonas vaginalis infection) was integrated for the exploration of the association between RBC folate and Trichomonas vaginalis infection. Multivariate regression analyses, subgroup analyses, and subsequent smooth curve fittings were conducted to estimate the relationship between RBC folate and Trichomonas vaginalis in women. RESULTS: In the multivariable logistic regression analyses, a negative association was observed between stratified RBC folate status and Trichomonas vaginalis infection with all confounders adjusted. Referencing the lowest RBC folate concentration quartile, the higher concentration quartiles reported a relatively lower infection ratio, while there was a weak correlation between total RBC folate concentration and T. vaginalis (Trichomonas vaginalis) infection. In subgroup analyses stratified by BMI and age, this association was only found significant in high age and BMI groups. CONCLUSIONS: The cross-sectional study indicated a negative association between RBC folic acid and Trichomonas vaginalis infection, and latent effects of BMI and age on the association were also found.

Clinicopathological significance of primitive phenotypes in early gastric cancer with differentiated histology.

BACKGROUND: Certain gastric cancers exhibit some primitive phenotypes, which may indicate a high malignancy. In histologically differentiated early gastric cancer (EGC), the presence and the clinicopathological significance of the primitive phenotype remain unclear. METHODS: Using immunohistochemical staining we detected the expression of three primitive phenotypic markers SALL4, Glypican-3(GPC3), and AFP in whole tissue sections of differentiated EGC (gastrectomy specimens, n = 302). For those cases with primitive phenotypes, we analyzed their clinicopathological features and evaluated whether the criteria for endoscopic resection were met. RESULTS: We found that 9.3% (28/302) of all differentiated EGC cases have primitive phenotypes, and most of these cases (25/28) exhibit a histomorphology similar to conventional differentiated EGC. Patients with primitive phenotypes had a deeper invasion, a higher rate of ulcer and lymphatic invasion than cases without primitive phenotype. Moreover, patients with primitive phenotypes displayed a significantly higher frequency of LNM than those without (57.1% vs 8.8%, P < 0.001). Multivariate analysis revealed that presence of primitive phenotypes was an independent risk factor for LNM (P = 0.001, HR 6.977, 95% CI: 2.199-22.138). Interestingly, we found 2 cases with primitive phenotypes developed LNM, and they both met the expanded indications of endoscopic resection for differentiated EGC. CONCLUSIONS: A small number of differentiated EGC have primitive phenotypes, which were closely related to LNM and were an independent risk factor for LNM. Given its highly aggressive behavior, differentiated EGC with primitive phenotypes should be evaluated with stricter criteria before endoscopic resection, or considered to give an additional surgical operation after endoscopic resection.

Jinfukang inhibits lung cancer metastasis by upregulating CX3CL1 to recruit NK cells to kill CTCs.

ETHNOPHARMACOLOGICAL RELEVANCE: Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown. AIM OF THE STUDY: To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs. MATERIALS AND METHODS: CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis. RESULTS: Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb. CONCLUSIONS: These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang.

Shift a laser beam back and forth to exchange heat and work in thermodynamics.

Although the equivalence of heat and work has been unveiled since Joule's ingenious experiment in 1845, they rarely originate from the same source in experiments. In this study, we theoretically and experimentally demonstrated how to use a high-precision optical feedback trap to combine the generation of virtual temperature and potential to simultaneously manipulate the heat and work of a small system. This idea was applied to a microscopic Stirling engine consisting of a Brownian particle under a time-varying confining potential and temperature. The experimental results justified the position and the velocity equipartition theorem, confirmed several theoretically predicted energetics, and revealed the engine efficiency as well as its trade-off relation with the output power. The small theory-experiment discrepancy and high flexibility of the swift change of the particle condition highlight the advantage of this optical technique and prove it to be an efficient way for exploring heat and work-related issues in the modern thermodynamics for small systems.

Multidisciplinary and Comprehensive Chinese Medicine for Advanced Non-Small Cell Lung Cancer Patients: A Retrospective Study of 855 Cases.

OBJECTIVE: To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis. METHODS: Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index. RESULTS: The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage IIIb-IIIc lung adenocarcinoma had the best outcomes. CONCLUSIONS: Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.

Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model.

OBJECTIVE: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe. METHODS: An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography. RESULTS: Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4+CD25+ T-cells and Foxp3+ T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells. CONCLUSION: The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.

C3-Luc Cells Are an Excellent Model for Evaluation of Cellular Immunity following HPV16L1 Vaccination.

C3 and TC-1 are the two model cell lines most commonly used in studies of vaccines and drugs against human papillomavirus (HPV) infection. Because C3 cells contain both the HPV16 E and L genes, but TC-1 cells contain only the HPV16 E genes, C3 cells are usually used as the model cell line in studies targeting the HPV16 L protein. However, expression of the L1 protein is difficult to detect in C3 cells using common methods. In our study, Short tandem repeat analysis (STR) was used to demonstrate that C3 cells are indeed derived from mice, PCR results show that HPV16 L1, E6 and E7 genes were detected in C3 genomic DNA, and RT-PCR results demonstrated that L1 transcription had occurred in C3 cells. However, the expression of C3 protein was not found in the results of western blot and immunohistochemistry (IHC). Growth and proliferation of C3 were inhibited by mice spleen lymphocytes that had been immunized with a vaccine against HPV16L1. The luciferase gene was integrated into C3 cells, and it was confirmed that addition of the exogenous gene had no effect on C3 cells by comparing cell growth and tumor formation with untransformed cells. Cells stably expressing luciferase (C3-luc) were screened and subcutaneously injected into the mice. Tumors became established and were observed using a Spectrum Pre-clinical in Vivo Imaging System. Tumor size of mice in the different groups at various time points was calculated by counting photons. The sensitivity of the animals to the vaccine was quantified by statistical comparison. Ten or 30 days following injection of the C3-luc cells, tumor size differed significantly between the PBS and vaccine groups, indicating that C3 cells were susceptible to vaccination even after tumors were formed in vivo.

One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice.

Human papillomavirus (HPV) is associated with various human diseases, including cancer, and developing vaccines is a cost-efficient strategy to prevent HPV-related disease. The major capsid protein L1, which an increasing number of studies have confirmed is typically expressed early in infection, is a promising antigen for such a vaccine, although the E6 and E7 proteins have been characterized more extensively. Thus, the L1 gene from HPV16 was inserted into a recombinant vector, AdHu5, and MVA viral vectors, and administered by prime-boost immunization. Virus-like particles were used as control antigens. Our results indicate that prime-boost immunization with heterologous vaccines induced robust and sustained cellular and humoral response specific to HPV16 L1. In particular, sera obtained from mice immunized with DNA + DNA + Ad + MVA had excellent antitumor activity in vivo. However, the data also confirm that virus-like particles can only elicit low levels cellular immunity and not be long-lasting, and are therefore unsuitable for treatment of existing HPV infections.

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: protocol for a randomized double-blind controlled trial.

BACKGROUND: Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN: This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles. Progression-free survival (PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score). Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION: Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov. (Identifier: NCT01780181).

Significance of TRIM29 and ß-catenin expression in non-small-cell lung cancer.

BACKGROUND: TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be up-regulated or be down-regulated in many cancer types, suggesting the oncogenic function of TRIM29 may be depend on different molecular signaling pathway. It was found that ß-catenin function (a key molecule in the Wnt signaling pathway) was required for TRIM29's oncogenic effects. TRIM29 gene expression was also found to be heterogeneous in non-small-cell lung cancer (NSCLC) subtypes. In this study, the possible associations of TRIM29 expression with clinicopathological factors, prognosis, and ß-catenin in human NSCLC were analyzed. METHODS: TRIM29 and ß-catenin expression of tumor and adjacent normal tissues in 251 cases of NSCLC treated by surgery was detected by the Immunohistochemical method. The relationship between clinical pathological data, ß-catenin, and TRIM29 expression was analyzed. RESULTS: TRIM29 expression of tumor tissues was significantly higher than adjacent normal tissues. Expression of TRIM29 in squamous cell carcinoma (SC) tissues was positively correlated with abnormal expression of ß-catenin, histological grade, tumor-node-metastasis (TNM) stage, and lymph node metastasis and that was positively correlated with tumor size, histological grading, TNM stage and lymph node metastasis in adenocarcinoma (AC). TRIM29 expression in SC and AC was significantly different and the intensity of poorly differentiated SC was significantly higher than that of AC. High-expression of TRIM29, poorly differentiated grade, and high clinical stage were independent prognostic indicators. CONCLUSION: We considered that TRIM29 may play a reference role in distinguish poorly differentiated AC and SC of NSCLC, combining with CK5/6 and CK7, and it could improve postoperative assessment and have the reference value for clinical treatment. The interaction between TRIM29 and ß-catenin may participate in the development of lung SC.

[Clinicopathological analysis of sudden cardiac death cases by autopsy].

OBJECTIVE: To explore the major correlation factors and cardiac pathological changes of sudden cardiac death (SCD). METHODS: The clinical and pathological profiles of 119 SCD cases at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 1985 to March 2012 were retrospectively analyzed. And the parameters of gender, age, causes of death and pathological changes of SCD were included. RESULTS: Among them, the primary etiologies were coronary atherosclerotic heart disease (n = 53, 44.5%), hypertensive heart disease (n = 9, 7.6%), myocarditis (n = 13, 10.9%), acute pulmonary embolism (n = 8, 6.7%) and myocardiopathy(n = 3, 2.5%). The heart weights of male and female cases were (407 ± 126) and (349 ± 101) g respectively. Among 53 cases of coronary heart disease, there were 28 cases (52.8%) of grade IV coronary artery atherosclerotic stenosis and 17 were involved with multiple branches. The differences of coronary artery stenosis were insignificant between gender and age (P > 0.05). Acute myocardial infarction occurred in 18 cases and 15 of them were complicated with old myocardial infarction (OMI) while there were 27 cases of simple OMI. Twenty cases (16.8%) without obvious cardiac organic pathological changes were classified as juvenile sudden unexplained death. CONCLUSIONS: Sudden and dangerous SCD frequently occurs in elders. Multiple severe coronary atherosclerotic stenosis is an important pathological hallmark of SCD.

A massive renal epithelioid angiomyolipoma with multiple metastatic lymph nodes.

A 47-year-old man presented with dull pain in the left upper abdomen for 1 year. Computed tomograph (CT) examination revealed a very large heterogeneously enhancing mass in the left kidney, measuring up to 28 cm. The mass was accompanied by several enlarged lymph nodes in the peri-aortic region. Radical nephrectomy was performed and pathologic evaluation revealed sheets of epithelioid cells and piecemeal necrosis consistent with malignant epithelioid angiomyolipoma (EAML) with regional lymph node metastases. The tumor cells were strongly positive for human melanosome-associated protein (HMB-45) on immunohistochemical staining. There was neither metastasis nor recurrence 2 years postoperatively. EAML is a rare tumor of mesenchymal tissue with potential for aggressive behavior. If this neoplasm is suspected based on CT features, EAML should be confirmed by pathology and immunohistochemistry.

Interdigitating dendritic cell tumor of the lymph node in the right submaxillary region: a case report and review of the literature.

Interdigitating dendritic cell tumor/sarcoma is an extremely rare neoplasm that mainly occurs in the lymph node, with only 51 cases reported in the literature to date. The authors report the case of a 41-year-old woman who presented with a 4-month history of a gradually enlarging painless mobile lymphadenopathy in the right submaxillary region. The lymph node mass was completely resected and was treated with 1 cycle of CHOP chemotherapy. After 10 months, she was alive with no evidence of disease. Because interdigitating dendritic cell sarcomas are rare and can show morphologic and immunohistochemical heterogeneity, correct diagnosis requires a high index of suspicion and complete pathological study.

Giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity: a distinctive form of thymic carcinoma?

Here, the authors describe a case of giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity-which could be a distinctive form of thymic carcinoma-which expressed CD5 and CD45. To the authors' knowledge, there has been no previous report on this subject. A 62-year-old woman presented with continuous pain in the left back associated with coughing and shortness of breath for more than 2 months prior to referral to the hospital. Palliative resection of a mediastinal tumor was performed. During the operation, it was found that the mass occupied most of the chest invading the chest wall, aorta, vena cava, and lung tissue. The patient soon died from diabetic complications in spite of anti-infection treatment. The tumor was composed of large areas of necrosis and anaplastic neoplastic giant cells with high mitotic activity, and osteoclast-like cells; there was marked inflammatory cell infiltration. The anaplastic neoplastic giant cells were immunoreactive for CKpan, CD5, CD45, VIM, and p53. Approximately 50% to 60% of the tumor cells showed immunoreactivity for Ki-67. In situ hybridization for Epstein-Barr virus-encoded RNA was negative for tumor cells and nonneoplastic osteoclastic giant cells. Because this tumor is very rare, extensive clinical, radiological, and morphological examinations as well as immunohistochemical studies are essential to make the diagnosis.

A randomized controlled pilot trial of "Feiji Recipe" on quality of life of non-small cell lung cancer patients.

In order to pilot a study observing the feasibility of applying the Core Quality of Life Questionnaire (QLQ-C30) version 2.0 to assess the quality of life (QOL) of patients with NSCLC treated with Feiji Recipe, a randomized, parallel controlled clinical trial was conducted in the university-affiliated hospital. Seventy inpatients who met the inclusion criteria were randomized into the study, and 60 cases were available as subjects for QOL data analysis. The subjects were randomly assigned to one of three groups: the Feiji Recipe group (A); the Feiji Recipe combined with chemotherapy group (B); and the chemotherapy group (C) in which the patients were treated with vinorelbine plus cisplatin (NP) or gemcitabine plus cisplatin (GP). QOL was assessed with the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Sixty cases that finished the questionnaires were analyzed, and we found that patients who received chemotherapy had low QOL, in terms of their global health, role, emotional, social, economic status and symptom burden including fatigue, nausea and vomiting, dyspnea, loss of appetite and abnormal bowel movements. Simultaneous treatment with Feiji Recipe and chemotherapy was able to prevent the worsening of function in terms of role, social, fatigue and global health. The Core Quality of Life Questionnaire (QLQ-C30) version 2.0 can be used to evaluate the QOL of patients with NSCLC treated by Chinese herbal medicine. Feiji Recipe might partially improve the QOL of NSCLC patients when administered alone or in combination with chemotherapy. No unexpected side effects were observed. However, further double-blinded placebo controlled studies are strongly recommended.

The expression and clinical significance of TGF-beta1 and MMP2 in human renal clear cell carcinoma.

The expression and clinical significance of transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinase-2 (MMP2) in human renal clear cell carcinoma (RCCC) were investigated. The intensity of TGF-beta1 and MMP2 expression in RCCC kidneys was significantly higher than that in normal kidneys. Expression of TGF-beta1 and MMP2 in RCCC tissues was positively correlated with pathological grade and clinical stage. There was also a significant correlation between TGF-beta1 and Msshese analyses indicate that upregulation of TGF-beta1 and MMP2 expression may occur during the progression of RCCC. Thus, TGF-beta1 and MMP2 may be useful molecular markers for evaluating prognosis in RCCC patients.