ABSTRACT
BACKGROUND: The appropriateness of hypertension thresholds for triggering action to prevent cardiovascular and renal complications among non-White populations in the UK is subject to question. Our objective was to establish ethnicity-specific systolic blood pressure (SBP) cutoffs for ethnic minority populations and assess the efficacy of these ethnicity-specific cutoffs in predicting adverse outcomes. METHODS: We analyzed data from UK Biobank, which included 444,418 participants from White, South Asian, Black Caribbean, and Black African populations with no history of cardiorenal complications. We fitted Poisson regression models with continuous SBP and ethnic groups, using Whites as the referent category, for the composite outcome of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. We determined ethnicity-specific thresholds equivalent to the risks observed in Whites at SBP levels of 120, 130, and 140 mm Hg. We adjusted models for clinical characteristics, sociodemographic factors, and behavioral factors. The performance of ethnicity-specific thresholds for predicting adverse outcomes and associated population-attributable fraction (PAF) was assessed in ethnic minority groups. RESULTS: After a median follow-up of 12.5 years (interquartile range, 11.7-13.2), 32,662 (7.4%) participants had incident composite outcomes. At any given SBP, the predicted incidence rate of the composite outcome was the highest for South Asians, followed by White, Black Caribbean, and Black African. For an equivalent risk of outcomes observed in the White population at an SBP level of 140 mm Hg, the SBP threshold was lower for South Asians (123 mm Hg) and higher for Black Caribbean (156 mm Hg) and Black African (165 mm Hg). Furthermore, hypertension defined by ethnicity-specific thresholds was a stronger predictor and resulted in a larger PAF for composite outcomes in South Asians (21.5% [95% CI, 2.4,36.9] vs. 11.3% [95% CI, 2.6,19.1]) and Black Africans (7.1% [95% CI, 0.2,14.0] vs. 5.7 [95% CI, -16.2,23.5]) compared to hypertension defined by guideline-recommended thresholds. CONCLUSIONS: Guideline-recommended blood pressure thresholds may overestimate risks for the Black population and underestimate risks for South Asians. Using ethnicity-specific SBP thresholds may improve risk estimation and optimize hypertension management toward the goal of eliminating ethnic disparities in cardiorenal complications.
Subject(s)
Ethnicity , Hypertension , Humans , Prospective Studies , Blood Pressure , UK Biobank , Biological Specimen Banks , Minority Groups , Hypertension/epidemiology , Risk FactorsABSTRACT
BACKGROUND: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset. METHODS: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined. RESULTS: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HRwomen = 1.323 [1.064-1.644]; HRmen = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HRwomen = 1.679 [1.355-2.081]; HRmen = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HRwomen = 1.424 [1.227-1.653]; HRmen = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases. CONCLUSIONS: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background.
Subject(s)
Dementia , Sarcopenia , Male , Humans , Female , Sarcopenia/complications , Sarcopenia/epidemiology , Cohort Studies , Obesity Paradox , Obesity/complications , Obesity/epidemiology , Genetic Risk Score , Chronic Disease , Dementia/etiology , Dementia/complicationsABSTRACT
OBJECTIVE: We aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity. METHODS: We included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (aged 56 ± 7.9 years). Based on metabolic status, obesity was grouped into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes; n = 26,989; BMI 33 ± 3.3 kg/m2) and metabolically unhealthy obesity (MUO; n = 82,312; BMI 34 ± 4.0 kg/m2). PA was categorized into four groups according to moderate-to-vigorous PA (MVPA): none, low, medium, and high. Multivariable Cox regression models were used for the main analyses adjusting for sociodemographic factors, lifestyles and comorbidities. RESULTS: There were 8,059 CVD events during a median follow-up of 8.1 years. MHO was associated with a 42% reduced risk of CVD compared with MUO (HR = 0.58, 95% CI: 0.53-0.63). A significant interaction effect between PA and metabolic status on CVD risk was found. Among MUO participants, individuals with PA had significantly decreased CVD risk when compared with no MVPA (HR = 0.87, 95% CI: 0.81-0.94 for low PA; HR = 0.85, 95% CI: 0.78-0.93 for medium PA; and HR = 0.86, 95% CI: 0.80-0.92 for high PA). The lowest CVD risk was observed in MHO & medium PA group when compared with MUO & no MVPA (HR = 0.45, 95% CI: 0.37-0.56). CONCLUSIONS: Both MHO and any MVPA were associated with reduced risk of CVD in adults with obesity, while PA could modify the relationship between metabolic status and CVD risk.
Subject(s)
Cardiovascular Diseases , Exercise , Obesity , Humans , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Male , Female , Exercise/physiology , Obesity/epidemiology , Obesity/complications , United Kingdom/epidemiology , Aged , Risk Factors , AdultABSTRACT
A series of side-chain liquid crystalline polymers P4VP(CN-DBE)x , where x is the molar ratio of cyanostilbene (CN-DBE) to poly(4-vinylpyridine) (P4VP) repeating unit, was synthesized based on the intermolecular hydrogen bonding between P4VP and CN-DBE. Their luminescent property, liquid crystalline structure and photo-thermo-electric property were elucidated using photoluminescence spectra, X-ray diffraction, thermal imaging and thermoelectric experiments. With the increase of x, the supramolecular system can be changed from lamellar structure to hexagonal columnar structure. Moreover, the P4VP(CN-DBE)x polymer with columnar structure exhibits more efficient photothermal effect. The temperature of P4VP(CN-DBE)0.6 can rise to 130 °C within 10â s under the irradiation of ultraviolet lamp. In addition, the supramolecular system possesses unique photo-thermo-electric conversion ability, and 25â mA current can be detected in the circuit coupled with the thermoelectric module. This work broadens the potential applications of hydrogen-bonded polymer, and provides a simple and facile strategy to prepare liquid crystalline polymers with photo-thermo-electric property.
ABSTRACT
Previous works have shown that zearalenone (ZEA), as an estrogenic pollutant, has adverse effects on mammalian folliculogenesis. In the present study, we found that prolonged exposure of female mice to ZEA around the end of pregnancy caused severe impairment of primordial follicle formation in the ovaries of newborn mice and altered the expression of many genes in oocytes as revealed by single-cell RNA sequencing (scRNA-seq). These changes were associated with morphological and molecular alterations of mitochondria, increased autophagic markers in oocytes, and epigenetic changes in the ovaries of newborn mice from ZEA-exposed mothers. The latter increased expression of HDAC2 deacetylases was leading to decreased levels of H3K9ac and H4K12ac. Most of these modifications were relieved when the expression of Hdac2 in newborn ovaries was reduced by RNA interference during in vitro culture in the presence of ZEA. Such changes were also alleviated in offspring ovaries from mothers treated with both ZEA and the coenzyme Q10 (CoQ10), which is known to be able to restore mitochondrial activities. We concluded that impaired mitochondrial activities in oocytes caused by ZEA are at the origin of metabolic alterations that modify the expression of genes controlling autophagy and primordial follicle assembly through changes in epigenetic histones.
Subject(s)
Ovary , Zearalenone , Animals , Female , Humans , Mammals , Mice , Mitochondria , Mothers , Oocytes/metabolism , Pregnancy , RNA Interference , Zearalenone/metabolism , Zearalenone/toxicityABSTRACT
The uncertainty of lidar measured atmospheric temperature T or line-of-sight (LOS) wind V is inversely proportional to the signal-to-noise ratio (SNR) of the received photocounts. We term the proportionality constant, which depicts the efficacy of the measurement method, the single-photon (or unity SNR) measurement uncertainty for T and/or V measurement. In this study, we use the single-photon measurement uncertainty as the figure of merit to compare and understand the practical differences between Cabannes scattering (CS), Rayleigh inversion (RI), rotational Raman (RR), and laser induced fluorescence (LIF) lidars for atmospheric temperature and wind measurements, and to optimize the choice and receiver design of a lidar system for a potential application.
ABSTRACT
BACKGROUND: Ulcerative colitis is associated with intestinal inflammation and dysbiosis. Previous studies have shown that probiotics are potential agents for treatment of inflammatory bowel disease (IBD). Jiang-shui is a traditional fermented vegetable that is rich in lactic acid bacteria (LABs), but the preventive effect of LABs in jiang-shui on IBD is not yet fully understood. RESULTS: We isolated 38 LAB strains from jiang-shui, and Lactobacillus plantarum JS19 exhibited the strongest antioxidant activity among them. Our data indicate that oral administration of L. plantarum JS19 significantly inhibited body weight loss, colon shortening and damage, and reduced the disease activity index score in the mice with dextran sulfate sodium (DSS)-induced colitis. In addition, L. plantarum JS19 also alleviated inflammatory responses and oxidative stress through reducing lipid peroxidation, tumor necrosis factor-α expression, and myeloperoxidase activity and enhancing the antioxidant enzyme activity. Importantly, L. plantarum JS19 significantly rebalanced DSS-induced dysbiosis of gut microbiota. CONCLUSION: L. plantarum JS19 may be used as a potential probiotic to prevent IBD, particularly ulcerative colitis. © 2022 Society of Chemical Industry.
Subject(s)
Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Lactobacillus plantarum , Probiotics , Mice , Animals , Lactobacillus plantarum/physiology , Dextran Sulfate/adverse effects , Dysbiosis/metabolism , Colitis/chemically induced , Inflammatory Bowel Diseases/microbiology , Colon , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
Polyphenol oxidase (PPO) is a metalloenzyme with a type III copper core that is abundant in nature. As one of the most essential enzymes in the tea plant (Camellia sinensis), the further regulation of PPO is critical for enhancing defensive responses, cultivating high-quality germplasm resources of tea plants, and producing tea products that are both functional and sensory qualities. Due to their physiological and pharmacological values, the constituents from the oxidative polymerization of PPO in tea manufacturing may serve as functional foods to prevent and treat chronic non-communicable diseases. However, current knowledge of the utilization of PPO in the tea industry is only available from scattered sources, and a more comprehensive study is required to reveal the relationship between PPO and tea obviously. A more comprehensive review of the role of PPO in tea was reported for the first time, as its classification, catalytic mechanism, and utilization in modulating tea flavors, compositions, and nutrition, along with the relationships between PPO-mediated enzymatic reactions and the formation of functional constituents in tea, and the techniques for the modification and application of PPO based on modern enzymology and synthetic biology are summarized and suggested in this article.
Subject(s)
Camellia sinensis , Catechol Oxidase/metabolism , Oxidation-Reduction , TeaABSTRACT
OBJECTIVE: To develop an alarm device for the mechanical compression device displacement (MCD), and further evaluate its effectiveness in clinical use. MATERIAL AND METHODS: The alarm device is mainly composed of buzzer, indicator light, magnetic sheet. This is a prospective randomized and controlled study. Four hundred patients who met the inclusion/exclusion criteria were included and randomly assigned to two groups (MCD group vs alarm + MCD group). The primary outcome measures were the sensitivity and specificity of the alarm device to detect MCD displacement, time to hemostasis (TTH), time to ambulation (TTA), time to hospital discharge (TTHD), hospital costs (HC), complication rates, and patient satisfaction. RESULTS: The sensitivity and specificity of the alarm device in detecting MCD displacement were 94.44% and 88.46%, respectively. The study group achieved shorter TTH (p = .034), shorter TTA (p = .021), lower complication rates (p = .025), and better patients' satisfaction (p < .001) compared to the control group. However, no significant difference was observed in TTHD (p = .361) and HC (p = .583). CONCLUSION: The alarm device is highly sensitive in detecting MCD displacement, while achieving better clinical outcomes compared with artificial monitoring.
Subject(s)
Femoral Artery , Hemostatic Techniques , Humans , Femoral Artery/surgery , Prospective Studies , Hemostasis , Punctures , Treatment OutcomeABSTRACT
OBJECTIVE: To analyze the timing of supplementary food and its effect on the development of infants at 6-8 months of age. METHODS: A total of 168 breastfed healthy infants in Beijing and Chenzhou were selected and followed up from birth to 8 months of age. According to the time of the first supplementary food addition, the survey subjects were divided into a reasonable supplementary food group and an unreasonable supplementary food group. Repeated measures analysis was used to compare the differences in the Z scores of the two groups of infants. RESULTS: Infants who added complementary food between 4-6 months accounted for 80.4%(n=135). There were 6.0%(n=10) of infants who added complementary food for more than 8 months of age(added too late), and the timing was earlier than 4 months old infants accounted for 6.5%(n=11). The result of repeated measurement analysis showed that the body mass index for age Z score(BAZ) of infants whose complementary foods were added at an unreasonable time was different from that of infants with reasonable complementary food addition(P=0.046). Infants whose complementary food was added at an unreasonable time had higher BAZ at the age of 6 months(ß=0.615, 95%CI 0.053-1.178). CONCLUSION: Few infants add complementary foods too early or too late, and the timing of complementary foods for most infants was between 4-6 months of age. Unreasonable complementary food addition time might have a short-term impact on the infants' BAZ.
Subject(s)
Breast Feeding , Infant Food , Female , Humans , Infant , Child Development , Infant Nutritional Physiological Phenomena , Body Mass IndexABSTRACT
Benzo[a]pyrene (B[a]P) is a typical complete carcinogen in tobacco, but its mechanism of inducing the development of chronic pneumonia and consequent lung cancer is unclear. Here we elucidated the role of myeloid-derived suppressor cells (MDSCs) in developing B[a]P-induced chronic lung inflammation and efficacy of immunotherapy in preventing subsequent malignant transformation. Our study showed that as B[a]P could induce the accumulation of MDSCs in lung tissues and enhance the immunosuppressive effect regulated by cytokines and metabolites, thereby promoting the formation of immunosuppressive microenvironment, where effector T cells were exhausted, NK cells were dysfunctional, regulatory T (Treg) cells were expanded, polarized alveolar macrophages were transformed from M1 to M2. Subsequently, we performed the immunotherapy to block TNFÉ only or both TNFÉ and PD-1 at the early- or middle-stage of B[a]P-induced chronic lung inflammation to ameliorate the immunosuppressive microenvironment. We found that TNFÉ antagonist alone or with PD-1 blocker was shown to exert therapeutic effects on malignant transformation at the early stage of B[a]P-induced chronic lung inflammation. Taken together, our findings demonstrated that B[a]P-induced chronic lung inflammation resulted in the accumulation of MDSCs in lung tissues and exercise their immunosuppressive functions, thereby developing an immunosuppressive microenvironment, thus TNFÉ antagonist alone or with PD-1 blocker could prevent or retard the malignant transformation of B[a]P-induced chronic lung inflammation.
Subject(s)
Lung Neoplasms , Myeloid-Derived Suppressor Cells , Pneumonia , Humans , Lung Neoplasms/chemically induced , Lung Neoplasms/metabolism , Lung Neoplasms/prevention & control , Pneumonia/chemically induced , Pneumonia/drug therapy , Pneumonia/prevention & control , Programmed Cell Death 1 Receptor/metabolism , Tumor Microenvironment , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.
Subject(s)
Histiocytosis, Langerhans-Cell/diagnosis , Adult , Aged , Cytarabine/therapeutic use , Female , Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/therapy , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
The use of chimeric antigen receptor-modified T cells (CAR T cells) is an effective therapy for advanced cancer, especially hematological malignancies, and this method has attracted widespread attention in the last several years. The type, number and vitality of the effector cells clearly play important roles in this approach. In this study, to expand the possibility of curing cancer through adoptive cell therapy (ACT), we developed a novel method for effectively obtaining abundant T cells in vitro. The fusion proteins of three cytokines, SA-hIL-2, SA-hIL-7 and SA-hIL-21, were anchored onto biotin magnetic beads to increase the number of cytokines on the surface of the magnetic beads, which increased the local concentration of cytokines and thus promoted the binding of cytokines to T cells. Next, we examined the effects of these modified magnetic beads on the proliferation rate of T cells and CD19 CAR T cells. In this study, we report the expression and purification of the active bifunctional fusion proteins SA-hIL-2, SA-hIL-7 and SA-hIL-21, which were bound to biotin magnetic beads to develop a platform that was employed to increase the local concentration of cytokines. When the cells had been cultured for 14 days, the proliferation rate of the CD3+ T cells in the group that received cytokine-coupled biotin magnetic beads (Beads-SA-CK) was higher than that of the cells in the groups that received soluble cytokines (Soluble-SA-CK) and that of the cells in the standard group (Standard-CK). We speculate that this difference may be the result of the increased expression of Bcl-2 and the increased phosphorylation of Stat5. Moreover, our results preliminarily indicate that compared with the other two treatments, Soluble-SA-CK and Standard-CK, adding cytokine-coupled biotin magnetic beads more effectively increases the proliferation rate of CD19 CAR-T cells. As expected, the CD19 CAR-T cells stimulated by Beads-SA-CK had a stronger anticancer effect than the cells stimulated by the other two treatments. An effective method of preparing abundant T cells in vitro was developed, and it may provide a novel strategy for ACT.
Subject(s)
Cell Culture Techniques/methods , Cell Proliferation , T-Lymphocytes/physiology , Animals , Antigens, CD19/genetics , Antigens, CD19/metabolism , Cytokines/metabolism , Cytotoxicity, Immunologic , Humans , Immunotherapy, Adoptive/methods , K562 Cells , Lymphocyte Activation , Male , Mice , Mice, Inbred NOD , Mice, Transgenic , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/cytologyABSTRACT
To investigate the effect of sea buckthorn puree consumption on reducing blood lipid and other risk factors of CVD. A total of 111 patients with hypercholesteromia who were treated with 90 ml sea buckthorn puree or placebo for 90 days were enrolled in this trial. Physical examination and analysis of lipid markers, hsCRP concentrations and cell adhesion protein concentrations with fasting blood samples were performed at 0-day, 45-day and 90-day after treatment. We found that the sea buckthorn puree did not affect the levels of serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG). However, the level of HDL-C was decreased by sea buckthorn puree in a short period (first 6 weeks), which was increased in the last 6 weeks (p < 0.05). Compared with placebo, diastolic blood pressure (DBP) was decreased after taking sea buckthorn puree (p > 0.05). There was moderately decreased in hsCRP concentration in sea buckthorn group. Nevertheless, there was no correlation between changes in ICAM-1 and VCAM-1 concentration. In conclusion, long term consumption of sea buckthorn puree has anti-inflammatory and anti-hypertensive effects on hypercholesterolemia in hypercholesterolemic patients. However, it did not translate into an effect on the concentration of lipid markers in the circulation.
Subject(s)
Cardiovascular Diseases , Hippophae , Hypercholesterolemia , Animals , Antihypertensive Agents/therapeutic use , C-Reactive Protein/analysis , C-Reactive Protein/therapeutic use , Cardiovascular Diseases/drug therapy , Cholesterol, LDL/therapeutic use , Hypercholesterolemia/drug therapy , Intercellular Adhesion Molecule-1/therapeutic use , Lipids , Risk Factors , Triglycerides , Vascular Cell Adhesion Molecule-1/therapeutic useABSTRACT
Halophilic phage are a type of virus that exist in salty environments within halophilic archaeal or bacterial hosts. However, relatively few reports on halophilic bacteriophages exist, and our overall understanding of halophilic bacteriophages is quite limited. We used SYBR Green I fluorescent staining to detect the abundance of viruses in Yuncheng Saline Lake, China. Using the double-layer plate method, a lytic phage that could infect halophilic bacterium Salinivibrio sp. YM-43 was isolated and named YXM43. We studied host range, optimal host, morphological characteristics, nucleic acid type, protein composition, and other biological characteristics of the virus. Results reveal a high abundance of this halophilic virus in Yuncheng Saline Lake. The newly isolated bacteriophage YXM43 has a narrow host range, with the most suitable host being Virgibacillus sp. SK39. After purification and enrichment, YXM43 is observed as a spherical particle with a diameter of approximately 30 nm, with no tail. No lipid envelope can be seen in YXM43. The capsid protein of the virus can be separated into seven proteins with molecular weights ranging from 62.0 to 13.0 kDa. YXM43 is a DNA virus with a genome approximately 23 kb. The virus is tolerant of low salinity, and its activity is highest at a temperature of 60 °C and a pH of 10. YXM43 is temperature and pH tolerant, and can adapt to environmental change, even withstanding chloroform treatment. The results indicate that bacteriophage YXM43 is a novel halophilic bacteriophage with broad tolerance to environmental change.
ABSTRACT
Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti-interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P < .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Castleman Disease/drug therapy , Adult , Aged , Castleman Disease/mortality , Cyclophosphamide/administration & dosage , Female , Humans , Male , Middle Aged , Prednisone/administration & dosage , Survival Analysis , Thalidomide/administration & dosage , Treatment OutcomeABSTRACT
Using an atomic/molecular vapor as an aerosol blocking filter for atmospheric temperature measurements with a Cabannes lidar is revisited. Different problems in previously used barium and iodine filters prevented them from delivering the 78 times signal advantage (8.8 times less uncertainty) over rotational Raman lidar. We conclude that, despite the sensitivity optimization in rotational Raman lidar, a proposed Cabannes lidar utilizing potassium vapor filters can have 6.1 times less temperature uncertainty. By tuning the laser frequency cyclically to above and below the potassium D1 transition, the lidar system can measure temperature and wind simultaneously.
ABSTRACT
Natural and synthetic environmental estrogens (EEs), interfering with the physiological functions of the body's estrogens, are widespread and are rising much concern for their possible deleterious effects on human and animal health, in particular on reproduction. In fact, increasing evidence indicate that EEs can be responsible for a variety of disfunctions of the reproductive system especially in females such as premature ovarian insufficiency (POI). Because of their great structural diversity, the modes of action of EEs are controversial. One important way through which EEs exert their effects on reproduction is the induction of apoptosis in the ovary. In general, EEs can exert pro-and anti-apoptotic effects by agonizing or antagonizing numerous estrogen-dependent signaling pathways. In the present work, results concerning apoptotic pathways and diseases induced by representative EEs (such as zearalenone, bisphenol A and di-2-ethylhexyl phthalate), in ovaries throughout development are presented into an integrated network. By reviewing and elaborating these studies, we propose inflammatory factors, centered on the production of tumor necrosis factor (TNF), as a major cause of the induction of apoptosis by EEs in the mammalian ovary. As a consequence, potential strategies to prevent such EE effect are suggested.
Subject(s)
Cytokines , Ovary , Animals , Apoptosis , Estrogens/toxicity , Female , Humans , Signal TransductionABSTRACT
The World Health Organization recommends that women exclusively breastfeed until their babies are 6 months old and continue to breastfeed while introducing complementary foods. A meta-aggregation methodology was used to systematically review and synthesise the qualitative studies on factors influencing breastfeeding practices of healthy Chinese women in Greater China. English and Chinese databases were searched to identify peer-reviewed qualitative studies (published 2008-2019). Relevant data were extracted, and key themes related to factors influencing breastfeeding practices were identified. Of 7587 articles identified, 22 qualitative studies met inclusion criteria for the review, 10 of which were published in Chinese. A total of 87 themes were extracted from all included studies and classified into 9 subcategories: government enactment of policies, implementation of policies in workplaces, social expectations, social support, medical and health services, services with Chinese characteristics, breastfeeding and pumping facilities, maternal perceptions of breastfeeding and self-efficacy to breastfeed. The nine subcategories were then grouped into four categories. Potential effect associations among these influence factors of breastfeeding practices emerged from categories and subcategories. Family members' influence on breastfeeding motivation and self-efficacy suggest a potential benefit of breastfeeding promotion interventions targeting the whole family. The role of primary care should be fully exploited in breastfeeding promotion, including both prenatal education and post-partum visits. Standardising the training and qualifications of maternity matrons (yuesao) and folk breastfeeding specialists (cuirushi) can promote evidence-based approaches to facilitating breastfeeding during the confinement period. Increased availability of breastfeeding and pumping facilities in the workplace would facilitate continuing breastfeeding after returning to work.
Subject(s)
Breast Feeding , Social Support , China , Female , Humans , Infant , Postpartum Period , Pregnancy , Qualitative ResearchABSTRACT
OBJECTIVE: To investigate the level of yogurt intake in the Chinese population and its relationship between the level of yogurt intake and metabolic syndrome. METHODS: Samples were taken from populations in 8 cities in China. Dietary surveys, physical examinations, and blood sample were collected. The level of yogurt intake of the population were calculated and evaluated. The relationship between yogurt intake and metabolic syndrome and its components was analyzed by multiple logistic regression. The yogurt intake was investigated using a diet frequency questionnaire to record the frequency and intake of yogurt in the past month. RESULTS: A total of 1508 respondents were included in this study, including 538 males and 970 females; the average age was 51.74 years; the distribution ratio in the North and South regions was 5â¶4.The rate of Chinese population in 8 cities which eat yogurt was 50.1%. The intake of yogurt was 3.7 g/d. Yogurt accounts for 27.22% of dairy products. There were differences in the distribution of different yogurt intake groups in different genders, age groups, Body Mass Index(BMI)groups, regions, education levels, monthly income, and smoking. The differences in calcium, fruit, and total dairy product intake among different yogurt intake groups were statistically significant difference. Sample analysis found that yogurt intake was negatively correlated with metabolic syndrome and its components. We adjusted gender, age group, body mass index group, region, education grade, monthly income, smoking, total energy, protein, fat, Ca, fruit, total dairy products for multi-factor analysis and found that this negative correlation was weakened. But this negative correlation remained on abnormal blood glucose[OR=0.61(95%CI 0.42-0.89)]. CONCLUSION: The yoghurt intake of Chinese residents is low. The intake of yogurt has a negative correlation with abnormal blood glucose.