Active forgetting requires Sickie function in a dedicated dopamine circuit in Drosophila.

Forgetting is an essential component of the brain's memory management system, providing a balance to memory formation processes by removing unused or unwanted memories, or by suppressing their expression. However, the molecular, cellular, and circuit mechanisms underlying forgetting are poorly understood. Here we show that the memory suppressor gene, sickie, functions in a single dopamine neuron (DAn) by supporting the process of active forgetting in Drosophila. RNAi knockdown (KD) of sickie impairs forgetting by reducing the Ca2+ influx and DA release from the DAn that promotes forgetting. Coimmunoprecipitation/mass spectrometry analyses identified cytoskeletal and presynaptic active zone (AZ) proteins as candidates that physically interact with Sickie, and a focused RNAi screen of the candidates showed that Bruchpilot (Brp)-a presynaptic AZ protein that regulates calcium channel clustering and neurotransmitter release-impairs active forgetting like sickie KD. In addition, overexpression of brp rescued the impaired forgetting of sickie KD, providing evidence that they function in the same process. Moreover, we show that sickie KD in the DAn reduces the abundance and size of AZ markers but increases their number, suggesting that Sickie controls DAn activity for forgetting by modulating the presynaptic AZ structure. Our results identify a molecular and circuit mechanism for normal levels of active forgetting and reveal a surprising role of Sickie in maintaining presynaptic AZ structure for neurotransmitter release.

Overexpression of blaGES-1 due to a strong promoter in the class 1 integron contributes to decreased ceftazidime-avibactam susceptibility in carbapenem-resistant Pseudomonas aeruginosa ST235.

Sequence type 235 (ST235) Pseudomonas aeruginosa, harboring so-called international, high-risk, or widespread clones, is associated with relatively high morbidity and mortality, partly due to multiantibiotic and high-level antibiotic resistance. Treatment of infections caused by such strains with ceftazidime-avibactam (CZA) is often successful. However, CZA resistance in carbapenem-resistant P. aeruginosa (CRPA) strains has been consistently reported with the increasing use of this drug. Likewise, we identified thirty-seven CZA-resistant ST235 P. aeruginosa strains from among 872 CRPA isolates. A total of 10.8% of the ST235 CRPA strains were resistant to CZA. Site-directed mutagenesis, cloning, expression, and whole-genome sequencing analysis revealed that overexpression of blaGES-1, which was carried in a class 1 integron of the complex transposon Tn6584, occurred due to a strong promoter, contributing to CZA resistance. Moreover, such overexpression of blaGES-1 combined with an efflux pump resulted in high-level resistance to CZA, considerably reducing the therapeutic options available for treating infections caused by ST235 CRPA. Considering the widespread presence of ST235 P. aeruginosa strains, clinicians should be aware of the risk of CZA resistance development in high-risk ST235 P. aeruginosa. Surveillance initiatives for preventing further dissemination of high-risk ST235 CRPA isolates with CZA resistance are essential.

αO-Conotoxin GeXIVA[1,2] Suppresses In Vivo Tumor Growth of Triple-Negative Breast Cancer by Inhibiting AKT-mTOR, STAT3 and NF-κB Signaling Mediated Proliferation and Inducing Apoptosis.

Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.

[Generational differences in overweight and obesity among Chinese adult resident].

OBJECTIVE: To analyze the generational differences in overweight/obesity prevalence and central obesity prevalence among Chinese adult residents aged 20 years and above at the same ages. METHODS: A total of 38 908 healthy adult residents aged 20 years and above from "the China Health and Nutrition Survey" in 1991, 2000, 2009, and 2018 were selected for this study. Based on age at the time of the survey, the study subjects were divided into 6 age groups(20-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old) corresponding to 9 different generations of births in 10, 20, 30, 40, 50, 60, 70, 80, and 90 generations, respectively. All analyses were stratified by sex. A chi-square test was used to compare generational differences in overweight/obesity and central obesity at similar ages in populations born in different generations. Non-parametric tests were used to compare generational differences in BMI and waist circumference. RESULTS: (1) Body mass index(BMI), overweight/obesity rate, waist circumference, and central obesity rate showed unfavorable generational differences(P<0.0001) among different generations of residents at similar ages. BMI, overweight/obesity prevalence, waist circumference, and central obesity prevalence were higher in the younger generation. Overweight/obesity and central obesity occurred at an earlier age in the younger generation. (2) Generational differences in overweight/obesity rates and central obesity rates followed gender specificity. Unfavorable generational differences(P<0.0001) occurred in overweight/obesity as well as central obesity between the two oldest generations of females, with maximum differences of 15.5% and 8.0%. Unfavorable generational differences(P<0.0001) occurred in overweight/obesity between the two adjacent generations of men and in central obesity between the two youngest generations of men, with maximum differences of 19.5% and 17.0%. CONCLUSION: The prevalence of overweight/obesity and central obesity among Chinese adults showed unfavorable generational differences. The prevalence of overweight/obesity and central obesity was higher in the younger generation. The younger generation develops overweight/obesity at an earlier age.

Redox-inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry.

Radiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time. To reduce adverse effects, several redox-inducible precursors are prepared as cancer cells have elevated levels of GSH and H2O2. These precursors respond to GSH or H2O2, releasing the active photosensitizer that captures DNA abasic (AP) sites and generates DNA radical cations upon photolysis, without disrupting the redox state of cells. DNA radical cations migrate freely and are eventually trapped by H2O and O2 to yield DNA lesions, thus triggering DNA damage response. Our study suggests that direct effects of radiotherapy suppress cancer cell proliferation mainly by inducing G2/M phase cell cycle arrest, rather than promoting apoptosis. Synergistic effects of the precursor and chemotherapeutic agents are also observed in combination phototherapy. Beyond highlighting an alternative strategy for phototherapy, this proof-of-concept study affords a facile cellular platform to study the direct effects of radiotherapy.

Imaging HOCl Generation during the Mitochondria Peripheral Fission with a Tailor-Made Fluorescent Probe.

Mitochondrial fission is a highly regulated process that can affect metabolism, proliferation, and apoptosis. Division at the periphery enables damaged material to be shed into smaller mitochondria destined for mitophagy, which is found preceded by increased Ca2+ and reactive oxygen species, as well as reduced membrane potential and pH. However, the variation of hypochlorous acid (HOCl) during the peripheral fission has not been well studied, and the existing fluorescent probes are unsuitable for detecting mitochondrial HOCl because of the 0.8-fold decreased pH during this process. Herein, we design a novel CCS (changeable π-conjugation system)-based probe (ON-mito) with a dibenzo[1,4]oxazepine core, which can selectively react with HOCl at pH 6.4, generating an oxazine-containing product that emits at 660 nm. The capability of ON-mito for imaging the HOCl generation in HeLa cells during mitophagy is demonstrated under weakly acidic condition. Further, with ON-mito, we find for the first time a burst increase of the mitochondrial HOCl in COS-7 cells during peripheral fission, which may serve as an important indicator of this process. Probe ON-mito may be useful for studying mitochondrial damage under diverse conditions.

Increases in BMI contribute to worsening inflammatory biomarkers related to breast cancer risk in women: a longitudinal study.

BACKGROUND: Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. METHODS: A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. RESULTS: BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (ß = 0.019, 95% CI 0.004 to 0.034) and sOB-R (ß = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (ß = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (ß = 0.045, 95% CI 0.001 to 0.088) and overweight (ß = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (ß = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. CONCLUSIONS: A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.

Daurisoline suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting MEK1/2 kinase.

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancers and has a high mortality rate worldwide. The 5-year survival rate of ESCC patients in developing countries is <20%. Hence, there is an urgent need for developing new and effective treatments that are based on newly-discovered emerging molecules and pathways to prevent ESCC occurrence and recurrence. We investigated the effects of Daurisoline, a bis-benzylisoquinoline alkaloid extracted from the rhizome of menisperum dauricum, on ESCC cell proliferation and elucidated the molecular mechanisms underlying its functions. To explore the effects of Daurisoline on ESCC growth in vitro and in vivo, cell proliferation assays and anchorage-independent growth assays were performed and a patient-derived xenograft (PDX) model was established. Subsequently, phosphoproteomics, molecular docking analysis, pull down assays, mutation experiments and in vitro kinase assay were performed to explore the mechanism of Daurisoline's function on ESCC. Daurisoline inhibited ESCC proliferation in vitro and reduced ESCC PDX exnograft growth in vivo by reducing ERK1/2 phosphorylation. Furthermore, it directly bound to MEK1 (at Asn78 and Lys97) and MEK2 (at Asp194 and Asp212) kinases to inactivate the ERK1/2 signaling pathway. Our results suggest that Daurisoline is a dual inhibitor of MEK1 and MEK2 and suppresses ESCC growth both in vitro and in vivo by inactivating the ERK1/2 signaling pathway. This is first report on the use of MEK inhibitor for ESCC and highlights its potential applications for ESCC treatment and prevention.

EndMT-derived mesenchymal stem cells: a new therapeutic target to atherosclerosis treatment.

Cardiovascular diseases, such as coronary artery disease and stroke, are the main threats to human health worldwide. Atherosclerosis, a chronic inflammatory disorder, plays a role as an initiator of all of the above-mentioned diseases. Cell therapy for diseases has attracted widespread attention. Mesenchymal stem cells (MSCs) are a type of stem cell that still exist in adults and have the characteristics of self-renewal ability, pluripotent differentiation potential, immunomodulation, tissue regeneration, anti-inflammation and low immunogenicity. In light of the properties of MSCs, some researchers have begun to target MSCs to create a possible way to alleviate atherosclerosis. Most of these studies are focused on MSC transplantation, injecting MSCs to modulate macrophages, the key inflammatory cell in atherosclerosis plaque. According to recent studies, researchers found that endothelial-to-mesenchymal transition (EndMT) has something to do with atherosclerosis development. A new cell type MSC might also appear during the EndMT process. In this article, we summarize the characteristics of MSCs, the latest progress of MSC research and its application prospects, and in view of the process of EndMT occurring in atherosclerosis, we propose some new ideas for the treatment of atherosclerosis by targeting MSCs.

GRg1 inhibits the TLR4/NF-kB signaling pathway by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR.

BACKGROUND: Diabetic retinopathy (DR) is a common diabetic neurodegenerative disease that affects vision in severe cases. Current therapeutic drugs are ineffective for some patients with severe side effects, and ginsenoside-Rg1 (GRg1) has been shown to protect against DR and may serve as a new potential drug for DR. This study aimed to confirm the protective effect of GRg1 against DR and its molecular mechanism. METHODS: Human retinal microvascular endothelial cells (hRMECs) and rats were used to construct DR models in vitro and in vivo. Cell proliferation was detected by BrdU assays, the cell cycle was detected by flow cytometry, and TNF-α, IL-6 and IL-1ß levels were detected by ELISA. qRT‒PCR, Western blotting and immunohistochemistry were used to detect the expression of related genes and proteins, and angiogenesis assays were used to assess angiogenesis. RIP and RNA pull down assays were used to determine the relationship between miR-216a-5p and TLR4; retinal structure and changes were observed by HE staining and retinal digestive spread assays. RESULTS: GRg1 effectively inhibited HG-induced hRMEC proliferation, cell cycle progression and angiogenesis and reduced the levels of intracellular inflammatory cytokines and growth factors. HG downregulated the expression of miR-216a-5p and upregulated the expression of TLR4/NF-kB signaling pathway-related proteins. Importantly, GRg1 inhibited TLR4/NF-kB signaling pathway activation by upregulating miR-216a-5p, thereby inhibiting HG-induced cell proliferation, cell cycle progression, angiogenesis, and the production of inflammatory cytokines and growth factors. In addition, animal experiments confirmed the results of the cell experiments. CONCLUSIONS: GRg1 inhibits TLR4/NF-kB signaling by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR, providing a potential therapeutic strategy for DR.

Anti-inflammatory activity of fluorine-substituted benzo[h]quinazoline-2-amine derivatives as NF-κB inhibitors.

Excessive inflammation can cause loss of tissue or organ function, leading to a number of chronic diseases and sometimes even death. Traditional treatment strategies for inflammation have mainly involved steroidal and non-steroidal anti-inflammatory drugs, but both have increasingly prominent side effects. Nuclear factor kappa B (NF-κB) inhibitors with anti-inflammatory properties and low toxicity are a new therapeutic strategy for the treatment of inflammatory diseases. To obtain novel NF-κB inhibitors, a series of 3,4-dihydronaphthalen-1(2H)-one derivatives (DHNs 6a-s), 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives (BQAs 7a-c) and 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (BQAs 8a-p) were designed and synthesized, and characterized by NMR and HRMS. By evaluating toxicity and anti-inflammatory properties, fluorine-substituted 8c showed more potential anti-inflammatory activity and lower toxicity. 8c significantly reduced the phosphorylation of IκBα and p65, thereby inhibiting the NF-κB signaling pathway. In addition, 8c markedly decreased reactive oxygen species (ROS) production and downregulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and cysteine aspartate protein hydrolase-1 (caspase-1). Therefore, compound 8c is expected to be a candidate compound for NF-κB inhibition and deserves further research and development.

Repeated Low-Level Red-Light Therapy for Controlling Onset and Progression of Myopia-a Review.

Repeated low-level red-light (RLRL), characterized by increased energy supply and cellular metabolism, thus enhancing metabolic repair processes, has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic application in myopia. This therapeutic revolution led by RLRL therapy is due to significant advances in bioenergetics and photobiology, for instance, enormous progresses in photobiomodulation regulated by cytochrome c oxidase, the primary photoreceptor of the light in the red to near infrared regions of the electromagnetic spectrum, as the primary mechanism of action in RLRL therapy. This oxidase is also a key mitochondrial enzyme for cellular bioenergetics, especially for the nerve cells in the retina and brain. In addition, dopamine (DA)-enhanced release of nitric oxide may also be involved in controlling myopia by activation of nitric oxide synthase, enhancing cGMP signaling. Recent evidence has also suggested that RLRL may inhibit myopia progression by inhibiting spherical equivalent refraction (SER) progression and axial elongation without adverse effects. In this review, we provide scientific evidence for RLRL therapy as a unique paradigm to control myopia and support the theory that targeting neuronal energy metabolism may constitute a major target for the neurotherapeutics of myopia, with emphasis on its molecular, cellular, and nervous tissue levels, and the potential benefits of RLRL therapy for myopia.

Effects of Long-Term Wear and Discontinuation of Orthokeratology Lenses on the Eyeball Parameters in Children with Myopia.

Objective: To evaluate the effects of long-term wear and discontinuation of the orthokeratology lenses (Orth-K) on the biological parameters of eyeballs in children with myopia. Methods: In this prospective study, a total of 308 subjects with myopia were randomized to receive Orth-K (n = 154) or single vision spectacles (SVS) (n = 154) for 12 months followed by a 1-month withdrawal period. The axial length (AL), the central corneal thickness (CCT), the anterior chamber depth (ACD) and the central lens thickness (CLT) were assessed at the baseline, 6 months, 12 months, and 13 months (1-month after lens withdrawal). Results: A total of 279 subjects completed the 13-month follow-up (142 in Orth-K group and 137 in SVS group). No statistical difference was noted in AL, CCT, ACD and CLT between the two groups at the baseline (all p > 0.05). However, compared with the baseline, the AL from the two groups became elongated 12 months after wearing Orth-K or SVS. The increase of AL in Orth-K group was 0.22 ± 0.11 mm, significantly smaller than 0.35 ± 0.08 mm in SVS group (p < 0.05). In addition, CCT in Orth-K group was 544.26 ± 11.69 µm at 12 months, significantly thinner than 550.49 ± 12.13 µm in SVS group (p < 0.05). Interestingly, the change in CCT between the baseline and 1-month after withdrawal of the lens was not statistically different in either group (all p > 0.05). Furthermore, at 12-months, CLT in Orth-K group was 3.35 ± 0.21 mm, significantly thicker than 3.31 ± 0.15 mm at baseline and thicker than 3.30 ± 0.05 mm in SVS group at 12 months (all p < 0.05). Lastly, ACD was not statistically different between Orth-K and SVS groups at any time point (p > 0.05). Conclusion: Orthokeratology lenses can effectively retard axial elongation, reversibly reduce CCT, increase CLT in myopic children, but have no obvious effect on ACD, indicating that Orth-K may significantly retard myopia without noticeable myopia rebound after interruption of Orth-K.

Hippocampus segmentation after brain tumor resection via postoperative region synthesis.

PURPOSE: Accurately segmenting the hippocampus is an essential step in brain tumor radiotherapy planning. Some patients undergo brain tumor resection beforehand, which can significantly alter the postoperative regions' appearances and intensity of the 3D MR images. However, there are limited tumor resection patient images for deep neural networks to be effective. METHODS: We propose a novel automatic hippocampus segmentation framework via postoperative image synthesis. The variational generative adversarial network consists of intensity alignment and a weight-map-guided feature fusion module, which transfers the postoperative regions to the preoperative images. In addition, to further boost the performance of hippocampus segmentation, We design a joint training strategy to optimize the image synthesis network and the segmentation task simultaneously. RESULTS: Comprehensive experiments demonstrate that our proposed method on the dataset with 48 nasopharyngeal carcinoma patients and 67 brain tumor patients observes consistent improvements over state-of-the-art methods. CONCLUSION: The proposed postoperative image synthesis method act as a novel and powerful scheme to generate additional training data. Compared with existing deep learning methods, it achieves better accuracy for hippocampus segmentation of brain tumor patients who have undergone brain tumor resection. It can be used as an automatic contouring tool for hippocampus delineation in hippocampus-sparing radiotherapy.

Associations between changes of smartphone pedometer-assessed step counts and levels of obesity-related breast cancer biomarkers in non-cancer women: A population-based observational study.

While a higher level of physical activity (PA) is inversely associated with a higher breast cancer (BC) risk, the health benefits of daily steps on obesity-related BC biomarkers remain unclear. We aimed to understand the associations of changes in step counts with levels of five obesity-related BC biomarkers during a two-year follow-up. In total, 144 non-cancer women (47.96 ± 5.72) were observed on both 2019 and 2021. A structured questionnaire, daily steps and fasting blood samples were collected before (t0, 2019) and after (t1, 2021). Levels of biomarkers (IGF-binding proteins 3, adiponectin, soluble leptin receptor, C-reactive protein, and resistin) were assayed by ELISA. Participants were divided into persistent low steps, decreasing steps, increasing steps, and persistent high steps. Associations of categories on proposed biomarkers were estimated using linear regression models, with persistent low steps as reference. Associations between time-varying step counts with biomarkers were quantified using mixed linear models. Compared with persistent low steps, increasing steps is associated with a reduction in C-reactive protein level (ß=-0.74, 95%CI=-1.23--0.26, P-value = 2.98 × 10-3). An inverse association between time-varying step counts with C-reactive protein level was identified, consistent across different obesity types and baseline step level categories. No association with daily step counts was observed for other proteins.

A Small-Molecule Fluorescent Probe for the Detection of Mitochondrial Peroxynitrite.

Reactive oxygen species (ROS) are pivotal signaling molecules that control a variety of physiological functions. As a member of the ROS family, peroxynitrite (ONOO-) possesses strong oxidation and nitrification abilities. Abnormally elevated levels of ONOO- can lead to cellular oxidative stress, which may cause several diseases. In this work, based on the rhodamine fluorophore, we designed and synthesized a novel small-molecule fluorescent probe (DH-1) for ONOO-. Upon reaction with ONOO-, DH-1 exhibited a significant fluorescence signal enhancement (approximately 34-fold). Moreover, DH-1 showed an excellent mitochondria-targeting capability. Confocal fluorescence imaging validated its ability to detect ONOO- changes in HeLa and RAW264.7 cells. Notably, we observed the ONOO- generation during the ferroptosis process by taking advantage of the probe. DH-1 displayed good biocompatibility, facile synthesis, and high selectivity, and may have potential applications in the study of ONOO--associated diseases in biosystems.

[Trajectories of body mass index and risk of hypertension and blood pressure among Chinese adults].

OBJECTIVE: To explore the relationship between trajectories of body mass index(BMI) and the risk of hypertension and blood pressure among Chinese adults. METHODS: The current study was based on data from 10 waves of the China Health and Nutrition Survey from 1991 to 2018. A multistage stratified random sample was used in this study.11885 adults whose BMI had been measured at least three times were included in the study. Group-based trajectory modeling(GBTM) was used to identify the BMI trajectories in different genders, Cox regression model was used to analyze the association between BMI trajectories and the risk of incident hypertension. Generalized linear model was used to analyze the association between BMI trajectories and the blood pressure level. RESULTS: Three distinct BMI trajectories were determined for both genders: normal-stable group, normal-overweight group, obesity-stable group. The numbers of each group among males were 3595(63.23%), 1412(24.83%) and 679(11.94%), and the numbers of each group among females were 4566(73.66%), 1214(19.58%) and 419(6.76%). Taking the normal-stable group as a reference, after adjusting for confounding factors, the normal-overweight group, obesity-stable group had 1.14(1.03-1.25), P=0.01 and 1.42(1.24-1.63), P<0.01 increased risk(HR(95% CI)) of developing hypertension in male. The normal-overweight group, obesity-stable group had 1.29(1.13-1.46), P<0.01 and 1.58(1.23-2.03), P<0.01 increased risk of developing hypertension in female. Taking the normal-stable group as a reference, after adjusting for confounding factors, the systolic blood pressure[ß(95% CI)] in the male normal-overweight group and obesity-stable group increased by 3.01(1.88-4.14)mmHg, P<0.01 and 5.44(3.85-7.03)mmHg, P<0.01 respectively. The diastolic blood-pressure level was increased by 2.20(1.48-2.91)mmHg, P<0.01 and 4.04(3.04-5.04)mmHg, P<0.01 respectively. The systolic blood pressure in the female normal-overweight group and obesity-stable group were increased by 3.65(2.44-4.85)mmHg, P<0.01 and 2.96(0.97-4.94)mmHg, P<0.01 respectively. The diastolic blood pressure level was increased by 3.11(2.38-3.86)mmHg, P<0.01 and 1.25(0.03-2.47)mmHg, P=0.05 respectively. CONCLUSION: Both the trajectory of BMI increasing with age and the trajectory of maintaining a high BMI level increased the risk of hypertension, and blood pressure also increased significantly compared with those who maintained normal BMI.

[Relationship between physical activity and muscle mass loss among people aged 60 and above in 15 provinces of China in 2015].

OBJECTIVE: To analyze the relationship between physical activity and muscle mass loss among Chinese elderly aged 60 years and above in 15 provinces. METHODS: Data was collected from 2015 China Nutritional Transition Cohort Study. Information on demographic characteristics and physical activity was investigated by questionnaire. Dietary intake was estimated from three consecutive 24-h recalls for each individual. Appendicular skeletal muscle mass(ASM) was assessed using the bioelectrical impedance analysis(BIA). Skeletal muscle mass(SMI) loss was diagnosed according Asian working group of sarcopenia(AWGS) 2019 recommendation(male: SMI <7.0 kg/m~2, female: <5.7 kg/m~2). A total of 4565 participants aged 60 years and above from 15 provinces in China with complete information were included in the final analysis. Different domains(occupational, domestic, travel and leisure), light physical activity(<3.0 METs), moderate physical activity(3.0-5.9 METs) and vigorous physical activity(≥6.0 METs) of physical activity among elderly adults were evaluated. Logistic multilevel model was used to analyze the relationship between low muscle mass and different intensity of physical activity duration. RESULTS: Among all participants aged 60 years and above in 15 provinces of China in 2015, women's participation rate in domestic physical activity was 91.7%, which was higher than men's rate of 62.3%. However, men's participation rate in occupational, travel and leisure physical activity were higher than those of women. The participation rate, duration of light physical activity and moderate physical activity were higher in women than in men(light physical activity: female duration 11.0 h/week vs. male duration 3.5 h/week; female participation rate 89.9% vs. male participation rate 62.8%; moderate physical activity: female duration 7.0 h/week vs. male duration 4.7 h/week; female participation rate 90.6% vs. male participation rate 75.2%). The median vigorous physical activity was 0 h/week in both male and female group. The prevalence of muscle mass loss was 13.9% among subjects. The median weekly light physical activity and moderate physical activity in muscle mass loss group were 5.8 h and 4.7 h, which were lower than in non-muscle mass loss group(9.3 h and 6.0 h). The OR of muscle mass lass was 0.71(95%CI 0.42-0.98, P<0.05) for the male with 3.5-6.9 hours of moderate physical activity per week, compared to moderate physical activity less than 3.5 h/week. And OR of the female was 0.67(95%CI 0.47-0.95, P<0.05). CONCLUSION: The vast majority of physical activity in China among the elderly is domestic and light physical activity. Light physical activity and moderate physical activity duration increments in female and moderate physical activity duration increments in male were associated with decreased risk of muscle mass loss.

[Evaluation of the front-of-package warning labels of prepackaged food in China based on focus group discussion].

OBJECTIVE: To understand the public's perceptions and preferences on the designed front-of-package warning labels of prepackaged food, and to evaluate and identify the effective warning label. METHODS: A total of 116 participants were recruited from six provinces(autonomous regions/municipalities) in China. Focus group discussions were conducted with four types of warning labels on prepackaged food. And the score of attitude on different warning labels were compared. RESULTS: There was no difference in the total score of the four warning labels. Total score of black shield label was higher in citizen participants and college education level participants than in their respective counterparts(P<0.05). Parents or primary caregiver of children under 16 years old gave higher scores to each labels than their respective counterparts(P<0.05). The black shield label was most likely to attract the attention of the respondents, most likely to influence the decision on eating and drinking, and most likely to have an unhealthy warning effect. The yellow hexagonal label was least likely to attract the attention of the respondents, least likely to affect the decision to eat and drink food, and least likely to have an unhealthy warning effect. CONCLUSION: Black shield warning label is the most effective.

[Effect of Interactions Among Obesity-Related Proteins on Breast Cancer Risk: A Preliminary Study].

Objective: To explore the potential interactions among obesity-related proteins in the pathogenic process of breast cancer (BC) in women. Methods: We conducted a case-control study, enrolling 279 primary breast cancer cases and 260 age-frequency-matched healthy women between April 2014 and May 2015. Based on the evidence of previous published literature on obesity-related proteins and BC risks, we selected proteins that received more attention and measured the plasma levels of these proteins by enzyme-linked immunosorbent assay (ELISA). After stratification of the subjects according to their menopausal status, an analytic strategy combining multivariate logistic regression and generalized multifactor dimensionality reduction (GMDR) was used to explore the effect of the possible interactions of these proteins on BC risk. Results: There were marginal high-order interactions among insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), C-reactive protein (CRP), resistin (RETN), soluble leptin receptor (sOB-R), and adiponectin (ADP) in premenopausal women (with the balanced accuracy for the testing set being 59.01%, cross-validation consistency being 10/10, and permutation test P=0.05). There were high-order interactions among leptin (LEP), sOB-R, ADP, CRP, IGFBP3 and visfatin (VF) in postmenopausal women (with the balanced accuracy for the testing set being 67.31%, cross-validation consistency being 10/10, and permutation test P=0.01). Along with an increase in the number of obesity-related proteins to which the subjects were exposed, the risk of developing breast cancer gradually increased in both pre- and postmenopausal women ( OR pre =2.18, 95% CI: 1.69-2.82; OR post =2.41, 95% CI: 1.75-3.32). Conclusions: This preliminary study suggested high-order interactions among obesity-related proteins on BC risk in both pre- and postmenopausal women. In future studies, close attention should be given to these potential interactions when these proteins are used jointly as predictors, as well as in developing a comprehensive risk scoring system for BC.