The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer's disease.

Maintaining mitochondrial homeostasis is crucial for cell survival and organismal health, as evidenced by the links between mitochondrial dysfunction and various diseases, including Alzheimer's disease (AD). Here, we report that lncMtDloop, a non-coding RNA of unknown function encoded within the D-loop region of the mitochondrial genome, maintains mitochondrial RNA levels and function with age. lncMtDloop expression is decreased in the brains of both human AD patients and 3xTg AD mouse models. Furthermore, lncMtDloop binds to mitochondrial transcription factor A (TFAM), facilitates TFAM recruitment to mtDNA promoters, and increases mitochondrial transcription. To allow lncMtDloop transport into mitochondria via the PNPASE-dependent trafficking pathway, we fused the 3'UTR localization sequence of mitochondrial ribosomal protein S12 (MRPS12) to its terminal end, generating a specified stem-loop structure. Introducing this allotropic lncMtDloop into AD model mice significantly improved mitochondrial function and morphology, and ameliorated AD-like pathology and behavioral deficits of AD model mice. Taken together, these data provide insights into lncMtDloop as a regulator of mitochondrial transcription and its contribution to Alzheimer's pathogenesis.

Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence.

Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear. Through a bioinformatics approach that allows integrated analyses of multiple single-nucleus transcriptome datasets from human brain samples, these rare cell populations were identified and selected for further characterization. Our analyses indicated that these cell cycle-related events occur predominantly in excitatory neurons and that cellular senescence is likely their immediate terminal fate. Quantitatively, the number of cell cycle re-engaging and senescent neurons decreased during the normal brain aging process, but in the context of late-onset Alzheimer's disease (AD), these cells accumulate instead. Transcriptomic profiling of these cells suggested that disease-specific differences were predominantly tied to the early stage of the senescence process, revealing that these cells presented more proinflammatory, metabolically deregulated, and pathology-associated signatures in disease-affected brains. Similarly, these general features of cell cycle re-engaging neurons were also observed in a subpopulation of dopaminergic neurons identified in the Parkinson's disease (PD)-Lewy body dementia (LBD) model. An extended analysis conducted in a mouse model of brain aging further validated the ability of this bioinformatics approach to determine the robust relationship between the cell cycle and senescence processes in neurons in this cross-species setting.

Determination of the ideal plate for medial femoral condyle fracture fixation: an anatomical fit and biomechanical study.

BACKGROUND: The aim of this study is to determine the best plate to use as a substitute to fix a medial femoral condyle fracture. MATERIALS AND METHODS: The first part is to measure the best fit between several anatomical plates including the Proximal Tibia Anterolateral Plate (PT AL LCP), the Proximal Tibia Medial Plate (PT M LCP), the Distal Tibia Medial Locking Plate (DT M LCP) and the Proximal Humerus (PHILOS) plate against 28 freshly embalmed cadaveric distal femurs. Measurements such as plate offset and number of screws in the condyle and shaft shall be obtained. The subsequent part is to determine the compressive force at which the plate fails. After creating an iatrogenic medial condyle fracture, the cadavers will be fixed with the two plates with the best anatomical fit and subjected to a compression force using a hydraulic press. RESULTS: The PT AL LCP offered the best anatomical fit whereas the PHILOS plate offered the maximal number of screws inserted. The force required to create 2 mm of fracture displacement between the two is not statistically significant (LCP 889 N, PHILOS 947 N, p = 0.39). The PT AL LCP can withstand a larger fracture displacement than the PHILOS (LCP 24.4 mm, PHILOS 17.4 mm, p = 0.004). DISCUSSION AND CONCLUSION: Both the PT AL LCP and the PHILOS remain good options in fixing a medial femoral condyle fracture. Between the two, we would recommend the PT AL LCP as the slightly superior option.

CAG RNAs induce DNA damage and apoptosis by silencing NUDT16 expression in polyglutamine degeneration.

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 (NUDT16) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.

Cross-talk between DNA damage response and the central carbon metabolic network underlies selective vulnerability of Purkinje neurons in ataxia-telangiectasia.

Cerebellar ataxia is often the first and irreversible outcome in the disease of ataxia-telangiectasia (A-T), as a consequence of selective cerebellar Purkinje neuronal degeneration. A-T is an autosomal recessive disorder resulting from the loss-of-function mutations of the ataxia-telangiectasia-mutated ATM gene. Over years of research, it now becomes clear that functional ATM-a serine/threonine kinase protein product of the ATM gene-plays critical roles in regulating both cellular DNA damage response and central carbon metabolic network in multiple subcellular locations. The key question arises is how cerebellar Purkinje neurons become selectively vulnerable when all other cell types in the brain are suffering from the very same defects in ATM function. This review intended to comprehensively elaborate the unexpected linkages between these two seemingly independent cellular functions and the regulatory roles of ATM involved, their integrated impacts on both physical and functional properties, hence the introduction of selective vulnerability to Purkinje neurons in the disease will be addressed.

Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Insulin stimulates atypical protein kinase C-mediated phosphorylation of the neuronal adaptor FE65 to potentiate neurite outgrowth by activating ARF6-Rac1 signaling.

Neurite outgrowth is a fundamental process in neurons that produces extensions and, consequently, neural connectivity. Neurite damage and atrophy are observed in various brain injuries and disorders. Understanding the intrinsic pathways of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration. Insulin is a pivotal hormone in the regulation of glucose homeostasis. There is increasing evidence for the neurotrophic functions of insulin, including the induction of neurite outgrowth. However, the associated mechanism remains elusive. Here, we demonstrate that insulin potentiates neurite outgrowth mediated by the small GTPases ADP-ribosylation factor 6 (ARF6) and Ras-related C3 botulinum toxin substrate 1 (Rac1) through the neuronal adaptor FE65. Moreover, insulin enhances atypical protein kinase Cι/λ (PKCι/λ) activation and FE65 phosphorylation at serine 459 (S459) in neurons and mouse brains. In vitro and cellular assays show that PKCι/λ phosphorylated FE65 at S459. Consistently, insulin potentiates FE65 S459 phosphorylation only in the presence of PKCι/λ. Phosphomimetic studies show that an FE65 S459E mutant potently activates ARF6, Rac1, and neurite outgrowth. Notably, this phosphomimetic mutation enhances the FE65-ARF6 interaction, a process that promotes ARF6-Rac1-mediated neurite outgrowth. Likewise, insulin treatment and PKCι/λ overexpression potentiate the FE65-ARF6 interaction. Conversely, PKCι/λ knockdown suppresses the stimulatory effect of FE65 on ARF6-Rac1-mediated neurite outgrowth. The effect of insulin on neurite outgrowth is also markedly attenuated in PKCι/λ knockdown neurons, in the presence and absence of FE65. Our findings reveal a novel mechanism linking insulin with ARF6-Rac1-dependent neurite extension through the PKCι/λ-mediated phosphorylation of FE65.

Determining meteorologically-favorable zones for seasonal influenza activity in Hong Kong.

Investigations of simple and accurate meteorology classification systems for influenza epidemics, particularly in subtropical regions, are limited. To assist in preparing for potential upsurges in the demand on healthcare facilities during influenza seasons, our study aims to develop a set of meteorologically-favorable zones for epidemics of influenza A and B, defined as the intervals of meteorological variables with prediction performance optimized. We collected weekly detection rates of laboratory-confirmed influenza cases from four local major hospitals in Hong Kong between 2004 and 2019. Meteorological and air quality records for hospitals were collected from their closest monitoring stations. We employed classification and regression trees to identify zones that optimize the prediction performance of meteorological data in influenza epidemics, defined as a weekly rate > 50th percentile over a year. According to the results, a combination of temperature > 25.1℃ and relative humidity > 79% was favorable to epidemics in hot seasons, whereas either temperature < 16.4℃ or a combination of < 20.4℃ and relative humidity > 76% was favorable to epidemics in cold seasons. The area under the receiver operating characteristic curve (AUC) in model training achieved 0.80 (95% confidence interval [CI], 0.76-0.83) and was kept at 0.71 (95%CI, 0.65-0.77) in validation. The meteorologically-favorable zones for predicting influenza A or A and B epidemics together were similar, but the AUC for predicting influenza B epidemics was comparatively lower. In conclusion, we established meteorologically-favorable zones for influenza A and B epidemics with a satisfactory prediction performance, even though the influenza seasonality in this subtropical setting was weak and type-specific.

Delta Infection After Vaccination Elicits Potent Neutralizing Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.

Antibody and T-cellular response to COVID-19 booster vaccine in SARS-CoV-1 survivors.

The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.

Prognostic significance of abdominal obesity and its post-diagnosis change in a Chinese breast cancer cohort.

PURPOSE: It is well-known that obesity has an adverse impact on breast cancer prognosis; nonetheless, the prognostic role of abdominal obesity, especially its post-diagnosis change, has been understudied. This study aims to examine the prospective associations of general and abdominal obesity and their post-diagnosis changes with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence in Chinese breast cancer patients. METHODS: From 2011 to 2014, 1460 Chinese breast cancer patients were recruited and followed up at 18, 36, and 60 months after diagnosis. Body mass index (BMI), waist-to-hip ratio (WHR), and their changes between baseline and 18-month follow-up were derived. Clinical records on diagnosis, treatment, and death were also obtained. In total, 1309 women who completed the 18-month follow-up were included for Cox regression analyses, stratified by follow-up periods. RESULTS: Within 18-48 months post-diagnosis, substantial WHR loss (5% or above) had reduced risk of all-cause (HR = 0.21 [95% CI 0.06-0.75]) and breast cancer-specific mortality (0.21 [0.06-0.77]) relative to stable WHR; whereas after 48 months post-diagnosis, substantial WHR gain showed elevated risks of all-cause mortality (2.67 [1.22-5.85])). Higher baseline WHR was also associated with both mortality outcomes. Nonetheless, no such associations were observed for BMI measures. Also, the effects of obesity measures on breast recurrence were less apparent. CONCLUSION: Abdominal obesity, rather than general obesity, was linked to worse survival in Chinese breast cancer patients. Prevention on abdominal obesity and waist gain following breast cancer diagnosis may have a beneficial effect on longer-term survival over and above conventional weight management. Waist assessment and abdominal obesity control should therefore be incorporated as a vital component of the evaluation and interventions of breast cancer prognosis.

Association of high adherence to vegetables and fruits dietary pattern with quality of life among Chinese women with early-stage breast cancer.

PURPOSE: Dietary intake and patients' quality of life (QoL) are important supportive care issues in breast cancer survivorship. This study aimed to identify dietary pattern before and after breast cancer diagnosis. In addition, the association between dietary patterns and QoL were cross-sectionally and longitudinally investigated. METHODS: A breast cancer cohort which included 1462 Chinese women were longitudinally interviewed at four time-points, namely baseline, 18-, 36-, and 60 months after diagnosis. At each follow-up, validated food frequency questionnaires (FFQ) were used to assess patients' dietary intake, and factor analysis was used to derive dietary patterns. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to measure QoL at each follow-up. This study included 1368, 1226, 1079 and 1095 patients with invasive disease who completed assessment at baseline, 18-, 36- and 60-month follow-up and had detailed data of dietary intake and QoL. RESULTS: Based on data obtained at 18-month follow-up, two major dietary patterns were identified: "grain and animal food pattern" and "vegetables and fruits pattern". Similar dietary patterns were obtained at baseline, 36- and 60- month follow-up. Generalized Estimating Equations (GEE) were used to analyze the longitudinal associations between dietary patterns and QoL over the four follow-ups. High intake of grain and animal food was inversely associated with scores for role functioning (B = - 0.744; 95%CI - 0.147 to - 0.017), dyspnea (B = - 0.092; 95%CI - 0.092 to - 0.092) and constipation (B = - 1.355; 95%CI - 2.174 to - 0.536). Vegetables and fruits intake were positively associated with scores for global health status/QoL (B = 1.282; 95%CI 0.545-2.019), physical functioning (B = 0.545; 95%CI: 0.037-1.053), emotional functioning (B = 1.426; 95%CI 0.653-2.200) and cognitive functioning (B = 0.822; 95%CI 0.007-1.637), while inversely associated with scores for nausea and vomiting (B = - 0.382; 95%CI - 0.694 to - 0.071), dyspnea (B = - 0.570; 95%CI - 0.570 to - 0.570), insomnia (B = - 1.412; 95%CI - 2.647 to - 0.177), loss of appetite (B = - 0.722; 95%CI - 1.311 to - 0.132), constipation (B = - 2.028; 95%CI - 2.775 to - 1.281) and diarrhea (B = - 0.929; 95%CI - 1.481 to - 0.377). CONCLUSION: This study suggested that high adherence to "grain and animal food pattern" or "vegetables and fruits pattern" was significantly associated with several aspects of QoL. For instance, vegetables and fruits pattern appears to have beneficial effect on global health status/QoL among Chinese breast cancer patients. Prospective follow-up data could further confirm whether a specific dietary pattern has impact on cancer outcomes.

Short-term association among meteorological variation, outdoor air pollution and acute bronchiolitis in children in a subtropical setting.

OBJECTIVES: To examine the association among acute bronchiolitis-related hospitalisation in children, meteorological variation and outdoor air pollution. METHODS: We obtained the daily counts of acute bronchiolitis-related admission of children≤2 years old from all public hospitals, meteorological data and outdoor air pollutants' concentrations between 1 January 2008 and 31 December 2017 in Hong Kong. We used quasi-Poisson generalised additive models together with distributed lag non-linear models to estimate the associations of interest adjusted for confounders. RESULTS: A total of 29 688 admissions were included in the analysis. Increased adjusted relative risk (ARR) of acute bronchiolitis-related hospitalisation was associated with high temperature (ambient temperature and apparent temperature) and was marginally associated with high vapour pressure, a proxy for absolute humidity. High concentration of NO2 was associated with elevated risk of acute bronchiolitis admission; the risk of bronchiolitis hospitalisation increased statistically significantly with cumulative NO2 exposure over the range 66.2-119.6 µg/m3. For PM10, the significant effect observed at high concentrations appears to be immediate but not long lasting. For SO2, ARR increased as the concentration approached the 75th percentile and then decreased though the association was insignificant. CONCLUSIONS: Acute bronchiolitis-related hospitalisation among children was associated with temperature and exposure to NO2 and PM10 at different lag times, suggesting a need to adopt sustainable clean air policies, especially to target pollutants produced by motor vehicles, to protect young children's health.

Weight and waist-to-hip ratio change pattern during the first five years of survival: data from a longitudinal observational Chinese breast cancer cohort.

BACKGROUND: Body weight management was an important component in breast cancer survivorship care. The present study described the change patterns of body weight and waist-to-hip ratio (WHR) during the first 5 years of survival, and investigated potential factors associated with very substantial changes. PATIENTS AND METHODS: Based on a longitudinal cohort with 1462 Chinese women with breast cancer, anthropometric measurements including body weight, height, waist and hip circumferences were measured by trained interviewers following standard protocol at four time-points: baseline at study entry, 18-, 36- and 60-months follow up assessments (termed as T0, T1, T2 and T3, respectively). Body height was measured at baseline and body weight at cancer diagnosis were retrieved from medical record. RESULTS: Compared to weight at breast cancer diagnosis, the median weight change was - 0.5 kg, 0 kg, + 0.5 kg, and + 1 kg at T0, T1, T2 and T3, respectively. During the first 5 years of survival, the proportion of women who were obese have slightly increased. At 60-months after diagnosis, only 14.3% of women had weight gain by > 5 kg; and the percentage of women who had weight gain by > 10% was 10.7%. Nearly half of patients had abdominal obesity at study entry, and this proportion were gradually increased to nearly 70% at 60-months follow-up. Multivariate analysis indicated that older age, and frequent sports participation during the first 5 years of survival were related to lower risk of very substantial weight gain (> 10%) at 60-month follow-up; patients aged 40-49 years, having ≥2 comorbidities and ER negative were associated with less likelihood of very substantial WHR substantial increase (> 10%) at 60-month follow-up. CONCLUSION: Weight gain was modest in Chinese breast cancer survivors during the first 5 years of survival, while central adiposity has become a contemporary public health issue. The incorporation of healthy weight and abdominal circumference patient education and management has a potential to improve cancer survivorship.

Metformin Hydrochloride Encapsulation by Alginate Strontium Hydrogel for Cartilage Regeneration by Reliving Cellular Senescence.

Cartilage lesion is a common tissue defect and is challenging in clinical practice. Trauma-induced cellular senescence could decrease the chondrocyte capability of maintaining cartilage tissue regeneration. A previous investigation showed that, by controlling the cellular senescence, the cartilage regeneration can be significantly accelerated. Based on this finding, we design a novel hydrogel, Alg/MH-Sr, that combines metformin, an established drug for inhibiting senescence, and strontium, an effective anti-inflammatory material for cartilage tissue engineering. A RT-PCR test suggests the significant inhibitory effect of the hydrogel on senescent, apoptotic, oxidative, and inflammatory genes' expression. Histological examinations demonstrate that the Alg/MH-Sr hydrogel accelerated cartilage repairment, and chondrocyte senescence was significantly inhibited. Our study demonstrates that the Alg/MH-Sr hydrogel is effective for cartilage defect treatment and provides a new clue in accelerating tissue repairment by inhibiting the senescence of cells and tissues.

Longitudinal change of quality of life in the first five years of survival among disease-free Chinese breast cancer survivors.

PURPOSE: This study aimed to investigate changes of QoL during the first 5 years of survival among disease-free Chinese breast cancer survivors. METHODS: A prospective cohort study enrolled 1462 Chinese women with early-stage breast cancer, and longitudinally visited those patients at four time-points, namely baseline (T0), 18- (T1), 36- (T2), and 60-month (T3) after diagnosis. This study included 992 patients who were disease-free during the first 5 years of survival and who had completed QoL assessments at all four time-points. RESULTS: The score of global health status/QoL improved gradually (T1, T2, T3 > T0; P < 0.001 for overall comparisons). Social functioning score significantly improved when compared to that of T0 (T1, T2, T3 > T0; P < 0.001 for overall comparisons). In contrast, cognitive functioning score decreased (T0 > T1, T2, T3; P < 0.001 for overall comparisons). Scores of physical functioning, role functioning and emotional functioning showed a fluctuated picture, with the highest score achieved at T1. In symptoms profile, most of them scored lowest at T1 (best QoL). Multivariate analysis showed that several characteristics significantly correlated to changes in QoL from T0 to T3. For instance, patients with higher education had better recovery of physical functioning, role functioning, and social functioning. CONCLUSION: During the first 5 years of survival, patients' global health status/QoL improved over time, social functioning consistently improved, but cognitive functioning steadily deteriorated. Most of functioning domains and symptoms improved at 18-month follow-up, but such improvements were not maintained and even deteriorated at 36- and 60-month post-diagnosis. This study suggested that some interventions should be investigated during such period.

The association between soy isoflavone intake and menopausal symptoms after breast cancer diagnosis: a prospective longitudinal cohort study on Chinese breast cancer patients.

PURPOSE: This study investigated the association between soy isoflavone intake and menopausal symptoms (MPS) among Chinese women with early stage breast cancer in a prospective cohort study. METHODS: In an on-going prospective cohort study that involved 1462 Chinese women with early stage breast cancer, MPS were assessed at 18, 36 and 60 months after cancer diagnosis using the validated menopausal rating scale (MRS) questionnaire. Daily soy food intake for the previous 12 months was assessed at the same time using a validated food frequency questionnaire. The associations between MPS and soy isoflavone intake were evaluated in multivariable logistic regression analyses. RESULTS: The prevalence of MPS was almost the same during the first 60 months after cancer diagnosis, which were 64.5%, 65.2%, and 63.9% at 18, 36, and 60 months, respectively. Patients with MPS tended to be younger than those without MPS. The intake of soy isoflavones was not associated with the total score of MRS at 18-month follow-up [highest vs lowest tertile, odds ratio (OR) = 1.00, 95% CI 0.75-1.34]. Similarly, no significant association was noted at 36-month (OR = 1.25, 95% CI 0.92-1.69) and 60-month (OR = 1.21, 95% CI 0.84-1.74) follow-up. With regards to specific domain within MRS, the risk of symptoms presenting in somatic domain was higher among breast cancer patients who were in the highest tertile of soy isoflavone intake at 36 months post-diagnosis (OR = 1.44, 95% CI 1.07-1.94, P-trend = 0.02), compared with the lowest tertile, where a stronger significant association was noted among patients who were younger than 60 years (OR = 1.52, 95% CI 1.05-2.20, P-trend = 0.03) and pre-menopausal (OR = 3.81, 95% CI 1.85-8.11, P-trend < 0.01). CONCLUSION: The present study provided further evidence that soy isoflavone consumption was not associated with MPS among Chinese breast cancer patients. In fact, patients with higher intake of soy isoflavone have increased risk of experiencing somatic symptoms.

Longitudinal changes in sports activity from pre-diagnosis to first five years post-diagnosis: a prospective Chinese breast cancer cohort study.

BACKGROUND: To compare change in level of physical activity between pre-and post- diagnosis of breast cancer in Chinese women. METHODS: Based on an on-going prospective study consisting of a sample of Chinese women with breast cancer, a validated modified Chinese Baecke questionnaire was used to measure physical activity at baseline (12 months before cancer diagnosis), 18-, 36- and 60-months after diagnosis (over the previous 12 months before each interview). RESULTS: In our cohort of 1462 Chinese women with a mean age of 52 years, the mean level of physical activity at post-diagnosis was 9.6 metabolic equivalent of task (MET)-hours/week, which was significantly higher than that at pre-diagnosis with mean level of 5.9 MET-hours/week (P < 0.001). The mean levels of physical activity at 18-, 36- and 60-months follow-up were 9.9, 9.8 and 9.3 MET-hours/week, respectively. There was no significant difference between any two of the three follow-ups at post-diagnosis. The proportions of participant who met World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) recommendation before and after cancer diagnosis were both low, being 20.7 and 35.1%, respectively. Compared to pre-diagnosis, most of the patients improved or had no change on level of physical activity at post-diagnosis, with the respective proportion being 48.2 and 43.8%. CONCLUSIONS: Adherence to current lifestyle recommendation for cancer survivors, Chinese women with breast cancer significantly increased level of physical activity level after cancer diagnosis, and such improvement was sustained to 5 years post-diagnosis. The proportion of patients who met the exercise recommendation for cancer survivors was still low. Encouraging patients on the importance of durable high level of physical activity in breast cancer survivorship is warranted.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research Guideline Is Associated With Better Health-Related Quality of Life Among Chinese Patients With Breast Cancer.

Background: The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guideline provides recommendations for cancer prevention among cancer survivors. Limited data have examined whether guideline adherence is related to health-related quality of life (HRQoL) among Chinese patients with breast cancer. Methods: An ongoing prospective cohort study involving 1,462 Chinese women with early-stage breast cancer assessed exercise, diet, and body mass index (BMI) at baseline and at 18-months follow-up after diagnosis. Each assessment recorded patient habits within the previous 12 months. HRQoL was evaluated by the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We first compared the level of adherence to WCRF/AICR recommendations before and after cancer diagnosis. We then examined whether adherence to these recommendations after diagnosis was associated with HRQoL at 18 months. Results: The mean adherence score significantly increased from baseline (3.2; SD, 1.1) to 18-month follow-up (3.9; SD, 1.1; P<.001). Overall, increasing adherence to the WCRF/AICR guideline was associated with higher scores of global health status/quality of life (QoL; Ptrend=.011), physical (Ptrend<.001) and role functioning (Ptrend=.024), and lower scores for fatigue (Ptrend=.016), nausea and vomiting (Ptrend<.001), pain (Ptrend=.004), dyspnea (Ptrend=.030), loss of appetite (Ptrend=.007), and diarrhea (Ptrend=.020). Patients with cancer who met the BMI recommendation had higher scores for physical functioning (P=.001) and lower scores for fatigue (P=.024), pain (P<.001), and dyspnea (P=.045). Adherence to physical activity recommendation was associated with better scores of global health status/QoL (P<.001), physical functioning (P=.003), fatigue (P=.002), pain (P=.018), and dyspnea (P=.021). Higher adherence to diet recommendation was associated with lower scores of nausea and vomiting (Ptrend=.005), loss of appetite (Ptrend=.026), constipation (Ptrend=.040), and diarrhea (Ptrend=.031). Conclusions: Chinese patients with breast cancer made positive lifestyle changes early after cancer diagnosis. Increased adherence to WCRF/AICR recommendations after cancer diagnosis may improve HRQoL. Our data suggest that Chinese patients with breast cancer should follow the WCRF/AICR guideline to improve overall well-being.