[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

[Research progress and prospects of artificial intelligence in diagnosis and treatment of colorectal cancer].

Colorectal cancer is one of the most common malignant tumors worldwide. Due to the heterogeneity in patient outcomes and treatment responses to standard therapy regimens, personalized diagnostic and therapeutic strategies have remained a focus of sustained interest in research. In recent years, with the rapid progression of artificial intelligence (AI) technology in the medical field, an abundance of phased research results has emerged in the decision-making for preoperative, intraoperative, and postoperative diagnostic and therapeutic plans for colorectal cancer, demonstrating great potential for application. This new and efficient solution provides for the personalized evaluations and auxiliary diagnoses and treatments of patients with colorectal cancer. In the future, AI systems may continue to advance towards multimodal, multi-omics, and real-time directions. This paper aims to explore the current state of research on the multi-faceted auxiliary applications of AI in the diagnosis and treatment of colorectal cancer, as well as to present a prospective view of the innovations that AI technology could bring to personalized colorectal cancer treatment in the future and the challenges it may face.

[Two cases of acute methyl acetate poisoning].

This article analyzed the clinical data and on-site occupational health survey results of a patient with occupational acute methyl acetate poisoning in Zhejiang. Based on the pathways of methyl acetate poisoning and the characteristics of target organ damage, diagnosis and treatment experience were summarized, providing reference for the diagnosis and treatment of occupational acute methyl acetate poisoning and occupational health monitoring of methyl acetate.

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer.

BACKGROUND: Eribulin mesylate is a novel, nontaxane, microtubule dynamics inhibitor. In this study, we assessed the efficacy and safety of eribulin versus eribulin plus the oral small-molecule tyrosine kinase inhibitor anlotinib in patients with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: In this single-center, open-label, phase II clinical study (NCT05206656) conducted in a Chinese hospital, patients with human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent or metastatic breast cancer previously treated with anthracycline- or taxane-based chemotherapy were randomized (1 : 1) to receive eribulin alone or in combination with anlotinib. The primary efficacy endpoint was investigator-assessed progression-free survival (PFS). RESULTS: From June 2020 to April 2022, a total of 80 patients were randomly assigned to either eribulin monotherapy or eribulin plus anlotinib combination therapy, with 40 patients in each group. The data cut-off was 10 August 2022. The median PFS was 3.5 months [95% confidence interval (CI) 2.8-5.5 months] for eribulin and 5.1 months (95% CI 4.5-6.9 months) for eribulin plus anlotinib (hazard ratio = 0.56, 95% CI 0.32-0.98; P = 0.04). The objective response rates were 32.5% versus 52.5% (P = 0.07), respectively, and disease control rates were 67.5% versus 92.5% (P = 0.01), respectively. Patients <50 years of age, with an Eastern Cooperative Oncology Group performance status score of 0, visceral metastasis, number of treatment lines of four or more, hormone receptor negative (triple-negative), and HER2 low expression appeared to benefit more from combined treatment. The most common adverse events in both groups were leukopenia (n = 28, 70.0%, patients in the eribulin monotherapy group versus n = 35, 87.5%, patients in the combination therapy group), aspartate aminotransferase elevations (n = 28, 70.0%, versus n = 35, 87.5%), neutropenia (n = 25, 62.5%, versus n = 31, 77.5%), and alanine aminotransferase elevations (n = 25, 62.5%, versus n = 30, 75.0%). CONCLUSION: Eribulin plus anlotinib can be considered an alternative treatment option for HER2-negative locally advanced or metastatic breast cancer.

[Comparative study of medical common data models for FAIR data sharing].

The common data model (CDM) is an important tool to facilitate the standardized integration of multi-source heterogeneous healthcare big data, enhance the consistency of data semantic understanding, and promote multi-party collaborative analysis. The data collections standardized by CDM can provide powerful support for observational studies, such as large-scale population cohort study. This paper provides an in-depth comparative analysis of the data storage structure, term mapping pattern, and auxiliary tools development of the three international typical CDMs, then analyzes the advantages and limitations of each CDM and summarizes the challenges and opportunities faced in the CDM application in China. It is expected that exploring the advanced technical concepts and practical patterns of foreign countries in data management and sharing will provide references for promoting FAIR (findable, accessible, interoperable, reusable) construction of healthcare big data in China and solving the current practical problems, such as the poor quality of data resources, the low degree of semantization, and the inabilities of data sharing and reuse.

Top-cited works about exercise for knee osteoarthritis: a bibliometric analysis from 2000 to 2021.

OBJECTIVE: Previous trials demonstrated the effectiveness of exercise in improving pain and functional impairment in patients with knee osteoarthritis (KOA). However, a bibliometric analysis of top-cited papers on exercise treatment for KOA has not yet been conducted. The aim of the present study was to critically analyze the bibliometric characteristics of the most frequently cited articles on exercise treatment for KOA. MATERIALS AND METHODS: Publications about exercise treatment for KOA from 2000 to 2021 were searched from the Web of Science database. Two authors independently collected 100 top-cited articles, and a consensus was reached to form the final list. The title, journal, author, year of publication, country and institution of origin, total citations, citations in 2021, main topics, research nature, and level of evidence were extracted, and the publication trends in exercise treatment for KOA were evaluated. RESULTS: A total of 1,258 papers were retrieved from the database. According to the final list, clinical research accounted for 81% of the studies, but no statistical difference in the number of citations was found among the four types of articles (p=0.194). Seventy articles had a level of evidence of Ib, and no statistical differences in citations were found per level of evidence (p=0.767). Most of the top-cited articles were published between 2005-2014, and Dr Messier was the prominent writer in this field. CONCLUSIONS: This bibliometric study is the first to identify the most cited papers in exercise treatment for KOA research. Traditional Chinese exercise, comorbidity, and exercise adherence may be the next popular research trends that will receive more attention in the future.

Improving the leak detection efficiency in water distribution networks using noise loggers.

Leak detection techniques are effective ways of controlling water leakage in real water distribution networks (WDNs). Nevertheless, developing detection techniques for real WDNs has received little attention compared to the detection models developed based on laboratory simulated leaks. On the other hand, ambient noises and irregular water usage are difficult to simulate in a laboratory environment so detection models based on the laboratory simulated leaks are usually of low efficiency in practical applications. To achieve a better understanding of the detection models of real WDNs, machine learning (ML)-based leak detection models were developed in this work. This study employs wireless sensors to record acoustic signals emitted by real WDNs for the development of the leak detection models. The acquired acoustic signals are de-noised using the discrete wavelet transform. Thereafter, seventeen features are extracted from both the raw and de-noised signals using the principle of linear prediction, and the features are subsequently used for the development of the ML-based leak detection models. A thorough comparison is made for the performances of the detection models in terms of metal and non-metal WDNs, different features, and different ML algorithms, namely decision tree (DT), support vector machine (SVM), artificial neural network (ANN), and k-nearest neighbor (K-NN). Generally, the performance of the ML-based detection models developed by using the features extracted from de-noised signals has a better classification accuracy as compared to the performance of the models developed based on the features extracted from raw signals. For the de-noised signals, the accuracy, precision, and recall for the models developed based on the DT, SVM, and ANN algorithms are 100% for metal and non-metal WDNs.

[Application of SF-36 scale in the survey of quality of life of occupational disease patients].

Objective: To explore the application of the Short Form of Quality of Life (SF-36) scale in the investigation of quality of life of occupational disease patients. Methods: In May 2019, SF-36 scale was used to investigate the occupational disease patients diagnosed in Hangzhou. The reliability of the scale was evaluated by Cronbach's α coefficient, and the validity of the scale was evaluated by exploratory factor analysis. Results: The Cronbach's α coefficients of PF, RP, BP, GH, VT, SF, RE and MH were 0.937, 0.977, 0.870, 0.908, 0.815, 0.701, 0.967 and 0.863 respectively, and the half reliability coefficient α=0.905. The two factor statistics representing physiological and psychological aspects were 0.870, and the approximate chi square value was 1784.337 (P<0.01) . Compared with the national norm, the scores of each dimension of quality of life of occupational disease patients were significantly lower, and the differences were statistically significant (P<0.01) ; Compared with the scores of each dimension of quality of life of pneumoconiosis patients, the scores of PF, RP and GH of occupational disease patients were significantly higher, and the differences were statistically significant (P<0.05) . Conclusion: SF-36 scale has good reliability and validity in measuring the quality of life of patients with occupational diseases, which can be used to evaluate the quality of life of patients with occupational diseases.

[Systematic review of the qualitative researches on care experience of caregivers of burn children].

Objective: To systematically review the care experience of caregivers of burn children, so as to provide references for guiding the continuing care in hospitals, communities, and homes. Methods: Databases including Cochrane Library, PubMed, ScienceDirect, ProQuest, Web of Science, and CINAHL were retrieved with the search terms of " burn" , " care/caregivers/nursing/father/mother/relatives" , " needs/perceptions/exceptions/attitudes/feelings/demands/experiences" , " qualitative research" , and the Chinese Journals Full-text Database, China Biology Medicine disc, VIP Database, and Wanfang Data were retrieved with the search terms in Chinese version of "//" , "//////" , "/////" , "" to search the qualitative researches on care experience of caregivers of burn children published from the establishment of the databases to November 2019. After screening and extracting the data, the quality evaluation criteria for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center and its integrative/aggregative synthesis method were used to assess the quality of the included literature and meta-integrate the research results respectively. Results: A total of 16 studies and 269 caregivers were enrolled. The quality of one included literature was grade A, and the quality of 15 included literature was grade B. A total of 65 research results were extracted with totally 6 categories formed after summarization, and 2 integrated results obtained as follows: (1) The caregivers experienced heavy psychological pressure and burden in the care process, which had a significant impact on family, social relations, and daily life. (2) With the care time lapsing, through the support of all sectors of society and self-adjustment, the caregivers gradually accepted the reality and actively took various countermeasures, but they still faced many challenges in disease care. Conclusions: The caregivers of burn children have many physical and mental health problems and face many care challenges. The government, medical and health institutions, and society should give a great attention to these issues, improve the social support system and security system, reduce the family-related pressure of burn children's families, and improve the quality of family life.

[Study on quality of life and influeming factors of occupational disease patients in hangzhou].

Objective: To investigate and analyze the quality of life of occupational patients in Hangzhou and its influencing factors, so as to improve their qol. Methods: From January 2007 to June 2018, patients with diagnosed occupational diseases in Hangzhou City were randomly sampled in October 2019. The patients＇basic condition and quality of life were investigated by self-made questionnaire and SF-36, a total of 303 valid questionnaires were collected and the influencing factors were analyzed by correlation analysis and multiple linear regression. Results: The scores of physiological function, physiological function, physical pain, general health status, energy, social function, emotional function and mental health of the patients with occupational diseases in Hangzhou were lower than those of the general population in China, the differences were statistically significant (P<0.01) . The main factors affecting the score of quality of life of occupational patients are the types of occupational diseases, the level of disability and the duration of illness, the condition of suffering from other diseases, age, educational level, whether they are entitled to Work Injury Insurance, economic income, medical security and social support, the difference was statistically significant (P<0.05) . Conclusion: The quality of life of the patients with occupational diseases in Hangzhou City is poor, and the corresponding measures should be established to improve the qulity of life.

Remifentanil improves myocardial ischemia-reperfusion injury in rats through inhibiting IL-18 signaling pathway.

OBJECTIVE: To explore the protective effect of remifentanil against myocardial ischemia-reperfusion injury (MIRI) in rats and its mechanism. MATERIALS AND METHODS: The rat models of IRI were established and randomly divided into 1) sham-operation group (S group), 2) IRI rat model group (M group), 3) low-dose remifentanil group (R-L group), 4) moderate-dose remifentanil group (R-M group), and 5) high-dose remifentanil group (R-H group). The rats in R-L group, R-M group, and R-H group were administrated with remifentanil at 0.4 µg/kg/min, 2 µg/kg/min, and 10 µg/kg/min, respectively. The activity of creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in myocardial cells was detected using the automatic biochemical analyzer, and the apoptosis rate of myocardial cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the messenger ribonucleic acid (mRNA) and protein levels of related cytokines in myocardial cells were determined through quantitative Polymerase Chain Reaction (qPCR) and Western blotting, and the content of interleukin-1ß (IL-1Symbol ) and IL-18 in peripheral blood was detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: Remifentanil at different concentrations could protect myocardium from IRI, and remifentanil at 2 µg/kg/min and 10 µg/kg/min could significantly down-regulate the myocardial enzyme indexes in IRI myocardial cells (p<0.01). Besides, remifentanil reduced the mRNA expressions of IL-18, INF-γ, TNF-ß, and IL-1ß (p<0.01), significantly decreased the protein expression of IL-18, and raised the protein expression of IL-18BP, thereby improving myocardial pathological damage. CONCLUSIONS: The protective mechanism of remifentanil on the myocardium of MIRI rats may be related to the inhibition on the IL-18 signaling pathway.

Recombinant Lactococcus lactis NZ3900 expressing bioactive human FGF21 reduced body weight of Db/Db mice through the activity of brown adipose tissue.

Fibroblast growth factor 21 (FGF21), a metabolism regulator, has an important effect on metabolic diseases, such as obesity and diabetes. It is also expressed in mice, and the murine source has high homology with human FGF21. Recently, it has been extensively studied and has become a potential drug target for the treatment of metabolic diseases. As it is a protein-based hormone, FGF21 cannot be easily and quickly absorbed into the blood through oral administration. Moreover, it has a 0-2 h half-life in vivo, as shown in a previous study, thus its efficacy lasts for a short period of time when used to treat metabolic diseases, limiting its clinical applications. To avoid these limitations, we used Lactococcus lactis, a food-grade bacterium, as the host to express FGF21. It could be used successfully for the expression and long-term effect of FGF21 in vivo. Instead of antibiotic resistance genes, the LacF gene was used as a selection marker in the NZ3900/PNZ8149 expression system, which is safe and could reduce the antibiotic resistance crisis. In this study, we a constructed human FGF21 expressing L. lactis strain and administered it to Db/Db mice by gavage. Compared with the control group, the body weight of mice in the experimental group was significantly reduced, and the overall homeostasis was improved in mice treated with human FGF21. Moreover, the activity of brown adipose tissue was enhanced. These results revealed that oral administration of FGF21 through heterologous expression in L. lactis appears to be an effective approach for its clinical application.

[Investigation and analysis of quality of life of some pneumoconiosis patients in Hangzhou].

Objective: To understand the quality of life and influencing factors of patients with pneumoconiosis, and to provide a basis for formulating targeted improvement strategies to improve the quality of life. Methods: From April to December 2018, Questionnaire survey was conducted on patients with pneumoconiosis that diagnosed in Hangzhou Hospital for the Prevention and Treatment of Occupational Disease, using self-made questionnaire and SF-36.237 valid questionnaires were used to investigate the basic conditions, health services, social assistance and quality of life of patients, and analyze the influencing factors of quality of life. Results: Hangzhou city's some pneumoconiosis patients were mostly with monthly income <3000 yuan (72.6%, 172/237) ; more patients with medical expenses of 8000 to 25000 yuan per year (60.3%, 143/237) ; The proportion of patients receiving medical assistance and work-related injury insurance was low, at 2.1% (5/237) and 23.8% (54/227) respectively. The scores of Pneumoconiosis patients in PhysicalFunction (PF) , Role-Physical (RP) , Bodily Pain (BP) , General Health (GH) , Vitality (VT) , Social Function (SF) , Role-Emotional (RE) and Mental Health (MH) were lower than the national norm (P<0.05) . The scores from high to low were BP, SF, MH, PF, VT, RE, RP and GH. There were significant differences in the quality of life scores of pneumoconiosis patients with different ages, work types, education levels and monthly income (P<0.05) . Conclusion: The quality of life of some patients with pneumoconiosis in Hangzhou is lower than that of the general population. Age, work types, and monthly income are factors influencing quality of life.

Effects of rumen-protected methionine and other essential amino acid supplementation on milk and milk component yields in lactating Holstein cows.

Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.

Effects of jugular infusions of isoleucine, leucine, methionine, threonine, and other amino acids on insulin and glucagon concentrations, mammalian target of rapamycin (mTOR) signaling, and lactational performance in goats.

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.

[Analysis of lens of 1720 medical application radiology workers in Hangzhou].

Objective: To analyze the lens opacity of some hospitals in Hangzhou to provide evidence for further improvement of radiation protection. Methods: Physical examination data of 1720 radiological workers who underwent occupational disease physical examination in our hospital on January1, 2016and December 31, 2017 were collected. Lens turbidity, gender, age, type of work, radiological working age and other influencing factors were statistically analyzed, and logistic regression analysis was used for multipactor analysis. Results: A total of 112 cases of lens turbidity (turbidity rate 6.51%) , after lens turbidity, subcapsular majority (64 cases (57.14%) ) ; lens turbidity increased with age, and showed an increasing trend of radiation working age; the lens turbidity rate was different in different types of work, including nuclear medicine (23.33%) 、radiology (6.76%) 、interventional radiology (6.06%) 、dental radiology (4.26%) and radiotherapy (4.21%) . Type of work、age and length of service are risk factors for lens opacity; Age and type of work were independent risk factors for lens opacity. Conclusion: The turbidity of lens of radiologcial workers is related to age and workering age. Radiological workers engaged in nuclear medicine should strictly strengthen radiation protection.

Short-term lactation and mammary metabolism responses in lactating goats to graded removal of methionine from an intravenously infused complete amino acid mixture.

To investigate the possible pathways of Met deficiency to depress milk protein synthesis, 4 lactating goats fitted with jugular vein, mammary vein, and carotid artery catheters and transonic blood flow detectors on the external pudic artery were used in a 4 × 4 Latin square experiment. Goats were fasted for 24 h followed by a 9-h intravenous infusion of an AA mixture plus glucose. Milk yield was recorded and samples were taken in h 2 to 8 of the infusion period, and mammary biopsy was performed in the last hour. Treatments were graded removal of Met from the infused AA mixture to achieve Met content in the infusate of 100 (complete), 60, 30, or 0% of that in casein. Graded Met removal decreased yield of milk, milk protein, and lactose linearly and tended to decrease yield of milk fat linearly. Milk protein yield decreased to 82, 78, and 69% that of complete mixture infusion, respectively, when the 60, 30, and 0% Met infusate was infused. Circulating Met decreased linearly with graded Met removal. Arterial and venous Met decreased to 36 and 23% that of complete mixture infusion, respectively, when all Met was removed out of the mixture. Concomitant with the decreased circulating concentration was a similar increase in mammary Met affinity as reflected by the linearly increased mammary Met clearance rate. The increased affinity plus the linearly increased mammary blood flow totally offset the negative effect of decreased circulating Met concentration on mammary Met uptake. The overall result was similar mammary Met uptakes across treatments ranging from 285.9 to 339.5 µmol/h. Mammary uptakes of the other AA measured were generally not affected by treatments except for a linearly decreased Thr uptake and a trend of linearly increased Glu uptake. Consistent with the behavior of an AA mainly catabolized in the liver and mainly used for protein synthesis in peripheral tissues, mammary uptake to milk output ratios of Met measured in the present study ranged from 1.25 to 1.49 and was not affected by treatments. For the other AA measured, the ratio of Thr was linearly decreased and that of Glu was linearly increased by graded Met removal. Graded Met removal linearly elevated circulating urea N and glucose concentrations, indicating enhanced whole-body catabolism of AA and hepatic gluconeogenesis. Treatments had no significant effects on circulating insulin, growth hormone, and the other hormones and metabolites measured. Phosphorylation status of eIF4E binding protein 1 tended to decrease linearly and that of p70S6k was linearly decreased by graded Met removal, indicating depressed signal in the intracellular mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. In conclusion, results of the present study indicated that the mTORC1 pathway and whole-body AA catabolism rather than mammary uptake appeared the drivers for changes in milk protein synthesis in response to varying Met supply.

[Comparison of clinical manifestations according to HLA-B(27) genotype in ankylosing spondylitis patients: real-world evidence from smart management system for spondyloarthritis].

Objective: The aim of this study was to set up a large, longitudinal and prospective database to compare the clinical manifestations in human leucocyte antigen (HLA)-B(27) positive and negative patients with ankylosing spondylitis(AS) based on real-world evidence in Chinese population. Methods: A total of 897 outpatients with confirmed AS were recruited consecutively by smart management system for spondyloarthritis (SMSP) from April 13, 2016 to June 6, 2017 in Chinese PLA General Hospital from 30 provinces and autonomous regions. 801 patients with HLA-B(27) data were included in the analysis. Demographic and clinical parameters including Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), ankylosing spondylitis disease activity score (ASDAS), arthritis, enthesitis, Bath ankylosing spondylitis metrology index (BASMI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were compared between HLA-B(27) positive and negative groups. Results: A total of 801 patients were included in the analysis with an average age of (30.7±8.8) years. There were 659 males and 142 females and HLA-B(27) was present in 88.0%(705/801). Males were significantly more in HLA-B(27) positive patients [83.3%(587/705) vs. 75.0%(72/96); P=0.047].The average age at disease onset was (22.3±7.6)years in HLA-B(27) positive patients and (24.4±8.7) years in HLA-B(2)7 negative ones (P=0.028).There was significant difference in diagnose delay between two groups [14.3(2.5,43.6)months in HLA-B(27) positive patients vs. 20.3(5.0,67.4) months in HLA-B(27) negative ones, P=0.041]. Anterior uveitis was found to be significantly more common in HLA-B(27) positive patients [18.9% (133/705)vs.7.3%(7/96),P=0.005], and knee involvement less common in HLA-B(27) positive patients [4.0%(27/682) vs.10.0%(9/90), P=0.010], conversely. CRP[6.5(3.0, 16.4)mg/L vs. 3.5(1.6, 12.3)mg/L] and ESR[11.0(4.0, 24.0)mm/1h vs. 7.0(3.0, 16.0)mm/1h] were significantly higher in HLA-B(27) positive patients(P=0.005,0.013, respectively).But no differences in BASDAI,ASDAS,BASFI and BASMI were obtained between two groups. Conclusions: HLA-B(27) positive patients had a higher proportion of males, a younger age of onset and a greater risk for occurrence of anterior uveitis, suggesting a poorer prognosis.