Development and validation of machine learning-augmented algorithm for insulin sensitivity assessment in the community and primary care settings: a population-based study in China.

Objective: Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the "common soil" of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings. Methods: We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models. Results: The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc. Conclusion: The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Reproductive and Developmental Toxicity Assessment of Human Umbilical Cord Mesenchymal Stem Cells in Rats.

Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown very attractive potential in clinical applications for the treatment of various diseases. However, the data about the reproductive and developmental toxicity of hUC-MSCs remains insufficient. Thus, we assessed the potential effects of intravenous injection of hUC-MSCs on reproduction and development in Sprague-Dawley rats. Methods: In the fertility and early embryonic development study, hUC-MSCs were administered at dose levels of 0, 6.0 × 106, 8.5 × 106, and 1.2 × 107/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo-fetal development study, the pregnant female rats received 0, 6.0 × 106, 1.2 × 107, and 2.4 × 107/kg of hUC-MSCs from gestation days (GD) 6-15. Assessments made included mortality, clinical observations, body weight, food consumption, fertility parameters of male and female, litter, and fetus parameters, etc. Results: No hUC-MSCs-related toxicity was observed on the fertility of male and female rats, and no teratogenic effect on fetuses. hUC-MSCs at 1.2 × 107/kg caused a mildly decrease in body weight gain of male rats, transient listlessness, tachypnea, and hematuria symptoms in pregnant female rats. Death was observed in part of the pregnant females at a dose of 2.4 × 107/kg, which could be due to pulmonary embolism. Conclusion: Based on the results of the studies, the no-observed-adverse-effect levels (NOAELs) are 8.5 × 106/kg for fertility and early embryonic development, 1.2 × 107/kg for maternal toxicity and 2.4 × 107/kg for embryo-fetal development in rats intravenous injected with hUC-MSCs, which are equivalent to 8.5-fold, 12-fold, and 24-fold respectively of its clinical dosage in humans. These findings may provide a rational basis for human health risk assessment of hUC-MSCs.

The Assessment of Sleep Quality in Patients Following Valve Repair and Valve Replacement for Infective Endocarditis: A Retrospective Study at a Single Center.

BACKGROUND The aim of this study was to measure sleep quality among patients who underwent infective endocarditis (IE) surgery and identify the risk factors involved in sleep disorders. MATERIAL AND METHODS In this study, we used actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleep Scale (ESS) to determine the clinical characteristics of sleep disorders in 116 patients with IE who were in rehabilitation after surgery. RESULTS Our results showed that 46 (39.7%) patients had sleep efficiency over 85%, while 70 (60.3%) patients had sleep efficiency below 85%. The correlation analysis showed that sleep efficiency was related to the duration of the disease, with a longer duration leading to lower sleep efficiency (P=0.031). The sleep efficiency of patients with IE following surgery was also affected by alcohol consumption; however, surprisingly, patients with "heavy" alcohol consumption had higher sleep efficiency (P=0.030). We found a significant correlation between sleep efficiency and postoperative interleukin-6 (IL) levels, C-reactive protein (CRP) levels, and preoperative erythrocyte sedimentation rate (P<0.05). No significant correlation was found between brain natriuretic peptide levels and sleep efficiency, PSQI score, or ESS score. Postoperative hemoglobin (Hb) level was associated with sleep efficiency (R=0.194, P=0.036), but there was no statistically significant correlation between the PSQI and ESS scores. Postoperative alanine transaminase (ALT) showed a significant negative correlation with sleep efficiency (R=-0.27, P=0.003). CONCLUSIONS We found a high prevalence of sleep disorders in patients with IE along with an increase in inflammatory factors, including postoperative IL-6, CRP, ALT, and Hb levels.

Not performing an OGTT results in underdiagnosis, inadequate risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years: a population-based prospective cohort study.

OBJECTIVE: To explore the influence by not performing an oral glucose tolerance test (OGTT) in Han Chinese over 40 years. DESIGN: Overall, 6682 participants were included in the prospective cohort study and were followed up for 3 years. METHODS: Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG), FPG and 2h-PG (OGTT), and HbA1c testing using World Health Organization (WHO) or American Diabetes Association (ADA) criteria were employed for strategy analysis. RESULTS: The prevalence of diabetes is 12.4% (95% CI: 11.6-13.3), while the prevalence of prediabetes is 34.1% (95% CI: 32.9-35.3) and 56.5% (95% CI: 55.2-57.8) using WHO and ADA criteria, respectively. 2h-PG determined more diabetes individuals than FPG and HbA1c. The testing cost per true positive case of OGTT is close to FPG and less than 2h-PG or HbA1c. FPG, 2h-PG and HbA1c strategies would increase costs from complications for false-positive (FP) or false-negative (FN) results compared with OGTT. Moreover, the least individuals identified as normal by OGTT at baseline developed (pre)diabetes, and the most prediabetes individuals identified by HbA1c or FPG using ADA criteria developed diabetes. CONCLUSIONS: The prevalence of isolated impaired glucose tolerance and isolated 2-h post-load diabetes were high, and the majority of individuals with (pre)diabetes were undetected in Chinese Han population. Not performing an OGTT results in underdiagnosis, inadequate developing risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years and great consideration should be given to OGTT in detecting (pre)diabetes in this population. Further population-based prospective cohort study of longer-term effects is necessary to investigate the risk assessment and cost of (pre)diabetes.

Simple instruments facilitating achievement of transanal total mesorectal excision in male patients.

AIM: To assess the efficacy of a modified approach with transanal total mesorectal excision (taTME) using simple customized instruments in male patients with low rectal cancer. METHODS: A total of 115 male patients with low rectal cancer from December 2006 to August 2015 were retrospectively studied. All patients had a bulky tumor (tumor diameter ≥ 40 mm). Forty-one patients (group A) underwent a classical approach of transabdominal total mesorectal excision (TME) and transanal intersphincteric resection (ISR), and the other 74 patients (group B) underwent a modified approach with transabdominal TME, transanal ISR, and taTME. Some simple instruments including modified retractors and an anal dilator with a papilionaceous fixture were used to perform taTME. The operative time, quality of mesorectal excision, circumferential resection margin, local recurrence, and postoperative survival were evaluated. RESULTS: All 115 patients had successful sphincter preservation. The operative time in group B (240 min, range: 160-330 min) was significantly shorter than that in group A (280 min, range: 200-360 min; P = 0.000). Compared with group A, more complete distal mesorectum and total mesorectum were achieved in group B (100% vs 75.6%, P = 0.000; 90.5% vs 70.7%, P = 0.008, respectively). After 46.1 ± 25.6 mo follow-up, group B had a lower local recurrence rate and higher disease-free survival rate compared with group A, but these differences were not statistically significant (5.4% vs 14.6%, P = 0.093; 79.5% vs 65.1%, P = 0.130). CONCLUSION: Retrograde taTME with simple customized instruments can achieve high-quality TME, and it might be an effective and economical alternative for male patients with bulky tumors.

[Diagnosis and risk assessment of postoperative complications of gastric cancer in Japan and Korea].

Radical surgery of gastric cancer (D2 lymph node dissection) as the standard operation is widely used in clinical practice and satisfactory prognosis can be obtained in patients who receive radical gastrectomy. But surgical invasion can cause high morbidity of complications and mortality. The data of large-scale evidence-based medical clinical trials and large databases in Japan and Korea showed that anastomotic leakage, pancreatic leakage and abdominal abscess were the most common complications after gastrectomy, and the morbidity of complication was about 20% and mortality was about 1%. The risk factors such as elderly, obesity, and comorbidities may increase the morbidity of complications and mortality, and these factors were regarded as poor predictors after operation. Postoperative complications criteria of gastric cancer surgery is mainly used with Clavien-Dindo classification of surgical complications as international standard, and this criteria is also used in Korea. The postoperative complications are evaluated with the Common Terminology Criteria for Adverse Events (CTCAE v4.0) and Japanese Clinical Oncology Group(JCOG) postoperative complications criteria for grading definitions of postoperative complications after gastric surgery in Japan. These classifications of postoperative complications criteria were adopted widely in Japan with large-scale evidence-based medical clinical trials of gastric cancer. PS, ASA, POSSUM, E-PASS, APACHE-II(, Charison weighted index of comorbidities (WIC), Frailty Score was used in predicting postoperative mortality and morbidity in gastric cancer patients. These risk factors were assigned points in scoring systems to objectively evaluate risk of surgery, and surgical operation method was one of the risk factors on the basis of these scoring systems. We can use these scoring systems for choosing reasonable surgical methods and proper perioperative management.

Ischemic heart disease deaths, disability-adjusted life years and risk factors in Fujian, China during 1990-2013: Data from the Global Burden of Disease Study 2013.

OBJECTIVES: Ischemic heart disease (IHD) is a large public health problem and is associated with a number of modifiable risk factors. The aim of this study was to estimate the IHD burden and attributable to risk factors in Fujian, China during 1990 to 2013. METHODS: IHD deaths, disability-adjusted life years (DALYs) and attributable to risk factors were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Statistical models were employed to produce comprehensive results of IHD deaths, DALYs and attributable to risk. Means and 95% uncertainty intervals (UIs) were calculated for mortality and DALYs. The median of the percent change and 95% UI were determined for the period between 1990 and 2013. RESULTS: The age-standardized IHD deaths rate increased by 15.3% from 1990 [74.7 (95% UI 62.9-99.1) per 100,000] to 2013 [82.7 (56.5-95.5) per 100,000]. The age-standardized IHD DALYs has slightly decreased 8.8% from 1990 to 2013[from 1356.2 (1134.3-1732.1) to 1202.7 (879.6-1404.6) per 100,000]. All risks combined account for 94.7% (92.9%- 96.0%) of IHD DALYs for all ages in 2013. The five leading risk factors for all ages IHD DALYs were high systolic blood pressure, high total cholesterol, smoking, diet high in sodium, and high fasting plasma glucose. CONCLUSION: Despite decreased age-standardized IHD deaths and DALY rate since 1990, population growth and aging led to a higher global burden of IHD in 2013. Behavioral, environmental, and metabolic risks can explain most of the IHD DALYs providing many opportunities for prevention.

Cost-effectiveness of different regimens of anesthesia for day surgery in China.

OBJECTIVES: To compare the cost-effectiveness of inhalation of sevoflurane, target-controlled infusion (TCI) of propofol, intravenous (IV) propofol for induction-inhalation of sevoflurane, and IV propofol for induction-inhalation of desoflurane for anesthesia maintenance in day surgery. METHODS: 240 patients, scheduled for elective day surgery, were randomly divided into 4 groups (n = 60 each): inhalation of sevoflurane anesthesia group (group S); TCI of propofol anesthesia (group P); and intravenous propofol for induction of anesthesia-inhalation of sevoflurane for maintenance of anesthesia group (group PS); and intravenous propofol for induction of anesthesia-inhalation of desoflurane for maintenance of anesthesia group (group PD). RESULTS: Group S was associated with less time to loss of consciousness, as well as the other three groups were associated with less time to recovery (P < 0.05). Group P was associated with a higher anesthetic agents cost than other 3 groups (P < 0.05), and group S was associated with a higher anesthetic agents costs than group PS and PD (P < 0.05). CONCLUSION: Induction with intravenous injection of propofol and maintenance with inhalation of desoflurane is the most cost-effective method of anesthesia for day surgery.

Quantitative assessment of gait and neurochemical correlation in a classical murine model of Parkinson's disease.

BACKGROUND: Gait deficits are important clinical symptoms of Parkinson's disease (PD). However, existing behavioral tests for the detection of motor impairments in rodents with systemic dopamine depletion only measure akinesia and dyskinesia, and data focusing on gait are scarce. We evaluated gait changes in the methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6 murine model of PD by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) were also investigated. RESULTS: The gait readouts, including the walking duration, variation of walking speed, step cycle, duty cycle, stance, initial dual stance, terminal dual stance, three- and four-point supports, and the base of support between hind limbs was noted to increase significantly one week after MPTP injection. In contrast, values of the stride length, cadence, swing speed, and diagonal dual support decreased substantially following MPTP treatment (p < 0.05). All of these changes lasted for three weeks after the last MPTP administration. Except for the stance in the fore limbs and the swing speed in the hind limbs, the gait variability in the PD mice showed a closer correlation with the protein levels of TH in the SN than the walking distances in the conventional open field test. Coordination parameters of the regularity index and step pattern were not affected in mice treated with MPTP. CONCLUSION: Data of the study suggest that the computer-assisted CatWalk system can provide reliable and objective criteria to stratify gait changes arising from MPTP-induced bilateral lesions in C57/BL6 mice. The extent of gait changes was noted to correlate with the expression of the biomarker for dopaminergic neurons. This novel analytical method may hold promise in the study of disease progression and new drug screening in a murine PD model.

Regulação autonômica das propriedades mecânicas em bioprótese valvar porcina / Autonomic regulation of mechanical properties in porcine mitral valve cusps / Regulación autonómica de las propiedades mecánicas en bioprótesis valvular porcina

FUNDAMENTO: A presença de nervos nas válvulas cardíacas foi demonstrada pela primeira vez há décadas e identificadas em subpopulações: simpáticas e parassimpáticas, e, portanto, é esperado que as válvulas sejam grandemente afetadas pelos nervos autônomos. Entretanto, poucos estudos têm se concentrado na regulação de válvulas cardíacas pelo sistema nervoso autônomo. OBJETIVO: Buscamos identificar o papel do sistema nervoso autônomo na regulação das propriedades mecânicas dos tecidos de válvulas mitrais porcinas. MÉTODOS: As propriedades mecânicas dos folhetos de válvulas mitrais porcinas foram avaliados em resposta à norepinefrina (NE) e acetilcolina (ACH), os principais neurotransmissores. Ao mesmo tempo, fentolamina (FENT), metoprolol (Metop), atropina (Atrop) e desnudamento endotelial foram adicionados ao sistema reativo. RESULTADOS: Sob condições fisiológicas, a rigidez não foi afetada pelo desnudamento endotelial (p > 0,05). A NE significantemente aumentou a rigidez valvar por aumento de 10 vezes na concentração (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Essa resposta foi amenizada por FENT, Metop ou desnudamento endotelial (p < 0,05); entretanto, manteve-se aumentada de maneira significante quando comparada aos Controles (p < 0,05). A ACH causou uma diminuição na rigidez acompanhada por um aumento em sua concentração (alteração significante na rigidez por aumento de 10 vezes na concentração de ACH, 10-6 vs Controle, p < 0,05; 10-5 vs 10-6, p < 0,05), que foi revertida pelo desnudamento endotelial e Atrop (p > 0,05 vs Controle). CONCLUSÃO: Esses achados ressaltam o papel do sistema nervoso autônomo na regulação das propriedades mecânicas das cúspides de válvula mitral porcina, o que reforça a importância do estado nervoso autônomo no funcionamento ideal da válvula.

BACKGROUND: The presence of nerves in heart valves was first depicted decades ago and identified into subpopulations: sympathetic, parasympathetic. So valves are expected to be greatly affected by the autonomic nerves. However, few studies have focused on the regulation of heart valves by the autonomic nervous system. OBJECTIVE: We sought to identify the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve tissues. METHODS: Mechanical properties of porcine mitral valve leaflets were evaluated in response to norepinephrine (NE) and acetylcholine (ACH), the main neurotransmitters. At the same time, phentolamine (Phent), metoprolol (Metop), atropine (Atrop) and endothelial denudation were added to the reactive system. RESULTS: Under physiological conditions, the stiffness was not affected by endothelial denudation (p > 0.05). NE elevated the valve stiffness significantly per 10-fold increase in concentration (10-6 vs 10-7, p < 0.05; 10-5 vs 10-6, p < 0.05). This response was mitigated by Phent, Metop or endothelial denudation (p < 0.05), however, it was still increased significantly when compared to Controls (p < 0.05). ACH caused a decrease in stiffness accompanied by an increase in its concentration (significant change in stiffness per 10-fold increase in ACH concentration, 10-6 vs Control, p < 0.05; 10-5 vs 10-6, p < 0.05), which were reversed by endothelial denudation and Atrop (p > 0.05 vs Control). CONCLUSION: These findings highlight the role of the autonomic nervous system in the regulation of the mechanical properties of porcine mitral valve cusps, which underline the importance of autonomic nervous status for optimal valve function.

FUNDAMENTO: La presencia de nervios en las válvulas cardíacas quedó demostrada por primera vez hace algunas décadas e identificadas en sub-poblaciones: simpáticas y parasimpáticas y por lo tanto, lo que se espera es que las válvulas reciban una gran afectación de los nervios autónomos. Sin embargo, pocos estudios se han concentrado en la regulación de válvulas cardíacas a través del sistema nervioso autónomo. OBJETIVO: Buscamos identificar el papel del sistema nervioso autónomo en la regulación de las propiedades mecánicas de los tejidos de las válvulas mitrales porcinas. MÉTODOS: Las propiedades mecánicas de las capas de válvulas mitrales porcinas fueron evaluadas en respuesta a la norepinefrina (NE) y a la acetilcolina (ACH), los principales neurotransmisores. Igualmente, la fentolamina (FENT), el metoprolol (Metop), la atropina (Atrop) y la denudación endotelial también se añadieron al sistema reactivo. RESULTADOS: Bajo condiciones fisiológicas, la rigidez no se afectó por el denudación endotelial (p > 0,05). La NE aumentó significativamente la rigidez valvular con un aumento de 10 veces en la concentración (10-6 vs 10-7, p < 0,05; 10-5 vs 10-6, p < 0,05). Esa respuesta fue amenizada por FENT, Metop o denudación endotelial (p < 0,05); pero se mantuvo aumentada de manera significativa cuando se le comparó con los Controles (p < 0,05). La ACH causó una disminución en la rigidez acompañada por un aumento en su concentración (alteración significativa en la rigidez por el aumento en 10 veces de la concentración de ACH, 10-6 vs Control, p < 0,05; 10-5 vs 10-6, p < 0,05), que fue revertida por la denudación endotelial y Atrop (p > 0,05 vs Control). CONCLUSIÓN: Esos hallazgos destacan el rol del sistema nervioso autónomo en la regulación de las propiedades mecánicas de las cúspides de la válvula mitral porcina, lo que refuerza la importancia del estado nervioso autónomo en el funcionamiento ideal de la válvula.