OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Percutaneous nephrolithotripsy is the first line treatment for complete staghorn calculi, but there are risks such as renal function damage, bleeding, and infection. A case of complete staghorn calculi 8.3 cm×4.5 cm and mean CT value of 1 321 HU was reported. Urine culture suggested proteus mirabilis infection. The patient was given sensitive antibiotics for 3 days, and was treated with one session of natural orifice transluminal endoscopic lithotripsy with intelligent control of renal pelvic pressure. KUB on the first postoperative day showed residual stones of 1.0 cm×0.5 cm. There were no complications.

Objective: To evaluate the clinical outcomes of computer aided design and computer aided manufacturing (CAD/CAM) ceramic endocrowns in endodontically treated posterior teeth after five years by a retrospective study. Methods: Patients who received CAD/CAM ceramic endocrowns after endodontically treatment in Department of Endodontics, School of Stomatology, The Fourth Military Medical University between January 2016 and June 2017 were invited for this clinical study. Clinical performance was evaluated in the aspect of color match, anatomic form,marginal adaptation, restoration integrity and secondary caries. Survival rate of the restorations was calculated by the use of Kaplan-Meier method. Log-rank test was applied as well for the sake of analyzing the effect of tooth position, sex and materials to the survival rate of the restorations. Results: Seventy-four patients, 25 men and 49 women with age of (38.8±10.2) years, participated in this study for a total of 101 CAD/CAM ceramic endocrowns after observation period of (62.8±12.0) months. There were 8 failed cases among 101 restorations, 5 were loss of retention, 2 were ceramic fracture and 1 was secondary caries respectively. In particular, 93% (89/96) restorations got score A on anatomic form and 95% (91/96) restorations got score A on marginal adaptation, while 38% (36/96) restorations showed the good color match compared with the abutment teeth. The estimated cumulative survival rate of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after 5 years was 93.0% (95%CI: 87.9%-98.1%). The single-factor Log-rank analysis demonstrated that there was no statistically significant difference in the survival rate of CAD/CAM ceramic endocrowns among men and women, premolars and molars, position in the dental arch, or different materials (χ²<0.01, P=0.957; χ²=0.64, P=0.422; χ²=0.69, P=0.407; χ²=0.88, P=0.349). Conclusions: Based on this clinical study, the clinical performance of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after five years is reliable, which could be a general option to restore nonvital teeth.
Humans ; Male ; Female ; Adult ; Middle Aged ; Crowns ; Dental Porcelain/therapeutic use* ; Retrospective Studies ; Dental Prosthesis Design ; Dental Stress Analysis ; Materials Testing ; Computer-Aided Design ; Ceramics

Objective: To summarize the clinical characteristics of coarctation of the aorta(CoA) associated with intracardiac anomalies in infants. Methods: The data from August 2009 to August 2017 of 86 infants who were diagnosed with CoA associated with intracardiac anomalies. Preoperative diagnosis, surgical findings and post-operation follow-up were analyzed retrospectively. There were 56 boys an 30 girls, aqed(95.1±78.0) days, weight(4.6±1.2) kg. Anatomical types included 37 cases of pre-ductal CoA, 44 cases of peri-ducutal CoA, and 5 cases of post-ductal CoA. And this group also included 73 infants complicating VSD, 59 infants complicating ASD, 2 infants complicating DORV, and 1 infant complicating TAPVC. Results: All of the included patients underwent single-stage repair of CoA associated with intracardiac anomalies. Mean operative time was(279.0±56.4) min, mean cardiopulmonary bypass time was(162.3±51.0) min, and mean aorta cross-clamp time was(74.7±25.2) min. Mean length of ICU stay and ventilation time were(7.4±4.7) days and(101.1±75.4) hours, respectively. The residual transcoarctation gradient before discharge was lower than pre-operative transcoarctation gradient significantly [(42.3±17.7) mmHg vs.(22.1±9.4)mmHg, P<0.001], and 7 early deaths were observed after surgery. The mean follow-up time of 79 hospital survivors was(31.0±27.4) months, and no late death was found. Transcoarctation gradient of hospital survivors in the last time follow-up was(21.2±11.0)mmHg. Transcoarctation gradient of 29 cases was higher than 20 mmHg, however, only 4 cases with significant clinical symptom of lower limbs retardation were recommended for ballon angioplasty consultant. The cumulative recoarctation-free survival in 2-year follow-up was 69.2%. Conclusion To avoid early second-stage operations, single-stage repair of CoA associated with intracardiac anomalies was effective and safe, and the outcomes of early to mid term follow-up were satisfactory.

OBJECTIVE: To find out the mortality trend and related factors in aged hospitalized patients with diabetes mellitus(DM). METHODS: The case information diabetic in patients who died during the period from 2005 to 2014 were collected and the mortality and causes of death were analyzed. RESULTS: From 2005 to 2014, 1297 diabetic patients died, and the mortality of elderly DM inpatients was 4.44%(1162 cases), significantly higher than that of the non-elderly of 0.94%(P<0.001). The death rate of elderly diabetic patients was significantly higher in males than in females(5.22% vs. 3.47%, P<0.001). The mortality of the aged diabetic patients decreased within 10 years(P<0.001), decreasing from 4.75% in 2005 to 3.01% in 2009(P<0.001) in the year of 2005-2009, while there were no differences in the year of 2010-2014. The main death causes of the aged diabetic in-patients were as follows: infections(27.71%), cardiovascular diseases(25.22%), tumor(21.34%), cerebral vascular diseases(10.41%) and diabetic complications(5.51%). The first death cause in the 60-79 yrs group was cardiovascular diseases, while in the ≥80 yrs group, it was infections. The constituent ratio of infection as death cause in the aged during 2010-2014 significantly increased(22.60% vs. 32.50%, P<0.001), increasing by 43.81%, and it became the first cause of death in 2010. CONCLUSION: The death rate of the elderly DM in-patients has decreased significantly within 10 years, from 2005 to 2014, while the rate has kept steady from 2010. Infections and cardiovascular diseases are the main cause of death. So it's important to prevent the elderly hospitalized DM patients from infection, in addition to cardiovascular diseases, and to control in time.

OBJECTIVETo investigate the correlation between liver and skeletal muscle fat contents and insulin resistance in obese individuals with different levels of glucose tolerance.

METHODSRESULTS: Ten non-obese individuals with normal glucose tolerance (NGT), 9 obese individuals with NGT, and 7 obese individuals with impaired glucose tolerance (IGT) were enrolled in this study. All the participants were examined for insulin sensitivity by hyperinsulinemic-euglycemic clamp and for liver and skeletal muscle fat accumulation quantified by proton magnetic resonance spectroscopy (1H MRS). The data were collected from the subjects including somatometric measurements, fasting plasma glucose, 2-h plasma glucose (2hPG), fasting insulin, and blood biochemistry. Linear correlation analysis and multiple linear stepwise regression analysis were used to analyze the relationship between ectopic fat accumulation and insulin resistance.

RESULTSThe glucose infusion rates (GIR, presented as the M value) differed significantly among IGT-obese (3.95∓1.66 mg·kg·min), NGT-obese (6.14∓1.90 mg·kg·min) and NGT-non-obese (8.78∓2.46 mg·kg·min) groups (P<0.05). The 3 groups also showed significant differences in liver fat contents [(15.23∓3.09)%, (6.25∓0.38)%, and (1.89∓0.90)%, respectively, P<0.05] and intramyocellular lipids in the tibialis anterior (2.69∓0.95, 2.61∓1.45, and 1.54∓0.66 mmol/kg, respectively, P<0.05). Linear analysis revealed that liver fat content, but not skeletal muscle fat content, was significantly correlated with the M value. Multiple linear stepwise regression analysis using M value as the dependent variable (Y) revealed that liver fat content (X) was an independent factor inversely correlated with the M value (regression equation: Y=-30.562X+9.007, R=0.717, P<0.01).

CONCLUSIONSLiver fat accumulation, but not skeletal muscle fat accumulation, is correlated with insulin resistance and impaired glucose metabolism.

Objective: To evaluate the inhibitory effect of dihydroartemisinin on neuroblastoma cell line SH-SY5Y, explore the possible mechanism of dihydroartemisinin against neuroblastoma cells. Methods: The cell viability of dihydroartemisinin treated SH-SY5Y cells was examined by MTT assay and morphology of cells was observed by using inverted microscope. Cell cycle was examined with flowcytometry assay, then cyclin D1 and caspase-3 proteins expression was detected by ELISA and western blotting assay. Results: MTT analysis results showed that cell viability significantly decreased after exposure to 0.05, 0.50, 5.00 and 50.00 μmol/L dihydroartemisinin in a dose-dependent manner, and the lower density of cells was observed in treated groups. The number of cells in sub-G1 phase was increased after treatment with different doses of dihydroartemisinin compared with the control group. The expression of cyclin D1 protein was decreased, while the expression of caspase-3 protein was increased in treated group. Conclusions: Dihydroartemisinin could inhibit the proliferation through stopping the cell cycle and inducing the apoptosis in neuroblastoma SH-SY5Y cells.

Objective Coronary arterial plaque rupture and secondary thrombosis are the major pathogenesis of acute coronary syndrome ( ACS) . Metalloprotease ( MMPs) secreted by monocyte/ macrophage was the main predisposing factor of the plaque rupture and peroxisotne proliferator-activated receptor-γ (PPAR-γ) is involved in a variety of inflammatory cytokine gene transcriptional regulations. We explored the possible role of PPAR-γ in the regulation of MMP-9 and TIMP-1 expressed by peripheral monocyte-derived macrophages (MDMs) from patients with ACS. Methods Peripheral blood mononuclear cells were isolated from 48 patients with ACS and 28 healthy controls and stimulated by macrophage colony-stimulating factor (0. 1 μg/ml for 24 hours) to form MDMs. MDMs were then incubated under various concentrations of rosiglitazone (0, 1, 10, 20 μmol/L) for 48 hours. The concentrations of MMP-9 and TIMP-1 in the supernatant were measured by enzyme linked immunosorbent assay, and the mRNA expression of PPAR-γ, MMP-9 by RT-PCR and nuclear factor-KB P65 ( NF-kB P65 ) expression by immunohistochemistry. Results PPAR-γ mRNA expression was significantly lower while NF-kB P65 and MMP-9 expression as well as MMP-9 and TIMP-1 concentrations in supernatant were significantly higher in ACS group than those in control group (all P <0. 05). After rosiglitazone intervention, PPAR-γ mRNA expression was significantly upregulated in both ACS and control groups in a dose-dependent manner. Both the MMP-9 concentration in the supernatant and MMP-9 mRNA expression were reduced post intervention with rosiglitazone in both groups. The TIMP-1 mRNA expression and concentration in supernatant were not affected by rosiglitazone in both groups. Rosiglitazone induced significant downregulation of NF-kB P65 expression in both groups. Conclusion Rosiglitazone intervention may downregulate MMP-9 expression by upregulating PPAR-γ expression, and by downregulaiting NF-kB expression in MDMs isolated from patients with ACS.