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

Objective To evaluate the clinical efficacy and safety of transcatheter arterial infusion with gemcitabine and nab-paclitaxel(GN)as first-line therapy in treating patients with advanced pancreatic cancer.Methods The clinical data of a total of 50 patients with advanced pancreatic cancer,who were treated with transcatheter arterial infusion chemotherapy with GN regimen at the Zhejiang Cancer Hospital of China between January 2016 and December2020,were collected The objective effective rate(ORR),progression-free survival(PFS),overall survival(OS)and treatment-related toxic reactions were analyzed.Results A total of 236 times of transcatheter arterial infusion chemotherapy were carried out in the 50 patients,with an average perfusion procedure of 4.72 times per patient.Complete remission(CR)was obtained in 0 patient,partial remission(PR)in 16 patients,and stable disease(SD)in 21 patients.The ORR was 32％,the median PFSwas5.1 months,and the OS was 9.8 months.The main adverse events included neutropenia,thrombocytopenia,vomiting,nausea,fatigue,etc.Conclusion For patients with advanced pancreatic cancer,transcatheter arterial infusion chemotherapy with GN regimen carries good short-term efficacy and safety,it can improve patient's PFS and OS to a certain extent.(J Intervent Radiol,2024,33:512-515)

Objective:To observe the effects of medium and long-term insulin pretreatment on the activity of main oxidase and antioxidant enzyme in the myocardium of burned rats with delayed fluid resuscitation.Methods:According to random number table method, forty male Sprague-Dawley (SD) rats were divided into pseudo-burn group, burn delayed resuscitation group, insulin glargine pretreatment group and neutral protamine hagedorn (NPH) insulin pretreatment group, with 10 rats in each group. 30% total body surface area (TBSA) as Ⅲ degree scald model was prepared by bathing the back of rats in 95 ℃ hot water for 15 s; the rats in the pseudo-burn group were immersed in 37 ℃ warm water for 15 s as control. Insulin glargine pretreatment group, NPH insulin pretreatment group and burn delayed resuscitation group were injected subcutaneously with insulin glargine, NPH insulin, and normal saline 1.0 U·kg -1·d -1 2 hours after injury, and intraperitoneal injection of normal saline 40 mL/kg simulated delay resuscitation 6 hours after injury. The pseudo-burn group didn't receive medicine and delayed resuscitation. Abdominal aortic blood samples and heart tissue were collected immediately after simulating scald in the pseudo-burn group, and 24 hours after scald in three burn groups. Blood glucose, xanthine oxidase (XOD), myeloperoxidase (MPO), CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) of the heart tissue were determined by spectrophotometry. Results:Compared with the pseudo-burn group, the burn delayed resuscitation group have significantly higher blood glucose level and the XOD and MPO in the heart tissue, while significantly lower CuZn-SOD, CAT, and GSH-Px in the heart tissue. Compared with the burn delayed resuscitation group, insulin glargine pretreatment group and NPH insulin pretreatment group have lower blood glucose level and heart tissue XOD [blood glucose (mmol/L): 6.37±1.22, 6.66±1.45 vs. 9.47±0.80; XOD (U/g): 271.93 (261.59, 275.91), 285.32 (251.96, 297.29) vs. 363.37 (354.12, 377.76), all P < 0.05], while significantly higher heart tissue CuZn-SOD, CAT, and GSH-Px [CuZn-SOD (U/g): 0.13±0.01, 0.14±0.01 vs. 0.10±0.01; CAT (U/g): 29.17±7.28, 27.16±7.37 vs. 18.36±4.53; GSH-Px (U/g): 0.33 (0.16, 0.41), 0.30 (0.17, 0.41) vs. 0.07 (0.04, 0.11), all P < 0.05]. MPO activity in insulin glargine pretreatment group was significantly lower than that in burn delayed resuscitation group (U/g: 0.016±0.002 vs. 0.020±0.002, P < 0.05), but there was no significant difference between insulin pretreatment group and NPH insulin pretreatment group (U/g: 0.019±0.003 vs. 0.020±0.002, P > 0.05). There was no significant difference in the blood glucose, and activities of XOD, MPO, CAT, GSH-Px between insulin glargine pretreatment group and NPH insulin pretreatment group, but the activity of CuZn-SOD in NPH insulin pretreatment group was further higher than that in insulin glargine pretreatment group (U/g: 0.14±0.01 vs. 0.13±0.01, P < 0.05). Conclusions:Medium and long-term insulin pretreatment can improve the antioxidant capacity of myocardium in delayed resuscitation rats after burns, inhibit the production of reactive oxygen species and improve the scavenging capacity of reactive oxygen species. However, only CuZn-SOD activity is different between the two groups, and further study needs to be carried out to determine whether it is related to the type if insulin.

Objective To investigate clinical effect and safety of eccentric reamer technique foraminoplasty during percutaneous endoscopic lumbar discectomy for the treatment of lumbar lateral recess stenosis.Methods All of 45 cases diagnosed of lumbar lateral recess stenosis between Apr 2010 to Jun 2012 were analyzed in our study.Among these cases,28 cases were male and 17 were female.The age of enrolled cases was 39-62 years old and the average age was 49.23±23.96 years old.All the cases were one-level,25 cases in L4,5 and 20 cases in L5S1.All the patients underwent percutaneous endoscopic lumbar discectomy.During surgery,eccentric reamer technique was applied for foraminoplasty.Perioperative data included surgical segment,surgical duration and blood loss during surgery.Oswestry Disability Index (ODI) and Visual analogue scale (VAS) for lower back and leg pain were recorded for the evaluation of surgical effect.All the data were recorded before surgery,1 day,1 month after surgery and final follow-up.Recurrent lumbar disc herniation,spinal canal hematoma,intervertebral disc infection,nerve root injury and post-operative dysthesia (POD) were recorded for complications.Results All the cases finished surgery and none of the cases was changed to other surgery method and no other electronic drill were used in these patients.Surgical duration was 45-76 min and average time was 61.23± 13.89 min.Blood loss during surgery was 10-25 ml and average blood loss was 15.02±4.33 ml.Post-operative hospitalization days were 1-3 days and 2.80±1.57 days.The follow-up time was 60-84 months and the average time was 73.23±8.47 months.ODI in one-day after surgery was 9.34±6.54％,significantly lower than 68.06±24.14％ before surgery and no statistically change had been observed in one-month after surgery and final follow-up.The VAS for lower back was 1.54±0.97 in one-day after surgery,significantly lower than 3.57±3.12 before surgery.The VAS for leg pain was 1.14±0.79 in one-day after surgery,significantly lower than 6.24±2.35 before surgery.During follow-up,1 case suffered from recurrent lumbar disc herniation (2.22％) and no intervertebral disc infection,spinal canal hematoma and POD was observed.Conclusion Eccentric reamer technique foraminoplasty in percutaneous endoscopic lumbar discectomy is an effective and safe surgical method for the treatment of lumbar lateral recess stenosis.

OBJECTIVETo establish a animal model of hepatic steatosis induced by chronic viral hepatitis in C(57)BL/6 mice.

METHODSC(57)BL/6 mice were randomly assigned to control group, high-fat diet group, mouse hepatitis virus strain A59 (MHV-A59) virus infection group, and high-fat diet plus virus infection group. At 13 weeks of the experiment, serum samples were collected to detect MHV antibodies and transaminase and lipid levels. The hepatic pathologies of the mice were examined with Oil red O staining of the frozen sections the and HE staining of paraffin-embedded sections.

RESULTSThe mice in the two virus infection groups showed strong positivity of MHV antibodies in the serum. Compared with the control group, the mice in high-fat diet group and the two virus infection groups had significantly increased AST and ALT levels with also elevated TC and LDL-C levels. The two virus infection groups both exhibited obvious pathologies in the liver characteristic of chronic viral hepatitis with increased lipid accumulation in the hepatocytes.

CONCLUSIONWe have successfully established a mouse model of hepatic steatosis induced by chronic viral hepatitis, which provides the basis for further study of the disease mechanism.

Animals ; Antibodies, Viral ; blood ; Chronic Disease ; Diet, High-Fat ; Disease Models, Animal ; Fatty Liver ; virology ; Hepatitis, Chronic ; virology ; Mice ; Mice, Inbred C57BL ; Murine hepatitis virus

0.05).On 1,3 and 5 days after the operation,the PHS and PVAS of Group B decreased significantly than those of Group A(P

The membrane microviscosity and insulin receptor of erythrocytes were determined by fluorescence polarization analysis and insulin radioligand binding assay simultaneously. The patients with Parkinson disease (PD) had increased membrane microviscosity (P