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 study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L

ObjectiveTo investigate the effect of Yiqi Jiedu prescription-containing serum on the proliferation of medullary thymic epithelial cells （mTEC） and regulatory T （Treg） cells in myasthenia gravis （MG） patients with thymus hyperplasia. MethodAccording to serological methods，35 SD rats were adaptively fed for one week and randomized into the low-，medium-， and high-dose Yiqi Jiedu prescription groups，control group， and prednisone group，with seven rats in each group， which were then gavaged with the corresponding drugs for one week for preparing the drug-containing serum. The effect of Yiqi Jiedu prescription-containing serum at different concentrations on the proliferation of mTEC and Treg cells were determined by cell counting kit-8 （CCK-8） assay. Besides， the effect of mTEC and Yiqi Jiedu prescription-containing serum on Treg cell proliferation were observed through co-culture. ResultThymocytes were cultured for a period of time. Their mean positive rate revealed by flow cytometry using mTEC characteristic marker Ulex europaeus agglutinin Ⅰ （UEAI） was 92.54%. Treg cells were sorted by magnetic beads. The purity of Treg cells after repeated magnetic bead sorting was as high as 92%. mTEC and Treg cells showed high positive expression rates，and their cell purity met the requirements of subsequent experiments. When the concentration of Yiqi Jiedu prescription-containing serum was 2.5%-15%，it exhibited an inhibitory effect against mTEC and Treg cells. When the concentration was equal to or greater than 20%，it promoted cell proliferation，which was further enhanced with the extension of action time. The results after 48 h of culture showed that compared with the control group，prednisone and low-dose Yiqi Jiedu prescription had no significant effect on the proliferation of these two kinds of cells，but the medium- and high-dose Yiqi Jiedu prescription remarkably reduced their proliferation inhibition rate （P<0.01）. After co-culture with mTEC， the control group was not significantly different from the prednisone group and the low-dose Yiqi Jiedu prescription-containing serum group in the proliferation of Treg cells，while the medium- and high-dose Yiqi Jiedu prescription-containing serum groups significantly lowered the proliferation inhibition rate （P<0.01）. ConclusionYiqi Jiedu prescription-containing serum affects the proliferation of mTEC and Treg cells in MG patients with thymus hyperplasia. Compared with the solely cultured Treg cells isolated from MG patients，the Treg cells co-cultured with mTEC exhibit enhanced proliferation in MG patients，suggesting that mTEC can regulate the proliferation of Treg cells. This effect becomes more obvious after the intervention with Yiqi Jiedu prescription-containing serum，indicating that intervention effect of Yiqi Jiedu prescription on Treg cells can be produced during its treatment of mTEC， which may be one of the mechanisms of Yiqi Jiedu prescription-containing serum in alleviating MG.

Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.
Adult ; Female ; Humans ; Lymph Nodes ; Male ; Middle Aged ; Neck Dissection ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Thyroidectomy ; Young Adult

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

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.

OBJECTIVETo investigate the surgical options and clinical effects of delayed osteoporotic vertebral collapse.

METHODSFrom May 2010 to October 2014, 19 patients (20 vertebrae) with delayed osteoporotic vertebral collapse(Kümmell's disease) were enrolled in this study. There were 7 males and 12 females, aged from 65 to 87 years old with a mean of (73.5±5.62) years. According to Li staging system of Kümmell's disease, 3 cases were stage II, 13 cases (14 vertebrae) were stage III without spinal cord injury, 3 cases were stage III with spinal cord injury. Patients were respectively treated with percutaneous vertebroplasty(PVP) or percutaneous kyphoplasty(PKP) on the basis of the degree of postural reduction during operation. Injected cement volume, cement leakage, vertebral height restoration and local kyphotic reduction were observed. Visual analogue scale (VAS) and Oswestry Disability Index(ODI) were respectively used to assess the pain and function before and after operation. Frankel grade were used to evaluate neurological status.

RESULTSSeven vertebrae with satisfactory postural reduction were treated with PVP, 13 vertebrae with unsatisfactory postural reduction were treated with PKP, 3 patients with spinal cord injury were treated with decompression and posterior short segment fixation at the same time. All patients were followed up from 10 to 48 months with an average of 21.2 months. Cement leakage occurred in 4 cases with no symptom, 1 cases in PVP group and 3 cases in PKP group, there was no significant difference between two groups(=0.561). The priming volume of cement was (6.40±0.94) ml in PVP group and (5.46±1.09) ml in PKP group (>0.05). Three days after operation vs preoperation, the vertebral height restoration and kyphotic improvement was(31.71±11.35)%, (9.79±4.64)° in PVP group and (24.77±8.51)%, (8.15±2.97)° in PKP. There was no significant difference between two groups(>0.05). Three days after operation, VAS of low back pain and ODI in all patients were improved than preoperative data(<0.05), but there was no significant difference between two groups or between postoperative at 3 d and final follow up(>0.05). Nerve function of 3 patients underwent decompression and fixation from Frankel D to E.

CONCLUSIONSAccording to Li staging system and the degree of introperative postural reduction, individualized surgical treatment for Kümmell's disease can obtain good clinical results. Bad postural reduction during operation maybe a risk factor of cement leakage.