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 improve the understanding of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma complicated with hemophagocytic syndrome (HPS) in children.Methods:A retrospective analysis was conducted on the diagnosis and treatment of a case of EB virus-associated ALK-negative anaplastic large cell lymphoma in a child with HPS as the clinical manifestation at Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University in December 2019, and literature review was conducted.Results:The patient was an 8-year-old boy who was admitted with facial yellowing and recurrent fever. After comprehensive examination, he was diagnosed with HPS. After 2 weeks of chemotherapy according to the hemophagocytic lymphohistiocytosis (HLH)-1994 regimen, lymph node biopsy was performed. Immunohistochemistry showed that CD30, CD5, CD4, CD7, EMA, TIA-1, and VIM were positive, ALK, CD2, CD3, CD8, CD117, CD20, INI-1, CD68, MyoD1, Myogenin, Desmin, Langerin, SALL4, CD56, GramB, and CK were negative, LCA was weakly positive, TFE3 was partially weakly positive, and Ki-67 positivity index was 90%. The clonality assay for TCRD gene rearrangement was positive. The supplementary diagnosis was ALK-negative anaplastic large cell lymphoma, and the clinical risk stratification was classified as high-risk group. After 2 courses of chemotherapy with the South China Children's Cancer Group-non-Hodgkin lymphoma 2017 regimen (SCCCG-NHL-2017), he was evaluated as complete remission (CR), and after 6 courses, he was still evaluated as CR. The patient received autologous hematopoietic stem cell transplantation. The patient was followed up until May 2024, his survival status was good.Conclusions:EB virus-associated ALK-negative anaplastic large cell lymphoma complicated with HPS in children is rare, chemotherapy combined with autologous hematopoietic stem cell transplantation is a feasible treatment option.

Objective To investigate the expression of circZNF652 in prostatic cancer(PCa)tissues and PCa cell lines,and its impact and possible mechanism on proliferation and migration.Methods Differential ex-pression of circRNAs in plasma tissues from PCa patients and benign prostatic hyperplasia(BPH)patients were detected by using gene chip technology.The expression levels of circZNF652 in PCa cell lines(22RV1,LNCaP,DU145,PC3)and normal prostate epithelial cells were measured by quantitative real-time PCR(qPCR).The correlation between different circZNF652 expression levels with the overall survival(OS)time and clinicopathological features of PCa patient were analyzed.The effects of interfering circZNF652 on PCa cell proliferation,colony formation,invasion and migration ability were assessed through CCK-8 assay,colony formation assay,Transwell assay,wound healing assay and EdU cell proliferation assay.The online database TargetScan was used to predict the binding sites between circZNF652 and miR-140-3p,and the dual-luciferase reporter gene assay and RNA pull-down assay confirmed the interaction of circZNF652 and miR-140-3p.This interaction was further validated in PC3 and DU145 cells by interfering circZNF652 as well as in blood sam-ples from PCa and BPH patients.StarBase predicted the binding sites between miR-140-3p and HMGB1,and the HMGB1 expression levels were tested after miR-140-3p overexpression in PC3 and DU145 cells.Western blot was used to detect the HMGB1 expression levels in PCa and BPH patient,PCa cell lines(DU145,PC3)as well as RWPE-1 cells.The dual-luciferase reporter gene assay,RNA immunoprecipitation(RIP)and RNA pull-down were conducted to verified the interaction between miR-140-3p and HMGB1,and the HMGB1expression in PC3 and DU145 cells were detected after transfecting different constructs(si-NC,si-cir-cZNF652#1,si-circZNF652#1+inhibitor NC,si-circZNF652#1+miR-140-3p inhibitor)to further confir-ming that miR-140-3p directly regulates HMGB1.Results The gene chip and qRT-PCR results showed that the expression level of circZNF652 in the plasma of PCa patients was higher than that in BPH patients,com-pared with low-grade PCa and BPH patients,the plasma cirZNF652 expression level in the patients with high grade PCa was upregulated(P<0.001,P<0.01).Compared with normal prostate epithelial cells,the expres-sion levels of circZNF652 in 22RV1,LNCaP,DU145 and PC3 cell lines were upregulated(P<0.05,P<0.05,P<0.001,P<0.01);The OS time in the PCa patients with circZNF652 high expression was shorter than that in PCa patients with circZNF652 low expression.Clinicopathological features analysis revealed that the circ-ZNF652 expression was correlated with the PCa stage(T stage and N stage)and Gleason score.Knocking down circZNF652 expression inhibited the proliferation,invasion and migration in DU145 and PC3 cells.The online database TargetScan predicted that there was the complementary sequences between circZNF652 and miR-140-3p,and dual-luciferase reporter gene and RNA pull-down assays confirmed thatcircZNF652 acted as a sponge for miR-140-3p in PCa cells,interfering circZNF652 experiment in PC3 and DU145 cells also proved this point.The expression of miR-140-3p in the plasma of PCa patients was significantly decreased compared with BPH patients(P<0.05),and the expression level of miR-140-3p was negatively correlate with the ex-pression level of circZNF652(r=-0.888,P<0.001).The database StarBase analysis results showed that there are complementary sequences of HMGB1 mRNA 3'-UTR and miR-140-3p,and the downstream target gene of miR-140-3p was HMGB1.The dual-luciferase reporter gene,RIP and pull-down assays confirmed the direct binding between miR-140-3p and HMGB1.The Western blot experiment found overexpression of miR-140-3p resulted in the HMGB1 expression decrease in DU145 and PC3 cells.Silencing circZNF652 expression resulted in the decrease of HMGB1 protein levels in the DU145 and PC3 cells,while inhibiting miR-140-3p could reverse this decrease.Conclusion Overexpression of circZNF652 could promote the progression and me-tastasis of PCa by regulating the miR-140-3p/HMGB1 axis.

Gender recognition based on the analysis of fingerprint residue can assist investigators in narrowing down the scope of investigation and play an important role in the field of criminal investigation.This study established a quantitative analysis method for lipid substances in fingerprints based on gas chromatography-mass spectrometry(GC-MS).Fatty acids in fingerprints were methylated using sulfuric acid methanol derivatization reagent(7%,V/V),the extraction reagent was dichloromethane-methanol(1∶1,V/V)solution,the reaction temperature was 70℃and the heating time was 45 min.Quantitative analysis of the relative content of 23 kinds of fatty acids and squalene in fingerprints residue by different genders was conducted,and orthogonal partial least squares-discriminant analysis(OPLS-DA)was used to reduce the dimensionality of the quantitative results.A total of 13 kinds of components in the fingerprints were selected to maximize the difference in relative content between male and female fingerprints.Three machine learning models,including binary logistic regression(BLR),support vector machine(SVM)and random forest(RF),were further used as feature variables to classify the gender of fingerprints.The classification performance of each model was compared through five indicators,and it was found that the most suitable model for binary classification of fingerprint gender was SVM model.The results showed that the SVM fingerprint residual gender binary classification model established based on the relative content data of 13 kinds of lipid substances in fingerprints achieved a classification accuracy of 90%and an area under the receiver operating characteristic curve(AUC)value of 0.98.This study provided a new research method for detecting lipid components in fingerprints and a methodological basis for gender recognition of fingerprints.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To study the effects of TCM ointment rubbing technique on pain, swelling, and knee joint function in patients with knee osteoarthritis (KOA) after total knee arthroplasty (TKA).Methods:A randomized controlled trial was conducted. In this study, 80 patients with KOA who underwent TKA treatment in the Department of Sports Medicine I, Wangjing Hospital, China Academy of Traditional Chinese Medicine from October 2022 to March 2024 were taken as the study subjects. They were divided into two groups with random number table method, with 40 cases in each group. Both groups were treated with conventional Western medicine + rehabilitation training after surgery, and the observation group was combined with TCM paste mo technique on this basis. VAS score was used to assess the degree of pain at different time points, and skin fold was used to measure the circumference of the upper knee circumference and the circumference of the lower knee circumference, and knee Injury and osteoarthritis outcome score (KOOS) was used to assess the degree of knee joint function recovery.Results:After treatment, the observation group after surgerythe at 7 d (2.57 ± 0.84 vs. 4.00 ± 0.85, t=7.54) and 14 d (0.80 ± 0.93 vs. 2.70 ± 1.04, t=8.56) VAS scores were lower than those in the control group ( P<0.001). After treatment, the observation group after surgerythe at 7 d the superior circumference [(48.32 ± 4.57) cm vs. (50.53 ± 3.97) cm, t=2.32], and inferior circumference [(36.71 ± 2.95) cm vs. (39.21 ± 6.86) cm, t=2.12], at 14 d the superior circumference [(45.68 ± 4.69) cm vs. (47.96 ± 3.89) cm, t=2.37], and inferior circumference [(34.96 ± 2.96) cm vs. (36.70 ± 4.35) cm, t=2.10] were lower than those in the control group ( P<0.05). The observation group after surgerythe at 14 d the the knee joint mobility [(115.32 ± 2.12) ° vs. (113.34 ± 2.16) °, t=4.14] and KOOS scores (85.52 ± 0.82 vs. 80.32 ± 1.13, t=23.56) were higher than those in the control group ( P<0.01). Conclusion:TCM ointment rubbing technique has significant advantages in improving pain, swelling and knee joint mobility after artificial knee arthroplasty, which can effectively restore knee joint function.

Objective Exploring the expression of sterol regulatory element-binding protein 1(SREBP1)and acetyl-CoA carboxylase alpha(ACCα)in prostate cancer tissues and their impact on proliferation,migration and in-vasion of prostate cancer cells DU145.Methods The expression levels of SREBP1 and ACCα in prostate cancer tis?sue were analyzed using online databases including TIMER,UALCAN,GEPIA,and THE HUMAN PROTEIN ATLAS.Paraffin?embedded specimens from 58 cases of prostate cancer(PCa)and 58 cases of benign prostatic hyper?plasia(BPH)diagnosed at the Fifth Affiliated Hospital of Zunyi Medical University from January 2016 to December 2018 were collected.Immunohistochemistry was used to detect the expression of SREBP1 and ACCα in these tissues.Following the knockdown of SREBP1 in DU145 cells using shRNA,the changes in ACCα expression were assessed by qRT?PCR.The CCK?8 assay was employed to evaluate cell proliferation,while flow cytometry was used to analyze cell cycle distribution.Western blot was performed to measure the expression of SREBP1 and ACCα.Transwell assays were conducted to assess changes in migration and invasion capabilities after silencing SREBP1 in DU145 cells.Scratch assays were used to examine the impact of SREBP1 knockdown on the healing capability of DU145 cells.EdU assays were performed to detect changes in cell proliferation following the silencing of SREBP1.Oil Red O staining was utilized to observe changes in lipid content within prostate cancer cells after interference with SREBP1 expression.Results Analysis using online databases such as TIMER and UALCAN revealed that ACCα expression was signifi?cantly elevated in prostate cancer tissues compared to normal prostate tissues(P<0.001).After silencing SREBP1,the proliferation,migration and invasion capability of DU145 cells were significantly reduced compared to the control group(P<0.01),and flow cytometric analysis showed G1 phase arrested in DU145 cells(P<0.01).Knockdown of SREBP1 resulted in a significant decrease in lipid content in prostate cancer cells(P<0.01).Conclusions SREBP1 may promote the proliferation,migration and invasion of prostate cancer cells through regulating the expres?sion of ACCα.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*