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

Background: Understanding the virulence and pathogenicity of invasive nontyphoidal Salmonella (iNTS) in children may support timely treatment and enable closer monitoring of chronic infections. iNTS epidemiology in Asia remains inadequately described. We analyzed the genetic diversity and virulence genes associated with extra-intestinal invasion in Korean children. Methods: Salmonella isolates from children < 18 yrs of age diagnosed with moderate-tosevere salmonellosis between January 2019 and December 2021 were subjected to antibiotic susceptibility testing and whole-genome sequencing. Results: In total, 58 cases were included. We identified 20 serotypes, the most prevalent being Salmonella Enteritidis (N = 21), followed by Infantis (N = 6), I 4,[5],12:i:- (N = 5), and Bareilly (N = 5). Extra-intestinal invasion occurred in 12 (20.7%) cases involving Salmonella Oranienburg (2/2), Give (1/1), Javiana (1/1), Paratyphi B var. L(+) tartrate+ (1/1), Schwarzengrund (1/1), Singapore (1/1), Montevideo (1/2), Saintpaul (1/2), I 4:b:- (1/2), Infantis (1/6), and Enteritidis (1/21). While the numbers of total virulence genes and genes belonging to major virulence categories did not significantly differ between iNTS and noniNTS, several genetic factors, including Salmonella pathogenicity island (SPI)-1 (P = 0.039), SPI-2 (P = 0.020), SPI-5 (P = 0.014), SPI-13 (P = 0.010), cytolethal distending toxin-related genes (P = 1.4 × 10 –4 ), fepC (P = 0.021), and tcpC (P = 0.040) were more frequent in invasive isolates. Conclusions Salmonella Enteritidis-ST11 predominated in infections among Korean children, but invasive isolates were rare. Early detection of genetic factors associated with extra-intestinal invasion will be helpful for prompt and appropriate treatment.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Objective To prepare a variety of quality control(QC)materials for SARS-CoV-2 variants as an addition to the conven-tional SARS-CoV-2 nucleic acid QC products for the laboratory detection of mutant strains by optimizing the preparation and purification process of MS2 phage virus-like particle(VLP)technique,and evaluate their performances.Methods The typical mutation sequence fragments or full length S genes were designed and synthesized according to the genomic information of SARS-CoV-2 variants.Then,they were inserted into the downstream of maturase gene,coat protein and the pac-site of MS2 phage to construct a series of recombi-nant expression vectors.After induced by the prokaryotic expression system,the VLP products were purified through the polyethylenei-mine precipitation,ultrafiltration,nuclease digestion,and gel filtration chromatography.The obtained VLP were validated by the nucle-ic acid electrophoresis,protein electrophoresis,protein concentration determination,and fluorescence PCR,and their performances such as nucleic acid residue and stability were also evaluated.Results A total of 10 kinds of VLP containing the targeted sequences of the gene to be tested were prepared.The length of the foreign sequence wrapped in them ranged from 297 bp to 3 822 bp,which could be combined into a variety of QC materials for the mutation detection of different SARS-CoV-2 variants.The prepared VLP QC materials could not be effectively amplified without nucleic acid extraction or reverse transcription steps during the routine nucleic acid detection.The simulated QC samples remained stable after repeated freeze-thaw cycles.They could be stored stably for 2 months at 25 ℃ and 4 weeks at 37 ℃.Conclusion The established preparation and combined purification process of VLP QC materials can encapsulate vari-ous exogenous nucleic acid sequences with different lengths into the viral coat protein to form VLP,with high production efficiency.The VLP QC products prepared by the above process have stable performance and almost no residual exogenous nucleic acid,which can ef-fectively meet clinical requirements and ensure the quality of laboratory testing.

Objective:To investigate the diagnostic value of pelvic floor ultrasound combined with electromyography physiological parameters for postpartum stress urinary incontinence(SUI)of different degrees and pelvic floor function of primipara.Methods:A total of 160 SUI patients who admitted to Yan'an hospital of Kunming City from January 2019 to January 2022 were selected,and they were divided into abnormal group(110 cases)and normal group(50 cases)according to pelvic floor function(the muscle voltage values of different muscle fibers).The SUI was graded according to the Chinese Guidelines for Diagnosis of Urological Diseases and the International Incontinence Advisory Committee's Incontinence Questionnaire(ICI-Q-SF).The posterior horn(α)of bladder and urethra at rest,the displacements of the bladder neck on y-axis(△y)and x-axis(△x)after the rest to the fatigue action,the proximal urethral rotation angle after the rest to the fatigue action(γ),the posterior horn of bladder and urethra(β)after the fatigue action were observed.The electromyography was used to draw and record the pelvic floor myoelectric activity signals of the patients of two groups at five stages(pre baseline rest period,class II muscle fiber systole period,class II and I muscle fiber systole period,class I muscle fiber systole period and post baseline rest period).And then,the muscle voltage values of different muscle fibers on the surface of pelvic floor were quantified.Results:There was no statistically significant difference in Δ x between patients with postpartum SUI of different degrees.There were significant differences in △y,α,β and γ between patients with postpartum SUI of different degrees(F=7.162,7.655,14.998,2.758,P<0.05).The differences of the means of muscle voltages of pre and post baseline rest period,and class I muscle fiber systole period among patients with postpartum SUI of different degrees were not significant.The differences of the means of muscle voltages of class II,and the class II and I muscle fiber systole period among patients with postpartum SUI of different degrees were significant(F=12.062,24.501,P<0.05),respectively.There was no statistically significant difference in △x between the two groups.The △y,α,β and γ of abnormal group were significantly higher than those of normal group(t=8.991,8.691,9.389,27.552,P<0.05),respectively.There were no statistically significant differences in the means of muscle voltage values of the pre and post baseline rest period,and class I muscle fibers systole period between the two groups.The means of muscle voltage values of class II,and class II and I muscle fibers systole period in the abnormal group was significantly higher than them in the normal group(t=9.613,14.452,P<0.05),respectively.The sensitivities of △y,α,β,γ,the means of class II muscle fibers systole period,and the means of class II and I muscle fibers systole period of pelvic floor ultrasound and electromyography physiological parameters were respectively 71.60%,79.40%,81.40%,91.20%,83.30%and 82.40%,and the specificities of them were respectively 41.40%,37.90%,37.90%,60.30%,41.40%,and 44.80%in diagnosing postpartum SUI of different degrees of primipara.The sensitivity and specificity of the combined diagnosis of them were respectively 92.20%and 82.80%in diagnosing postpartum SUI of different degrees of primipara.The sensitivities of △y,α,β,γ,the means of class II muscle fibers systole period,and the means of class II and I muscle fibers systole period of pelvic floor ultrasound and electromyography physiological parameters were respectively 79.10%,77.30%,88.20%,89.10%,77.30%,87.30%,and the specificities of them were respectively 64.00%,64.00%,52.00%,46.00%,70.00%and 66.00%in diagnosing pelvic floor function of primipara.The sensitivity and specificity of the combined diagnosis were respectively 98.20%and 80.00%in diagnosing pelvic floor function of primipara.Conclusion:Pelvic floor electromyography physiological parameters and pelvic floor ultrasonic parameters have a certain value in diagnosing postpartum SUI of different degrees and pelvic floor function,and the value of the combined diagnosis of them is higher.

Raynaud's syndrome is a kind of small arterial spasmodic disease of limbs caused by the obstruction of blood circulation of extremities,which is typically manifested by the three-colour conversion of pallor,redness and cyanosis in the extremities upon exposure to cold or during emotional excitement.This article summarizes the clinical experience of associate chief physician WANG Jie in treating Raynaud's syndrome.WANG Jie proposed the treatment principle of"double warming and triple unblocking",i.e.,warming the meridians and collaterals,warming the interstices,unblocking the meridians and collaterals,unblocking qi and blood,and unblocking yang qi.The treatment method combining fire needling with Chinese medicine fumigation has proven to be quite effective.

Objective To construct prognostic model of disulfidptosis-related LncRNA (DRLncs) and explore the mechanism of LncRNA-small nucleolar RNA host genes（SNHG4） in promoting the progression of gastric cancer. Methods The multi-omics features of disulfidptosis genes in gastric cancer were first analyzed based on The Cancer Genome Atlas(TCGA) database. DRLncs were further screened, and disulfidptosis related gene recurrence score (DRG-RS) model was constructed to predict the overall survival(OS) and correlation with the clinical characteristics of gastric cancer patients. Differential gene analysis, functional enrichment and the correlation between chemotherapy efficacy in high- and low-risk groups were analyzed. Cell-counting kit-8 (CCK-8) assay and migration assay confirmed that LncRNA-SNHG4 promoted the malignant phenotype of gastric cancer cells. Western Blotting assay was used to detect the signaling pathway regulated by LncRNA-SNHG4. Results DRG-RS model including 8 DRLncs was successfully constructed, showing good performance in predicting OS of the patients with gastric cancer. DRG-RS model was significantly correlated with tumor-related signaling pathways, clinical characteristics and drug sensitivity of gastric cancer patients. LncRNA-SNHG4 expression was significantly increased in gastric cancer. LncRNA-SNHG4 promoted the proliferation and migration of gastric cancer cells. LncRNA-SNHG4 promoted the activation of Wnt signaling pathway in gastric cancer cells. Conclusions The DRG-RS model constructed in our study can stratify the prognosis of gastric cancer, and is closely related to malignant characteristics and chemotherapy efficacy of gastric cancer patients. The expression of LncRNA-SNHG4 significantly increased in gastric cancer tissues, and LncRNA-SNHG4 promoted the malignant phenotype of gastric cancer cells through the Wnt signaling pathway, suggesting that LncRNA-SNHG4 may play an important role in the progression of gastric cancer.

OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
Child ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Clinical Relevance ; Disease-Free Survival ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prednisone/therapeutic use* ; Prognosis ; Recurrence ; Immunoglobulin Light Chains, Surrogate/genetics*

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m²·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.
Humans ; Aged ; Azacitidine/therapeutic use* ; Prospective Studies ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Proto-Oncogene Proteins c-bcl-2