BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

Objective:To analyze factors associated with complications after radical surgery for colorectal cancer (CRC).Methods:The clinical data of 150 patients who underwent radical surgery for CRC at Xi'an Aerospace General Hospital between March 2017 and March 2023 were retrospectively analyzed. The incidence of postoperative complications was statistically evaluated. Based on the occurrence of complications, the patients were divided into two groups: an occurrence group ( n = 31) and a non-occurrence group ( n = 119). Univariate analysis was performed to identify factors associated with the incidence of postoperative complications, while logistic regression analysis was performed to determine the independent risk factors for complications following radical surgery for CRC. Results:Complications occurred in 31 patients among 150 patients who underwent radical surgery for CRC, resulting in an overall incidence of 20.67%. The most common complications were pulmonary infections and wound infections. There were no significant differences between the occurrence and non-occurrence groups regarding sex, age, body mass index, history of smoking, history of hypertension, preoperative white blood cell count, preoperative hemoglobin level, anesthesia method, tumor location, tumor size, or intraoperative blood loss (all P > 0.05). However, significant differences were observed in Dukes staging: the occurrence group had 21 patients in stage C, while the non-occurrence group had 50 patients in the same stage. In the occurrence group, there were 8 patients with poorly differentiated tumors, compared to 3 patients in the non-occurrence group. Additionally, 24 patients in the occurrence group had a history of diabetes, while 112 patients in the non-occurrence group reported the same. Open surgery was performed in 14 patients in the occurrence group, compared to 28 patients in the non-occurrence group. The American Society of Anesthesiologist classification indicated that there were 23 patients in the Ⅲ-Ⅳ category in the occurrence group, compared to 45 patients in the non-occurrence group. Furthermore, 21 patients in the occurrence group had surgical durations of 150 minutes or more, compared to 25 patients in the non-occurrence group. All these factors exhibited statistically significant differences between the two groups (all P < 0.05). Logistic multivariate regression analysis indicated that the independent risk factors for postoperative complications in CRC patients included Dukes stage C ( OR = 2.149, P < 0.001, 95% CI: 1.423-2.875), poorly differentiated tumors ( OR = 2.487, P = 0.001, 95% CI: 1.225-3.749), a history of diabetes ( OR = 2.812, P < 0.001, 95% CI: 1.605-4.20), open surgery ( OR = 2.67, P = 0.002, 95% CI: 1.166-4.174), The American Society of Anesthesiologist classification Ⅲ-Ⅳ category ( OR = 3.32, P < 0.001, 95% CI: 2.091-4.549), and surgical duration ≥ 150 minutes ( OR = 6.514, P < 0.001, 95% CI: 3.168-9.861). Conclusions:Numerous factors can influence the occurrence of complications following radical surgery for CRC. Clinicians should pay special attention to these factors and implement targeted prevention and control measures to reduce the incidence of postoperative complications.

Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

Objective:To analyze factors associated with complications after radical surgery for colorectal cancer (CRC).Methods:The clinical data of 150 patients who underwent radical surgery for CRC at Xi'an Aerospace General Hospital between March 2017 and March 2023 were retrospectively analyzed. The incidence of postoperative complications was statistically evaluated. Based on the occurrence of complications, the patients were divided into two groups: an occurrence group ( n = 31) and a non-occurrence group ( n = 119). Univariate analysis was performed to identify factors associated with the incidence of postoperative complications, while logistic regression analysis was performed to determine the independent risk factors for complications following radical surgery for CRC. Results:Complications occurred in 31 patients among 150 patients who underwent radical surgery for CRC, resulting in an overall incidence of 20.67%. The most common complications were pulmonary infections and wound infections. There were no significant differences between the occurrence and non-occurrence groups regarding sex, age, body mass index, history of smoking, history of hypertension, preoperative white blood cell count, preoperative hemoglobin level, anesthesia method, tumor location, tumor size, or intraoperative blood loss (all P > 0.05). However, significant differences were observed in Dukes staging: the occurrence group had 21 patients in stage C, while the non-occurrence group had 50 patients in the same stage. In the occurrence group, there were 8 patients with poorly differentiated tumors, compared to 3 patients in the non-occurrence group. Additionally, 24 patients in the occurrence group had a history of diabetes, while 112 patients in the non-occurrence group reported the same. Open surgery was performed in 14 patients in the occurrence group, compared to 28 patients in the non-occurrence group. The American Society of Anesthesiologist classification indicated that there were 23 patients in the Ⅲ-Ⅳ category in the occurrence group, compared to 45 patients in the non-occurrence group. Furthermore, 21 patients in the occurrence group had surgical durations of 150 minutes or more, compared to 25 patients in the non-occurrence group. All these factors exhibited statistically significant differences between the two groups (all P < 0.05). Logistic multivariate regression analysis indicated that the independent risk factors for postoperative complications in CRC patients included Dukes stage C ( OR = 2.149, P < 0.001, 95% CI: 1.423-2.875), poorly differentiated tumors ( OR = 2.487, P = 0.001, 95% CI: 1.225-3.749), a history of diabetes ( OR = 2.812, P < 0.001, 95% CI: 1.605-4.20), open surgery ( OR = 2.67, P = 0.002, 95% CI: 1.166-4.174), The American Society of Anesthesiologist classification Ⅲ-Ⅳ category ( OR = 3.32, P < 0.001, 95% CI: 2.091-4.549), and surgical duration ≥ 150 minutes ( OR = 6.514, P < 0.001, 95% CI: 3.168-9.861). Conclusions:Numerous factors can influence the occurrence of complications following radical surgery for CRC. Clinicians should pay special attention to these factors and implement targeted prevention and control measures to reduce the incidence of postoperative complications.

Objective To evaluate the correction rate,accuracy of pedicle screw fixation and overall clinical efficacy of intravertebral osteotomy and internal fixation surgery with the assistance of 3D printing guide plates in treatment of severe kyphosis.Methods A single-center nonrandomized clinical pilot study was conducted on 19 patients(8 males and 11 females)with severe kyphosis undergoing intravertebral osteotomy between December 2018 and June 2023.Seven of them(CAD group)had preoperative planning with computer-aided design(CAD)and intraoperative guidance of individualized 3D printing guide plates.And another 12 patients(control group)were corrected with conventional pedicle screw placement.Postoperative evaluation included assessment of posterior Cobb angle,spinal angular correction rate,accuracy of pedicle screw placement and Oswestry Dysfunction Index(ODI)questionnaire.Results The 19 patients were at a mean age of 48.0 years,and followed up for 26.4(9～54)months.All of them achieved relatively satisfactory corrective results,with those of the CAD group having a correction rate of 96.83％and those of the control group of 86.61％.There were no statistical differences in average intraoperative blood loss(857 vs 1 045 mL)and average operative time(344 vs 402 min),but significant difference was observed in average length of hospital stay(11 vs 18 d,P＜0.05)between the 2 groups.A total of 278 nails were placed in this study,including 70 guide-assisted pedicle screws,97.1％of which were grade A or B.In the control group,208 pedicle screws were placed,93.8％of which were grade A or B.Postoperative CT/X-ray scanning displayed that both groups achieved certain correction for kyphosis.No obvious difference was found in the average spinal angular correction(43.37° vs 36.10°),and significantly higher correction rate was seen in the CAD group than the control group(96.83％vs 86.61％,P＜0.01).The ODI value was notably lower in the CAD group than the control group(P＜0.05).Conclusion CAD-assisted preoperative planning,surgical simulation and individualized 3D printing guide plates can promote surgical correction and accuracy of pedicle screw placement and improves the quality of life of patients with severe kyphotic deformity.

BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.

Humans ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis ; Immunotherapy, Adoptive ; Hematopoietic Stem Cell Transplantation ; Receptors, Antigen, T-Cell ; Recurrence

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Objective To evaluate the clinical efficacy of ventricle -peritoneal or ventricle-atrial shunt in the treatment of skull defect with craniocerebral trauma combined with hydrocephalus in the same period. Methods Sixty-four patients with skull defect after craniocerebral trauma combined with hydrocephalus were randomly divided into observation group (n=32) and control group (n=32) The ventricle-peritoneal or ventricle-atrial shunt and skull repair were conducted simultaneously following surgical operation in observation group whereas ventricle-peritoneal or ventricle-atrial shunt and the skull defect were performed within 3 months and after 3 months following operation, respectively. The hydrocephalus symptoms, prognosis after three months ,clinical outcomes and the postoperative complications were evaluated. Results There was no significant difference in hydrocephalus symptoms between the observation group and control group (χ2=0.005,P>0.05). The GCS score, GOS score and neurological function score after three months were better than those before the treatment in these two groups (P<0.05). These functional parameters were significantly better in the observation group than in control group (P<0.05). The good rate in three months was significantly higher in the observation group than in control group (59.38％vs 31.25％,χ2=7.23, P<0.05). The incidence of complication was 6.25％(2/32) in the observation group, which was significantly lower than that in the control group (31.25％, 10/32) (χ2=7.13, P<0.05).Conclusion Cranioplasty combined with shunt in the treatment of skull defect complicated with craniocerebral trauma-associated hydrocephalus has low postoperative complications, good clinical prognosis and reliable efficacy, which is worthy of clinical application.