OBJECTIVE To investigate the potential mechanism of Sanqi danshen tablets in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Core targets of Sanqi danshen tablets in the treatment of NAFLD were explored by network pharmacological methods. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were also performed. Based on the results obtained from network pharmacological studies， using SD rats as subjects， the NAFLD model was induced by feeding them high-fat diet. The effects of Sanqi danshen tablets on pathological changes such as lipid droplet vacuoles and lipid accumulation in the liver tissue of NAFLD rats， as well as its impact on relative indicators of lipid metabolism， inflammatory responses and oxidative stress， were investigated. RESULTS A total of 20 core targets for the treatment of NAFLD with Sanqi danshen tablets were screened， primarily involved in GO functions such as biological regulation， cellular membrane and binding， and enriched in signaling pathways related to inflammatory responses， oxidative stress and lipid metabolism. Compared with the model group， lipid droplet vacuoles were reduced significantly in low-dose， medium-dose， high-dose groups of Sanqi danshen tablets and positive control （simvastatin） group， the number of lipid droplets decreased significantly and the color became lighter. The contents of total cholesterol， triglyceride （except for medium- dose group of Sanqi danshen tablets）， aspartate transaminase， alanine transaminase， tumor necrosis factor-α （except for low-dose group of Sanqi danshen tablets）， interleukin-17 （except for Sanqi danshen tablets groups） and malondialdehyde （except for low- dose group of Sanqi danshen tablets） in liver tissue were significantly decreased， while the content of superoxide dismutase was significantly increased （P＜0.01 or P＜0.05）. CONCLUSIONS Sanqi danshen tablets exert anti-inflammatory， antioxidant and lipid metabolism regulating effects by influencing the levels of inflammation， oxidative stress and lipids metabolism-related indicators， thereby improving NAFLD in rats.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Objective:To explore expression of each member of miR17-92 cluster in peripheral blood mononuclear cells(PBMCs)of patients with gout,to predict their possible targets and pathways of action,and to evaluate their possible mechanism and clinical significance in gout.Methods:A total 67 gouty arthritis(GA)patients were selected,including 22 patients with acute gout arthritis(AG)and 45 patients with intermittent gout(IG),and 35 normal health control(HC)were selected in Affiliated Hospital of North Sichuan Medical College.RT-qPCR measured expressions of miR17-92 cluster,IFN-γ,IL-10 and some members of JAK-STAT pathway,and relevant laboratory indicators were collected to analyze correlation between each other.Results:Relative expressions of miR17,miR18a,miR19a,miR20a and miR19b were significantly changed in AG,IG and HC(H=8.753,P<0.05;H=6.338,P<0.05;H=6.523,P<0.05;H=9.061,P<0.05;H=9.729,P<0.01).JAK3 and STAT2 expressions were statistically different in AG,IG and HC groups(H=10.349,P<0.01;H=14.801,P<0.01).Expression of IFN-γ was statistically different among AG,IG and HC groups(H=8.734,P<0.05).In AG patients,miR18a expression was inversely correlated with IBIL,Crea,MO and HGB.miR19a ex-pression was negatively associated and TC,UA and HGB.miR20a expression was negatively associated with Crea.miR19b expression was negatively associated with UA and HGB.In IG patients,miR17 expression was negatively associated with IBIL,WBC,LY and MO.miR18a expression was positively associated with ALP,miR19a expression was negatively associated with TC and UA,and miR20a expression was negatively associated with ADA and UA.Conclusion:miR17-92 cluster may regulate development and partici-pate in clinical pathology of gout by targeting JAK-STAT pathway.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Objective To investigate the levels of serum folate and vitamin B12(VB12)and their association with the level of neurodevelopment in preschool children with autism spectrum disorder(ASD).Methods A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited.Serum levels of folate and VB12 were measured using chemiluminescent immunoassay.The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children,and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment.Results The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children(P＜0.05).Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients(P＜0.05),and serum VB12 levels were positively correlated with adaptive behavior,fine motor,and language developmental quotients(P＜0.05).In ASD children aged 2 to＜4 years,serum folate levels were positively correlated with developmental quotients in all domains(P＜0.05),and serum VB12 levels were positively correlated with language developmental quotient(P＜0.05).In male ASD children,serum VB12 levels were positively correlated with language and personal-social developmental quotients(P＜0.05).Conclusions Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels,especially in ASD children under 4 years of age.Therefore,maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children,especially in ASD children under 4 years of age.[Chinese Journal of Contemporary Pediatrics,2024,26(4):371-377]

Objective To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis,by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis.Methods Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected,and the samples of necrotic osteonecrosis from chronic osteomyelitis(necrotic group),and normal bone tissue(control group)were collected.Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform,and the gene expression in bone tissue was calculated by FPKM.The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group.Genes were enriched by GO and KEGG.MAP3K7 and NFATC1 were selected as differential targets in the verification experiments,by using rat osteomyelitis animal model and im-munohistochemical analysis.Results A total of 5548 differentially expressed genes were obtained by high throughput sequenc-ing by comparing the necrotic group and control group,including 2701 up-regulated and 2847 down-regulated genes.The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened,the common genes expressed in both MAPK and osteoclast differentiation pathway were(inhibitor of nuclear factor κ subunit Beta,IκBKβ),(mitogen-activated protein ki-nase 7,MAP3K7),(nuclear factor of activated t cells 1,NFATC1)and(nuclear factor Kappa B subunit 2,NFκB2).In rat os-teomyelitis model,MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue.Conclusion Based on the transcriptome analysis,the MAPK signaling and osteoclast differentiation pathways were closely related to chronic os-teomyelitis,and the key genes IκBKβ,MAP3K7,NFATC1,NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Female ; Humans ; Antibodies, Antineutrophil Cytoplasmic ; Organizing Pneumonia ; Autoantibodies ; Glomerulonephritis ; Anti-Glomerular Basement Membrane Disease ; Pneumonia ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications*

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m² d1 + oxaliplatin 100 mg/m² d 1 + etoposide 60 mg/m² d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
Humans ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies ; Etoposide ; Neoplasm Recurrence, Local/drug therapy* ; Asparaginase ; Deoxycytidine ; Lymphoma, T-Cell, Peripheral/drug therapy* ; Lymphoma, Extranodal NK-T-Cell/therapy* ; Oxaliplatin/therapeutic use*

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.