ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

This study explored a novel digital design and fabrication method for a double constrained split orthodontic miniscrew guide to improve the accuracy and safety of clinical miniscrew implantation and reduce related complications. A patient requiring miniscrew implantation was selected, and data were acquired using cone beam computed tomography (CBCT) and intraoral optical scanning. For the construction of a double constrained split guide including a screw-hole guide and an insertion rod guide, different types of software such as Mimics 24.0, Geomagic wrap 2021, and Materialise magics 21.0 were utilized for 3D reconstruction, model integration, and guide design. The guide was then fabricated via laser metal 3D printing. Model and intraoral try-in results demonstrated that the guide fitted well and was stable. Postoperative CBCT verified that the final miniscrew implantation site was consistent with the preoperative design, and no related complications occurred. This double constrained split orthodontic miniscrew guide provides a precise and safe digital solution for clinical miniscrew implantation.
Humans ; Bone Screws ; Cone-Beam Computed Tomography ; Printing, Three-Dimensional ; Orthodontic Anchorage Procedures/instrumentation* ; Imaging, Three-Dimensional ; Computer-Aided Design

Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

BACKGROUND:Existing neuroimaging techniques,including magnetic resonance imaging,computed tomography,and high-resolution ultrasound,lack the capability to provide real-time intraoperative positioning images to surgeons.However,the clinical implementation of near-infrared fluorescence imaging technology has made it possible to directly visualize surgical target areas,offering a novel solution for real-time nerve identification during surgery. OBJECTIVE:To provide a summary and overview of the research progress in near-infrared fluorescence imaging technology for intraoperative neuroimaging. METHODS:The first author used the computer to search for the documents published from January 2010 to July 2023 in WanFang,CNKI,and PubMed with the key words of"near-infrared fluorescence imaging,optical imaging,nerve imaging"in Chinese and English.A few classic old documents were also included.Initial screening was performed by reading the titles and abstracts;duplicate,low-quality,and irrelevant content documents were excluded.A total of 69 articles were finally included for review. RESULTS AND CONCLUSION:Near-infrared fluorescence imaging guided by indocyanine green has been clinically used to identify and locate tubular organs such as blood vessels,ureters,and bile ducts,as well as various tumors during surgery.This technique is currently considered a well-established imaging method in precision surgery.In the field of intraoperative neurofluorescence imaging,indocyanine green is currently the only near-infrared fluorescent dye used in clinical research.The ideal neuroimaging agent should possess certain characteristics,including easy administration in the perioperative period,logD between 0.5 and 3 at pH=7.4,molecular mass below 500 Da,excitation and emission wavelengths within the near-infrared window,long-term retention in nerve tissue,high signal-to-background ratio,and high safety.In the future,the development of near-infrared neurofluorescence imaging agents should focus on synthesizing complexes of indocyanine green and neural-specific targets.This technology not only enables intraoperative neurofluorescence imaging,but also holds promising prospects for in-situ monitoring of nerve regeneration and diagnosis of neurological diseases.

Objective To evaluate the clinical efficacy of kissing-stent implantation in the treatment of chronic iliac-vena cava occlusion.Methods The clinical data of 22 patients with chronic iliac-vena cava occlusion,who received kissing-stent implantation,were retrospectively analyzed.The surgical success rate and the procedure-related complications were recorded,the postoperative 3-,6-and 12-month stent patency rates were calculated,and the postoperative 6-month Villalta score was compared with its preoperative value.Results The technical success rate of kissing-stent implantation was 100％.No procedure-related surgical complications occurred.The postoperative 3-,6-and 12-month stent patency rates were 95.5％,90.9％and 86.1％respectively.The postoperative 6-month Villalta score was(12.14±2.80)points,which was remarkably lower than preoperative(20.91±3.16)points,the difference was statistically significant(P＜0.05).Conclusion The implantation of kissing-stent can successfully reconstruct iliac-vena cava with satisfactory short-term efficacy for chronic iliac-vena cava occlusion.

Objective:To observe the effect of epigallocatechin gallate (EGCG) on intestinal injury in sepsis, and to investigate the effect on endoplasmic reticulum stress (ERS) apoptotic pathway.Methods:Sixty male SD rats were selected and divided into five groups according to the randomized numeric table method: the sham operation group (Sham group), the cecal ligation and puncture sepsis group (CLP group), the sepsis+EGCG low-dose group (postoperative intraperitoneal injection of EGCG 25 mg/kg, EL group), the sepsis+EGCG medium-dose group (postoperative intraperitoneal injection of EGCG 50 mg/kg, EM group), and sepsis+EGCG high-dose group (postoperative intraperitoneal injection of EGCG 75 mg/kg, EH group), each group with 12 rats. The rats in each group were executed 24 h after modeling and specimens were collected. Inflammatory factors in serum were detected by enzyme-linked immunosorbent assay. Pathological changes of ileum were observed under light microscope after hematoxylin eosin staining and evaluated according to the Chiu's score. The intestinal tissues were stained for tight junction protein-1 (CLDN1, Claudin-1), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), cysteinyl aspartate specific protein-12 (Caspase-12), and CCAAT enhancer-binding protein homologous protein (C/EBP-homologous protein antibody, CHOP) protein expression was detected by protein immunoblotting assay. The positive areas of Claudin-1, p-PERK, CHOP, and Caspase-12 in intestinal tissue were detected by immunohistochemistry.Results:Compared with the Sham group, the serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and the Chiu's score of rats in the CLP group were increased (all P<0.05). The ileal mucosal tissues showed reduced expression of Claudin-1, ERS apoptosis-associated protein p-PERK, CHOP, and Caspase-12 expression were increased (all P<0.05). Compared with the CLP group, the intestinal injury in rats was alleviated after the administration of low, medium and high dose EGCG intervention (all P<0.05). The serum inflammatory factor level, Chiu's score and the protein expression level and positive area of ERS apoptosis-related proteins, p-PERK, CHOP, and Caspase-12 in the small intestinal tissues of EL group were further reduced compared with that of the CLP group were further decreased, and EM group was further decreased than EL group, and EH group was further decreased than EM group (all P<0.05). The protein expression level and positive area of Claudin-1 in small intestinal tissues of EL group were further increased compared with that of CLP group (both P<0.05), and EM group was further increased compared with that of EL group and EH group was further increased compared with EM group (all P<0.05). Conclusions:EGCG may have a protective effect on intestinal injury in septic rats by inhibiting the activation of ERS-induced apoptotic pathway, and the efficacy of high-dose EGCG has a better effect.

Objective:To investigate the clinicopathological, immunophenotypic and molecular genetic characteristics, and differential diagnosis of NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) in the gastrointestinal tract.Methods:Two NTRK-RSCNs diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China and one case diagnosed at Zhengzhou Central Hospital, Zhengzhou, China from 2019 to 2022 were collected. The clinical data, histopathology, immunophenotypes and prognosis were analyzed. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect NTRK gene rearrangements, while relevant literature was also reviewed and discussed.Results:Two patients were male and one was female, with the age of 17, 47 and 62 years, respectively. The tumors were located in the duodenum, ascending colon and descending colon, respectively. The tumors were protuberant masses with gray and rubbery sections. Their maximum diameter was 2.5, 5.0 and 10.0 cm, respectively. Histologically, the tumors invaded mucosa, intrinsic muscle and serosal adipose tissue. Tumor cells consisted of spindle or oval shaped cells with monotonous morphology and arranged in bundles or stripes pattern. Spindle cells were mildly to moderately atypical, with slightly eosinophilic cytoplasm and inconspicuous nucleoli. Necrosis and mitotic figures were observed in one high-grade tumor. All tumors expressed CD34, S-100 and pan-TRK in varying degrees. FISH analysis showed that NTRK1 gene was break-apart in 1 case and NTRK2 gene break-apart in 2 cases. NGS technologies showed LMNA::NTRK1 fusion in one case, STRN::NTRK2 fusion in another case. All patients recovered well after the surgery without recurrence at the end of the follow-up.Conclusions:NTRK-RSCN is rarely diagnosed in the gastrointestinal tract and has significant variations in morphology. It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.

Objective To analyze the relationship between serum exosomal microRNA(miR)-7-5p expression levels in children with asthma and their short-term prognosis.Methods A total of 132 asthmatic children(asthma group)and 30 healthy children(control group)from Tangshan Vocational & Technical College Affiliated Hospital between October 2021 and May 2023 were included as study subjects.These asthmatic children were categorized into a good prognosis group(n=91)and a poor prognosis group(n=41)based on their Childhood Asthma Control Test results.The levels of allergy history,forced vital capacity(FVC),fractional exhaled nitric oxide(FeNO),and miR-7-5p level among groups were compared,and logistic regression analysis was conducted to identify risk factors for the short-term prognosis of asthmatic children.The Kappa test,receiver operating characteristic(ROC)curve,and mean absolute error(MAE)value were used to evaluate indicators in predicting short-term prognosis in children with asthma.Results The level of miR-7-5p in the asthma group[0.53(0.49,0.64)]was lower than that in the control group[1.03(0.97,1.10)],with significant difference(Z=8.548,P＜0.001).The poor prognosis group exhibited a higher proportion of allergy history(68.29％)and FeNO[38(36,41)ppb]levels,and lower FVC[1.86(1.84,2.05)L]and miR-7-5p levels[0.47(0.43,0.52)]compared to the good prognosis group[46.15％,35(30,40)ppb,1.94(1.87,2.06)L,0.60(0.50,0.68)],and the differences were significant(x2/Z=2.854～6.450,all P＜0.05).Multivariate logistic regression analysis revealed that a history of allergies(OR=3.388,95％CI:1.328～8.643,P=0.011)and high FeNO levels(OR=1.161,95％CI:1.064～1.267,P=0.001)were independent risk factors,while a high level of miR-7-5p(OR=0.090,95％CI:0.033～0.248,P＜0.001)was an independent protective factor for the short-term prognosis of asthmatic children.The area under the ROC curve for miR-7-5p+allergy history+FeNO in predicting the short-term prognosis of asthmatic children was 0.851,which was higher than that for miR-7-5p alone(0.851,Z=2.097,P=0.036)and allergy history+FeNO(0.726,Z=4.239,P＜0.001).The Kappa value for miR-7-5p+allergy history+FeNO was 0.67,which was higher than miR-7-5p(0.44)and allergy history+FeNO(0.41).The MAE for miR-7-5p+allergy history+FeNO was 0.022,which was lower than miR-7-5p alone(0.067)and the combination of allergy history+FeNO(0.035).Conclusion Elevated level of miR-7-5p in the serum exosomes of asthmatic children is linked to a favorable short-term prognosis.The combination of miR-7-5p,allergy history,and FeNO may have certain value in evaluating the short-term prognosis of asthmatic children.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.