Objective To investigate the alleviating effect of jujuboside B (JuB) on acute epilepsy in mice and its protective effect on hippocampal neurons. Methods An in vitro epilepsy model was established by stimulating primary hippocampal neurons with cyclothiazide (CTZ). Spontaneous epileptiform discharge was recorded using patch clamp technique. An acute epilepsy model was induced in adult male C57BL/6 mice by intraperitoneal injecting pentylenetetrazol (PTZ) following pretreatment with JuB, and severity of epilepsy was recorded. Mice were euthanized and brain tissues were collected 24 hours after model establishment. The expression levels of mitoptosis related proteins in the hippocampus were detected by Western blotting. Neuronal damage in the hippocampal CA1 and CA3 regions was observed using pathological staining. Results JuB reduced the frequency of CTZ-induced epileptiform discharges (P＜0.001). Pretreatment with 30 mg/kg and 50 mg/kg JuB decreased the maximal behavioral seizure score and prolonged the latency to Racine stage Ⅲ seizures in PTZ-induced epileptic mice (P＜0.001). Compared with the PTZ group, JuB treatment downregulated Bax protein level (P＜0.01) and upregulated Bcl-2 protein level (P＜0.05) in acute epileptic mice. Furthermore, JuB protected neuronal viability in the hippocampal CA1 (P＜0.05) and CA3 (P＜0.01) regions, and ameliorated pathological morphological changes including cellular disarray, unclear boundaries, pyknosis, fragmentation, and dissolution. Conclusions JuB exhibits antiepileptic effects both in vivo and in vitro. It exerts potential antiepileptic effects by inhibiting mitoptosis and attenuating neuronal damage in the hippocampus in an acute epilepsy model.

Objective To investigate the activation of microglia and astrocytes, the secretion of pro-inflammatory factors, and the survival of neurons in the hippocampus of mice with acute seizures induced by pentylenetetrazol (PTZ) 24 hours after the onset of seizures. Methods Adult male C57BL/6 mice were randomly assigned to the control group and the PTZ-induced acute epileptic seizure group using random numbers, with 28 mice in each group. The activation status of microglia and astrocytes in the CA1 region of the hippocampus was evaluated by immunofluorescence 24 hours after the onset of seizures. RNA was extracted from the hippocampal tissue to detect the expression level of inflammatory factor mRNA, and HE staining was used to assess the survival of neurons in the hippocampus. Results Twenty-four hours after PTZ-induced acute seizures in mice, the numbers of activated Iba1⁺ microglia (55.72±4.29 vs 35.71±9.66, P＜0.001) and GFAP⁺ astrocytes (51.61±8.21 vs 37.64±5.27, P＜0.01) in the CA1 region were significantly increased compared with the control group; the proportion of M1 microglia was significantly increased (0.58±0.02 vs 0.35±0.08, P＜0.0001), while the proportion of M2 microglia was significantly decreased (0.25±0.08 vs 0.44±0.09，P＜0.01); the mRNA level of pro-inflammatory factor IL-1β in the hippocampus was significantly higher than that in the control group (2.49±1.61 vs 1.02±0.68, P＜0.05); the numbers of neurons in the CA1 (284.91±73.32 vs 498.88±176.79, P＜0.05) and CA3 (247.42±50.20 vs 457.78±150.08, P＜0.05) regions during the acute phase was significantly reduced compared with the control group. Conclusions Twenty-four hours after PTZ-induced acute epileptic seizures in mice, microglia and astrocytes in the CA1 region of the hippocampus are activated, with microglia mainly presenting the M1 phenotype to exert pro-inflammatory effects, secretions of pro-inflammatory factors increasing, and surviving hippocampal neurons decreasing.

Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective To investigate the diagnostic value of endoscopic sign of light blue crest(LBC)capsuling papillary lesion(LCPL)for high-risk intestinal metaplasia(IM).Methods A total of 314 patients(352 biopsy specimens)who underwent endoscopic examination and biopsy in Department of Gastroenterology of Army Medical Center of PLA from January 2021 to June 2023 were recruited,and HE and HID-AB staining(the golden standard of high-risk IM)were apllied to detect the histological types and IM types.The samples were subsequently divided into chronic inflammation group,low-risk IM group,high-risk IM group,well-differentiated intestinal-type gastric cancer group,and poorly-differentiated intestinal-type gastric cancer group.The positive rate of LCPL in each group and its diagnostic efficacy were analyzed based on endoscopic images of the biopsy sites.Logistic regression analysis was used to investigate the relationship between LCPL sign and high-risk IM,as well as the clinical and pathological features associated with LCPL sign.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of LCPL for high-risk IM,using indicators such as sensitivity,specificity,Youden index and area under the curve(AUC).Results The positive rate of the LCPL sign in high-risk IM group was 75.70%,significantly higher than that of the other groups(all P<0.001).Logistic regression analysis showed that LCPL sign was significantly correlated with high-risk IM(OR=30.286,95%CI:13.528～67.804,P<0.001).When the sign was employed in diagnosing high-risk IM,the sensitivity was 69.84%,the specificity was 93.75%,the Youden's index was 0.636,and the AUC value was 0.818(95%CI:0.773～0.857).Besides sensitivity,all above parameters of LCPL sign showed significantly better diagnostic efficacy than those of traditional LBC sign,which is used as a sign for diagnosing IM(P<0.001).Moreover,recognition of LCPL sign was not easily affected by age(OR=1.130,95%CI:0.709～1.800,P=0.607),lesion site(Angular incisure:OR=2.360,95%CI:0.732～7.613,P=0.151;Autrum:OR=2.257,95%CI:0.756～6.744,P=0.145),and presence of peptic ulcers(OR=1.085,95%CI:0.208～5.652,P=0.923).Significantly,94.12%of positive and 66.94%of negative LCPL signs could be rapidly recognized within 3 s(OR=4.536,95%CI:1.372～14.997,P=0.013).Conclusion LCPL sign shows high efficacy and potential clinical application value for high-risk IM in gastric mucosa of endoscopic diagnosis.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Objective To explore the expression of serum lipocalin-2(LCN2)and latent transforming growth factor-β binding protein 2(LTBP2)in ovarian cancer patients and their relationship with clinicopathological features and prognosis.Methods A total of 108 ovarian cancer patients treated in Baoji Hospital Affiliated to Xi'an Medical College from February 2020 to December 2021 were included in the ovarian cancer group.Another 108 patients with benign ovarian lesions during the same period were included and labeled as the lesion group,and 108 healthy female volunteers undergoing physical examination were assigned to the control group.ELISA method was used to detect serum LCN2 and LTBP2 levels.The relationship between serum LCN2 and LTBP2 levels and prognosis survival rate in ovarian cancer patients was analyzed using the Kaplan-Meier method.Multivariate Cox regression analysis was performed to identify the risk factors affecting the prognosis of ovarian cancer patients.Results Serum LCN2 and LTBP2 levels increased in the control group,lesion group,and ovarian cancer group in sequence(P<0.05).Among patients with high expression of serum LCN2 and LTBP2,the proportions of FIGO stage Ⅲ-Ⅳ,tumor maximum diameter>3 cm,and postoperative lymph node metastasis were higher than those of FIGO stages Ⅰ-Ⅱ,tumor maximum diameter≤3 cm,and non lymph node metastasis(P<0.05).The median survival time of ovarian cancer patients with high serum LCN2 and LTBP2 expression was lower than that of patients with low expression(Log-rank χ2=5.367、6.305,P<0.05).The survival rate of patients with FIGO stage Ⅲ～Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,LCN2 and LTBP2 high expression was lower than that of patients with FIGO stage Ⅰ～Ⅱ,tumor maximum diameter≤3 cm,no postoperative lymph node metastasis,and low LCN2 and LTBP2 expression(P<0.05).FIGO stages Ⅲ-Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,high LCN2,and high LTBP2 were independent risk factors affecting the 3-year survival rate of ovarian cancer patients(P<0.05).Conclusion Serum LCN2 and LTBP2 are upregulated in ovarian cancer patients,and are closely related to FIGO staging,tumor maximum diameter,and postoperative lymph node metastasis.They are important factors affecting prognosis and may serve as biomarkers for evaluating prognosis.

Objective:To investigate the protective effect of a composite hydrogel against hydrogen peroxide(H2O2)-induced oxidative stress injury in the cardiomyocytes,and to clarify its possible mechanism.Methods:The mice were subcutaneously injected with 100 μL of hydrogel.After normal feeding for 1,14,and 28 d,the mice were sacrificed.Tissue samples were collected and subjected to HE staining to observe the histocompatibity of the hydrogel.The primary cardiomyocytes isolated from 1-day-old SD rats were used to establish an oxidative stress injury model.The primary cardiomyocyties were divided into control,H2O2 and H2O2+Hydrogel groups.The primary cardiomyocytes in control group were cultured normally,the primary cardiomyocytes in H2O2 group were treated with 200 μmol·L-1 H2O2 for 24 h,and the primary cardiomyocytes in H2O2+Hydrogel group were incubated with 1 g·L-1 composite hydrogel and 200 μmol·L-1 H2O2 for 24 h.The viabilities of cardiomyocytes in various groups were assessed by cell counting kit-8(CCK-8)method.Dihydroethidium(DHE)and 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining were used to assess the reactive oxygen species(ROS)levels in the cells.The expressions of filamentous actin(F-actin)in the cells in various groups were detected by phalloidin fluorescence staining;the expressions of connexin 43(Cx43)and cardiac troponin T(cTnT)proteins in the cardiomyocytes in various groups were detected by immunofluorescence method.The apoptotic rates of cardiomyocytes in various groups were assessed with TUNEL staining method.The expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in the cardiomyocytes in various groups were assessed by Western blotting method.Results:The HE staining results showed that the inflammatory cells around the implanted hydrogel were less infiltrated,and the inflammatory reaction of subcutaneous implantation was less.Compared with control group,the viability of cardiomyocytes in H2O2 group was significantly decreased(P＜0.05),the level of ROS in the cells was increased(P＜0.05),the expression levels of Cx43,cTnT and F-actin proteins in the cells were decreased(P＜0.001),the apoptosis rate of cardiomyocytes were decreased(P＜0.01),the expression level of Bcl-2 protein in the cells was increased(P＜0.001),and the expression level of Bax protein was decreased(P＜0.01).Compared with H2O2 group,the viability of cardiomyocytes was significantly increased(P＜0.05),the level of ROS in the cells was decreased(P＜0.01),the expression levels of cTnT,Cx43 and F-actin proteins were increased(P＜0.01),the apoptotic rate of cardiomyocytes were significantly decreased(P＜0.001),the expression level of Bcl-2 protein in the cells were decreased(P＜0.01),and the expression level of Bax protein was increased(P＜0.01).Conclusion:Hydrogel may promote the expression of cardiomyocyte-related proteins by scavenging ROS in the environment and inhibit the cardiomyocyte apoptosis to achieve the protective effect on the cardiomyocytes under oxidative stress.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective To investigate the value of chest contrast-enhanced CT(C-CECT)combined with artificial intelligence iterative reconstruction(AIIR)for bronchial artery(BA)imaging.Methods Seventy patients who underwent C-CECT were prospectively enrolled.The images were reconstructed with AIIR(AIIR group)and hybrid iterative reconstruction(HIR,HIR group),respectively.The overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were subjectively graded using a 5-point scale by two radiologists,respectively.The subjective scores and inter-observer agreement were compared between groups.The noise(SD)in reconstructed images of thoracic aorta,pulmonary trunk,BA and spinal erectors,the contrast-to-noise ratio(CNR)of the above 3 arteries relative to spinal erectors,and the diameters of BA at the origin,bifurcation and pulmonary hilum were compared between groups.Results The scores of the overall image quality,the traceability of BA,the sharpness of BA and the diagnostic confidence of abnormalities of BA were all significantly higher in AIIR group than those in HIR group(all P＜0.001),all with good inter-observer agreement(Kappa=0.46-0.73).SD of the aorta,pulmonary artery trunk,BA and erector spinal muscle in AIIR group were lower than those in HIR group,while CNR of above 3 arteries were higher than those in HIR group(all P＜0.05).No significant difference of the diameter of BA at each position was found between groups(all P＞0.05),while the consistency of measurement of AIIR group was higher than that of HIR group(intra-class correlation coefficient:0.89-0.94 vs.0.63-0.78).Conclusion C-CECT combined with AIIR could significantly improve imaging quality and diagnostic confidence of BA.