Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To assess the clinical value of conventional contrast enhanced CT(CECT),multi parameter energy spectrum CT,and contrast enhanced MR(CEMR)imaging methods in evaluating hepatocellular carcinoma(HCC)after TACE treatment.Methods The clinical data of 66 HCC patients,who underwent TACE treatment at authors' hospital and received CECT,multi parameter energy spectrum CT and CEMR in 1-3 months after treatment,were retrospectively analyzed.Taking DSA results as the gold standard,the recurrent or residual lesions detected by DSA were classified as positive lesions,while the lesions having no obvious recurrence or residues were classified as negative lesions.The positive lesions that were detected by both DSA and other imaging methods were regarded as true positive lesions.The accuracy,sensitivity,specificity,Kappa value were used to compare the values of CECT,multi parameter energy spectrum CT and CEMR in evaluating the positive/negative lesions of HCC after TACE treatment,and the number of detected lesions and accuracy rate were used to evaluate the values of the above imaging methods in demonstrating the iodine oil deposition status and in diagnosing true positive lesions.Results A total of 133 positive lesions and 35 negative lesions were detected by DSA.The accuracy of CEMR in diagnosing lesions was highest,the accuracy rate was 88.70％(both P＜0.05);CEMR and energy spectrum CT had the highest diagnostic efficiency,the sensitivity for positive lesions was 92.31％and 81.95％respectively,and the difference between the two methods was not statistically significant(P＞0.05).No statistically significant difference in the ability of diagnosing negative lesions existed between each other among the three groups(all P＞0.05).The Kappa value suggested that the ability for diagnosing lesions after TACE treatment of CEMR was stronger than that of energy spectrum CT(Kappa value was 0.68 and 0.56 respectively,both P＜0.05).CECT and multi parameter energy spectrum CT had the same accuracy in evaluating the iodine oil deposition status(both were 91.7％).No statistically significant difference in diagnosing even iodine oil deposition of the true positive lesions existed between each other among the three groups(all P＞0.05).For diagnosing uneven iodine oil deposition of the true positive lesions,CEMR had the highest accuracy(92.50％,all P＜0.05).Conclusion CEMR and multi parameter energy spectrum CT have more reliable diagnostic performance than conventional CECT,besides,CEMR has the highest diagnostic performance.However,multi parameter energy spectrum CT and CECT are the better choice for evaluating the deposition status of iodine oil.

Purpose To summarize the clinical and imaging features of neonatal herpes simplex encephalitis(NHSE).Materials and Methods Clinical and imaging data of 5 NHSE from January 2016 to June 2023 in Beijing Children's Hospital,Capital Medical University were retrospectively collected.All five children underwent MRI examinations,with three of them undergoing enhanced scanning simultaneously.Two children had previously undergone CT scans.The location,density/signal,enhancement characteristics as well as follow-up imaging changes of the lesions were reviewed.Results The main clinical manifestations of NHSE were fever(5 cases)and seizure(4 cases),sometimes accompanied by herpes(2 cases).Imaging examinations in NHSE typically presented with symmetric(1 case)or diffuse/multifocal(4 cases)lesions in bilateral cerebral hemispheres,along with involvement of the bilateral thalamus(5 cases).Early CT scans showed either no abnormalities(1 case)or extensive areas of low density(1 case).MRI examinations usually demonstrated restricted diffusion of acute phase lesions(3 cases)and significant leptomeningeal enhancement in affected areas(3 cases).Intracranial lesions often led to the diffuse atrophy of brain parenchyma and polycystic encephalomalacia(3 cases),indicating a poor prognosis.Conclusion The clinical manifestations of NHSE are nonspecific.Early MRI examinations are of great value for accurate diagnosis and disease evaluation.

Objective:To analyze high-risk factors for poor neurological prognosis in full-term neonatal purulent meningitis based on clinical and brain MRI features.Methods:This study was a case-control study. The clinical and brain MRI data of 79 neonates with purulent meningitis were retrospectively collected at Beijing Children′s Hospital, Capital Medical University from January 2016 to January 2022. Follow-up assessments including growth and development, as well as neurological sequelae, were conducted over a minimum follow-up period of 6 months. The patients were divided into two groups with good ( n=49) and poor prognosis ( n=30) according to follow-up results. Chi-square tests were used to compare clinical and brain MRI features between the two groups, and a multivariate logistic regression analysis was performed to explore the high-risk factors for poor neurologic prognosis in full-term neonates with purulent meningitis. Results:There were statistically differences between two groups regarding the incidence of seizures, early-onset manifestations, positive cerebrospinal fluid (CSF) culture, CSF white cell counts, and CSF protein concentration ( P<0.05). Statistically differences were also found in the occurrence rates of ependymitis, obvious ventricular dilatation/hydrocephalus, spotty and patchy brain injury/hemorrhage, and destructive lesions within the brain parenchyma ( P<0.05). The results of multivariate logistic regression analysis indicated that seizures ( OR=5.722, 95% CI 1.126-29.072, P=0.035), early-onset neonatal purulent meningitis ( OR=3.657, 95% CI 1.073-12.459, P=0.038), ependymitis ( OR=8.851, 95% CI 1.169-67.017, P=0.035), obvious ventricular dilatation/hydrocephalus ( OR=12.675, 95% CI 1.085-148.110, P=0.043), and destructive lesions within the brain parenchyma ( OR=16.370, 95% CI 1.575-170.175, P=0.019) were independent risk factors for poor prognosis. Conclusions:The occurrence of seizures, early-onset manifestations as well as ependymitis, obvious ventricular dilatation/hydrocephalus, and destructive lesions within the brain parenchyma on MRI are high-risk factors for poor prognosis in the full-term neonate with purulent meningitis.

Pulmonary hypertension has a high mortality rate,and although targeted therapy is available,it is still incurable,and the long-term prognosis for patients is poor.As a tyrosine kinase inhibitor,imatinib was approved for marketing in China in 2002 for the treatment of chronic myelogenous leukemia and other tumor diseases.In addition to the antitumor effects,imatinib was found to improve hemodynamics and exercise tolerance in patients with severe pulmonary arterial hypertension,but the safety was suboptimal.With the emergence of new formulations of imatinib targeted at the lungs,it is expected to become a new targeted drug for pulmonary arterial hypertension.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6.Methods·The HN6 cell line was selected,cultivated,and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis:control group,3.125 μg/mL group,6.25 μg/mL group,12.5 μg/mL group,25 μg/mL group,50 μg/mL group,and 100 μg/mL group.After 24 and 48 h of cultivation,CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity.Subsequent experiments were divided into control group,25 μg/mL group and 50 μg/mL group.Flow cytometry was used to examine the effects of gingipain extract on cell cycle.Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability.Real-time PCR(RT-PCR)and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells.Results·Stimulated with gingipain extract for 24 h,the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL(P=0.025),50 μg/mL(P=0.000),and 100 μg/mL(P=0.049)groups compared to the control group.After 48 h,proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024),12.5 μg/mL(P=0.006),25 μg/mL(P=0.000),50 μg/mL(P=0.000),and 100 μg/mL(P=0.000)groups compared to the control group.Cell cycle analysis revealed that,after 24 h of gingipain stimulation,the proportion of HN6 cells in the G1 phase decreased,while the proportion in the S+G2 phase significantly increased compared to the control group(25 μg/mL group:P=0.024;50 μg/mL group:P=0.001).Compared to the control group,the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased(P=0.001).Compared to the control group,the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased.RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased,the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased,while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group.Conclusion·Gingipain extract could promote proliferation,migration,and invasion of oral squamous cell carcinoma HN6 cells.

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China. Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5. Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV. Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.