Chronic kidney disease has become a worldwide public health problem, and it negatively affects oral health. However, the data of the hemodialysis (HD) patients in Chinese population is unknown. This study was aimed to evaluate the dental health status and oral hygiene behavior of the HD patients in China. Patients undergoing HD therapy at two hospitals were asked to finish a questionnaire and receive dental examination (DMF-T). A total of 306 patients, aged 24-88 (58.09 ± 14.06), took part in this study. Although majority of the patients (77.78%) brushed their teeth at least twice a day, few (less than 5%) had ever used dental floss or mouthwash. More than half of the patients have not visited a dentist since the commencement of HD therapy. The dental examination showed that DMF-T was 9.63 ± 7.54, and the number of filled teeth (F-T) was only 0.70 ± 1.48. Moreover, the average caries restoration ratio and replacement index were 17.57% and 32.59%, respectively. HD therapy seems to prevent patients from visiting a dentist, and there is a great need for dental treatment for Chinese HD patients.
Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1β (IL-1β) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla’s rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1β pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1β/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1β pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1β pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.
Background This study aimed to evaluate the efficiency and prognostic factors of lenvatinib plus programmed death 1 (PD-1) blockades in patients with advanced hepatocellular carcinoma (HCC), especially for those with tumor occupation ≥50% volume of liver (TO ≥50%) or invasion in Vp4, who were excluded from the trial KEYNOTE-524. Methods We reviewed the clinical data of patients with unresectable HCC who received lenvatinib plus PD-1 blockades. The Kaplan-Meier method was performed to compare the progression-free survival (PFS) and the overall survival (OS). Cox proportional hazards model was adopted to identify independent prognostic factors. Results The median PFS and OS of the enrolled 84 HCC patients (31 patients with TO ≥50% and 30 patients with Vp4 invasion) were 6.6 and 11.4 months respectively. TO ≥50% had significantly negative impact on the objective response rates (ORR) (p = 0.015). HCC patients with TO ≥50% had significantly worse PFS and OS than those with TO < 50% (both p value < 0.001). Conversely, invasion in Vp4 did not significantly affect the ORR, PFS or OS for HCC patients receiving lenvatinib plus PD-1 blockades (p = 0.419, 0.528 and 0.855). After multivariate analyses, TO ≥50% was the independent predictor for PFS and OS (both p value < 0.001). No significant correlation was found between any kind of AEs and TO ≥50% or invasion in Vp4. Conclusion Lenvatinib plus PD-1 blockades can provide survival benefits for HCC patients with invasion in Vp4 and the indications of lenvatinib plus pembrolizumab may be further expanded. Locoregional treatments should be considered for patients with TO ≥50% during systemic therapy.
Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A > T (p.Asn35Ile) and the recurrent mutation c.101C > T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A > T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A > T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.
Introduction: Hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) have worse survival. Whether the presence of MVI indicates the necessity of more aggressive locoregional treatments for recurrences remains to be elucidated. Methods: We reviewed patients who underwent curative hepatectomy for primary HCC in our institution, and 379 patients with recurrent HCC up to three nodules smaller than 3 cm were enrolled. The Kaplan-Meier method was adopted to compare the secondary recurrence-free survival (sRFS) and post-recurrence survival (PRS) among patients undergoing hepatectomy, RFA and transarterial chemoembolization plus RFA (TACE-RFA). Cox regression analyses were performed to identify independent prognostic factors. Results: Both the sRFS and PRS of the MVI (À) group were significantly longer than those of the MVI (þ) group (p ¼ 0.001 and 0.011). For patients with MVI (À), no significant difference was found in sRFS or PRS among recurrent HCC patients receiving hepatectomy, RFA or TACE-RFA (p ¼ 0.149 and 0.821). A similar trend was found in patients with MVI (þ) (p ¼ 0.851 and 0.960). Further analysis found that TACE-RFA provided better sRFS than hepatectomy or RFA alone in patients with MVI (þ) and early recurrence within two years (p ¼ 0.036 and 0.044). Conclusion:For HCC patients with MVI (þ) and early small recurrence, TACE-RFA could achieve better prognosis than hepatectomy or RFA alone, while RFA alone provided comparable survival benefits compared with hepatectomy or TACE-RFA in other HCC patients with small recurrence.
Background In consideration of no standard exclusion criteria for hepatitis B virus (HBV) loads in hepatocellular carcinoma (HCC)-related clinical trials, this study aimed to investigate the prevalence of HBV-related exclusion criteria among current clinical trials and evaluate whether antiviral treatments could eliminate the adverse effects from high HBV loads for HCC patients. Methods This is a retrospective study including 772 HCC clinical trials on ClinicalTrials.gov and 1784 HCC patients receiving antiviral treatment. The Kaplan–Meier (K-M) method was used to compare the progression-free survival (PFS) and overall survival (OS) between different groups, and Cox regression analyses were performed to validate possible risk factors on PFS and overall survival OS. Results Among 772 clinical trials, 58.3% did not adopt baseline HBV loads as exclusion criteria, 18.0% was 2000 IU/mL, and 10.5% was receiving antiviral therapy. We observed baseline HBV loads had no significant impact on PFS (p = 0.491, 0.155, 0.119, 0.788, 0.280, 0.683 respectively) and OS (p = 0.478, 0.741, 0.263, 0.039, 0.999, 0.581 respectively) in all patients or each treatment group including hepatectomy, radiofrequency ablation, interventional therapy, targeted drugs and anti-programmed cell death immunotherapy, except for the OS of interventional therapy group, where patients with high HBV loads had higher BCLC stage, serum AFP level and ALBI grade (p = 0.009, 0.015 and 0.003, respectively). Conclusion Antiviral treatments could eliminate the adverse impacts of high HBV loads on the survival of HCC patients. Simplified eligibility criteria can be adopted for HCC patients with HBV infection where regular antiviral therapy should be enough.
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