Antitumor effects of dioscin in A431 cells via adjusting ATM/p53-mediated cell apoptosis,DNA damage and migration

Skin cancer is the deadliest type of malignant disease and causes primary mortality worldwide. Dioscin, which exists in medicinal plants, has potent anticancer effects. However, its effects on skin cancer remain unknown. In the present study, the activity and mechanism of dioscin on the human skin cancer A431 cell line were investigated, MTT, colony formation, Transwell, wound-healing, TUNEL, Comet, immunofluorescence and western blot assays were used to assess the effects of dioscin on A431 cells. The results of MTT, colony formation, Transwell and wound-healing assays revealed that dioscin suppressed proliferation, colony formation and invasion of the cancer cells. TUNEL and comet assays demonstrated that dioscin exhibited significant effects on cell apoptosis and DNA damage. Investigations into the mechanism revealed that the expression levels of phosphorylated Ataxia telangiectasia-mutated (ATM) were considerably activated by dioscin, which significantly upregulated the expression levels of p53 to activate mitochondrial apoptosis signaling. Furthermore, the expression levels of BAX, cleaved caspase-3/9 and cleaved poly (ADP-ribose) polymerase were upregulated, and the expression levels of BCL-2 were downregulated by dioscin. Additionally, dioscin markedly downregulated the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, RHO and cdc42, which are all associated with tumor invasion. In addition, p53-small interfering RNA transfection experiments indicated that dioscin exhibited excellent activity against skin cancer in vitro by decreasing p53 expression. Overall, the present results suggested that dioscin inhibited skin cancer cell proliferation via adjusting ATM/p53-mediated cell apoptosis, migration and DNA damage, which should be considered as a potential option for future treatments of skin cancer.     

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

Thinned-out skin paddle versus collagen matrix as an optimized peri-implant soft tissue following fibula osteoseptocutaneous free flap: 3-year retrospective study

The objective of this study was to compare the implant longevity following two methods of peri-implant soft tissue optimization following free fibula flap (FFF): thinning of skin paddle (SP) and collagen matrix (CM). All patients who underwent rehabilitation with dental implants after mandibular reconstruction with FFF between June 2009 to May 2014 were retrospectively reviewed. Two methods of peri-implant soft tissue optimization were applied: (1) SP group, (2) CM group. Outcome measurements were: modified plaque index (mPI), modified sulcus bleeding index (mSBI), probing depth (PD), marginal bone loss (MBL), implant success rate and complication rates. A total of 24 patients with 69 implants were included in the study, with 8.7% (n = 6) of implants lost in 3 years. No statistically significant difference was found regarding the outcome measurements in both groups. Failed implants presented with statistically significant higher mPI, mSBI, PD and MBL scores during prosthesis delivery and subsequent follow-ups (P<0.03). In the SP group, one patient experienced SP necrosis which later underwent soft tissue optimization using CM. CM is an alternative peri-implant soft tissue, while thinning of SP is feasible if thickness is well controlled.     

Oral implant treatment for elderly patients

随着材料和技术的进步,现代口腔种植学得到了快速的发展。种植牙已成为恢复缺失牙的首选治疗方式。尽管在健康成人中,种植牙已经取得了很高的成功率,但对于老龄患者,随着身体机能的下降和伴发其他系统性疾病,种植治疗的风险相应地增加。老龄患者在进行种植治疗时应该考虑哪些影响因素以及如何预防可能的风险和并发症,应引起口腔种植医生的高度重视。本文对老龄患者口腔种植治疗的特殊性、种植成功率、老年患者的全身系统疾病考量和用药考量等方面进行探讨,以供临床参考。     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

子宫内膜功能亢进性疾病的“异病同治”诊治研究思路＊

笔者根据现代临床子宫内膜的病理演变过程结合中医“异病同治”理念，提出“子宫内膜功能亢进性疾病”概念，涵盖5种常见的子宫内膜疾病：无排卵性异常子宫出血（Abnormal Uterine Bleeding Ovulatory dysfunction，AUB-O），子宫内膜息肉（Endometrial Polyp，EP），子宫内膜异位症（Endometriosis，EMs），子宫腺肌病（Adenomyosis，AM），子宫内膜癌（Endometrial Carcinoma，EC）。基于文献的汇总，分析得到此类疾病的子宫内膜病理演变与中医病因病机的关联性，为寻找关键通路、创新性治疗此类疾病提供了重要的参考方向，对深化中医妇科学常见疾病的共性病因病机提供了理论依据和探索思路。