Morphological analyses and a novel de novo DLX3 mutation associated with tricho–dento–osseous syndrome in a Chinese family

Tricho–dento–osseous (TDO) syndrome, an autosomal‐dominant disorder, affects the morphological appearance of the tooth enamel, hair, and bone. Previous studies have confirmed that mutations in the DLX3 gene are responsible for TDO. In this study, we describe a Chinese patient with the typical traits of TDO – kinky hair, enamel hypoplasia, skull and jaw bones thickening, and sclerosis. Unfortunately, as a result of excessive attrition, we were unable to assess taurodontism. Examination of the tooth ground section showed a thin layer of enamel with no rods on the patient's tooth and abnormalities in Tomes' granular layer and the dentinal tubules. Scanning electron microscopy and energy‐dispersive X‐ray spectroscopy of the tooth enamel showed significant differences between the patient and the control individuals. A hair sample from the patient observed under a laser‐scanning microscope showed longitudinal grooves in the hair shaft. Dual‐energy X‐ray absorptiometry measurement showed that the bone mineral density values of the patient's bones was much higher than normal. Finally, genetic analysis revealed a novel de novo missense mutation c.533A>G (p.Q178R) in the conserved homeodomain of the DLX3 gene. This DLX3 mutation is the sixth causative mutation for TDO to be identified so far.     

髋臼横韧带定位髋臼假体前倾校正骨盆旋转

目的通过观察后外侧入路全髋关节置换术中骨盆的旋转变化，探讨术中骨盆旋转对髋臼假体前倾角植入的影响，评估使用髋臼横韧带作髋臼假体前倾定位的准确性以及对骨盆旋转角度变化的校正作用。 方法2015年1月至2016年1月河池市第三人民医院关节外科收治的行初次THA的40例44髋的髋关节疾病患者纳入本研究。纳入标准为：初次THA术的患者，术前、术后CT扫描质量符合标准、能确定髋臼解剖前倾角、髋臼假体前倾角的患者。排除标准：髋臼发育不良、强直性脊柱炎、既往有髋关节严重创伤手术史以及翻修术等，术前、术后双髋关节CT扫描，CT横断面上骨盆明显倾斜、两侧髋关节的中心显示明显不在同一层面、难以确定水平线测量前倾角的患者，予以排除。手术均采用侧卧位后外侧入路，切皮前将1枚施氏针以垂直于地面方向打入髂骨嵴，术中髋臼假体的前倾角，以髋臼横韧带为参照标志，通过直接参照或间接参照髋臼横韧带进行髋臼挫磨及安装臼杯，使髋臼假体开口平行韧带进行安放，在此过程中用摄像机记录施氏针相对于地面的角度变化，确定手术过程中骨盆旋转度数，同时测量并记录挫磨髋臼及安放假体时，相对于身体长轴髋臼手术前倾角的数值。术后通过CT测量髋臼假体前倾角，对术中手术前倾角和术后髋臼假体的前倾角、术前髋臼解剖前倾角数据进行t检验分析。 结果术中骨盆旋转发生在本研究中的平均度数为(18±4)°。44个髋关节中，所有的病例都能对髋臼横韧带进行辨认，术中手术前倾角平均为(33±5)°，有93%(41髋)的病例大于Lewinnek提出的"安全区"的前倾角上限25°，余下的7%(3个髋)也全部大于24°。术后CT测量髋臼假体的解剖前倾角为(21±10)°，与术前髋臼解剖前倾角度(19±7)°比较，差异无统计学意义(t＝1.264，P >0.05)。 结论在后外侧入路THA术中，体位改变骨盆前旋转会影响髋臼假体植入的准确性，使用髋臼横韧带作为解剖标志指导髋臼假体前倾角度的植入，可以排除患者体位改变骨盆旋转对前倾角的影响，提高髋臼假体放置的准确性。     

Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice

Objective To investigate the influence of earlier renal fibrosis on ischemia and reperfusion induced acute kidney injury. Methods Male C57BL/6 mice at eight to twelve weeks old age were divided into 4 groups randomly: (1)Sham (n=3); (2)Unilateral ureter obstruction (UUO, n=6): UUO for 3 days (UUO3d, n=3) and UUO for 5 days (UUO5d, n=3)；(3)Ischemia and reperfusion (IR, n=7): bilateral kidney ischemia for 40 minutes followed by 24 hours of reperfusion; (4)UUO for 3 days plus IR (UUO3d+IR, n=6): bilateral kidney ischemia after UUO 2 days for 40 minutes followed by 24 hours of reperfusion, and the real time for UUO was 3 days. Pathologic analysis for acute or chronic injury was performed on paraffin embedded kidney sections with hematoxylin and eosin (HE) or Masson staining. Apoptosis was detected by immunohistochemistry(IHC) and Western blotting with anti-caspase-3 antibody, and proliferation was observed by IHC with anti-ki67 antibody. Results On kidney sections with HE or Masson staining, it showed that the chronic kidney lesions and fibrosis got more severe as time of UUO prolonged from 3 days to 5 days; the area of matrix deposition increased in UUO5d and UUO3d mice significantly compared to Sham mice (P＜0.05) and was smaller in UUO3d mice compared with UUO5d mice obviously (P＜0.05). Acute kidney injury could be observed in UUO3d+IR mice, such as massive inflammatory cells infiltration, tubules dilation, brush border disappearance, tubular epithelial cells vacuolar degeneration, necrosis, casting formation, coexisting with chronic lesions: thinner cortex, broadened interstitial space, and increased blue stained matrix. Acute kidney injury score in UUO3d+IR mice was higher than that in IR mice significantly (P＜0.05), and serum creatinine level increased significantly in UUO3d+IR mice compared to Sham mice (P＜0.05). Caspase-3 expression increased and ki67 positive tubular cells decreased in UUO3d+IR mice than those in IR mice obviously (P＜0.05). Conclusion Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice through increasing apoptosis and decreasing proliferation of tubular epithelial cells.     

ALDH1 and tumor infiltrating lymphocytes as predictors for neoadjuvant chemotherapy response in breast cancer

Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC. Forty patients who underwent NAC were enrolled in this study. ALDH1 and TIL (T cells and tumor associated macrophages) were evaluated before and after NAC. The influences of ALDH1 expression status and TIL populations on both prognosis and chemotherapeutic response were evaluated. ALDH1 positivity was related to estrogen receptor (p?=?0.026) and progesterone receptor negativity (p?=?0.025). Positive change of ALDH1 after NAC tended to be associated with a poor NAC response (p?=?0.078). Patients with more CD8+ T cells before NAC and fewer CD68 (+) macrophages after NAC tended to have better OS, respectively (p?=?0.086, p?=?0.096). The chemotherapeutic response and prognosis of patients with breast cancer who received NAC are thought to be determined by the tumor microenvironment. Further research with more patients and a longer study period is needed.     

T4N (+)Ⅲ期食管胸中下段癌3DRT长期生存分析

目的 观察T₄N (+)Ⅲ期食管胸中下段癌IMRT长期生存情况及不良反应。方法 2004-2010年间300例T₄N (+)Ⅲ期食管中下段癌患者采用3DCRT 202例、IMRT 98例,常规分割照射剂量60 Gy。比较两种不同治疗方式的长期生存情况及不良反应。Kaplan Meier法计算生存率并Logrank法检验。结果 5、7年样本量分别为239、120例。3DCRT和IMRT组1、3、5、7年LC率分别为64.4%、40.6%、38.3%、34.2%和68.3%、55.3%、51.9%、51.9%(P=0.048),OS率分别为54.5%、19.8%、14.7%、10.9%和63.3%、34.7%、24.4%、20.3%(P=0.013)。分层分析显示年龄>65岁、放疗前食管造影长度>8.0 cm、CT最大横径>4.6 cm、GTV>60 cm³、邻近组织或器官受累、非手术 N₂期、未行化疗者,IMRT组OS率高于3DCRT组(P=0.022、0.003、0.022、0.034、0.016、0.044、0.047)。IMRT组GTVD_min、GTVD₁₀₀高于3DCRT组(P=0.000、0.000),脊髓D_max低于3DCRT组(P=0.000)。IMRT组急性放射性食管炎发生率明显高于3DCRT组,以轻度(1-2级)食管炎为著(P=0.000)。3DCRT组死于肿瘤局部因素的比率明显高于IMRT组(P=0.039)。结论 局部晚期食管胸中下段癌IMRT安全有效,LC率明显提高,正常组织保护良好,长期生存获益显著。基于回顾分析结果还有待前瞻性随机对照研究的证实。     

Invasive cutaneous squamous cell carcinoma incidence in US health care workers

Little data on cutaneous squamous cell carcinoma (SCC) epidemiology within the United States are currently available. Prior studies have focused on populations outside of the United States or been limited to regions within the US. In this study, prospective data were collected via biennial questionnaires from a total of 261,609 participants, which included women in the Nurses’ Health Study (NHS, 1976–2008) and Nurses’ Health Study II (NHS II, 1989–2009), and men in the Health Professionals Follow-Up Study (HPFS, 1986–2008). History of physician-diagnosed invasive SCC was confirmed by pathology record review. Over the entire follow-up period for each cohort, there were 1,265 invasive SCC cases per 100,000 persons in the NHS cohort, 389 cases per 100,000 persons in NHS II, and 2,154 cases per 100,000 persons in HPFS. An 18-year follow-up of participants in these cohorts revealed increasing invasive SCC incidence rates over time, with rates for men being consistently higher than those for women. In women, a larger proportion of invasive SCC lesions occurred on the lower extremities as compared to men (21 % in NHS vs. 6 % in HPFS, p < 0.0001; 14 % in NHS II vs. 6 % in HPFS, p < 0.0001), while in men, a larger proportion occurred on the head/neck (43 % in NHS vs. 60 % in HPFS, p < 0.0001; 48 % in NHS II vs. 60 % in HPFS, p < 0.0001). In summary, invasive SCC incidence rates among US men have been greater than those for women with distinct sites of common occurrence between men and women.     

Fate of mandibular canals displaced by enlarged cystic lesions: does the inferior alveolar neurovascular bundle relocate to its original position?

Our aim was to identify the positional changes of the inferior alveolar neurovascular bundle and evaluate the relocation of the displaced mandibular canal after enucleation of a cyst. Seventy patients (72 sites) who had had cysts enucleated were divided into three groups based on the degree of encroachment of the cystic lesion into the mandibular canal and whether a bone graft had been inserted after the cyst had been enucleated. The mean (range) of patients’ ages was 45 (18–75) years, and there were 29 male and 41 female patients. Group A comprised cysts with encroachment on the mandibular canal that were enucleated without a bone graft; Group B consisted of cysts with no encroachment of the mandibular canal, but were enucleated without a bone graft; and Group C comprised cysts with encroachment of the mandibular canal that were enucleated with a bone graft. The displacement of the mandibular canal was identified from analysis of computed tomographic (CT) images. Changes in the position of the mandibular canal were measured on panoramic radiographs. The mandibular canal was repositioned superiorly by a mean (SD) of 2.4 (1.65) mm after enucleation of the cyst, which was significant in Group A (p < 0.001), but not in Groups B and C. These results indicate that the displaced inferior alveolar neurovascular bundles that were not surrounded by bony canal tended to relocate towards a supposedly normal position, and after enucleation of the cyst the mandibular canal was remodelled in this new location. This tendency to relocate was blocked by bone grafting. Bone grafts are therefore recommended in cases where enough bony height is required for future insertion of implants.