MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1 / 国际口腔科学杂志·英文版

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.

To study the extent of lymph mode dissection and prognostic factors in patients with intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the impact of patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent surgical resection with or without lymph node dissection (LND), negative or positive lymph node metastasis detected by LND, different extents of LND, and prognostic factors on long-term prognosis of these patients.Methods:The clinical data of 162 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to October 2019 and underwent surgical resection with postoperative histopathological results confirming ICC were retrospectively analyzed. According to the degree of LND, these patients were divided into three groups: the undissected group ( n=68), N0 dissected group (prophylactic dissection) ( n=41) and N1 dissected group (positive dissection, n=53). Of 94 patients who underwent LND, 23 patients underwernt the first station LND (the routine dissection group, n=23), and 71 patients underwent extended LND (the extended dissection group, n=71). The Kaplan-Meier method was used to construct survival curves. Cox regression analysis was used to detect independent factors affecting survival and long-term prognosis of patients. Results:In this study, there were 87 males and 75 females, with a median age of 60 years.The median survival time of these 162 ICC patients was 10 months. The cumulative survival rates at 1-, 3- and 5-year after surgery were 37.6%, 16.5% and 7.9%, respectively. The 1-, 3- and 5-year cumulative survival rates of the N0 dissection group were 52.1%, 31.7% and 25.4%, respectively, which were significantly better than those of the undissected group (34.2%, 12.7%, 3.4%), and the N1 dissection group (30.3%, 11.4%, 0) ( P<0.05). There were no significant differences in postoperative survival between the extended dissection group and the routine dissection group ( P>0.05). Preoperative CA19-9 >50 U/ml ( RR=1.425, 95% CI: 0.962-2.112), maximum tumor diameter > 5 cm ( RR=0.672, 95% CI: 0.456-0.989), without LND ( RR=1.715, 95% CI: 1.140-2.580), positive margin ( RR=0.591, 95% CI: 0.390-0.897), and without postoperative adjuvant therapy ( RR=0.663, 95% CI: 0.504-0.872) were independent risk factors affecting postoperative survival ( P<0.05). Conclusions:LND in ICC patients improved long-term survival outcomes. However, extended LND did not improve prognosis of these patients. The preoperative CA19-9 level, maximum tumor diameter, lymph node dissection, surgical margin status, and postoperative adjuvant therapy were independent risk factors affecting long-term prognosis of these patients.

Observation on Biophysical Nature and the Special Complication of Basilar Fracture of the Skull / 中华创伤杂志

Among 109 patienta with basilar fracture of skull, 24 with special complications were analysed retrospectively, The complications included: delayed severe intracranial infection or brain abscess (7 cases), intracranial artery damage (9 cases), multiple cranial nerve injury (5 cases), and acute massive rhinorrhea and pneumocephalus (3 cases). Thirteen patients were operated on with various methods according to the clinical diagnosis. The relations between the biophysiological nature of the base of the skull and the mechanism of the complications were discussed. Forehead injury may cause "craniofacial cleavage fracture", and unilateral or bilateral temporal crush may caues "hinge fracture". All the basilar fractures mentioned above may damage the internal carotid artery and cranial nerves.

TUMORS ON THE BASE OF THE SKULL / 第二军医大学学报

30 cases of tumors on the base of the skull were reported. The symptoms and signs, the pathological types and the relationship between the location. and the histological findings of these tumors were analysed. 40 operations were carried out on 26 patients. 2/26 patients died postoperatively, the operative mortality was 7.7%.The choice of the operative procedure depended upon the tumor's location, size, nature and consistency, we suggested that the operative procedure of choice should be transcranial resection for the tumors located at the anterior or lateral region of the base of the skull, or at the cerebellepontine angle, because it would offer a wider operative field without any important structures there.The dumbbell tumors involving both intracranially and extracranially were difficult to remove. In such a case it was necessary for the neurosurgeon to cel-laberate with the otolaryngologist. The operative procedure in two stages was successful with no complication.

FOLLOW-UP RESULT OF IRRIGATION AND DRAINAGE OF CHRONIC SUBDURAL HEMATOMA / 解放军医学杂志

Affiliated Hospital. Second Military Medical College. ShanghaiForty-two cases of chronic subdural hematoma were treated by irrigation and drainage. Symptoms of elevated intracranial -pressure, localizing neurologic signs and cerebral angiography established the diagnosis. Operative treatment consisted of evacuation of the hematoma by repeated irrigation through burr holes made on the frontal and parietal side of the hematoma. A plastic tube was placed through the parietal hole for continuous drainage for three to four days. The above mentioned treatment is simple to perform and rather safe even for the senile and debilitated patients. Among 44 patients all 19 preoperatively unconscious patients regained consciousness postoperatively. Twenty-three cases were followed up from one to seventeen years. All patients recovered completely without recurrence of hema-toma or epilepsy, except one patient who is still having hemiparesis at present.