Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8⁺ T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.

Bacillus spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
Anti-Bacterial Agents ; Anti-Infective Agents/pharmacology* ; Bacillus ; Bacillus subtilis ; Lipopeptides/pharmacology* ; Peptides, Cyclic/pharmacology*

Objective:To investigate the effect of lentivirus-mediated silencing of mitochondrial ribosomal protein L35 (MRPL35) gene on the growth of human esophageal cancer TE-1cells, and to clarify its mechanism.Methods:Three kinds of human esophageal cancer cells, TE-1, ECA109and KYSE150, were selected.The relative expression levels of MRPL35mRNA in three kinds of cells by real-time quantitative PCR.The esophageal cancer TE-1cells were divided into shMRPL35group and shCtrl group, and the cells were infected with si-RNA lentivirus and si-RNA lentivirus;the esophageal cancer cell line stably silenting the MRPL35gene was established.Real-time quantitative PCR and Western blotting methods were used to detect the efficiency of MRPL35gene silencing.The cell growth curves in various groups were detected by CCK-8method, and the apoptotic rates were detected by flow cytometry after AnnexinⅤ-PE/7AAD double staining.Results:Three kinds of esophageal cancer cells expressed MRPL35gene, and the expression levels were not statistically significant between them (P＞0.05) .The results of real-time quantitative PCR and Western blotting methods showed that the mRNA and protein levels of MRPL35in the TE-1cells in shMRPL35group were significantly lower than those in shCtrl group (P＜0.05) .Compared with shCtrl group, the cell growth speed in shMRPL35group was decreased (P＜0.05) , and the apoptotic rate was significantly increased (P＜0.01) .Conclusion:Silencing MRPL35gene can inhibit the proliferation of esophageal cancer TE-1cells and plays a role through the apoptotic pathway.

Objeetive To investigate the clinical efficacy of inverted intmmedullary nail combined with medial minimally invasive plate in treatment of type C2 and C3 distal femoral fractures.Methods A retrospective case control study was conducted on 38 patients with complex distal fractures of the femur treated from January 2015 to January 2017.There were 22 males and 16 females,aged 24-72 years [(45.6 ± 2.5)years].AO fracture classification was type C2 in 24 patients and type C3 in 14.All of them were fresh closed fractures.The time duration from injury to operation was 4-16 days (average,7.5 days).Based on the different surgical methods,the patients were divided into lateral single plate fixation group (single plate group,20 patients) and inverted intramedullary nail combined with medial minimally invasive locked plate fixation group (locked plate group,18 patients).The two groups were compared in terms of operation condition,early weight bearing time,fracture healing time,postoperative complications,postoperative knee function and activity of living.Hospital for Special Surgery (HSS) score was used for evaluating postoperative knee function and Barthel index for activity of living.Results The patients were followed up for 10-24 months [(12.2 ± 1.8) months].The operation duration was (110.5 ± 35.4) min for single plate group and (116.7 ± 42.3) min min for locked plate group(P ＞0.05).Intraoperative blood loss in single plate group was [(450.5 ± 120.7)ml] and [(455.2 ± 130.4) ml] in locked plate group (P ＞ 0.05).The early weight bearing time in single plate group was (28.5 ± 8.6)days and 18.7 ± 4.9 (P ＜ 0.01)days in the locked plate group.The fracture healing time in single plate group was (8.5 ± 2.2) months,and [(6.5 ± 1.6) months] in locked plate group (P ＜ 0.01).After 3 weeks,6 months and 12 months,HSS scores of knee joint function of the locked plate group was significantly better than that of single plate group (P ＜ 0.01).At 6 months and 12 months after operation,Barthel index score of locked plate group was significantly better than that of single plate group (P ＜ 0.01).No infection occurred in two groups after operation.There were no complications such as internal fixation failure,knee valgus,external rotation deformity or fat embolism in locked plate group.There were two cases of internal fixation failure,one knee eversion,and two knee varus in single plate group (P ＜ 0.01).Conclusion Compared with single plate fixation,the therapeutic method of inverted intramedullary nail combined with medial minimally invasive locked plate has the advantages of early weight bearing time,quick recovery,better function restoration and fewer complications,and hence is a preferable choice for treatment of type C2 and C3 complex distal femoral fractures.

Objective To investigate the risk of death between older and non-older critical patients in intensive care unit (ICU) in Shuyang People's Hospital.Methods A retrospective cohort study was conducted. The critical patients who aged 15 or above, and admitted to ICU of Shuyang People's Hospital from January 2014 to December 2016 were enrolled, and all the data was collected from theregistration and electronic medical records in the ICU. The prevalence and causes of death in ICU critical patients during the study period were observed. The patients were divided into elderly group (65 years and older) and non-elderly group (15-65 years), and logistic regression analysis was performed for the risk of death in the two groups.Results During the study period, 2707 critical patients in emergency were admitted to the ICU of Shuyang People's Hospital, and patients not satisfied the inclusion criteria were excluded. Finally, a total of 2466 patients were enrolled in the analysis with the male and female ratio of 1.6 : 1, an average age of (61.8±17.3) years, a median Glasgow coma scale (GCS) score of 6 (4, 8), and with a median ICU stay of 3 (1, 6) days. In 2466 critical patients, the most common cause of critical state was spontaneous intracerebral hemorrhage (25.5%) and traumatic brain injury (17.0%), with a fatality rate of 46.0% and 39.5% within first 7 days respectively. Compared with the non-elderly patients (n = 1415), the incidences of death of the elderly patients (n = 1051) due to traumatic brain injury, cerebral infarction, heart failure/cardiovascularcrisis, and respiratory critically ill were significantly increased (9.4% vs. 4.7%, 2.9% vs. 0.8%, 5.0% vs. 2.1%, 2.5% vs. 1.0%, respectively), while the incidence of death for pesticide/drug poisoning in the elderly group was significantly lower than that in the non-elderly group (0.2% vs. 1.2%, allP < 0.01). Stepwise logistic regression analysis showed that traumatic brain injury [hazard ratio (HR) = 1.878, 95% confidence interval (95%CI) = 1.233-2.864,P = 0.003), cerebral infarction (HR = 0.435, 95%CI = 0.229-0.826, P = 0.011), heart failure/cardiovascular crisis (HR = 0.399, 95%CI = 0.238-0.668,P = 0.000), and respiratory critically ill (HR = 0.239, 95%CI = 0.126-0.453,P= 0.000) in the older patients were significantly high risk factors of death as compared with those in non-older patients.Conclusions In the general ICU, the most common cause is spontaneous intracerebral hemorrhage and traumatic brain injury in critical patients with a high fatality rate. The risk of death in elderly patients with severe traumatic brain injury, cerebral infarction, heart failure/cardiovascular crisis, respiratory critically ill is higher than that of the non-elderly patients.

Objective To explore the microsurgery methods in patients with early intracranial aneurysm rupture. Methods Sixty-seven patients with early intracranial aneurysm rupture received the emergency microsurgery after releasing cerebrospinal fluid from improved Paine point via pterion craniotomy. Thirty-nine patients received surgery within 1 d after intracranial aneurysm rupture, and the other 28 patients were within 1-3 d. Results The therapeutic effect was evaluated by Glasgow outcome score (GOS) at discharge. Among the 45 patients with Hunt-Hess Ⅰ-Ⅲ grade, cure was in 41 cases, improved in 4 cases. Among the 22 patients with Hunt-HessⅣ-Ⅴgrade, cure was in 6 cases, improved in 6 cases, moderate disability in 4 cases, severe disability in 1 case, and death was in 5 cases. Conclusions The microsurgery of clipping aneurysm directly via pterion approach is still by far the most reliable treatment. And releasing cerebrospinal fluid from improved Paine points can effectively reduce the acute brain swelling of early operation, which will make it an effective adjuvant therapy to emergency microsurgery of clipping aneurysm.

Objective To investigate whether the presence of sepsis associated encephalopathy (SAE) would predict nosocomial coma (NC) and poor outcome in patients with supratentorial intracerebral hemorrhage (SICH). Methods A retrospective cohort study was conducted. The adult acute SICH patients with or without coma admitted to intensive care unit (ICU) of Shuyang People' Hospital Affiliated to Xuzhou Medical University from December 2012 to December 2015 were enrolled. Brain computed tomography (CT) scans were analyzed and the patients were divided into pre-hospital coma (PC) and NC groups. The clinical data and the incidence of SAE of patients in two groups were compared, and the 30-day prognosis was followed up. Univariate and Cox regression analyses were performed to analyze whether SAE would predict NC and poor outcome in patients with SICH. Results A total of 330 patients with acute SICH and coma were enrolled, excluding 60 cases of infratentorial cerebral hemorrhage, 3 cases of primary intraventricular hemorrhage, and 6 cases of unknown volume hematoma. Finally, 261 patients were included, with 111 patients of NC events, and 150 patients of PC events. 69 (62.2%) SAE in SICH with NC and 33 (22.2%) SAE in SICH with PC was diagnosed, and the incidence of SAE between two groups was statistically significant (P < 0.01). Compared with PC group, SICH patients in the NC group had lower incidence of hypertension (81.1% vs. 96.0%), longer time from onset to NC [days: 2.3 (23.9) vs. 0 (0.5)] and length of ICU stay [days: 5.0 (34.0) vs. 3.0 (12.0)], higher initial Glasgow coma score (GCS, 10.2±1.5 vs. 6.6±1.6) and sequential organ failure assessment (SOFA) score [4.0 (6.0) vs. 3.0 (3.0)], lower initial National Institutes of Health Stroke Scale (NIHSS) score (19.4±6.6 vs. 30.2±6.8), as well as more frequent sepsis (78.4% vs. 38.0%), vegetative state (24.3% vs. 14.0%), acute respiratory failure (24.3% vs. 10.0%), pneumonia (37.8% vs. 24.0%), septic shock (8.1% vs. 0), acute liver failure (5.4% vs. 0), hypernatremia (8.1% vs. 0), CT indicating that more frequent vasogenic edema (64.9% vs. 16.0%) and white matter lesion (13.5% vs. 2.0%), and less mannitol usage (94.6% vs. 100.0%), and less brain midline shift (32.4% vs. 68.0%) and hematoma enlargement (8.1% vs. 30.0%), less hematoma volume (mL: 28.0±18.8 vs. 38.3±24.4) in CT, and higher 30-day mortality (54.1% vs. 26.0%) with statistical differences (all P < 0.05). It was shown by Cox regression analyses that SAE [hazard ratio (HR) = 3.5, 95% confidence interval (95%CI) = 1.346-6.765, P = 0.000] and SOFA score (HR = 1.8, 95%CI = 1.073-1.756, P = 0.008) were independent risk factors of death of SICH patients with NC, and hematoma enlargement was independent risk factor of death of SICH patients with PC (HR = 3.0, 95%CI = 1.313-5.814, P = 0.000). Conclusion SAE is the independent factor of inducing NC event and poor prognosis in SICH patients.

Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE).Methods From Jan 2013 to Oct 2014,we used the criteria of systemic inflammatory response syndrome (SIRS)positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU).Results Among 6 comatose patients with evidence of infection,3 cases were secondary infection after hemorrhagic stroke,1 case was secondary infection after trauma,and the other 2 cases were primary infection.All patients met the diagnosis of SIRS -positive sepsis with encephalopathy.Among them,the presence of SIRS 3 criteria was in 2 cases,four criteria in 4 cases. All patients with severe brain failure (100%),in addition to 5 cases with acute respiratory failure caused by lung injury,one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases (33.3%),the cerebral ischemic lesions in four cases(66.7%).The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions,and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case,eventually with a poor prognosis.Conclusion SAE is a common critically illness,the use of the new classifi-cation criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy.

Castleman Disease ; Heart Neoplasms ; Humans ; Myxoma ; Retroperitoneal Space

Objective To study the ability of human embryonic stem cells to integrate into mouse liver and to repair chronic liver injury of the recipient.Methods On day 1,day-7 and day-15 after human embryonic stem cells were induced to differentiate into hepatocyte-like cells and were transplanted into mice with chronic liver failure,liver histopathology,liver function,liver tissue regeneration and mature hepatocytes of mice were tested respectively.Results Hepatic tissue pathology of mice significantly improved after transplantation and necrotic foci diminished,hemorrhage and congestion of hepatic cells relieved,and liver function improved.It was observed that human embryonic stem cells survived,proliferated,integrated with host liver,and differentiated into mature hepatocytes.Conclusions Human embryonic stem cells xenotransplanted into mice can participated liver tissue regeneration to some extent,and differentiated into functional liver cells.