Objective To observe the value of FOLFOX-hepatic arterial infusion chemotherapy(HAIC)combined with programmed cell death receptor-1(PD-1)inhibitor+targeted drug for treating China liver cancer staging(CNLC)stageⅢa hepatocellular carcinoma(HCC).Methods Sixty-one patients with CNLC stage Ⅲa HCC who underwent PD-1 inhibitor+targeted drug treatment were retrospectively enrolled and divided into observation group(n=30)and control group(n=31)based on whether received FOLFOX-HAIC treatment or not.The general information,treatment strategy,adverse reactions and therapeutic effects were compared between groups,and the value of treatment strategy in observation group was analyzed.Results No significant difference of general information nor PD-1 inhibitor+targeted drug strategy was found between groups(both P＞0.05).Among 1-2 grade adverse reactions,the incidence of nausea,vomiting and abdominal pain in observation group were higher than those in control group(both P＜0.05),while no significant difference of the other 1-2 grade nor 3 grade adverse reactions was observed(all P＞0.05).The objective response rate(ORR),progression free survival(PFS)and overall survival(OS)of observation group were all higher than those of control group(all P＜0.05).Conclusion FOLFOX-HAIC combined with PD-1 inhibitor+targeted drug was more effective for treating CNLC stage Ⅲa HCC with acceptable safety.

Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under low-power microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H2O2 decompo-sition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTTand chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and pro-vides a reference for developing new microwave sensitizers.

Objective:To analyze the immunology-related risk factors for short-term prognosis in patients with demyelinating diseases of central nervous system, and to evaluate their predictive value.Methods:From January 2012 to October 2022 in Beijing Tiantan Hospital of Capital Medical University and General Hospital of Tianjin Medical University, the clinical data of 362 patients with demyelinating diseases of central nervous system were analyzed, including neuromyelitis optic spectrum disease (NMOSD) 181 cases, multiple sclerosis (MS) 129 cases, anti-myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) 38 cases, acute disseminated encephalomyelopathy (ADEM) 14 cases. According to the expanded disability status scale (EDSS) score at discharge, the patients were divided into good prognosis group (EDSS≤3 scores, 267 cases) and poor prognosis group (EDSS>3 scores, 95 cases). The clinical data, admission severity (admission EDSS score), treatment, autoantibodies and immunoglobulin level and serum inflammatory factor level were compared between two groups. Multivariate Logistic regression was used to analyze the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system; and the predictive efficacy was evaluated by receiver operating characteristic (ROC) curve.Results:Compared with the good prognosis group, the admission EDSS score in the poor prognosis group was significantly higher: 2.5 (1.5) scores vs. 6.5 (3.5) scores. The positive rates of autoimmune disease-related antibody, systemic autoantibody, anti-nuclear antibody, anti-extractable nuclear antigen antibody, thyroid peroxidase antibody and thyroid globulin antibody were significantly higher: 89.5% (85/95) vs. 59.6% (159/267), 75.8% (72/95) vs. 52.1% (139/267), 65.3% (62/95) vs. 38.6% (103/267), 42.1% (40/95) vs. 23.2% (62/267), 40.0% (38/95) vs. 19.1% (51/267) and 42.1% (40/95) vs. 19.9% (53/267). The serum IgM was significantly lower: 0.84 (0.78) g/L vs. 1.00 (0.75) g/L. The serum tumor necrosis factor-α, interleukin-2 receptor and cerebrospinal fluid IgG were significantly higher: 8 055 (3 118) pg/L vs. 6 830 (3 515) pg/L, 348 (175) kU/L vs. 314 (146) kU/L and 47.50 (46.50) g/L vs. 33.00 (24.00) g/L. And there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the admission EDSS score and anti-nuclear antibody positive were the independent risk factors of short-term prognosis in patients with demyelinating diseases of central nervous system ( OR = 5.034 and 6.942, 95% CI 3.289 to 7.705 and 2.250 to 21.422, P<0.01). ROC curve analysis result showed that the area under the curve of anti-nuclear antibody positive combined with admission EDSS score predicted the short-term prognosis in patients with demyelinating diseases of central nervous system was 0.972, with a sensitivity of 90.5%, and a specificity of 92.5%. Conclusions:The admission EDSS score and anti-nuclear antibody positive are the independent risk factors for poor prognosis in patients with demyelinating diseases of central nervous system. And the combination of two indexes can better predict the short-term prognosis.

Objective:To summarize the clinical outcomes and experience of redo median sternotomy on proximal aortic repair. Investigate the relationship between first operation and reoperation, reoperation indications, cardiopulmonary bypass strategy, intraoperative technical details, early and mid-term postoperative results.Methods:There were 28 patients underwent 29 times of redo median sternotomy on proximal aorta from April 2017 to December 2019. There were 23 males (79.3%) with an average age of (45.1±12.7) years (26-79 years), 15 Marfan syndrome (15/29, 51.7%) and 3 Behcet's disease (3/29, 10.3%). The primary operation included aortic valve or mitral valve replacement, Bentall procedure, ascending aortic replacement, simultaneous abdominal aortic replacement, Sun's procedure and coronary artery bypass grafting. The indications for reoperation were: aortic root aneurysm or coronary artery aneurysm, anastomotic leakage, perivalvular leakage due to inflammatory aortic disease, acute or chronic type A aortic dissection and aortic root abscess, aortic arch aneurysm. The surgical methods were Bentall, Cabrol, wheat, aortic valve sparing root replacement with replantation, anastomotic leakage repair, CABG, total arch replacement + stent elephant trunk implantation (Sun's procedure), ascending aorta to abdominal aorta bypass, abdominal aortic replacement.Results:One patient (3.4%) died in hospital because of severe postoperative pulmonary complications, consolidation of both lungs, ARDS and hypoxia. Postoperative low cardiac output was occurred in 2 cases (6.9%), 1 case was cured by ECMO, and 1 case died half a year after operation during follow up period. Re-exploration for postoperative hemorrhage was occurred in three cases (10.3%). Renal failure requires dialysis was 3 cases (10.3%), and transient paresis was 1 cases (3.4%), respectively. All of them were recovered before discharge. During the follow-up period, one patient died of multiple organ failure due to low cardiac output, and one patient underwent total thoracoabdominal aortic replacement. One patient underwent Cabrol for aneurysm of the coronary artery after Bentall procedure. One year later, type A dissection occurred again and Sun's procedure was performed through a median sternotomy.Conclusion:Reoperation of proximal aorta after cardiac and aortic surgery is safe and effective, with good short-term and medium-term results. Comprehensive preoperative evaluation, successful sternotomy, establishment of cardiopulmonary bypass and effective organ protection are the key to successful operation. Patients with aortic diseases, especially Marfan syndrome, are more likely to undergo reoperation. Close follow-up and timely reoperation are necessary to avoid aortic rupture. Sun's procedure is suitable for redo complex arch operation.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To investigate the expression and significance of T helper cell 17 (Th17), soluble intercellular adhesion molecule-1 (sICAM-1) and coagulation function in patients with infectious endocarditis(IE).Methods:From December 2016 to December 2018, IE patients in Beijing Anzhen Hospital Affiliated to Capital Medical University who met the inclusion criteria were selected for cardiac surgery to analyze prospectively, 38 IE patients were selected as the observation group, and 30 healthy people were selected as the control group.The concentrations of serum Th17 related factors (IL-1β, IL-6, IL-17 and IL-21), sICAM-1 and coagulation index(P selectin(sP-SLT)) were measured by enzyme-linked immunosorbent assay(ELISA) and the difference between the two groups were statistically analyzed.Results:The concentrations of serum IL-1β, IL-6, IL-17 and IL-21((29.88±6.49), (14.89±3.31), (21.89±3.01), (563.26±67.36) ng/L) in the observation group were significantly higher than those in the control group((16.56±4.11), (7.52±2.34), (12.91±1.01), (423.38±56.49) ng/L)(all P<0.05). The level of serum sICAM-1 and sP-SLT ((1 247.57(581.39, 1 794.66) μg/L, (60.29±6.61) mg/L)in the observation group were significantly higher than those in the control group((837.28(405.68, 954.47) μg/L, (27.37±5.56) mg/L), and the difference was statistically significant( Z=12.37, t=22.30, all P<0.05). The level of serum IL-1β, IL-6, IL-17 and IL-21 in patients with postoperative infective endocarditis((16.19±4.07), (7.73±2.40), (13.83±0.94), (425.33±52.12) ng/L) were significantly lower than those before operation((29.88±6.49), (14.89±2.31), (21.89±3.01), (563.26±67.36) ng/L), and the differences were statistically significant(t values were 11.02, 13.25, 15.76, 9.98, all P<0.05). The levels of sICAM-1 and sP-SLT1 in patients with postoperative infective endocarditis((901.46(472.15, 1276.58) μg/L, (30.70±5.31) mg/L) were significantly lower than those before operation((1 057.26±463.06) μg/L, (60.29±6.61) mg/L)and the differences were statistically significant( Z=11.16, t=21.51, P<0.05). Conclusion:Th17 related factors, sICAM-1 and sP-SLT were highly expressed in IE patients, and the concentrations of these factors decreased after operation, suggesting that the above factors may be used as related factors for the diagnosis and prognosis of IE patients.

Objective:To explore the effect of functional electrical stimulation on cognition and on the expression of the brain-derived neurotrophic factor (BDNF), synaptophysin (SYN) and microtubule-associated protein 2 (MAP2) using a rat model of vascular dementia.Methods:Ninety pathogen-free male Wistar rats were randomly divided into a sham operation group, a placebo stimulation group and an electrical stimulation group. Both the placebo and electrical stimulation groups underwent bilateral occlusion of the common carotid artery to establish a model of vascular dementia. In the sham operation group the arteries were exposed without occlusion. Each group was then sub-divided into 3, 7 and 14 days subgroups with 10 rats in each subgroup. Beginning seven days after the surgery, the rats in the electrical stimulation group were given 30-minutes of stimulation every day while those in the sham operation group and the placebo stimulation group were given false electrical stimulation. After 3, 7 or 14 days the rats′ cognitive functioning was quantified using the Morris water maze test. The rats were then sacrificed and the expression of BDNF mRNA was measured using in situ hybridization. MAP2 and SYN levels were quantified immunohistochemically.Results:After 14 days the average latency in the placebo stimulation group was significantly longer than in the other groups. On the sixth day the average time in the target zone among the placebo stimulation group was significantly shorter than the other two groups′ averages. After only 3 days of simulation, the average expression of BDNF mRNA in the CA1 area of the hippocampus was significantly lower in the placebo stimulation group than among the others. After 7 days of stimulation the placebo group′s average was significantly lower than that of the sham operation group. The average expression of MAP2 had decreased significantly in the placebo stimulation group compared with the other two groups after 7 and 14 days of simulation. After 7 days the average expression of SYN in the placebo stimulation group was significantly lower than in the sham operation group, and after 14 days it was significantly lower than in the other two groups.Conclusions:Functional electrical stimulation may improve learning and memory in rats modelling vascular dementia through increasing BDNF, SYN and MAP2 expression levels.

Objective To evaluate the safety and efficiency in aortic root disease .Methods From April 2017 to April 2018,46 cases of aortic root disease accepted DavidⅠ[20 cases, 15 males and 5 females, aged(39.6 ±15.8)years, aortic root diameter was(58.3 ±4.4)mm] or Bentall[26 cases, 22 males and 4 females, aged(50.8 ±12.6)years,aortic root diam-eter was(59.5 ±5.0)mm], the data in the peri-operation and heart function in recent period after operation.Results No mortality was observed in the study.Morbidity occurred in both group was comparable.Mean cross-clamp time(129.5 ±28.6) min vs.(94.3 ±35.3)min(P<0.05).Blood transfusion(342.0 ±476.4)ml vs.(330.8 ±651.3)ml(P>0.05).ICU sta-ying time(1.0 ±0.2)day vs.(1.1 ±0.3)day(P>0.05).At the latest visit(10.5 ±6.8)months in David Ⅰ, no obviously regurgitation of aortic valve were observed 0.75 ±0.44 vs 1.0 ±1.3(P>0.05).Conclusion Except for the prolonged cross-clamp time, David Ⅰ is safely and effective in aortic root disease compared with Bentall in peri-operative period .The long term results need further follow-up.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cisplatin ; administration & dosage ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Female ; Humans ; Interleukin Receptor Common gamma Subunit ; deficiency ; genetics ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; pathology ; Transplantation, Heterologous ; methods ; Xenograft Model Antitumor Assays

Objective: To summarize experience and result in surgical treatment of Stanford type A intramural hematoma. Methods: 60 patients with Stanford type A intramural hematoma were operated from February 2015 to August 2017. Surgery was indicated in complicated cases with penetrating ulcer or ulcer-like projection in ascending aorta, maximum aorta diameter≥50 mm, progressive maximum aortic wall thickness≥10 mm, pericardial or pleural effusion, persistent or recurrent pain. Aortic valve regurgitation. In our group, 46 patients recieved ascending aorta replacement+ Sun' s procedure. 6 patients recieved Bentall+ Sun' s procedure. 4 patients recieved asceding aorta+ hemiarch replacement. 2 patients recieved Bentall+ hemiarch replacement. 2 patients recieved asceding aorta replacement. Results: In the whole group, there was 1(1.7%)operative death because of multiple organ failure after operation. Hyoxemiaoccured in 5(8.3%) patients, 2(3.3%) patients occurred new renal failure and required CRRT treatment, cerebrovascular complication occurred in 1 (1.7%)patient, re-sternotomy due to bleeeding occured in 1 (1.7%)patient and paraplegia occured in 1(1.7%) patient after operation. but they recoved quickly after proper treatment. During follow up period, there were 4 cases need reintervention, including TEVAR for type B dissection at 3 months and distal stent-graft new entry at 1 year. Two other reinterventions were performed for endoleak by interventional occlusion. During the follow-up, hematoma absorption rates after treatment 1、3 and 6 months were 68.6%, 84.7% and 94.8%. Conclusion Given the dynamic evolution of acute type A IMH pre-operative accurate indications and the proper surgical strategy maybe the keys for success.