Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation. As an essential trace element, iron is vital for many biological processes. Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation. Ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs), is a promising therapeutic target for therapy-resistant cancers. Previous studies have reported that long noncoding RNA (lncRNA) is a group of critical regulators involved in modulating cell metabolism, proliferation, apoptosis, and ferroptosis. In this review, we summarize the associations among iron metabolism, ferroptosis, and ferroptosis-related lncRNA in tumorigenesis. This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
Fatty Acids, Unsaturated ; Ferroptosis ; Humans ; Iron/therapeutic use* ; Neoplasms/metabolism* ; RNA, Long Noncoding/genetics* ; Trace Elements/therapeutic use*

BACKGROUND:Extracellular matrix can simulate microenvironment and make the stem cells proliferate maintaining the characteristics of stem cells wel in vitro. OBJECTIVE:To prepare the extracellular matrix from human bone marrow cells and to analyze its microstructure and composition preliminarily. METHODS:Human bone marrow cells of passage 4 were cultured for 14 days, and the induction medium was used during the last 8 days. After decellularization, cells were removed to prepare human bone marrow cells-derived extracellular matrix. The surface morphology of human bone marrow cells-derived extracellular matrix was observed by inverted microscope and scanning electron microscope. Changes of col agen I and biglycan before and after decellularization were observed by immunofluorescence staining. Human periodontal ligament stem cells were seeded onto human bone marrow cells-derived extracellular matrix, fibronectin coated 6-wel plate and normal culture plate to compare the influence of different matrix on cellmorphology and adhesion. RESULTS AND CONCLUSION:We obtained intact human bone marrow cells-derived extracellular matrix by chemical combined with physical decellularization. The structure and amount of col agen I and biglycan had not been compromised dramatical y after decellularization. Human periodontal ligament stem cells growing on the human bone marrow cells-derived extracellular matrix developed in accordance with the orbit of the extracellular matrix, differing from the original cellmorphology. There were more human periodontal ligament stem cells adhering to the extracellular matrix during the same time. These findings indicate that effective decellularization can produce intact the extracellular matrix membrane without destroying its microstructure. Extracellular matrix protein is not compromised due to decellularization. The extracellular matrix affects cellmorphology and promotes celladhesion. We can use the extracellular matrix model to simulate stem cellmicroenvironment and thereafter, acquire a large number of adult stem cells with high quality in vitro.

BACKGROUND:Human bone marrow cells-derived extracellular matrix can promote proliferation of human periodontal ligament stem cells and maintain stem cellproperties.
OBJECTIVE:To preliminarily investigate the effect of human bone marrow cells-derived extracellular matrix on the proliferation of human periodontal ligament stem cells.
METHODS:Human periodontal ligament stem cells and bone marrow cells were separately derived from human periodontal tissue and jaw bone marrow, and human bone marrow cells-derived extracellular matrix was prepared. Human periodontal ligament stem cells were cultured and purified using limited dilution cloning method, and transmission electron microscope was used for ultrastructure observation. Human periodontal ligament stem cells at passage 2 were cultured with human bone marrow cells-derived extracellular matrix and normal culture medium (control group). The cellcounting kit-8 and flow cytometry were used to determine the proliferation potential of human periodontal ligament stem cells cultured on human bone marrow cells-derived extracellular matrix.
RESULTS AND CONCLUSION:Compared with the control group, human periodontal ligament stem cells cultured on human bone marrow cells-derived extracellular matrix had a superior capacity of proliferation (P<0.05), and the cells met their morphological and biological characteristics, and grew in good conditions. Human bone marrow cells-derived extracellular matrix is a promising matrix for large-scale expanding human periodontal ligament stem cells for future use in stem cel-based therapy.

BACKGROUND:Many studies have showed that enough blood supply is an essential condition of bone repair and regeneration. OBJECTIVE:To construct the endothelial progenitor cells/bone marrow mesenchymal stem cells (EPCs/BMSCs) composite sheet. METHODS:After isolation and culture, EPCs and BMSCs were co-cultured directly to form EPCs/BMSCs sheet by cellsheet-inducing medium. After 10 days of induction, the sheet was investigated by gross observation, inverted microscope and hematoxylin-eosin staining. The distribution and communication of EPCs and BMSCs during the process of cellsheet induction were observed after the fluorescence labeling separately. Alkaline phosphatase assay and alizarin red staining were applied to examine the ability of osteogenic differentiation of EPCs/BMSCs sheet.
RESULTS AND CONCLUSION:EPCs/BMSCs sheet was harvested after 10-day induction. Cel-cellcontact between EPCs and BMSCs could be observed during the process of the cellsheet preparation. The harvested sheet was composed of multiple layers of cells and cel-produced extracellular matrix. Alkaline phosphatase assay and alizarin red staining both demonstrated that EPCs/BMSCs sheet had good osteogenic differentiation ability. These results suggested that EPCs/BMSCs sheet can be constructed successful y, and the sheet has strong osteogenic differentiation capability in vitro, providing the foundation for the repair of bone defects.

Objective To understand the influence of personal feature on nurses' professional identity.Methods Nurses of 6 military hospitals were assessed and analyzed by general data questionnaire,Nursing Professional Identity Scale.Results Nurses' professional identity in military hospital was on the moderate level.Nursing age,department,monthly income,position,gender entered into the regression equation of nurses' occupation,which affected positively nursing professional identity.Conclusions The military nursing managers should raise the income of nurses appropriately,especially pay attention to training of professional identity of seniority nurses and local recruitment nurses,and enhance master concept in order to increase their understanding and recognition of their occupation.

OBJECTIVETo evaluate the efficacy and safety of PMC therapy (Prednisone, Methotrexate, Chloroquine) combined Langchuang Fuzheng Jiedu Capsule (LFJC), thus choosing a better therapy of integrative medicine for SLE in the period of glucocorticoid use.

METHODSSixty active SLE patients were randomly assigned to two groups, the control group and the treatment group. Those in the control group received PMC therapy (As for Prednisone, it was given at the daily dose of 1 mg/kg till 2 weeks after the condition being stable or after 8 weeks of treatment. Then the dose was reduced by 10% every two weeks. When the dose was reduced to 0.5 mg/kg daily, it was reduced by 2.5 mg per two weeks. When the dose was reduced to 15 mg daily, the dose was reduced to 2.5 mg per four weeks. As for Methotrexate, 10 mg each time, once a week. As for Chloroquine, 100 mg each time, twice daily), while those in the treatment group received PMC therapy (the same way as that for the control group) combined with LFJC (consisting of Astragalus membranaceus 50 g, Angelica sinensis 20 g, Ligusticum Chuanxiong 20 g, prepared Rehmannia Rhizome 30 g, Herba Serissae 30 g, Centella 30 g, centipede 4 g, scorpions 10 g, nidus versace 12 g, et al., 0.5 g per pill, containing 5.7 g crude drug. When the hormone was given at a large dose, LFJC was administered at 12 pills each time, three times daily). When the hormone was given at a middle dose, LFJC was administered at 8 pills each time, three times daily. When the hormone was given at a small dose, LFJC was administered at 6 pills each time, three times daily. The treatment course was six months. The improvement of symptoms and signs between before and after treatment, SLE disease activity index (SLEDAI), efficacy of Chinese medical syndrome, UPro quantitation, erythrocyte sedimentation rate (ESR), complement 3 (C3), C-reactive protein (CRP), the reduction and withdrawal of hormones, and infection of the respiratory tract were observed.

RESULTSThe difference in post-SLEDAI was obviously larger in the treatment group than in the control group (P < 0.05). The fatigue severity scale (FSS) was less after treatment than before treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.05). The total effective rate was 93.33% in the treatment group, showing statistical difference when compared with that of the control group (86.66%; chi2 = 6.736, P < 0.05). The ESR decreased after treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.01). C3 increased after treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.05). The hormone was reduced to (13.70 +/- 5.42) mg/d by the end of the therapeutic course in the treatment group, obviously less than that of the control group [(17.63 +/- 7.80) mg/d, P < 0.05). Seven patients suffered from secondary infection of the respiratory tract infection in the treatment group (5 from upper respiratory tract infection and 2 from lower respiratory tract infection), obviously less than those of the control group (25 from upper respiratory tract infection and 10 from lower respiratory tract infection) (P < 0.05).

CONCLUSIONSPMC combined LFJC was a better treatment program for severe active SLE (SLEDAI > or = 15). It was more safe and effective when compared with using Western medicine alone. It could enhance the efficacy of hormones and help reduction/withdrawal of hormones.

Adolescent ; Adult ; Anti-Inflammatory Agents ; therapeutic use ; Chloroquine ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Integrative Medicine ; Lupus Erythematosus, Systemic ; drug therapy ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Phytotherapy ; methods ; Prednisone ; therapeutic use ; Young Adult

Objective To understand the prevalence of alcohol dependence in individuals living in Guangxi Zhuang Autonomous Region,China. Methods From July 2007 to December 2007,21290 subjects aged more than 15 were randomly selected for 6 Prefecture-level cities and 10 counties by stratified multi-stage cluster sampling method. All subjects were investigated by face to face interview. The Chinese version of Composite International Diagnostic Interview (CIDI3.0) Provided by the Chinese Center for Disease Control And Prevention was used as the screening tool and the diagnoses were made with the 10th edition of international classification of Disease Criteria. Results 18 219 subjects completed the screening,the Completion rate was 85.58‰. The general point prevalence and the general lifetime prevalence of alcohol dependence in individuals living in Guangxi was both 4.50‰. The general lifetime prevalence was higher in rural (6.17‰) than in urban (1.85‰) ( RR =0.31,95% CI =0. 17 ～0.57, P=0. 000) ,higher in men (8.59‰) than in women (0. 33‰) ( RR =0.04,95% CI =0. 01 ～ 0.13, P = 0.000 ) and higher in Zhuang (9.63‰) than in Han(1.95‰) ( RR = 5. 01,95% CI = 3.02 ～8.34, P = 0.000). The lifetime prevalence of alcohol dependence tends upwards as age increasing (P＜0.05 ) and it differs in different marital status,higher in divorce groups (P ＜ 0.05). Conclusion Schizophrenia, Depression disorder, Alcohol dependence disorder are the most common mental disorders and have become the public health problem in Guangxi. To do this,it is necessary to carry out targeted research in prevention and rehabilitation.

BACKGROUND: Many experiments indicate that the angiogenesis of tissue engineered bone graft plays a key role in the osteogenesis.OBJECTIVE: An experimental pattern was set up designed to prepare a kind of vascularized engineered-bone graft for repairing rhesus tibia defects and analyze the relation of angiogenesis and osteogenesis in vivo by rontgenographic and morphological approaches.DESIGN: Random controlled animal experiment.SETTING: Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University.MATERIALS: The composite graft was constructed by seeding the induced bone marrow stem cells (BMSCs) on to a beta-tricalcium phosphate(3-TCP) scaffold in vitro, a circular cylinder (20 mm × 8 mm diameter) with a slit (width 2 mm and length 3 mm ) open to both ends and slot. Porosity 60% and pore diameter 100-150 μm. Twenty-nine healthy rhesuses aged 4-5 years and weighted 3.5-5 kg were adopted without gender limitation.METHODS: The experiment was conducted in the Department of Orthopaedics and Traumatology, Nanfan Hospital, Southern Medical University from October 2003 to July 2005. ①Bone-periosteum defect of 20 mm was made in the middle part of right tibia of the 27 rhesuses, and randomly divided into 3 groups equally. ②The defect gaps in fascia-blood vessel group (A) were plugged with in vitro engineered composites constructed by bone marrow stem cells and 3-TCP scaffold, which were totally hugged by a sheet of pedicled deep fascia and additionally a corresponding portion of saphenous artery and veins. The gaps in fascia group (B) and control group(C), however, were inserted with fascia-coated tissue engineered bone and tissue engineered bone only, respectively. Furthermore, two rhesuses without filling materials on the defect were picked up as blanks fixed by steel pins. ③The angiogenesis and osteogenesis for each treatment was assessed by radioactive imaging, roentgenographic analyses, blocking density and vaso-area image analysis at time intervals of 4, 8 and 12 weeks postoperative.MAIN OUTCOME MEASURE: The score of radioactive imaging,roentgenographic, morphological and vaso-area image analyses RESULTS: Totally 29 rhesuses were involved in the result analysis.① General observation of samples: In group A, all the surfaces of the implanted material and the central part were wholly wrapped up or replaced by bonelike tissues which were hard and could not be broken. And 2/3 materials had been absorbed; In group B and C, partial materials of the medial surface and the front were not coated or replaced by bonelike tissues, which could be broken with force, and 1/3 material had been absorbed.②Histological observation of scaffolds: With time passing, the scaffold materials were absorbed to different degrees in group A, B and C, among which, group A was most significant; Under the microscope, the implanted materials at 12 weeks were completely coated with the bonelike tissues, while the blood vessels structures in the materials were mostly alveoli alike and multi-braches. In group B, most of the materials at 12 weeks were wrapped up by the new bone, and few blood vessels could be seen in the center of the materials. In group C, the implanted materials at 12 weeks were slightly absorbed. The new bone and the vascular structures were both increased a little, but still very few.③Analyses of vaso-area: The vaso-areas of both central and peripheral parts in group A were significantly bigger than those of group B and C (P ＜ 0.05). Furthermore, it tended to increase with the time.④X-rays observation: At 12 weeks, group A's images presented obviously decreased density which was lower than that of the normal bone in individual areas and the continual bony callus manifested. Whereas group B and C's images showed slightly decreased density and the continual bony callus appeared on the sections. ⑤The roentgenographic scores of bone defects: The results indicates that the scores of group A was better than those of group B and C at 4, 8 and 12 weeks, respectively (P ＜ 0.05).CONCLUSION: ①This study shows that a feasible and effective angiogenesis approach of tissue engineered bone can accelerate osteogenesis in vivo. ②The absorption level is positively related to local angiogenesis.