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According to the Global Cancer Statistics 2020 report, breast cancer is the most commonly diagnosed cancer worldwide. Patients with mammary cancer live longer due to the continuous optimization of chemotherapy, targeted drugs, and hormone therapy, which will inevitably lead to an increase in the prevalence of metastatic bone tumors. Bone metastasis affects approximately 8% of patients with mammary cancer, with the spine being the most common site. Metastatic neoplasms can invade the centrum and its attachments, leading to local pain, spinal instability, vertebral pathological fractures, spinal cord compression, impaired neurological function, and paralysis, ultimately reducing the quality of life. Multidisciplinary and personalized management using analgesic drugs, endocrine therapy, corticosteroid therapy, chemotherapy, bisphosphonates, immunotherapy, targeted drugs, radiotherapy, and surgery has been advocated for the treatment of spinal metastases. Multiple paradigms and systems have been proposed to determine suitable treatments. In the early stages, the occurrence of metastasis indicates a terminal stage of the tumor process in patients with malignant tumors, implying that their lifespan is limited. As a result, the choice of treatment is heavily influenced by longevity. However, with the development of treatment methods, the lifespan of patients with tumors has considerably increased in recent years. This leads to the choice of patient’s treatment, which depends not only on the patient’s survival, but also on the radiotherapy or postoperative functional outcomes. Nevertheless, they fall short of determining the variables that affect survival and functional outcomes in histology-specific subgroups of breast cancer. To accurately predict the bone survival and functional outcomes of patients with breast cancer spine metastases a review of prognostic factors was performed.

Background Using effective scolicidal agents intraoperatively is essential to lessen the recurrence rate of hepatic echinococcosis. However, severe hypernatremia may occur after hypertonic saline (HS) has been applied as the scolicidal agent. The aim of this study is to report on pediatric patients with severe hypernatremia after hepatic echinococcus surgery. Methods Patients who presented to West China Hospital between January 2010 and February 2017 were retrospectively analyzed. Children under 16 years with echinococcosis treated by resection were included in the study. Results A total of 26 children were enrolled in this study, including 16 boys and 10 girls with a median age of 8 (2–16). 24 (92.3 %) cases were cystic echinococcosis (CE) and two (7.7 %) were alveolar echinococcosis (AE). According to Clavien-Dindo classification of surgical complications, the complication rate of all 26 patients was 19.2 %, among which three cases belonged to Grade I, one to Grade III b and 1 to Grade IV. Two children encountered severe hypernatremia (sodium: 155.3 mmol/L and 190.0mmol/L). Data showed classic clinical features of severe hypernatremia: profound and persistent bradycardia, hypotension and coma. After treatment, they recovered well without any neurologic sequelae. All patients were followed up regularly for a median time of 38 months (range 4–89 months); the overall disease-free survival was 100.0 %. Conclusions HS irrigation of intra-abdominal echinococcosis may cause acute hypernatremia and severe consequences. Diagnostic suspicion and early intervention are vital tools for avoiding morbidity and mortality.

The life expectancy of patients with advanced cancer has been prolonged with the development of systemic treatment technology. Spinal metastasis is one of the common ways of metastasis of advanced tumors, leading to spinal cord compression and compression fractures, which often lead to a significant reduction in patients’ quality of life and physical function. Therefore, surgical treatment is still needed for functional recovery and local control. Separation surgery has been known since 2014 when it was purposed. Combined with radiotherapy, it can achieve an ideal goal of local control. This paper gives a brief introduction to separation surgery, hoping to increase the reader's understanding and consider this method in the course of treatment.

Background: Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. Methods: Forty patients with both-column acetabular fractures were recruited in the randomized prospective case-control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, n = 20; conventional method group, n = 20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. Results: The operation and instrumentation times in the 3D printing group were significantly shorter (130.8 ± 29.2 min, t = －7.5, P < 0.001 and 32.1 ± 9.5 min, t = －6.5, P < 0.001, respectively) than those in the conventional method group. The amount of blood loss and blood transfusion in the 3D printing group were significantly lower (500 [400, 800] mL, Mann-Whitney U= 74.5, P < 0.001 and 0 [0,400] mL, Mann-Whitney U = 59.5, P < 0.001, respectively) than those in the conventional method group. The number of the approach performed in the 3D printing group was significantly smaller than that in the conventional method group (pararectus + Kocher-Langenbeck [K-L] approach rate: 35% vs. 85%; x2 = 10.4, P < 0.05). The time of intra-operative fluoroscopy in the 3D printing group was significantly shorter than that in the conventional method group (4.2 ± 1.8 vs. 7.7 ± 2.6 s; t = －5.0, P < 0.001). The post-operative fracture reduction quality in the 3D printing group was significantly better than that in the conventional method group (good reduction rate: 80% vs. 30%; x2 = 10.1, P < 0.05). The hip joint function (based on the Harris score 1 year after the operation) in the 3D printing group was significantly better than that in the conventional method group (excellent/good rate: 75% vs. 30%; x2 = 8.1, P < 0.05). The complication was similar in both groups (5.0% vs. 25%; x2 = 3.1, P = 0.182). Conclusions: The use of a pre-operative virtual simulation and 3D printing technology is a more effective method for treating bothcolumn acetabular fractures. This method can shorten the operation and instrumentation times, reduce blood loss, blood transfusion and the time of intra-operative fluoroscopy, and improve the post-operative fracture reduction quality. Clinical trail registration: No.ChiCTR1900028230; http://www.chictr.org.cn Key words: Both-column; Acetabulum fractures; Computer simulation; Three-dimensional printing; Internal fracture fixation

Homeobox B9 (HOXB9), a homeodomain-containing transcription factor, may play a role in hepatocellular carcinoma (HCC) progression. However, the exact mechanisms underlying its action remain unclear.HOXB9 expression was significantly increased in HCC tissues and cell lines. Patients with higher HOXB9 levels were associated with poor prognosis. Overexpression of HOXB9 in BEL-7405 cells promoted proliferation, migration, and invasion, whereas knockdown of HOXB9 in HepG2 cells significantly reduced cell proliferation, migration, and invasion abilities. Mechanically, a positive correlation was found between HOXB9 expression and transforming growth factor-These findings validated that HOXB9 promoted proliferation, migration, and invasion in HCC cells by stimulating the TGF

The most commonly used clinical methods are enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR) in which ELISA was applied for the detection of protein biomarkers and qPCR was especially applied for nucleic acid biomarker analysis. Although these constructed methods have been applied in wide range, they also showed some inherent shortcomings such as low sensitivity, large sample volume and complex operations. At present, many methods have been successfully constructed on the basis of DNA nanotechnology with the merits of high accuracy, rapid and simple operation for cancer biomarkers assay. In this review, we summarized the bioassay strategies based on DNA nanotechnology from the perspective of the analytical attributes for the first time and discussed and the feasibility of the reported strategies for clinical application in the future.

Stimuli-responsive nanomachines are attractive tools for biosensing, imaging, and drug delivery. Herein, we demonstrate that the orientation of macromolecules and subsequent dynamic interactions at the biomolecule-nanoparticle (bio-nano) interfaces can be rationally controlled to engineer stimuli-responsive DNA nanomachines. The success of this design principle was demonstrated by engineering a series of antibody-responsive DNA walkers capable of moving persistently on a three-dimensional track made of DNA functionalized gold nanoparticles. We show that drastically different responses to antibodies could be achieved using DNA walkers of identical sequences but with varying number or sites of modifications. We also show that multiple interfacial factors could be combined to engineer stimuli-responsive DNA nanomachines with high sensitivity and modularity. The potential of our strategy for practical uses was finally demonstrated for the amplified detection of antibodies and small molecules in both buffer and human serum samples. Unlike many DNA-based nanomachines, the performance of which could be significantly hindered by the matrix of serum, our system shows a matrix-enhanced sensitivity as a result of the engineering approach at the bio-nano interface.

Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.

Dee EC, Freret ME, Horick N, et al. Patterns of failure and the need for biliary intervention in resected biliary tract cancers after chemoradiation. Ann Surg Oncol. 2020/08/01 2020. https://doi.org/10.1245/s10434-020-08967-9. Hoehn RS, Wima K, Ertel AE, et al. Adjuvant therapy for gallbladder cancer: an analysis of the National Cancer Data Base. J Gastrointest Surg. 2015;19(10):1794–801. https://doi.org/10.1007/s11605-015-2922-0. Article PubMed Google Scholar Lee GC, Ferrone CR, Tanabe KK, et al. Predictors of adjuvant treatment and survival in patients with intrahepatic cholangiocarcinoma who undergo resection. Am J Surg. 2019;218(5):959–66. https://doi.org/10.1016/j.amjsurg.2019.02.036. Article PubMed Google Scholar Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33(24):2617–22. https://doi.org/10.1200/JCO.2014.60.2219. CAS Article PubMed Google Scholar Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30(16):1934–40. https://doi.org/10.1200/jco.2011.40.5381. Article PubMed Google Scholar Ma WJ, Jin YW, Wu ZR, et al. Meta-analysis of randomized clinical trials of adjuvant chemotherapy for resected biliary tract cancers. HPB. 2020;22(7):939–49. https://doi.org/10.1016/j.hpb.2020.02.001. Article PubMed Google Scholar Download references The authors acknowledge the Sichuan Science and Technology Program (2018JY0019), the Fundamental Research Funds for the Central Universities (2019SCUH0021), the Post-Doctor Research Project, West China Hospital, Sichuan University (2019HXBH025), and the Sichuan University Postdoctoral Interdisciplinary Innovation Start-up Fund (0040204153244). Department of Biliary Surgery, West China Hospital of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China Wen-Jie Ma MD & Rong-Xing Zhou MD You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar W-J M performed the majority of manuscript; R-X Z revised the manuscript critically and gave the final approval of the version to be published. Correspondence to Rong-Xing Zhou MD. The authors declare no conflict of interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Ma, W., Zhou, R. Do Any Subgroups of Resected Biliary Tract Cancers Patients That Benefit the Most from Adjuvant Chemoradiation Therapy?. Ann Surg Oncol (2020). https://doi.org/10.1245/s10434-020-09128-8 Download citation Received: 06 August 2020 Accepted: 13 August 2020 Published: 11 September 2020 DOI: https://doi.org/10.1245/s10434-020-09128-8

To evaluate the effects of thermosensitive hydrogels loaded with human-induced pluripotent stem cells transfected with the growth differentiation factor-5 (GDF5-hiPSCs) on rat intervertebral disc regeneration. GDF5-hiPSCs were cocultured with rat nucleus pulposus (NP) cells in vitro. Real-time PCR and western blot were used to determine the differentiation of hiPSCs. Rat caudal intervertebral discs were punctured using a needle under X-ray, and groups of coccygeal (Co) discs were subject to various treatments: Puncture group (Co6/7, punctured without treatment); Hydrogel group (Co7/8, 2 μl of hydrogel injected without cells); GDF5-hiPSCs + Hydrogel group (Co8/9, 2 μl of GDF5-hiPSCs-loaded hydrogel injected); and Normal control (Co5/6). X-ray, MRI, and histological evaluations were performed at 1, 2, and 3 months after cell transplantation and relative changes in the disc height index (DHI%) and voxel count were calculated and compared. GDF5-hiPSCs were successfully differentiated to a chondrogenic linage after cocultured with rat NP cells. In terms of X-ray, MRI, and HE staining scores, the GDF5-hiPSCs + Hydrogel group was significantly superior to the Puncture and Hydrogel groups (p .05). Compared with the Normal group, the MRI-based voxel count of the GDF5-hiPSCs + Hydrogel group was significantly lower at 1, 2, and 3 months after cell transplantation (p .05). However, there were no significant differences in histological scores at 1 and 2 months after cell transplantation compared with the Normal group (p .05). In conclusion, thermosensitive hydrogel-encapsulated hiPSCs overexpressing the GDF5 gene ameliorated intervertebral disc degeneration.

Unraveling the molecular mechanisms by which genetic variants of cytochrome P450 2A6 lead to different metabolic phenotypes remains a long-standing but important challenge. CYP2A6 is an enzyme involved in the metabolism of several clinical drugs as well as the metabolic activation of carcinogenic nitrosamines. Herein, CYP2A6 genotypes and phenotypes, as indicated by protein content [by liquid chromatography-mass spectrometry (MS)/MS] and metabolic activities [Vmax, clearance (CL)], were determined for 90 human liver samples. We determined the median, range, and interindividual and intraindividual variation of CYP2A6 content and activity at the microsomal, liver tissue, and whole liver level and predicted hepatic in vivo clearance by in vitro-in vivo extrapolation based on CYP2A6-mediated coumarin metabolism by each CYP2A6 genotype. These results reveal how different CYP2A6 genotypes yield different phenotypic traits in protein content and enzyme activity. For relative Vmax, CL, and protein content, the intraindividual percentage coefficients of variation (ICVs) were 41.0% (18.8%-125.1%), 28.5% (2.39%-133.5%), and 27.8% (2.68%-88.0%), respectively. The high ICVs implied large intraindividual variation at different levels, sometimes in a genotype-dependent manner. Intergenotype analysis revealed that the CYP2A6*4 allele demonstrated the most obvious effect on phenotypic outcomes, both in protein content and in metabolic activity. Indeed, decreased CYP2A6 protein content with the CYP2A6*4 genotype might explain the decreased metabolic activity from the molecular to the organismal level. These findings may allow useful predictions for CYP2A6-mediated drug metabolism on an individual patient basis in accord with the goal of achieving personalized medicine. SIGNIFICANCE STATEMENT: We provide the median, range, and interindividual and intraindividual variation in CYP2A6 content at the microsomal, liver tissue, and whole liver level by liquid chromatography-mass spectrometry (MS)/MS as well as activities at the protein, microsomal, liver tissue, and whole liver level both in vitro and at the organismal level based on CYP2A6-mediated coumarin metabolism with each CYP2A6 genotype, thereby allowing us to elucidate how different CYP2A6 genotypes yield differing phenotypic traits (protein content and enzyme activity), facilitating the development of personalized medicine.

Nuclear factor erythroid-2 related factor 2 (NRF2) is a pivotal transcription factor that maintains cellular redox homeostasis and facilitates the development of malignant tumor phenotypes. At the molecular level, NRF2 promotes de novo serine synthesis and SUMOylation affects its function. Our results indicated that the SUMO1 acceptor site of NRF2 is the conserved lysine residue 110 (K110), and that NRF2 SUMOylation deficiency inhibited tumorigenesis in hepatocellular carcinoma (HCC). Mechanistically, NRF2 SUMOylation promoted de novo serine synthesis in HCC by enhancing the clearance of intracellular reactive oxygen species (ROS) and up-regulating phosphoglycerate dehydrogenase (PHGDH). More importantly, serine starvation increased the level of NRF2 SUMOylation, leading to sustained HCC growth. Collectively, our results indicate the presence of a novel NRF2 SUMOylation-mediated signaling process that maintains HCC tumorigenesis in normal conditions and in response to metabolic stress.

Objectives TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism. Methods The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701. Key findings The results of CCK-8 assay showed that TNBG-5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG-5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG-5602 could remarkably inhibit the growth of tumours. During in-vitro and in-vivo studies, we noted that TNBG-5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG-5602 may be exerted through activating peroxisome proliferator-activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA). Conclusions Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.

Prediction of early postoperative recurrence is of great significance for follow‐up treatment. However, there are few studies available that focus on high‐risk factors of early postoperative recurrence or even the definition the exact time of early recurrence for hilar cholangiocarcinoma. Thus, we aimed to examine the optimal cut‐off value for defining the early in patients with R0 resection of hilar cholangiocarcinoma and to investigate prognostic factors associated with early recurrence. Two hundred and fifty‐eight patients with R0 resection of hilar cholangiocarcinoma between 2000 and 2015 were included. The minimum P value approach was used to define the optimal cut‐off of early recurrence. The prognostic factors associated with early recurrence were investigated. The optimal cut‐off value for dividing patients into early and non‐early recurrence groups after R0 resection of hilar cholangiocarcinoma was 12 months. Sixty‐two patients were recorded as early recurrence, and the remaining 196 patients were labeled as non‐early recurrence. Multivariate logistic regression analysis indicated lymph node metastasis (OR = 2.756, 95% CI 1.409‐5.393; P = 0.003), poor differentiation (OR = 1.653; 95% CI 1.040‐2.632; P = 0.034), increased postoperative CA 19‐9 levels (OR = 1.965, 95% CI 1.282‐3.013; P = 0.002), neutrophil‐to‐lymphocyte ratio > 3.41 (OR = 5.125, 95% CI 2.419‐10.857; P 60 years (OR = 2.018, 95% CI 1.032‐3.947; P = 0.040) were independent determinants of early and non‐early recurrence. Poor differentiation (HR = 2.609, 95% CI 1.600‐4.252; P

To measure the myocardial extracellular volume (ECV) in patients with heart failure with preserved ejection fraction (HFpEF) using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and to evaluate the relationship between ECV and risk of HFpEF and cardiac structure and function.A total of 112 consecutive patients with HFpEF and 80 consecutive subjects without heart disease (control group) who underwent LIE-DECT were included. All patients were divided into ischaemic and non-ischaemic groups according to the LIE patterns detected using iodine maps. The ischaemic scar burden was calculated in the ischaemic HFpEF group. Iodine maps and haematocrit were used to measure ECV in the non-ischaemic HFpEF group and remote ECV of the non-scarred myocardium in the ischaemic HFpEF group, respectively. Cardiac structural and functional variables were collected.ECV in patients with non-ischaemic HFpEF (n = 77) and remote ECV in patients with ischaemic HFpEF (n = 35) were significantly higher than those in control subjects (p 0.001). Multivariate logistic regression analysis revealed that after adjusting for age, sex, body mass index, smoking, and drinking, a higher ECV/remote ECV was still associated with non-ischaemic HFpEF and ischaemic HFpEF (p 0.001). A positive correlation was established between ECV and cardiac structural and functional variables (p 0.05) in all participants. Subgroup analysis showed that ECV/remote ECV and ischaemic scar burden positively correlated with heart failure classification in the HFpEF subgroup (p 0.05).ECV/remote ECV elevation was significantly associated with non-ischaemic and ischaemic HFpEF. Remote ECV and LIE may have synergistic effects in the risk assessment of ischaemic HFpEF.• ECV/remote ECV elevation is associated not only with non-ischaemic HFpEF but also with ischaemic HFpEF. • ECV/remote ECV and ischaemic scar burden are correlated with cardiac structure and function.

Optimal treatment of patients with various types of liver tumors or certain liver diseases frequently demands major liver resection, which remains a clinical challenge especially in children. Eighty seven consecutive pediatric liver resections including 51 (59%) major resections (resection of 3 or more hepatic segments) and 36 (41%) minor resections (resection of 1 or 2 segments) were analyzed. All patients were treated between January 2010 and March 2018. Perioperative outcomes were compared between major and minor hepatic resections. The male to female ratio was 1.72:1. The median age at operation was 20 months (range, 0.33–150 months). There was no significant difference in demographics including age, weight, ASA class, and underlying pathology. The surgical management included functional assessment of the future liver remnant, critical perioperative management, enhanced understanding of hepatic segmental anatomy, and bleeding control, as well as refined surgical techniques. The median estimated blood loss was 40 ml in the minor liver resection group, and 90 ml in major liver resection group (P

Cells take advantage of the spatial organization to accelerate the reaction kinetics of diverse components within a crowded intracellular environment. Inspired by this, we hereby designed a principle of spatial constraint to overcome limitations of response kinetics in DNAzyme-powered DNA nanomachines. First, we proposed the type-1 of spatially constrained DNA nanomachines (scDN-1) by co-localizing the aptamer probe and power unit (DNAzyme), allowing the DNA nanomachines to accomplish faster cyclic cleavage of DNAzyme as intramolecular reactions. To expand the scDN into the clinical practice, Type 2 spatially constrained DNA nanomachines (scDN-2) with constrained antibody probes were then constructed through Holliday junction assembly, which increased the effective local concentration to obtain the improved kinetics. With an accelerated response kinetics, this design principle allows DNA nanomachines to accomplish the response to tumor markers in real patients' samples within 30 min, significantly broadening the bioanalytical applications of DNA nanomachines to clinical practice.

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.

Herein, we describe two homogeneous conversion systems that can convert protein recognition into the release of predesigned output DNA for the activation of DNA nanomachines. With high conversion efficiency, this strategy allows us to initiate DNA nanomachines to respond to any proteins, opening up the possibility of applying DNA nanomachines in clinical practice.

With effective adsorption and quenching efficiency, graphene oxide (GO) can be utilized for sensing biomolecules such as nucleic acids and proteins. In these assays, the fluorophore-labeled nucleic acid (reporter) is usually adsorbed by GO first, followed by adding the target molecules to bind the reporter, thus restoring the fluorescence signal. However, the kinetics of fluorescence recovery is usually very slow because the target is probably adsorbed by GO and compromises the binding of the target and the reporter. Herein, we proposed a toehold-regulated strand displacement strategy to accelerate the kinetics of GO-based biosensing. In this strategy, the toehold of the duplex mediated a competitive assembly with the aim of eliminating the adsorption of the target by GO, facilitating the binding of the target and the reporter. While the duplex with the toehold of the target-blocker DNA or reporter-blocker DNA was formed, the rigid structure of the duplex weakened the adsorption of the target by GO and enhanced the recognition of the target by the reporter. This strategy achieved up to 2.6-fold enhancement in fluorescence signal restoration for nucleic acid detection, while there was 3.2-fold enhancement in fluorescence signal restoration for thrombin detection. It has also been demonstrated that this strategy can be used for the determination of DNA and thrombin in diluted serum with excellent specificity.

Herein, a DNAzyme-powered nanomachine responsive to multiple hepatocellular carcinoma (HCC)-related miRNAs derived from clinical samples was designed. Initially, three types of nanomachines were constructed with dye molecule [(fluorescein (FAM), tetramethylrhodamin (TMR), and Cyanine 5 (Cy5)]-labeled DNA-RNA chimeric substrates and a specific recognized probe for the corresponding miRNAs target. Once the target miRNAs were captured by two recognizing probes, the DNA nanomachine was initiated, leading to the hybridization between the DNAzyme and the substrates. With the help of a cofactor, the automatic operation of the nanomachine was driven by cyclic cleavage of the DNAzyme. Meanwhile, we also explored the recognition behavior between the recognizing probe and the target miRNA. Subsequently, these DNAzyme-powered nanomachines were developed for the homogeneous and simultaneous detection of three target miRNAs at the femtomloar level. Furthermore, the potential in clinical diagnosis was proven by the successful determination of target miRNA in real clinical samples. Thus, this nanomachine-based strategy possesses significant potential to be an innovation in miRNA analysis methodology.

We systematically studied and explored intraindividual variation and correlation in the activities of cytochrome P450 (CYP) using 105 normal liver samples. The intraindividual percentage coefficients of variation of relative Km, Vmax, and CLint were 45.9% (18.3–140%), 44.0% (16.8–127%), and 52.0% (24.2–134%). Overall values of relative Km, Vmax, and CLint for 10 CYPs were sorted. The order, from highest to lowest, was CYP2D6, 3A4/5, 2C19, 2C9, 2B6, 1A2, 2A6, 2C8, and 2E1 for Km; CYP3A4/5, 2C19, 2D6, 2C8, 2E1, 2B6, 1A2, 2A6, and 2C9 for Vmax; and CYP2D6, 2B6, 3A4/5, 2C19, 2C9, 1A2, 2E1, 2C8, and 2A6 for CLint. CYP2A6*4, 2B6 785A>G, and 2D6 100C>T contributed to intraindividual variation of CYP activities. The correlations and similarities among 10 CYP activities were analyzed, and it was found that the highest correlation and similarity for Vmax, Km, and CLint occurred between CYP2C9 and 2C8, CYP2C9 and 1A2, and CYP2C9 and 2C8, respectively. In conclusion, CYP activities exhibit considerable intraindividua...

With advances in tumor treatment, metastasis to bone is increasing, and surgery has become the only choice for most terminal patients. However, spinal surgery has a high risk and is prone to heavy bleeding. Controlled hypotension during surgery has outstanding advantages in reducing intraoperative bleeding and ensuring a clear field of vision, thus avoiding damage to important nerves and vessels. Antihypertensive drugs should be carefully selected after considering the patient's age, different diseases, etc, and a single or combined regimen can be used. Hypotension also inevitably leads to a decrease in perfusion of important organs, so the threshold of hypotension and the maintenance time of hypotension should be strictly limited, and the monitoring of important organs during the operation is particularly important. Information such as blood perfusion, blood oxygen saturation, cardiac output, and neurophysiological conduction potential changes should be obtained in a timely fashion, which will help to reduce the risk of hypotension. In short, when applying controlled hypotension, it is necessary to choose an appropriate threshold and duration, and appropriate monitoring should be conducted during the operation to ensure the safety of the patient.

Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7.

// Dejun Bao 2, 3, 4, * , Chuandong Cheng 2, 3, 4, * , Xiaoqiang Lan 1, 5, * , Rong Xing 1 , Zhuo Chen 7 , Hua Zhao 8 , Junyan Sun 1 , Yang Wang 1 , Chaoshi Niu 2, 3, 4 , Bo Zhang 5 , Shengyun Fang 6 1 Department of Pathophysiology, School of Basic Medical Science, Dalian Medical University, Dalian, China 2 Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China 3 Anhui Provincial Stereotactic Neurosurgical Institute, Hefei, China 4 Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, China 5 Department of Neurosurgery, 2nd Hospital of Dalian Medical University, Dalian, China 6 Center for Biomedical Engineering and Technology, Department of Physiology, Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, Maryland, USA 7 Anhui Provincial Cancer Hospital (West Branch of Anhui Provincial Hospital), Hefei, China 8 Department of Clinical Laboratory, Cancer Hospital, Chinese Academy of Science, Hefei, China * These authors contributed equally to this work Correspondence to: Yang Wang, email: wang_yang10@aliyun.com Chaoshi Niu, email: niuchaoshi@163.com Bo Zhang, email: zhangbo@126.com Shengyun Fang, email: sfang@umaryland.edu Keywords: AR signaling, SVIP, cell proliferation, serum testosterone, p53 Received: November 22, 2016 Accepted: February 08, 2017 Published: February 19, 2017 ABSTRACT The incidence of glioma in men is higher than that in women; however, little is known about the expression and basic function of the androgen receptor (AR) in gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the transcriptional level was previously reported. The present study shows that the protein level of AR is highly expressed in cell lines of the nervous system. Moreover, the AR expression is increased while SVIP expression is decreased in tumor tissue of glioma patients, which is in agreement with the progressing WHO grades. A statistically significant increase in serum testosterone level of glioma patients compared with that of non-cancer patients was also detected. Furthermore, it has been proved that SVIP is down-regulated as well as AR is up-regulated in glioma cell lines with R1881 treatment. Interestingly, the depletion of SVIP using siRNA facilitated cell proliferation and decreased p53 expression. In addition, overexpression of SVIP increased cell death only in p53 wt cell lines. Moreover, U87MG cells, p53 wt cell line was susceptible to AR antagonists in vitro and in vivo . The current study provides insight into the biological role of AR in suppressing SVIP and p53 and promoting the progression of glioma as well as the clinical treatment of glioma patients.

The diagnosis and treatment for colon cancer have been greatly developed, but the prognosis remains unsatisfactory. There is still a great clinical need to explore new efficacious drugs for colon cancer treatment. Tetrandrine (Tet) is a bis-benzylisoquinoline alkaloid. It has been shown that Tet may be a potential candidate for cancer treatment, but the explicit mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Tet in human colon cancer cells and dissected the possible mechanism. With cell viability assay and flow cytometry analysis, we confirmed that Tet can effectively inhibit the proliferation and induce apoptosis in HCT116 cells. Mechanically, we found that Tet greatly increases the mRNA and protein level of TGF-β1 in HCT116 cells. Exogenous TGF-β1 enhances the anti-proliferation and apoptosis inducing effect of Tet in HCT116 cells, which has been partly reversed by TGF-β1 inhibitor. Tet decreases the phosphorylation of Akt1/2/3 in HCT116 cells. This effect can be enhanced by exogenous TGF-β1, but partly reversed by TGF-β1 inhibitor. Tet exhibits no effect on total level of PTEN, but decreases the phosphorylation of PTEN; exogenous TGF-β1 enhances the effect of Tet on decreasing the phosphorylation of PTEN, which was partly reversed by TGF-β1 inhibitor. Our findings suggested that Tet may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating TGF-β1 to decrease the phosphorylation of PTEN.

The inability to visualize the sternum tip and T1 vertebra on radiographs may decrease the accuracy of the measurements of cervical sagittal parameters. The object of this study is to investigate the value of MRI to measure cervical sagittal parameters and to compare the data of cervical sagittal parameters on radiographs and MR images. Fifty-two asymptomatic adults were recruited. Each subject had both an MRI and radiographs of the cervical spine. Data, including C2–7 lordosis (CL), T1 slope (T1S), thoracic inlet angle (TIA), neck tilt (NT), and T1S minus C2–7 lordosis (T1S-CL), on radiographs and MRI were collected and analyzed. There were significant differences in CL, T1S, and T1S-CL, between X-ray and MR imaging, but not in TIA and NT. Each of the radiographic cervical sagittal parameters had a significant relationship with the corresponding value on MRI, and the correlation between radiographic and MRI measurement of TIA was the most significant of all parameters. Positional change may significantly influence most sagittal parameters. Supine MRI cannot substitute for upright cervical radiographs to measure most cervical sagittal parameters except for TIA in an asymptomatic population.

To evaluate the relationship between myocardial extracellular volume (ECV) fraction measured using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and risk of heart failure (HF) in patients without coronary artery disease (CAD), and to evaluate the relationship between ECV and left ventricular structure and function.Sixty consecutive HF patients without CAD and 60 consecutive participants without heart disease who underwent coronary CT angiography (CCTA) following LIE-DECT were included. ECV of the left ventricle was calculated from the iodine maps and hematocrit levels using the American Heart Association (AHA) 16-segment model. Cardiac structural and functional parameters were collected including left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left atrial volume (LAV), interventricular septal thickness (IVST), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP).ECV in HF patients without CAD (31.3 ± 4.0 %) was significantly higher than that in healthy subjects (27.1 ± 3.7 %) (P 0.001). Multivariate linear analysis revealed that ECV was associated with age (β = 0.098, P = 0.010) and hypertension (β = 2.093, P = 0.011) in all participants. Binary logistic regression analysis showed that after adjusting for age, sex, body mass index (BMI), smoking, and drinking, ECV was a risk factor affecting the occurrence of HF in those without CAD (OR = 1.356, 95 %CI：1.178-1.561, P 0.001). A positive correlation was found between ECV and NT-pro-BNP, LVEDV, LVESV, and LAV (r = 0.629, 0.329, 0.346, and 0.338, respectively; all P 0.001) in all participants.ECV could be measured using LIE-DECT iodine maps. ECV elevation was a risk factor for HF without CAD and correlated with cardiac structure and function.

// Wang Mi Liu 1, * , Rong Xing 1, * , Chong Bian 1 , Yun Liang 1 , Libo Jiang 1 , Chen Qian 1 , Jian Dong 1 1 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Jian Dong, email: dong.jian@zs-hospital.sh.cn Keywords: MRI, spine metastases, pedicle Received: February 19, 2016 Accepted: June 17, 2016 Published: July 28, 2016 ABSTRACT Objectives: The study aimed to retrospectively evaluate the accuracy and value of magnetic resonance imaging (MRI) in predicting pedicle involvement for patients with spine metastases. Methods: Forty-five patients with a vertebral metastasis encroaching at least one pedicle were studied using MRI before surgery and regularly after surgery. Patients were categorized on the basis of their numbers of pedicle involvement (Group 1: one pedicle was involved, n = 23; Group 2: two pedicles were involved, n = 22). The diagnostic accuracy was calculated, and comparisons of intraoperative blood loss and recurrence rate between the two groups were performed. Results: The overall performance of MRI in predicting the pedicle involvement was as follows: accuracy, 94.4%; sensitivity, 95.5%; and specificity, 91.3%. Less intraoperative blood loss was observed for Group 1 compared with Group 2 (1,661 ± 672 ml and 2,173 ± 790 ml, respectively, P = 0.024). Tumor relapse occurred in 8.7% (2/23) of Group 1 and in 22.7% (5/22) of Group 2 with median recurrence free survival time 14 and 9 months, respectively. Conclusions: MRI is a reliable approach to assess pedicle involvement. It has potential for use in the evaluation of the clinical characteristics of patients with spine metastases.

1. Magnesium isoglycyrrhizinate (MgIg) has been extensively used in treating liver injury which is the common adverse reaction of docetaxel (DOC). Due to the narrow therapeutic window, small changes in pharmacokinetic profiles can alter the toxicity and therapeutic efficacy of DOC significantly. The study aimed to explore the effects of MgIg on the disposition of DOC and the potential mechanism in DOC-induced liver injury.2. Pharmacokinetics and tissues distribution behaviors showed that there was no significant difference between DOC group (DOCG) and MgIg + DOC group (MDOCG). The mRNA and protein levels of cytochrome P450 3A1 (CYP3A1) in liver, intestine, and kidney were significantly upregulated, and the P-glycoprotein (P-gp) was obviously downregulated in MDOCG when compared with DOCG.3. Immunoglobulin M (IgM), CD8+ were upregulated in DOCG; while in MDOCG, IgM, CD8+ recovered to normal levels and complement C3; CD4+ were upregulated.4. MgIg had no significant effects on the disposition of DOC...

Chemokines are a family of small 8-10 kDa inducible cytokines. Initially characterized as chemotactic factors, they are now considered to affect not just cellular recruitment. CX3CL1 is a unique chemokine that can exist in a soluble form, as a chemotactic cytokine, or in a membrane-attached form that acts as a binding molecule. Recently, the effects of CX3CL1 on diseases, such as inflammation and cancer, have been supported and confirmed by numerous publications. However, due to its dual effects, CX3CL1 exerts numerous effects on pathophysiological conditions that have both negative and positive consequences on pathogenesis and outcome. This review article summarizes the important scientific and clinical data that now point to a critical role for CX3CL1 in diseases.

Diarrheal irritable bowel syndrome (IBS-D) is a chronic functional bowel disease with no clear diagnostic markers and no satisfactory treatment strategies. In recent years, the importance of intestinal microstructure and function in IBS-D has been emphasized. However, the intestinal tissue proteomics of IBS-D patients has not been analyzed. Here, we systematically analyzed the molecule profiling of the intestinal tissues in IBS-D patients through tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for diagnosis and treatment of IBS-D. Five IBS-D patients and five healthy subjects were selected, biopsy tissue samples from the junction of sigmoid and rectum were analyzed by TMT proteomics. Differentially expressed proteins were obtained and bioinformatics analysis was performed. Furthermore, parallel reaction monitoring (PRM) and q-PCR detection were applied to validate the differentially expressed proteins. Eighty differentially expressed proteins were screened, 48 of which were up-regulated and 32 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis showed that these proteins were significantly enriched in the nutrient ingestion pathways which are related to immune molecules. SELENBP1, VSIG2, HMGB1, DHCR7, BCAP31 and other molecules were significantly changed. Our study revealed the underlying mechanisms of IBS-D intestinal dysfunction. SIGNIFICANCE: Irritable bowel syndrome with diarrhea (IBS-D) is a worldwide chronic intestinal disease with no definite diagnostic markers. It is still a challenge to accurately locate the pathogenesis of patients for appropriate treatment strategy. Established proteomics studies of IBS-D are only based on urine, blood, or tissue samples from animals. Our study was the first TMT proteomics analysis on intestinal biopsy tissues of patients with IBS-D, which revealed the changes of molecular spectrum of actual intestinal conditions in patients with IBS-D. Some important molecules and signaling pathways have been found abnormal in our study, which were related with nutrient uptake. They not only provided preliminary clues for low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, an unsolved conundrum of IBS-D, but also revealed obscure problems of protein, lipid, and other nutrients ingestion in IBS-D patients. Some of these differentially expressed molecules have been preliminarily verified, and will may be potential candidate molecules for diagnostic markers of IBS-D.

To diagnose and treat the first imported active case of Plasmodium knowlesi infection in China.The clinical information of the patient was collected. Microscopy of blood smear was conducted after Giemsa staining. Genomic DNA was extracted from blood, and PCR was conducted to amplify rDNA. The PCR products were sequenced and analyzed with BLASTThe patient returned from a one-week tour in a tropical rain forest in Malaysia. The first disease attack occurred in Guangzhou on Oct. 16, 2014, with fever, shivering and sweating. The patient was initially diagnosed as malaria and hospitalized on Oct. 26, 2014. Microscopic observation revealed typical forms of P. knowlesi in blood smear. The red blood cells became enlarged, with big trophozoites appearing as a ring with dual cores and dark brown malaria pigment. The trophozoites were slightly bigger and thicker than P. falciparum. The schizont had 6-8 merozoites, with obvious brown malaria pigment. PCR resulted in a specific band of 1 099 bp. BLAST analysis showed that the sequence of the PCR product was 99% homologous to P. knowlesi (acession No. AM910985.1, L07560.1 and AY580317.1). The patient was diagnosed as P. knowlesi infection, and was then given an 8-day treatment with chloroquine and primaquine, together with dihydroartemisinin piperaquine phosphate tablet. The patient was discharged after recovery on Oct. 28, 2014.According to the clinical symptoms, epidemiological history and laboratory test, the patient has been confirmed as P. knowlesi infection. It may also be the first active case of knowlesi malaria reported in China.

Colon cancer is a prevalent malignancy affecting the gastrointestinal tract. Oridonin (ORI) is a promising chemotherapeutic drug used in the treatment of colon cancer. In this study, we examined the anticancer activity of ORI against colon cancer and elucidated the underlying molecular mechanisms. Cell counting kit-8, flow cytometric and western blot analyses were conducted to analyze the growth inhibitory effects of ORI on SW620 cells; we employed BMP7 and p53 recombinant adenovirus to detect the influence of ORI on the p38 MAPK signal pathway; PT-qPCR, cell immunofluorescence staining and western blot analysis were used to detect the expression of BMP7, p38 and p-p38, p53 and p-p53. A xenograft tumor model and histological evaluation were introduced to detect the effects of ORI and BMP7 in SW620 cells in vivo. ORI inhibited the proliferation of SW620 cells and induced apoptosis. ORI also increased the total and phosphorylated levels of p53. The overexpression of p53 was found to enhance the anti-proliferative effects of ORI on the SW620 cells, while the inhibition of p53 partially reversed these effects. ORI increased the expression of bone morphogenetic protein 7 (BMP7) in the SW620 cells. The overexpression of BMP7 also enhanced the antiproliferative effects of ORI on the SW620 cells and reduced the growth rate of tumors in mice. BMP7-induced immunosuppression markedly decreased the anti-proliferative effects of ORI. ORI was not found to exert any substantial effect on the phosphorylation levels of Smad1/5/8, although it increased the level of p-p38 significantly. The inhibition of p38 significantly attenuated the ORI-induced increase in the levels of p-p53. The overexpression of BMP7 enhanced the promoting effects of ORI on the p-p53 and p-p38 levels, while BMP7-induced immunosuppression reduced the effects of ORI on p-p38 and p-p53. On the whole, the findings of this study suggest that ORI may be a promising agent for use in the treatment of colon cancer, and the anticancer effects of ORI may be partially mediated through the BMP7/p38 MAPK/p53 signaling pathway.

We aimed to examine whether inflammation-based prognostic scores could predict tumor resectability in a cohort of hilar cholangiocarcinoma patients with preoperative hyperbilirubinemia. We also sought to investigate the prognostic factors associated with overall survival in the subgroup of patients with an R0 resection. A total of 173 patients with potentially resectable hilar cholangiocarcinoma, as judged by radiological examinations, were included. The potential relationship of the Glasgow prognostic score (GPS), modified GPS, platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI) with tumor resectability were investigated using univariate and multivariate analysis. Among the 173 patients, 134 had R0 resection margins. Univariate analysis identified that patients with PLR ≥ 150, NLR ≥ 3, PNI ≥ 45, GPS (0.1/2), modified GPS (0.1/2), preoperative CA 125 > 35 U/mL, and a tumor size ≥ 3 cm were more likely to have unresectable tumors. Multivariate analysis indicated that tumor size ≥ 3 cm (OR = 2.422, 95% CI: 1.053–5.573; P = 0.037), PLR ≥ 150 (OR = 3.324, 95% CI: 1.143–9.667; P = 0.027), preoperative CA 125 > 35 U/mL (OR = 3.184, 95% CI: 1.316–7.704; P = 0.010), and GPS (0.1/2) (OR = 2.440, 95% CI: 1.450–4.107; P = 0.001) were independent factors associated with tumor resectability. In selected patients with an R0 resection in this cohort, nodal status (P = 0.010) and tumor differentiation (P = 0.025) were predictive of poor survival outcome. Patients with higher GPS, CA 125, and PLR levels, and a larger tumor size, tend to have unresectable tumors even if they were judged as potentially resectable using preoperative radiological examinations.

Rationale: Pancreatic mucoepidermoid carcinoma (MEC) is a rare disease with no more than 10 cases reported in literature. The prognosis is poor and few patients can survival more than 1 year. Patient concerns: We presented a case of patient manifested as left upper abdominal pain. Computed tomography demonstrated a low-density shadow measuring 2.1 × 2.4 cm situated at the transition area of neck and body of the pancreas with obscure boundary and irregular enhancement. The preoperative symptoms and imaging features were unspecific. Diagnoses: Pancreatic MEC. Interventions: Curative surgery of distal pancreatectomy was conducted. Postoperatively, the patient subsequently underwent 8 cycles of chemotherapy using cisplatin (25 mg/m2) on day 1 to day 3; and gemcitabine (1000 mg/m2) on day 1 and day 8, repeated every 21 days. Outcomes: The patient was monitored on a regular basis at our outpatient department and survived 23 months after surgery. Lessons: Preoperative diagnosis of pancreatic MEC is difficult. Patients with pancreatic MEC may have a survival benefit from the multimodal treatment of curative surgery combined with chemotherapy.

Rationale: Pancreatic alveolar echinococcosis (AE) is an exceptionally rare disease; no more than 10 cases have been published to date. It is characterized as extensive local tissue infringement and destruction; thus, extended surgical resection, such as duodenopancreatectomy, is often needed to obtain a negative resection margin so as to improve the long-term outcome and prognosis. Patient concerns: A middle-aged Tibetan man was admitted due to a 16-year history of recurrent pain in the right upper abdomen. Magnetic resonance imaging scan showed a cystic lesion in the VI segment of his liver and several cystic lesions in the head of pancreas. Diagnoses: Pancreatic AE. Interventions: The patient adopted a preserved surgery of partial cystectomy and completely removing the content of the cyst and then soaking by hypertonic saline combined with adjuvant medical therapy of albendazole. Outcomes: The patient was monitored on a regular basis at the outpatient department; the patient is still alive and has already survived 8 years till now. Lessons: A preserved surgery combined with adjuvant medical therapy of albendazole can also contribute to a good survival outcome for AE located at the head of pancreas.

Hepatocellular carcinoma (HCC) with sarcomatous change (SC) is a rare malignancy associated with high aggressiveness and poor prognosis; however, its prognostic significance remains unclear. From January 1994 to April 2012, surgically resected HCCs with SC (n = 52) at West China Hospital were retrospectively reviewed. HCC with SC was defined as the concomitant presence of the sarcomatous component occupying at least 10 % (but not predominantly) of the HCC-bearing tissue. To validate its prognostic significance, we compared the clinicopathological features and survival rates of these patients with a cohort of 214 randomly selected ordinary HCC patients during the same period. The clinicopathological characteristics of HCC with SC were similar to those of ordinary HCC, with the exception of capsule formation, adjacent organ invasion, lymph node metastasis, and TNM staging. A total of 45 (86.5 %) HCC patients with SC experienced a recurrence, with a median time to recurrence of 6.0 months. Overall survival (OS) rates in the sarcomatous HCC group at 1, 2, and 3 years were 55.8, 25, and 17.3 %, respectively, which were significantly lower than those in the ordinary HCC group (p

The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.

To observe the clinical effect of acupuncture therapy in the treatment of postpartum obesity subjects.A total of 71 postpartum obesity subjects were allocated to treatment group (After the treatment, the BW, BMI, PBF and WHR in the acupuncture group, and the BW and WHR in the control group were significantly decreased (Acupuncture therapy combined with nutritional calorie control has a positive role in relieving obesity in postpartum obesity participants.

To observe the clinical effectiveness of acupuncture intervention in weight reduction by modulating body compositions in obesity patients.A total of 71 obesity patients during weight-loss procedure were allocated to acupuncture+nutrition-consultation group (After 4 weeks' treatment, the body mass, BMI, fat mass and fat percentage in both acupuncture+nutrition-consultation and simple nutrition-consultation groups were significantly decreased (Acupuncture plus nutrition consultation is effective in reducing body mass, fat mass and percentage of body fat in obesity patients.

Background Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms and avoid complications. The timing of appendicectomy for appendiceal phlegmon or abscess is controversial. Objectives To assess the effects of early versus delayed appendicectomy for appendiceal phlegmon or abscess, in terms of overall morbidity and mortality. Search methods We searched the Cochrane Library (CENTRAL; 2016, Issue 7), MEDLINE Ovid (1950 to 23 August 2016), Embase Ovid (1974 to 23 August 2016), Science Citation Index Expanded (1900 to 23 August 2016), and the Chinese Biomedical Literature Database (CBM) (1978 to 23 August 2016). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform search portal (23 August 2016) and ClinicalTrials.gov (23 August 2016) for ongoing trials. Selection criteria We included all individual and cluster-randomised controlled trials, irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. Data collection and analysis Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Main results We included two randomised controlled trials with a total of 80 participants in this review. 1. Early versus delayed open appendicectomy for appendiceal phlegmon Forty participants (paediatric and adults) with appendiceal phlegmon were randomised either to early appendicectomy (appendicectomy as soon as appendiceal mass resolved within the same admission) (n = 20), or to delayed appendicectomy (initial conservative treatment followed by interval appendicectomy six weeks later) (n = 20). The trial was at high risk of bias. There was no mortality in either group. There is insufficient evidence to determine the effect of using either early or delayed open appendicectomy onoverall morbidity (RR 13.00; 95% CI 0.78 to 216.39; very low-quality evidence), the proportion of participants who developed wound infection (RR 9.00; 95% CI 0.52 to 156.91; very low quality evidence) or faecal fistula (RR 3.00; 95% CI 0.13 to 69.52; very low quality evidence). The quality of evidence for increased length of hospital stay and time away from normal activities in the early appendicectomy group (MD 6.70 days; 95% CI 2.76 to 10.64, and MD 5.00 days; 95% CI 1.52 to 8.48, respectively) is very low quality evidence. The trial reported neither quality of life nor pain outcomes. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess Forty paediatric participants with appendiceal abscess were randomised either to early appendicectomy (emergent laparoscopic appendicectomy) (n = 20) or to delayed appendicectomy (initial conservative treatment followed by interval laparoscopic appendicectomy 10 weeks later) (n = 20). The trial was at high risk of bias. The trial did not report on overall morbidity or complications. There was no mortality in either group. We do not have sufficient evidence to determine the effects of using either early or delayed laparoscopic appendicectomy for outcomes relating to hospital stay between the groups (MD −0.20 days; 95% CI −3.54 to 3.14; very low quality of evidence). Health-related quality of life was measured with the Pediatric Quality of Life Scale-Version 4.0 questionnaire (a scale of 0 to 100 with higher values indicating a better quality of life). Health-related quality of life score measured at 12 weeks after appendicectomy was higher in the early appendicectomy group than in the delayed appendicectomy group (MD 12.40 points; 95% CI 9.78 to 15.02) but the quality of evidence was very low. This trial reported neither the pain nor the time away from normal activities. Authors' conclusions It is unclear whether early appendicectomy prevents complications compared to delayed appendicectomy for people with appendiceal phlegmon or abscess. The evidence indicating increased length of hospital stay and time away from normal activities in people with early open appendicectomy is of very low quality. The evidence for better health-related quality of life following early laparoscopic appendicectomy compared with delayed appendicectomy is based on very low quality evidence. For both comparisons addressed in this review, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities, quality of life and the length of hospital stay.

The specific binding peptide pd20 of gastric cancer cells with a high potential for liver metastasis was fused with human tumour necrosis factor (TNF) α, and a prokaryotic expression vector was established to express the pd20-TNFα fusion protein. After purification and identification, the preventive effects of the fusion protein on liver metastasis of gastric cancer were observed in mice. The whole gene synthesis method was used for pd20-TNFα fusion gene preparation, and a pd20-TNFα prokaryotic expression vector was constructed. The vector was induced and expressed in Escherichia coli BL21. The expression products were analysed and verified by SDS-PAGE electrophoresis and Western blot analysis. The Ni-NTA column method was used to purify the fusion protein, and the L929 cytotoxicity method was used to detect biological activity. Flow cytometry apoptosis experiments and invasion assays were performed to observe the effects of the fusion protein on apoptosis and metastasis of gastric cancer cells with high potential for liver metastasis. Thirty nude mice with liver metastasis of gastric cancer were established and then randomly divided into three groups of ten mice each. The Pd20-TNFα recombinant protein (1.2 × 10(6) U/kg day) or standard TNFα (1.2 × 10(6) U/kg day) saline was administered via tail vein injection for 7 consecutive days. The pathological changes in various organs of nude mice were observed 4 weeks later. The size of the gastric cancer, the incidence of liver metastasis and the number of liver metastases were measured and calculated. We successfully constructed a Pd20-TNFα recombinant plasmid and prepared the fusion protein. Detection of the pd20-TNFα protein by immunofluorescence showed a very strong expression in liver tissue, suggesting a targeting of the fusion protein to the liver. The L929 cytotoxicity assays showed that the pd20-TNFα fusion purified protein had a significant lethal effect on L929 cells, with a killing activity of up to 7.6 × 10(6) IU/ml. The apoptosis experiments showed that as the concentration of the fusion protein increased, the early gastric cancer cell apoptosis also increased, with the early apoptosis rate increasing from 5.99 % to 9.04 %. Cell invasion experiments showed that the purified pd20-TNFα fusion protein significantly inhibited the in vitro invasion of XGC9811-L cells, with the penetrating cells being significantly decreased compared with the control group per unit time (P 0.01). Vector experiments showed that the pd20-TNFα recombinant protein group had significantly reduced cancer lesions and liver metastasis in nude mice compared with the control group. We successfully purified a pd20-TNFα fusion protein and confirmed that it had significant biological activity promoting early gastric cancer cell apoptosis, thereby inhibiting gastric cancer cell invasion.

No consensus exists regarding the optimal management of concomitant gallbladder stones and common bile duct stones (CBDS). Previous studies showed a significant association between the presence of obstructive jaundice and increased risk of postoperative complications and conversion to open surgery. This retrospective study evaluated the effectiveness and safety of one-stage (laparoscopic cholecystectomy [LC] plus laparoscopic common bile duct exploration) management versus two-stage (preoperative endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy 1 LC) management for patients with obstructive jaundice, concomitant gallbladder stones, and CBDS. One-stage management (n = 88) or two-stage management (n = 122) was used for 210 eligible patients between January 2009 and March 2011. Both types of management proved to be effective and safe. No significant difference was observed in terms of stone clearance from the common bile duct (CBD), postoperative morbidity, mortality, or conversion to open surgery. However, one-stage management was more cost-effective and decreased the number of procedures. In addition, postoperative hospital stay and operative time were shorter for patients who received one-stage management. Especially for patients with CBD greater than 1 cm in diameter, one-stage management is a better choice.

A comparative study of the spinopelvic sagittal alignment in patients with lumbar disc degeneration or herniation (LDD/LDH) in normal population was designed to analyse the role of sagittal anatomical parameter (pelvic incidence, PI) and positional parameters in the pathogenesis and development of the disease. Several comparative studies of these patients with asymptomatic controls have been done. However, in previous studies without lumbar MRI, a certain number of asymptomatic LDD patients should have been included in the control group and then impacted on the results.Based on MRI findings, we divided 60 LDD or LDH patients and 110 asymptomatic volunteers into the normal group (NG) and the degeneration group (DG), which was further subdivided into the symptomatic (SDG) and asymptomatic (ADG) subgroups according to patients' symptoms. Standing full spine radiographs were used to measure sagittal parameters, including PI, sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and sacrum-bicoxofemoral distance (SFD).The PI, SS and LL in DG were significantly lower than NG, while the SVA and SFD were significantly greater (P0.05). PI correlated well with the SS and LL in all subjects. However, the trend lines of SS or LL over PI were downward in DG. PI was similar in SDG and ADG (P = 0.716) but SS and LL were significantly lower and SVA was significantly greater (P0.05).PI may play a predisposing role in the pathogenesis of lumbar disc degenerative diseases. The secondary structural and compensatory factors would lead to a straighter spine after disc degenerative change.

Macrophages, in response to different environmental cues, undergo the classical polarization (M1 macrophages) as well as the alternative polarization (M2 macrophages) that involve the functions of stimulus-specific transcription factors.Kruppel-like factor 4 (KLF4), a member of a subfamily of the zinc-finger class of DNA-binding transcription factors, plays as a critical regulator of macrophage polarization. KLF4 has been reported as a SUMOylated protein. In this study, we showed that SUMOylation of KLF4, is induced by IL-4 treatment in macrophages. IL4-induced KLF4 SUMOylation promotes RAW264.7 cells and bone marrow derived macrophages (BMDMs) to polarize into M2 subset. Thus, we identified an important post-translational modification (PTM), SUMOylation, plays a crucial role in regulating KLF4 activity during IL-4 induced macrophage M2 polarization. SUMOylation of KLF4 can be a potential therapeutic target in the resolution of inflammation.