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Weifeng Zou,1 Xiaoqian Wang,2 Wei Hong,3 Fang He,4 Jinxing Hu,1 Qing Sheng,1 Tao Zhu,1 Pixin Ran5 1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4The Research Center of Experiment Medicine, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Pixin RanState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, Guangdong 510120, People’s Republic of China, Tel +86 13922765811Email pxran@gzhmu.edu.cnBackground and Purpose: Recently, fine particulate matter (PM2.5) was identified as the main exposure risk for COPD, and inflammation is central to the development of COPD. In this study, we investigated whether PM2.5 can induce the secretion of interleukin-6 (IL-6), IL-8 and IL-1β in human bronchial epithelial cells (HBECs) in vitro via the wingless-related integration site 5A (Wnt5a)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling.Methods: The expression of Wnt5a and Ror2 was assessed by immunohistochemistry in motor vehicle exhaust (MVE)-induced Sprague-Dawley rats. HBECs were transfected with small interfering RNA (siRNA) targeting Wnt5a or Ror2 and subsequently stimulated with PM2.5.The secretion of IL-6, IL-8 and IL-1β was assessed by ELISAs, and the expression of Wnt5a/Ror2 signaling were assessed by RT-PCR and Western blotting.Results: Both Wnt5a and Ror2 protein were increased in the lung of MVE-induced rats. HBECs exposed to PM2.5 for 24 h significantly upregulated Wnt5a and Ror2 expression and subsequently promoted the nuclear translocation of NF-κB, which increased the production of IL-1β, IL-6 and IL-8. Wnt5a siRNA prevented these outcomes. Wnt5a antagonist (BOX5) also prevented inflammatory effects. Furthermore, Ror2 siRNA blocked the NF-κB activity and inhibited the release of IL-6, IL-8 and IL-1β from PM2.5-exposed HBECs.Conclusion: PM2.5 induces the secretion of IL-6, IL-8 and IL-1β in HBECs via the Wnt5a/Ror2 signaling, demonstrating a novel mechanism for PM2.5-associated airway inflammation.Key words: COPD, PM2.5, Wnt5a/ROR2, inflammatory cytokines, HBECs

The coordinated rehabilitation of the upper limb is important for the recovery of the daily living abilities of stroke patients. However, the guidance of the joint coordination model is generally lacking in the current robot-assisted rehabilitation. Modular robots with soft joints can assist patients to perform coordinated training with safety and compliance. In this study, a novel coordinated path planning and impedance control method is proposed for the modular exoskeleton elbow–wrist rehabilitation robot driven by pneumatic artificial muscles (PAMs). A convolutional neural network-long short-term memory (CNN-LSTM) model is established to describe the coordination relationship of the upper limb joints, so as to generate adaptive trajectories conformed to the coordination laws. Guided by the planned trajectory, an impedance adjustment strategy is proposed to realize active training within a virtual coordinated tunnel to achieve the robot-assisted upper limb coordinated training. The experimental results showed that the CNN-LSTM hybrid neural network can effectively quantify the coordinated relationship between the upper limb joints, and the impedance control method ensures that the robotic assistance path is always in the virtual coordination tunnel, which can improve the movement coordination of the patient and enhance the rehabilitation effectiveness.

Wenguang Luo,1,2 Wei Liu,2 Jie Yao,3 Wenjing Zhu,4 Hongyan Zhang,2 Qi Sheng,2 Lin Wang,2 Lei Lv,5 Liting Qian61School of Medicine, Shandong University, Jinan, Shandong 250100, People’s Republic of China; 2Department of Radiation Oncology, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230031, People’s Republic of China; 3Department of Oncology, The 161 Hospital of PLA, Wuhan, Hubei Province 430010, People’s Republic of China; 4Department of Geriatric Medicine, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230031, People’s Republic of China; 5Cancer Epigenetics Program, Anhui Cancer Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230031, People’s Republic of China; 6Department of Radiation Oncology, Anhui Provincial Cancer Hospital, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230031, People’s Republic of ChinaBackground: Radiotherapy is one of the most common treatments for esophageal squamous cell carcinoma (ESCC). Radioresistance is a major obstacle that limits the efficacy of radiotherapy. H19 has been considered as a factor affecting radioresistance, whereas the specific mechanism of H19 in ESCC radioresistance remains to be further elucidated.Purpose: The objective of this study was to identify the relationship between H19 and radioresistance. The findings are expected to provide new insights into the treatment of radioresistant ESCC.Methods: The expression levels of H19 in ESCC was analyzed using the online database starBase. The Oncomine database was used to further verify the association between H19 expression and patient age, gender, and tumor stage. The overall survival rates of ESCC patients were analyzed using the KM plotter database. Clonogenic survival was conducted to identify the value of survival fraction. The optical density values were obtained via MTS assays. Cells migration and stemness were observed through Transwell and sphere formation assays. The expression levels of H19, miR-22-3p and WNT1 were analyzed using qPCR.Results: In our study, we firstly screened the H19 according to the online database starBase, and then the Oncomine database and KM plotter database showed that H19 expression was significantly upregulated in the ESCC tissues and associated with poor prognosis. Secondly, an ESCC radioresistant cell line, KYSE150R was established. Clonogenic survival showed that radiation decreased the value of survival fraction. MTS assays suggested that optical density values in KYSE150R cells were significantly higher than that in KYSE150 cells. Transwell and sphere formation assays showed radiation enhanced cell migration and stemness in ESCC cells. In addition, qPCR showed that H19 was upregulated in KYSE150R cells, and survival fraction assays showed that knockdown of H19 decreased the survival fraction values. MTS assays, migration and invasion assays suggested that H19 inhibited cells proliferation, migration and stemness in radioresistant KYSE150 cells. Moreover, qPCR assay showed that miR-22-3p expression levels was downregulated, but WNT1 was upregulated in KYSE150R cells as well as protein levels. Luciferase activity assay further showed that miR-22-3p inhibits the WNT1 expression.Conclusion: Our results demonstrate that H19 knockdown downregulates the WNT1 via upregulating miR-22-3p expression, which leads to the inhibition of cells proliferation, migration and stemness in the radioresistant ESCC cells.Keywords: ESCC, radioresistance, KYSE150R, H19, miR-22-3p, WNT1

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several ca

Qingfeng Sheng,1 Weijue Xu,1 Jiangbin Liu,1 Baiyong Shen,2 Xiaxing Deng,2 Yibo Wu,1 Wei Wu,1 Shenghua Yu,1 Xueli Wang,3 Zhibao Lv1 1Department of General Surgery, Shanghai Children’s Hospital, 2Department of General Surgery, Rui Jin Hospital, 3Department of Pathology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Solitary fibrous tumor (SFT) of the pancreas is rare, with 15 adult cases reported in the English literature. We described a 14-month-old boy who presented with obstructive jaundice. Dominantly elevated serum CA19-9 was detected. Imaging studies revealed a well-circumscribed, solid mass in the pancreatic head. A pancreaticoduodenectomy (child procedure) was performed using Shen’s anastomosis technique. After resection of the tumor, liver function and serum tumor markers normalized and clinical signs receded. The boy was disease free after a follow-up of 12 months. Histological examination showed the tumor consisted of “patternless pattern” arranged spindle tumor cells and keloid-like hyalinized collagen. Immunohistochemical staining was positive for CD34 and vimentin. Mutation analysis of CTNNB1 was negative. To the best of our knowledge, our patient was the first case of pancreatic SFT in a pediatric population. SFT should be considered in differential diagnosis when confronted with a pancreatic tumor in children. Complete resection should be meticulously pursued. Keywords: pancreas, rare tumors, children, rare pediatric tumors

Traditional compliance control of a rehabilitation robot is implemented in task space by using impedance or admittance control algorithms. The soft robot actuated by pneumatic muscle actuators (PMAs) is becoming prominent for patients as it enables the compliance being adjusted in each active link, which, however, has not been reported in the literature. This paper proposes a new compliance control method of a soft ankle rehabilitation robot that is driven by four PMAs configured in parallel to enable three degrees of freedom movement of the ankle joint. A new hierarchical compliance control structure, including a low-level compliance adjustment controller in joint space and a high-level admittance controller in task space, is designed. An adaptive compliance control paradigm is further developed by taking into account patient’s active contribution and movement ability during a previous period of time, in order to provide robot assistance only when it is necessarily required. Experiments on healthy and impaired human subjects were conducted to verify the adaptive hierarchical compliance control scheme. The results show that the robot hierarchical compliance can be online adjusted according to the participant’s assessment. The robot reduces its assistance output when participants contribute more and vice versa, thus providing a potentially feasible solution to the patient-in-loop cooperative training strategy.

A rehabilitation robot plays an important role in relieving the therapists’ burden and helping patients with ankle injuries to perform more accurate and effective rehabilitation training. However, a majority of current ankle rehabilitation robots are rigid and have drawbacks in terms of complex structure, poor flexibility and lack of safety. Taking advantages of pneumatic muscles’ good flexibility and light weight, we developed a novel two degrees of freedom (2-DOF) parallel compliant ankle rehabilitation robot actuated by pneumatic muscles (PMs). To solve the PM’s nonlinear characteristics during operation and to tackle the human-robot uncertainties in rehabilitation, an adaptive backstepping sliding mode control (ABS-SMC) method is proposed in this paper. The human-robot external disturbance can be estimated by an observer, who is then used to adjust the robot output to accommodate external changes. The system stability is guaranteed by the Lyapunov stability theorem. Experimental results on the compliant ankle rehabilitation robot show that the proposed ABS-SMC is able to estimate the external disturbance online and adjust the control output in real time during operation, resulting in a higher trajectory tracking accuracy and better response performance especially in dynamic conditions.

Background: Our aim was to summarize our experience with the diagnosis and surgical treatment of solid pseudopapillary neoplasm (SPN) of the pancreas to provide a reference for the management of this rare condition. Methods: We collected and analyzed retrospective data on the clinical presentation, laboratory investigations, radiologic imaging, pathology and operative details of patients with SPN of the pancreas diagnosed between February 2001 and December 2009. Results: In all, 23 of 24 patients were women, and the mean age of all patients was 31 years. The most common clinical presentation was vague abdominal pain. Abdominal imaging showed solid or solid cystic masses in the pancreas, mostly in the tail or head of the gland. All patients were treated surgically. There were no postoperative deaths. After follow-up ranging from 4 to 109 months (median 68 mo), 20 of 22 patients who underwent curative resection were alive with no evidence of disease recurrence. Of the 2 patients with R1 resections, 1 died 42 months after surgery, whereas the other underwent a second operation and was alive after 36 months' follow-up. Conclusion: Solid pseudopapillary neoplasm of the pancreas is a relatively indolent tumour. The initial diagnosis of SPN of the pancreas is suggested by radiologic imaging findings but should be considered in the context of clinical and histopathologic characteristics. We advocate for complete surgical resection once SPN is diagnosed. Contexte : Nous voulions resumer notre experience du diagnostic et du traitement chirurgical du neoplasme pseudo-papillaire solide (NPS) du pancreas afin d'etablir un point de reference pour la prise en charge de ce probleme rare. Methodes : Nous avons reuni et analyse des donnees retrospectives sur la manifestation clinique, les examens de laboratoire, l'imagerie radiologique, la pathologie et les details operatoires de patients atteints de NPS du pancreas diagnostique entre fevrier 2001 et decembre 2009. Resultats : Au total, 23 des 24 patients etaient des femmes et l'age moyen de tous les patients s'etablissait a 31 ans. La manifestation clinique la plus courante etait une vague douleur abdominale. L'imagerie abdominale a revele la presence de masses solides ou kystiques solides au pancreas, surtout a la queue ou a la tete de la glande. Tous les patients ont ete traites par chirurgie. Il n'y a pas eu de deces apres l'intervention. Apres un suivi echelonne sur 4 a 109 mois (mediane de 68 mois), 20 des 22 patients qui ont subi une resection curative etaient vivants et ne presentaient aucun signe de reapparition de la maladie. Des 2 patients qui ont subi une resection R1, 1 est decede 42 mois apres l'intervention tandis que l'autre a subi une deuxieme intervention et etait vivant apres un suivi de 36 mois. Conclusion : Le neoplasme pseudo-papillaire solide du pancreas est une tumeur relativement indolente. Le diagnostic initial de NPS du pancreas est indique par les resultats d'imagerie radiologique, mais il faudrait l'envisager en presence de caracteristiques cliniques et histopathologiques. Nous preconisons la resection chirurgicale complete apres le diagnostic., A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare pancreatic tumour. It was first described by Dr. Frantz in 1959,1 and was defined by the World Health Organization [...]

Summary: Immune tolerance is one of the leading causes of chemotherapy resistance in carcinoma cases. Studies have shown that programmed cell death ligand‐1 (PD‐L1), an inhibitory molecule expressed by cancer cells, plays a significant role in immune tolerance through the induction of T cell dysfunction. The results of our RNA sequencing in previous studies revealed that microRNA‐145 (miR‐145), which is known to be down‐regulated by cisplatin in cisplatin‐resistant ovarian cancer cells, also represses gene PD‐L1 expression. However, the mechanism by which miR‐145 contributes to regulate PD‐L1 expression in cisplatin resistance of ovarian cancer is yet to be fully understood. Here, we show that cisplatin‐mediated miR‐145 down‐regulation increased PD‐L1 expression via targeting the c‐Myc transcription factor, thereby inducing T cell apoptosis in vitro. We also report that expression of miR‐145 is negatively correlated with PD‐L1 expression in human ovarian cancer tissues, malignant grades and the recurrent risks of ovarian cancer after chemotherapy. In summary, our findings suggest that the miR‐145/c‐Myc/PD‐L1 axis contributes to cisplatin resistance in ovarian cancer and support that miR‐145 might act as an adjuvant therapeutic target in chemotherapy of ovarian cancer. [ABSTRACT FROM AUTHOR]