STAT3-induced ZBED3-AS1 promotes the malignant phenotypes of melanoma cells by activating PI3K/AKT signaling pathway.

Melanoma is considered as the most frequent primary malignancy occurring in skin. Accumulating studies have suggested that long non-coding RNAs (lncRNAs) play critical parts in multiple cancers. In this study, we explored the molecular mechanism of ZBED3 antisense RNA 1 (ZBED3-AS1) in melanoma. We observed that ZBED3-AS1 expression was remarkably up-regulated in melanoma tissues, and high ZBED3-AS1 level was linked to unsatisfactory survival of melanoma patients. Then, we discovered that ZBED3-AS1 was overexpressed in melanoma cells compared with human epidermal melanocytes. In addition, loss-of-function assays verified that ZBED3-AS1 knockdown restrained cell proliferation, migration, epithelial-mesenchymal transition (EMT), and stemness in melanoma. In addition, signal transducer and activator of transcription 3 (STAT3), which also showed tumour-facilitating functions in melanoma, was confirmed as a transcriptional activator of ZBED3-AS1. Moreover, ZBED3-AS1 enhanced the expression of AT-rich interaction domain 4B (ARID4B) through sequestering miR-381-3p. Importantly, we further confirmed that ZBED3-AS1 promoted the malignant progression of melanoma by regulating miR-381-3p/ARID4B axis to activate the phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) signalling pathway. In a word, our research might provide a novel therapeutic target for melanoma.

Peroxisome proliferator-activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro.

Glial glutamate transporter 1 (GLT-1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator-activated receptor gamma (PPARγ) participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT-1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up-regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT-1 was studied in rat cortical astrocyte-neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up-regulation of GLT-1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT-1 up-regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT-1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose-dependently attenuated the up-regulation of GLT-1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT-1 during the acquisition of BIT induced by IPC. Cover Image for this issue: doi: 10.1111/jnc.14532. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

Chinese regulation of off-label use of drugs.

China has significant gaps and weaknesses in its regulatory oversight of the off-label use of drugs. As in the United States, the off-label prescribing of drugs is not prohibited in China if there is a sound scientific basis. Physicians are allowed to prescribe off-label drugs based on their medical judgment if they follow certain requirements. There is some constraint on the right to prescribe by the imposition of malpractice liability if patients are harmed from improper off-label prescribing. However, damages awarded to successful plaintiffs are usually insignificant compared to malpractice damage awards in the U.S. Advertisement of off-label use is prohibited in China. All drug advertisements in China are subject to pre-approval, and must be based on information included in the approved package insert. However, the term "advertisement" is poorly defined. As a result, non-advertisement promotion of drugs for on-label or off-label use exist in a unregulated gray area. To better address the problem of inappropriate off-label promotion and use, China should (i) regulate both drug advertisements and non-advertisement promotion under a standard requiring off-label use to have a sound scientific basis, (ii) introduce harsher regulatory penalties, and (iii) increase compensation available for victims of medical malpractice. Such reform would not only discourage improper off-label use by introducing penalties (or increasing existing penalties) for improper promotion, but would also provide reasonable compensation for victims harmed by off-label use.

Case report: Occult Listeria monocytogenes invasion leading to prosthetic hip joint infection in a patient with rheumatoid arthritis taking tofacitinib.

It has been suggested that targeted therapy may potentially increase the risk of listeriosis. However, no reported cases of Listeria monocytogenes prosthetic joint infection have been documented during Janus Kinase (JAK) pathway inhibitor use. Herein, we present a 70-year-old female with rheumatoid arthritis who had undergone bilateral hip joint replacement and subsequently developed Listeria monocytogenes prosthetic joint infection following tofacitinib therapy. We suggest that the use of tofacitinib may potentially heighten susceptibility to listeriosis in patients afflicted with rheumatoid arthritis.

Effective evaluation of HGcnMLP method for markerless 3D pose estimation of musculoskeletal diseases patients based on smartphone monocular video.

Markerless pose estimation based on computer vision provides a simpler and cheaper alternative to human motion capture, with great potential for clinical diagnosis and remote rehabilitation assessment. Currently, the markerless 3D pose estimation is mainly based on multi-view technology, while the more promising single-view technology has defects such as low accuracy and reliability, which seriously limits clinical application. This study proposes a high-resolution graph convolutional multilayer perception (HGcnMLP) human 3D pose estimation framework for smartphone monocular videos and estimates 15 healthy adults and 12 patients with musculoskeletal disorders (sarcopenia and osteoarthritis) gait spatiotemporal, knee angle, and center-of-mass (COM) velocity parameters, etc., and compared with the VICON gold standard system. The results show that most of the calculated parameters have excellent reliability (VICON, ICC (2, k): 0.853-0.982; Phone, ICC (2, k): 0.839-0.975) and validity (Pearson r: 0.808-0.978, p<0.05). In addition, the proposed system can better evaluate human gait balance ability, and the K-means++ clustering algorithm can successfully distinguish patients into different recovery level groups. This study verifies the potential of a single smartphone video for 3D human pose estimation for rehabilitation auxiliary diagnosis and balance level recognition, and is an effective attempt at the clinical application of emerging computer vision technology. In the future, it is hoped that the corresponding smartphone program will be developed to provide a low-cost, effective, and simple new tool for remote monitoring and rehabilitation assessment of patients.

[In situ temperature measurement by absorption spectroscopy based on time division multiplexing technology].

Tunable diode laser absorption spectroscopy (TDLAS) technology is a kind of high sensitivity, high selectivity of non contacting gas in situ measurement technique. In the present paper, in situ gas temperature measurement of an open environment was achieved by means of direct scanning multiple characteristic lines of H2O and combined with least-squares algorithm. Through the use of HITRAN spectral database, the boundary effect on the gas temperature and concentration measurements was discussed in detail, and results showed that the combination of scanning multiple characteristic lines and least-squares algorithm can effectively reduce the boundary effect on the gas temperature measurements under the open environment. Experiments using time division multiplexing technology to simultaneously scan 7444.36, 7185.60, 7182.95 and 7447.48 cm(-1), the four characteristic H2O lines, the gas temperature of tubular furnace in the range of 573-973 K was measured under different conditions. The maximum temperature difference between absorption spectrum measurement and thermocouple signal was less than 52.4 K, and the maximum relative error of temperature measurement was 6.8%.

A Portable Wearable Inertial System for Rehabilitation Monitoring and Evaluation of Patients With Total Knee Replacement.

Knee osteoarthritis is a degenerative disease, which greatly affects the daily life of patients. Total knee replacement (TKR) is the most common method to treat knee joint disorders and relieve knee pain. Postoperative rehabilitation exercise is the key to restore knee joint function. However, there is a lack of a portable equipment for monitoring knee joint activity and a systematic assessment scheme. We have developed a portable rehabilitation monitoring and evaluation system based on the wearable inertial unit to estimate the knee range of motion (ROM). Ten TKR patients and ten healthy adults are recruited for the experiment, then the system performance is verified by professional rehabilitation equipment Baltimore Therapeutic Equipment (BTE) Primus RS. The average absolute difference between the knee ROM and BTE Primus RS of healthy subjects and patients ranges from 0.16° to 4.94°. In addition, the knee ROM of flexion-extension and gait activity between healthy subjects and patients showed significant differences. The proposed system is reliable and effective in monitoring and evaluating the rehabilitation progress of patients. The system proposed in this work is expected to be used for long-term effective supervision of patients in clinical and dwelling environments.

Automatic Fall Protection for Hips Based on Micromechanical Double Gas Cylinder Rapid Puncture and Bionic Capsule Inflation.

Wearable hip-protection airbags can effectively protect hip joints when elderly people fall. This has been studied all over the world, but similar products need to use special gas cylinders and replacement of new gas cylinders needs to return to the factory; The team previously designed a mechanical puncture protection system based on standard gas cylinders and standard threaded interfaces, but the airbag still has shortcomings such as the small protective area caused by a single gas cylinder. To solve the above problems, a set of wearable hip automatic protection systems based on micromechanical double gas cylinder rapid puncture (MDGCRP) is now designed. Through a large number of experiments, it was found that the response time of MDGCRP was 92ms and the execution time was 177.5ms. Compared with the single gas cylinder approach, the airbag provides greater protection to the hip while the filling time and module weight remain essentially unchanged. The system is triggered by physical and mechanical methods. Compared with chemical blasting or hot-melt methods, the system has the characteristics of low cost and consumables that can be safely and easily replaced by themselves.

Long-term carbon black inhalation induced the inflammation and autophagy of cerebellum in rats.

Carbon black (CB) has been demonstrated to have adverse effects on the lung tissue. Few studies explored the effects of CB on the cerebellum, widely recognized to contribute to gait and balance coordination and timing in the motor domain. Some studies have reported that inflammatory response and damaged autophagy are important mechanisms of CB toxicity and can be repaired after the recovery. The present study aimed to determine whether long-term CB exposure could induce the inflammation and damaged autophagy of the cerebellum. The rats were randomly divided into four groups. The control group received the filtered air for 90 days; the carbon black (CB) group received CB particles for 90 days; the recovery (R) group received CB for 90 days and recovered for another 14 days; the recovery control (RC) group received filtered air for 104 days. The purpose of the R group was to test whether neuroinflammation and autophagy could be repaired after short-term recovery. The western blot and immunohistochemistry revealed that long-term CB exposure induced augmented level of pro-inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6, IL-6; and Tumor Necrosis Factor-α, TNF-α) and anti-inflammatory cytokine (Interleukin-10, IL-10). The autophagic markers (Beclin1 and LC3) were increased in both CB group and R group. These findings clearly demonstrated that long-term CB exposure induced inflammation and autophagy in the cerebellum, which were not obviously improved after short-term recovery.

Isolation of stem-like cells from human MG-63 osteosarcoma cells using limiting dilution in combination with vincristine selection.

To isolate stem-like cells from the human MG-63 osteosarcoma cell line, different subpopulations of MG-63 cells were cloned by limiting dilution and passaged to obtain different sublines. The subline with highest clonogenicity was identified using a proliferation assay, cell-cycle analysis, and soft-agar colony-forming assay. The sublines were further selected in serum-free medium containing 20 ng/ml vincristine to identify cells that could form suspended sarcospheres. Identified cells were then characterized based on morphology, cell surface markers, adipogenic and osteogenic differentiation, and tumorigenicity in nude mice. A total of 19 holoclones that could be stably passaged were obtained. Sublines A1, A3, and D1 were markedly different from other sublines and the parental cell line. Subline D1 not only had a higher colony-forming efficiency and formed larger colonies, but also possessed a shorter latency of tumorigenesis in vivo. After subline D1 was cultured in suspension in medium containing vincristine, a highly enriched subpopulation of cells that could form sarcospheres and be stably passaged were obtained. These cells, designated as MG-63-M expressed multiple markers of multipotent or embryonic stem cells and possessed the capacity for self-renewal, multilineage differentiation, and significant multi-drug resistance. Thus, our results suggest that a subpopulation of stem-like cells can be isolated from human MG-63 osteosarcoma cell line.

Reprogramming factors induce proliferation and inhibit apoptosis of melanoma cells by changing the expression of particular genes.

Uncontrolled proliferation and defective apoptosis are two major factors responsible for maintaining the malignant properties of melanoma cells. Our previous study demonstrated that induced expression of four reprogramming factors remodeled the phenotype of B16­F10 mouse melanoma cells into melanoma stem cells. The present study was conducted to investigate the effect of the four Yamanaka reprogramming factors, namely Oct4, Sox2, Klf4 and c­Myc (OSKM), on the proliferation and apoptosis of melanoma cells, and to identify the responsible molecular signals. The results identified that expression of the four reprogramming factors was highly induced by doxycycline treatment in the stable melanoma cell clone that was transfected with a plasmid expressing these factors, driven by the Tet­On element. It was further confirmed that induced expression of these factors enhanced the proliferation and suppressed the apoptosis of the melanoma cells. In addition, induced OSKM expression increased cell proliferation, accelerated the progression of the cell cycle, and upregulated the mRNA expression levels of Janus kinase 2 (JAK2) and Cyclin­B1. Induced expression of these factors also decreased the apoptosis, as well as upregulated B­cell lymphoma 2 (BCL­2) and downregulated BCL­2­associated X (BAX) mRNA expression levels. Taken together, the results suggested that upregulated JAK2 and Cyclin­B1 may be responsible for the enhanced proliferation of melanoma cells, and that BCL­2 upregulation and BAX downregulation may account for the suppressed apoptosis of these cells.

The mechanism of GLT-1 mediating cerebral ischemic injury depends on the activation of p38 MAPK.

The previous studies have shown that glial glutamate transporter-1 (GLT-1) participates in cerebral ischemic injury in rats. However, the mechanism involved remains to be elucidated. This study was undertaken to investigate whether p38 MAPK was involved in regulating GLT-1 in the process. At first, it was observed that global brain ischemia for 8 min led to obvious delayed neuronal death, GLT-1 down-regulation and p-p38 MAPK up-regulation in CA1 hippocampus in rats. Then, whether p-p38 MAPK was involved in regulating GLT-1 during cerebral ischemic injury was studied in vitro. Astrocyte-neuron co-cultures exposed to oxygen and glucose deprivation (OGD) were used to mimic brain ischemia. It was observed that lethal OGD (4-h OGD) decreased GLT-1 expression and increased p-p38 MAPK expression in astrocytes. The p-p38 MAPK protein rised from 0 min to 48 h that is the end time of the observation, and the peak value was at 12 h, which was 12.45 times of the control group. Moreover, pre-administration of p38 MAPK inhibitor SB203580 or its siRNA dose-dependently increased GLT-1 expression, and meanwhile alleviated the neuronal death induced by lethal OGD. The above results indicated that p38 MAPK signaling pathway participated in regulating GLT-1 during OGD injury in vitro. Finally, back to in vivo experiment, it was found that pre-administration of SB203580 by intracerebroventricular injection dose-dependently reversed the down-regulation of GLT-1 expression and attenuated the delayed neuronal death normally induced by global brain ischemia in CA1 hippocampus in rats. Taken together, it can be concluded that the mechanism of GLT-1 mediating cerebral ischemic injury depends on the activation of p38 MAPK.

Arthroscopic Removal of Suprapatellar Fibroma of Tendon Sheath.

Intra-articular fibroma of tendon sheath is a rare disease. To our knowledge, less than 20 cases have been reported in the literature, and none of them was a Chinese patient. In this case report, we present a Chinese patient with intra-articular fibroma of tendon sheath of the knee joint which was excised arthroscopically. We also summarized the clinical presentation, diagnosis, and subsequent management of intra-articular fibroma of tendon sheath.

Septic arthritis caused by Brucella melitensis in urban Shenzhen, China: a case report.

INTRODUCTION: Brucellosis is a systemic infectious disease which is still a challenging medical problem in rural areas such as northern China. It rarely occurs in urban areas such as Shenzhen in southern China. Osteoarticular involvements are frequently seen in brucellosis, and rarely is arthritis the only clinical presentation. We report a case of hip septic arthritis caused by Brucella melitensis in an urban area of Shenzhen, China. CASE PRESENTATION: A 29-year-old Chinese woman, Han ethnical group presented to our hospital with left hip pain persisting for one month. She had a history of contact with goats one month before admission. Her clinical examination showed marked tenderness and limited movement of her left hip. Further imaging showed effusion of her left hip joint. Inflammatory markers including erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were raised. Our clinical diagnosis was septic arthritis of the left hip. A left hip arthroscopy was performed and the culture was positive for Brucella melitensis. She returned to normal activity after completing a standard antibiotic regimen, including gentamicin at 120mg daily for 2 weeks, doxycycline at 100mg daily and rifampicin at 450mg for a total of 12 weeks. CONCLUSIONS: Brucellosis is endemic in some rural areas of China, but rare in urban areas such as Shenzhen in southern China. However, more cases will be expected in urban areas due to increasing migration within China. Physicians should consider brucellosis as one of the differential diagnosis of arthritis. Early surgical intervention is recommended to prevent further joint destruction.