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Jie Ren,1,* Jingzhou Wang,2,* Xingchen Yao,1 Yue Wu,1 Ming Shi,1 Xiangjun Shi,3 Xinru Du1 1Department of Orthopaedics, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China; 2Department of Orthopaedics, Beijing Daxing District People’s Hospital, Beijing, 102600, People’s Republic of China; 3Department of Hematology, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinru Du, Department of orthopaedics, Beijing Chao-yang Hospital, No. 8 of Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 13683156652, Email duxinru@163.comObjective: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia.Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry.Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG.Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.Keywords: multiple myeloma, SOST, multiple myeloma mouse model, ethology, sarcopenia, myoblast differentiation

Imaging examination plays an important role in the early diagnosis of myeloma. The study focused on the segmentation effects of deep learning-based models on CT images for myeloma, and the influence of different chemotherapy treatments on the prognosis of patients. Specifically, 186 patients with suspected myeloma were the research subjects. The U-Net model was adjusted to segment the CT images, and then, the Faster region convolutional neural network (RCNN) model was used to label the lesions. Patients were divided into bortezomib group (group 1, n = 128) and non-bortezomib group (group 2, n = 58). The biochemical indexes, blood routine indexes, and skeletal muscle of the two groups were compared before and after chemotherapy. The results showed that the improved U-Net model demonstrated good segmentation results, the Faster RCNN model can realize the labeling of the lesion area in the CT image, and the classification accuracy rate was as high as 99%. Compared with group 1, group 2 showed enlarged psoas major and erector spinae muscle after treatment and decreased bone marrow plasma cells content, blood M protein, urine 24 h light chain, pBNP, ß-2 microglobulin (β2MG), ALP, and white blood cell (WBC) levels ( P < 0.05 ). In conclusion, deep learning is suggested in the segmentation and classification of CT images for myeloma, which can lift the detection accuracy. Two different chemotherapy regimens both improve the prognosis of patients, but the effects of non-bortezomib chemotherapy are better.

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. The disease clinically manifests as anemia, hypercalcemia, renal insufficiencies, and osteolytic damage. Osteolytic damage goes with severe bone pain, spinal instability, and pathological fracture, symptoms that are collectively referred to as multiple myeloma bone disease (MMBD). Polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery, owing to its excellent biomechanical properties and fast curing. To date, however, efficacy of drug-loading PMMA in inhibition of tumor growth and angiogenesis remains unknown. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. In addition, 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.

Psoriasis is a systemic inflammatory disease that is associated with increased risk of several diseases, such as psoriatic arthritis (PsA), inflammatory bowel disease, and cardiovascular diseases. About 20 to 30% patients with psoriasis subsequently develop PsA. IgA nephropathy is the most common primary glomerular disease world-wide. Psoriasis and IgA nephropathy appear to be associated, but the mechanism underlying this connection is unclear. Tofacitinib and leflunomide are common treatments for psoriatic arthritis. We administered tofacitinib combined with leflunomide to a 38-year-old female patient who presented with PsA and IgA nephropathy. After treatment, she experienced significant reductions in the psoriatic lesions, pain in the right knee joint, and proteinuria. Administration of tofacitinib combined with leflunomide for treatment of a patient who had PsA complicated with IgA nephropathy led to significant resolution of the symptoms of both conditions. These results suggest similarities in the pathogenesis of PsA and IgA nephropathy and a possible new treatment for IgA nephropathy.

Background We report a case of spine infection with mucormycosis that manifested signs of paraplegia in a patient suffering from disseminated mucormycosis. Timely and effective surgery was performed. A review of the literature is included. Case presentation A patient with diabetic ketoacidosis complained of back pain and fatigue for one month, and his right lower extremity activity had been limited for 10 days. T4–T6 vertebral and paravertebral soft tissue-involved infections were identified by MRI, which were derived from right lung pneumonia. He underwent abscess debridement, spinal canal decompression, pedicle screw fixation and amphotericin B liposome injection. Histopathological examination revealed broad aseptate hyphae suggestive of invasive mucormycosis. There was improvement in neurological function after surgical and medical treatment. Three months after the surgery, the patient died of uncontrollable massive bleeding of the urinary system. Mucormycosis is characterized by rapid development and a high mortality rate. This case shows the significance of a multidisciplinary team in the diagnosis and treatment of patients with mucormycosis. In addition, orthopedic surgeons should design appropriate surgery plans for spine-involved mucormycosis patients. Conclusion This case present a patient with paraplegia caused by the spread of pulmonary mucormycosis to the vertebral and paravertebral soft tissue of levels T4–T6. After medical treatment, surgical debridement and internal fixation, the patient recovered well but later patient died of possible disease dissemination to the renal or urinary tract which resulted in massive haemorrhage.

Background: Although emerging cell- or animal-based evidence supports the correlation between AXIN1(Axis inhibition protein 1) and cancers，no pan-cancer analysis is accessible. Method: We thus investigate the possible oncogenic characters of AXIN1 by 33 tumor types based on the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). Result: AXIN1 has a high expression in lots of tumors, and obvious relevance between AXIN1 expression and prognosis of cancer patients, such as LICH (Liver hepatocellular carcinoma) and breast cancer. We observed an increase phosphorylation level of S486/S493 in breast cancer and UCEC (Uterine Corpus Endometrial Carcinoma). AXIN1 expression shows a correlation with T cell regulatory in several cancers such as LIHC and LUAD (Lung adenocarcinoma). Furthermore, enrichment exist between Wnt signaling pathway, Hippo signaling pathway and pathways in cancer and the functional mechanisms of AXIN1.Conclusions: Our first pan-cancer study provides a relatively complete interpretation of oncogenic characters of AXIN1 though different tumors.

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. Its main clinical symptoms are osteolytic damage, severe bone pain, spinal instability, and pathological fracture and are collectively referred to as multiple myeloma bone disease (MMBD). Due to its good biomechanical properties and fast curing, polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery. However, whether drug-loading PMMA can inhibit tumor growth and angiogenesis has not been reported. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.

A cascade reaction of isoquinoline N-oxides with alkynones was developed, delivering a fluorescent benzoazepino[2,1-a]isoquinoline derivative. The reaction worked smoothly without requirement of any catalyst or additive, making this method economical and easy to handle.

Medicinal leeches have been widely utilized in medical procedures for thousands of years. The application of leeches depends on the components of leech saliva secretions and active molecules, but many components of the secretions are not well characterized due to their low concentration and abundance. Determination of the profiles of leech salivary secretions is important to its medicinal application. In this study, we performed an in-depth proteomic analysis of leech salivary glands and deduced 434 full-length protein sequences from combined leech proteome and transcriptome databases. After integrating data from both datasets, forty-four proteins and two hundred twenty-one transcripts of bioactive molecules were involved in leech sucking pathways. Using gene expression analysis, we found that two-thirds of bioactive genes played key roles in leech bite processes and were associated cave-dwelling habitats. Our results indicate that the treatment efficiency can differ depending on the sucking leech species. Moreover, combining high-throughput proteomic and transcriptomic analyses is effective for the determination of wide profiles of proteins that are present at low concentrations in secretions. These findings highlight the extensive diversity of bioactive molecules and provide a new foundation for performing novel investigations and discovering future pharmacological agents or targets in leech medicinal therapy. SIGNIFICANCE: Medicinal leech therapy has been used for many centuries depending on the components of leech saliva secretions and active actions, but many components of the secretions were less known due to its low concentration and abundance. Determination of the profiles of leech salivary secretions is important to its medicinal application. Hereby, the molecular information provided by proteomic and transcriptomic analysis can be used to develop a more thorough understanding of leech sucking pathway and medicinal application. It provided a new foundation for performing novel investigations and discovering future pharmacological agents or targets in leech medicinal therapy.

Background: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, which SINS scoring system may not be fully applicable to MM patients. We designed a stability evaluation system to evaluate the spinal stability of patients with MM spinal involvement in order to guide clinical treatment.Methods: By using Delphi method, information was collected and extracted through a series of questionnaires and improved via feedback and we preliminary establishment of a spinal stability scoring system for multiple myeloma.Results: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The scoring system consisted of the following six components. The MM spinal stability scoring system was created by calculating the scores of the six separate components: Location, Pain, Number of segments, Physiological curvature, Comorbidities and Neurological function. The minimum value was ‘0’, and the maximum value was ‘24’. A score of ‘0-10’ indicated ‘spine stability’, a score of ‘11-17’ indicated ‘potential instability’, and a score of ‘18-24’ indicated ‘spine instability’. Patients with a score of ‘11-24’ need an intervention such as surgery.Conclusions: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM. Trial registration: The conducted study contains a retrospective analysis of medical records of our hospital database. Beijing Chao-yang Hospital Human Research Ethics Committee classifies this as a retrospective audit. The ethics approval and consent was given for the conducted retrospective data analysis.

Background: The phenomenon of spontaneous resorption of a herniated disc (HD) is a common occurrence. In literature, there are many studies attempting to explain the mechanism for regression, including imaging techniques and immunohistologic analyses. Nevertheless, the exact mechanism remains uncertain. In addition, the connection between HD regression and general conditions of patients is not concerned yet. Here we report a case of spontaneous resorption of a lumbar disc herniation in a patient with multiple myeloma, which had not reported before.Case presentation: An illustrative patient, a 42-year-old Chinese man, was admitted to our hospital with a disc herniation at L5-S1, experiencing 2-months history of low back pain and 1-month left leg pain. He was treated conservatively with medication and physical therapy. Then he was symptom-free after 2 months. The low back pain of the patient recurred with the herniated lumbar disc disappearing after 2 years. The disappearance demonstrated by magnetic resonance imaging (MRI). And besides, the patient was diagnosed with multiple myeloma (MM). The emergence of MM might result in the recurred backache, and the process of HD resorption might be accelerated by the high serum Vascular endothelial growth factor (VEGF) of the MM patient.Conclusions: For patients who suffering from intervertebral disc herniation together with diseases upregulating VEGF level, such as MM, surgical treatment should be limited and the conservatively treating time can be lengthened.

Enzymatic browning is one of the major difficulties for the preservation and commercial value of fresh-cut products. To research more healthy and inexpensive anti-browning methods, we investigated the effect of ultrasonic coupling purslane extract on the browning resistance of fresh-cut potato during 8d storage at 4 °C. Firstly, the optimal ultrasonic time (10 min) was obtained. Then, the results showed that the combined application with lower purslane extract concentration (0.02%, w/w) could achieve a better anti-browning effect than the optimal concentration of alone purslane extract (0.05%, w/w). The combined application not only significantly inhibited the key enzyme activities of polyphenol oxidase (PPO) and peroxidase (POD), but also effectively reduced the damage to cell membrane, maintained its integrity and permeability. Meanwhile, it also improved antioxidant capacity during storage. Overall, the ultrasonic cavitation combined with purslane extract would be a promising method for fresh-cut industry.

Summary Ameliorating T cell exhaustion and enhancing effector function are promising strategies for the improvement of immunotherapies. Here, we show that the HPK1-NFκB-Blimp1 axis mediates T cell dysfunction. High expression of MAP4K1 (which encodes HPK1) correlates with increased T cell exhaustion and with worse patient survival in several cancer types. In MAP4K1KO mice, tumors grow slower than in wild-type mice and infiltrating T cells are less exhausted and more active and proliferative. We further show that genetic depletion, pharmacological inhibition, or proteolysis targeting chimera (PROTAC)-mediated degradation of HPK1 improves the efficacy of CAR-T cell-based immunotherapies in diverse preclinical mouse models of hematological and solid tumors. These strategies are more effective than genetically depleting PD-1 in CAR-T cells. Thus, we demonstrate that HPK1 is a mediator of T cell dysfunction and an attractive druggable target to improve immune therapy responses.

Background Multiple myeloma (MM) is a blood system malignant tumor, which often leads to osteolytic bone destruction, and the vertebral column is the primary site of involvement. However, the efficacy and prognosis of percutaneous kyphoplasty/vertebroplasty (PKP/PVP) for simple vertebral pathological fractures in patients with multiple myeloma are not yet unified. The primary objective of this study was to investigate the efficacy and prognosis of PKP/PVP in the treatment of multiple myeloma patients with vertebral pathological fractures. Methods A total of 108 patients with MM from Beijing Chao-Yang Hospital from 2007 to 2013 were enrolled. Of these, 52 patients underwent PKP/PVP surgery and chemotherapy (surgery group) and 56 received only chemotherapy (chemotherapy group). The age, gender, International Staging System (ISS), fracture location, segment, visual analog scale (VAS), Oswestry Disability Index (ODI), comprehensive treatment satisfaction, stem cell transplantation, overall survival (OS), mortality rate, and the cause of death of patients were recorded; the mean follow-up time was 42.46 months. Results The average age of patients in surgery and chemotherapy groups was 60.8 years and 58.1 years, and the mean survival time was 41.98 months and 43.30 months, respectively. The VAS score at 1 month and last follow-up after treatment in surgery group were significantly lower than those in the chemotherapy group (P

Interpersonal nodes in the social networking sites reflect the para-virtual and para-real relationships, and form a complex social network. To reveal the properties of the interpersonal nodes and their interrelations effectively, this paper develops an evaluation index system, which contains fuzzy comentropy, fuzzy node degree, fuzzy condensation degree, fuzzy cluster coefficient and fuzzy geographic concentration, and particularly proposes a fuzzy social network centrality analysis (FSNCA) model, which combines "node distribution", "node connection strength" and "node condensation and cluster", based on the fuzzy graph-theory. The FSNCA model has been successfully applied to study the interpersonal nodes' spatial relations in three social networking services (SNS) cases, in which three progressive layers, "nodes", "node connections" and "differences between node connections", are analyzed respectively. In the first case, the "friend group nodes" are studied to evaluate the equilibrium of node distribution in the network space by use of the fuzzy comentropy index. In the second case, the "connections between BBS group regional nodes" are studied to evaluate the centrality status and types of nodes in the network space by use of the fuzzy node degree index. The third case analyzes the "node connections of two kinds of chance relation groups" to evaluate the differences of centrality status in different networks by use of the fuzzy condensation degree, fuzzy cluster coefficient and fuzzy geographic concentration indexes. The systematic cognition of the interpersonal node spatial relations in the SNS community proves that the proposed method can effectively reveal the essence of fuzzy centralities. It sheds some light on the para-virtual and para-real geographical research, which is of significance to enrich the para-virtual and para-real geographical spatial relation theory, and it can also directly support the management and development of social networks of online services.

The surface browning usually occurs on fresh-cut potato during storage. The effect of short-time high oxygen pretreatment on anti-browning of fresh-cut potato slices was investigated. The whole potato tubers were firstly immersed in the oxygen concentration of 21%, 60% and 80% for 20 min. Then, the potatoes were peeled, cut and stored at 4 °C for 8 days. The results showed that the short-time 80% oxygen pretreatment possessed significantly anti-browning effect by retarding the increase of polyphenol oxidase (PPO) activity and the accumulation of malondialdehyde (MDA) content, maintaining the cell integrity. Meanwhile, the 80% oxygen treatment could increase the activities of phenylalanine ammonia lyase (PAL) and peroxidase (POD), and the total phenolic content. Importantly, the 80% oxygen treatment could effectively improve the antioxidant capacity. Overall, all results suggest that the short-time high oxygen pretreatment holds great promise on anti-browning of fresh-cut potato.

We report a 38-year-old man of multiple myeloma with bilateral femoral nerve entrapment caused by bilateral huge protruding masses in the inguinal areas. The masses were identified as iliopsoas muscular amyloidoma after the operation. He was diagnosed with multiple myeloma 1 year ago before he was admitted to our hospital. He complained of muscle weakness in the bilateral thigh and protruding lumps in the bilateral inguinal areas with tenderness for 6 month. The pelvic MRI revealed round masses in the iliopsoas muscles of bilateral inguinal areas. To implement the nerve decompression, the resection of the bilateral masses was done. The pathological result showed Congo red-positive substance with green birefringence to polarized light in a dense fibrous background. Before the operation, six cycles of chemotherapy with VAD (vincristine, adriamycin, dexamethasone) and two cycles of chemotherapy with PAD (bortezomib, adriamycin, dexamethasone) regimen were performed. One month after the operations, one cycle of chemotherapy with PADT (bortezomib, adriamycin, dexamethasone, thalidomide) regimen was used and the patient reached complete remission. The function of the bilateral femoral nerves restored to normal 7 months after the operation with a Karnofsky score of 100. Twenty-two months follow-up showed that there was no evidence of the recurrence of the iliopsoas muscular amyloidoma and no progression of multiple myeloma.