BACKGROUND:Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication,while repairing skeletal muscles and promoting skeletal muscle regeneration,which is expected to be a novel treatment modality for sarcopenic obesity. OBJECTIVE:To review the biogenesis of extracellular vesicles,their biological functions,their relationship with sarcopenic obesity,and recent advances in the pathogenesis,diagnosis,and treatment of sarcopenic obesity. METHODS:The first author performed a computer search of PubMed,Embase,CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity.The search keywords were"extracellular vesicle,exosome,sarcopenic obesity,obese sarcopenia,skeletal muscle regeneration,skeletal muscle mass regulation"in English and Chinese,respectively.The search period was from June 2022 to November 2022.After screening,87 articles were included for further review. RESULTS AND CONCLUSION:Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine,paracrine and endocrine ways.Sarcopenic obesity is a complex multi-factor disease.Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells.Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis,which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity.Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers,but also are a valuable diagnostic indicator of sarcopenic obesity.Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration.Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.

Neuropathic pain (NP) is a common complication following spinal cord injury, with an incidence rate ranging from 38% to 70%. NP typically presents as sensation of burning, electric shocks, tingling or squeezing pain resulting from somatosensory nerve damage, which exerts a negative impact on patients′ physical and psychological well-being. After spinal cord injury, glial cells are activated to induce inflammatory cascade. Accordingly, various inflammatory mediators that may disrupt the neuronal function are released to promote abnormally increased neuronal excitability and pain signal transduction. Additionally, spinal cord injury can disrupt the release of neurotransmitters and neurotrophic factors, alter ion channel activity, and thereby impair the normal pain regulatory mechanisms and further increase pain perception. The interaction of these mechanisms contributes to the occurrence and persistence of NP after spinal cord injury. However, the precise pathogenesis of NP remains incompletely elucidated, making its therapeutic efficacy uncertain and clinical management difficult. It is of great significance to thoroughly understand the underlying pathophysiological mechanisms of NP following spinal cord injury for its treatment. For this reason, the authors reviewed the research progress on the characteristics and pathophysiological mechanisms of NP following spinal cord injury, aiming to serve as a reference for further research and development of more effective targeted therapies and management strategies.

Objective To investigate the chemical composition from the flowers of Callerya speciosa,and reveal the metabolites difference at different flowering periods based on metabolomics technology.Methods The primary and secondary metabolites,volatile chemical components in flowers of C.speciosa were analyzed combined by GC-MS and UPLC-Q-Exactive MS.Principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and hierarchical cluster analysis(HCA)were performed to identify differential metabolites.Results A total of 332 compounds were identified by UPLC-Q-Exactive MS,mainly including secondary metabolites such as flavonoids,triterpenoids,phenylpropanoids.A total of 297 compounds were identified by GC-MS,mainly including primary metabolites and volatile chemical components,such as organic acids,amino acids,saccharides,heterocycles,alcohols.The PCA analysis demonstrated that the metabolites of the four flowering periods were divided into two groups:bud,initial bloom and blooming periods clustered into one group,while wilting period clustered into the other group,the main differences were filtered and identified as flavonoids and triterpenoids,organic acids,respectively.Compared to the upright type,the flowers of vine type contained more characteristic flavonoids as differential metabolites during the bud,initial bloom and blooming periods,and some flavonoids decrease gradually with the development of flowering.Conclusion The results indicated that the flowers of C.speciosa possessed abundant active flavonoid metabolites for further utilization,and the best harvest stage is initial bloom,the best harvest plant is vine type.This study provides a scientific basis for the scientific development and rational use of the flowers of C.speciosa.

OBJECTIVE: To review the research progress in the construction strategy and application of bone/cartilage immunomodulating hydrogels. METHODS: The literature related to bone/cartilage immunomodulating hydrogels at home and abroad in recent years was reviewed and summarized from the immune response mechanism of different immune cells, the construction strategy of immunomodulating hydrogels, and their practical applications. RESULTS: According to the immune response mechanism of different immune cells, the biological materials with immunoregulatory effect is designed, which can regulate the immune response of the body and thus promote the regeneration of bone/cartilage tissue. Immunomodulating hydrogels have good biocompatibility, adjustability, and multifunctionality. By regulating the physical and chemical properties of hydrogel and loading factors or cells, the immune system of the body can be purposively regulated, thus forming an immune microenvironment conducive to osteochondral regeneration. CONCLUSION Immunomodulating hydrogels can promote osteochondral repair by affecting the immunomodulation process of host organs or cells. It has shown a wide application prospect in the repair of osteochondral defects. However, more data support from basic and clinical experiments is needed for this material to further advance its clinical translation process.
Hydrogels ; Cartilage ; Bone and Bones ; Tissue Engineering/methods*

Objective:To establish the mouse model with radiation-induced pulmonary fibrosis, and to identify and analyze it from the aspects of function, imaging and pathology.Methods:Thirty C57BL/6 mice were randomly divided into the control group, 16 Gy irradiation group and 20Gy irradiation group. The mice in the irradiation groups received a single 16 Gy or 20 Gy chest X-ray irradiation, and underwent functional examination, imaging examination and pathological examination at 3 and 6 months after irradiation.Results:At 6 months after irradiation, hair on the chest and back of the mice turned white and fell off, and the airway resistance was increased significantly. CT images showed extensive patch shadows and consolidation in the lung. Three dimensional reconstruction suggested that the lung of mice was distorted and deformed, and the volume was decreased significantly. Pathological examination confirmed that there was extensive pulmonary fibrosis.Conclusions:Significant pulmonary fibrosis occurs after 6 months of chest irradiation in mice. The animal model of radiation-induced pulmonary fibrosis in C57BL/6 mice was successfully established.

Osteoporosis seriously threatens the living quality of people, especially the elderly, and causes a huge economic burden to society. In the past, bisphosphonates, denosumab and other first-line drugs were used in the treatment of osteoporosis. However, these drugs can only inhibit bone resorption, but can not promote bone formation. Studies have shown that mesenchymal stem cells (MSCs) can be used to treat osteoporosis, however, it has some defects and deficiencies, such as genetic instability, limited cell survival and increased risk of cancer. However, mesenchymal stem cell-derived exosomes (MSCs-Exos) can regulate the differentiation and proliferation of osteoblasts by mediating wingless and int-1 (Wnt)/β-catenin and mitogen-activated protein kinase (MAPK) signaling pathways, promote bone regeneration, and thus has an impact on osteoporosis. In this paper, preclinical studies on MSCs and MSCs-Exos in the treatment of osteoporosis in recent years were reviewed, in order to provide a new idea for the treatment of osteoporosis.

For non-small cell lung cancer (NSCLC) patients with positive surgical margins, the survival rates can be dramatically decreased. However, high-level evidence is lacking in the standard adjuvant treatment for NSCLC patients with positive surgical margins. In this article, consensus and disputes on the adjuvant therapy for NSCLC patients with positive surgical margins were reviewed.

BACKGROUNDPelvic fractures are uncommon in elderly patients and so are infrequently addressed in the literature. The purpose of this study was to investigate the management and outcome of pelvic fractures in elderly patients.

METHODSWe retrospectively reviewed the records of pelvic fractures in elderly patients (age ≥55 years) who were treated in our department from September 1997 to May 2010.

RESULTSA total of 40 elderly patients with pelvic fractures were identified. Their mean age was 65.8 years (range 55-87 years). About 68% (n = 27) were men. The average Injury Severity Score (ISS) was 17.8 (range 6-45). Twelve (30%) patients required blood transfusion (mean 10 units) during the first 24 hours. The fractures were most frequently due to falling from a standing position (48%). Almost half (48%) were grade I breaks. Associated injuries were present in 70% (n = 28) of patients, and 65% (n = 26) had medical co-morbidities. Altogether, 29 patients (73%) underwent non-surgical management of their pelvic fracture. The average hospital stay was 25 days. There were five in-hospital deaths and one death 10 months after discharge. High ISSs (>25) were associated with increased in-hospital mortality (P = 0.018). At the final assessment (mean follow-up 15 months), 52% of the surviving patients had experienced decreased self-sufficiency.

CONCLUSIONSPelvic fractures in elderly patients result in high morbidity and mortality rates. A high ISS (>25) can be used to identify a patient at high risk. We recommend aggressive resuscitation and intensive care for that patient. For patients with an unstable pelvic or displaced acetabular fracture (≥2 mm) who can endure surgery, open reduction and internal fixation can provide adequate fixation for early weight-bearing and restoration of the bone stock.

Aged ; Aged, 80 and over ; Blood Transfusion ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; etiology ; surgery ; therapy ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Pelvic Bones ; injuries ; Retrospective Studies

BACKGROUND: Based on previous technique prepared for encapsulating living cells with alginate-polysine- alginate (APA) microcapsules, it has been confirmed that microencapsulated chromaffin cells have good analgesic effects. The immunoisolated effects of such microcapsule materials need to be evaluated. OBJECTIVE: This study aimed to investigate the immunological rejections of APA microencapsulated chromaffin cells transplanted into rat anterior chamber of eyes and tendon of feet, and to evaluate the immunoisolated effect of microencapsulation.DESIGN: A randomized controlled animal experiment. SETTING: Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Forty-eight female SD rats, with the age of 3 months, were provided by the Laboratory Animal Center, Tongji Medical College, Huazhong University of Science and Technology. The protocol was carried out in accordance with ethical guidelines for the use and care of animals. Alginate and polylysine used in the experiment were the products of Sigma Company, USA. Microcapsule generator was gifted by Germany. METHODS: This study was performed at the Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology from September 2002 to September 2003. Suprarenal medulla was taken from 6 healthy adult cadavers of brain death. After isolated, digested and cultured, suprarenal medulla was prepared into chromaffin cell suspension. Written informed consents were obtained from the family members of donors, and the protocol was given approval by the Ethics Committee of the hospital. Empty microcapsules and microencapsulated cells were prepared by APA. The 48 rats were randomly divided into the human chromaffin cell (HCC) group, the empty microcapsule group and the microencapsulated HCC (ME-HCC) group. In each group, there were two transplanted regions of anterior chamber of eyes and tendon of feet, with 8 rats used for each region. Each rat in the HCC group was perfused 2×1010 L-1 cell suspension into the anterior chamber of eyes and tendon of feet. Those in the empty microcapsule group and the ME-HCC group were perfused 100 empty capsules and ME-HCCs (100 microcapsules, 400-500 HCCs per microcapsule) into the same regions, respectively. MAIN OUTCOME MEASURES: On day 7 after transplantation, serum interleukin (IL)-2 level was determined by ELISA. Serum IgG and IgM levels were determined with a laser turbidimeter. On day 28 after transplantation, rat right eyeball and left feet were harvested, routinely sliced and stained by haematoxylin-eosin (HE). Histo-morphological structure was observed under a 40×light microscope. RESULTS: Forty-eight rats were included in the final analysis. Serum IL-2, IgG and IgM levels were significantly lower in the empty microcapsule group and ME-HCC group than in the HCC group (t=8.544-21.64, P < 0.01). A lot of lymphocyte and neutrophile infiltration could be found in the anterior chamber of eyes and tendon of feet of rats in the HCC group, but a little seen in that of the empty microcapsule group and ME-HCC group. CONCLUSION: APA microencapsulation has an effective immunoisolated effect on immunological rejection due to its good biocompatibility and mechanical stability.

Objective To compare the catecholamine (CA ) and M enkephalin(M ENK) release from human chromaffin cells (HCC) and microencapsulated HCC (ME HCC ) and investigate the effects of microencapsulation on the growth and activity of chromaffin cells Methods Adrenal glands were taken from brain death healthy adults The chromaffin cells were isolated and primarily cultured in vitro During culture the chromaffin cells were HE stained and assessed by labelling the cells with tyrosine hydroxylase monoclonal antibody The percentage of tyrosine positive cells were counted under microscope (1) The chromaffin cells were microencapsulated with 2% alginate and cultured in vitro (experimental group) HCC which were not microencapsulated were used as control The culture media of both groups were replaced every 48h and collected and stored under -20℃ for determination of CA and M ENK concentration (2) On the 6th day of culture, nicotine was added to HCC and MC HCC suspension After 30 min incubation, the suspension was centrifuged and the supernate collected and stored under -20 ℃ for determinatoin of CA and M ENK concentration with radioimmunoassay Results (1) ME HCC grew fairly well in vitro in the culture medium and was morphologically similar to HCC (2) There was no significant difference in CA and M ENK concentration in HCC and ME HCC culture media (3) CA and M ENK concentrations in supernate were increased by nicotine stimulation and there was no difference in the CA and M ENK concentration in the supernate between the two groups Conclusions Alginate and microencapsulation technique are not harmful to HCC, ME HCC has fairly good activity and release function and can be effectively used for transplantation