Rational design of mitochondria-targeted fluorescent biosensors for in vivo elucidation of the interaction between breast cancer metastasis and mitochondrial autophagy.

Breast cancer lung metastases (BCLM) are a major cause of high mortality in patients. The shortage of therapeutic targets and rapid drug screening tools for BCLM is a major challenge at present. Mitochondrial autophagy, which involves the degradation of proteins associated with cancer cell aggressiveness, represents a possible therapeutic approach for the treatment of BCLM. Herein, four fluorescent biosensors with different alkyl chains were designed and synthesized to monitor mitochondrial autophagy. Among them, PMV-12 demonstrated the highest sensitivity to viscosity variance, the least impact on polarity, and the longest imaging time. The introduction of the C12-chain made PMV-12 anchored in the mitochondrial membrane without being disturbed by changes of the mitochondrial membrane potential (MMP), thereby achieving the long-term monitor in situ for mitochondrial autophagy. Mitochondria stained with PMV-12 induced swelling and viscosity increase after treating with apigenin, which indicated that apigenin is a potential mitochondrial autophagy inducer. Apigenin was subsequently verified to inhibit cancer cell invasion by 92%. Furthermore, PMV-12 could monitor the process of BCLM in vivo and evaluate the therapeutic effects of apigenin. This work provides a fluorescent tool for elucidating the role of mitochondrial autophagy in the BCLM process and for anti-metastatic drug development.

Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury.

PURPOSE: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). MATERIALS AND METHODS: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. RESULTS: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFß1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. CONCLUSIONS: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review.

Background and Objective: Although epimedium herb (EH) has been widely used in ancient Chinese medicine to enhance sexual activity, its pharmacological mechanism is not clear. Modern studies have shown that epimedium herb is rich in icariin (ICA, a flavonoid compound), and 91.2% of icariin is converted to icariside II (ICA II) by hydrolytic enzymes in intestinal bacteria after oral administration. YS-10 is a synthetic derivative of icariside II. The aim of this review was to summarize the contemporary evidence regarding the pharmacokinetics, therapeutic properties, and molecular biological mechanisms of ICA and some ICA derivatives for erectile dysfunction therapy. Methods: A detailed search was conducted in the PubMed database using keywords and phrases, such as "icariin" AND "erectile dysfunction", "icariside II" AND "erectile dysfunction". The publication time is limited to last 20 years. Articles had to be published in peer reviewed journals. Key Content and Findings: ICA and its some derivatives showed the specific inhibition on phosphodiesterase type 5 (PDE5) and the promotion of testosterone synthesis. In addition, by regulating various reliable evidence of signaling pathways such as PI3K/AKT, TGFß1/Smad2, p38/MAPK, Wnt and secretion of various cytokines, ICA and ICA derivatives can activate endogenous stem cells (ESCs) leading to endothelial cell and smooth muscle cell proliferation, nerve regeneration and fibrosis inhibition, repair pathological changes in penile tissue and improve erectile function. Conclusions: ICA and some of its derivatives could be a potential treatment for restoring spontaneous erections. In addition ICA and his derivatives may also be valuable as a regenerative medicine approach for other diseases, but more clinical and basic researches with high quality and large samples are recommended.

A new mitochondria-targeted fluorescent probe for exogenous and endogenous superoxide anion imaging in living cells and pneumonia tissue.

As a precursor of all reactive oxygen species (ROS), superoxide anions play an important role in organisms. However, excessive superoxide anions can cause various diseases. Thus, it is highly urgent to develop efficient tools for in situ superoxide anion detection. In this work, a novel boric acid-based, mitochondria-targeted fluorescent probe Mito-YX for superoxide anion detection was designed by regulating its intramolecular charge transfer (ICT) effect. The probe exhibited turn-on fluorescence enhancement within 4 min of reaction with the superoxide anion. In addition, Mito-YX also exhibited high selectivity and a low detection limit down to 0.24 µM with good mitochondrial targeting characteristics, which provided a necessary basis for in vivo detection of superoxide anions. What is more, Mito-YX was successfully applied for the in situ monitoring of superoxide anions in living MCF-7 cells, RAW 264.7 cells and a mouse model of lung inflammation stimulated by LPS. This work provided an important and promising tool for rapid in situ diagnosis and research of the progression of pneumonia.

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction.

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level. Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB. Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED. Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

Acetyl-L-carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration.

BACKGROUND: Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl-L-carnitine (ALCAR) has been proven to promote nerve repair. OBJECTIVES: To investigate the effect and potential mechanism of ALCAR in the treatment of NED. MATERIALS AND METHODS: Thirty-two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower-dose ALCAR (50 mg/kg/day) group, BCNI + higher-dose (100 mg/kg/day) group, and sham-operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro. RESULTS: We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up-regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher-dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down-regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22-kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site. DISCUSSION AND CONCLUSION: ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED.

Circ_0001686 Promotes Prostate Cancer Progression by Up-Regulating SMAD3/TGFBR2 via miR-411-5p.

PURPOSE: As the mechanism of interaction between circular RNAs (circRNAs) and microRNAs (miRNAs) in regulating the development of prostate cancer (PCa) is not clear, this study focuses on investigating these effects. MATERIALS AND METHODS: Sample tissues were collected from the PCa of patients, and microarray analysis of human circRNAs was conducted. The expression of circ_0001686, hsa_miR-411-5p (miR-411-5p) were also detected by qRT-PCR. Circ_0001686 and miR-411-5p mimics were transfected into the PCa cell lines (CWR22RV1and LNCaP) and MTT, colony formation, Transwell, and scratch wound assays were used to analyze the biological behaviors of PCa cells. Si-circ_0001686 and ASO-miR-411-5p were used as negative controls, and dual-luciferase reporter assays were performed to verify the interactions among circ_0001686, miR-411-5p, and SMAD3/TGFBR2. The levels of SMAD3 and TGFBR2 in different treated PCa cells were measured by western blot, and in vivo experiments in a nude mouse model were carried out to strengthen the in vitro findings of miR-411-5p. RESULTS: The expression of circ_0001686 was up-regulated, while the expression of miR-411-5p was down-regulated in PCa cells. Moreover, circ_0001686 promoted cell proliferation, migration, and invasion. Molecular mechanism exploration revealed that circ_0001686 could reduce miR-411-5p, affecting the downstream target genes of SMAD3 and TGFBR2. In vitro and in vivo studies verified that miR-411-5p inhibits PCa progression. CONCLUSIONS: Circ_0001686 can reduce miR-411-5p to increase the expression of SMAD3/TGFBR2, which consequently promotes the proliferation, invasion, and migration of PCa cells.

Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145.

BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. RESULTS: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014). CONCLUSIONS: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.

Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review.

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.

Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-ß1/EMT pathway.

BACKGROUND: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. METHODS: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. RESULTS: Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-ß1 is responsible for EMT in AR knockout TRAMP tumor cells. CONCLUSIONS: In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell's EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy.

Temporal trends of bladder cancer incidence and mortality from 1990 to 2016 and projections to 2030.

BACKGROUND: Bladder cancer is a leading cause of cancer-related deaths all over the world. Epidemiological studies of bladder cancer are therefore crucial for policy making. This study was carried out to describe the characteristics of changes in the incidence and mortality of bladder cancer from 1990 to 2016 by age group, gender, geographical region, and sociodemographic index (SDI) and to simultaneously project future trends up to 2030. METHODS: Incidence and mortality trends in bladder cancer from 1990 to 2016 were described based on data and methodologies from the Global Burden of Disease (GBD) Study. The data also allowed the future trends of bladder cancer incidence and mortality to be predicted by ARIMA model. Trends were analyzed by age group, gender, and SDI. Projections to 2030 were sub-analyzed by SDI countries. R software (x64 version 3.5.1), SAS (version 9.3), and SPSS (version 22.0) were used throughout the process. RESULTS: Globally, in 2016, there were 437,442 [95% uncertainty interval (UI), 426,709-447,912] new bladder cancer cases and 186,199 (95% UI, 180,453-191,686) bladder cancer-associated deaths. Between 1990 and 2016, changes in the age-standardized incidence rate (ASIR) of bladder cancer decreased by 5.91% from 7.11 (95% UI, 6.93-7.27) in 1990 to 6.69 (95% UI, 6.52-6.85) in 2016. The age-standardized death rate (ASDR) decreased from 3.58 (95% UI, 3.49-3.68) to 2.94 (95% UI, 2.85-3.03) over the same period of time. In future, the greatest occurrence of bladder cancer will be in high SDI countries, followed by high-middle SDI countries. Moreover, bladder cancer incidence rates may increase substantially in middle SDI countries, while the incidence rates will remain relatively stable for men and women in other SDI countries. From 2017 to 2030, bladder cancer deaths will continue to increase in low SDI countries, while deaths in other SDI countries will continue to decrease. CONCLUSIONS: There was a regional difference in the incidence and mortality trends of bladder cancer between 1990 and 2016. Overall, the situation is not optimistic. From 2017 to 2030, the incidence of bladder cancer will continue to rise, especially in high and high-middle SDI countries, where decision-makers should propose appropriate policies on the screening and prevention of bladder cancer.

Temporal trends of kidney cancer incidence and mortality from 1990 to 2016 and projections to 2030.

BACKGROUND: This study aims to present the trends of incidence and mortality of kidney cancer from 1990 to 2016 by age, gender, geographical region, regional, and sociodemographic index (SDI), and then forecast the future trends to 2030. METHODS: Data of this study were gathered from the Global Burden of Disease Study (GBD), including 195 countries and territories, accounting for 21 regions. Over-time trends from 1990 to 2016 were analyzed by gender, geographical region, age range and SDI. Based on the big data, we forecasted the future trends to 2030 by ARIMA model. All the data were analyzed by R software (x64 version 3.5.1), SAS (version 9.3) and SPSS (version 22.0). RESULTS: Globally, in 2016, there were 342,100 [95% uncertainty interval (UI), 330,759-349,934] incident cases of kidney cancer and the number of deaths were 131,800 (127,335-136,185). The age-standardized incidence rate (ASIR) and death rate (ASDR) were 4.97 (4.81-5.09) per 100,000 and 2.00 (1.93-2.06) per 100,000, respectively. Globally, the estimated risk of kidney cancer for male within the age of 30 and 70 is around 0.79% compared to 0.41% for female. In other words, the probability of developing kidney cancer was generally higher in male than in female. By 2030, incidence of kidney cancer in both sexes are projected to increase substantially in high SDI, followed by middle SDI, low-middle SDI, and low SDI countries. High SDI and low SDI countries will also have increased mortality rates of kidney cancers. Globally, the trends in deaths due to kidney cancer will remain stable. CONCLUSIONS: The incidence and death rate of kidney cancer are highly variable among SDI countries and regions but have increased uniformly from 1990 to 2016. By 2030, the future incidence of kidney cancer will grow continuously especially in high SDI countries, middle SDI, low-middle SDI, and low SDI countries.

Estimates of over-time trends in incidence and mortality of testicular cancer from 1990 to 2030.

BACKGROUND: This study aims to explore and project the temporal trends in incidence and mortality of testicular cancer. Moreover, it can provide theoretical guidance for the rational allocation of health resources. METHODS: This study analyzed existing data on testicular cancer morbidity and mortality from 1990 to 2016 and predicted time-varying trends of age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) from 2017 to 2030 in different ages, regions and sociodemographic index (SDI) quintile sub-groups. RESULT: Globally, numbers of testicular cancer cases in 2016 [66,833; 95% uncertainty interval (UI), 64,487-69,736] are 1.8 times larger than in 1990 (37,231; 95% UI, 36,116-38,515). The testicular cancer-related death cases increased slightly from 8,394 (95% UI, 7,980-8,904) in 1990 to 8,651 (95% UI, 8,292-9,027) in 2016. In aspect of ASIR, the data showed an up-trend from 0.74 (95% UI, 0.72-0.77) in 1990 to 0.88 (95% UI, 0.85-0.92) in 2016. The ASDR of testicular cancer declined from 0.18 (95% UI, 0.17-0.19) in 1990 to 0.12 (95% UI, 0.11-0.12) in 2016. From 2017 to 2030, predictions of trends in testicular cancer indicate that the ASIRs of most SDI countries are rising, but the ASDRs trends in testicular cancer will decrease. CONCLUSIONS: By analyzing the available and reliable data in different ages, regions and SDI, this study shows a significant upward trend in incidence and a slow upward trend in mortality of testicular cancer from 1990 to 2016, and simultaneously, predicts the increase of ASIR and the downward trend of ASDR in 2017-2030.

Estimates of over-time trends in incidence and mortality of prostate cancer from 1990 to 2030.

BACKGROUND: This research aims to identify the current and future trends in the incidence and death rate of prostate cancer and to provide the necessary data support for making relevant health decisions. METHODS: This study used the collected data and methodologies to describe the incidence and mortality trends of prostate cancer from 1990 to 2016. Based on the data, this paper projected the future trends in prostate cancer incidence and death rate. RESULTS: In 2016, prostate cancer cases [1,435,742; 95% uncertainty interval (UI), 1,293,395-1,618,655] were nearly 2.5-fold the number in 1990 (579,457; 95% UI, 521,564-616,107). Deaths increased by 2.0-fold from 191,687 (95% UI, 168,885-209,254) in 1990 to 380,916 (95% UI, 320,808-412,868) in 2016. The global age-standardized incidence rate (ASIR) increased from 17.75 (95% UI, 18.91-15.95) in 1990 to 22.12 (95% UI, 19.92-24.91) in 2016, changing 24.62%. The global change of age-standardized death rate (ASDR) has declined slightly, but in some regions it shows a trend of growth. By sociodemographic index (SDI) sub-types, prostate cancer will frequently occur in high SDI countries from 1990 to 2030. Simultaneously, the highest mortality will present in low SDI countries. CONCLUSIONS: Through projecting and analyzing incidence and mortality rate of prostate cancer, from 1990 to 2030, by different ages, regions and SDI sub-types, this result may reveal the relationship between prostate cancer and financial development. At the same time, the result also showed a sufficiently heavy burden of prostate cancer, but the burden varies greatly in each region. The burden is a challenge and will require attention for all levels of society. The current study is beneficial to formulate more specific and efficient policies.

Role and mechanism of micro-energy treatment in regenerative medicine.

With the continuous integration and intersection of life sciences, engineering and physics, the application for micro-energy in the basic and clinical research of regenerative medicine (RM) has made great progress. As a key target in the field of RM, stem cells have been widely used in the studies of regeneration. Recent studies have shown that micro-energy can regulate the biological behavior of stem cells to repair and regenerate injured organs and tissues by mechanical stimulation with appropriate intensity. Integrins-mediated related signaling pathways may play important roles in transducing mechanical force about micro-energy. However, the complete mechanism of mechanical force transduction needs further research. The purpose of this article is to review the biological effect and mechanism of micro-energy treatment on stem cells, to provide reference for further research.

[PROGRESS AND CLINICAL APPLICATION OF ALLOGRAFT BONE SPACER IN CERVICAL AND LUMBAR INTERBODY FUSION].

OBJECTIVE: To review the research progress and clinical application of allograft bone spacer in cervical and lumbar interbody fusion. METHODS: Literature about allograft bone spacer in cervical and lumbar degenerative disease was reviewed and analyzed, including the advantages and disadvantages of allograft material, fusion rate, effectiveness, and complications. RESULTS: Fusion rate and effectiveness of allograft bone spacers were similar to those of autograft and polyetheretherketone spacers, and they were recommended by many orthopedists. However, indications, long-term effectiveness, and complications were not clear. CONCLUSION: Further study on allograft bone spacer in cervical and lumbar interbody fusion should be focused on optimal indications and long-term effectiveness.