Comparative analysis of different treatment strategies for septic spondylitis: a retrospective study of one hundred and twelve patients.

PURPOSE: To compare the clinical efficacy and prognosis differences between conservative treatment and surgical treatment in patients with non-serious neurologically intact pyogenic spondylitis (Nsi-Nsni-PS), and to provide theoretical reference for the clinical treatment of Nsi-Nsni-PS patients. METHODS: A retrospective analysis was conducted on 112 cases of Nsi-Nsni-PS patients treated in our hospital from June 2016 to June 2021. According to different treatment methods, they were divided into conservative treatment group (53 cases) and surgical treatment group (59 cases). The general data, laboratory tests, imaging examinations, length of hospital stay, duration of antibiotic use, VAS for pain before and after treatment, ODI, local kyphotic angle correction of diseased vertebrae, and recurrence rate were collected and analyzed in both groups. SPSS 26.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation, and independent sample t-test or rank sum test was used for comparison between groups, while variance analysis was used for intra-group comparison. Count data were expressed as number (%) and compared between groups using chi-square test or Fisher's exact test. Mann-Whitney U test was used to evaluate the changes in local kyphotic angle between the two groups. A p value < 0.05 was considered statistically significant. RESULTS: There were no significant differences in general data and imaging characteristics between the two groups (P > 0.05); there were no statistically significant differences in the positive culture rate of pathogens, length of hospital stay, duration of antibiotic use, treatment complications, WBC, CRP, ESR levels at admission and discharge, VAS and ODI at admission and last follow-up between the two groups (P > 0.05). The WBC and CRP levels of patients in the conservative group at discharge were lower than those in the surgical group (P < 0.05), and there was no significant difference in the decrease in inflammatory indicators (WBC, CRP, ESR) between the two groups (P > 0.05). By the last follow-up, the neurological function of patients in both groups had significantly improved compared to admission (P < 0.05), with 12 out of 15 ASIA grade D patients in the conservative group recovering to grade E, and 21 out of 25 grade D patients in the surgical group recovering to grade E, with no worsening of neurological function in either group. The differences in VAS and ODI scores at the last follow-up compared to before treatment were statistically significant in both groups (P < 0.05), and all patients regained normal activity. Compared with before treatment, the correction degree of local kyphotic angle in the surgical group at the last follow-up was 0.93 ± 4.94°, slightly higher than that in the conservative group (-0.83 ± 3.37°), and the difference was statistically significant(P < 0.05). CONCLUSIONS: During our follow-up, we found that both conservative and surgical treatments achieved satisfactory clinical outcomes in patients with Nsi-Nsni-PS. Compared to conservative treatment, surgical intervention did not demonstrate significant advantages in reducing hospitalization time and antibiotic usage duration, increasing pathogen culture positivity rate, lowering treatment complications, or controlling recurrence. However, surgical intervention showed superiority in correcting the local kyphotic angle of spinal lesions, albeit with relatively increased surgical trauma, risks, and treatment costs. At the last follow-up, the surgical group did not exhibit better long-term efficacy. Therefore, when formulating clinical treatment strategies for patients with Nsi-Nsni-PS, it may be preferable to prioritize conservative treatment, supplemented by the use of sensitive or empiric antibiotics for infection management, to improve patient prognosis.

Biomass-Derived Hard Carbon for Sodium-Ion Batteries: Basic Research and Industrial Application.

Sodium-ion batteries (SIBs) have significant potential for applications in portable electric vehicles and intermittent renewable energy storage due to their relatively low cost. Currently, hard carbon (HC) materials are considered commercially viable anode materials for SIBs due to their advantages, including larger capacity, low cost, low operating voltage, and inimitable microstructure. Among these materials, renewable biomass-derived hard carbon anodes are commonly used in SIBs. However, the reports about biomass hard carbon from basic research to industrial applications are very rare. In this paper, we focus on the research progress of biomass-derived hard carbon materials from the following perspectives: (1) sodium storage mechanisms in hard carbon; (2) optimization strategies for hard carbon materials encompassing design, synthesis, heteroatom doping, material compounding, electrolyte modulation, and presodiation; (3) classification of different biomass-derived hard carbon materials based on precursor source, a comparison of their properties, and a discussion on the effects of different biomass sources on hard carbon material properties; (4) challenges and strategies for practical of biomass-derived hard carbon anode in SIBs; and (5) an overview of the current industrialization of biomass-derived hard carbon anodes. Finally, we present the challenges, strategies, and prospects for the future development of biomass-derived hard carbon materials.

Biodegradation enhancement of high concentrations formaldehyde waste gas and verification of the metabolic mechanism.

The enhanced effects of formaldehyde biodegradation in a biofilm packing tower are investigated in this study. Three experimental groups were established: a blank control group, a biochar addition group, and a lanthanum addition group. The inlet gas flow rate, the inlet gas concentration, and the structural succession characteristics of the microbial community in the tower were investigated by regular sampling. The intracellular metabolites and key enzymes of the dominant functional bacteria, Pseudomonas P1 and Methylobacterium Q1, in the tower were analyzed. The results indicated that with the biochar addition, the formaldehyde purification efficiency increased significantly from 91.67-94.67 % to 94.12 96.85 %, and the bio-elimination capacity increased with an increase in the inlet gas flow rate from 2.314 to 13.988 mg L-1h-1 to 2.697-15.051 mg L-1h-1. With the addition of lanthanum, the purification efficiency increased significantly from 90.80-93.98 % to 94.36-96.78 %, and the bio-elimination capacity increased with an increase in the inlet gas concentration from 1.099-11.284 mg L-1h-1 to 1.266-11.961 mg L-1h-1. The microbial community structure in the tower changed with system operation, and the formaldehyde degrading functional bacteria formed the dominant bacteria. It was verified that P1 and Q1 metabolized high concentrations of formaldehyde by the serine cycle and the ribulose monophosphate (RuMP) cycle.

Dietary intervention reprograms bone marrow cellular signaling in obese mice.

Objectives: The current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity. Methods: Mice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt). Results: Weight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-ß-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group. Conclusions: Our findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual.

Exploring the common diagnostic gene KCNJ15 and shared pathway of ankylosing spondylitis and ulcerative colitis through integrated bioinformatics.

Introduction: The similarity between ankylosing spondylitis (AS) and ulcerative colitis (UC) in incidence rate and pathogenesis has been revealed. But the common pathogenesis that explains the relationship between AS and UC is still lacked, and the related genetic research is limited. We purposed to explore shared biomarkers and pathways of AS and UC through integrated bioinformatics. Methods: Gene expression data of AS and UC were obtained in the GEO database. We applied weighted gene co-expression network analysis (WGCNA) to identify AS-related and UC-related co-expression gene modules. Subsequently, machine learning algorithm was used to further screen hub genes. We validated the expression level and diagnostic efficiency of the shared diagnostic gene of AS and UC in external datasets. Gene set enrichment analysis (GSEA) was applied to analyze pathway-level changes between disease group and normal group. Finally, we analyzed the relationship between hub biomarker and immune microenvironment by using the CIBERSORT deconvolution algorithm. Results: 203 genes were obtained by overlapping AS-related gene module and UC-related gene module. Through SVM-RFE algorithm, 19 hub diagnostic genes were selected for AS in GSE25101 and 6 hub diagnostic genes were selected for UC in GSE94648. KCNJ15 was obtained as a common diagnostic gene of AS and UC. The expression of KCNJ15 was validated in independent datasets, and the results showed that KCNJ15 were similarly upregulated in AS samples and UC samples. Besides, ROC analysis also revealed that KCNJ15 had good diagnostic efficacy. The GSEA analysis revealed that oxidative phosphorylation pathway was the shared pathway of AS and UC. In addition, CIBERSORT results revealed the correlation between KCNJ15 gene and immune microenvironment in AS and UC. Conclusion: We have explored a common diagnostic gene KCNJ15 and a shared oxidative phosphorylation pathway of AS and UC through integrated bioinformatics, which may provide a potential diagnostic biomarker and novel insight for studying the mechanism of AS-related UC.

Scientometric analysis of kidney disease and gut microbiota from 2001 to 2020 based on Web of Science.

This study aims to demonstrate current research priorities and predict future trends in the link between kidney disease and gut microbiota by means of scientometric analysis. We collected nearly 20 years (2001-2020) of publications related to kidney disease and gut microbiota in the Web of Science database. CiteSpace was used to evaluate the knowledge mapping. There are 965 manuscripts about kidney disease and gut microbiota in total, and faster growth after 2016. The country, institution, and author who posted the most are the USA, Univ Calif Irvine, and DENISE MAFRA, respectively. The frequencies are 109, 16, and 17. The most important of them are FRANCE (0.23), Fed Univ Parana UFPR (0.13), and VAZIRI ND (1.14), owing to their highest centrality. In addition, the cited documents that have contributed the most to the co-citations are Wong J (2014); the most key cited reference is Rossi M (2016); the most commonly used keywords are chronic kidney disease, gut microbiota and indoxyl sulfate. Through scientometric analysis of the past 20 years, we obtained the knowledge map of this information, which has important guiding significance for accurately and quickly locating trends in this field.

[Visual acupotomy intervention mitigates pain reaction by improving intervertebral disc degeneration and inhibiting apoptosis of nucleus pulposus cells in rabbits with cervical spondylosis].

OBJECTIVE: To investigate the effect of visual acupotomy intervention on intervertebral disc degeneration, nucleus pulposus cell apoptosis and expression of apoptosis related proteins in rabbits with cervical spondylosis (CS), so as to explore its mechanism underlying improvement of CS. METHODS: A total of 48 male New Zealand rabbits were randomly divided into blank control, model, acupotomy and medication (meloxicam) groups, with 12 rabbits in each group. The neck type CS model was established by forcing the rabbit to make a neck flexion for 5 hours in a restrained chamber, once daily for 12 weeks. Rabbits of the medication group received an intramuscular injection of meloxicam (0.35 mg/kg), once daily for 4 consecutive weeks, and those of the acupotomy group received ultrasound-guided acupotomy intervention, once a week for 4 weeks. The pain threshold (PT) was measured by using a VonFrey electronic pain detector. The levels of prostaglandin E2 (PGE2), 5-hydroxytryptamine (5-HT) and substance P (SP) in serum were detected by ELISA. The severity of intervertebral disc degeneration was observed by using magnetic resonance imaging (MRI) and given scores in accordance with Suzuki's and colleague's "new classification system of cervical disk degeneration". The apoptosis of nucleus pulposus cells was analyzed by TUNEL staining. The protein expression levels of apoptosis-related protein Fas, cysteinyl aspartate-specific protease-3 (Caspase-3), B-cell lymphoma-2 asso-ciated X protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) were measured by Western blot. RESULTS: Compared with the blank control group, the PT and Bcl-2 expression and MRI score were significantly down-regulated (P<0.01, P<0.001), whereas the contents of serum PGE2, 5-HT and SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax were considerably up-regulated (P<0.001, P<0.05, P<0.01) in the model group. In contrast to the model group, both the medication and acupotomy groups had an obvious increase in the levels of PT and Bcl-2 expression and MRI score (P<0.05, P<0.01), and a significant decrease in the contents of serum PGE2, 5-HT, SP, ratios of TUNEL-positive cells, and expression of Fas, Caspase-3 and Bax proteins (P<0.05). No significant differences were found between the medication and acupotomy groups in all the indexes mentioned above (P>0.05). CONCLUSION: Visual acupotomy intervention can mitigate the pain state of CS rabbits, which may be related to its functions in improving the intervertebral disc degeneration, reducing inflammatory reactions and apoptosis of nucleus pulposus cells.

[Acupotomy relieves pain and improves motor function by regulating autophagy and apoptosis of cartilage in rabbits with knee osteoarthritis apoptosis].

OBJECTIVE: To observe the effect of acupotomy on the expression of Beclin-1, Bcl-2 and Caspase-3 in the cartilage tissue in rabbits with knee osteoarthritis (KOA), so as to explore its mechanism underling improvement of KOA. METHODS: Twenty-four healthy male New Zealand rabbits were randomly and equally divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman's methods, the KOA model was established by left hind limb immobilization with a plaster cast for 6 weeks. The severity of KOA (knee pain, swelling and motor function) was assessed using Lequesne score, and the rabbits with a score below 4 were excluded. The acupotomy was applied to "Hedingci" (the attachment of the quadriceps tendon to the patella at the upper edge), "Binneixia" (the medial patellar supporting band attachment of medial inferior patellar margin), "Binwaixia" (the lateral patellar supporting band attachment of the lower lateral patellar margin), "Chengfeijian" (the lateral collateral ligament of the knee passes over the lateral joint space), "Weiyangci" (the medial margin of biceps femoris at the lateral end of popliteus), "Yinlingci" (the medial tibial attachment of anserinus tendon) on the left hind limb once a week for 4 weeks. One week after the last intervention, the left knee joint dysfunction severity(pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne score. Histopathological changes of the cartilage were observed under light microscope after H.E. staining. The apoptosis of chondrocytes was observed after terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling (TUNEL) staining. The autophagolysosomes of chondrocytes were observed using transmission electron microscopy. The expression levels of Beclin-1, Bcl-2 and Caspase-3 (related factors of autophagy and apoptosis) were detected using Real-time PCR and Western blot separately. RESULTS: In comparison with the blank control group, the Lequesne score, apoptosis rate, expression levels of Caspase-3 mRNA and protein were significantly increased (P<0.001), and the number of autophagolysosomes, expression levels of Beclin-1 and Bcl-2 mRNAs and proteins considerably decreased (P<0.001) in the model group. Relevant to the model group, the acupotomy group had an obvious decrease in Lequesne score, rate of apoptosis, and expression levels of Caspase-3 mRNA and protein (P<0.001) and an apparent increase in the number of autophagolysosomes and expression levels of Beclin-1 and Bcl-2 mRNAs and proteins (P<0.001). Findings of H.E. staining showed severe damaged cartilage surface, with a large number of exfoliation defects, few chondrocytes on the surface and disordered arrangement of transitional cells in the model group, which was relatively milder in the acupotomy group. CONCLUSION: Acupotomy can mitigate knee-joint pain and improve functional activity in KOA rabbits, which may be associated with its functions in promoting autophagy and suppressing apoptosis by up-regulating expressions of Beclin-1 and Bcl-2 mRNAs and proteins and down-regulation of Caspase-3 mRNA and protein.

Proteomic Analyses Reveals the Mechanism of Acupotomy Intervention on the Treatment of Knee Osteoarthritis in Rabbits.

Acupotomy intervention (AI) is an available treatment for knee osteoarthritis (KOA) in China, which is a common health problem over the world. However, the underlying mechanism of AI on the KOA treatment is still unknown. To further understand the mechanism of acupotomy in treating KOA, the morphological observation and TMT proteomic analyses were conducted in rabbits. By using X-ray and MRI, we found that the space of the knee joint was bigger in AI than in KOA. Moreover, the chondrocytes were neatly arranged in AI but disordered in KOA. With proteomic analyses in chondrocytes, 68 differently accumulated proteins (DAPs) were identified in AI vs. KOA and DAPs related to energy metabolism and the TCA cycle were suggested to play a central role in response to AI. Furthermore, AIFM1 was proposed to be an important regulator in controlling the energy production in mitochondrial. Besides, FN1, VIM, COL12A1, COL14A1, MYBPH, and DPYSL3 were suggested to play crucial roles in AI for the treatment of KOA. Our study was systematically elucidating the regulation mechanism of acupotomy intervention in the treatment of KOA.

Vitamin D receptor (VDR) contributes to the development of hypercalciuria by sensitizing VDR target genes to vitamin D in a genetic hypercalciuric stone-forming (GHS) rat model.

Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.

Comparative proteomic analysis identifies differentially expressed proteins and reveals potential mechanisms of traumatic heterotopic ossification progression.

Background: Traumatic Heterotopic Ossification (tHO) is one of complications of elbow fractures to the detriment of patients' rehabilitation, and the severity of tHO corresponds to the size of ectopic bone. It has yet to be elucidated which proteins and pathways underlying the progression of tHO, and biomarkers to predict the severity of tHO at early stage of the disease also need further investigation. Methods: In this study, a new rat model with distinct volume of ectopic bone was established first. Then a data-independent acquisition proteomics approach was used to investigate injured site tissues sequentially obtained from these rats (2, 7, 14, and 28 days post-injury). Differentially expressed analysis, functional annotation and co-expression analysis and protein-protein interaction network were performed to explore the pathways and hub proteins in the tHO progression. Clinical samples from a nest case-control study were used to validate the selected proteins for predicting the severity of tHO. Results: The Achilles Tenotomy (AT) induced significantly larger sizes of ectopic bone compared to Partial Achilles Tenotomy (PAT) in rat models. A total of 3547 quantifiable proteins were screened for differential expression analysis among the AT, PAT and control groups. The hierarchical clustering and expression pattern analysis revealed more apparent difference in the pathways such as oxidative phosphorylation, mitochondrial function, and sirtuin signaling between AT and PAT group at the early stage (2 dpi) of tHO. The co-expression analysis identified five hub proteins, UBA1, EIF3E, RPL17, RPL27, and RPS28. qPCR assay, immunoblot assay and immunohistochemistry assay verified that these proteins had higher expression level in the tissue samples of clinically relevant HO patients and clinically irrelevant HO patients than HO negative patients. Conclusion: The new established animal model and proteome profile could serve as a solid foundation for the comprehensive investigation of the progression of traumatic heterotopic ossification. And the identified 5 proteins (UBA1, EIF3E, RPL17, RPL27, and RPS28) may serve as potential biomarkers to predict the severity of tHO. The translational potential of this article: The proteins identified in this study may be the potential biomarkers and therapeutic targets for predicting and treating the tHO at early stage.

[Effect of acupotomy intervention on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effect of acupotomy on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis and to reveal the possible therapeutic mechanism involved in the effect of acupotomology on the treatment of knee osteoarthritis(KOA). METHODS: Twenty-four male New Zealand rabbits aged 6 months and weighed (2.0±0.5) kg were randomly divided into blank group, model group and acupotomy group, 8 rabbits in each group. KOA model was established by modified Videman method with left hind limb extended plaster immobility for 6 weeks. In acupotomy group, the transfascial focal points of quadriceps femoris muscle were released by acupotomy under the guidance of Jingjin theory for 4 times and once a week, and the treatment points include Hedingci, Binwaixia, Binneixia. Blank group and model group were fed normally without intervention. One week after the end of the intervention, the pennation angle(PA), muscle thickness(MT), cross-sectional area(CSA) and strain ratio(SR) of rectus femoris were measured by ultrasound. HE staining was used to observe the changes of the tissue morphology, the number of muscle fibers and the average area of muscle fibers. The myofibril of rectus femoris, sarcomere and myofilament were observed by transmission electron microscope. RESULTS: The PA of rectus femoris muscle in the blank group was (9.05±0.21)°. The MT was(1.09±0.09) cm and the CSA was(1.30±0.01) cm2. The PA of rectus femoris muscle in the model group was (3.06±0.15)°. The MT was (0.71±0.02) cm and the CSA was(0.77±0.02) cm2. The PA of rectus femoris muscle in the acupotomy group was (6.94±0.28)°. The MT was (0.80±0.05) cm and the CSA was(0.94±0.03) cm2. The muscle PA, MT and CSA of rectus femoris in the model group were significantly smaller than those in the blank group (P<0.05). Those in acupotomy group were significantly increased compared with those in model group (P<0.05). The SR of rectus femoris muscle was 1.19±0.02 in the blank group, 3.50±0.05 in the model group and 1.99±0.07 in the acupotomy group. The elastic SR of the model group was significantly higher than that of the blank group (P<0.05). These in acupotomy group was significantly lower than that in model group(P<0.05). The results of HE staining showed:in blank group, the fascicles of rectus femoris were arranged neatly, the number of beam of muscle fibers within the fixed visual field was 94.38±3.50 and the average CSA was(0.75±0.22) mm2. In model group, the fascicles of rectus femoris with different sizes were disorganized with a small amount of inflammatory cell infiltration, the number of beam of muscle fibers within the fixed visual field was 196.63±2.62 and the average CSA was(0.26±0.03) mm2. Compared to the blank group, a significant increase in the number of muscle fibers in the fixed field in the model group (P<0.05) and the average CSA decreased significantly(P<0.05). In acupotomy group, the rectus femoris fascicles in the acupotomy group tended to be arranged in a more orderly manner, with the inflammatory cells decreased, the number of beam of muscle fibers within the fixed visual field was 132.88±4.61 and the average CSA was(0.70±0.07) mm2. Compared to the model group, a significant decrease in the number of muscle fibers in the fixed field in the model group(P<0.05) and the average CSA increased significantly(P<0.05). The results of transmission electron microscope showed:compared with the blank group, the overall arrangement of the myofibrils of the rectus femoris in the model group was less structured. There was fracture between the muscle fibers and the sarcomere, the myofilaments were disordered, and the fracture of the Z line was discontinuous. Compared with the model group, the myofibrillar texture of rectus femoris in acupotomy group was clearer, and the Z line was more continuous. CONCLUSION: Based on the jingjin theory, the release of quadriceps femoris by acupotomy can effectively improve the morphology and structure of rectus femoris, and promote the repair and reconstruction of chronic skeletal muscle injury in rabbits with KOA, which may be one of the mechanisms of acupotomy in the treatment of KOA.

Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy.

BACKGROUND: Osteoporosis is a chronic condition affecting patients' morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity. RESULTS: Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C-X-C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis. CONCLUSIONS: In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats.

Hydromorphone vs sufentanil in patient-controlled analgesia for postoperative pain management: A meta-analysis.

BACKGROUND: Patient-controlled analgesia (PCA) is an effective method of postoperative pain, there have been many studies performed that have compared the efficacy of hydromorphone with continuous sufentanil. The purpose of this systematic review is to compare the efficacy and safety of hydromorphone and sufentanil. METHODS: Seven databases were searched for controlled trials to compare the efficacy and safety of hydromorphone and sufentanil. After selecting the studies, extracting the data, and assessing study quality, the meta-analysis was performed on several of the studies with RevMan 5.3. RESULTS: Thirteen studies comprised of 812 patients were found. The pain intensity of the hydromorphone group was significantly lower than that of the sufentanil group at 12 hours. With no statistical difference at 24 to 48 hours (MD12 = -1.52, 95% CI [-2.13, -1.97], P <.05). The sedation intensity of the hydromorphone group at 12, 24, and 48 hours were lower than those of the sufentanil group, with no statistical difference (MD12 = -0.03, 95% CI [-0.18, 0.12], P > .05; MD24 = -0.20, 95% CI [-0.42, 0.03], P > .05; MD48 = -0.03, 95% CI [-0.18, 0.11)], P > .05). The PCA requests in the hydromorphone group were less than that in the sufentanil group, and there was no significant difference (RR = -0.20, 95% CI [-1.93,1.53], P > .05). The incidence of adverse events in the hydromorphone group was less than that in the sufentanil group, and there was a statistical difference: (RR = 0.61, 95% CI [0.47,0.79], P < .05). CONCLUSION: Compared with sufentanil, PCA with hydromorphone was more effective in relieving pain and PCA requests 12, 24, and 48 hours after operation, and significantly reduced the incidence of adverse events, but it did not have an advantage in sedation intensity.

Effect of acupotomy intervention on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To observe the effect of acupotomy on the morphology and ultrastructure of rectus femoris muscle in rabbits with knee osteoarthritis and to reveal the possible therapeutic mechanism involved in the effect of acupotomology on the treatment of knee osteoarthritis(KOA).@*METHODS@#Twenty-four male New Zealand rabbits aged 6 months and weighed (2.0±0.5) kg were randomly divided into blank group, model group and acupotomy group, 8 rabbits in each group. KOA model was established by modified Videman method with left hind limb extended plaster immobility for 6 weeks. In acupotomy group, the transfascial focal points of quadriceps femoris muscle were released by acupotomy under the guidance of Jingjin theory for 4 times and once a week, and the treatment points include Hedingci, Binwaixia, Binneixia. Blank group and model group were fed normally without intervention. One week after the end of the intervention, the pennation angle(PA), muscle thickness(MT), cross-sectional area(CSA) and strain ratio(SR) of rectus femoris were measured by ultrasound. HE staining was used to observe the changes of the tissue morphology, the number of muscle fibers and the average area of muscle fibers. The myofibril of rectus femoris, sarcomere and myofilament were observed by transmission electron microscope.@*RESULTS@#The PA of rectus femoris muscle in the blank group was (9.05±0.21)°. The MT was(1.09±0.09) cm and the CSA was(1.30±0.01) cm2. The PA of rectus femoris muscle in the model group was (3.06±0.15)°. The MT was (0.71±0.02) cm and the CSA was(0.77±0.02) cm2. The PA of rectus femoris muscle in the acupotomy group was (6.94±0.28)°. The MT was (0.80±0.05) cm and the CSA was(0.94±0.03) cm2. The muscle PA, MT and CSA of rectus femoris in the model group were significantly smaller than those in the blank group (P<0.05). Those in acupotomy group were significantly increased compared with those in model group (P<0.05). The SR of rectus femoris muscle was 1.19±0.02 in the blank group, 3.50±0.05 in the model group and 1.99±0.07 in the acupotomy group. The elastic SR of the model group was significantly higher than that of the blank group (P<0.05). These in acupotomy group was significantly lower than that in model group(P<0.05). The results of HE staining showed:in blank group, the fascicles of rectus femoris were arranged neatly, the number of beam of muscle fibers within the fixed visual field was 94.38±3.50 and the average CSA was(0.75±0.22) mm2. In model group, the fascicles of rectus femoris with different sizes were disorganized with a small amount of inflammatory cell infiltration, the number of beam of muscle fibers within the fixed visual field was 196.63±2.62 and the average CSA was(0.26±0.03) mm2. Compared to the blank group, a significant increase in the number of muscle fibers in the fixed field in the model group (P<0.05) and the average CSA decreased significantly(P<0.05). In acupotomy group, the rectus femoris fascicles in the acupotomy group tended to be arranged in a more orderly manner, with the inflammatory cells decreased, the number of beam of muscle fibers within the fixed visual field was 132.88±4.61 and the average CSA was(0.70±0.07) mm2. Compared to the model group, a significant decrease in the number of muscle fibers in the fixed field in the model group(P<0.05) and the average CSA increased significantly(P<0.05). The results of transmission electron microscope showed:compared with the blank group, the overall arrangement of the myofibrils of the rectus femoris in the model group was less structured. There was fracture between the muscle fibers and the sarcomere, the myofilaments were disordered, and the fracture of the Z line was discontinuous. Compared with the model group, the myofibrillar texture of rectus femoris in acupotomy group was clearer, and the Z line was more continuous.@*CONCLUSION@#Based on the jingjin theory, the release of quadriceps femoris by acupotomy can effectively improve the morphology and structure of rectus femoris, and promote the repair and reconstruction of chronic skeletal muscle injury in rabbits with KOA, which may be one of the mechanisms of acupotomy in the treatment of KOA.

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells.

BACKGROUND: Heterotopic ossification (HO) can limit joint activity, causes ankylosis and impairs the function and rehabilitation of patients. Endothelial to mesenchymal transition (EndMT) plays an important role in the pathogenesis of HO, and high expression of SMAD7(Mothers Against Decapentaplegic Homolog 7) in endothelial cells can effectively reverse the TGF-ß1 mediated EndMT. This article studied an appropriately engineered exosome with high biocompatibility and good targeting property to administrate SMAD7 gene therapy to inhibit the EndMT. METHODS: Exosomes from mouse aortic endothelial cells were cultured and harvested. DSPE-PEG and antibody CD34 were combined to exosomes to synthesize the endothelial cell targeting exosome vector (Exosome-DSPE-PEG-AbCD34). The biocompatibility, stability, targeting and cell internalization of exosome vector were tested, then the Exosome-DSPE-PEG-AbCD34 was loaded with Smad7 plasmid and administrated to MAECs to examine its therapeutic effect on EndMT of MAEC mediated by TGF-ß1. RESULTS: The Exosome-DSPE-PEG-AbCD34 has no impact on MAEC cell viability at high concentration, and exosome-DSPE-PEG-AbCD34 could be stably stored at 4°C and 37°C for at least 8 days. Exosome-DSPE-PEG-AbCD34 has better targeting property to MAEC cells and can enter into the cells more effectively. The Exosome-DSPE-PEG-AbCD34-Smad7 could significantly increase the level of SMAD7, decrease the expression of TGF-ß1, and effectively reverse the EndMT of MAEC mediated by TGF- ß1 in MAEC cells. CONCLUSIONS: The synthesized Exosome-DSPE-PEG-AbCD34-Smad7 has good biological properties and can effectively reverse the EndMT of MAEC mediated by TGF-ß1. Thus, Exosome-DSPE-PEG-AbCD34-Smad7 may has the potential for the prevention and treatment of HO.

Structural definition of the discrete hotspot sites of BMP-2 conformational wrist epitope and rational design of the hotspot-derived osteogenic peptides against chondrocyte senescence.

The bone morphogenetic protein-2 (BMP-2) is an essential regulator of bone formation and remodeling, which has also been implicated in the pathogenesis of osteoarthritis and its closely related chondrocyte senescence. The BMP-2 uses a conformational wrist epitope and a linear knuckle epitope to interact with type-I (BMPR-I) and type-II (BMPR-II) receptors, respectively. Previously, the knuckle epitope has been intensely studied, but the wrist epitope still remains largely unexplored due to its discontinuous nature. In the present work, the intermolecular interaction of BMP-2 with BMPR-I was investigated systematically at structural, energetic and dynamic levels. Three discrete hotspots that represent the key BMPR-I recognition sites of BMP-2 were identified; they are spatially dispersed over the two monomers of BMP-2 dimer and totally account for 83.5 % binding potency of BMP-2 to BMPR-I (hotspot 1: residues 49-70 in monomer 1; hotspot 2: residues 24-31 in monomer 2; hotspot 3: residues 88-107 in monomer 2). Therefore, we defined the three discrete hotspot sites as the core region of wrist epitope; their contribution to the binding increases in the order: hotspot 2 < hotspot 3 < hotspot 1. We demonstrated that the primary hotspot 1 site has a native U-shaped conformation in the full-length BMP-2 protein context, but it cannot maintain in the native conformation when split from the context to obtain a free hotspot-1 peptide, thus largely impairing its binding potency to BMPR-I. We further employed disulfide-bonded cyclization and head-to-tail cyclization to constrain the peptide conformation, and found that only the former can effectively constrain the peptide into native conformation, thus considerably improving its binding affinity to BMPR-I, whereas the latter totally disorders the native conformation, thus rendering the peptide as a full nonbinder of BMPR-I.

[Ultrasound anatomy and needle-knife insertion approach of common tendon lesions in knee osteoarthritis based on meridian sinew theory].

OBJECTIVE: To explore the ultrasonic anatomical characteristics and needle-knife insertion approach of common tendon lesions in knee osteoarthritis (KOA), so as to provide the references for accurate release of KOA by needle- knife along tendon lesions based on meridian sinew theory. METHODS: Sixty patients with one-knee KOA were selected. High-frequency musculoskeletal ultrasound was used to collect sonograms at the anatomical positions of "Hedingci" "Binwaixia" "Binneixia" and "Yinlingshang". The anatomic levels were marked on the sonograms. The anatomic levels and sonographic features of lesions were compared and analyzed, and the relevant data of needle-knife simulation approach was measured. RESULTS: The "Hedingci" lesions were mainly located at the attachment of quadriceps tendon to patella and suprapatellar bursa. The "Binwaixia" and "Binneixia" lesions were mainly located at the attachment of retinaculum patellae laterale and retinaculum patellae mediale to patella and infrapatellar fat pad. The "Yinlingshang" lesions were mainly located at the attachment of goose foot tendon to medial tibial condyle and bursa of goose foot. With "Hedingci" as an example, when the needle-knife entry point was 1 cm above the patella, the attachment of quadriceps tendon to patella was released, and the average depth of needle-knife was (3.60±0.10) cm, and the needle body was perpendicular to the skin. The average depth of needle-knife for releasing suprapatellar bursa was (2.35±0.17) cm, and the needle body was 45° towards head. CONCLUSION: The musculoskeletal ultrasound could clearly show the local detailed anatomical level, ultrasonic characteristics and anatomical level of common tendon lesions of KOA, and could improve the accuracy of needle-knife along tendon lesions with non-direct vision, which has important reference value for needle-knife medical standardization and standardized operation.

[Effects of "knot-loosing" of acupotomy on motor function and morphological changes of knee joint in knee osteoarthritis rabbits].

OBJECTIVE: To observe the effect of "knot-loosing method" of acupotomy on morphological changes in knee osteoarthritis (KOA) rabbits, so as to provide experimental basis for clinical acupotomy treatment of KOA. METHODS: Male New Zealand rabbits were randomly divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman method, the left hindlimb was immobilized for 6 weeks with a plaster cast to replicate the KOA model. The knot-loosing manipulation of acupotomy was applied to "Hedingci" (located at the attachment of the positive upper margin of the quadriceps tendon and the patella),"Binneixia"（at "Neixiyan" ［EX-LE4］, the medial side of ligamentum patella）, "Binwaixia" （at "Waixiyan" ［ST35］, the lateral side of patellar ligament）, "Chengfeijian" (at the lateral collateral ligament of the knee in the la-teral joint space), "Weiyangci"(at the medial margin of the biceps femoris and the lateral side of the transverse striation), and "Yinlingci"(at the end-point of the medial tibia of the goose foot tendon), respectively, once a week for 4 times. One week after the last intervention, the left knee joint dysfunction severity (pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne Index score. X-ray and magnetic resonance imaging(MRI)examinations were conducted to assess the articular space size, effusion and cartilage smoothness of the left knee for which the MRI Osteoarthritis Knee Score (MOAKS) was given according to their severity. The histopathologic changes of the cartilage of the left knee were observed by Hematoxylin-eosin (H.E.) staining and light microscope, which Mankin score was given. In addition, the surface of the cartilage was also examined by macroscopic observation. RESULTS: ①Following modeling, the Lequesne Index score, MOAKS, macroscopic observation score and Mankin score were significantly increased in the model group (P<0.05). X-ray and MRI imaging showed a narrower joint space, more effusion, rough cartilage surface; and H.E. staining displayed rough cartilage surface, and disordered arrangement and occasional clusters of the chondrocytes in the left knee joint. ②In comparison with the blank control group, the Lequesne Index, MOAKS, macroscopic observation and Mankin scores were significantly down-regulated in the acupo-tomy group (P<0.05). The abovementioned injury changes shown by X-ray, MRI, macroscopic and microscopic observations were relatively milder in the acupotomy group. CONCLUSION: Acupotomy loosing based on the "Jingjin theory" of traditional Chinese medicine can effectively improve the motor ability of knee joint and repair pathological changes of the cartilage in KOA rabbits.

MiRNA-132 regulates the development of osteoarthritis in correlation with the modulation of PTEN/PI3K/AKT signaling.

BACKGROUND: Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the functions of miRNA-132 (miR-132) in the modulation of PTEN/PI3K/AKT signaling pathway in the development and progression of osteoarthritis. METHODS: Eight male osteoarthritic patients and eight healthy males were recruited. Male Sprague Dawley (SD) rats were used for cellular experiments. QRT-PCR was performed to detect the expression levels of miR-132, PTEN, PI3K and AKT. MTT assay and apoptosis assay were carried out to measure the cell proliferation rate and cell apoptosis rate, respectively. Western blotting was employed to detect the protein expression of related RNAs and inflammatory factors. RESULTS: In osteoarthritic patients, the expression level of miR-132 was decreased, compared with that in the normal group. Over-expression of miR-132 elevated cell proliferation and decreased apoptosis of chondrocytes. Down-regulation of miR-132 decreased cell proliferation and induced apoptosis in chondrocytes. In addition, down-regulation of miR-132 promoted the expression of Bax protein and activated caspase-3/9, increased inflammation divisors. PTEN inhibitor antagonized the destructive effect of the miR-132 inhibitor on cell proliferation of chondrocytes. PI3K inhibitor increased the destructive effect of the miR-132 inhibitor on osteoarthritis. CONCLUSION: In conclusion, miR-132 is an important regulator of osteoarthritis in chondrocytes through the PTEN/PI3K/AKT signaling pathway.