An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

The diagnostic value of machine learning for the classification of malignant bone tumor: a systematic evaluation and meta-analysis.

Background: Malignant bone tumors are a type of cancer with varying malignancy and prognosis. Accurate diagnosis and classification are crucial for treatment and prognosis assessment. Machine learning has been introduced for early differential diagnosis of malignant bone tumors, but its performance is controversial. This systematic review and meta-analysis aims to explore the diagnostic value of machine learning for malignant bone tumors. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched for literature on machine learning in the differential diagnosis of malignant bone tumors up to October 31, 2022. The risk of bias assessment was conducted using QUADAS-2. A bivariate mixed-effects model was used for meta-analysis, with subgroup analyses by machine learning methods and modeling approaches. Results: The inclusion comprised 31 publications with 382,371 patients, including 141,315 with malignant bone tumors. Meta-analysis results showed machine learning sensitivity and specificity of 0.87 [95% CI: 0.81,0.91] and 0.91 [95% CI: 0.86,0.94] in the training set, and 0.83 [95% CI: 0.74,0.89] and 0.87 [95% CI: 0.79,0.92] in the validation set. Subgroup analysis revealed MRI-based radiomics was the most common approach, with sensitivity and specificity of 0.85 [95% CI: 0.74,0.91] and 0.87 [95% CI: 0.81,0.91] in the training set, and 0.79 [95% CI: 0.70,0.86] and 0.79 [95% CI: 0.70,0.86] in the validation set. Convolutional neural networks were the most common model type, with sensitivity and specificity of 0.86 [95% CI: 0.72,0.94] and 0.92 [95% CI: 0.82,0.97] in the training set, and 0.87 [95% CI: 0.51,0.98] and 0.87 [95% CI: 0.69,0.96] in the validation set. Conclusion: Machine learning is mainly applied in radiomics for diagnosing malignant bone tumors, showing desirable diagnostic performance. Machine learning can be an early adjunctive diagnostic method but requires further research and validation to determine its practical efficiency and clinical application prospects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023387057.

Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review.

PURPOSE: The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee mobility, and pain and discomfort, which seriously affects the quality of life. HUC-MSCs can promote cartilage production and have been widely used in research in the past decade. This article systematically summarizes that it is well used in basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA. Provide a theoretical basis for clinical treatment. PATIENTS AND METHODS: This study collected CNKI, Wanfang, PubMed, and articles related to the treatment of OA with HUC-MSCs since their publication, excluding non-basic and clinical studies such as reviews and meta-analysis. A total of 31 basic experimental studies and 12 clinical studies were included. Systematically analyze the effects of HUC-MSCs on inhibiting inflammatory factors, promoting chondrocyte production, and current clinical treatment. RESULTS: HUC-MSCs can reduce inflammatory factors such as MMP-13, ADAMTS-5, IL-1ß, IL-1, IL-6, TNF-α, induced conversion from M1 to M2 in OA to protect cartilage damage and reduce OA inflammation. Synthesize ColII, SOX9, and aggrecan at the same time to promote cartilage synthesis. CONCLUSION: HUC-MSCs not only have typical stem cell biological characteristics, but also have rich sources and convenient material extraction. Compared with stem cells from other sources, HUC-MSCs have stronger proliferation, differentiation, and immune regulation abilities. Furthermore, there are no ethical issues associated with their use. SAFETY: Primarily attributed to pain, the majority of individuals experience recovery within 24 h following injection. HUC-MSCs possess the ability to alleviate pain, enhance knee joint function, and potentially postpone the need for surgical intervention in both non-surgical and other cases, making them highly deserving of clinical promotion and application.

The potential of Klebsiella and Escherichia-Shigella and amino acids metabolism to monitor patients with postmenopausal osteoporosis in northwest China.

BACKGROUND: Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown. METHODS: This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group. RESULTS: We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups (p < 0.05). Some short-chain fatty acid (SCFAs) producing bacteria, Lactobacillus, Akkermansia, Prevotella, Alistipes, and Butyricicoccus, were reduced in patients with LBM and OST compared to the control. Moreover, fecal metabolomic analyses suggested that the metabolites of indole-3-acetic acid and 7-ketodeoxycholic acid were altered in the LBM and OST groups compared to the control (p < 0.05). Enrichment analysis suggested that valine, leucine, and isoleucine biosynthesis; aromatic amino acid biosynthesis; and phenylalanine metabolism were significantly associated with the identified microbiota biomarkers and OST. Moreover, metabolite marker signatures distinguished patients in the OST from those in the control group with an area under the curve (AUC) of 0.978 and 1.00 in the negative and positive ion modes, respectively. Finally, we also found that the fecal level of interleukin-10 (IL-10) in the OST group was significantly lower than that in the control group and LBM group (p < 0.05), while tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly higher in the OST group than that in the control group (p < 0.05). CONCLUSIONS: This study provides robust evidence connecting the intestinal flora and fecal metabolomics with PMO. Integrated metabolite and microbiota analyses demonstrated that in addition to dysregulated bacteria, indole-3-acetic acid, 7-ketodeoxycholic acid, and other metabolites can be used for the distinguish of LBM and PMO.

[Effect of electroacupuncture on the expression of Iba-1 in spinal dorsal horn and hippocampus of chronic pain rats with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on pain-ralated behaviors, morphology of hippocampus, concentrations of inflammatory cytokines and expression of ionized calcium binding adapter molecule 1(Iba-1) in dorsal horn of the spinal cord and the hippocampus, and brain-derived neurotrophic factor (BDNF) in hippocampus of rats with knee osteoarthritis (KOA), so as to explore the mechanism of EA in improving chronic pain of KOA. METHODS: Forty SD rats were randomly divided into blank group, saline group, model group and EA group, with 10 rats in each group. Monosodium iodoacetate(MIA, 80 mg/mL, 50 µL) was injected into the left knee joint cavity of rats in the model group and EA group to establish the chronic pain model of KOA, while the same volume of normal saline was injected into the left knee joint cavity of rats in the saline group. Rats in the EA group received EA stimulation(2 Hz/100 Hz, 1-2 mA) at left "Yanglingquan"(GB34) and "Neixiyan"(EX-LE4) for 15 min, 14 d after MIA injection. The treatment was given once daily, 5 d as 1 session and 2 sessions of treatment were required. Methanical withdrawl threshold(MWT) and weight-bearing capacity tests on left hind limbs were carried out 1 d before, 7 d，14 d, 20 d and 26 d after MIA injection. At the 27th day, rats were sacrificed and HE staining was used to observe the morphology of hippocampal CA1 area. Concentrations of interleukin(IL)-1ß and tumor necrosis factor(TNF)-α in the left L3-L5 spinal dorsal horn and hippocampal CA1 area were detected by ELISA, the expressions of Iba-1 in the spinal dorsal horn and hippo-campal CA1 area were detected by immunofluorescence, and the expression of BDNF in left hippocampal CA1 area was detected by Western blot. RESULTS: The HE staining results of the hippocampal CA1 area showed reduced number of neurons, unclear cell contour and boundary between nucleus and cytoplasm, and nuclear pyknosis in the model group, which was relatively milder in the EA group. Compared with the blank group, MWT and weight-bearing capacity of rats' left hind limbs, and expression of BDNF protein in hippocampal CA1 area were significantly decreased (P<0.01), while the contents of IL-1ß and TNF-α, the expression of Iba-1 in spinal dorsal horn and hippocampal CA1 area were significantly increased (P<0.01) in the model group. In comparison with the model group, MWT and weight-bearing capacity of rats' left hind limbs, and protein expression of BDNF in hippocampal CA1 area were significantly increased (P<0.01), while the contents of IL-1ß and TNF-α, and the expression of Iba-1 protein in spinal dorsal horn and hippocampal CA1 area were significantly decreased after EA intervention(P<0.01). CONCLUSION: EA at GB34 and EX-LE4 can alleviate the pain-related behaviors of KOA rats. The mechanism might be related to the inhibition of inflammatory reaction mediated by microglia in spinal dorsal horn and hippocampus, and the up-regulation of BDNF expression in hippocampus.

[Clinical study on core decompression in treating osteonecrosis of the femoral head of the necrotic bone-in different site].

OBJECTIVE: To analyze the clinical effect of decompression and bone grafting on osteonecrosis of the femoral head(ONFH) at different sites of necrotic lesions. METHODS: A total of 105 patients with ARCOⅡstage ONFH admitted from January 2017 to December 2018 were retrospectively analyzed. There were 71 males and 34 females, with an average age of (55.20±10.98) years old. The mean course of all patients was(15.91±9.85) months. According to Japanese Inveatigation Committee (JIC) classification, all patients were divided into 4 types:17 cases of type A, 26 cases of type B, 33 cases of type C1 and 29 cases of type C2. All four groups were treated with decompression of the pulp core and bone grafting. Visual analogue scale(VAS) and Harris hip joint score were used before and at 3, 6, 12, and 24 months after the operation, and the collapse of the femoral head was observed by X-ray examination within 2 years. RESULTS: All 105 patients were successful on operation without complications, and the mean follow-up duration was (24.45±2.75) months. Harris score showed that there was no statistical difference among four groups before surgery and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in intragroup Harris scores at preoperative and postoperative time points among four groups (P<0.01). VAS showed that there was no statistical difference among four groups before and 3, 6 months after surgery (P>0.05);at 12 and 24 months after surgery, there were significant differences among all groups (P<0.01). There were significant differences in VAS at preoperative and postoperative time points among four groups (P<0.01). None of the patients in four groups had femoral head collapse before and 3, 6 months after surgery. At 12 months after operation, there were 3 cases of femoral head collapse in group C and 4 cases in group C2(P>0.05);At 24 months after operation, 1 case of femoral head collapse occurred in group B, 6 cases in group C1 and 8 cases in group C2(P<0.05). CONCLUSION: Core decompression and bone grafting can improve the effect of ONFH and hip preservation. The effect of hip preservation for ONFH is closely related to the location of the osteonecrosis lesion, so the influence of the location of lesion on the effect of hip preservation should be considered in clinical treatment, so as to make better preoperative hip preservation plan.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging Findings of Infrapatellar Fat Pad Signal Abnormalities: Comparison Between Symptomatic and Asymptomatic Knee Osteoarthritis.

RATIONALE AND OBJECTIVES: Infrapatellar fat pad (IPFP) proton density-weighted images (PdWI) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (KOA) and are thought to represent inflammation which may induce knee pain. The aim of the study was to compare the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) findings of PdWI hyperintense regions of IPFP between symptomatic and asymptomatic KOA and to determine whether IVIM-DWI parameters can be used as an objective biomarker for symptomatic KOA. MATERIALS AND METHODS: In total, 84 patients with symptomatic KOA, 43 asymptomatic KOA persons, and 30 healthy controls with MRI were retrospectively reviewed. Demographic, IPFP-synovitis, Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain sub-score, IPFP volume and depth and quantitative parameters of IVIM-DWI were collected. The chi-square test, Binary logistic regression and receiver operating characteristic curve (ROC) analysis were used for diagnostic performance comparison. RESULTS: The IPFP volume and depth were statistically significant differences between the non-KOA and sKOA groups (p<0.05). The IPFP PdWI hyperintense regions demonstrated significantly higher values of D and D* in the symptomatic KOA compared to those in the asymptomatic KOA (1.51±0.47 vs. 1.73±0.40 for D and 19.24±6.44 vs. 27.09±9.75 for D*) (both p<0.05). Multivariate logistic regression analyses showed that Higher D and D* values of IPFP hyperintense region were significantly associated with higher risks of knee pain (OR: 1.97; 95% CI: 1.21-3.19; p=0.006 for D and OR: 1.24; 95% CI: 1.09-1.41; p=0.001 for D*). Sensitivity and specificity of D value for symptomatic KOA were 80.28% and 83.33%, with an AUC of 0.78 (0.68-0.86). D* value had the sensitivity with 92.96% and a specificity of 58.33%, with an AUC of 0.82 (0.73-0.89) for symptomatic KOA. CONCLUSION: IVIM-DWI can be used as an additional functional imaging technique to study IPFP with signal abnormalities on PdWI, and the D and D* values may have potential value to predict the symptom in mild-to-moderate KOA patients.

LncRNA nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) aggravates nucleus pulposus cell apoptosis and extracellular matrix degradation.

Emerging reports uncover that long noncoding RNAs (lncRNAs) help regulate intervertebral disc degeneration (IVDD). Here, we probe the function of lncRNA nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) in IVDD. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to verify the expression of NR2F1-AS1 and miR-145-5p in nucleus pulposus (NP) tissues from IVDD patients or NP cells dealt with IL-1ß or TNF-α. Flow cytometry or the TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to validate the apoptosis of NP cells with selective regulation of NR2F1-AS1 and miR-145-5p. ECM-related genes, FOXO1, Bax, and Bcl2 were evaluated by qRT-PCR or Western blot (WB). The targeted relationships between NR2F1-AS1 and miR-145-5p, miR-145-5p and FOXO1 were testified by the dual-luciferase reporter assay and the RNA immunoprecipitation (RIP) assay. Our outcomes substantiated that NR2F1-AS1 was up-regulated, while miR-145-5p was down-regulated in intervertebral disc tissues of IVDD patients or NP cells treated with IL-1ß or TNF-α. Besides, overexpressing NR2F1-AS1 intensified ECM degradation and NP cell apoptosis induced by IL-1ß, while knocking down NR2F1-AS1 or up-regulating miR-145-5p reversed IL-1ß-mediated effects in NP cells. Meanwhile, NR2F1-AS1 choked miR-145-5p and abated its effects in NP cells. This study confirms that NR2F1-AS1 modulates IVDD progression by up-regulating the FOXO1 pathway through the sponge of miR-145-5p as a competitive endogenous RNA (ceRNA).

Olfactory ensheathing cell transplantation alters the expression of chondroitin sulfate proteoglycans and promotes axonal regeneration after spinal cord injury.

Cell transplantation is a potential treatment for spinal cord injury. Olfactory ensheathing cells (OECs) play an active role in the repair of spinal cord injury as a result of the dual characteristics of astrocytes and Schwann cells. However, the specific mechanisms of repair remain poorly understood. In the present study, a rat model of spinal cord injury was established by transection of T10. OECs were injected into the site, 1 mm from the spinal cord stump. To a certain extent, OEC transplantation restored locomotor function in the hindlimbs of rats with spinal cord injury, but had no effect on the formation or volume of glial scars. In addition, OEC transplantation reduced the immunopositivity of chondroitin sulfate proteoglycans (neural/glial antigen 2 and neurocan) and glial fibrillary acidic protein at the injury site, and increased the immunopositivity of growth-associated protein 43 and neurofilament. These findings suggest that OEC transplantation can regulate the expression of chondroitin sulfate proteoglycans in the spinal cord, inhibit scar formation caused by the excessive proliferation of glial cells, and increase the numbers of regenerated nerve fibers, thus promoting axonal regeneration after spinal cord injury. The study was approved by the Animal Ethics Committee of the Medical College of Xi'an Jiaotong University, China (approval No. 2018-2048) on September 9, 2018.

Electroacupuncture Alleviates Osteoarthritis by Suppressing NLRP3 Inflammasome Activation in Guinea Pigs.

Osteoarthritis (OA) is an increasingly prevalent disease affecting synovial joints, which includes joint degeneration, inflammation, and joint pain. The activation of nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) could promote synovial inflammation. Previous studies have shown that electroacupuncture (EA) has potential anti-inflammatory effect. However, the effect of EA treatment on OA remains unclear. The aim of this study was to investigate the effect of applied EA on OA and joint pain and its relationship with NLRP3 inflammasome. The Hartley guinea pigs with naturally occurring OA at age 18 months were chosen as the OA model and treated with EA for 4 weeks. Mechanical allodynia was quantified by using von Frey filaments. The expression of NLRP3 inflammasome and the downstream proinflammatory factors in the cartilage tissue were quantified. Our results showed that EA treatment significantly reduces mechanical allodynia, improves the articular cartilage structure, and decreases the fibrillation on the cartilage surface in guinea pigs with spontaneous osteoarthritis. Moreover, we also found that EA treatment attenuates the NLRP3 inflammasome activation and suppresses the protein expression levels of caspase-1 and IL-1ß in the cartilage tissue. Our findings suggest that EA treatment attenuates OA and joint pain by suppressing NLRP3 inflammasome activation and support further investigation of the potential therapeutic tactics.

Accuracy and Reliability of Computer-aided Anatomical Measurements for Vertebral Body and Disc Based on Computed Tomography Scans.

OBJECTIVE: To assess whether the computed tomography (CT)-based method of three-dimensional (3D) analysis (Mimics) was accurate and reliable for spine surgical anatomical measurements. METHODS: A total of 40 lumbar segments and 32 inter-vertebral discs from eigth adult male cadavers without fractures or deformities fixed with the classical formaldehyde method were included in this research on 5 June 2017. CT scans including seven dimensions: anterior height of the vertebral body (VBHa), middle height of the vertebral body (VBHm), posterior height of the vertebral body (VBHp), width of the upper endplate (EPWu), depth of the upper endplate (EPDu), anterior height of the inter-vertebral disc in the median sagittal plane (IDHa), and posterior height of the inter-vertebral disc in the median sagittal plane (IDHp). They were performed based on uniform conditions (slice thickness: 0.625 mm) using a CT scanner on 8 June 2017. Afterwards, the surgical anatomical measurements were conducted with a Vernier caliper on 12 June 2017. The computer-aided anatomical measurements were conducted by three investigators using Mimics 16.0 to perform 3D reconstructions of CT bone on 16 June 2017. Finally, the length and angle were measured with associated measurement tools, yielding a verified accuracy of 0.01 mm and 0.01°, respectively. Each measurement was repeated three times, and all anatomical data was analyzed using the statistical software and P-value < 0.05 was considered statistically significant. RESULTS: The results showed no statistically significant difference was observed between the surgical anatomical and computer-aided anatomical measurements (P > 0.05) for lumbar vertebra measurements, and the absolute difference between surgical and computer-aided data were all less than 1.0 mm (for the VBHa, VBHm, VBHp, EPWu, and EPDu were 0.12, 0.03, 0.03, 0.31, and 0.03 mm, respectively). Moreover, although the absolute differences of discs was larger than those of lumbar vertebras, no significant differences were detected between the computer-aided and surgical anatomical measurements for the IDHa, as well as IDHp in the vast majority of measurements (P = 0.543, 0.079 or 0.052 for IDHa, and P = 0.212, 0.133 or 0.042 for IDHp). In addition, excellent reliability correlation was observed between the measurements of each investigator, and the reliability coefficients in the intra-groups were all greater than 0.9 except for IDHp (reliability coefficient = 0.892). Additionally, the reliability coefficients were greater than 0.9 for the all between-group correlations, and a significant correlation was also observed. Furthermore, no statistically significant difference for three anatomical values was found in the computer-assisted measurements of the lumbar bone structure (P > 0.05). Similarly, we did not observe a statistical difference in the anatomical data of the lumbar discs from the three measures (P > 0.05). CONCLUSIONS: Computer-aided anatomical measurement for spine based on CT scans presents the high accuracy and reliability for improving spinal surgical procedures.

[Effects of electroacupuncture on pain behavior and pain-related factors in spinal cord dorsal horn and dorsal root ganglia of rats with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the pain behavior and prostaglandin E2 (PGE2), calcitonin gene-related peptide (CGRP) and substance P (SP) in the spinal cord dorsal horn and dorsal root ganglia (DRG) of rats with knee osteoarthritis (KOA), so as to explore the mechanisms of EA underlying improvement of chronic pain in KOA rats. METHODS: Thirty-two female SD rats were randomly divided into blank group, control group, model group and EA group, with 8 rats in each group. Rats in the control group were injected with 50 µL of 0.9% sodium chloride solution into the left knee joint cavity, and rats in the model and EA groups were injected with 50 µL of Monosodium iodoacetate in the left knee joint. EA(2 Hz/100 Hz, ＜2 mA) was applied to left "Yanglingquan"(GB34) and "Neixiyan" (EX-LE4) for 15 min, once daily, 5 days a course with a total of 2 courses. Paw withdrawal latency (PWL) and mechanical pain threshold (PWT) were tested by Plantar Test and Von Frey, separately. After the last pain test, the contents of PGE2, CGRP and SP in the left lumbar (L) 3-L5 DRG and L3-L5 spinal dorsal horn were detected by ELISA. RESULTS: Compared with the blank group, the PWL and PWT of the rats in the model group were significantly decreased (P<0.01), and the contents of PGE2, CGRP and SP in the DRG and spinal dorsal horn were significantly increased (P<0.01, P<0.05). There were no statistically significant differences in PWL, PWT, contents of PGE2, CGRP and SP in DRG and spinal dorsal horn between the blank group and the control group (P>0.05). Compared with the model group, the PWL and PWT of rats in the EA group were significantly increased (P<0.01), and the contents of PGE2, CGRP and SP in the DRG and spinal dorsal horn were significantly decreased (P<0.01, P<0.05). CONCLUSION: EA of GB34 and EX-LE4 can reduce the levels of pain-related factors PGE2, CGRP and SP in the DRG and spinal dorsal horn, thereby relieving spinal hyperalgesia in rats with KOA.

Cryptotanshinone inhibits RANKL-induced osteoclastogenesis by regulating ERK and NF-κB signaling pathways.

Osteoporosis (OS) is one of the most common healthy problems characterized by low bone mass. Osteoclast, the primary bone-resorbing cell, is responsible for destructive bone diseases including osteoporosis (OS). Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza bunge, has been shown to prevent the destruction of cartilage and the thickening of subchondral bone in mice osteoarthritis models. However, its molecular mechanism in osteoclastogenesis needs to be determined. The aim of the current study was to explore the effect of CTS on osteoclastogenesis and further evaluate the underlying mechanism. Our results showed that CTS inhibited receptor activator of NF-κB ligand (RANKL)-induced the increase in tartrate-resistant acid phosphatase (TRAP) activity in bone marrow-derived macrophages (BMMs). In addition, the expressions of osteoclastogenesis-related marker proteins and nuclear factor of activated T-cells (NFAT) activation were suppressed by CTS treatment in BMMs. Furthermore, CTS attenuated RANKL-induced ERK phosphorylation and NF-κB activation in BMMs. These findings indicated that CTS inhibited RANKL-induced osteoclastogenesis by inhibiting ERK phosphorylation and NF-κB activation in BMMs. Thus, CTS may function as an inhibitor of osteoclastogenesis and may be considered as an alternative medicine for the prevention and treatment of OS.

Core decompression, lesion clearance and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head: A retrospective cohort study.

The aim of this study was to evaluate the clinical effect of core decompression (CD), lesion clearance, and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head (ONFH).A total of 75 patients (92 hips), with ONFH at Association Research Circulation Osseous (ARCO) stages II to IIIA, were studied and divided into treatment group and control group. In control group, patients were treated with the CD in combination with autologous or artificial ceramic bone graft. In treatment group, patients were treated with the above method combined with Tongluo Shenggu decoction. Patients were followed-up at 1 month, 6 months, and 24 months after surgery. The visual analogue scale (VAS) scores, Harris Hip Score (HSS), and total effective rates were measured and recorded.The total effective rate of the treatment group was significantly higher than that of the control group (97.2% vs. 89.9%, P < .05). Compared with preoperative, the VAS and HSS scores were both improved at final follow-up, and there was significant difference between 2 groups (P < .01).The combination of CD, lesion clearance, and the bone graft with Tongluo Shenggu decoction is safe and effective for the treatment of ONFH, owing to which it can provide higher postoperative functional outcomes, reduce pain, and achieve smaller osteonecrosis area and better bone changes.

Down-regulation of miR-193a-3p promotes osteoblast differentiation through up-regulation of LGR4/ATF4 signaling.

Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR-193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling.

The relationship between apolipoprotein genes polymorphisms and susceptibility to osteonecrosis of the femoral head: a meta-analysis.

BACKGROUND: The objective of this study was to evaluate whether apolipoprotein gene polymorphisms confer susceptibility to osteonecrosis of the femoral head (ONFH). METHODS: The relevant literature was screened from databases of Pubmed, Embase, Wanfang, Weipu and China National Knowledge Internet (CNKI) until May, 2017. In addition, odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as a measure of effect size for calculating effect size. RESULTS: Totally, six case-control studies were included in this meta-analysis. It revealed that ApoB-C7623T polymorphism frequency was increased in ONFH group than in control group under three genetic models, including allele model (T vs. C, OR = 4.5149, 95% CI: 1.6968-12.0134); additive model (TC vs. CC, OR = 6.2515, 95% CI: 2.0939-18.6640); and dominant model (TT + TC vs. CC, OR = 5.4998, 95% CI: 1.9246-15.7163). In addition, the increased risk of ONFH were related to ApoA1-rs1799837 polymorphism under additive model (AA vs. GG, OR = 1.4175, 95% CI: 1.0522-1.9096) and recessive model (AA vs. GG + AG, OR = 1.7727, 95% CI: 1.3399-2.3452). However, four ApoB rs1042031, rs693, 3'-VNTR and G12619A polymorphisms under the all genetic models were not associated with susceptibility to ONFH. CONCLUSION: The T allele and TC genotype of ApoB-C7623T and AA genotype of ApoA1-rs1799837 may contribute to increase the risk of ONFH.

Meta-analysis of the potential role of extracorporeal shockwave therapy in osteonecrosis of the femoral head.

BACKGROUND: We aimed to evaluate the role of extracorporeal shockwave therapy (ESWT) in improving osteonecrosis of the femoral head (ONFH). METHODS: We searched studies focusing on the role of ESWT in ONFH using PubMed, Embase, the Cochrane Library, WanFang, VIP, and CNKI databases updated up to July 28, 2017, without language restriction. Standardized mean difference (SMD) values and 95% confidence intervals (95% CIs) were pooled to compare the pain score and Harris hip score for ESWT treatment and other treatment strategies. RESULTS: Four articles, including 230 ONFH patients, were eligible for the meta-analysis. No significant differences were found in the pain score (SMD = - 1.0104; 95% CI - 2.3279-0.3071) and Harris hip score (SMD = 0.3717; 95% CI - 0.3125-1.0559) between the two groups before treatment. After treatment, significant differences were found between the experimental and control groups in the pain score (SMD = - 2.1148; 95% CI - 3.2332-0.9965) and Harris hip score (SMD = 2.1377; 95% CI 1.2875-2.9880). There were no significant differences in pain score before and after treatment between the two groups (SMD = - 0.7353; 95% CI - 2.1272-0.6566), but significant differences were found in the Harris hip score (SMD = 1.2969; 95% CI 0.7171-1.8767). CONCLUSION: For patients at an early stage, ESWT may be safe and effective for relief of pain and improvement of motor function.

Bioinformatic Analysis of Differentially Expressed Genes in Peripheral Blood of Human Immunodeficiency Virus/Tubercle Bacilli Co-infected Patients.

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions were analyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.

Predicting novel genes and pathways associated with osteosarcoma by using bioinformatics analysis.

This aim of this study was to explore novel biomarkers related to osteosarcoma. The mRNA expression profile GSE41293 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which included seven osteosarcoma and six control samples. After preprocessing, the FASTQ format reads of 13 samples were mapped to the reference sequences to screen for unique mapping reads. Differentially expressed genes (DEGs) were selected, which were then used for pathway and protein-protein interaction (PPI) network analyses. Moreover, the microarray data GSE63631 were downloaded from GEO database to verify our results. The percentages of unique mapping reads for osteosarcomas and control samples were both >85%. A total of 6157 DEGs were identified between the two groups. DEGs that were upregulated were significantly enriched in 19 pathways, and those that were downregulated were enriched in 14 pathways. In the PPI network, DEGs such as SRC, ERBB2, and CAV3 in cluster 1 were enriched in the pathway responsible for focal adhesions. The DEGs in cluster 2, such as CDK4 and CDK6, were enriched in the cell cycle pathway. In GSE63631, DEGs were significantly enriched in focal adhesion pathway, which was in accordance with the result in GSE41293. Thus, the focal adhesion and cell cycle pathways may play important roles in osteosarcoma progression, and SRC, ERBB2, CAV3, CDK4, and CDK6 may be used as critical biomarkers of osteosarcoma.