Percutaneous Curved Vertebroplasty Versus Unilateral Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous curved vertebroplasty (PCVP), a modified traditional unilateral percutaneous vertebroplasty (UPVP) technique, is increasingly being used to treat osteoporotic vertebral compression fractures (OVCFs); however, its advantages remain controversial. This meta-analysis was conducted to determine whether PCVP is superior to traditional UPVP in treating OVCFs. METHODS: Six databases were searched for studies comparing the clinical efficacy of PCVP and UPVP in treating patients with OVCFs published until March 2023. After study selection, data extraction, and risk of bias evaluation, a meta-analysis was conducted. The study protocol was registered in the PROSPERO platform (registration number: CRD42023417190). RESULTS: Eight studies (6 randomized controlled trials and 2 cohort studies) were eligible for the final analysis. The pooled results revealed no between-group differences in operation time (P = 0.85), intraoperative fluoroscopy (P = 0.58), or postoperative short-term visual analog scale scores (P = 0.15). However, PCVP was associated with more injected cement (P = 0.003), a lower cement leakage rate (P = 0.006), and a lower final follow-up visual analog scale score (P < 0.0001). CONCLUSIONS: PCVP was superior to UPVP in terms of reducing the bone cement leakage rate and providing long-term pain relief. Further trials with larger sample sizes and longer follow-up periods are required to verify these findings owing to the potential risk of bias.

Structural Versus Nonstructural Bone Grafting Via the Posterior Approach in the Treatment of Thoracic and Lumbar Tuberculosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Bone grafting is necessary in spinal tuberculosis surgery. Structural bone grafting is considered the gold standard treatment for spinal tuberculosis bone defects; however, nonstructural bone grafting via the posterior approach has recently gained attention. In this meta-analysis, we evaluated the clinical efficacy of structural versus nonstructural bone grafting via the posterior approach in the treatment of thoracic and lumbar tuberculosis. METHODS: Studies comparing the clinical efficacy of structural and nonstructural bone grafting via the posterior approach in spinal tuberculosis surgery were identified from 8 databases from inception to August 2022. Study selection, data extraction, and evaluation of the risk of bias were performed, and meta-analysis was conducted. RESULTS: Ten studies including 528 patients with spinal tuberculosis were enrolled. Meta-analysis revealed no between-group differences in fusion rate (P = 0.29), complications (P = 0.21), postoperative Cobb angle (P = 0.7), visual analog scale score (P = 0.66), erythrocyte sedimentation rate (P = 0.74), or C-reactive protein level (P = 0.14) at the final follow-up. Nonstructural bone grafting was associated with less intraoperative blood loss (P < 0.00001), shorter operation time (P < 0.0001), shorter fusion time (P < 0.01), and shorter hospital stay (P < 0.00001), while structural bone grafting was associated with lower Cobb angle loss (P = 0.002). CONCLUSIONS: Both techniques can achieve a satisfactory bony fusion rate for spinal tuberculosis. Nonstructural bone grafting has the advantages of less operative trauma, shorter fusion time, and shorter hospital stay, making it an attractive option for short-segment spinal tuberculosis. Nevertheless, structural bone grafting is superior for maintaining corrected kyphotic deformities.

Isolated cryptococcal osteomyelitis of the sacrum in an immunocompetent patient: a case report and literature review.

BACKGROUND: Cryptococcus neoformans, an opportunistic fungal pathogen, seldom causes infection in immunocompetent people. Cryptococcal osteomyelitis is an uncommon condition in which Cryptococcus invades the bone. It usually occurs as part of a disseminated infection and rarely in isolation. The spine has been reported as the most common site of cryptococcal osteomyelitis; however, isolated case of sacrum involvement in immunocompetent patients has never been reported. CASE PRESENTATION: We report the case of a 37-year-old man without underlying disease who presented with progressive low back and sacrococcygeal pain. The patient was initially diagnosed with sacral tumour by a local doctor, and subsequently, after admission, was diagnosed with sacral tuberculosis. He was empirically treated with antitubercular drugs. The patient failed to respond to antitubercular drugs and complained of worsening low back pain. Additionally, he developed persistent radiating pain and numbness in his legs. For further diagnosis, we performed a computed tomography-guided puncture biopsy of the sacrum, which revealed granulomatous inflammation with massive macrophage infiltration and special staining revealed a fungal infection. We performed sacral debridement and drainage and obtained purulent specimens for pathological examination and microbial culture. Microbial identification and drug susceptibility tests revealed a Cryptococcus neoformans infection sensitive to fluconazole. Postoperatively, the persistent radiating pain and numbness in the legs resolved. After 12 consecutive weeks of antifungal therapy, all his symptoms resolved. The patient remained without any signs of recurrence at the 8-month follow-up. CONCLUSION: We reported a rare case of isolated sacrum cryptococcal osteomyelitis in an immunocompetent patient. Furthermore, we identified and reviewed 18 published cases of spine cryptococcal osteomyelitis. Immunocompetent individuals are also at risk for cryptococcal osteomyelitis. Clinical manifestation and imaging are insufficient to diagnose cryptococcal osteomyelitis of the spine, and invasive examinations, such as puncture biopsy and fungal examinations, are needed. Antifungal therapy yields satisfactory results for the treatment of cryptococcal osteomyelitis of the spine, however, if the infective lesion is large, especially when it compresses the spinal cord and nerves, a regimen combining aggressive surgery with antifungal therapy is indispensable.

The role of PI3K/Akt signalling pathway in spinal cord injury.

Spinal cord injury (SCI) is a severely disabling central nervous system injury with complex pathological mechanisms that leads to sensory and motor dysfunction. The current treatment for SCI is aimed at symptomatic symptom relief rather than the pathological causes. Several studies have reported that signaling pathways play a key role in SCI pathological processes and neuronal recovery mechanisms. The PI3K/Akt signaling pathway is an important pathway closely related to the pathological process of SCI, and activation of this pathway can delay the inflammatory response, prevent glial scar formation, and promote neurological function recovery. Activation of this pathway can promote the recovery of neurological function after SCI by reducing cell apoptosis. Based on the role of the PI3K/Akt pathway in SCI, it may be a potential therapeutic target. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.

Long non-coding RNA-small nucleolar RNA host gene 7 regulates inflammatory responses following spinal cord injury by regulating the microRNA-449a/TNF-α-induced protein 3-interacting protein 2 axis.

The current study aimed to explore the anti-inflammatory effects of long non-coding RNA-small nucleolar RNA host gene 7 (lncRNA-SNHG7) and its mechanism in spinal cord injury (SCI) models. SCI models were established both in vivo and in vitro. Reverse transcription-quantitative PCR was performed to determine the expression levels of lncRNA-SNHG7 in SCI models. Bioinformatics analysis and dual-luciferase reporter assays were carried out to confirm the interaction between lncRNA-SNHG7 with microRNA (miR)-499a and TNF-α-induced protein 3-interacting protein 2 (TNIP2). In addition, cell viability, apoptosis, and the secretion of inflammatory cytokines were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometric analysis, and enzyme linked immunosorbent assay (ELISA), respectively. The results showed that lncRNA-SNHG7 was markedly downregulated in the SCI model group. LncRNA-SNHG7 directly bound to miR-499a, which in turn directly targeted TNIP2. In addition, TNIP2 was significantly decreased in SCI rats and lipopolysaccharide (LPS)-treated PC-12 cells. The in vitro results in PC-12 cells revealed that lncRNA-SNHG7 overexpression attenuated neuronal cell death and SCI-mediated inflammatory responses by regulating miR-449a expression. Furthermore, miR-499a knockdown inhibited LPS-induced PC-12 cell injury by targeting TNIP2. In conclusion, lncRNA-SNHG7 modulates the apoptosis and inflammation of PC-12 cells by regulating the miR-449a/TNIP2/NF-κB signaling pathway.

Misdiagnosis of brown tumour caused by primary hyperparathyroidism: a case report with literature review.

BACKGROUND: Brown tumour is a rare tumour-like lesion of the bone, which is considered as an end-stage lesion of abnormal bone metabolism caused by persistently high parathyroid hormone (PTH) levels. Brown tumour can be found in any part of the skeleton; in some cases, it can occur in multiple bones and can be easily misdiagnosed as a metastatic tumour. CASE PRESENTATION: We report the case of a 44-year-old man who presented to the Department of Oncology in our hospital with a 2-month history of local pain in his left shoulder joint. The initial diagnosis was an aneurysmal bone cyst by biopsy, for which the patient underwent tumour resection surgery. The diagnosis of a malignant tumour was made again following postoperative pathological examination. The pathological sections and all clinical data were sent to the Department of Pathology of the First Affiliated Hospital of Sun Yat-sen University; the diagnosis made there was brown tumour. His blood PTH level was 577 pg/ml (15-65 pg/ml). Colour Doppler ultrasonography of the parathyroid gland suggested a parathyroid adenoma. For further treatment, the left parathyroid adenoma was removed by axillary endoscopic resection. Postoperatively, a pathologic examination was performed, and the diagnosis of a parathyroid adenoma was confirmed. One year after the surgery, the left humerus was completely healed, and the left shoulder joint had a good range of movement. CONCLUSIONS: In summary, histopathological diagnosis is not sufficient for the diagnosis of brown tumours. A comprehensive analysis combining clinical symptoms with findings of imaging and laboratory tests is also required. Generally, the treatment of brown tumour includes only partial or complete resection of the parathyroid glands. However, when the tumour is large, especially when it involves the joint, surgery is indispensable.

Single Posterior Approach versus Combined Anterior and Posterior Approach in the Treatment of Spinal Tuberculosis: A Meta-Analysis.

BACKGROUND: Spinal tuberculosis is the most common form of tuberculosis affecting bone and often needs surgical treatment. Single anterior, single posterior, and combined anterior and posterior approaches are the 3 most commonly used approaches in surgical treatment. Clinically, the choice of optimal surgical approach remains controversial. The purpose of this meta-analysis was to evaluate clinical efficacy of single posterior approach versus combined anterior and posterior approach. METHODS: Studies comparing surgical treatment of spinal tuberculosis by single posterior approach versus combined anterior and posterior approach were identified in a literature search conducted from study inception to July 2020. Selection of studies, extraction of data, and evaluation of bias risk of studies were performed independently by 2 authors, and meta-analysis was conducted using RevMan 5.3 software. RESULTS: The meta-analysis included 15 studies and 793 spinal tuberculosis cases. Single posterior approach was used in 397 patients, and combined anterior and posterior approach was used in 396 patients. There were no statistical differences in visual analog scale score (P = 0.51), correction of Cobb angle (P = 0.14), neurological improvement (P = 0.71), erythrocyte sedimentation rate (P = 0.32), C-reactive protein after operation (P = 0.81), and loss of correction at final follow-up (P = 0.44) between approaches. Single posterior approach was associated with less intraoperative hemorrhage (P < 0.00001), shorter operative time (P < 0.00001), shorter length of hospital stay (P < 0.00001), and fewer complications (P < 0.00001). Combined anterior and posterior approach was associated with shorter fusion time (P = 0.04). CONCLUSIONS: Both approaches can achieve satisfactory clinical outcomes. Posterior-only approach can safely and effectively achieve lesion débridement, decompression, and stability reconstruction and maintenance with advantages of less invasive surgery, less bleeding, shorter surgery time and hospital stay, and fewer complications and seems to be superior to combined posterior-anterior approach.

Ferric Ion Induction of Triggering Receptor Expressed in Myeloid Cells-2 Expression and PI3K/Akt Signaling Pathway in Preosteoclast Cells to Promote Osteoclast Differentiation.

OBJECTIVE: Iron plays a significant role in multiple biological processes. The purpose of this study was to measure whether iron mediated osteoclast differentiation through regulation of triggering receptor expressed in myeloid cells-2 (Trem-2) expression and the PI3K/Akt signaling pathway. METHODS: The effects of six different concentrations of ferric ammonium citrate (FAC) (100, 80, 40, 20, 10 and 0 µmol/L) on RAW 264.7 cells proliferation were assessed by Cell Counting Kit-8 (CCK-8) gassay. Tartrate resistant acid phosphatase (TRAP) assay was performed to detect the effects of FAC on osteoclast formation. The expression of osteoclast differentiation-related (TRAP, NFATc-1, and c-Fos) and Trem-2 mRNA and proteins was analyzed by reverse transcription-polymerase chain reaction and western blot, respectively. Si-Trem-2 was constructed and transfected to RAW264.7 to measure the effects of Trem-2 on FAC-mediated osteoclast formation. TRAP assay and osteoclast differentiation-related gene analyses were further performed to identify the role of Trem-2 in osteoclastogenesis. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to explore the target genes of Trem-2. Trem-2-related gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used for further in-depth analysis. PI3K/Akt pathway-related proteins were detected by immunofluorescence and western blot. RESULTS: In groups with FAC concentration of 10 (102.5 ± 3.1), 20 (100.5 ± 1.5), and 40 µmol/L (98.7 ± 3.1), compared with the control group (100.1 ± 2.2), cell viability was not significantly different from the control (P > 0.05). When the concentration of FAC exceeded 80 µmol/L, cell viability was significantly decreased (87.5 ± 2.8 vs 100.1 ± 2.2, P < 0.05). FAC promotes Trem-2 expression and osteoclast differentiation in a dose-response manner (P < 0.05). The number of osteoclast-like cells was found to be reduced following transfection with the siRNA of Trem-2 (42 ± 3 vs 30 ± 5, P < 0.05). We observed that most of Trem-2 target genes are primarily involved in response to organic substance, regulation of reactive oxygen species metabolic process, and regulation of protein phosphorylation. The STRING database revealed that Trem-2 directly target two gene nodes (Pik3ca and Pik3r1), which are key transcriptional cofactors of the PI3K/Akt signaling pathway. KEGG pathways include the "PI3K-Akt signaling pathway," the "thyroid hormone signaling pathway", "prostate cancer," the "longevity regulating pathway," and "insulin resistance." Expression of p-PI3K and p-Akt protein, measured by immunofluorescence and western blotting, was markedly increased in the FAC groups. Trem-2 siRNA caused partial reduction of these two proteins (p-PI3K and p-Akt) compared to the FAC alone group. CONCLUSION: The FAC promoted osteoclast differentiation through the Trem-2-mediated PI3K/Akt signaling pathway. However, its regulation osteoclastogenesis should be verified through further in vivo studies.

Hirayama Disease Treated by Anterior Cervical Diskectomy and Fusion: Case Report and Literature Review.

OBJECTIVE: We present the case of a 19-year-old boy who had the classic radiologic and clinical presentations of Hirayama disease treated with anterior cervical diskectomy and fusion (ACDF). We also propose ACDF as promising surgery for the treatment of Hirayama disease. Hirayama disease is an initially progressive disease caused by cervical neck flexion compressing the anterior horns of the lower cervical spinal cord. CASE DESCRIPTION: Our patient presented with an insidious, progressive weakness in his right hand, which had been ongoing for 1 year. Physical examination revealed various degrees of right forearm and hand muscle wasting, and decreased right hand extend power with motor grade Ш. Cervical flexed magnetic resonance imaging showed a spinal cord was being compressed-most noticeably at the level of the fifth cervical vertebral body-and that the dorsal epidural space was abnormally expanding. The patient underwent ACDF at the C4-6 level. The pain and paresthesia improved immediately after the surgery. His motor grade improved immediately after the operation, and there were improvements of a modest reversal of muscle wasting at 1 year postoperatively. CONCLUSIONS: ACDF could be considered as an effective treatment option for the treatment of Hirayama disease. Our patient's finger function improved. Therefore we believe that anterior fusion might be the best choice of treatment.

Dynesys system vs posterior decompression and fusion for the treatment of lumbar degenerative diseases.

BACKGROUND: The Dynesys dynamic stabilization system is an alternative to rigid instrumentation and fusion for the treatment of lumbar degenerative disease. The purpose of this study is to evaluate the clinical efficacy between Dynesys and posterior decompression and fusion for lumbar degenerative diseases. METHODS: The computer was used to retrieve the Cochrane library, Medline, Embase, CNKI, Wanfang database and Chinese biomedical literature database; and the references and main Chinese and English Department of orthopedics journals were manually searched. All the prospective or retrospective comparative studies on the clinical efficacy and safety of Dynesys and posterior decompression and fusion were collected, so as to evaluate the methodological quality of the study and to extract the data. The RevMan 5.2 software was used for data analysis. RESULTS: A total of 17 studies were included in the meta-analysis. There were no significant differences in Oswestry disability index and visual analogue score for leg pain, visual analogue score for back pain, L2-S1 ROM between Dynesys and fusion group. Operation time, blood loss, length of stay and complications in the Dynesys group were significantly less than that in the fusion group. Adjacent-segment degeneration in the fusion group was significantly higher than that in the Dynesys group. In addition, postoperative operated segment ROM was significantly less in the fusion group as compared to the Dynesys group. CONCLUSIONS: Our meta-analysis suggests that Dynesys system acquires comparable clinical outcomes compared to fusion in the treatment of lumbar degenerative diseases. Moreover, compared with fusion, Dynesys could remain ROM of surgical segments with less operation time, blood loss, length of stay, adjacent-segment degeneration, and lower complication. Further studies with large samples, long term follow up and well-designed are needed to assess the two procedures in the future.

Effects and Mechanism of Chlorogenic Acid on Weight Loss.

BACKGROUND: Chlorogenic Acid (CA) has diverse, recognized health effects. OBJECTIVE: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects. MATERIALS AND METHODS: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways. RESULTS: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells. CONCLUSION: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.

Correlations between Modic change and degeneration in 3-joint complex of the lower lumbar spine: A retrospective study.

BACKGROUND: Modic changes (MCs) associated with low back pain (LBP) have been assessed in a few studies. It has been documented that patients with LBP have MCs in a specific segment, but the relationship between facet joint or disc degeneration and MCs is still disputed. Thus, we aimed to evaluate the correlation between MC and facet joint or disc degeneration using imaging. METHODS: Imaging data of patients were retrospectively analyzed at the Orthopedic Department of the First Affiliated Hospital of Nanchang from January 2014 to August 2017. MCs, facet joint degeneration, and disc degeneration in L3-S1 were evaluated by lumbar MRI. χ test and contingency correlation coefficient were used for the statistical analyses, and a P value < .05 was considered statistically significant. RESULTS: In the descriptive statistical analysis, MCs were found to have the highest incidence in the L4-5 segment. Type II MCs had a higher incidence than type I and type III MCs regardless of whether they were in the L3-4, L4-5, or L5-S1 segment. On one hand, MCs were more frequently distributed in grades 3, 4, and 5 of the degenerative lumbar discs regardless of whether they were in the L3-4, L4-5, or L5-S1 segment (P < .000, V: contingency coefficient >0); particularly, type II MCs were closely related to lumbar disc degeneration (P < .05, V > 0). On the other hand, MCs were more frequently distributed in grades 1, 2, and 3 of the degenerative lumbar facet regardless of whether they were in the L3-4, L4-5, or L5-S1 segment (P < .05, V > 0). Particularly, type II MCs were frequently distributed in grades 1, 2, and 3 of the facet joint in the L4-5 and L5-S1 segments (P < .05, V > 0). CONCLUSION: MCs are correlated with the grade of lumbar spine degeneration, including lumbar disc and facet joint degeneration. MCs, especially type II, frequently occurred in severe degeneration of the lumbar disc and facet joint. Thus, MC may be one of the manifestations of lumbar disc and facet joint degeneration.

Immunosuppressive effects of hydroxychloroquine and artemisinin combination therapy via the nuclear factor-κB signaling pathway in lupus nephritis mice.

Lupus nephritis (LN) is one of the most common and severe manifestations of systemic lupus erythematosus, leading to permanent renal damage and chronic kidney disease. Hydroxychloroquine (HCQ) serves a protective role against lupus-associated clinical manifestations and medical complications; however, it results in numerous adverse reactions, limiting its long-term use. The aim of the present study was to investigate the combined effect of HCQ and artemisinin (ART) on LN, and to elucidate the underlying mechanisms. An in vivo LN mouse model was prepared, and the animals were administered prednisone (PDS; serving as a positive control), high-dose HCQ (H-HCQ) or low-dose HCQ combined with ART (L-HCQ + ART) once daily for 8 weeks. The body weight, serum biochemical parameters, immune and inflammatory indicators, renal and spleen histological alterations, and mRNA expression levels of Kruppel-like factor 15 (KLF15) and nuclear factor-κB (NF-κB) were analyzed. It was observed that L-HCQ + ART and H-HCQ ameliorated the LN-induced body weight decrease, and significantly decreased the levels of anti-double stranded DNA, antinuclear antibodies, immunoglobulin G, interferon γ, tumor necrosis factor-α and transforming growth factor-ß1, as well as improved the kidney and spleen pathology, when compared with the model group. In addition, L-HCQ + ART and H-HCQ treatments induced KLF15 upregulation and NF-κB downregulation. These results indicated that treatment with L-HCQ + ART exerted renoprotective effects by regulating the expression levels of cytokines, KLF15 and NF-κB. This combination treatment may have a similar immunosuppressive effect as PDS and H-HCQ, and may be a promising alternative for LN treatment.

Paeoniflorin ameliorates Adriamycin-induced nephrotic syndrome through the PPARγ/ANGPTL4 pathway in vivo and vitro.

Paeoniflorin (PF), an effective composition that is extracted from Radix Paeoniae Alba, plays a role in protecting against various kidney diseases. However, the mechanism of PF on nephrotic syndrome (NS) remains unclear. The aim of this study was to investigate the protective role of PF on Adriamycin (ADR)-induced NS in vivo and vitro as well as its potential mechanism. In animal study, PF significantly decreased the levels of 24-h urine protein, blood urea nitrogen, serum creatinine, total cholesterol and triglycerides in NS rats, but increased the total protein and albumin levels. Hematoxylin-eosin (HE) staining revealed that the kidney lesion was resolved upon PF treatment. After treatment with PF, the morphology and number of podocytes in renal tissue were restored to normal. PF increased expression of synaptopodin and decreased expression of desmin, demonstrating a protective effect in podocyte injury. Further studies revealed that PF upregulated Peroxisome proliferator-activated receptor gamma (PPARγ) and restrained Angiopointin-like 4 (ANGPTL4) in kidney tissue. In vitro study, PF reduced Caspase3 and Bax and increased Bcl-2, indicating that the apoptosis rate of podocytes induced by ADR was reduced by PF. Furthermore, PF ameliorated podocyte injury by upregulating synaptopodin and reducing desmin. In accordance with animal study, PF downregulated ANGPTL4 by activating PPARγ. However, the therapeutic effects of PF were reversed by GW9662 (PPARγ inhibitor), likely by suppressing ANGPTL4 degradation. In general, these results demonstrate that PF has a good therapeutic effect on NS by activating PPARγ and subsequently inhibiting ANGPTL4.

Zhen-wu-tang attenuates cationic bovine serum albumin-induced inflammatory response in membranous glomerulonephritis rat through inhibiting AGEs/RAGE/NF-κB pathway activation.

Zhen-wu-tang (ZWT), a traditional Chinese compound formula recorded in the Treatise on Febrile Diseases, has significant inhibitory effects on inflammatory damage and oxidative lesions in rats, but its mechanism of action remains unclear. The aim of the present study was to explore whether the anti-inflammatory and anti-oxidative effects of ZWT were mediated by the AGEs/RAGE/NF-κB signaling pathway in rats with cationic bovine serum albumin (C-BSA)-induced membranous glomerulonephritis (MGN). We found that ZWT significantly reduced the production of malondialdehyde (MDA), but enhanced the superoxide dismutase (SOD) activity. The ELISA results showed that ZWT not only reduced the serum levels of AGEs but also decreased the release of inflammatory mediators (TNF-α, IL-1ß, and IL-6). Meanwhile, HE staining showed that pathological kidney injury was alleviated by ZWT. In addition, ZWT suppressed the expression of RAGE1 and NF-κB p65, as well as the nuclear translocation of NF-κB p65. The accumulation of AGEs, oxidative lesions and inflammation damage were reduced by an AGE inhibitor. Thus, the present study demonstrates that AGEs play a role in the pathogenesis of MGN and that AGE inhibition could reduce the inflammatory reactions and oxidative lesions in MGN. In general, ZWT attenuated MGN, in part, by inhibiting the AGEs/RAGE/NF-κB pathway.

Effect of Maxing Shigan Tang on H1N1 Influenza A Virus-Associated Acute Lung Injury in Mice.

OBJECTIVE: This study is aimed at examining the effects of Maxing Shigan Tang (MST) treatment on H1N1-associated acute lung injury (ALI) and exploring the possible mechanism. MATERIAL AND METHODS: Mice were randomly divided into a control group, model group, peroxisomal proliferator activator receptor γ (PPARγ) inhibition group (PPARγ-), PPARγ activation group (PPARγ+), and MST group. Influenza A (H1N1) virus of the Fort Monmouth 1 (FM1) strain was used to induce an ALI mice model. Hematoxylin and eosin staining was performed to investigate the effect of MST treatment on H1N1-associated ALI. Cell apoptosis of lung tissues of each group were conducted through transferase-mediated dUTP nick end-labeling methods. Moreover, the expression level of caspase 3, activity of caspase 3, and serum level of tumor necrosis factor (TNF)-α of each group were also analyzed. Finally, quantitative real-time polymerase chain reaction and Western blotting analysis were carried out to detect angiopoietin-like 4 (ANGPTL4) expression level. RESULTS: We found that mice infected with the FM1 strain of H1N1 influenza A virus developed severe ALI, and MST could improve H1N1-induced ALI. Moreover, MST decreased lung cell apoptosis and reduced the serum content of TNF-α. In addition, MST significantly induced the ANGPTL4 expression in H1N1-induced ALI. CONCLUSION: MST improves H1N1-associated ALI maybe through targeting ANGPTL4 in mice.

Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy.

BACKGROUND: Plasmodium falciparum malaria is a significant public health problem in Comoros, and artemisinin combination therapy (ACT) remains the first choice for treating acute uncomplicated P. falciparum. The emergence and spread of artemisinin-resistant P. falciparum in Southeast Asia, associated with mutations in K13-propeller gene, poses a potential threat to ACT efficacy. Detection of mutations in the P. falciparum K13-propeller gene may provide the first-hand information on changes in parasite susceptibility to artemisinin. The objective of this study is to determinate the prevalence of mutant K13-propeller gene among the P. falciparum isolates collected from Grande Comore Island, Union of Comoros, where ACT has been in use since 2004. METHODS: A total of 207 P. falciparum clinical isolates were collected from the island during March 2006 and October 2007 (n = 118) and March 2013 and December 2014 (n = 89). All isolates were analysed for single nucleotide polymorphisms (SNPs) and haplotypes in the K13-propeller gene using nested PCR and DNA sequencing. RESULTS: Only three 2006-2007 samples carried SNPs in the K13-propeller gene, one having a synonymous (G538G) and the other having two non-synonymous (S477Y and D584E) substitutions leading to two mutated haplotypes (2.2%, 2/95). Three synonymous mutations (R471R, Y500Y, and G538G) (5.9%, 5/85) and 7 non-synonymous substitutions (21.2%, 18/85) with nine mutated haplotypes (18.8%, 16/85) were found in isolates from 2013 to 2014. However, none of the polymorphisms associated with artemisinin-resistance in Southeast Asia was detected from any of the parasites examined. CONCLUSION: This study showed increased K13-propeller gene diversity among P. falciparum populations on the Island over the course of 8 years (2006-2014). Nevertheless, none of the polymorphisms known to be associated with artemisinin resistance in Asia was detected in the parasite populations examined. Our data suggest that P. falciparum populations in Grande Comore are still effectively susceptible to artemisinin. Our results provide insights into P. falciparum populations regarding mutations in the gene associated with artemisinin resistance and will be useful for developing and updating anti-malarial guidance in Comoros.

[Inhibitory effects of vascular endothelial growth factor antibody on wear particle-induced osteolysis].

OBJECTIVE: To observe the effect of local injection of vascular endothelial growth factor (VEGF) and VEGF antibody on the wear particle-induced osteolysis in the mouse air pouch model and to investigate the role of VEGF in the process of aseptic loosening of prosthesis. METHODS: The stem of metal hip prosthesis was obtained from the revision surgery. Metallic wear particles were made by vacuum ball milling. Wear particles suspension was prepared into the concentration of 10 mg/mL with PBS. Fifty female Kunming mice (aged 8-10 weeks, weighing about 25 g) were selected. Of 50 mice, 10 were used as the donors of bone graft, the other 40 were equally divided into control group (group A), particle group (group B), VEGF group (group C), and VEGF inhibited group (group D). Air pouches were made on the back of 40 mice by injecting sterile air subcutaneously. At 8th day, a graft of calvaria from the donor mice was implanted in air pouch. In groups B, C, and D, 0.5 mL wear particles suspension was injected into the air pouches, and in group A, 0.5 mL PBS was injected. Once a day at 6th and 7th days during the air pouch preparation and one time every two days after bone implantation, 0.2 mL recombinant human VEGF (rhVEGF) and VEGF antibody (Bevacizumab) were injected into the air pouches in groups C and D, respectively. In group A and group B, 0.2 mL saline was injected. Pouch tissues and bone were harvested at 2 weeks after bone implantation for HE staining, real-time fluorescent quantitative PCR and ELISA analyses. RESULTS: All mice survived to the end of experiment. The gross observation showed that there were mild redness, swelling, and less neovascularization in air pouches in group A. There were obvious redness, swelling, and more exudative and neovascularization in groups B, C, and D, most obvious in group C, the next in group B, then in group D. The histological and molecular biological analysis showed that inflammatory responses and osteolysis were obvious in group B and the pouch membrane thickness, the cell density, transforming growth factor alpha, interleukin 1beta, and VEGF were significantly higher than those in group A (P < 0.05). The inflammatory responses and osteolysis were most obvious in group C and the above-mentioned indexes were significantly higher than those in group B (P < 0.05). There were some inflammatory responses and osteolysis in group D, but the indexes were significantly lower than those in group B (P < 0.05) and were significantly higher than those in group A (P < 0.05). CONCLUSION: VEGF can promote inflammatory responses and osteolysis in aseptic loosening of prosthesis. VEGF antibody can effectively inhibit wear particle-induced osteolysis.