LncRNA LINC00205 stimulates osteoporosis and contributes to spinal fracture through the regulation of the miR-26b-5p/KMT2C axis.

BACKGROUND: Osteoporosis (OP) is a common bone disease marked by decreased bone strength. Increasing evidence suggests that long non-coding RNA (lncRNAs) play important roles in the occurrence and progression of OP. This study aimed to investigate the role and mechanism of LINC00205 in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and OP. METHODS: Bone tissue samples were obtained from healthy controls and patients with osteoporosis with a spinal fracture (OP-Frx) or without a spinal fracture (OP-no-Frx). HMSCs were cultured and induced to undergo osteogenic differentiation. The expression of LINC00205, lysine (K)-specific methyltransferase 2C (KMT2C), and miR-26b-5p in bone tissues and cells was evaluated using western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of LINC00205, miR-26b-5p, and KMT2C on calcium deposition, alkaline phosphatase (ALP) activity, and mRNA levels of the osteogenic differentiation marker genes [ALP, osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2)] were investigated using alizarin red S staining, an ALP activity assay, and qRT-PCR, respectively. Dual-luciferase reporter assay was performed to ascertain the binding relationship between miR-26b-5p and LINC00205/KMT2C. RESULTS: LINC00205 and KMT2C were upregulated in patients with OP-Frx and OP-no-Frx, whereas miR-26b-5p was downregulated. Furthermore, LINC00205 and KMT2C expression decreased, whereas that of miR-26b-5p increased over time from day 7 to 21 of the osteogenic differentiation of hMSCs. The knockdown of LINC00205 and KMT2C significantly increased ALP activity, calcium deposition, and the expression of RUNX2, ALP, and OCN. In contrast, the inhibition of miR-26b-5p yielded the opposite result. These data suggest that LINC00205 inhibits the osteogenic differentiation of hMSCs by modulating the miR-26b-5p/KMT2C signaling axis. CONCLUSION: LINC00205 promotes OP and is involved in spinal fractures. LINC00205 is also a potential negative regulator of the osteogenic differentiation of hMSCs.

Outcome of Percutaneous Transforaminal Endoscopic Lumbar Decompression for Multisegment Lumbar Spinal Stenosis and the Effect on VAS Scores.

Purpose: To investigate the efficacy of percutaneous transforaminal endoscopic lumbar decompression (PTED) in the treatment of multisegment lumbar spinal stenosis (LSS) and its effect on VAS scores. Methods: 126 patients with multisegment LSS admitted between August 2017 and August 2021 were selected and divided into the PTED group and the traditional open surgery group (TOS group) according to the different treatment methods. There were 70 cases in the PTED group, treated with PTED, and 56 cases in the TOS group, treated with traditional open surgery. The clinical outcomes, the preoperative and postoperative pain visual analogue scale (VAS), the Oswestry disability index (ODI), the SF-36 quality of life questionnaire scores, the perioperative indicators (operative time, days in hospital, intraoperative blood loss), the postoperative complications, and imaging data were compared between the two groups. Results: After the operation, the excellent and good rate in the PTED group (91.43%) was significantly higher than that in the TOS group (75.00%) (P < 0.05). At each time after the operation, the VAS and ODI scores of the two groups were lower than those before the operation, and the VAS scores of the PTED group at 1 day and 3 months after operation were lower than those of the TOS group, and the ODI scores of the PTED group at 3 months after operation were lower than those of the TOS group (P < 0.05). 3 months after the operation, the SF-36 scores in both groups were higher than those before the operation, and those in the PTED group were higher than those in the TOS group (P < 0.05). The operation time and days in hospital in the PTED group were shorter than those in the TOS group, and the intraoperative dominant blood loss and recessive blood loss were less than those in the TOS group (P < 0.05). The total incidence of complications in the PTED group (15.71%) was significantly lower than that in the TOS group (32.14%) (P < 0.05). Conclusion: Both PTED and traditional open surgery are effective in treating patients with multisegmental LSS, and both show positive postoperative changes in all indicators, but the former has more promising near -term results in improving lumbar spine pain, function and quality of life than the latter, and has the advantages of less trauma, less bleeding, and fewer complications.

Genistein attenuates LPS-induced inflammatory injury of rat dorsal root ganglion neuron via down-regulating HDAC6. / é‡‘é›€å¼‚é»„ç´ é€šè¿‡ä¸‹è°ƒHDAC6减轻LPSè¯±å¯¼çš„å¤§é¼ èƒŒæ ¹ç¥žç»èŠ‚ç¥žç»å ƒç‚Žæ€§æŸä¼¤.

OBJECTIVES: Neuropathic pain (NP) is a chronic pain caused by somatosensory neuropathy or disease, and genistein (Gen) might be a potential drug for the treatment of NP. Therefore, this study aims to investigate the effect of Gen on lipopolysaccharide (LPS)-induced inflammatory injury of dorsal root ganglion neuron (DRGn) in rats and the possible molecular mechanism. METHODS: The DRGn of 1-day-old juvenile rats were taken for isolation and culture. The DRGn in logarithmic growth phase were divided into a control group, a LPS group, a tubastatin hydrochloride (TSA)+LPS group, a Gen1+LPS group, a Gen2+LPS group, a Gen2+LPS+TSA group, a Gen2+pcDNA-histone deacetylase 6 (HDAC6)+LPS group, and a Gen2+pcDNA3.1+LPS group. The LPS group was treated with 1 µg/mL LPS for 24 h; the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group were treated with 5 µmol/L TSA, 5 µmol/L Gen, 10 µmol/L Gen respectively for 0.5 h, and then added 1 µg/mL LPS for 24 h; the Gen2+TSA+LPS group was treated with 10 µmol/L Gen and 5 µmol/L TSA for 0.5 h and then added 1 µg/mL LPS for 24 h; the Gen2+pcDNA-HDAC6+LPS group and the Gen2+pcDNA3.1+LPS group received 100 nmol/L pcDNA-HDAC6 and pcDNA3.1 plasmids respectively, and 24 h after transfection, 10 µmol/L Gen was pretreated for 0.5 h, and then added 1 µg/mL LPS for 24 h. Real-time RT-PCR was used to detect the HDAC6 mRNA expression in DRGn; CCK-8 method was used to detect cell viability of DRGn; flow cytometry was used to detect cell apoptosis of DRGn; ELISA was used to detect the levels of IL-1ß, IL-6, and TNF-α in DRGn culture supernatant; Western blotting was used to detect the protein expression of HDAC6, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κB p65 in DRGn. RESULTS: Compared with the control group, the expression levels of HDAC6 mRNA and protein, the expression levels of TLR4 and MyD88 protein in DRGn of LPS group rats were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, and the activity of DRGn was significantly decreased, the apoptosis rate was significantly increased, and the levels of IL-1ß, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05). Compared with the LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group and the Gen2+TSA+LPS group were significantly down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly decreased, the activity of DRGn was significantly increased, the apoptosis rate was significantly decreased, and the levels of IL-1ß, IL-6 and TNF-α in the DRGn culture supernatant were significantly decreased (all P<0.05), and the above changes were most obvious in the Gen2+TSA+LPS group. Compared with the Gen2+LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the Gen2+pcDNA-HDAC6+LPS group were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, the activity of DRGn was significantly decreased, and the apoptosis rate was significantly increased, and the levels of IL-1ß, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05). CONCLUSIONS: Gen can alleviate LPS-induced DRGn inflammatory injury in rats, which might be related to down-regulating the expression of HDAC6 and further inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.

Customized treatment protocols for patients with closed fracture in hospitals at varying coronavirus disease 2019 (COVID-19) risk.

BACKGROUND: To determine an optimized treatment protocol during the COVID-19 epidemic for patients with closed fracture and delayed surgery. METHODS: The epidemic data of three hospitals, randomly selected from different administrative regions of Wuhan, were analyzed retrospectively from 23 January to 31 March 2020. Changes in the number of confirmed cases per day (cumulative and new) of each region were tracked as a reflection of changing epidemic risk levels. The risk level map was drawn. The epidemic status, treatment protocols, and treatment efficiencies for patients with closed fracture in the three hospitals were compared. RESULTS: Overall, 138 patients with closed fracture were admitted. Each hospital had established its own protocol, according to the initial perceived risk. Based on the risk level map, over the study period, the risk levels of the three regions changed independently and were not in sync. All patients recovered and were timely discharged. No staff member was detected with COVID-19. CONCLUSIONS: The COVID-19 risk level of each area is dynamic. To optimize medical resources, avoid cross-infection, and improve efficiency, changes in epidemic risk should be monitored. For patients with closed fracture, treatment protocols should be adjusted according to changes in epidemic risk.

Child compound Endothelium corneum attenuates gastrointestinal dysmotility through regulating the homeostasis of brain-gut-microbiota axis in functional dyspepsia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. MATERIALS AND METHODS: FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. RESULTS: CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CONCLUSION: CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment.

Association between heme oxygenase-1 gene promoter polymorphisms and cancer susceptibility: A meta-analysis.

Numerous studies have focused on the association between heme oxygenase-1 (HO-1) gene promoter polymorphisms and susceptibility to cancer; however, results remain ambiguous. The present systematic Human Genome Epidemiology review and meta-analysis aimed to clarify this association. A systematic search was used to assess the association of HO-1 gene polymorphisms with cancer susceptibility in the PubMed, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure databases, with all reviewed studies published before April 10, 2017. Review Manager 5.3 and Stata 12.0 software were used to perform the meta-analysis. A total of 14 studies were included in the analysis. Overall, no significant associations of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility were identified. However, subgroup analyses by ethnicity and cancer type indicated that the LL and L-allele (LL+LS) genotypes of HO-1 (GT)n were associated with increased susceptibility to cancer compared with the SS+SL and SS genotypes in the following subgroups: East Asian [LL+LS vs. SS: odds ratio (OR)=1.51, 95% confidence interval (CI)=1.11-2.05, P=0.0003; LL vs. SS+SL: OR=1.44, 95% CI=1.04-2.01, P=0.03; LL vs. SS: OR=1.64, 95% CI=1.07-2.52, P=0.02]; squamous cell carcinoma (LL+LS vs. SS: OR=1.78, 95% CI=1.35-2.34, P<0.05; LL vs. SS+SL: OR=1.71, 95% CI=1.34-2.18, P<0.05; LL vs. SS: OR=2.26, 95% CI =1.62-3.14, P<0.05); and digestive tract cancer + East Asian (LL+LS vs. SS: OR=1.56, 95% CI=1.22-1.98, P<0.05; LL vs. SS: OR=1.80, 95% CI=1.06-3.05, P<0.05). These findings indicated that there was no association of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility, while the L-allele genotypes (LL and LS) of HO-1 (GT)n may be susceptibility factors for cancer in East Asian, digestive tract cancer in East Asian and squamous cell carcinoma populations. Due to limitations of the reviewed studies, additional large-scale and refined studies are now required to confirm the present findings.

[Development of measurement and control technologies for hyperthermia treatments of tumors with AC magnetic field].

Hyperthermia therapy with AC magnetic field heating magnetic nanoparticles is a new kind of treatment method. The paper reviews the research progresses about AC magnetic heating setups for hyperthermia therapy measurements of magnetic field temperature control, and so on.