Hsa_circ_0001485 promoted osteogenic differentiation by targeting BMPR2 to activate the TGFß-BMP pathway.

BACKGROUND: Circular RNAs (circRNAs) are a new type of stable noncoding RNA and have been proven to play a crucial role in osteoporosis. This study explored the role and mechanism of hsa_circ_0001485 in osteogenic differentiation. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) enrichment analysis were performed according to the previous sequencing data in human bone marrow mesenchymal stem cells (BMSC) before and after the induction of osteogenic differentiation on the differentially expressed circRNAs, to screen out signaling pathways associated with osteogenic differentiation. The hFOB 1.19 cells were used to verify the function and mechanism of specific circRNAs in osteogenic differentiation. Additionally, small interfering fragments and overexpression plasmids were used to determine the role of specific circRNAs during osteogenic differentiation. Furthermore, pull-down experiments and mass spectrometry were performed to determine the proteins that bind to specific circRNAs. RESULTS: The KEGG and GO enrichment analyses showed that the TGFß-BMP signaling pathway was related to the osteogenic differentiation process, and four circRNAs were associated with the pathway. The quantitative polymerase chain reaction analysis revealed that hsa_circ_0001485 expression was increased during the osteogenic differentiation process of BMSCs. Knockdown of hsa_circ_0001485 suppressed the activity of the alkaline phosphatase enzyme and the expression of RUNX2, osteopontin, and osteocalcin in the osteogenic hFOB 1.19 cells, whereas overexpression of hsa_circ_0001485 promoted their expression. Additionally, we found that hsa_circ_0001485 and BMPR2 targeted binding to activate the TGFß-BMP signaling pathway and promoted osteogenic differentiation through mass spectrometry analysis. CONCLUSION: This study demonstrates that hsa_circ_0001485 is highly expressed in the osteogenic hFOB 1.19 cells, which activate the TGFß-BMP pathway through targeted binding of BMPR2, and plays a positive role in regulating osteogenic differentiation.

[Meta-analysis of calcium chemotherapeutic effect of anterior cervical subtotal vertebroplasty and posterior laminoplasty].

OBJECTIVE: To systematically assess the efficacy of anterior cervical corpectomy and fusion (ACCF) versus posterior laminoplasty (LAMP) for cervical ossification of posterior longitudinal ligament (OPLL). METHODS: PubMed and EMBASE, Cochrane Library, CBM, CNKI, Wanfang and VIP were collected from 7 databases of ACCF, LAMP from 1970 to May 2018. According to the criteria, the articles were included and independently screened by two authors. The quality of the articles was assessed by using the MINORS scale (methodological index for non randomized studies). After extracting the data from the article, the JOA score, cervical curvature, operation time, bleeding volume, excellent and good rate, recovery rate, adverse events and secondary surgery were analyzed by using Review Manager 5.3 software. RESULTS: Finally, a total of 22 articles with 1 678 patients were included in this Meta-analysis, with 810 patients in ACCF group and 868 patients in LAMP group. Meta analysis results showed that the ACCF group had higher postoperative JOA scores[MD=0.63, 95%CI(0.05, 1.20), P= 0.03], higher excellent rate [OR=1.85, 95%CI (1.14, 3.02), P=0.01] and higher recovery rate [OR=11.90, 95%CI (5.75, 18.05), P=0.000 1]. But the LAMP group has a shorter operative time [MD=52.19, 95%CI (29.36, 75.03), P<0.000 01], less complications [OR=1.56, 95%CI (1.03, 2.35), P=0.04] and less reoperations [OR=3.73, 95%CI (1.62, 8.57), P=0.002]. There was no significant different in postoperative lordosis [MD=3.15, 95%CI(-0.14, 6.43), P=0.06] and blood loss[SMD= 0.26, 95%CI(-0.05, 0.57), P=0.10] between two groups. CONCLUSION: The recovery of functionof ACCF group was better, but operation time, complications and reoperations of LAMP group were all better than ACCF group. There was no difference in postoperative lordosis and intraoperative blood loss between two groups. However, there are some limitations in this study. Therefore, higher quality and larger sample size clinical studies are needed to further verify.

[Auxiliary analgesic effect of wrist-ankle acupuncture on patients undergoing transforaminal endoscope surgery].

OBJECTIVE: To observe the auxiliary analgesic effect of wrist-ankle acupuncture on patients undergoing transforaminal endoscope surgery. METHODS: A total of 64 patients with lumbar disc herniation who underwent percutaneous lateral transforaminal endoscope surgery were randomly divided into an observation group and a control group, 32 cases in each group. The patients in the control group were treated with injection of 1% lidocaine for routine local infiltration anesthesia. The patients in the observation group were treated with wrist-ankle acupuncture at lower 5 area and lower 6 area for 30 min, 5 min before routine local infiltration anesthesia; immediately, 15 min, 30 min after insertion the left-right technique, up-down technique, and rotation technique were applied for six times, respectively. The mean arterial pressure (MAP), heart rate (HR), blood oxygen saturation (SpO2) and pain visual analogue scale (VAS) were compared between the two groups at the time points of intraoperative puncture (T1), circular saw grinding (T2), and placement of working channel (T3). The intention of reoperation was recorded immediately after operation and 24 h after operation. The expectation and treatment credibility scale (ETCS) was used to evaluate the relationship between patients' expectation and efficacy 5 min before operation and immediately after operation. RESULTS: At T2 and T3 during the operation, the MAP and HR in the obserrvation group were lower than those in the control group, while SpO2 was higher than that in the control group (P<0.05). At T1, there was no significant difference of MAP, HR and SpO2 between the two groups (P>0.05). At T2, the peak VAS and average VAS in the observation group were lower than those in the control group (P<0.05), but there was no significant difference at T1 and T3 (P>0.05). The intention of reoperation in the observation group was higher than that in the control group both immediately after operation and 24 h after operation (P<0.05). In the observation group, the scores of each item in ETCS immediately after operation were higher than those 5 min before operation (P<0.05), while in the control group there was no significant difference between immediately after operation and 5 min before operation (P>0.05). The scores of ETCS1, ETCS2 and ETCS3 immediately after operation in the observation group were higher than those in the control group (P<0.05). CONCLUSION: The wrist-ankle acupuncture has positive auxiliary analgesic effect on lumbago during transforaminal endoscope surgery, and strengthens the patients' confidence on the operation effect.

Review: Autologous blood transfusion drainage compared with no drainage in total knee arthroplasty: A meta-analysis and systematic review.

This is the first meta-analysis to assess the clinical efficiency, safety and potential advantages regarding the use of ABT drains compared with no drainage which is controversial in total knee arthroplasty (TKA).A comprehensive literature search was carried out in March 2015 using the PubMed, Embase, and Cochrane Library databases. A metaanalysis was carried out on two retrospective comparative studies (RCSs) and five randomized controlled trials (RCTs). The number of patients receiving homologous blood transfusion was the primary outcome of the meta-analysis; the secondary outcome measure was the mean drop in Hb level in comparison to the mean pre-operative HB level, the range of flexion of the knee joint, and infections of the wound after surgery. A total of 868 patients, who were included in two retrospective studies and five RCTs, were distributed into subgroups for the meta-analysis. This pooled data showed no benefit of ABT drainage compared no drainage in the homologous blood transfusion rate (13.05% and 16.91%, OR:0.73[0.47,1.13], Z=1.41, P=0.016; and 3.49% and 6.54%, OR: 0.50[0.12,2.01], Z=0.98,P=0.033,respectively in subgroups), Hb drop (Weight mean differences (WMD): 0.20[-0.28,0.68], Z=0.82, P=0.41; WMD:0.16[-0.41,0.55], Z=0.93, P=0.35, respectively), range of flexion of the knee joint (WMD:-0.82 [-3.35,1.70], Z =0.64,P=0.52)and wound infection (OR:0.25[0.61,10.20]; Z =1.28, p=0.2) after TKA surgery. Our findings do not recommend the routine use of postoperative ABT drainage in total knee arthroplasty. Well-designed RCTs with large sample sizes, longer term measures and extensive follow-up period should be performed in the future to update the findings of this study.

Treating metastatic triple negative breast cancer with CD44/neuropilin dual molecular targets of multifunctional nanoparticles.

Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved components for treating metastatic triple negative breast cancer (TNBC). The enhanced specific targeting of tLyP-1-HT NPs to both metastatic tumor cells and metastasis-supporting tumor neovasculature was contributed by means of CD44/neuropilin dual receptor-mediated interaction. The NPs not only effectively suppress the invasive capability of tumor cells themselves, but also significantly restrain the metastasis incidence via extravasation as well as the eventual colonization in lungs. In all the three types of TNBC-bearing mice models, orthotopic, post-metastasis and metastasis prevention models, the docetaxel-loaded tLyP-1-HT NPs exhibited markedly enhanced anti-tumor and anti-metastasis efficacy. The inhibitory rates of tLyP-1-HT NPs against orthotopic tumor growth and lung metastasis achieved 79.6% and 100%, respectively. The metastasis inhibition rate and life extension rate of the tLyP-1-HT NPs against post-pulmonary metastasis mice reached 85.1% and up to 62.5%, respectively. All the results demonstrated the designed dual receptor-targeting multifunctional NPs hold great potential in treating metastatic TNBC and lung metastasis.

Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity.

Low density lipoprotein (LDL), which is a principal carrier for the delivery of cholesterol, has been used as a great candidate for the delivery of drugs to tumor based on the great requirements for cholesterol of many cancer cells. Mimicking the structure and composition of LDL, we designed a synthetic low-density lipoprotein (sLDL) to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. The PALA loaded sLDL (PALA-sLDL) and PALA-loaded microemulsion (PALA-ME, without the binding domain for LDLR) displayed uniform sizes with high drug loading efficiency (> 90%). In vitro studies demonstrated PALA-sLDL exhibited enhanced cellular uptake capacity and better cytotoxicity to LDLR over-expressed U87 MG cells as compared to PALA-ME. The uptake mechanisms of PALA-sLDL were involved in a receptor mediated endocytosis and macropinocytosis. Furthermore, the in vivo biodistribution and tumor growth inhibition studies of PALA-sLDL were investigated in xenograft U87 MG tumor-bearing mice. The results showed that PALA-sLDL exhibited higher tumor accumulation than PALA-ME and superior tumor inhibition efficiency (72.1%) compared to Taxol® (51.2%) and PALA-ME (58.8%) but with lower toxicity. These studies suggested that sLDL is potential to be used as a valuable carrier for the selective delivery of anticancer drugs to tumor with low systemic toxicity.

[Mercury Distribution Characteristics and Atmospheric Mercury Emission Factors of Typical Waste Incineration Plants in Chongqing].

Waste incineration is one of the important atmospheric mercury emission sources. The aim of this article is to explore the atmospheric mercury pollution level of waste incineration industry from Chongqing. This study investigated the mercury emissions from a municipal solid waste incineration plant and a medical waste incineration plant in Chongqing. The exhaust gas samples in these two incineration plants were obtained using USA EPA 30B method. The mercury concentrations in the fly ash and bottom ash samples were analyzed. The results indicated that the mercury concentrations of the municipal solid waste and medical waste incineration plant in Chongqing were (26.4 +/- 22.7) microg x m(-3) and (3.1 +/- 0.8) microg x m(-3) in exhaust gas respectively, (5279.2 +/- 798.0) microg x kg(-1) and (11,709.5 +/- 460.5) microg x kg(-1) in fly ash respectively. Besides, the distribution proportions of the mercury content from municipal solid waste and medical waste in exhaust gas, fly ash, and bottom ash were 34.0%, 65.3%, 0.7% and 32.3%, 67.5%, 0.2% respectively; The mercury removal efficiencies of municipal solid waste and medical waste incineration plants were 66.0% and 67.7% respectively. The atmospheric mercury emission factors of municipal solid waste and medical waste incineration plants were (126.7 +/- 109.0) microg x kg(-1) and (46.5 +/- 12.0) microg x kg(-1) respectively. Compared with domestic municipal solid waste incineration plants in the Pearl River Delta region, the atmospheric mercury emission factor of municipal solid waste incineration plant in Chongqing was lower.

[Gut microbiota and osteoporosis].

OBJECTIVE: The rapidly evolving aging society in China is associated with increased incidences of osteoporosis and fractures, which have become common health problems that threaten the quality of life of the elderly. Gut microbiota colonizing in the human intestinal tract form a mutual symbiotic relationship with the host and play an important role in the metabolism and immune regulation of the host. In recent years increasing studies have demonstrated that gut microbiota not only affect the digestive system but also contribute to the disease conditions involving the immune system, and have a close relationship with the occurrence and progression of osteoporosis. This review summarizes the progress and hotspots in recent researches of the associations among gut microbiota, the immune system, osteoporosis.

[Mercury Emission Characteristics and Mercury Concentrations of Municipal Solid Waste in Waste Incineration Plants].

Municipal solid waste (MSW) incineration is one of the most important atmospheric mercury emission sources. To investigate the mercury concentrations of MSW and mercury emission characteristics in incineration plants, this study analyzed the MSW sampled in 3 typical MSW incineration plants in Shanghai, Guangzhou and Wuhu respectively. The exhaust gas samples in incineration plants were sampled by using OH (Ontario Hydro) method. The mercury concentrations in fly ash, and bottom ash samples were also analyzed. The results indicated that mercury concentrations of MSW in Shanghai, Guangzhou, and Wuhu incineration plants were (0.39±0.04) mg·kg-1, (0.57±0.05) mg·kg-1, and (0.27±0.08) mg·kg-1 respectively. The mercury concentrations of exhaust gas in Guangzhou, Wuhu MSW incineration plants were (9.5±3.9) µg·m-3 and (24.1±6.0) µg·m-3 respectively; Particulate mercury (Hgp), gaseous oxidized mercury (Hg2+), and gaseous elemental mercury (Hg0) represented (0.9±0.8)%, (89.0±5.4)%, (10.1±4.6)% in Guangzhou MSW incineration plant, and (1.0±0.8)%, (65.4±27.6)%, (33.6±27.5)% in Wuhu MSW incineration plant, respectively. Gaseous oxidized mercury (Hg2+) of exhaust gas in different incineration process showed different distribution proportions. Besides, mercury removal efficiency of Guangzhou, Wuhu MWS incineration plants was 96.7% and 33.7%, respectively. The atmospheric mercury emission factors of Shanghai, Guangzhou, and Wuhu MSW incineration plants were (0.156±0.016) mg·kg-1, (0.019±0.002) mg·kg-1, (0.178±0.027) mg·kg-1 respectively. Compared with MSW incineration plants in Japan and Korea, the atmospheric mercury emission factor of Guangzhou incineration plant was slightly lower; Atmospheric mercury emission factors of Shanghai and Wuhu MSW incineration plants were close to those of domestic fractional MSW incineration plants.

Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers.

Poor site-specific delivery and incapable deep-penetration into tumor are the intrinsic limitations to successful chemotherapy. Here, the tumor-homing penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs), composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean diameter, high drug encapsulation efficiency (93%), and sustained drug release behavior. In vitro studies demonstrated that the tLPTS/HATS NPs exhibited enhanced intracellular delivery and much better anti-invasion ability, cytotoxicity, and apoptosis against both invasive PC-3 and MDA-MB-231 cells as compared to the non-tLyP-1-functionalized HATS NPs. The remarkable penetrability and inhibitory effect on both PC-3 and MDA-MB-231 multicellular tumor spheroids were also identified for the tLPTS/HATS NPs. In vivo biodistribution imaging demonstrated the tLPTS/HATS NPs possessed much more lasting accumulation and extensive distribution throughout tumor regions than the HATS NPs. The higher in vivo therapeutic efficacy with lower systemic toxicity of the tLPTS/HATS NPs was also verified by the PC-3 xenograft model in athymic nude mice. These results suggested that the designed novel tLPTS/HATS NPs were endowed with tumor recognition, internalization, penetration, and anti-invasion, and thus might be a promising anticancer drug delivery vehicle for targeted cancer therapy.

[An experimental study on the prevention of enteral bacterial translocation in scalded rats by smectite powder].

OBJECTIVE: To explore the preventive and treatment effects of smectite powder on enteral bacterial translocation in scalded rats. METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three groups, i.e. normal control (A, n = 6), burn control (B, n = 24), and burn treatment (T, n = 24) groups. The rats in B and T groups were fed with tracing bacteria JM109, which was transfected with PUC19 plasmid in advance. The rats were subjected to 30% TBSA scald injury after the plasmid was shown to have colonized in the intestine. Smectite powder (0.6 g/day/kg) was fed to rats of T group immediately after the scalding, while those in B group received no smectite powder. Bacterial translocation in blood and mesenteric lymph nodes in all groups was observed and identified by enzyme digestion at 12 post scald hour (PSH) and on 1, 3 and 5 post-scald days (PSD). The contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in rat intestinal tissue. And the degree of injury to the entire small intestine was observed pathologically. The villus height of intestinal mucosa was measured, and the rate of epithelial nuclear splitting of mucosal crypts was calculated. RESULTS: The number of rats with positive blood bacterial culture in B group was obviously higher than that in A and T groups (P < 0.05) on 1 and 5 PSD. The bacterial quantity in mesenteric lymph nodes (MLN) in T group on 1 PSD (38 +/- 16 CFU/g) and 5 PSD (68 +/- 20 CFU/g) were obviously lower than those in B group (228 +/- 67 vs 183 +/- 29 CFU/g, P < 0.05). There was significant difference in the intestinal contents of MDA and SOD between B and T groups at each time point (P < 0.05). The rat jejunum villus height and the epithelial nuclear splitting in the small intestine mucosa in T group were evidently higher than those in B group (P < 0.05 or 0.01). CONCLUSION: Smectite powder is beneficial to the protection of the intestinal mucosa in scalded rats, and can effectively prevent postburn intestinal bacterial translocation in rats.

[Clinical study on the relationship among the dermis, fat dome and postburn hyperplastic scar formation].

OBJECTIVE: To explore the influence of dermal defect and fat dome structure destruction in burn wounds on the formation of hyperplastic scar. METHODS: Fifty two wounds in 24 burn patients with deep partial thickness burn indicating tangential excision in the extremities were enrolled in the study, and they were divided into three groups according to the extent of exposure of dermal fat granules, i.e. A (without fat exposure), B (with little fat exposure) and C (with much fat exposure) groups. These three groups were subdivided into A1 (without grafting), A2 (grafting with razor thin skin), B1 (without grafting), B2 (with razor thin skin grafting), C1 (without grafting) and C2 (with split-thickness skin grafting) groups, with 9 wounds in each group. The dermal depth and exposure rate of the fat granules in each group were measured and analyzed by KS400 photography analysis apparatus. The follow-up conditions of the scars 6 months after operation were evaluated with Vancouver remark system by Vancouver score assessment. RESULTS: There was obvious difference in the dermal depth and exposure rate of the fat granules among all the groups (P < 0.05 or 0.01). The fat exposure rate was positively correlated with the extent of the dermal defect (gamma = 0.554, P < 0.05). The Vancouver score in group A was lower than that in B and C groups (P < 0.05), while that in B1 group (3.714 +/- 2.498) was evidently higher than that in other groups (P < 0.01). The scar score was lowered when the wounds were grafted with the dermis with its thickness similar to the depth of the defect, The scar score was increased along with the elevation of fat exposure rate (P < 0.05). CONCLUSION: There was a positive correlation between the degree of dermal defect and that of hyperplastic scar after burns. The disruption of fat dome structure might also be an important factor in the scar development.

[The influence of dermal template application on the p53 gene expression and apoptosis during wound repairing in burn patients].

OBJECTIVE: To observe dynamically the influence of the application of dermal template on the p53 gene expression and apoptosis during wound repairing in burn patients. METHODS: Twenty burn patients were enrolled in the study and were divided into experiment (E, n = 11) and control (C, n = 9) groups. The escharectomy wounds in patients with 3rd degree burn in E group were covered with dermal template overlain with thin split-thickness autograft, while those in C group were covered with thin split-thickness autograft only. Specimens were harvested from wounds of both groups at 1st, 2nd, 3rd, 4th and 5th post operative week (POW). The P53 expression and the apoptosis were assessed respectively by immunohistochemistry and by TUNEL kit. The change in cell number was observed after HE staining. RESULTS: The P53 expression increased gradually along with the wound healing process from 1st to 4th POW, which was significantly higher than that in C group at 2nd, 3rd, and 4th POW (P < 0.05), and it reached the peak at 4th POW. Fibroblasts underwent apoptosis at 1st POW in E group, while apoptosis of the endothelial cells occurred mainly at 2nd and 3rd POW. There was obvious difference in the rate of apoptosis between the two groups in 3rd and 4th POW (P < 0.05). The numbers of fibroblasts and vascular endothelial cells in E group were smaller than those in C group. CONCLUSION: Application of dermal template overlain with thin split-thickness autograft to wounds could induce P53 expression and cell apoptosis, thereby reduce scar formation, resulting in improvement of the quality of wound healing.