IL1R2 polymorphisms and their interaction are associated with osteoporosis susceptibility in the Chinese Han population.

AIMS: Interleukin 1 (IL-1) inhibitory receptor type 2 (IL1R2) serves as a negative regulator of IL-1 signalling and is involved in the pathogenesis of osteoporosis. This study aimed to determine the correlation between IL1R2 polymorphism and osteoporosis susceptibility in the Chinese Han population. METHODS: We recruited 594 osteoporosis patients and 599 healthy controls. Six single nucleotide polymorphisms (SNPs) in IL1R2 were selected for genotyping using the Agena MassARRAY platform. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis with adjustment for age and sex. Linkage disequilibrium analysis was plotted using Haploview v4.2. Multifactor dimension reduction (MDR) was performed to estimate the SNP-SNP interactions of IL1R2 variants. RESULTS: Rs11674595 (OR = 1.86, p = 0.020), rs2072472 (OR = 1.26, p = 0.019) and rs4851527 (OR = 0.78, p = 0.007) were related to the risk of osteoporosis. Moreover, the contribution of IL1R2 polymorphisms to osteoporosis risk was associated with age, sex and body mass index. We found the relationships of Trs11674595 Ars4851527 (OR = 0.80, p = 0.015), Crs11674595 Grs4851527 (OR = 1.22, p = 0.043) and Ars3218977 Grs2072472 (OR = 1.25, p = 0.022) haplotypes to osteoporosis occurrence, and a potential accumulated effect of IL1R2 SNPs (testing accuracy = 0.5783 and cross validation consistency = 10/10) on osteoporosis susceptibility. CONCLUSION: IL1R2 polymorphisms (rs11674595, rs4851527, rs2072472 and rs3218977) may contribute to osteoporosis risk in the Chinese Han population. Our findings may increase our understanding of the effects of IL1R2 polymorphisms on the predisposition to osteoporosis.

Comparing the efficacy of pain managements after total hip arthroplasty: A network meta-analysis.

The aim of our current study is to compare efficiency of various interventions implemented for pain management after total hip arthroplasty (THA). PubMed and EMBASE were searched for randomized clinical trials (RCTs) reporting the pain scales for evaluate the efficacy of pain control after THA including at least one pair of direct control groups. Pain scale values and the associated 95% credible interval (CrI) were used to describe efficacy. Surface under the cumulative ranking curve (SUCRA) of each means of pain control was calculated to compare the relative ranking of different interventions. Thirty-five eligible literatures were involved in data analysis. The interventions for postoperative pain management we examined were psoas compartment block (PCB), posterior nerve block (PNB), fascia iliaca block (FIB), periarticular injection (PAI), femoral nerve block (FNB), lumbar plexus block (LPB), spinal anesthesia (SA), epidural analgesia (EPI), intrathecal morphine (IA), intravenous patient-controlled analgesia (IV-PCA), patient-controlled analgesia (PCA), onsteroidal anti-inflammatory drug (NSAID), local infiltration analgaesia (LIA), and reverse LIA (rLIA). In 0 to 6 hours analysis, patients under SA were found to have significantly lower pain score and SA was ranked the best. In 6 to 12 hours analysis, SA was found to be significantly more effective than other interventions and its SUCRA was the highest. No intervention showed a significant effect on reducing pain score for 12 to 24 hours and 24 to 48 hours after THA. SA is the best intervention to reduce THA postoperative pain in the first 24 hours. LPB is a better choice to reduce pain 12 to 48 hours after THA.

Poly (ADP-ribose) polymerase inhibitors combined with other small-molecular compounds for the treatment of ovarian cancer.

Ovarian cancer is a heterogeneous disease with complex molecular and genetic hallmarks. Benefitting from profound understanding of molecular mechanisms in ovarian cancer pathogenesis, novel targeted drugs have been actively explored in preclinical studies and clinical trials. Considered as one of the most potent and effective targeted therapies for the treatment of ovarian cancer, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) take advantages of synthetic lethality mechanisms to prevent DNA damage repair in cancer cells and cause their death, especially in cancers with BRCA mutations. Mounting evidence has indicated that the combination of PARPis with cytotoxic drugs or other targeted drugs has shown favorable synergistic effects. Excitingly, the antitumor activity of combination therapy of PARPis has been actively tested in multiple clinical trials and in-vitro or in-vivo experiments. In this review, we will briefly discuss the molecular mechanisms of PARPis combined with other therapeutic small-molecular compounds for the treatment of ovarian cancer.

Surgical site infection following elective orthopaedic surgeries in geriatric patients: Incidence and associated risk factors.

The purposes of this study were to investigate the incidence of surgical site infection (SSI) following geriatric elective orthopaedic surgeries and identify the associated risk factors This was a retrospective two-institution study. Between January 2014 and September 2017, patients aged 60 years or older undergoing elective orthopaedic surgeries were included for data collection and analysis. SSI was identified through the review of patients' medical records for the index surgery and through the readmission diagnosis of SSI. Patients' demographics, characteristics of disease, surgery-related variables, and laboratory examination indexes were inquired and documented. Univariate and multivariate logistic analyses were performed to determine independent risk factors for SSI. There were 4818 patients undergoing elective orthopaedic surgeries, and within postoperative 1 year, 74 patients were identified to develop SSIs; therefore, the overall incidence of SSI was 3.64%, with 0.4% for deep and 1.1% for superficial infection. Staphylococcus aureus (25/47, 53.2%) and coagulase-negative staphylococci (11/47, 23.4%) were the most common causative pathogens; half of S. aureus SSIs were caused by Methicillin-resistant Staphylococcus aureus (MRSA) (12/25, 48.0%). Five risk factors were identified to be independently associated with SSI, including diabetes mellitus (odds ratio [OR], 3.7; 95% confidence interval [95% CI], 1.7-5.6), morbid obesity (OR, 2.6; 95% CI, 1.3-3.9), tobacco smoking (OR, 4.2; 95% CI, 2.1-6.4), surgical duration>75th percentile (OR, 1.9; 95% CI, 1.0-2.9), and ALB < 35.0 g/L (OR, 2.3; 95% CI, 1.3-3.4). We recommend the optimisation of modifiable risk factors such as morbid obesity, tobacco smoking, and lower serum albumin level prior to surgeries to reduce the risk of SSI.

[ARTICLE WITHDRAWN] Study Brain Derived Neurotrophic Factor Gene Modified Schwann Cells Combined Chitosan Materials Treatment Peripheral Nerve Injury.

THIS ARTICLE WAS WITHDRAWN BY THE PUBLISHER IN January 2021.

NOD-like receptor signaling in inflammation-associated cancers: From functions to targeted therapies.

BACKGROUND: Recently, many studies have reported that some botanicals and natural products were able to regulate NOD-like receptor signaling. NOD-like receptors (NLRs) have been established as crucial regulators in inflammation-associated tumorigenesis, angiogenesis, cancer cell stemness and chemoresistance. NLRs specifically sense pathogen-associated molecular patterns and respond by activating other signaling regulators, including Rip2 kinase, NF-κB, MAPK and ASC/caspase-1, leading to the secretion of various cytokines. PURPOSE: The aim of this article is to review the molecular mechanisms of NOD-like receptor signaling in inflammation-associated cancers and the NLRs-targeted botanicals and synthetic small molecules in cancer intervention. RESULTS: Aberrant activation of NLRs occurs in various cancers, orchestrating the tissue microenvironment and potentiating neoplastic risk. Blocking NLR inflammasome activation by botanicals or synthetic small molecules may be a valuable way to prevent cancer progression. Moreover, due to the roles of NLRs in regulating cytokine production, NLR signaling may be correlated with senescence-associated secretory phenotype. CONCLUSION: In this review, we discuss how NLR signaling is involved in inflammation-associated cancers, and highlight the NLR-targeted botanicals and synthetic small molecules in cancer intervention.

Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy.

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.

Effect of emodin on chondrocyte viability in an in vitro model of osteoarthritis.

Emodin is an anthraquinone isolated from the Chinese herb Radix et Rhizoma Rhei and has been used to treat various diseases for centuries. The aim of the present study was to investigate the effect of emodin on the inflammatory mediators in rat chondrocytes. In the present study, chondrocytes were isolated from rats, cultured and harvested when they reached generation P3. Cells were treated with different doses of emodin (10, 20, and 30 µg/ml) followed by interleukin 1ß (IL-1ß, 10 ng/ml). Control cells were either untreated or treated with IL-1ß alone. An enzyme-linked immunosorbent assay was used to measure levels of nitric oxide (NO) and prostaglandin E2 (PGE2). Reverse transcription-quantitative polymerase chain was performed to measure levels of matrix metallopeptidase (MMP)-3 and -13 mRNA. The expression of MMP-3, MMP-13, extracellular-signal regulatory kinase (ERK)1/2, phosphorylated ERK1/2 and ß-catenin proteins were detected by western-blot analysis. The results demonstrated that treatment with emodin treatment reduced the cytotoxicity of IL-1ß and inhibited the expression of NO and PGE2 in rat chondrocytes. Furthermore, emodin inhibited the expression of MMP3 and MMP13, and the phosphorylation of various proteins involved in the ERK and Wnt/ß-catenin pathway. Therefore, emodin is able to promote the proliferation of chondrocytes by inhibiting the ERK and Wnt/ß-catenin pathway and downregulating the expression of a series of inflammatory mediators in chondrocytes.

Incidence and risk factors for infection in spine surgery: A prospective multicenter study of 1764 instrumented spinal procedures.

BACKGROUND: Surgical site infection (SSI) is a common complication in spinal surgery, imposing a high burden on patients and society. However, information about its characteristics and related risk factors is limited. We designed this prospective, multicenter study to address this issue. METHODS: From January 2015 through February 2016, a total of 1764 patients who had spinal trauma or degenerative spinal diseases were treated with instrumented surgeries and followed up for 1 year with complete data. Data on all patients were abstracted from electronic medical records, and SSIs were prospectively inspected and diagnosed by surgeons in our department. Any disagreement among them was settled by the leader of this study. SPSS 19.0 was used to perform the analyses. RESULTS: A total of 58 patients (3.3%, 58 of 1764) developed SSI; 1.1% had deep SSI, and 2.2% had superficial SSI. Of these, 60.6% (21 of 33) had a polymicrobial cause. Most of them (51 of 58) occurred during hospitalization. The median occurrence time was 3 days after operation (range: 1-123 days). SSI significantly prolonged hospital stays, by 9.3 days on average. The univariate analysis revealed reason for surgery as the only significant risk factor. The multivariate analysis, however, revealed 8 significant risk factors, including higher BMI, surgical site (cervical), surgical approach (posterior), surgery performed in summer, reasons for surgery (degenerative disease), autograft for fusion and fixation, and higher preoperative platelet level. CONCLUSION: Identification of these risk factors aids in stratifying preoperative risk to reduce SSI incidence. In addition, the results could be used in counseling patients and their families during the consent process.

[Expression, purification, and characterization of the first three immunoglobulin-like domains of human stem cell factor receptor].

OBJECTIVE: To express the first three immunoglobulin-like domains of human stem cell factor receptor (c-Kit/Ig1-3) in E. coli and HEK293 ET cells and study their binding activity for stem cell factor (SCF). METHODS: In prokaryotic expression system, a double mutant form of c-Kit /Ig1-3 (c-Kit /Ig1-3(DM) was produced by overlap PCR and cloned into pET16b. The recombinant protein was expressed in E. coli BL21 (DE3) and refolded by dilution. In eukaryotic expression system, the gene of c-Kit/Igl13 with eight histidine segments was cloned into pEAK12 and the recombinant plasmid was transfected into HEK293 ET cells. The fusion protein was harvested from the growth medium and purified on Ni-NTA agarose column. The recombinant protein was tested for the receptor binding activity with his-tag pull-down and enzyme-linked immunosorbent binding assay. RESULTS: In E. coli c-Kit /Ig1-3(DM) as produced as an inclusion body and showed low binding activity for SCF after refolding. Two HEK293 ET cell clones that express high levels of c-Kit/Ig1-3 were produced and each clone secreted 2p micro/ml of recombinant protein, whose relative molecular mass was about 58,000. Eukaryotically expressed c-Kit/Ig1-3 had specific binding activity for SCF, and the dissociation constant (Kd) was 9.39 nmol/L. CONCLUSION: c-Kit/Ig1-3 with high receptor binding activity is successfully produced in HEK293 ET cells.

Organophosphorus flame retardants and plasticizers: sources, occurrence, toxicity and human exposure.

Due to the restricted use and ban of brominated flame retardants, organophosphorus compounds (OPs), extensively used as flame retardants and plasticizers, are ubiquitous in various environmental compartments worldwide. The present study shows that the release of OPs from a wide variety of commercial products and wastewater discharge might be considered as primary emission sources and that high potential of long-range atmospheric transport and persistence of OPs would be responsible for their presence in various matrices on a global scale. The occurrence and environmental behaviors of OPs in diverse matrices (e.g., dust, air, water, sediment, soil and biota) are reviewed. Human exposures to OPs via dermal contact, dust ingestion, inhalation and dietary intake are comprehensively evaluated. Finally, this study identifies gaps in the existing issues and generates a future agenda for the emerging contaminants OPs.

[Comparison of clinical results between high-flexion and standard cruciate-stabling prostheses in total knee arthroplasty].

OBJECTIVE: To compare the clinical results between high-flexion and standard cruciate-stabling prostheses in total knee arthroplasty (TKA) by using the 36-item short form health survey (SF-36). METHODS: Between August 2007 and January 2009, 98 patients (106 knees) underwent TKA with standard cruciate-stabling prostheses (standard group), and 46 patients (50 knees) underwent TKA with high-flexion prostheses (high-flexion group). In standard group, there were 30 males (32 knees) and 68 females (74 knees) with an age of (70.0 +/- 3.5) years, including 78 cases (82 knees) of osteoarthritis (OA) and 20 cases (24 knees) of rheumatoid arthritis (RA) with a disease duration of (14.5 +/- 3.3) years; the Hospital for Special Surgery Scoring System (HSS) and the range of motion (ROM) were 56.1 +/- 21.6 and (89.0 +/- 16.1) degrees, respectively. In high-flexion group, there were 8 males (10 knees) and 38 females (40 knees) with an age of (68.6 +/- 8.9) years, including 44 cases (47 knees) of OA and 2 cases (3 knees) of RA with a disease duration of (13.9 +/- 4.1) years; the HSS and ROM were 58.9 +/- 25.3 and (91.0 + 19.3) degrees, respectively. There was no significant difference in the general data (P > 0.05) between 2 groups, so the clinical data of 2 groups had comparability. RESULTS: In standard group, poor wound healing and persistent headache caused by cerebrospinal fluid leakage occurred in 1 case, respectively. In high-flexion group, transient common peroneal nerve palsy occurred in 1 case. There was significant difference (P < 0.05) in the hospitalization expense between standard group [yen(39,000 +/- 6000)] and high-flexion group [yen (52,000 +/- 8 000)]. The follow-up time was 12-26 months (18 months on average) in standard group (91 cases, 98 knees) and 11-19 months (13 months on average) in high-flexion group (44 cases, 47 knees). The SF-36 showed significant difference in role-physical score (P < 0.05), but no significant difference in other 7 indices scores (P > 0.05). At the final follow- up, the ROM was (129.1 +/- 19.2) degrees in high-flexion group and (123.6 +/- 16.7) degrees in standard group; showing significant difference (P < 0.05). The HSS was 91.2 +/- 17.6 in high-flexion group and 92.5 +/- 14.5 in standard group; showing no significant difference (P > 0.05). CONCLUSION: After TKA, the ROM in high-flexion group is superior to that in standard group, but there is no obvious advantages in terms of the HSS and SF-36 outcomes.

Cloning and expression of human stem cell factor fused with thrombopoietin mimetic peptide in Escherichia coli.

Thrombopoietin (TPO) acts synergistically with stem cell factor (SCF) in hematopoiesis and megakaryopoiesis. In this work, we designed the expression of SCF fused with the monomer or the dimer of TPO mimetic peptide through a flexible peptide linker. The recombinant fusion proteins were produced in E. coli DH5alpha at up to 25% of total cell proteins. The resultant inclusion bodies were refolded by dilution and purified by ion-exchange chromatography. Subsequent biological activity assays showed that the fusion proteins exhibited higher potency than recombinant human SCF, indicating that they have a potential role for pharmaceutical applications.

High-level expression of human stem cell factor fused with erythropoietin mimetic peptide in Escherichia coli.

Stem cell factor (SCF) and erythropoietin are essential for normal erythropoiesis and induce proliferation and differentiation synergistically for erythroid progenitor cells. Here, we report our work on construction of SCF/erythropoietin mimetic peptide (EMP) fusion protein gene, in which human SCF cDNA (1-165aa) and EMP sequence (20aa) were connected using a short (GGGGS) or long (GGGGSGGGGGS) linker sequence. The SCF/EMP gene was cloned into the pBV220 vector and expressed in the Escherichia coli DH5alpha strain. The expression level of the fusion protein was about 30% of total cell protein. The resulting inclusion bodies were solubilized with 8 M urea, followed by dilution refolding. The renatured protein was subsequently purified by Q-Sepharose FF column. The final product was >95% pure by SDS-PAGE and the yield of fusion protein was about 40 mg/L of culture. UT-7 cell proliferation and human cord blood cell colony-forming assays showed that the fusion proteins exhibited more potent activity than recombinant human SCF, suggesting a new strategy to enhance biological activities of growth factors.