The effect of preoperative different dexamethasone regimens on postoperative glycemic control in patients with type 2 diabetes mellitus undergoing total joint arthroplasty: a retrospective cohort study.

BACKGROUND: Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA. METHODS: This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified. RESULTS: Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl. CONCLUSIONS: Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl.

[Fingerprint of sophorolipids based on ultra-high performance liquid chromatography-charged aerosol detection].

Sophorolipids are secondary metabolites produced during fermentation by nonpathogenic yeasts. These molecules are amphiphilic and consist of a hydrophilic sophora sugar moiety and a hydrophobic hydroxylated fatty acid. Based on their degree of esterification, sophorolipids can be divided into the acid and lactone types. Sophorolipids are highly promising biosurfactants with good antibacterial, antiviral, and other biological activities. Moreover, they are characterized by mildness, low toxicity, and environmental friendliness. However, their composition is quite complex, and effective methods for their quality evaluation are lacking. Since sophorolipids do not absorb ultraviolet (UV) light, common UV detectors are unsuitable for fingerprint establishment. In this study, we first selected a charged aerosol detector (CAD) to establish the ultra-high performance liquid chromatography (UHPLC) fingerprint of sophorolipids. The detector had high sensitivity, good reproducibility, and excellent suitability for the detection of substances with no or weak ultraviolet absorption. We then evaluated the similarities between 17 batches of sophorolipid samples. The samples were extracted by ultrasound for 10 min in 80% ethanol aqueous solution at a liquid-solid ratio of 10∶1 (mL/g) and then separated on a Thermo Fisher Scientific Hypersil Gold chromatographic column (150 mm×2.1 mm, 1.9 µm). Separation was performed using acetonitrile-0.01% (v/v) formic acid aqueous solution as the mobile phase via gradient elution. The flow rate was 0.2 mL/min, and the column temperature was 40 ℃. The CAD was used under the following conditions: power function of 1.0, data rate of 5 Hz, filter constant of 3.6, and evaporation temperature of 45 ℃. The chromatograms and retention times of the sophorolipids were compared, and 16 common peaks with strong responses, good resolutions, and stable retention times were selected as characteristic peaks. Oleic acid was chosen as the reference peak because it achieved good separation and a strong chromatographic response in all batches of samples. UHPLC-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to identify chromatographic peaks in the sophorolipid fingerprints. The results were combined with the retention time rule of the sophorolipids, leading to their identification based on matching with the results of the primary database, the precise relative molecular mass and fragmentation rule of secondary fragments, a self-built database, and the PubChem database. Sixteen compounds were identified, including eight acid sophorolipids, six lactone sophorolipids, and two aliphatic acids. The results of precision, repeatability, and 24 h stability tests indicated that the relative standard deviations (RSDs) of the retention times and peak areas of the 15 characteristic peaks relative to the control peak (oleic acid) were less than 3.0% (n=6). Seventeen batches of sophorolipid samples were analyzed, and the similarity values of all fingerprints were found to be 0.965 or higher. Little differences in chemical composition were observed among the different batches of sophorolipid samples, and the quality of the sophorolipids was relatively consistent. The fingerprint established in this study is stable and reliable; it can be used for the quality evaluation of sophorolipids and lays a solid foundation for future research on production technology and the development and utilization of sophorolipids. The successful application of a universal CAD to the fingerprint establishment of sophorolipids also provides a reliable solution for the fingerprint establishment of substances with no or weak ultraviolet absorption.

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

Composition, metabolism and postharvest function and regulation of fruit cuticle: A review.

The cuticle of plants, a hydrophobic membrane that covers their aerial organs, is crucial to their ability to withstand biotic and abiotic stressors. Fruit is the reproductive organ of plants, and an important dietary source that can offer a variety of nutrients for the human body, and fruit cuticle performs a crucial protective role in fruit development and postharvest quality. This review discusses the universality and diversity of the fruit cuticle composition, and systematically summarizes the metabolic process of fruit cuticle, including the biosynthesis, transport and regulatory factors (including transcription factors, phytohormones and environmental elements) of fruit cuticle. Additionally, we emphasize the postharvest functions and postharvest regulatory technologies of fruit cuticle, and propose future research directions for fruit cuticle.

Sex differences in short- and mid-term survival of femoral neck fracture in patients aged over 90 years: A retrospective cohort study.

OBJECTIVES: The primary purpose of this retrospective study was to evaluate the sex differences in short- and mid-term mortality in femoral neck fracture patients aged >90 years treated operatively and nonoperatively over a 10-year period. METHODS: From January 2007 to December 2016, all femoral neck fractures patients (aged over 90 years) admitted to our hospital were included for evaluation. The survival time and mortality rate were compared between patients treated by arthroplasty and those treated nonoperatively. Additionally, a Cox proportional hazards model was built to explore the treatment effect difference between the arthroplasty group and the nonoperative group with sex-stratified subgroups. RESULTS: The difference in the survival distribution between the nonoperative and arthroplasty groups were significant for women (P = 0.002) but not for men (P = 0.6222). The adjusted hazard ratio (95% confidence interval) of nonoperative treatment to arthroplasty was 3.93 (1.86, 8.31). The adjusted risk ratios of nonoperative treatment to arthroplasty for males and females were 1.24 (0.58, 2.67) and 34.04 (8.68, 133.47), respectively. The data also showed higher short- and midterm survival rates in women than in men among the arthroplasty group, especially within the first 1-3 years after injury. CONCLUSIONS: Arthroplasty can significantly improve short- and mid-term survival in femoral neck fracture patients aged over 90 years, especially females. The most significant difference in mortality between the two sexes was observed within the first three years following the fracture.

A tomato NAC transcription factor, SlNAM1, positively regulates ethylene biosynthesis and the onset of tomato fruit ripening.

Fruit ripening in tomato (Solanum lycopersicum) is the result of selective expression of ripening-related genes, which are regulated by transcription factors (TFs). The NAC (NAM, ATAF1/2, and CUC2) TF family is one of the largest families of plant-specific TFs and members are involved in a variety of plant physiological activities, including fruit ripening. Fruit ripening-associated NAC TFs studied in tomato to date include NAC-NOR (non-ripening), SlNOR-like1 (non-ripening like1), SlNAC1, and SlNAC4. Considering the large number of NAC genes in the tomato genome, there is little information about the possible roles of other NAC members in fruit ripening, and research on their target genes is lacking. In this study, we characterize SlNAM1, a NAC TF, which positively regulates the initiation of tomato fruit ripening via its regulation of ethylene biosynthesis. The onset of fruit ripening in slnam1-deficient mutants created by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) technology was delayed, whereas fruit ripening in OE-SlNAM1 lines was accelerated compared with the wild type. The results of RNA-sequencing (RNA-seq) and promoter analysis suggested that SlNAM1 directly binds to the promoters of two key ethylene biosynthesis genes (1-aminocyclopropane-1-carboxylate synthase: SlACS2 and SlACS4) and activates their expression. This hypothesis was confirmed by electrophoretic mobility shift assays and dual-luciferase reporter assay. Our findings provide insights into the mechanisms of ethylene production and enrich understanding of the tomato fruit ripening regulatory network.

A Three-Generation Pedigree of Multifocal Heterotopic Ossification With Bilateral Involvement.

Heterotopic ossification (HO) can be classified as nonhereditary HO (NHHO) or hereditary HO (HHO). Hereditary HO includes 2 different forms: fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). Each of these disorders is caused by mutations in a single (different) gene. Clinical diagnosis of FOP can be confirmed by sequence analysis of the ACVR1 gene. Fewer than 10 families with autosomal dominant inheritance of FOP have been reported. The authors report clinical manifestations, pedigree analysis, and mutational analysis of the ACVR1 in a 3-generation Chinese family with 4 individuals presenting multifocal and bilateral involvement of HO. Clinical features of affected individuals of the family were not consistent with the classic FOP or atypical FOP. Exon sequencing was performed on every family member and 3 sporadic NHHO patients who did not belong to this family. All family members and 3 sporadic NHHO patients carried 2 hereditary homozygous silent mutations- c.270C>T and c.690G>A-the new and unique mutations in ACVR1. These results may suggest that the affected individuals in this family present a novel FOP-variant syndrome or a new form of HHO. To the authors' knowledge, this is the first well-documented instance of a 3-generation Chinese family with multifocal and bilateral involvement of HO. [Orthopedics. 2021;44(1):e139-e145.].

Lingering risk: A meta-analysis of outcomes following primary total knee arthroplasty for patients with post-traumatic arthritis.

BACKGROUND: Currently, no meta-analysis exists to elucidate the outcomes of primary total knee arthroplasty (TKA) in patients with post-traumatic arthritis (PTA). The primary aim of this meta-analysis was to compare revision and complication rates for patients with PTA versus osteoarthritis (OA). METHODS: The following databases were used for searching existing literature (from their inception to October 2019): PubMed, Scopus, EMBASE, Cochrane Library, and Web of Science. The primary outcomes were the incidences of revision and complications, Secondary outcomes included operative time and patient-reported outcomes (PRO) scores. RESULTS: Nine studies with a total of 6,783,990 patients were included. This study found that there was a statistically significant difference in the rates of superficial wound infection, periprosthetic infection, stiffness, wound complications, and revision, with these outcomes occurring more frequently in patients with PTA. However, PTA did not increase the risks for periprosthetic fracture, aseptic loosening or instability, and VTE. Moreover, PTA was associated with increased operative time, worse postoperative PRO scores, and similar changes in PRO scores. CONCLUSIONS: This meta-analysis highlight the complexity of PTA and demonstrates increased risks of infection, wound complications, stiffness, and revision. Surgeons can use this information to help aid in counseling patients preoperatively.

Long-term survival of femoral neck fracture patients aged over ninety years: Arthroplasty compared with nonoperative treatment.

BACKGROUND: The aging of the Chinese population is expected to lead to an increase in nonagenarians and centenarians. The mortality rate in nonagenarian hip fracture patients is equivalent to the mortality rate in the average population at 5 years after injury. It is imperative to evaluate 5-year mortality in this small but very challenging subgroup of patients to optimize patient management. The primary purpose of the current retrospective study was to compare five-year survival in patients aged over 90 years who received arthroplasty or nonoperative treatment for femoral neck fracture during a 16-year period. METHODS: From January 1998 to December 2014, all consecutive nonagenarian and centenarian patients with femoral neck fracture admitted to our hospital were included in the evaluation. The primary outcome was defined as thirty-day, 1-year, 3-year, and 5-year mortality after injury. Survival analysis was performed with the Kaplan-Meier method. Using the log-rank test, stratified analyses were performed to compare differences in the overall cumulative mortality and mortality at three time points (1 year, 3 years, and 5 years) after injury and differences in survival distributions. RESULTS: Over the 16-year study period, the arthroplasty group and the nonoperative treatment group included 33 and 53 patients, respectively. The long-term survival probability of the arthroplasty group was significantly higher than that of the nonoperative treatment group (p = 0.002). The survival time of the arthroplasty group was significantly higher than that of the nonoperative treatment group (median (P75-P25) = 53 (59) versus median (P75-P25) = 22 (52), p = 0.001). The mortality differences, except for 30-day mortality, at five time points (1, 2, 3, 4, and 5 years) between the nonoperative group and arthroplasty group were significant. The stratified analyses of overall cumulative mortality and mortality at three time points (1, 3, and 5 years) after injury demonstrated that the nonoperative treatment group had significantly higher cumulative mortality than the arthroplasty group. CONCLUSIONS: Our study demonstrates that arthroplasty is more likely to improve long-term survival in femoral neck fracture patients aged over 90 years than nonoperative treatment. It can be expected that nearly half of patients will survive more than 5 years after surgery.

Early and mid-term results of transarticular external fixation in the treatment of supination-external rotation type IV equivalent ankle fractures.

PURPOSE: To investigate the early and mid-term results of open reduction and internal fixation (ORIF) with transarticular external fixation (TEF) but no deltoid ligament repair (DLR) in the treatment of supination-external rotation type IV equivalent (SER IV E) ankle fractures (AO/OTA classification 44-B 3.1) and provide evidence for clinical practice. METHODS: This study cohort consisted of 22 patients with SER IV E ankle fractures that underwent ORIF with TEF but no DLR between December 2011 and December 2014. There were 13 males and 9 females, mean age 38.9 years (range, 17-73 years). Eight cases involved the left side and 14 the right side. The causes of fractures included road traffic accidents (11 cases), falling from height (6 cases) and sports injuries (5 cases). The mean period of hospitalization was 9.8 days (range, 6-14 days). For all the patients, MRI and three-dimensional CT were done before surgery and X-rays done preoperatively and during follow-ups. The external frame was kept for 8-10 weeks. The preoperative American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was 56.86 ± 4.400, the Medical Outcomes Short Form 36-item (SF-36) questionnaire score was 57.41 ± 4.102 and the visual analog score (VAS) was 5.50 ± 1.058. Patients' main complaints about inconvenience of daily life were also recorded. RESULTS: All the 22 patients were followed up for 24-63 months (mean, 33.6 months). None of them developed nonunion during the follow-up; pin site infection was observed in one patient and posttraumatic osteoarthritis in another. At the final follow-up, the average AOFAS score, SF-36 score and VAS score were respectively 90.59 ± 5.096, 79.59 ± 5.394 and 1.82 ± 1.181, which were significantly improved compared with the preoperative data (t = 26.221, p < 0.001; t = 11.910, p < 0.001; t = 11.571, p < 0.001). The therapeutic effect was excellent in 13 cases, good in 7 cases and fair in 2 cases, with a good-excellent rate of 90.9%. Patients' main complaints were inconvenience of clothing (17 cases) and extremity cleaning (5 cases). CONCLUSION: In the treatment of SER IV E ankle fractures, ORIF with TEF but no DLR can achieve satisfactory outcome, but long-term effect should be confirmed by large sample randomized controlled trials.

Middle-term follow-up results of Pipkin type IV femoral head fracture patients treated by reconstruction plate and bioabsorbable screws.

PURPOSE: To investigate the mid-term curative effects of the treatment of Pipkin type IV femoral head fractures using a reconstruction plate and bioabsorbable screws and provide the evidence for clinical practice. METHODS: From February 2010 to September 2014, 21 patients with Pipkin type IV femoral head fractures were treated surgically. There were 13 males and 8 females with an average age of 41.1 years (range, 20-65 years). The causes of the fractures included traffic accidents (13 cases), falls from a height (four cases), heavy lifting injuries (three cases), and sport injury (one case). All patients were followed up with radiography and three-dimensional reconstruction computed tomography and other checks and any complications were actively managed. Closed reduction of fracture-dislocation of the hip was attempted under general anesthesia using the Kocher-Langenbeck approach. Femoral head fractures were treated with internal fixation or excision based on the size of the fracture fragments, whereas acetabular fractures were fixed with a reconstruction plate and screws following anatomic reduction. RESULTS: The incisions healed by primary intention in all patients after surgery, without any infection, deep venous thrombosis, or other complications. All 21 patients were followed up for 36-76 months, with an average follow-up duration of 49 months. Postoperative imaging data showed that all dislocations and fractures were anatomically reduced, and bony union of the fractures was achieved. Heterotopic ossification was found in four patients, post-traumatic osteoarthritis in three, and avascular necrosis of the femoral head in two. At the final follow-up, the assessment of hip joint function according to the Thompson-Epstein scoring scale was excellent in 10 cases, good in six cases, fair in three cases, and poor in two cases. The rate of excellent and good functional outcomes was 76.1%. CONCLUSION: The mid-term curative effects of a reconstruction plate and bioabsorbable screws in the treatment of Pipkin type IV femoral head fractures is significant, and such the treatment can significantly improve the patient's joint function and quality of life.

The quantification and assessment of depression and anxiety in patients with postoperative gastroparesis syndrome.

BACKGROUND: This study aimed to analyze the stage-situation depression and anxiety as well as independent influential factors in patients with postsurgical gastroparesis syndrome (PGS) and to provide dependent indications for treatment. PATIENTS AND METHODS: The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to test the depression and anxiety of 53 patients with PGS, who were treated in the Department of Gastroenterological Surgery of Gansu Provincial Hospital from January 2012 to October 2016. A comparison between the SDS or SAS scores of patients with PGS and without PGS was undertaken; then, we retrospectively analyzed the factors influencing depression and anxiety in PGS patients. RESULTS: The patients with PGS' mean scores of depression and anxiety were 49.92±11.37 and 50.91±6.57, respectively, which were higher than that of patients without PGS in the Chinese population (P<0.05). The results of multivariate logistic regression analysis indicated that the independent influential factors of depression and anxiety in patients with PGS included course of disease, pancreatic juice leakage, preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication (P<0.05). Patients with a disease course longer than 30 days; with pancreatic juice leakage; and who suffered from preoperative outflow tract obstruction, postoperative abdominal infection, and anastomotic complication had higher ratios of depression and anxiety. CONCLUSION: Depression and anxiety are clearly evident in patients with PGS, and we should pay attention to this phenomenon and provide appropriate treatment.

MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

[Protective Effect and Its Possible Mechanism of Ulinastatin on Lung Injury Induced by Hip Fracture].

OBJECTIVE: To investigate the protective effect and its possible mechanism of ulinastatin on lung injury caused by hip fracture. METHODS: Total 24 SD rats were randomly divided into control,hip fracture and hip fracture+ulinastatin groups (n=8). The rats of hip fracture and hip fracture+ulinastatin groups made the left hip fracture. The tail vein of rats of hip fracture+ulinastatin group were injected with 50 000 U/kg ustodin before made fracture model. Killed rats 24 h after mold building. Serum mtDNA,tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid,Toll like receptor-9 (TLR9) and nuclear factor (NF)-κB protein expression in lung tissue,wet/dry ratio and pathological scores of lung were detected in all three groups. RESULTS: Serum mtDNA,TNF-α and IL-6 in bronchoalveolar lavage fluid,TLR9 and NF-κB protein expressions in lung tissue,wet/dry ratio and pathological scores of lung in hip fracture group were significantly higher than those in control group ( P<0.05). Ulinastatin significantly reduced the levels of serum mtDNA,TNF-α and IL-6 in bronchoalveolar lavage fluid,TLR9 and NF-κB protein expressions in lung tissue,as well as wet/dry ratio and pathological scores of lung ( P<0.05). CONCLUSION: Ulinastatin might could provide protection on lung injury in hip fracture,and mtDNA-TLR9-NF-κB pathway may play the role of reducing inflammatory level in the process.

Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer.

AIM: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer. RESULTS: CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration (P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells (P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway. CONCLUSION: Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.

Epigallocatechin Gallate Attenuates Hip Fracture-Induced Acute Lung Injury by Limiting Mitochondrial DNA (mtDNA) Release.

BACKGROUND To study the protective effects and explore the mechanism of epigallocatechingallate (EGCG) on the hip fracture-induced acute lung injury. MATERIAL AND METHODS Thirty male Sprague-Dawley (SD) rats were randomly divided into the control group, hip fracture group, and hip fracture + EGCG (10 mg/Kg) group. After 24 h, blood samples, bronchoalveolar lavage fluid (BALF), and lung tissue were collected. Serum mitochondrial DNA (mtDNA) was measured by RT-PCR and BALF was used to perform cytological analysis and enzyme-linked immunosorbent assay (ELISA) assay. Lung tissue was used to evaluate the injury level. RESULTS EGCG significantly reduced the hip fracture-induced high level of serum mtDNA (p<0.05). HE staining showed protective effects of EGCG. Lower lung injury score and wet/dry ratio were identified in the hip fracture + EGCG group than in the hip fracture group (p<0.05). We found significantly lower levels of infiltration of inflammatory cells and production of inflammatory cytokines in the BALF of the hip fracture + EGCG group than in the hip fracture group (p<0.05). CONCLUSIONS Our study found that EGCG had protective effects on hip fracture-induced acute lung injury and suggests that EGCG exerts its protective effects through limiting the release of mtDNA. Our results provide a novel pharmacological agent to attenuate hip fracture-induced acute lung injury, as well as a potential theory to better explain the anti-inflammatory property of EGCG.

ERCC1 and XRCC1 but not XPA single nucleotide polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

Our study aimed to investigate the correlation between single nucleotide polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy and prognosis of endometrial carcinoma. Our study included 108 patients with endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1 rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Then the chemotherapy efficacy and toxic effects of the patients were assessed. The genotype and allele frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly different from that in the control group (all P<0.05). The patients with AA + GA in ERCC1 rs11615 had an increased risk of endometrial carcinoma than those with GG, and the risk of endometrial carcinoma for patients with AA + GA was also higher in comparison with patients with GG genotype in XRCC1 rs25487 (all P<0.05). GG on both ERCC1 rs11615/XRCC1 rs25487 had a higher effective rate of chemotherapy than GA + AA (all P<0.05). ERCC1 rs11615/XRCC1 rs25487 gene polymorphisms were linked with toxic effects in liver, kidney, and nervous system. ERCC1 rs11615/XRCC1 rs25487, muscular invasion, and tumor stage were independent risk factors for the prognosis of endometrial carcinoma (all P<0.05). However, no significant associations were observed between XPA rs1800975 polymorphism and chemotherapy efficacy and prognosis of endometrial carcinoma (all P>0.05). These results indicated that ERCC1 and XRCC1 but not XPA polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

Role of the Tomato Non-Ripening Mutation in Regulating Fruit Quality Elucidated Using iTRAQ Protein Profile Analysis.

Natural mutants of the Non-ripening (Nor) gene repress the normal ripening of tomato fruit. The molecular mechanism of fruit ripening regulation by the Nor gene is unclear. To elucidate how the Nor gene can affect ripening and fruit quality at the protein level, we used the fruits of Nor mutants and wild-type Ailsa Craig (AC) to perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis. The Nor mutation altered tomato fruit ripening and affected quality in various respects, including ethylene biosynthesis by down-regulating the abundance of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO), pigment biosynthesis by repressing phytoene synthase 1 (PSY1), ζ-carotene isomerase (Z-ISO), chalcone synthase 1 (CHS1) and other proteins, enhancing fruit firmness by increasing the abundance of cellulose synthase protein, while reducing those of polygalacturonase 2 (PG2) and pectate lyase (PL), altering biosynthesis of nutrients such as carbohydrates, amino acids, and anthocyanins. Conversely, Nor mutation also enhanced the fruit's resistance to some pathogens by up-regulating the expression of several genes associated with stress and defense. Therefore, the Nor gene is involved in the regulation of fruit ripening and quality. It is useful in the future as a means to improve fruit quality in tomato.

Three-Dimensional Tricuspid Annular Motion Analysis from Cardiac Magnetic Resonance Feature-Tracking.

Right ventricular (RV) dysfunction is known to be highly correlated with mortality and morbidity; nevertheless, imaging-based assessment of RV anatomy and physiology lags far behind that of the left ventricle. In this study, we advance RV imaging using cardiac magnetic resonance (CMR) to accomplish the following aims: (i) track the motion of six tricuspid annular (TA) sites using a semi-automatic tracking system; (ii) extract clinically important TA measurements-systolic velocity (Sm), early diastolic velocity (Em), late diastolic velocity (Am), and TA plane systolic excursion (TAPSE)-for each TA site and compare these CMR-derived measurements in healthy subjects vs. patients with heart failure, repaired tetralogy of Fallot, pulmonary hypertension, and hypertrophic cardiomyopathy; (iii) investigate how the TA motion related measurements compare with information provided by invasive right heart catheterization (RHC); (iv) evaluate the rate of change in surface area swept out by the reconstructed tricuspid annulus over time and (v) assess the reproducibility of this CMR-based technique. Results indicate that TA motion parameter data obtained in three dimensions using the proposed CMR-based systematic methodology achieve superior diagnostic performance (Sm: AUC = 0.957; TAPSE: AUC = 0.981) compared to two-dimensional CMR imaging. Both Sm and TAPSE from CMR correlated positively with dP/dt max/IP from RHC (Sm: r = 0.621, p < 0.01; TAPSE: r = 0.648, p < 0.01). Our highly reproducible and robust methodology holds potential for extending CMR imaging to characterization of TA morphology and dynamic behaviour, eventually leading to deeper understanding of RV function and improved diagnostic capability.

Schedule-dependent cytotoxicity of sunitinib and TRAIL in human non-small cell lung cancer cells with or without EGFR and KRAS mutations.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients who do initially respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) may eventually develop resistance, which may at least partly be due to the acquisition of a secondary EGFR mutation (T790M). Additionally, it has been found that KRAS mutations may serve as poor prognostic biomarkers. Here, we aimed at establishing a suitable treatment regimen for the multi-target TKI sunitinib and the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in NSCLC-derived cells with or without EGFR and KRAS mutations. METHODS: Four NSCLC-derived cell lines with or without EGFR and KRAS mutations were exposed to different sunitinib and TRAIL treatment regimens. Alterations in cell viability, cell cycle distribution, apoptosis, phosphorylation of AKT and expression of the death receptors DR4 and DR5 were evaluated using CCK8, flow cytometry and Western blotting assays, respectively. RESULTS: A synergistic cytotoxic effect was observed in all four cell lines treated with sunitinib (1 nM) followed by TRAIL (100 ng/ml), as well as after simultaneous treatment with both agents. We found that sunitinib enhances TRAIL-induced G0/G1-phase cell cycle arrest and blocks TRAIL-triggered activation of AKT as the underlying mechanism. In contrast, we observed antagonistic effects when sunitinib was administered after TRAIL to the cell lines tested. A decreased DR4 and DR5 expression was found to be correlated with this antagonism. CONCLUSION: From our data we conclude that administration of sunitinib followed by TRAIL, as well as a simultaneous administration of both agents, serve as favorable treatment regimens for NSCLC-derived cells, irrespective of their EGFR and/or KRAS mutation status.