High lipoprotein(a) concentration is associated with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology. METHODS: Data for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted. RESULTS: A cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6-37.8) mg/dL vs. 14.9 (7.8-30.5) mg/dL, P < 0.001]. The odds ratios and 95% confidence intervals for Lp(a) were calculated in three models: unadjusted model, model 1 (adjusted for body mass index and systolic blood pressure), and model 2 (adjusted for model 1 plus triglyceride, C-reactive protein, homocysteine, and low-density lipoprotein cholesterol). Results were [1.613 (1.299-2.002), P < 0.001], [1.598 (1.286-1.986), P < 0.001], and [1.661 (1.330-2.074), P < 0.001], respectively. Furthermore, age, sex, or hypertension status had nothing to do with this relationship. CONCLUSIONS: Positive relationship exists between Lp(a) and MMD.

CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications.

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

CircZSWIM6 mediates dysregulation of ECM and energy homeostasis in ageing chondrocytes through RPS14 post-translational modification.

BACKGROUND: Circular RNAs (CircRNAs) are important and have different roles in disease progression. Herein, we aim to elucidate the roles of a novel CircRNA (CircZSWIM6) which is upregulated in ageing chondrocytes. METHODS: We verified the roles of CircZSWIM6 in senescent and osteoarthritis (OA) development in vitro through CircZSWIM6 knockdown and overexpression. RNA pulldown assay and RNA binding protein immunoprecipitation were performed to identify the interaction between CircZSWIM6 and Ribosomal protein S14 (RPS14). The roles of CircZSWIM6 in ageing-related OA were also confirmed in non-traumatic and traumatic model respectively. RESULTS: CircZSWIM6 regulates extracellular matrix (ECM) and energy metabolism in ageing chondrocyte. Mechanistically, CircZSWIM6 competitively bound to the E3 ligase STUB1 binding site on RPS14 (K125) to inhibit proteasomal degradation of RPS14 to maintain RPS14 function. CircZSWIM6-RPS14 axis is highly associated with AMPK signaling transduction, which keeps energy metabolism in chondrocyte. Furthermore, CircZSWIM6 AAV infection leads to senescent and OA phenotypes in a non-traumatic model and accelerates OA progression in a traumatic model. CONCLUSION: Our results revealed a significant role of CircZSWIM6 in age-related OA by regulating ECM metabolism and AMPK-associated energy metabolism. We highlight the CircZSWIM6-RPS14-PCK1-AMPK axis is a potential biomarker for OA.

In Situ Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration.

A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic-inorganic cocross-linking, here, we built a strong organic-inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the in situ mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement in vitro. The BOH exhibited acceleration of osteogenesis in vivo, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The in situ mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic-inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.

The patient-generated subjective global assessment is a promising screening tool for cancer cachexia.

BACKGROUND: Cancer cachexia is a complex metabolic syndrome characterised by a loss of muscle with or without loss of fat mass, and is associated with high morbidity and mortality. Despite its clinical importance, there is a lack of simple tools to screen patients for cancer cachexia. The aim of this study was to evaluate and validate the patient-generated subjective global assessment (PG-SGA) as a screening tool for cancer cachexia. METHODS: This is a secondary analysis of a multicentre, cross-sectional, observational study. Cancer cachexia was diagnosed when there was weight loss ≥5% during the past 12 months and at least three of the five following conditions were present: decreased muscle strength, fatigue, anorexia, low Fat-Free Mass Index (FFMI) and abnormal laboratory findings. A quadratic discriminant analysis was conducted for the ability of PG-SGA to predict cachexia. RESULTS: A total of 4231 patients with cancer were included in this analysis, and 351 patients (8.3%) were diagnosed as having cachexia. The highest incidence of cachexia was found among patients with pancreatic cancer (32.5%), oesophageal cancer (21.5%) and gastric cancer (17.9%). Compared with patients without cachexia, patients with cachexia had a lower body mass index, FFMI, hand grip strength, total protein, prealbumin, albumin, haemoglobin and Karnofsky performance status (p<0.05), while they had a higher C reactive protein level and PG-SGA Score (4.71±3.71 vs 10.87±4.84, p<0.05). The best cut-off value for PG-SGA was 6.5, with 79.8% of sensitivity and 72.3% specificity for cachexia, and the area under the receiver operating characteristic curve was 0.846 (95% CI 0.826 to 0.866, p<0.001). CONCLUSIONS: PG-SGA is a highly specific tool that can be used to screen patients for cancer cachexia.

Gemcitabine plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer.

PURPOSE: To investigate the efficacy and safety of gemcitabine plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: Eligible patients received gemcitabine 1,000 mg/m2 on days 1 and 8, and capecitabine 1,000 mg/m2 twice daily on days 1-14. The treatment was repeated every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR). The secondary endpoint included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Forty-eight patients with a median age of 72 years (range, 65-83) were included. The ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) was 29.2% (95% confidence interval [CI], 16.3% to 42.1%). After a median follow-up of 17.4 months, median PFS and OS were 6.4 months (95% CI, 5.2-7.6) and 18.0 months (95% CI, 14.8-21.2), respectively. Grade 3 to 4 adverse events included neutropenia (20.8%), asthenia (8.3%), hand-foot syndrome (6.3%), abnormal liver function (6.3%), diarrhea (6.3%), constipation (2.1%) and thrombocytopenia (2.1%). Neutropenic fever occurred in one patient. CONCLUSIONS: Gemcitabine plus capecitabine are active and safe in elderly patients with anthracycline- and taxane-pretreated MBC.

Ubiquitin-Specific Peptidase 22 Contributes to Colorectal Cancer Stemness and Chemoresistance via Wnt/ß-Catenin Pathway.

BACKGROUND/AIMS: Two major barriers to the successful treatment of colorectal cancer (CRC) are the development of stem cell-like characteristics (stemness) and chemoresistance. Ubiquitin-specific peptidase 22 (USP22) is a deubiquitinating enzyme and putative CRC marker that has emerged as a potential cause of both phenomena in CRC. There is evidence that USP22 acts through the Wnt/ß-catenin pathway and that downregulation of the latter may reduce chemoresistance. METHODS: In this study, we used CRC tissue specimens from human patients as well as human CRC cell lines to evaluate the role of USP22 in CRC stemness and chemoresistance in vitro and in vivo. RT-PCR and western blot were used for gene expression analyses. Immunohistochemistry was performed for USP22 expression in clinical samples. CD133 levels were analyzed by flow cytometry. Sphere formation and MTT assays were used for self-renewal and proliferation analysis. Chemoresistance was evaluated by cell viability and sphere formation assays. RESULTS: We found a significant increase of USP22 in recurrent CRC and chemoresistant CRC cells as compared to primary CRC and non-chemoresistant CRC cells, respectively. We then demonstrated that USP22 mediates CRC cell chemoresistance through the Wnt/ß-catenin pathway and that reducing USP22 in CRC cells diminishes chemoresistance. CONCLUSIONS: Having established the crucial role of USP22 in CRC stemness and chemoresistance, this study suggests that USP22 may be an ideal genetic target in the treatment of chemoresistant CRC.

An Interdisciplinary Nutrition Support Team Improves Clinical and Hospitalized Outcomes of Esophageal Cancer Patients with Concurrent Chemoradiotherapy.

BACKGROUND: The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups. RESULTS: At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group. CONCLUSIONS: A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.

[Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

OBJECTIVE: To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. METHODS: From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. RESULTS: After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P < 0.05). And albumin, red blood cell count, white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group. During treatment, compared to control group, the incidences of infection-associated complication were lower (6% vs 19%, P < 0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%, P < 0.05). CONCLUSION: Supplements of glutamine, EPA and branched-chain amino acids can help maintain nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

Six cases of chylous leakage after axillary lymph node dissection.

BACKGROUND: Chylous leakage has been described after several surgical procedures, especially in the region of the neck and thorax. However, it has rarely been reported after axillary lymph node dissection. PATIENTS AND METHODS: We encountered 6 cases of chylous leakage after axillary lymph node dissection out of a total of 882 breast cancer patients between July 2005 and June 2007 in Shandong Provincial Hospital. These 6 cases were confirmed by axillary white fluid and chylomicron interpretation. The patients were treated conservatively, including a low fat diet, compression bandage, and suction drainage. RESULTS: All 6 cases were successfully treated without any complications such as infection, dystrophy, and lymphoceles. The chylous leakage disappeared within a median of 5 days (range: 3-7 days). Adjuvant chemotherapy and radiotherapy were not delayed. After a median follow-up period of 12 months (range: 6-20 months), no chronic complications were observed. CONCLUSION: Chylous leakage after axillary lymph node dissection is quite rare. It can be cured by conservative treatment. Lymphatic vessels should be identified carefully, and the main duct should be carefully ligated during surgical procedures, especially when level II and III lymph nodes are removed.