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Background: Patients with frailty get more and more attention in clinical practice. Yet, no large-scale studies have explored the impact of frailty on the perioperative acute medical and surgical complications following TJA. what is more, comorbid diseases may lead, at least additively, to the development of frailty. There also no studies to find the possible interaction between comorbidity and frailty on the postoperative complications after TJA.Methods: Discharge data of 2,029,843 patients who underwent TJA from 2005 to 2014 from the National Inpatient Sample (NIS) database, which was analyzed using cross-tabulations and multivariate regression modeling. Frailty was defined based on frailty-defining diagnosis clusters from frailty-defining diagnosis indicator of Johns Hopkins Adjusted Clinical Groups.Results: Among patients who underwent total joint replacement surgeries, 50,385 (2.5%) were identified as frail. Frailty is highly associated with old age, especially for those over the age of 80, meanwhile females and black races have a high Charlson comorbidity index (CCI) of ≥ 3, together with emergency/urgent admission and teaching hospital. While comorbidity is associated with greater odds of acute medical complications, and frailty has a better predictive effect on in-hospital deaths, acute surgical complications. Furthermore, frailty did not show an enhancement in the predictive power of the Charlson comorbidity score for postoperative complications or in-hospital deaths but postoperative LOS and hospitalization costs.Conclusion: Frailty can be used to independently predicted postoperative surgical and medical complications, which also has a synergistic interaction with comorbidity for patients who are preparing to undergo TJA. [ABSTRACT FROM AUTHOR]

Background: Definite prognostic clinical factors of benefit for decitabine-based induction chemotherapy in elderly patients newly diagnosed with acute myeloid leukaemia (AML) are not identified. This study was designed to explore the potential biomarker, especially regeneration of haematopoiesis, of treatment response and survival in elderly patients with newly diagnosed AML.Method: We analysed the clinical data of 117 elderly AML patients who were treated with a decitabine dose of 15 mg/m2 for 5 days, granulocyte colony-stimulating factor of 300 μg/d for priming, plus cytarabine 10 mg/m2 q12h for 7 days and aclarubicin 10 mg/d for 4 days (D-CAG).Results: After initial induction chemotherapy, the overall response rate and complete remission (CR) were 71.8% and 58.1%, respectively. Patients responding to the D-CAG regimen achieved higher platelet counts on day 14 after initial treatment (p < 0.001). Median counts were 59.5 × 109/L in the CR group, 37 × 109/L in the partial remission group and 28 × 109/L in the non-responsive group. We then classified patients into those who achieved platelet counts≥60 × 109/L or 100 × 109/L on day 14 after D-CAG vs. those who did not. Platelet counts≥60 × 109/L or 100 × 109/L on day 14 were significantly associated with superior CR, overall survival and disease-free survival (80.9% vs. 45.3% p < 0.001,16.5 vs. 9.1 months p = 0.009 and 16.3 vs. 7.4 months p = 0.024; 85.2% vs. 50% p = 0.001, 31 vs. 10.1 months p = 0.003 and 16.9 vs. 8.9 months p = 0.006). Multivariate analysis confirmed that poor cytogenetics (p = 0.010) and FLT3-ITD mutation (p = 0.007) were identified as independent factors of OS, but not platelet count (p = 0.091). However, platelet count≥100 × 109/L on day 14 was an independent prognostic factor of CR and DFS.Conclusion: Platelet count recovery on day 14 after D-CAG induction chemotherapy is associated with response.Trial Registration: D-CAG regimen was registered on ChicTR with number 11001700 . [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the clinical characteristics of cerebral venous sinus thrombosis (CVT) patients with new-onset headache and to identify the risk factors for headache in this population., Methods: We retrospectively reviewed the demographic and clinical data of 69 CVT patients recruited between September 2017 and September 2019. Patients were classified into two groups, the headache group and the non-headache group, according to the presence or absence of new-onset headache symptoms at admission. The following characteristics and parameters were measured and analyzed, including gender, age, amount of thromboembolic cerebral venous sinus(ATCVS), and other relevant indicators., Results: The incidence of headache was 75% in this cohort. The proportion of female patients in the headache group was higher than that in the non-headache group. Patients in the headache group were younger than those without headache. CVT patients of headache group showed higher lymphocyte ratio (LR), blood urea nitrogen (BUN), and intracranial pressure (ICP) compared to the non-headache group, whereas mean corpuscular volume (MCV) and levels of protein (cerebrospinal fluid, CSF) and lactic dehydrogenase (LDH) in CSF were lower in headache patients. The data also revealed younger age and the increased level of chloride ion CI-(CSF) were the risk factors for the occurrence of headache in CVT patients., Conclusion: Age, LR, MCV, BUN levels, ICP, protein (CSF), and LDH (CSF) in patients with headache were significantly different from those in the non-headache group at admission. Younger age and a level of CI- (CSF) were risk factors for headache in CVT patients. These findings may provide guidance for clinical diagnosis and treatment of CVT., (© 2023. The Author(s).)

Background: Trypsin has many applications in food and pharmaceutical manufacturing. Although commercial trypsin is usually extracted from porcine pancreas, this source carries the risks of infectivity and immunogenicity. Microbial Streptomyces griseus trypsin (SGT) is a prime alternative because it possesses efficient hydrolysis activity without such risks. However, the remarkable hydrolysis efficiency of SGT causes autolysis, and five autolysis sites, R21, R32, K122, R153, and R201, were identified from its autolysate., Results: The tbcf (K101A, R201V) mutant was screened by a directed selection approach for improved activity in flask culture (60.85 ± 3.42 U mL -1 , increased 1.5-fold). From the molecular dynamics simulation, in the K101A/R201V mutant the distance between the catalytical residues D102 and H57 was shortened to 6.5 Å vs 7.0 Å in the wild type, which afforded the improved specific activity of 1527.96 ± 62.81 U mg -1 . Furthermore, the production of trypsin was increased by 302.8% (689.47 ± 6.78 U mL -1 ) in a 3-L bioreactor, with co-overexpression of chaperones SSO2 and UBC1 in Pichia pastoris., Conclusions: SGT protein could be a good source of trypsin for insulin production. As a result of the hydrolysates analysis and direct selection, the activity of the tbcf (K101A, R201V) mutant increased 1.5-fold. Furthermore, the production of trypsin was improved threefold by overexpressing chaperone protein in Pichia pastoris. Future studies should investigate the application of SGT to insulin and pharmaceutical manufacturing.

Background: Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear., Methods: We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters. In vivo and in vitro, we tested whether glycolysis may induce TIGAR expression and evaluated the combination effect of glycolysis inhibitor and TIGAR knockdown on human leukemia cell proliferation., Results: High TIGAR expression was an independent predictor of poor survival and high incidence of relapse in adult patients with CN-AML. TIGAR also showed high expression in multiple human leukemia cell lines and knockdown of TIGAR activated glycolysis through PFKFB3 upregulation in human leukemia cells. Knockdown of TIGAR inhibited the proliferation of human leukemia cells and sensitized leukemia cells to glycolysis inhibitor both in vitro and in vivo. Furthermore, TIGAR knockdown in combination with glycolysis inhibitor 2-DG led leukemia cells to apoptosis. In addition, the p53 activator Nutlin-3α showed a significant combinational effect with TIGAR knockdown in leukemia cells. However, TIGAR expression and its anti-apoptotic effects were uncoupled from overexpression of exogenous p53 in leukemia cells., Conclusions: TIGAR might be a predictor of poor survival and high incidence of relapse in AML patients, and the combination of TIGAR inhibitors with anti-glycolytic agents may be novel therapies for the future clinical use in AML patients.