Risk Factors for 30- and 90-Day Readmission due to Intestinal Bowel Obstruction after Posterior Lumbar Fusion

Methods@#Data on demographic characteristics and medical comorbidities of patients who underwent PLF with subsequent readmission were obtained from the HCUP-NRD. The perioperative characteristics that were significantly different between patients readmitted with and without an active diagnosis of IBO were identified with bivariate analysis for both 30-day and 90-day readmissions. The significant characteristics were then included in a multivariate analysis to identify those that were independently associated with 30- day and 90-day readmissions. @*Results@#Drug abuse (odds ratio [OR], 4.00), uncomplicated diabetes (OR, 2.06), having Medicare insurance (OR, 1.65), age 55–64 years (OR, 2.42), age 65–79 years (OR, 2.77), and age >80 years (OR, 3.87) were significant risk factors for 30-day readmission attributable to IBO after a PLF procedure. @*Conclusions@#Of the several preoperative risk factors identified for readmission with IBO after PLF surgery, drug abuse had the strongest association and was likely to be the most clinically relevant factor. Physicians and care teams should understand the risks of opioid-based pain management regimens, attempt to manage pain with a multimodal approach, and minimize the opioid use.

Human telomere double G-quadruplex recognition by berberine-bisquinolinium imaging conjugates in vitro and cells.

Molecular tools of double or multimeric G-quadruplexes have been given higher requirements on detection sensitivity, thermal stabilization and cell imaging to establish functions of these G-quadruplex aggregates and biological mechanisms as anticancer reagents. Here, two smart berberine-bisquinolinium conjugates (Ber-360A and Ber-PDS) by linking the berberine fluorophore ligand and an established G-quadruplex binder (i.e. bisquinolinium scaffold), have been designed and evaluated their activities and mechanisms for G-quadruplex aggregation. Two conjugates, especially Ber-PDS, are two highly selective, sensitive and fluorescent sensors which can distinguish human telomere double G-quadruplexes from other type G-quadruplexes and ds DNA. These two ligands could be the first example to stack two adjacent G-quadruplex units and fluorescently recognize human telomere double G-quadruplexes. Furthermore, conjugate Ber-PDS could enter the nucleoli and target G-quadruplex DNA through microscopy experiments, and also display strong telomerase inhibition and antitumor activities.

Dimers formed with the mixed-type G-quadruplex binder pyridostatin specifically recognize human telomere G-quadruplex dimers.

By choosing pyridostatin (PDS) with high thermal stabilization towards mixed-type G-quadruplexes as the monomer in dimers, three novel polyether-tethered PDS dimers (1a-c) were first synthesized and their interaction with human telomere G-quadruplex dimers (G2T1) was studied. Through the regulation of the linker length in PDS dimers, the dimer with a medium-length polyether linker (1b) showed higher binding selectivity and thermal stabilization (ΔTm = 29.5 °C) towards antiparallel G2T1 over G-quadruplex monomers (G1). Furthermore, the dimer with the longest-length polyether linker (1c) showed higher binding selectivity and thermal stabilization towards mixed-type G2T1 over mixed-type G1, c-kit 1, c-kit 2, c-myc and ds DNA. This work provides new insights into the development of G2T1 binders, especially mixed-type G2T1 binders, which could be promoted by a polymer formed with a mixed-type G-quadruplex binder. In addition, dimer 1c exhibited stronger telomerase inhibition than dimers 1a and 1b.

A Comparative Study on High Selectivities of Human Telomeric Dimeric G-Quadruplexes by Dimeric G-Quadruplex Binders.

Three new polyether-tethered bisquinolinium dimers (3 a-c) were synthesized, and their binding affinities, selectivities, and thermal stabilization towards dimeric G-quadruplex DNA (G2T1) in human telomeric regions were studied. The bisquinolinium dimer with a medium-length polyether linker (3 b) showed 30-425-fold higher binding affinity and selectivity towards antiparallel G2T1 than towards monomeric quadruplexes, which included human telomeric monomeric G-quadruplexes (G1), c-kit 1, c-kit 2, and c-myc. In addition, compound 3 b induced the formation of quadruplexes and displayed the highest level of thermal stabilization (ΔTm >28.1 °C) among all reported multimeric G-quadruplex binders. Compound 3 b also displayed a higher selectivity towards antiparallel G2T1 than monomer 360 A and bisquinolinium dimers 3 a and c. In contrast with our recent research on the analogous berberine dimer 1 b and dinickel-salphen complex 2 c, polyether linkers and their monomeric G-quadruplex binders in these dimeric G-quadruplex binders play a crucial role in regulating the binding affinities, selectivities, and thermal stabilization towards G2T1. More interestingly, these dimeric G-quadruplex compounds bind through end-stacking with the two adjacent G-quadruplex units in G2T1, and they showed high selectivity towards antiparallel G2T1 rather than mixed-type G2T1. In addition, compound 3 b, which displayed high selectivity towards antiparallel G2T1, showed strong telomerase inhibition and potent anticancer activities against HeLa and MCF-7 cells.

A novel square-planar Pt(ii) complex as a monomeric and dimeric G-quadruplex DNA binder.

A novel phenanthroimidazole ethylenediamine Pt(ii) complex with coumarin derivative (1) was synthesized and showed higher affinity, selectivity and thermal stabilization for mixed-type dimeric G-quadruplexes (G2T1) over monomeric G-quadruplexes (G1) and duplex DNA. Complex 1 could bind to G-quadruplexes via end-stacking and external-binding modes.

Application of robotic and laparoscopic radical total gastrectomy to gastric cancer patients with body mass index ≥24 kg/m / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the short-term outcomes between robotic and laparoscopic radical total gastrectomy in gastric cancer patients with BMI index ≥24 kg/m.</p><p><b>METHOD</b>Clinical data of 93 gastric cancer patients who underwent robotic and laparoscopic radical total gastrectomy at PLA General Hospital from April 2016 to April 2017 were retrospectively analyzed. The retrospective cohort study was adopted.</p><p><b>INCLUSION CRITERIA</b>preoperatively definite diagnosis of primary gastric cancer by endoscopy and biopsy; preoperative BMI ≥24 kg/m; no previous abdominal surgery; no previous chemotherapy and radiotherapy; no distant metastasis or invasion into adjacent organs before operation or during operation; receiving radical gastrectomy; Roux-en-Y reconstruction of digestive tract in open procedure. According to approaches of minimally invasive surgery, 24 patients underwent robotic surgery and 69 underwent laparoscopic surgery. The intraoperative parameters (overall operative time, pneumoperitoneal time, open procedure time, intraoperative blood loss, transfusion rate, number of total retrieved lymph nodes and metastatic lymph nodes) and postoperative parameters (drainage in the first postoperative day, the first defecation time, morbidity of postoperative complication and hospital stay) were compared between two groups. Correlation of the above parameters were analyzed.</p><p><b>RESULTS</b>Of 93 patients, 77 were male and 16 female with an average age of (60.0±10.6) years. The average BMI was (26.8±1.3) kg/m in whole patients, (26.9±1.6) kg/m in robotic group and (26.8±1.7) kg/m in laparoscopic group. No significant differences in age, gender, BMI, preoperative ASA class, postoperative pathological findings and clinical classification were observed between two groups, which made short-term parameters between two groups comparable. The robotic group had a significantly longer overall operative time [(301.2±68.9) minutes vs. (247.3±59.6) minutes, P=0.000], longer open procedure time [(141.5±26.3) minutes vs. (92.5±36.7) minutes, P=0.029] and higher cost than laparoscopy group[(17.5×10 ± 9.7×10) yuan vs. (10.0×10 ± 2.3×10) yuan, P=0.001]. Pneumoperitoneal operative time, intraoperative blood loss, transfusion rate, number of total retrieved lymph nodes, number of harvested metastatic lymph nodes and postoperative short-term efficacy were similar between the two groups (all P>0.05). In robotic group, pneumoperitoneal operative time was positively correlated with overall operative time (r=0.708, P=0.010); total cost was positively correlated with postoperative hospital stay (r=0.493, P=0.000) and open procedure time was negatively correlated with the first defecation time (r=-0.962, P=0.038). In laparoscopy group, total cost was positively correlated with overall operative time (r=0.411, P=0.046), drainage volume in the first postoperative day was positively correlated with the number of total dissected lymph node (r=0.540, P=0.006), postoperative hospital stay was positively correlated with intraoperative blood loss (r=0.574, P=0.003), total cost was positively correlated with intraoperative blood loss and hospital stay (r=0.609, P=0.002; r=0.865, P=0.000), drainage volume in the first postoperative day was positively correlated with BMI (r=0.533, P=0.007).</p><p><b>CONCLUSION</b>For gastric cancer patients with BMI ≥24 kg/m, robotic radical total gastrectomy is associated with longer operative time and higher cost, but is less vulnerable to the change of BMI and more in favor of the realization of enhanced recovery after surgery (ERAS) than laparoscopic radical total gastectomy.</p>

Specifically targeting mixed-type dimeric G-quadruplexes using berberine dimers.

Three polyether-tethered berberine dimers (1a-c) were studied for their binding affinity, selectivity and thermal stabilization towards human telomeric dimeric quadruplex DNA (G2T1). Compound 1a with the shortest polyether linker showed the highest affinity (Ka > 108 M-1) and 76-508-fold higher selectivity for mixed-type G2T1 over antiparallel G2T1 and three monomeric G-quadruplexes, which are human telomeric monomeric quadruplex G1, c-kit 1 and c-kit 2. Compound 1a induced the formation of quadruplex structures and showed higher thermal stabilization for mixed-type G2T1 than for anti-parallel G2T1, G1 and ds DNA. Spectroscopic studies suggest that compound 1a could bind to mixed-type G2T1 via end-stacking and external binding modes. These results suggest that the polyether linkers in these compounds play an important role in regulating the binding affinity and selectivity towards mixed-type G2T1 and that compound 1a could target mixed-type G2T1 at other genome regions with antiparallel G2T1 and monomeric G-quadruplexes. These results may provide useful guidance for the rational design of selective multimeric G-quadruplex binders and potential anticancer agents.

Dinickel-Salphen Complexes as Binders of Human Telomeric Dimeric G-Quadruplexes.

Three new polyether-tethered dinickel-salphen complexes (2 a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV/Vis titrations, fluorescence spectroscopy, CD spectroscopy, and electrophoresis. These studies have shown that the dinickel-salphen complex with the longest polyether linker (2 c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the dinickel-salphen complexes with the shorter polyether linkers (2 a and 2 b). Complex 2 c also has higher selectivity towards human telomeric dimeric quadruplexes with one TTA linker than the monometallic complex 1. Based on the spectroscopic data, a possible binding mode between complex 2 c and the dimeric G-quadruplex DNA under study is proposed.

Recent advances in the quantification of drug metabolizing enzymes and transporters by proteomic approach / 药学学报

With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.