The effect of parecoxib sodium on postoperative delirium in elderly patients with hip arthroplasty.

Objective: This study aimed to clarify the effect of parecoxib sodium on the occurrence of postoperative delirium and to investigate its possible mechanism. Methods: A total of 80 patients who underwent elective hip arthroplasty in our hospital between December 2020 and December 2021 were selected and randomly divided into two groups: a parecoxib sodium group (group P, n = 40) and a control group (group C, n = 40). Patients in group P were intravenously injected with 40 mg of parecoxib sodium 30 min before anesthesia and at the end of the surgery. Patients in group C were intravenously injected with the same volume of normal saline at the same time points. The primary endpoint was the incidence of POD, and the secondary endpoints were the levels of inflammatory factors (tumor necrosis factor- α [TNF-α], interleukin [IL]-1ß, IL-6, and IL-10), nerve injury-related factors (brain-derived neurotrophic factor [BDNF], S-100ß protein, neuron-specific enolase [NSE], and neurofilament light chain [NfL]), and antioxidant factors (heme oxygenase-1 [HO-1]), as well as the Visual Analogue Scale (VAS) and Confusion Assessment Method-Chinese Reversion (CAM-CR) scores. Results: The incidence of POD was 10% in group P and 27.5% in group C. Intergroup comparison revealed that the levels of TNF-α, IL-1ß, S-100ß, NfL, and NSE were lower, and BDNF was higher, in group P than in group C at each postoperative time point. The levels of IL-6 were lower, and the levels of IL-10 and HO-1 were higher, in group P than in group C at 1 h and 1 day postoperatively (p < 0.05). Three days after surgery, the differences in the levels of IL-6, IL-10, and HO-1 were not statistically significant between the two groups (p > 0.05). The VAS and CAM-CR scores were lower at each postoperative time point in group P than in group C (p < 0.05). Conclusion: Parecoxib sodium could reduce postoperative pain, decrease the plasma levels of inflammatory and nerve injury-related factors, upregulate HO-1 levels, and reduce the incidence of POD. The results of this study suggest that parecoxib sodium may reduce the occurrence of POD through the effects of anti-inflammation, analgesia, and antioxidants.

Salvianolic Acid B Attenuates Iopromide-Induced Renal Tubular Epithelial Cell Injury by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Postcontrast acute kidney injury (PC-AKI) is directly caused by the use of contrast, indicating a clear causal relationship between the contrast and the injury. Salvianolic acid B (Sal B), a water-soluble compound of Salvia miltiorrhiza, has a potent anti-inflammatory effect. We conducted a study to explore whether the protective effect of Sal B on iopromide-induced injury in human proximal tubular epithelial cells (HK-2 cells) is related to inhibition of the TLR4/NF-κB/NLRP3 signal pathway. The results showed that 100 µmol/L Sal B counteracted the decrease in cell viability, the increase of ROS and the number of apoptotic cells, and the decrease of mitochondrial membrane potential (ΔΨm) induced by iopromide. Molecular docking analysis showed that Sal B binds TLR4 and NLRP3 proteins. Moreover, 100 µmol/L Sal B also decreased the expression of TLR4, NLRP3, ASC, Caspase-1, IL-18, IL-1ß, TNF-α, p-NF-κB, cleaved caspase-3, and the ratio of Bax/Bcl-2 induced by iopromide. TAK-242, a TLR4 antagonist, was added to further explore the mechanism of Sal B. However, the cotreatment group with TAK-242 and Sal B had no significant difference in cell viability and apoptosis rate compared to the treatment group with TAK-242 or Sal B alone. These results indicated that Sal B can inhibit the TLR4/NF-κB/NLRP3 signal pathway, resulting in the alleviation of iopromide-induced HK-2 cell injury.

Global Transcriptional Analyses of the Wnt-Induced Development of Neural Stem Cells from Human Pluripotent Stem Cells.

The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN, PAX6, SOX2, and SOX1; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/ß-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4, HOXA7, HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2, were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis.

A Palladium Complex as an Asymmetric π-Lewis Base Catalyst for Activating 1,3-Dienes.

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating the electrons from the d-orbitals to the empty antibonding molecular orbitals of double bonds (π*) via back-bonding. Thus, the uncoordinated double bond, as a more reactive partner on the basis of the principle of vinylogy, can directly attack imines, furnishing a formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between 1,3-dienes and imines with a nucleophilic group is also compatible, by trapping in situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, vinylogous activation, and compatibility with both conjugated neutral polyenes and electron-deficient polyenes, is elucidated by control experiments and density functional theory (DFT) calculations.

Enantioselective H-bond-directed vinylogous iminium ion strategy for the functionalization of vinyl-substituted heteroaryl aldehydes.

In this work the first H-bond-directed vinylogous iminium ion strategy has been developed as a convenient strategy for the γ,δ-functionalization of vinyl-substituted heteroaromatic aldehydes. Their reaction with α-mercaptoketones proceeds in a cascade manner involving 1,6-addition followed by intramolecular aldol reaction. Excellent stereoselectivities have been obtained as a result of the H-bond interactions controlling the outcome of the cyclization step. The application of the strategy for the synthesis of tricyclic compounds bearing furan, tetrahydrothiophene and dihydropyran moieties has also been demonstrated.

Regioselectivity Umpolung in Asymmetric Diels-Alder Reaction of ortho-Formyl-Substituted Cinnamates and Dienals via Double Aminocatalysis.

The cinnamates having an ortho-formyl group can potentially form vinylogous iminium ion species under the catalysis of chiral amines, which facilitates the Diels-Alder cycloaddition reaction with the concurrently generated trienamines between dienals and amine catalysts in a regioselectivity umpolung manner. A cascade intramolecular aldol reaction was followed, finally furnishing polyhydrophenanthrene frameworks with excellent diastereo- and enantioselectivity.

Effects and Mechanism of Salvianolic Acid B on the Injury of Human Renal Tubular Epithelial Cells Induced by Iopromide.

With the increasing application of medical imaging contrast materials, contrast-induced nephropathy (CIN) has become the third major cause of iatrogenic renal insufficiency. CIN is defined as an absolute increase in serum creatinine levels of at least 0.50 mg/dl or an increase >25% of serum creatinine from baseline after exposure to contrast. In this study, the protective effects of salvianolic acid B (Sal B) were detected in human renal tubular epithelial cells (HK-2) exposed to iopromide. The results showed that different concentrations of Sal B counteract the loss of cell viability induced by iopromide, and reduce cell apoptosis, the reactive oxygen species (ROS) levels, and the levels of endoplasmic reticulum stress (ERS)-related and apoptosis-related proteins such as p-IRE-1α, p-eIF-2α/eIF-2α, p-JNK, CHOP, Bax/Bcl-2, and cleaved caspase-3. In addition, Sal B at a concentration of 100 µmol/L inhibited ERS and reduced cell damage to a similar extent as the ERS inhibitor 4-PBA. Importantly, treatment with Sal B could abolish the injury induced by ERS agonist tunicamycin, increasing cell viability and the mitochondrial membrane potential, as well as significantly reducing ROS levels and the expression of Bax/Bcl-2, cleaved-caspase-3, GRP78, p-eIF2α, p-JNK, and CHOP. These results suggested that the protective effect of Sal B against HK-2 cell injury induced by iopromide may be related to the inhibition of ERS.

Asymmetric Formal Vinylogous Iminium Ion Activation for Vinyl-Substituted Heteroaryl and Aryl Aldehydes.

The vinyl group tethered to furfurals could be LUMO-lowered by forming formal vinylogous iminium ion intermediates catalyzed by a chiral secondary amine and underwent asymmetric [3 + 2] cycloaddition reactions with N-trifluoroethyl-substituted isatin imines, furnishing a variety of spirooxindoles incorporating a 3,2'-pyrrolidine motif with excellent stereoselectivity. In addition, this strategy has been successfully expanded to a number of vinyl-substituted electron-rich heteroaryl aldehydes and even some specific aryl aldehydes.

Asymmetric Reactions involving Lewis Base Catalyst Tethered Dearomatized Intermediates.

Numerous protocols have been developed for the functionalization of aromatic substances. Among them, the strategy by which aromatic substrates are activated in situ to generate dearomatized intermediates is highly efficient but challenging, especially in the field of asymmetric catalysis. In this Concept article, the application of some well-established chiral Lewis base catalysis, including primary/secondary amines and N-heterocyclic carbenes, that can covalently form catalyst-tethered dearomatized ortho/para-quinodimethane species with diverse heteroaryl and aryl carbonyl substrates is summarized in a number of asymmetric cycloaddition and addition reactions with diverse reagents generally having electrophilic properties. As a result, a variety of enantioenriched aromatic products with higher molecular complexity are constructed effectively through a rearomatization process.

Asymmetric Benzylic Functionalizations of 3-Vinyl Benzofurans via Cascade Formal Trienamine-Vinylogous Iminium Ion Activation.

An efficient approach to construct chiral 1,1-disubstituted ethane derivatives is presented. This strategy relies on the formation of the key dearomatizative vinylogous iminium ion species through protonation of the formal trienamine intermediates between 2-(3-vinylbenzofuran-2-yl)ethan-1-ones and a chiral primary amine. An array of nucleophiles, including 4-hydroxycoumarins, indoles, etc., have been effectively assembled at the benzylic site, delivering the expected 1,1-disubstituted ethane products in moderate to excellent enantioselectivity.

[Effects of L. lactis recombinant heme oxygenase-1 gene on the intestinal barrier in rats with hemorrhagic shock].

OBJECTIVE: To evaluate the effect of gavage of L. lactis recombinant heme oxygenase-1 (HO-1) gene on protection of the intestinal mucosa and the inflammation of lower intestine during hemorrhagic shock. METHODS: A model of hemorrhagic shock was reproduced in 30 SD healthy male rats. They were randomly divided into the L. lactis recombinant HO-1 gene group (HO group, n=10), L. lactis group (LL group, n=10), and glutamine group (Glu group, n=10). Glu was gavaged 6 hours and other agents were gavaged 24 hours before the experiment. Samples were collected 1 hour after hemorrhagic shock and fluid resuscitation. The mortality, mean arterial pressure (MAP) during hemorrhagic shock and fluid resuscitation, myeloperoxidase (MPO) activity, the pathological changes, and the contents of HO-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) of the lower intestine were determined immunohistochemically and compared. RESULTS: When the results of HO group were compared with Glu and LL groups, the mortality was significantly decreased in the former (both P<0.05). In HO group, MAP values at 5, 10, 20 and 30 minutes after fluid resuscitation were significantly elevated (all P<0.05). Compared with LL group, the gray levels of IL-10 and HO-1 in HO group and Glu group were significantly increased (all P<0.05). Compared with Glu group, the gray level of HO-1 was significantly increased in HO group (P<0.05). There were no significant differences in the gray levels of TNF-alpha among three groups. The Chiu's grade of HO group [(1.41+/-0.28) scores] was significantly lower than those of LL group and Glu group [(1.93+/-0.49) scores and (1.75+/-0.58) scores, respectively, both P<0.05]. CONCLUSION: The L. lactis recombinant HO-1 has the virtue to deliver HO-1 activity in rats with hemorrhagic shock, which is beneficial for the maintenance of intestinal barrier and anti-inflammation response of the lower intestine.

[Effect of hydroxyethyl starch on vascular reactivity of rat during hemorrhagic shock].

OBJECTIVE: To study the effect of hydroxyethyl starch (HES) on vascular reactivity of rat during hemorrhagic shock and its mechanism. METHODS: Forty SD rats were randomly divided into 5 groups: normal control group, shock group, sodium chloride (SC) group, HES 130/0.4 group and HES 200/0.5 group with 8 rats in each group. Rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mm Hg (1 mm Hg=0.133 kPa) for 30 minutes, then rats were infused with fluids to restore and maintain MAP at 70 mm Hg for 60 minutes. The infusion volumes of each fluid to maintain MAP were recorded. The responses of MAP to norepinephrine (NE) were measured before shock, at 30, 60 and 90 minutes during hemorrhagic shock. Concentrations of nitric oxide (NO) and nitric oxide synthase (NOS) of plasma were measured at 90 minutes during hemorrhagic shock. RESULTS: The infusion volumes of each fluid to maintain MAP were significantly different (all P<0.01). HES 200/0.5 group

[Effects of gavage with lactococcus lactis recombinant heme oxygenase-1 gene on inflammation of intestine and bacterial translocation in rats with hemorrhagic shock].

OBJECTIVE: To evaluate the effects of gavage with lactococcus lactis (L. Lactis) recombinant heme oxygenase-1 (HO-1) gene on alleviation of intestinal inflammation and protection of the intestinal mucosa in rats with hemorrhagic shock. METHODS: A model of rats with hemorrhagic shock was reproduced in 30 healthy SD male rats. The rats were randomly divided into the L. Lactis recombinant HO-1 gene group (HO group, n=10), L. Lactis group (LL group, n=10) and phosphate buffer group (PBS group, n=10). These agents were respectively gavaged 24 hours before the experiment. Rats were re-anesthetized 1 hour after fluid resuscitation. The mortality, myeloperoxidase (MPO) activity, bacterial translocation, the pathologic changes, the contents of HO-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in the intestine were determined and compared. RESULTS: Compared with LL group and PBS group, the mortality, Chiu's grade and the bacterial translocation rate of HO group were significantly decreased (all P<0.05) but the content of HO-1 and the level of IL-10 in HO group were markedly increased (both P<0.05). Compared with HO group and LL group, the MPO activity of PBS group was obviously increased (P<0.05). CONCLUSION: The recombinant L. Lactis has the effect to deliver HO-1, which has protective effect on the intestinal mucosa in lessening the inflammation of the intestine and the incidence of bacterial translocation.

[Comparison of effects of two kinds of fluid for resuscitation on bacterial translocation and inflammation of small intestine in rats with hemorrhagic shock].

OBJECTIVE: To investigate the effects of Ringer's solution (RS) or 6% hydroxyethyl saline (HES) on bacterial translocation and inflammation of the small intestine in rats with hemorrhagic shock. METHODS: Fifty healthy male SD rats were randomly divided into the sham group (SHA group, n=10), the Ringer's solution group (RS group, n=20) and 6% hydroxyethyl saline group (HES group, n=20). Controlled hemorrhagic shock model was reproduced in RS and HES groups. Bacterial translocation to the liver, the content of tumor necrosis factor-alpha (TNF-alpha) in intestinal tissue, and the myeloperoxidase (MPO) activity in the intestinal tissue were determined and compared among the groups, and the pathologic changes in the small intestine were observed. RESULTS: The mortality rate, bleeding volume and Chiu's scores were same in HES and RS groups (all P>0.05). Compared to SHA group, bacterial count and TNF-alpha level were increased significantly in HES and RS groups, and they were higher at 1 hour and lower at 24 hours in HES group than those in RS group. Compared to the SHA group, MPO activity increased at 1 hour in RS and HES groups, but no significant difference between the groups was found at 24 hours. CONCLUSION: RS prevents compromise of the intestinal barrier function better than the HES at 1 hour after fluid resuscitation. However, HES seems to be better in protecting the intestinal barrier function compared with RS at 24 hours after fluid resuscitation.