Risk factors and prediction model of delirium in elderly patients after hip arthroplasty.

Objective: To analyze the risk factors of delirium in elderly patients after hip arthroplasty and to construct a prediction model. Methods: Clinical data of 248 elderly patients who underwent hip arthroplasty in the Department of Traumatology and Orthopedics at Wuhan Fourth Hospital were retrospectively collected from November 2021 to February 2023. Logistic regression analysis was used to identify the risk factors of delirium after hip arthroplasty, and a nomogram prediction model was constructed using the RMS package of R4.1.2 software. The accuracy and stability of the model was evaluated based on the Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic (ROC) curve. Results: Age, nighttime sleep, anesthesia method, intraoperative blood loss, hypoxemia, and C-reactive protein (CRP) level were all risk factors of delirium after the hip arthroplasty (P<0.05). These factors were used to construct a nomogram prediction model that was internally validated using the Bootstrap method. The prediction model had the area under ROC curve (AUC) of 0.980 (95% CI: 0.964-0.996), indicating that it has certain predictive value for postoperative delirium. When the optimal cut off value was selected, the sensitivity and specificity were 92.7% and 92.3%, respectively, indicating that the prediction model is effective. Conclusions: Age, short nighttime sleep, general anesthesia, high intraoperative blood loss, hypoxemia, and high CRP levels are independent risk factors for delirium after hip arthroplasty. The nomogram prediction model constructed based on these risk factors can effectively predict delirium in elderly patients after hip arthroplasty.

Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis.

Background: The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug. Methods: Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated in vitro through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice. Results: The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth in vitro and crypt cell proliferation in vivo. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes in vivo and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner. Conclusion: Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.

Cdc42 upregulation under high glucose induces podocyte apoptosis and impairs ß-cell insulin secretion.

Objectives: The progressive impairment of ß-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet ß-cells. Methods: Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and ß-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in ß-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells. Results: Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of ß-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of ß-TC6 cells. The expression of Cdc42 and p-p38 in ß-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells. Conclusions: Cdc42 in podocytes plays a crucial role in insulin secretion by ß-cells, which may provide a new therapeutic target to prevent the vicious cycle of ß-cell dysfunction in T2DM.

The different hypoglycemic effects between East Asian and non-Asian type 2 diabetes patients when treated with SGLT-2 inhibitors as an add-on treatment for metformin: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was performed through August 2020 with the following keywords: Sodium-Glucose Transporter 2 Inhibitors, Sodium Glucose Transporter 2 Inhibitors, SGLT2 inhibitor, SGLT-2 inhibitors, type 2 diabetes, and randomized controlled trials. Double-blinded RCTs comparing SGLT-2 inhibitors as an add-on treatment for metformin and metformin monotherapy in adults with type 2 diabetes were included. A random effects model was used to calculate overall effect sizes. RESULTS: 5 RCTs with 1193 Asian patients and 7 RCTs with 2098 non-Asian patients were investigated. The improvement in HbA1c and fasting blood glucose in the Asian patients (WMD, -0.73%; 95% CI, -1.01% to -0.46%, p < 0.01; WMD, -1.51; 95% CI, -1.81 to -1.21, p < 0.01, respectively) were both significantly better than in the non-Asians (WMD, -0.45%; 95% CI, -0.62% to -0.29%, p < 0.01; WMD, -1.03; 95% CI, -1.27 to -0.78, p < 0.01, respectively). The effect of weight loss was similar in the non-Asian patients and Asian patients. There was little difference in the improvement of systolic blood pressure between them. The risk of serious adverse events was not significantly increased between the Asian and non-Asian patients. CONCLUSION: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events.

Lin28a up-regulation is associated with the formation of restenosis via promoting proliferation and migration of vascular smooth muscle cells.

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double-balloon injury surgery and mono-balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α-smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up-regulated by transfection of Lenti-Lin28a and inhibited by Lenti-Lin28a-shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up-regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up-regulation of Lin28a exerts its modulatory effect on VSMCs' proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

High-performance porous spherical or octapod-like single-crystalline BiVO4 photocatalysts for the removal of phenol and methylene blue under visible-light illumination.

Monoclinic BiVO(4) single-crystallites with a polyhedral, spherical or porous octapod-like morphology were selectively prepared using the triblock copolymer P123 (HO(CH(2)CH(2)O)(20)(CH(2)CH(CH(3))O)(70)(CH(2)CH(2)O)(20)H)-assisted hydrothermal method with bismuth nitrate and ammonium metavanadate as metal source and various bases as pH adjustor. The BiVO(4) materials were well characterized and their photocatalytic activities were evaluated for the removal of methylene blue (MB) and phenol in the presence of a small amount of H(2)O(2) under visible-light illumination. It is shown that the pH value of the precursor solution, surfactant, and hydrothermal temperature had an important impact on particle architecture of the BiVO(4) product. The introduction of P123 favored the generation of BiVO(4) with porous structures. The BiVO(4) derived hydrothermally with P123 at pH 3 or 6 possessed good optical absorption performance both in UV- and visible-light regions and hence showed excellent photocatalytic activities for the degradation of MB and phenol. It is concluded that the high visible-light-driven catalytic performance of the porous octapod-like BiVO(4) single-crystallites is associated with the higher surface area, porous structure, lower band gap energy, and unique particle morphology. Such porous BiVO(4) materials are useful in the solar-light-driven photocatalytic treatment of organic-containing wastewater.

P123-PMMA dual-templating generation and unique physicochemical properties of three-dimensionally ordered macroporous iron oxides with nanovoids in the crystalline walls.

Three-dimensionally (3D) ordered macroporous (3DOM) iron oxides with nanovoids in the rhombohedrally crystallized macroporous walls were fabricated by adopting the dual-templating [Pluronic P123 and poly(methyl methacrylate) (PMMA) colloidal microspheres] strategy with ferric nitrate as the metal precursor in an ethanol or ethylene glycol and methanol mixed solution and after calcination at 550 °C. The possible formation mechanisms of such architectured materials were discussed. The physicochemical properties of the materials were characterized by means of techniques such as XRD, TGA/DSC, FT-IR, BET, HRSEM, HRTEM/SAED, UV-vis, XPS, and H(2)-TPR. The catalytic properties of the materials were also examined using toluene oxidation as a probe reaction. It is shown that 3DOM-structured α-Fe(2)O(3) without nanovoids in the macroporous walls was formed in the absence of P123 during the fabrication process, whereas the dual-templating strategy gave rise to α-Fe(2)O(3) materials that possessed high-quality 3DOM structures with the presence of nanovoids in the polycrystalline macropore walls and higher surface areas (32-46 m(2)/g). The surfactant P123 played a key role in the generation of nanovoids within the walls of the 3DOM-architectured iron oxides. There was the presence of multivalent iron ions and adsorbed oxygen species on the surface of each sample, with the trivalent iron ion and oxygen adspecies concentrations being different from sample to sample. The dual-templating fabricated iron oxide samples exhibited much better low-temperature reducibility than the bulk counterpart. The copresence of a 3DOM-structured skeleton and nanovoids in the macropore walls gave rise to a drop in the band-gap energy of iron oxide. The higher oxygen adspecies amounts, larger surface areas, better low-temperature reducibility, and unique nanovoid-containing 3DOM structures of the iron oxide materials accounted for their excellent catalytic performance in the oxidation of toluene.