Combined ROS Sensitive Folate Receptor Targeted Micellar Formulations of Curcumin Effective Against Rheumatoid Arthritis in Rat Model.

Introduction: Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. Methods: We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. Results: TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. Conclusion: The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.

Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation.

Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.

Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Constructing models for Crohn's disease diagnosis and prediction of infliximab non-response based on angiogenesis-related genes.

Background: Angiogenesis response plays a crucial role in the occurrence and development of Crohn's disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn's disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response. Methods: CD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built. Results: Based on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset. Conclusion: Comprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making.

Comparative peptidomics analysis of preeclamptic placenta and the identification of a novel bioactive SERPINA1 C-terminal peptide.

Preeclampsia (PE) is a life-threatening disease that severely harms pregnant women and infants' health but has a poorly understood etiology. Peptidomics can supply important information about the occurrence of diseases. However, application of peptidomics in preeclamptic placentas has never been reported. We conducted a comparative peptidomics analysis of PE placentas and performed bio-informatics analysis on differentially expressed peptides. Effects of differential peptide 405SPLFMGKVVNPTQK418 on the behaviors of trophoblasts and angiogenesis were assessed by CCK8, transwell assays, and tube network formation assays. And we also confirmed the role of peptide in the zebrafish xenograft model. A total of 3582 peptide were identified. 48 peptides were differentially expressed. Bioinformatics analysis indicated that precursor proteins of these differentially expressed peptides correlate with "complement and coagulation cascades," and "platelet activation" pathways. Of the 48 differential peptides, we found that peptide 405SPLFMGKVVNPTQK418 can significantly increase proliferation, migration of trophoblasts and stimulate angiogenesis of HUVECs in vitro and zebrafish model. These findings suggest peptidomes can aid in understanding the pathogenesis of PE more comprehensively. Peptide 405SPLFMGKVVNPTQK418 can be novel target and strategy to alleviate the condition of preeclampsia.

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway.

This study explored the effect of Regenerating Islet-Derived 3-Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real-time polymerase chain reaction (qRT-PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 µM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit-8 and methyl-thiazolyl-tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT-PCR, Western blot and immunohistochemistry. As a result, REG3A was over-expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR-1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.

Analysis of tobacco exposures and high-risk HPV infection in American women: National Health and Nutrition Examination Survey.

Nicotine is a known toxin, but its relationship with cervicovaginal high-risk human papillomavirus (HR-HPV) infection is uncertain. This study aimed to investigate whether tobacco exposure is associated with elevated cervicovaginal HR-HPV infection in US women, and if the strength of this association varies with the degree of exposure. Cross-sectional data from the 2011-2016 National Health and Nutrition Examination Survey (NHANES), which included a nationally representative sample of US women, were used for the study. Out of 12436 women aged 18-59 who participated in the interview, 3833 were ultimately enrolled in this study. Weighted logistic regression was used to estimate the link between tobacco exposure and cervicovaginal HR-HPV infection. The mean age of participants was 38.6 (SD 12.1) years, and non-Hispanic White individuals accounted for 37.3% of the sample. Those with any tobacco exposure tended to be younger (mean age 37.7 [SD 12.4] years vs 40.3 [11.2] years), non-Hispanic Black (27.8% vs. 15.1%), lower educated (41.8% vs. 29.4%), and have lower family income (39.9% vs. 23.5%). After adjustment, the odds of having HR-HPV infection were 1.32 (95% CI, 1.09-1.59) for those exposed to tobacco, remaining significant in multiple sensitivity analyses and across subgroups. This study, based on a nationally representative sample from the United States, suggests that tobacco exposure is a risk factor for elevated HR-HPV infection in women, highlighting the need for further research into reducing this modifiable risk factor.

Using the PEAR1 Polymorphisms Rs12041331 and Rs2768759 as Potential Predictive Markers of 90-Day Bleeding Events in the Context of Minor Strokes and Transient Ischemic Attack.

In this study, we explored the relationship between the platelet endothelial aggregation receptor 1 (PEAR1) polymorphisms, platelet reactivity, and clinical outcomes in patients with minor stroke or transient ischemic attack (TIA). Randomized controlled trial subgroups were assessed, wherein patients received dual antiplatelet therapy for at least 21 days. Platelet reactivity was measured at different time intervals. Genotypes were categorized as wild-type, mutant heterozygous, and mutant homozygous. Clinical outcomes were evaluated after 90 days. The rs12041331 polymorphism predominantly influenced adenosine diphosphate channel platelet activity, with the AA genotype displaying significantly lower residual platelet activity to the P2Y12 response unit (p < 0.01). This effect was more evident after 7 days of dual antiplatelet treatment (p = 0.016). Mutant A allele carriers had decreased rates of recurrent stroke and complex endpoint events but were more prone to bleeding (p = 0.015). The rs2768759 polymorphism majorly impacted arachidonic acid (AA) channel platelet activity, which was particularly noticeable in the C allele carriers. Our regression analysis demonstrated that rs12041331 AA + GA and rs2768759 CA predicted 90-day post-stroke bleeding. In conclusion, the PEAR1 polymorphisms rs12041331 and rs2768759 interfere with platelet aggregation and the performance of antiplatelet drugs. These genetic variations may contribute to bleeding events associated with minor stroke and TIA.

Granulocyte-macrophage colony-stimulating factor promotes endometrial repair after injury by regulating macrophages in mice.

Intrauterine adhesion (IUA) caused by endometrial injury is a common cause of female infertility and is challenging to treat. Macrophages play a critical role in tissue repair and cyclical endometrial regeneration. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has significant reparative and anti-fibrotic effects in various tissues. However, there is limited research on the role of GM-CSF in the repair of endometrial injury and the involvement of macrophages in GM-CSF-mediated endometrial repair. In this study, using a mouse model of endometrial scratching injury, we found that GM-CSF treatment accelerated the repair of endometrial injury and improved fertility. At the molecular level, we observed that GM-CSF can downregulate the transcript levels of tumor necrosis factor (TNF) in mouse bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) and upregulate the expression of Arginase-1 (Arg-1) and mannose receptor C-type 1 (MRC1). Importantly, during the early and middle stages of injury, GM-CSF increased the proportion of M1-like, M2-like, and M1/M2 mixed macrophages, while in the late stage of injury, GM-CSF facilitated a decline in the number of M2-like macrophages. These findings suggest that GM-CSF may promote endometrial repair by recruiting macrophages and modulating the LPS-induced M1-like macrophages into a less inflammatory phenotype. These insights have the potential to contribute to the development of novel therapeutic approaches for the treatment of intrauterine adhesion and related infertility.

Dynamic nomogram for predicting acute kidney injury in patients with community-acquired pneumonia.

INTRODUCTION: Acute kidney injury (AKI) is a common complication in patients with community-acquired pneumonia (CAP) and negatively affects both short-term and long-term prognosis in patients with CAP. However, no study has been conducted on developing a clinical tool for predicting AKI in CAP patients. Therefore, this study aimed to develop a predictive tool based on a dynamic nomogram for AKI in CAP patients. METHODS: This retrospective study was conducted from January 2014 to May 2017, and data from adult inpatients with CAP at Nanjing First Hospital were analysed. Demographic data and clinical data were obtained. The least absolute shrinkage and selection operator (LASSO) regression model was used to select important variables, which were entered into logistic regression to construct the predictive model for AKI. A dynamic nomogram was based on the results of the logistic regression model. Calibration and discrimination were used to assess the performance of the dynamic nomogram. A decision curve analysis was used to assess clinical efficacy. RESULTS: A total of 2883 CAP patients were enrolled in this study. The median age was 76 years (IQR 63-84), and 61.3% were male. AKI developed in 827 (28.7%) patients. The LASSO regression analysis selected five important factors for AKI (albumin, acute respiratory failure, CURB-65 score, Cystatin C and white cell count), which were then entered into the logistic regression to construct the predictive model for AKI in CAP patients. The dynamic nomogram model showed good discrimination with an area under the receiver operating characteristics curve of 0.870 and good calibration with a Brier score of 0.129 and a calibration plot. The decision curve analysis showed that the dynamic nomogram prediction model had good clinical decision-making. CONCLUSION: This easy-to-use dynamic nomogram may help physicians predict AKI in patients with CAP.

High expression of peroxisomal D-bifunctional protein in cytosol regulates apoptosis and energy metabolism of hepatocellular carcinoma cells via PI3K/AKT pathway.

Peroxisomal D-bifunctional protein (DBP) is an indispensable enzyme of the fatty acid ß-oxidation in the peroxisome of humans. However, the role of DBP in oncogenesis is poorly understood. Our previous studies have demonstrated that DBP overexpression promotes hepatocellular carcinoma (HCC) cell proliferation. In this study, we evaluated the expression of DBP in 75 primary HCC samples using RT-qPCR, immunohistochemistry, and Western blot, as well as its correlation with the prognosis of HCC. In addition, we explored the mechanisms by which DBP promotes HCC cell proliferation. We found that DBP expression was upregulated in HCC tumor tissues, and higher DBP expression was positively correlated with tumor size and TNM stage. Multinomial ordinal logistic regression analysis indicated that lower DBP mRNA level was an independent protective factor of HCC. Notably, DBP was overexpressed in the peroxisome and cytosol and mitochondria of tumor tissue cells. Xenograft tumor growth was promoted by overexpressing DBP outside peroxisome in vivo. Mechanistically, DBP overexpression in cytosol activated the PI3K/AKT signaling axis and promoted HCC cell proliferation by downregulating apoptosis via AKT/FOXO3a/Bim axis. In addition, overexpression of DBP increased glucose uptake and glycogen content via AKT/GSK3ß axis, as well as elevated the activity of mitochondrial respiratory chain complex III to increase ATP content via the mitochondrial translocation of p-GSK3ß in an AKT-dependent manner. Taken together, this study was the first to report the expression of DBP in peroxisome and cytosol, and that the cytosolic DBP has a critical role in the metabolic reprogramming and adaptation of HCC cells, which provides a valuable reference for instituting an HCC treatment plan.

Kinetically inert manganese (II)-based hybrid micellar complexes for magnetic resonance imaging of lymph node metastasis.

The localization and differential diagnosis of the sentinel lymph nodes (SLNs) are particularly important for tumor staging, surgical planning and prognosis. In this work, kinetically inert manganese (II)-based hybrid micellar complexes (MnCs) for magnetic resonance imaging (MRI) were developed using an amphiphilic manganese-based chelate (C18-PhDTA-Mn) with reliable kinetic stability and self-assembled with a series of amphiphilic PEG-C18 polymers of different molecular weights (C18En, n = 10, 20, 50). Among them, the probes composed by 1:10 mass ratio of manganese chelate/C18En had slightly different hydrodynamic particle sizes with similar surface charges as well as considerable relaxivities (∼13 mM-1 s-1 at 1.5 T). In vivo lymph node imaging in mice revealed that the MnC MnC-20 formed by C18E20 with C18-PhDTA-Mn at a hydrodynamic particle size of 5.5 nm had significant signal intensity brightening effect and shortened T1 relaxation time. At an imaging probe dosage of 125 µg Mn/kg, lymph nodes still had significant signal enhancement in 2 h, while there is no obvious signal intensity alteration in non-lymphoid regions. In 4T1 tumor metastatic mice model, SLNs showed less signal enhancement and smaller T1 relaxation time variation at 30 min post-injection, when compared with normal lymph nodes. This was favorable to differentiate normal lymph nodes from SLN under a 3.0-T clinical MRI scanner. In conclusion, the strategy of developing manganese-based MR nanoprobes was useful in lymph node imaging.

Diagnostic value of anti-Müllerian hormone combined with androgen-levels in Chinese patients with polycystic ovary syndrome.

OBJECTIVE: To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS. MATERIALS AND METHODS: This is a prospective case control study, 550 women recruited (aged 20-40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. RESULTS: The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS. CONCLUSION: The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.

Ovarian tissue cryopreservation in the pediatric with rare diseases- experience from China's first and the largest ovarian tissue cryobank.

Background: There is limited information about the efficacy of ovarian tissue cryopreservation (OTC) in children. In the present study, we report eight patients with rare diseases who underwent OTC in China's first and largest ovarian tissue cryobank. Procedure: Data from girls with rare diseases who underwent OTC between September 2020 and November 2022 were retrospectively analyzed. We also compared the number of cryopreserved cortex pieces, follicle number, and AMH in those with rare diseases and age-matched children with non-rare diseases who also underwent OTC in our cryobank. Results: The median age of the children was 5.88 ± 3.52 (range 2-13) years old. Unilateral oophorectomy was undertaken via laparoscopy in all of the children. The diseases in the 8 patients were: 4 mucopolysaccharidoses (MPS I two cases, IVA two cases), 1 Diamond-Blackfan anemia (DBA), 1 Fanconi anemia (FA), 1 hyperimmunoglobulin E syndrome (HIES), 1 Niemann-Pick disease. The number of cryopreserved cortex pieces was 17.13 ± 6.36, and the follicle count per 2 mm biopsy was 447.38 ± 524.35. No significant difference in age, the count of cryopreserved cortex pieces, follicle number per 2 mm biopsy, and AMH level was seen between the 20 children with non-rare diseases and those with rare diseases. Conclusions: The reports help practitioners counsel girls with rare diseases about fertility preservation. The demand for OTC in pediatrics will likely grow as a standard of care.

DNA-Guided One-Dimensional Plasmonic Nanostructures for the SERS Bioassay.

Plasmonic nanostructures have a desirable surface-enhanced Raman scattering (SERS) response related to particle spacing. However, precisely controlling the distance of plasmonic nanostructures is still a challenge. DNA has the merit of specific recognition, and flexible modification of functional groups, which can be used to flexibly adjust the gaps between plasmonic nanostructures for improving the stability of SERS. In this paper, DNA-guided gold nanoparticles formed one-dimensional ordered structures and they were self-assembled at the water-oil interface by a bottom-up approach. Notably, an output switching strategy successfully transfers a small amount of target into a large amount of reporter DNA; thereby, Raman probes are captured on the sensing interface and achieve the SERS assay of microRNA 155 (miRNA-155). This study is an exciting strategy for obtaining ordered plasmonic structures and providing surveillance, which is important for the clinical diagnosis of early-stage cancer.

Chiral plasmonic Au-Ag core shell nanobipyramid for SERS enantiomeric discrimination of biologically relevant small molecules.

The identification of enantiomers is of great importance in chiral separations and medicinal chemistry. While Surface-enhanced Raman spectroscopy (SERS) is a technique that provides vibrational fingerprints of analytes. The enantiomers identification relies on the SERS difference between left and right-handed circularly polarized light or additional selectors for indirect distinction. In this work, Au-Ag core shell nanobipyramid (L/D-Au@Ag BPs) were synthesized guiding by chiral encoder of L/D-cysteine. L/D-Au@Ag BPs produced plasmon-induced circular dichroism signals in the plasmon resonance absorption band, which can be tuned by modulation the amount of cysteine. Moreover, the chiral anisotropy factor of L/D-Au@Ag BPs at 532 nm can reach 5.11 × 10-3. Due to the selective resonance coupling between L/D-Au@Ag BPs and different enantiomers, L/D-Au@Ag BPs were further used as SERS substrates for efficient discrimination of biologically relevant small molecules. Chiral Au@Ag BPs display the potential for chiral drug identification.

Association between the reactivity of local cerebral oxygen saturation after hypo-to-hypercapnic tests and delirium after abdominal surgery in older adults: A prospective study.

Objective: This study aimed to investigate the correlation between changes in regional cerebral oxygen saturation (rSO2) and postoperative delirium in older adults undergoing major abdominal surgery. Materials and methods: This prospective study enrolled older adults scheduled for elective major abdominal surgery at the Second Affiliated Hospital of Anhui Medical University from August 2021 to January 2022. The change in rSO2 from baseline was determined using the hypo-to-hypercapnic test. The main study outcome was the occurrence of postoperative delirium. Results: A total of 101 participants were included for analysis, of whom 16 (15.8%) developed postoperative delirium. Compared with non-delirium participants, the mean arterial pressure and heart rate were not significantly different in the postoperative delirium group at T0, T1, T2, T3, T4, and T6 (all Pinteraction > 0.05), but the delirium group had lower pH, lower PaO2, and higher lactate levels at T4, T5, and T6 (all Pinteraction < 0.05). rSO2 at T0, T1, T2, T3, T4, and T6 was 69.0 (63.2-75.2), 70.7 ± 7.3, 68.2 ± 7.5, 72.1 ± 8.0, 69.9 ± 7.8, 67.4 ± 7.2, and 71.7 ± 8.1, respectively. The postoperative change in rSO2 during the hypercapnia test (TΔrSO2%) was 6.62 (5.31-9.36). Multivariable analysis showed that the Cumulative Illness Rating Scale (odd ratio, OR = 1.89, 95% confidence interval, CI: 1.10-3.25, P = 0.021), preoperative albumin levels (OR = 0.67, 95% CI: 0.48-0.94, P = 0.022), rSO2 at T4 (OR = 0.61, 95% CI: 0.41-0.89, P = 0.010), and postoperative TΔrSO2% (OR = 0.80, 95% CI: 0.66-0.98, P = 0.028) were independently associated with postoperative delirium in older adults undergoing elective abdominal surgery. Conclusion: The rSO2 measured at T4 and postoperative TΔrSO2% were independently associated with postoperative delirium in older adults undergoing elective abdominal surgery.

Dexmedetomidine postconditioning provides renal protection in patients undergoing laparoscopic partial nephrectomy: A randomized controlled trial.

Background: For localized disease, partial nephrectomy of small tumors continues to be the gold-standard treatment. However, temporary clamping is routinely performed during this process to control renal blood flow, which can cause renal ischemic/reperfusion injury. We evaluated whether dexmedetomidine postconditioning (DPOC) can reduce renal ischemic/reperfusion injury for patients receiving laparoscopic partial nephrectomy (LPN). Methods: This randomized double-blind controlled trial included 77 patients who were scheduled for LPN at our hospital. Patients were randomly allocated to the DPOC or control group. DPOC was performed via intravenous administration of dexmedetomidine at 0.6 µg kg-1 for 10 min immediately after unclamping the renal artery. In the control group, saline was administered in place of dexmedetomidine under the same protocol. All participants underwent a 6-month follow-up. The primary outcome were the values of 99mTc-DTPA-GFR in the affected kidney at one and 6 months post-LPN. Result: The GFR values in the DPOC group (35.65 ± 4.89 ml min-1.1.73 m-2) were significantly higher than those the control group (33.10 ± 5.41 ml min-1.1.73 m-2; p = 0.022) at 1 month after LPN. There was no statistically significant difference in GFR value between the two groups at 6 months after LPN. Conclusion: DPOC provides therapeutic benefits to LPN patients, at least on a short-term basis, by alleviating renal ischemic/reperfusion injury. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR-TRC-14004766].