Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting ...stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery.
Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days.
Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 1.8% of 857 patients) than in the general anesthesia group (43 5.0% of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 49% vs. 288 33%; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 58% vs. 387 45%; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001).
Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.
Standard management for intrauterine lesions typically involves initial imaging followed by operative hysteroscopy for suspicious findings. However, the efficacy of routine outpatient hysteroscopy in ...women undergoing assisted reproductive technology (ART) remains uncertain due to a lack of decisive high-quality evidence. This study aimed to determine whether outpatient hysteroscopy is beneficial for infertile women who have unremarkable imaging results prior to undergoing ART.
A systematic review and meta-analysis were conducted following PRISMA guidelines, incorporating data up to May 31, 2023, from databases such as PubMed, Embase, and the Cochrane Library. The primary outcome assessed was the live birth rate, with secondary outcomes including chemical pregnancy, clinical pregnancy rates, and miscarriage rates. Statistical analysis involved calculating risk ratios with 95% confidence intervals and assessing heterogeneity with the I
statistic.
The analysis included ten randomized control trials. Receiving outpatient hysteroscopy before undergoing ART was associated with increased live birth (RR 1.22, 95% CI 1.03-1.45, I
61%) and clinical pregnancy rate (RR 1.27 95% CI 1.10-1.47, I
53%). Miscarriage rates did not differ significantly (RR 1.25, CI 0.90-1.76, I
50%). Subgroup analyses did not show a significant difference in clinical pregnancy rates when comparing normal versus abnormal hysteroscopic findings (RR 1.01, CI 0.78-1.32, I
38%). We analyzed data using both intention-to-treat and per-protocol approaches, and our findings were consistent across both analytical methods.
Office hysteroscopy may enhance live birth and clinical pregnancy rates in infertile women undergoing ART, even when previous imaging studies show no apparent intrauterine lesions. Treating lesions not detected by imaging may improve ART outcomes. The most commonly missed lesions are endometrial polyps, submucosal fibroids and endometritis, which are all known to affect ART success rates. The findings suggested that hysteroscopy, given its diagnostic accuracy and patient tolerability, should be considered in the management of infertility.
The study was registered in the International Prospective Register of Systemic Review database (CRD42023476403).
A novel turn-on fluorescence probe L has been designed that exhibits high selectivity and sensitivity with a detection limit of 9.53 × 10−8 mol/L for the quantification of Zn2+. 1H-NMR spectroscopy ...and single crystal X-ray diffraction analysis revealed the unsymmetrical nature of the structure of the Schiff base probe L. An emission titration experiment in the presence of different molar fractions of Zn2+ was used to perform a Job’s plot analysis. The results showed that the stoichiometric ratio of the complex formed by L and Zn2+ was 1:1. Moreover, the molecular structure of the mononuclear Cu complex reveals one ligand L coordinates with one Cu atom in the asymmetric unit. On adding CuCl2 to the ZnCl2/L system, a Cu-Zn complex was formed and a strong quenching behavior was observed, which inferred that the Cu2+ displaced Zn2+ to coordinate with the imine nitrogen atoms and hydroxyl oxygen atoms of probe L.
Pediatric cancer survivors experiencing gonadotoxic chemoradiation therapy may encounter subfertility or permanent infertility. However, previous studies of cryopreservation of immature testicular ...tissue (ITT) have mainly been limited to in vitro studies. In this study, we aim to evaluate in vitro and in vivo bioluminescence imaging (BLI) for solid surface-vitrified (SSV) ITT grafts until adulthood. The donors and recipients were transgenic and wild-type mice, respectively, with fresh ITT grafts used as the control group. In our study, the frozen ITT grafts remained intact as shown in the BLI, scanning electron microscopy (SEM) and immunohistochemistry (IHC) analyses. Graft survival was analyzed by BLI on days 1, 2, 5, 7, and 31 after transplantation. The signals decreased by quantum yield between days 2 and 5 in both groups, but gradually increased afterwards until day 31, which were significantly stronger than day 1 after transplantation (p = 0.008). The differences between the two groups were constantly insignificant, suggesting that both fresh and SSV ITT can survive, accompanied by spermatogenesis, until adulthood. The ITT in both groups presented similar BLI intensity and intact cells and ultrastructures for spermatogenesis. This translational model demonstrates the great potential of SSV for ITT in pre-pubertal male fertility preservation.
Copper (Cu) is an essential micronutrient for all living organisms but is also highly toxic in excess. Cellular homoeostasis of Cu is maintained by various transporters and metallochaperones. Here, ...we investigated the biological function of OsCOPT7, a member of the copper transporters (COPT) family, in Cu homoeostasis in rice. OsCOPT7 was mainly expressed in the roots and the expression was upregulated by Cu deficiency. OsCOPT7 was localized at the tonoplast and the endoplasmic reticulum. Knockout of OsCOPT7 increased Cu accumulation in the roots but decreased Cu concentrations in the shoots and grain. The knockout mutants contained higher concentrations of Cu in the roots cell sap but markedly lower concentrations of Cu in the xylem sap than wild‐type plants. Seed setting and grain yield were reduced significantly in the knockout mutants grown in a low Cu soil. Knockout mutants were more tolerant to Cu toxicity. Yeast two‐hybrid and bimolecular fluorescence complementation assays showed that OsCOPT7 interacts physically with the rice Cu chaperone antioxidant protein 1 (OsATX1). Taken together, our results indicate that OsCOPT7 is a specific Cu transporter functioning to export Cu from the vacuoles and the ER and plays an important role in controlling the root‐to‐shoot Cu translocation in rice.
Summary statement
Copper (Cu) is an essential micronutrient for all living organisms but is also highly toxic in excess. Cellular homoeostasis of Cu is maintained by various transporters and metallochaperones. We show that OsCOPT7 is a Cu transporter functioning to export Cu from the vacuoles and the endoplasmic reticulum and plays an important role in controlling the root‐to‐shoot Cu translocation in rice.
Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of ...breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.
The inflammatory response is one of the most important factors in the occurrence and development of acute lung injury (ALI). Hypoxia‑inducible factor‑1α (HIF‑1α) and the NOD‑like receptor 3 (NLRP3) ...inflammasome have been demonstrated to serve an important role in the pathogenesis of ALI. The objective of the present study was to investigate whether HIF‑1α could regulate activation of the NLRP3 inflammasome and its potential function and specific mechanism in bleomycin (BLM)‑induced ALI. Activation of the NLRP3 inflammasome and secretion of IL‑1β were detected following silencing of HIF‑1α or NF‑κB, respectively, in BLM‑treated A549 and RLE‑6TN cells. The results demonstrated that the NLRP3 inflammasome could be activated after BLM treatment. HIF‑1α and NF‑κB expression significantly increased in the BLM group. The levels of NF‑κB‑ and NLRP3 inflammasome‑associated proteins, including NLRP3, apoptosis‑associated speck‑like protein containing CARD and caspase‑1, markedly decreased after treating A549 and RLE‑6TN cells with HIF‑1α small interfering RNA. Activation of the NLRP3 inflammasome was also inhibited after silencing NF‑κB. Furthermore, the levels of IL‑1β markedly decreased in the cellular culture supernatants following inhibition of HIF‑1α and NF‑κB. Therefore, the present study indicated that HIF‑1α could modulate the activation of the NLRP3 inflammasome and the secretion of IL‑1β through NF‑κB signaling in BLM‑induced ALI. The current results improve understanding of the mechanism of ALI and may provide new ideas for identifying therapeutic targets of ALI.
Engineering the band-edge of photocatalysts is one of the important strategies to adjust the photocatalytic performance. Herein, we successfully prepare Cu-Fe2O3/Ni-ZnO nanoplate photocatalysts and ...confirm by a series of materials characterization. The prepared Cu-Fe2O3/Ni-ZnO nanoplate exhibits the highest photodegradation performance of tetracycline among all the prepared samples. The experimental results demonstrate that introducing elements into Fe2O3/ZnO regulates the potentials of the conduction band and valence band, accelerating the recombination of Cu-Fe2O3 photogenerated electrons with Ni-ZnO holes. Furthermore, electron spin resonance (ESR) spectroscopy reveals that rapid production of reactive oxygen species (ROS) such as •O2 – and •OH can improve the photodegradation activity of Cu-Fe2O3/Ni-ZnO. This work reveals that engineering the band-edge of photocatalysts can be considered as an effective method to improve the photocatalytic activity.
The shear mechanical behavior of discontinuities under unloading conditions induced by intensive rock mass excavation differs from that under loading conditions. Therefore, the mechanical parameters ...obtained from the conventional direct shear test cannot effectively be used to assess the stability of excavated rock masses. To solve this problem, we conducted a series of experiments on saw-toothed discontinuities with different undulating angles and initial shear stresses under unloading normal stress with constant shear stress. The test results showed that the shear pattern transformed from climbing to climbing-gnawing and then to gnawing patterns as the undulating angle and initial shear stress increased. The shear stress remained stable with increasing shear displacement after instability in the climbing pattern, decreased with fluctuations in the climbing–gnawing pattern, and dropped steeply in the gnawing pattern. A negative linear correlation exists between the unloading magnitude and the initial shear stress. Unloading normal stress promoted deformation rebound and sawtooth damage, reducing the mobilizing shear strength. Modified Patton and Barton shear strength criteria considering the undulating angle, initial stress, and failure pattern under unloading normal stress were proposed.
Highlights
The shear mechanical behavior of saw-toothed discontinuities with different undulating angles and initial shear stresses under unloading normal stress with constant shear stress are investigated.
The failure pattern changes from the climbing pattern to the climbing–gnawing pattern and then to the gnawing pattern as the undulating angle and the initial shear stress increase.
Unloading promotes the increase in rebound deformation and the area of the damage zone, leading to the decrease in shear strength of saw-toothed discontinuities.
The modified Patton criterion and the Barton criterion are proposed for unloading normal stress considering the undulating angle, initial stress state, and failure pattern.
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