AIM: To explore the factors influencing heart rate(HR)changes during small incision lenticule extraction(SMILE)surgery by monitoring HR trends at different time points of the procedure.METHODS: Prospective cohort study. A total of 69 patients who underwent SMILE surgery at the Laser Vision Correction Center of Xi'an No.1 Hospital from April to May 2024 were enrolled. Before the surgery, patients completed the State Anxiety Inventory(S-AI, questions 1-20)to assess their preoperative anxiety scores related to the next day's surgery. Baseline HR was recorded using medical pulse oximeter, and real-time HR was recorded during patient positioning, lenticule scanning, lenticule separation and extraction, and the application of postoperative eye drops.RESULTS: The HR during patient positioning was 83.61±13.87 bpm, which was significantly different from the baseline HR(77.52±10.88 bpm), HR during lenticule separation and extraction(75.54±12.52 bpm), and HR during postoperative eye drop application(76.65±10.54 bpm; all P<0.001). When stratified by median age, older patients(>26 years)had the HR during lenticule separation and extraction 76.27±9.93 bpm, which differed from the HR at positioning(84.82±14.10 bpm)and at lens scanning(82.76±13.72 bpm; all P<0.005). Stratified by gender, the HR of male patients at positioning was the highest(85.31±16.61 bpm), which differed significantly from the baseline HR(78.26±12.63 bpm), HR during lenticule separation and extraction(77.14±14.59 bpm), and HR during postoperative eye drop application(77.11±12.49 bpm; all P<0.005). There was no correlation between HR during positioning and preoperative anxiety scores(r=0.124, P=0.418).CONCLUSION: HR changes during SMILE surgery vary with different procedural stages, peaking during patient positioning and reaching the lowest point during lenticule separation and extraction. Older patients showed higher HR during positioning, and male patients exhibited higher HR during positioning.

Mobile computed tomography (CT) can be used for critically ill patients’ bedside CT scans in an operating room or intensive care unit because of its flexibility and convenience compared to conventional CT. Meanwhile, attention has been paid to the ionizing radiation hazards brought by mobile CT scans due to a lack of wall shielding protection from a fixed machinery room, especially the control of radiation dose to the surrounding medical staff and the public. This article mainly discusses the radiation protection of mobile CT from aspects such as radiation protection principles, protection management, and protection of examinees, staff, and the public by summarizing relevant standards, guidelines, and literature in China and globally to provide a reference for the standardized use of mobile CT.

Objective: To investigate the effects of autologous platelet-rich plasma (aPRP) collected using a continuous blood cell separator on blood conservation and prognosis in patients with type A aortic dissection. Methods: The clinical data of patients who underwent emergency aortic replacement for acute type A aortic dissection at our hospital from January 2020 to December 2023 were respectively analyzed. Patients were divided into two groups based on whether they received aPRP collection before surgery for subsequent reinfusion: the aPRP group (n=32) and the control group (n=35). The volume of aPRP collected and the platelet concentration in the aPRP were recorded. The volumes of allogeneic blood and blood products transfused, and the associated costs during hospitalization were compared between two groups. Intraoperative blood loss, perioperative laboratory parameter changes, 24-hour postoperative drainage volume, duration of ICU stay and mechanical ventilation, length of hospital stay, and mortality rate of the two groups were also compared. Results: The platelet concentration in aPRP was (491.5±85.4)×10 /L, accounting for (24.1±9.6)% of the patient's total platelet count. The volume of aPRP collected accounted for (23.0±6.3)% of the patient's total plasma volume. Compared with the control group, the aPRP group demonstrated significantly reduced transfusion volumes of allogeneic red blood cells, plasma, and platelets (P<0.05), along with significantly lower blood-related costs during hospitalization (P<0.05). Postoperative coagulation parameters (APTT, PT, INR, and TEG) were significantly improved (P<0.05), and platelet counts were markedly increased (P<0.05) in aPRP group as compared with the control group. No statistically significant differences were observed in postoperative use of prothrombin complex concentrate and fibrinogen between the two groups. Similarly, there were no significant differences in postoperative 24-hour drainage volume, 24-hour extubation rate, ICU length of stay, duration of mechanical ventilation, or total hospital length of stay. The incidence of complications and mortality did not differ significantly between the two groups. Conclusion: The administration of aPRP significantly reduces the requirement for perioperative allogeneic blood transfusion in patients undergoing surgery for type A aortic dissection. Furthermore, it enhances coagulation function and reduces associated transfusion costs, thereby establishing itself as an effective and safe strategy for blood conservation.

Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.