Exploring bleeding in oral anticoagulant users: assessing incidence by indications and risk factors in the entire nationwide cohort.

Background: Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment. Objectives: We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors. Methods: This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations. Results: Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63). Conclusion: These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding.

Inflammation-related markers and prognosis of alpha-fetoprotein producing gastric cancer.

BACKGROUND: Inflammation-related markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) could reflect tumor immune microenvironment and predict prognosis of cancers. However, it had not been explored in alpha-fetoprotein (AFP) producing gastric cancer (GC). AIM: To determine the predictive value of inflammation-related peripheral blood markers including as NLR, PLR, MLR, SII, SIRI and PNI in the prognosis of AFP- producing GC (AFPGC). Besides, this study would also compare the differences in tumor immune microenvironment, clinical characteristics and prognosis between AFPGC and AFP- GC patients to improve the understanding of this disease. METHODS: 573 patients enrolled were retrospectively studied. They were divided into AFP+ group (AFP ≥ 20 ng/mL) and AFP- group (AFP < 20 ng/mL), comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis. In AFP+ group, the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored. RESULTS: Compared with AFP- patients, AFP+ patients had higher NLR/PLR/MLR/SII/SIRI and lower PNI levels and poorer overall survival (OS). In the AFP+ group, mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group. Moreover, the dynamic increase (NLR/PLR/MLR/SII/SIRI) or decrease (PNI) was associated with the rise of mortality within 1 year of follow-up. CONCLUSION: Compared with AFP- patients, the level of inflammation-related peripheral blood markers significantly increased in AFP+ patients, which was correlated with OS of AFP+ patients. Also, the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+ patients. AFPGC should be considered as a separate type and distinguished from AFP- GC because of the difference in tumor immune microenvironment. It requires basic experiments and large clinical samples in the future.

Diabetic uveopathy.

Diabetes can involve several ocular structures -- including the cornea, lens, and retina -- and cause vascular and neural changes in these tissues. Although retinopathy is the most common ocular complication of diabetes, uveopathy can also be observed. This includes vascular, neural, muscular, and basement membrane changes. The main clinical manifestations of diabetic uveopathy are anterior uveitis and abnormal pupillary dynamics. Fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography are ideal for the imaging of vascular changes of the iris and choroid, while dynamic pupillometry is a simple screening tool to detect neuropathy. Additionally, ultrasound biomicroscopy can provide clear images of the ciliary body. Iris abnormalities, primarily angiopathy and neuropathy, can appear as alterations in vascular diameter, neovascularization, and abnormal pupillary dynamics. Choroidal abnormalities primarily affect blood vessels, including alterations in vascular diameter, microaneurysm formation, and neovascularization. The abnormal manifestations in the ciliary body include a decrease in vessel count, alterations in their diameter, isolated angiomatous dilatation, and diffuse thickening of the basal membrane of the pigment epithelium.

Five-year analysis of isolated pathogens and antibiotic resistance of ocular infections from two large tertiary comprehensive hospitals in east China.

AIM: To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China. METHODS: Ocular specimen data were collected from January 2019 to October 2023. The pathogen spectrum and positive culture rate for different infection location, such as keratitis, endophthalmitis, and periocular infections, along with antibiotic resistance were analyzed. RESULTS: We included 2727 specimens, including 827 (30.33%) positive cultures. A total of 871 strains were isolated, 530 (60.85%) bacterial and 341 (39.15%) fungal strains were isolated. Gram-positive cocci (GPC) were the most common ocular pathogens. The most common bacterial isolates were Staphylococcus epidermidis (25.03%), Staphylococcus aureus (7.46%), Streptococcus pneumoniae (4.59%), Corynebacterium macginleyi (3.44%), and Pseudomonas aeruginosa (3.33%). The most common fungal genera were Fusarium spp. (12.74%), Aspergillus spp. (6.54%), and Scedosporium spp. (5.74%). Staphylococcus epidermidis strains showed more than 50% resistance to fluoroquinolones. Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90% resistance to erythromycin. The percentage of bacteria showing multidrug resistance (MDR) significantly decreased (χ 2=17.44, P=0.002). CONCLUSION: GPC are the most common ocular pathogens. Corynebacterium macginleyi, as the fourth common bacterium, may currently be the local microbiological feature of east China. Fusarium spp. is the most common fungus. More than 50% of the GPC are resistant to fluoroquinolones, penicillins, and macrolides. However, the proportion of MDR strains has been reduced over time.

Massive water production from lunar ilmenite through reaction with endogenous hydrogen.

Finding water resources is a crucial objective of lunar missions. However, both hydroxyl (OH) and natural water (H2O) have been reported to be scarce on the Moon. We propose a potential method for obtaining water on the Moon through H2O formation via endogenous reactions in lunar regolith (LR), specifically through the reaction FeO/Fe2O3 + H → Fe + H2O. This process is demonstrated using LR samples brought back by the Chang'E-5 mission. FeO and Fe2O3 are lunar minerals containing Fe oxides. Hydrogen (H) retained in lunar minerals from the solar wind can be used to produce water. The results of this study reveal that 51-76 mg of H2O can be generated from 1 g of LR after melting at temperatures above 1,200 K. This amount is ∼10,000 times the naturally occurring OH and H2O on the Moon. Among the five primary minerals in LR returned by the Chang'E-5 mission, FeTiO3 ilmenite contains the highest amount of H, owing to its unique lattice structure with sub-nanometer tunnels. For the first time, in situ heating experiments using a transmission electron microscope reveal the concurrent formation of Fe crystals and H2O bubbles. Electron irradiation promotes the endogenous redox reaction, which is helpful for understanding the distribution of OH on the Moon. Our findings suggest that the hydrogen retained in LR is a significant resource for obtaining H2O on the Moon, which is helpful for establishing a scientific research station on the Moon.

Functional Role of Piezo1 in the Human Eosinophil Cell Line AML14.3D10: Implications for the Immune and Sensory Nervous Systems.

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.

Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.

Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Molecular phylogeny and species diversity of the genus Dichaetophora Duda and related taxa (Diptera: Drosophilidae).

Our intensive surveys of wild drosophilids in East and Southeast Asia discovered a great species diversity (more than 100 putatively new species) of the genus Dichaetophora, which is currently comprised of 67 formally described species assigned into five species groups, i.e., agbo, tenuicauda, acutissima, sinensis and trilobita. In the present study, we delimited species from a huge amount of samples of Dichaetophora and allied taxa (the genus Mulgravea and the subgenus Dudaica of Drosophila) collected from a wide range of the Oriental and east Palearctic regions. We first sorted all specimens into morpho-species, and representative specimen(s) selected from each morpho-species were subjected to barcoding of COI (the cytochrome c oxidase subunit I gene) sequences. The applied ASAP (Assemble Species by Automatic Partitioning) analysis estimated a total of 166 to 168 MOTUs (molecular operational taxonomic units). Integrating this result with morphological evidence from re-examined, detailed structures of male terminalia, we recognized a total of 144 (109 new and 35 known) species in our sample. Out of them, 83 species representing the supraspecific taxa of Dichaetophora, Mulgravea and Dudaica were selected, along with 33 species from major genera and subgenera of Drosophila in the tribe Drosophilini, as in-group and four species from the tribe Colocasiomyini as out-group for phylogenetic reconstruction based on 12 nuclear gene markers. In the trees constructed by the maximum likelihood and Bayesian inference methods, the three focal taxa (i.e., Dichaetophora, Mulgravea and Dudaica) formed a clade provisionally called the "pan-Dichaetophora". Within this large clade, the agbo, tenuicauda, sinensis and trilobita groups of Dichaetophora, Mulgravea and Dudaica were recovered as monophyletic groups, but Dichaetophora and its acutissima group were regarded as paraphyletic. In addition, two clusters were recognized among ungrouped species of Dichaetophora. Thus, the present study has uncovered some issues concerning the taxonomy of the pan-Dichaetophora. Such issues will be addressed elsewhere in the phylogenetic reclassification of the pan-Dichaetophora, along with descriptions/redescriptions of a large number of new/known species delimited in the present study.

Oral administration enhances directly mucosal immune system in intestine of olive flounder (Paralichthys olivaceus).

Aquaculture is notably vulnerable to diseases, with Edwardsiella tarda causing significant mortality across various commercially important fish species in both freshwater and marine environments. In the aquaculture industry, sustainable disease control hinges on the effective development of vaccines. Oral vaccines present an appealing approach to immunization in fish due to their ease of antigen administration, reduced stress compared to non-oral delivery methods, and their potential applicability to both small and large finfish species. In mammals, the exposure of mucosal surfaces to antigens results in the secretion of antigen-specific IgA at these locations. Mammals have a common mucosal immune system, in which stimulation of one epithelium can also give rise to specific IgA or IgM responses in other mucosal organs. Mucosal immunoglobulins are particularly important in developing vaccines that provide mucosal immunity. However, it remains unclear whether fish share a common mucosal system. Moreover, neither Peyer's patches nor intestinal lymph nodes were identified. Nevertheless, oral vaccination remains an attractive method for inducing immunity. We investigated whether the activation of the mucosal immune response was induced by direct injection of the antigen. After oral antigen administration, antigen-specific antibody titers increased in the experimental group (E. tarda FKC vaccine). In the challenge experiment, the cumulative survival rate was 72% (E. tarda). This suggests that oral administration of antigens can activate intestinal mucosal immunity in flounders. Additionally, these results help understand the intestinal mucosal immune system of teleost fish. In the future, research on the signaling mechanisms of these genes is expected to provide helpful information for developing vaccine adjuvants.

Effect of cerebrospinal dual-site magnetic stimulation on freezing of gait in Parkinson's disease.

Addressing levodopa-unresponsive freezing of gait (FOG) in Parkinson's disease (PD) presents a significant challenge. A randomized double-blinded trial evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in conjunction with transcutaneous magnetic spinal cord stimulation among 57 PD individuals experiencing levodopa-unresponsive FOG. Patients were randomized to receive dual-site stimulation involving bilateral primary motor cortex of the lower leg (M1-LL) and the lumbar spinal cord, single-site stimulation targeting bilateral M1-LL alone, or sham stimulation for 10 sessions. Low-frequency rTMS induced remarkable improvements in FOG, gait, and motor functions compared to sham at 1 day and 1 month postintervention. Notably, the dual-site protocol demonstrated superior efficacy in mitigating FOG and improving gait compared to the single-site approach, which correlated with a pronounced increase in short-interval intracortical inhibition of the abductor pollicis brevis. These findings underscore the potential of the cerebrospinal dual-site regimen as a promising approach for levodopa-unresponsive FOG and gait in PD.

Rapid Diagnostic PCR Assay Method for Species Identification of Mantidis Ootheca (Sangpiaoxiao) Based on Cytochrom C Oxidase I (COI) Barcode Analysis.

Mantidis Ootheca (sangpiaoxiao), the egg case of the mantis, is a type of insect-derived traditional medicine widely used in East Asia. However, species identification based on egg morphology is challenging, leading to the distribution of counterfeit and adulterated products. The use of inauthentic ingredients can pose serious health risks to consumers. This study aimed to develop PCR markers that can rapidly and accurately differentiate between authentic and counterfeit Mantidis Ootheca. The mitochondrial cytochrome c oxidase I (COI) region was sequenced in thirteen samples from four mantis species: Tenodera angustipennis, Statilia maculata, Hierodula patellifera, and T. sinensis. Four sets of SCAR primers were designed based on species-specific nucleotide polymorphisms, and a multiplex SCAR assay was developed by combining all sets of the primers. The sequence-characterized amplified region (SCAR) primers successfully produced amplicons for each target species, even with low-DNA templates or templates containing DNA from multiple samples. No amplification was observed for nontarget species. This study presents a novel approach for identifying authentic Mantidis Ootheca species using DNA-based diagnostic marker assays, which enable rapid and precise species identification. The SCAR assays developed in this study will aid in maintaining quality control and promoting the standardization of commercial Mantidis Ootheca products.

FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2-STAT3 signaling.

Direct cardiac reprogramming represents a novel therapeutic strategy to convert non-cardiac cells such as fibroblasts into cardiomyocytes (CMs). This process involves essential transcription factors, such as Mef2c, Gata4, Tbx5 (MGT), MESP1, and MYOCD (MGTMM). However, the small molecules responsible for inducing immature induced CMs (iCMs) and the signaling mechanisms driving their maturation remain elusive. Our study explored the effects of various small molecules on iCM induction and discovered that the combination of FGF4 and ascorbic acid (FA) enhances CM markers, exhibits organized sarcomere and T-tubule structures, and improves cardiac function. Transcriptome analysis emphasized the importance of ECM-integrin-focal adhesions and the upregulation of the JAK2-STAT3 and TGFB signaling pathways in FA-treated iCMs. Notably, JAK2-STAT3 knockdown affected TGFB signaling and the ECM and downregulated mature CM markers in FA-treated iCMs. Our findings underscore the critical role of the JAK2-STAT3 signaling pathway in activating TGFB signaling and ECM synthesis in directly reprogrammed CMs. Schematic showing FA enhances direct cardiac reprogramming and JAK-STAT3 signaling pathways underlying cardiomyocyte maturation.

Phase Behavior Modulation of a Unary DNA Origami System through Allosteric Stimuli.

A unary system is the most conceptually concise design for conducting self-assembly. However, in most DNA-guided self-assembly schemes, a unary system has rarely been adopted because of the inherent challenge of strictly decoupling the monomer synthesis process from the assembly process, which may directly lead to the inaccurate control over assembly. Herein, we provide a multi-stimulus-triggered assembly strategy based on the DNA origami structure, which allows the unary system to realize controllable crystallization and phase transition by exerting allosteric stimuli. We intentionally introduced a specific DNA stimulus to convert the self-aggregation of functionalized groups into the connection of nearby monomers, thus producing multidimensional high-quality crystals. Furthermore, this unary system can undergo a phase transition from simple cubic to face-centered cubic with the introduction of more cation stimuli. We believe that this dynamic stimulation strategy can offer a novel solution for fabricating materials with on-demand modulation.

Efficacy and comfort following the implantation of extended depth of focus, multifocal, and monofocal intraocular lenses in cataract patients.

BACKGROUND: Extended depth of focus (EDOF) and multifocal (Multi) intraocular lenses (IOL) can provide a fixed distance of near vision, which may result in some discomfort for patients who prefer different near distances. The aim of this study was to compare the vision, comfortable near distance (CND) and visual comfort in patients who underwent implantation of EDOF, Multi, and monofocal (Mono) IOLs. METHODS: A total of 100 eyes were implanted with Tecnis ZXR00, ZMB00 or ZCB00 IOLs. Uncorrected distance, intermediate, and near visual acuity (UDVA, UIVA, and UNVA, respectively), corrected distance visual acuity (CDVA), the fluctuations of CND, the ability to see at comfortable or standard near distance and visual comfort were evaluated at 3-month postoperative. RESULTS: At 3 months postoperative, the EDOF and Multi groups showed non-inferiority compared to the Mono group in the UDVA (P > 0.05) and CDVA (P > 0.05) but superiority in the UNVA (P < 0.001). The UIVA was better in the EDOF group, with comparable results for the Multi and Mono groups. There was no difference in preoperative and postoperative CND in the three groups. The CND visual acuity (CNDVA) was lower than the UNVA in the three groups, especially in the EDOF and Multi groups (P < 0.05). The CND effectively improved patients' near visual comfort and visual clarity, except for one patient in the Multi group who complained of severe fatigue and was unable to tolerate the experience at month 3. CONCLUSION: The EDOF and Multi IOLs achieved excellent visual quality and superior UNVA compared to the Mono IOL, but the CNDVA was significantly inferior to the UNVA. Patients' near visual experience can be effectively improved at their CND.

Long-Lasting, Transparent Antibacterial Shield: A Durable, Broad-Spectrum Anti-Bacterial, Non-Cytotoxic, Transparent Nanocoating for Extended Wear Contact Lenses.

The increasing incidence of serious bacterial keratitis, a sight-threatening condition often exacerbated by inadequate contact lens (CLs) care, highlights the need for innovative protective technology. This study introduces a long-lasting antibacterial, non-cytotoxic, transparent nanocoating for CLs via a solvent-free polymer deposition method, aiming to prevent bacterial keratitis. The nanocoating comprises stacked polymer films, with poly(dimethylaminomethyl styrene-co-ethylene glycol dimethacrylate) (pDE) as a biocompatible, antibacterial layer atop poly(2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane) (pV4D4) as an adhesion-promoting layer. The pD6E1-grafted (g)-pV4D4 film shows non-cytotoxicity toward two human cell lines and antibacterial activity of >99% against four bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacteria and Pseudomonas aeruginosa, which causes ocular diseases. Additionally, the film demonstrates long-lasting antibacterial activity greater than 96% against MRSA for 9 weeks in phosphate-buffered saline. To the best knowledge, this duration represents the longest reported long-term stability with less than 5% decay of antibacterial performance among contact-killing antibacterial coatings. The film exhibits exceptional mechanical durability, retaining its antibacterial activity even after 15 washing cycles. The pD6E1-g-pV4D4-coated CL maintains full optical transmittance compared to that of pristine CL. It is expected that the unprecedentedly prolonged antibacterial performance of the coating will significantly alleviate the risk of infection for long-term CL users.

Hyaluronan and proteoglycan link protein 1 - a novel signaling molecule for rejuvenating aged skin.

The skin seems to rejuvenate upon exposure to factors within the circulation of young organisms. Intrinsic factors that modulate skin aging are poorly understood. We used heterochronic parabiosis and aptamer-based proteomics to identify serum-derived rejuvenating factors. We discovered a novel extracellular function of hyaluronan and proteoglycan link protein 1 (HAPLN1). Its serum levels decreased with age, disturbing the integrity of the skin extracellular matrix, which is predominantly composed of collagen I and hyaluronan; levels of various markers, which decrease in aged skin, were significantly restored in vivo and in vitro by the administration of recombinant human HAPLN1 (rhHAPLN1). rhHAPLN1 protected transforming growth factor beta receptor 2 on the cell surface from endocytic degradation via mechanisms such as regulation of viscoelasticity, CD44 clustering, and hyaluronan cross-linking. Moreover, rhHAPLN1 regulated the levels of nuclear factor erythroid 2-related factor 2, phosphorylated nuclear factor kappa B, and some cyclin-dependent kinase inhibitors such as p16 and p21. Therefore, rhHAPLN1 may act as a novel biomechanical signaling protein to rejuvenate aged skin.

Hepatic perivascular epithelioid cell tumor: a retrospective analysis of 36 cases.

Background and aims: Hepatic perivascular epithelioid cell tumor (PEComa) is a rare type of mesenchymal neoplasm and lacks systematic reports. The aim was to analyze the features of hepatic PEComa in order to provide our own experience for diagnosis and management from a single center. Methods: We retrospectively analyzed clinical data, imaging findings, pathology, treatments and prognosis of 36 patients with hepatic PEComa in the First Affiliated Hospital of Zhengzhou University from January 2016 to September 2023. Results: 29 females and 7 males (median age, 47.8 years) were included in this study. The majority (26/36, 72.2%) of patients were diagnosed incidentally with non-specific symptoms. Abnormal enhancement of enlarged blood vessels (27/36,75%) can be observed on CT/MRI and only 7 patients (19.4%) were correctly diagnosed by imaging examinations. The positive immunohistochemical expressions were HMB-45(35/36,97.2%), Melan-A (34/35,97.1%), SMA (23/26,88.5%) and CD34(86.7%,26/30). Treatments include resection (24/36,67.7%), radiofrequency ablation (6/36,16.7%), transcatheter arterial chemoembolization(1/36,2.7%), conservative clinical follow-up(2/36,5.6%), and sirolimus-chemotherapy (3/36,8.3%). During the follow-up period (range, 2-81 months), except for one patient with a single intrahepatic recurrence and 3 malignant patients died in 6 months, the remaining patients had no signs of recurrence and metastasis. Conclusions: Hepatic PEComa has no specific clinical features and mainly depends on clinicopathological characteristics for accurate diagnosis. Resection is the best treatment for benign PEComa, but TACE and radiofrequency ablation can also be considered in case of contraindications for surgery.

Safety, reactogenicity, and immunogenicity of ZR-202-CoV and ZR-202a-CoV recombinant vaccines compared with Comirnaty®: a randomized, observer-blind, controlled, phase 1 study.

OBJECTIVES: ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH)3 and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali. DESIGN: Sixty healthy 18-55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or Comirnaty® 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year. RESULTS: Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and Comirnaty®. CONCLUSIONS: Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and Comirnaty® support further clinical investigation in a wider population.

Efficacy and Safety of General Anesthesia Induction with Ciprofol in Hip Fracture Surgery of Elderly Patients: A Randomized Controlled Trial.

Background: Ciprofol is a new intravenous sedative / anesthetic drug. In recent years, many clinical studies have also confirmed the sedative effect of ciprofol. However, more clinical research is still needed on its clinical application characteristics in special populations. Objective: The aim of this study was to compare the clinical effects of ciprofol and propofol in general anesthesia induction of elderly patients. Methods: 60 elderly (aged ≥ 75 years) patients underwent hip fracture surgery were randomly into two groups of a 1:1 ratio. Group C (ciprofol group): 0.3mg/kg ciprofol was infused. Group P (propofol group): 1.5mg/kg propofol was infused. The observation period was from the infusion of test drug to 5 min after endotracheal intubation. The primary outcomes included the incidence of severe hypotension and hypotension during the observation period. The secondary outcomes were as follows: the success rate of general anesthesia induction, the number of additional sedation, the time of loss of consciousness (LOC), Δ MAP, Δ HR, adverse events and the frequency of vasoactive drugs used. Results: Finally, 60 subjects completed the study. Compared with Group P, the incidence of severe hypotension in Group C was lower (26.7% vs 53.3%, P = 0.035), the incidence of hypotension was also lower (36.7% vs 63.3%, P = 0.037), Δ MAP in Group C was significantly lower (31.4 ± 11.4 vs 39.6 ± 15.7, P = 0.025), the frequency of ephedrine used and the incidence of injection pain in Group C were also significantly lower. Conclusion: Ciprofol showed similar efficacy to propofol when used for general anesthesia induction in elderly patients underwent hip fracture surgery and could maintain more stable blood pressure.

Development of a diagnostic model for detecting mild cognitive impairment in young and middle-aged patients with obstructive sleep apnea: a prospective observational study.

Objectives: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing condition linked to the accelerated onset of mild cognitive impairment (MCI). However, the prevalence of undiagnosed MCI among OSA patients is high and attributable to the complexity and specialized nature of MCI diagnosis. Timely identification and intervention for MCI can potentially prevent or delay the onset of dementia. This study aimed to develop screening models for MCI in OSA patients that will be suitable for healthcare professionals in diverse settings and can be effectively utilized without specialized neurological training. Methods: A prospective observational study was conducted at a specialized sleep medicine center from April 2021 to September 2022. Three hundred and fifty consecutive patients (age: 18-60 years) suspected OSA, underwent the Montreal Cognitive Assessment (MoCA) and polysomnography overnight. Demographic and clinical data, including polysomnographic sleep parameters and additional cognitive function assessments were collected from OSA patients. The data were divided into training (70%) and validation (30%) sets, and predictors of MCI were identified using univariate and multivariate logistic regression analyses. Models were evaluated for predictive accuracy and calibration, with nomograms for application. Results: Two hundred and thirty-three patients with newly diagnosed OSA were enrolled. The proportion of patients with MCI was 38.2%. Three diagnostic models, each with an accompanying nomogram, were developed. Model 1 utilized body mass index (BMI) and years of education as predictors. Model 2 incorporated N1 and the score of backward task of the digital span test (DST_B) into the base of Model 1. Model 3 expanded upon Model 1 by including the total score of digital span test (DST). Each of these models exhibited robust discriminatory power and calibration. The C-statistics for Model 1, 2, and 3 were 0.803 [95% confidence interval (CI): 0.735-0.872], 0.849 (95% CI: 0.788-0.910), and 0.83 (95% CI: 0.763-0.896), respectively. Conclusion: Three straightforward diagnostic models, each requiring only two to four easily accessible parameters, were developed that demonstrated high efficacy. These models offer a convenient diagnostic tool for healthcare professionals in diverse healthcare settings, facilitating timely and necessary further evaluation and intervention for OSA patients at an increased risk of MCI.