Search

Fluorene was previously reported to have anticancer activity against human cancer cells. In this study, we examined the in vitro function of 9-methanesulfonylmethylene-2, 3-dimethoxy-9 H -fluorene (MSDF), a novel fluorene derivative, its anticancer potential in human hepatocellular carcinoma (HCC) cells and its underlying molecular mechanism. The disruption of cellular homeostasis caused by MSDF was found to promote reactive oxygen species (ROS) generation, leading to the activation of cellular apoptosis. As a survival strategy, cells undergo autophagy during oxidative stress. MSDF-induced apoptosis occurred through both receptor-mediated extrinsic and mitochondrial-mediated intrinsic routes. The development of acidic vesicular organelles and the accumulation of LC3-II protein suggest an increase in the autophagic process. Apoptosis was detected by double staining. The MAPK/ERK and PI3K/Akt signaling pathways were indeed suppressed during treatment. Along with elevated ROS generation and apoptosis, MSDF also caused anoikis and cell death by causing cells to lose contact with their extracellular matrix. ROS production was induced by MSDF and sustained by an NAC scavenger. MSDF-induced apoptosis led to increased autophagy, as shown by the suppression of apoptosis by Z-VAD-FMK. However, inhibition of autophagy by inhibitor 3-MA increased MSDF-induced apoptosis. More evidence shows that MSDF downregulated the expression of immune checkpoint proteins, suggesting that MSDF could be used in the future as an adjuvant to improve the effectiveness of HCC immunotherapy. Altogether, our results highlight the potential of MSDF as a multitarget drug for the treatment of HCC., Competing Interests: Declaration of competing interest We declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the associations of meeting intensive systolic blood pressure (SBP) control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China. Methods: We used data from adult hypertensive patients from the China Kadoorie Biobank. logistic regression models evaluated the influencing factors of meeting intensive and standard SBP control goals. Cox proportional hazard models evaluated the associations between meeting intensive vs. standard SBP control goals and risk for incident cardiovascular and cerebrovascular diseases. Results: A total of 3 628 hypertensive patients who reported continuous medication use were included in this study, of which 5.0% of the participants met the goals of intensive SBP control (≤130 mmHg). Participants with higher educational attainment ( OR =2.36,95% CI : 1.32-4.04), healthier diet ( OR =2.09,95% CI : 1.45-2.96), daily intake of fresh fruit ( OR =1.67,95% CI: 1.17-2.36) and combination treatment ( OR =1.82,95% CI : 1.03-3.09) were more likely to meet intensive SBP control goal after adjustment of age, sex and urban/rural areas. During an average follow-up of (10.0±3.7) years, 1 278 cases of composite cardiovascular outcome were recorded. This study did not find a statistical correlation between achieving the goal of enhanced SBP control and the occurrence of composite cardiovascular and cerebrovascular outcomes ( HR =0.89, 95% CI : 0.63-1.25). For major adverse cardiovascular events (MACE), cerebrovascular diseases, stroke, and ischemic stroke, we observed a trend of decrease in risk of outcomes with more intensive SBP control (trend test P <0.05). Conclusions: We observed decreased risk for MACE and cerebrovascular diseases with more intensive SBP control. However, there was no significant risk reduction for cardiovascular and cerebrovascular diseases when meeting the intensive SBP control goal, compared to the standard SBP control goal.

Al-containing catalysts, e.g., Al(OTf) 3 , show good catalytic performance toward the conversion of cellulose to fructose in methanol solution. Here, we report the catalytic isomerization and alcoholysis mechanisms for the conversion of cellobiose to fructose at the PBE0/6-311++G(d,p), aug-cc-pVTZ theoretical level, combining the relevant experimental verifications of electrospray ionization mass spectrometry (ESI-MS), high-performance liquid chromatography (HPLC), and the attenuated total reflection-infrared (ATR-IR) spectra. From the alcoholysis of Al(OTf) 3 in methanol solution, the catalytically active species involves both the [CH 3 OH 2 ] + Brønsted acid and the [Al(CH 3 O)(OTf)(CH 3 OH) 4 ] + Lewis acid. There are two reaction pathways, i.e., one through glucose (glycosidic bond cleavage followed by isomerization, w-G ) and another through cellobiulose (isomerization followed by glycosidic bond cleavage, w-L ). The Lewis acid ([Al(CH 3 O)(OTf)(CH 3 OH) 4 ] + ) is responsible for the aldose-ketose tautomerization, while the Brønsted acid ([CH 3 OH 2 ] + ) is in charge of ring-opening, ring-closure, and glycosidic bond cleavage. For both w-G and w-L , the rate-determining steps are related to the intramolecular [1,2]-H shift between C1-C2 for the aldose-ketose tautomerization catalyzed by the [Al(CH 3 O)(OTf)(CH 3 OH) 4 ] + species. The Lewis acid ([Al(CH 3 O)(OTf)(CH 3 OH) 4 ] + ) exhibits higher catalytic activity toward the aldose-ketose tautomerization of glycosyl-chain-glucose to glycosyl-chain-fructose than that of chain-glucose to chain-fructose. Besides, the Brønsted acid ([CH 3 OH 2 ] + ) shows higher catalytic activity toward the glycosidic bond cleavage of cellobiulose than that of cellobiose. Kinetically, the w-L pathway is predominant, whereas the w-G pathway is minor. The theoretically proposed mechanism has been experimentally testified. These insights may advance on the novel design of the catalytic system toward the conversion of cellulose to fructose.

Scientists are increasingly relying on astronomical and remote sensing technologies to gain deeper insights into the Earth and the universe. In these fields, the optical spectrum analyzer (OSA) or spectrometer plays a pivotal role. This Review offers a comprehensive overview of the fundamental principles, key parameters, and applications of various branches of traditional OSAs, including prisms, gratings, interferometers, tunable filters, and reconstructive spectrometers. We specifically focus on their latest major applications in astronomy and remote sensing. Additionally, we present a mathematical model of the generalized reconstructive spectrometer and provide a summary of its principles pertaining to spectral mapping, reconstruction, and imaging. Despite its limited aperture and étendue, the reconstructive spectrometer holds great potential for future use in astronomy and remote sensing due to its compact size and exceptional ultrahigh spectral resolution., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Background: Williams syndrome is an autosomal dominant multisystem disorder caused by a 1.5-1.8 Mb deletion on chromosome 7q11.23. It is characterized by facial deformations, cardiovascular abnormalities, developmental delays, gastrointestinal manifestations, and endocrine disorders., Case Description: A 1-year-old child presenting with developmental delays, special facial features, gastrointestinal bleeding, renal calcium deposition, and hypotonia was admitted to the hospital for "hypercalcemia and gastrointestinal bleeding." Genetic testing showed a deletion mutation in the 7q11.23 region. Currently, the child receiving treatment to promote calcium excretion and rehabilitation training, but hypercalcemia has recurred., Conclusion: The clinical phenotype of Williams syndrome is complex, and different severities, characterized by developmental delays, facial deformities, cardiovascular abnormalities, gastrointestinal symptoms and endocrine disorders, should be considered in children. The syndrome may require thorough genetic testing for diagnosis and early intervention treatment to improve patient quality of life., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVβ5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer., (© 2023 Wiley Periodicals LLC.)

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: As a theoretical framework for understanding illness self-management, the commonsense model of self-regulation (CSM) has been commonly used to promote health behaviors. However, its application to examining gambling disorder (GD) is still in an exploratory stage., Objectives: Based on CSM, the current study aimed to address this knowledge gap and test whether illness representations (i.e., perceived consequences, illness coherence, and emotional representations) of GD are associated with gambling behaviors (i.e., responsible gambling [RG] and superstitious gambling). We also aimed to explore the potential mediating role of positive gambling beliefs (i.e., personal responsibility about gambling and gambling literacy) in such associations., Methods: An online questionnaire survey with snowballing sampling method was administered to Chinese adult past-year gamblers, and 603 valid responses were collected. The structural equation modeling (SEM) analysis with a bootstrapping approach was utilized to test the associations of illness representations with gambling behaviors and the hypothesized mediation effects of positive gambling beliefs., Results: We found that (a) perceived consequences of GD had significant, positive associations with RG and negative associations with superstitious gambling, with positive gambling beliefs acting as full mediators; (b) emotional representations for GD showed significant, negative correlations with RG and positive ones with superstitious gambling, with positive gambling beliefs acting as full and partial mediators, respectively; (c) the direct effect of illness coherence of GD on superstitious gambling behaviors was unexpectedly positive, and its indirect effects via positive gambling beliefs were nonsignificant., Discussion: Under the framework of CSM, the current findings provided new insights in understanding both controlled and at-risk gambling patterns from a perspective of illness self-management. We suggest future GD prevention campaigns may adopt psychoeducational programs to help gamblers form a better understanding about GD as an illness, which may promote RG practices and hence lower the risk of developing GD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Yang, Zhou, Dang and Chen.)

In this study, using immunohistochemistry with fresh cadavers, deliberate histological profiling was performed to determine which fibers are predominant within each compartment. To verify the fascial compartmentation of the SSC and elucidate its histological components of type I and II fibers using macroscopic, histological observation and cadaveric simulation for providing an anatomical reference of efficient injection of the BoNT into the SSC. Seven fixed and three fresh cadavers (six males and four females; mean age, 82.5 years) were used in this study. The dissected specimens revealed a distinct fascia demarcating the SSC into the superior and inferior compartments. The Sihler's staining revealed that the upper and lower subscapular nerves (USN and LSN) innervated the SSC, with two territories distributed by each nerve, mostly corresponding to the superior and inferior compartments of the muscle, although there were some tiny communicating twigs between the USN and LSN. The immunohistochemical stain revealed the density of each type of fiber. Compared with the whole muscle area, the densities of the slow-twitch type I fibers were 22.26 ± 3.11% (mean ± SD) in the superior and 81.15 ± 0.76% in the inferior compartments, and the densities of the fast-twitch type II fiber were 77.74% ± 3.11% in the superior and 18.85 ± 0.76% in the inferior compartments. The compartments had different proportions of slow-fast muscle fibers, corresponding to the functional differences between the superior compartment as an early-onset internal rotator and the inferior compartment as a durable stabilizer of the glenohumeral joint., (© 2023. The Author(s).)

Paired pigeons only lay 2 eggs in a laying period, which is closely related to ovarian follicle development, but this process is not well understood. In this study, 60 pairs of 12-mo-old White King pigeons were selected and serum and follicles were collected at 4 stages of laying interval (LI), including the first (LI1), the third (LI3), the fifth (LI5), and the seventh day (LI7). Morphological results showed that paired pigeons normally had 2 preovulatory follicles and the second-largest follicle (F2) developed from LI3 and had been selected in LI5. Prehierarchical follicles were coupled and hierarchical, which was in accordance with its clutch size. The P 4 concentration increased gradually from LI1 to LI5, reaching a maximum of 30.67 ng/mL in LI5 and decreasing to 27.83 ng/mL in LI7 (P < 0.05). The levels of T in LI1 and LI5 were higher than LI3 and LI7 (P < 0.05), although there was no significant difference in E 2 in LI (P > 0.05), but it stayed at high levels. In the TCs of the largest follicle (F1), HSD3B1 mRNA and HSD17B1 mRNA levels peaked in LI7. The expression pattern of CYP17A1 and CYP19A1 was similar, increasing from LI3 to LI5 and then decreasing. In the TCs of F2, the expressions of HSD3B1 and CYP17A1 had no significant difference between LI5 and LI7 (P > 0.05), while the expression pattern of HSD17B1 and CYP19A1 was the opposite. In TCs of SF1, HSD3B1 mRNA level peaked in LI3 while CYP19A1 mRNA levels peaked in LI7. The expression of CYP17A1 had a minor change (P > 0.05) and the expression pattern of HSD17B1 was similar to F1. It was concluded that the morphological characteristics of follicles during the LI for the first time, including the number and diameter of small follicles (SFs) and hierarchical follicles in pigeon and the concentrations of steroid hormones and expressions of steroidogenic genes in TCs of different follicles could explain the growth and selection of 2 preovulatory follicles. This study facilitates further research into the regulation of ovulation and egg production in pigeons., (Copyright © 2023. Published by Elsevier Inc.)

Aflatoxin B 1 (AFB 1 ) is the predominant mycotoxin that originated toxicity in broilers through oxidative damage, intestinal barrier dysfunction, reduced immune system and dysfunction of microorganisms and enzymes in target organs. The intestine is the first AFB 1 target organ destroyed after the bird's body is induced. This review summarises the current knowledge of the negative results of AFB 1 -induced intestinal damage on broiler production. It was conducted in accordance with the relevant studies in the cited literatures being retrieved from PubMed, Google Scholar, Science Direct and Web of Science. First, AFB 1 can change the intestinal barrier function by destroying the intestinal architecture, tissue and cell integrity of the gut epithelium. Second, AFB 1 can damage the immune barrier function of the gastrointestinal mucosa. Third, the microbiota of birds interacts closely with the ingested aflatoxin. Finally, because broilers are tremendously sensitive to AFB 1 contamination, the poisonous and noxious effects of this mycotoxin in the broiler industry cause millions of dollars in losses every year. This review briefly discussed that the AFB 1 , which affects the intestines of broiler chickens, was reduced the immune apparatus, antioxidant protection system, gastric system, and broiler production status and its impact on human health. Therefore, this review will improve our perception of the important intestine in a bird's health and the adverse effect of AFB 1 ., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Recurrence is considered a vital problem for assessing the prognosis of Henoch-Schonlein purpura (HSP). The objective of this study was to evaluate factors affecting the recurrence in children with HSP., Methods: We retrospectively reviewed records of 368 patients under the age of 16 years diagnosed with HSP from October 2019 to December 2020 in Beijing Children's Hospital. Patients were divided into a non-recurrence group and a recurrence group according to whether there was a recurrence. Incidence of manifestation, possible cause, age, and treatment were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of recurrence in HSP., Results: Percentages of patients were 65.2% for the non-recurrence group and 34.8% for the recurrence group. The percentage of patients with renal involvement was significantly higher in the recurrence group (40.6%) than in the non-recurrence group (26.3%). Respiratory tract infection was the most frequent trigger: 67.5% in the non-recurrence group and 66.4% in the recurrence group. Recurrence was more likely to occur in patients aged >6 years (53.3% vs . 71.9%). Logistic regression analysis revealed that hematuria plus proteinuria was an independent risk factor for the recurrence of HSP. Conversely, animal protein, exercise restriction, and age ≤6 years were independent favorable factors for the non-recurrence of HSP., Conclusion: These results suggest that organ involvement, exercise, and diet management during the initial episode of HSP should be strictly monitored for children with HSP. Adequate clinical intervention for these risk factors may limit or prevent HSP recurrence. Moreover, renal involvement is associated with the long-term prognosis of HSP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Cao, Yang, Huang and Hu.)

Al-rich zeolites such as NaA (Si/Al = 1.00) have been widely applied to remove radioactive 90 Sr 2+ because of their high surface charge density enabling efficient ion-exchange of multivalent cations. However, due to the small micropore diameters of zeolites and large molecular size of strongly hydrated Sr 2+ , Sr 2+ -exchange with zeolites suffers from very slow kinetics. In principle, mesoporous aluminosilicates with low Si/Al ratios close to unity and tetrahedrally coordinated Al sites can exhibit both high capacity and fast kinetics in Sr 2+ -exchange. Nonetheless, the synthesis of such materials has not been realized yet. In this study, we demonstrate the first successful synthesis of an Al-rich mesoporous silicate (ARMS) using a cationic organosilane surfactant as an efficient mesoporogen. The material exhibited a wormhole-like mesoporous structure with a high surface area (851 m 2 g -1 ) and pore volume (0.77 cm 3 g -1 ), and an Al-rich framework (Si/Al = 1.08) with most Al sites tetrahedrally coordinated. Compared to commercially applied NaA, ARMS exhibited a dramatically improved Sr 2+ -exchange kinetics (>33-fold larger rate constant) in batch adsorption while showing similarly high Sr 2+ capture capacity and selectivity. Due to the fast Sr 2+ -exchange kinetics, the material also exhibited 3.3-fold larger breakthrough volume than NaA in fixed-bed continuous adsorption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a powerful early sign of Parkinson's disease (PD), but the pathogenetic mechanism involved in RBD remains largely unexplored. α-Synuclein has been verified to form Lewy bodies in the orexin neurons, whose activity and function rely on the orexin 1 receptor (OX1R). Dysfunction of the OX1R may induce the occurrence of RBD. Here, we determined the role of the interaction between α-Synuclein and OX1R in the pathogenesis of RBD, in vitro and in vivo. We found that injection of α-Synuclein into the lateral hypothalamus area (LHA) damaged orexin neurons and induced the RBD-like sleep pattern, to further damage dopaminergic neurons and result in locomotor dysfunction in mice. α-Synuclein interacted with OX1R, promoting the degradation of OX1R through proteasomal and lysosomal pathways. In addition, overexpression of α-Synuclein downregulated OX1R-mediated signaling, subsequently leading to orexin neuron damage. We conclude that α-Synuclein induced the occurrence of RBD via interaction with OX1R and modulated its degradation. These findings provide evidence for a novel mechanism by which the association of α-Synuclein with OX1R was attributed to α-Synuclein-induced orexin neuron damage, which may be a new molecular target for an effective therapeutic strategy for RBD pathology., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A precise anatomical understanding of the adductor canal (AC) and its neural components is essential for discerning the action mechanism of the AC block. We therefore aimed to clarify the detailed anatomy of the AC using micro-computed tomography (micro-CT), histological evaluation, and immunofluorescence (IF) assays., Methods: Gross dissections of 39 thighs provided morphometric data relevant to injection landmarks. Serial sectional images of the AC were defined using micro-CT and ultrasonography. The fascial and neural structures of the AC proper were histologically evaluated using Masson's trichrome and Verhoeff-Van Gieson staining, and double IF staining using choline acetyltransferase (ChAT) and neurofilament 200 antibodies., Results: The posteromedial branch insertion of the nerve to vastus medialis (NVM) into the lateral border of the AC proper was lower (14.5 ± 2.4 cm [mean ± SD] above the base of the patella) than the origin of the proximal AC. The AC consists of a thin subsartorial fascia in the proximal region and a thick aponeurosis-like vastoadductor membrane in the distal region. In the proximal AC, the posteromedial branch of the NVM (pmNVM) consistently contained both sensory and motor fibers, and more ChAT-positive fibers were observed than in the saphenous nerve (27.5 ± 11.2 / 104 vs. 4.2 ± 2.6 / 104 [counts/µm2], P < 0.001)., Conclusions: Anatomical differences in fascial structures between the proximal and distal AC and a mixed neural component of the neighboring pmNVM have been visualized using micro-CT images, histological evaluation, and IF assays.

Importance: Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking., Objective: To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes., Design, Setting, and Participants: This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021., Interventions and Exposures: Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes., Main Outcomes and Measures: The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up., Results: Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71)., Conclusion and Relevance: In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status., Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Background: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology., Methods: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding., Results: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P <0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P =0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P =0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event., Conclusions: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02601157.

Purpose: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG)., Methods: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups., Results: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment., Conclusions: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P =0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P =0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P =0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P =0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.

Aims: Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS., Methods and Results: Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints., Conclusion: In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy., Study Registration Number: This study was registered in the PROSPERO (ID: CRD42021245477)., Competing Interests: Conflict of interest K.W.P. reports speaker fees from Daichi Sankyo, InnoN Pharmaceutical, and DaeWoong Pharmaceutical, outside of the submitted work. All other authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The visual cryptography scheme (VCS) distributes a secret to several images that can enhance the secure transmission of that secret. Quick response (QR) codes are widespread. VCS can be used to improve their secure transmission. Some schemes recover QR codes with many errors. This paper uses a distribution mechanism to achieve the error-free recovery of QR codes. An error-correction codeword (ECC) is used to divide the QR code into different areas. Every area is a key, and they are distributed to n shares. The loss of any share will make the reconstructed QR code impossible to decode normally. Stacking all shares can recover the secret QR code losslessly. Based on some experiments, the proposed scheme is relatively safe. The proposed scheme can restore a secret QR code without errors, and it is effective and feasible.

Aims: The aim of this study was to evaluate the efficacy and safety of prasugrel dose de-escalation therapy in patients with diabetes mellitus (DM)-acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI)., Methods and Results: This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and Bleeding Academic Research Consortium (BARC) class ≥2 bleeding events. The secondary ischaemic outcome was major adverse cardiovascular and cerebrovascular events, defined as the composite of cardiac death, non-fatal MI, ST, or ischaemic stroke. Of 2338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM [hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.43-0.99; P = 0.049]. Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischaemic events (HR 1.03; 95% CI 0.56-1.88; P = 0.927) but decreased BARC class ≥2 bleeding in patients with DM (HR 0.44; 95% CI 0.23-0.84; P = 0.012)., Conclusion: Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischaemic events in patients with DM. Trial Registration: HOST-REDUCE-POLYTECH-ACS, NCT02193971, https://clinicaltrials.gov/ct2/show/NCT02193971., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To investigate the predictive factors for bronchitis obliterans in refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods: A restrospective case summary was conducted 230 patients with RMPP admitted to the Department of No.2 Respiratory Medicine of Beijing Children's Hospital, Capital Medical University from January 2013 to June 2017 were recruited. Clinical data, laboratory results, imaging results and follow-up data were collected. Based on bronchoscopy and imaging findings 1 year after discharge, all patients were divided into two groups: one group had sequelae of bronchitis obliterans (sequelae group) and the other group had not bronchitis obliterans (control group), independent sample t -test and nonparametric test were used to compare the differences in clinical features between the two groups. Receiver operating characteristic (ROC) curve to explore the predictive value of Bronchitis Obliterans in RMPP. Results: Among 230 RMPP children, there were 115 males and 115 females, 95 cases had sequelae group, the age of disease onset was (7.1±2.8) years;135 cases had control group, the age of disease onset was (6.8±2.7) years. The duration of fever, C-reative protein (CRP) and lactate dehydrogenase (LDH) levels, the proportion of ≥2/3 lobe consolidation, pleural effusion and the proportion of airway mucus plug and mucosal necrosis were longer or higher in the sequelae group than those in the control group ((17±9) vs. (12±3) d, (193±59) vs. (98±42) mg/L,730 (660, 814) vs. 486 (452, 522) U/L, 89 cases (93.7%) vs. 73 cases (54.1%), 73 cases (76.8%) vs. 59 cases (43.7%), 81 cases (85.3%) vs. 20 cases (14.8%), 67 cases (70.5%) vs. 9 cases (6.7%), t =5.76, 13.35, Z =-6.41, χ 2 =14.64, 25.04, 22.85, 102.78, all P <0.001). Multivariate Logistic regression analysis showed that the duration of fever ≥10 days ( OR =1.200, 95% CI 1.014-1.419), CRP levels increased ( OR =1.033, 95% CI 1.022-1.044) and LDH levels increased ( OR =1.001, 95% CI 1.000-1.003) were the risk factors for sequelae of bronchitis obliterans in RMPP. ROC curve analysis showed that CRP 137 mg/L had a sensitivity of 82.1% and a specificity of 80.1%; LDH 471 U/L had a sensitivity of 62.7% and a specificity of 60.3% for predicting the development of bronchitis obliterans. Conclusions: The long duration of fever (≥10 d), CRP increase (≥137 mg/L) may be used to predict the occurrence of sequelae of bronchitis obliterans in RMPP. It is helpful for early recognition of risk children.

1. An experiment feeding three concentrations of betaine was conducted using breeding geese to analyse the reproductive performance, serum biochemical indexes, egg quality and intestinal immunity.2. A total of 450 female and 90 male Jiangnan White breeding geese were divided into three treatments, with five pen replicates each containing 30 female geese and 6 male geese.3. The results showed that there was no significant effect on the reproductive performance, serum biochemical indexes or jejunal villi goblet cells of geese with different levels of betaine in the diet (P > 0.05). Compared with the control group, the addition of 2.5 g/kg betaine to the diet showed a tendency to increase egg mass (P > 0.05) the betaine content in the yolk (P < 0.05). Feeding betaine significantly increased the height of jejunal villi and egg yolk total cholesterol content in female geese (P < 0.05).4. In conclusion, adding betaine to the goose diet was effective in its ability to improve intestinal structures. Adding 2.5 g/kg betaine to feed significantly increased the content of TCHOL and betaine in goose eggs.

With increasing population aging, osteoporosis vertebral compression fractures (OVCFs), resulting in severe back pain and functional impairment, have become progressively common. Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) as minimally invasive procedures have revolutionized OVCFs treatment. However, PVP- and PKP-related complications, such as symptomatic cement leakage and adjacent vertebral fractures, continue to plague physicians. Consequently, progressively more implants for OVCFs have been developed recently to overcome the shortcomings of traditional procedures. Therefore, we conducted a literature review on several new implants for OVCFs, including StaXx FX, Vertebral Body Stenting, Vesselplasty, Sky Bone Expander, Kiva, Spine Jack, Osseofix, Optimesh, Jack, and V-strut. Additionally, this review highlights the individualized applications of these implants for OVCFs. Nevertheless, current clinical studies on these innovative implants remain limited. Future prospective, randomized, and controlled studies are needed to elucidate the effectiveness and indications of these new implants for OVCFs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Yang, Yang, Wu and Xie.)

This study aimed to identify the whole innervation pattern of the platysma using the Sihler's staining, and the axonal composition profile of the sensory-motor anastomosis identified by immunofluorescence assays. The findings provide a comprehensive understanding of the neural anatomy of the platysma and facilitate efficient and safe manipulation for neurotoxin injection. Ten fixed and two fresh hemifaces were included in this study. Sihler's staining was used to the study 10 fixed hemifaces and two fresh hemifaces were used for immunofluorescence assays. In all cases, the cervical branch of facial nerve (Cbr) broadly innervated the platysma, and the marginal mandibular branch of facial nerve (MMbr) provided supplementary innervation to the uppermost part of the platysma. The transverse cervical nerve (TCN), great auricular nerve (GAN), and supraclavicular nerve (SCN) were observed in the lower half of the platysma. In 30% of all cases, there was a communicating loop between the Cbr and TCN. In 20% of all the cases, a communicating branch joined between the Cbr and GAN. For successful esthetic rejuvenation procedures, a clinician should consider the Cbr distribution to the overall platysma and additionally innervation by individual nerves (MMbr, GAN, TCN, and SCN) to the middle and lower portions of the platysma muscle., (© 2022 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hyun Mo Yang reports a relationship with UNICAMP - University of Campinas that includes: employment.

Background: Although vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA., Methods and Results: With 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51, p < 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca 2+ -ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier (SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13, p < 0.01)., Conclusions: Our findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA., (© 2023. The Author(s).)

This experiment investigated the effects of different dietary starch sources on the growth and glucose metabolism of geese. A total of 240 healthy 35-day-old male geese were selected and randomly divided into 4 groups, with 6 replicates per group and 10 geese per replicate. Four types of diets were prepared, with glutinous rice (rapidly-digestible starch), corn, indica rice and high amylose as their starch sources, and fed for 28 d. Results showed that after consuming different feeds, the blood glucose of geese first increased and then decreased, reaching its maximum value 0.5 h after feeding, and there were significant differences between the groups (P < 0.05). The body weight of the corn and indica rice group geese at 63 d was higher than that of the high amylose group (P < 0.05). The serum total cholesterol (TCHO) content in the glutinous rice and corn groups was higher than in the high amylose group (P < 0.05). The serum insulin content in the glutinous rice group was lower than in the corn and high amylose groups (P < 0.05), while the glucagon content was higher (P < 0.05). The α-amylase activities of the pancreas, jejunal chyme, and jejunal mucosa in the glutinous rice group were higher than in the indica rice and high amylose groups (P < 0.05). The liver glycogen content in the glutinous rice group was higher than the other groups (P < 0.05). The liver glucose-6-phosphate dehydrogenase (G-6-PD) content in the glutinous rice group was higher than the high amylose group's (P < 0.05), but the glycogen synthase kinase-3 β (GSK-3β) content was lower (P < 0.05). In conclusion, the corn and indica rice diets had a positive effect on the growth performance of the geese, while the high amylose diet had a negative effect. The glutinous rice diet leads to rapid release of glucose, strengthening glucose metabolism pathways such as glycogen synthesis and the pentose phosphate pathway, and further influencing lipid metabolism., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A visible jowl is a reason patients consider lower facial rejuvenation surgery. The anatomical changes that lead to formation of the jowl remain unclear. The aim of this study was to elucidate the anatomy of the jowl, the mandibular ligament and the labiomandibular crease, and their relationship with the marginal mandibular branch of the facial nerve., Materials and Methods: Forty-nine cadaver heads were studied (16 embalmed, 33 fresh, mean age 75 years). Following preliminary dissections and macro-sectioning, a series of standardized layered dissections were performed, complemented by histology, sheet plastination and micro-CT., Results: The jowl forms in the subcutaneous layer where it overlies the posterior part of the mandibular ligament. The mandibular ligament proper exists only in the deep, sub-platysma plane, formed by the combined muscular attachment to the mandible of the specific lower lip depressor muscles and the platysma. The mandibular ligament does not have a definitive subcutaneous component. The labiomandibular crease inferior to the oral commissure marks the posterior extent of the fixed dermal attachment of depressor anguli oris., Conclusion: Jowls develop as a consequence of aging changes on the functional adaptions of the mouth in humans. To accommodate wide jaw opening with a narrowed commissure requires hypermobility of the tissues overlying the mandible immediately lateral to the level of the oral commissure. This hypermobility over the mandibular attachment of the lower lip depressor muscles occurs entirely in the subcutaneous layer to allow the mandible to move largely independent from the skin. The short, elastic subcutaneous connective tissue, which allows this exceptional mobility without laxity in youth, lengthens with aging, resulting in laxity. The development of subcutaneous and dermal redundancy constitutes the jowl in this location., Level of Evidence Iv: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .", (© 2022. The Author(s).)

The investigation aimed to explore the suitable amino acid (AA) supplementation pattern for goslings under low-protein diets. A total of 364 1-day-old male goslings were randomly divided into 4 experimental groups, with 7 pens containing 13 goslings each. The 4 groups were control (CP, 18.55%), LPM (CP, 15.55% + major AA), LPA (CP, 15.55% + all AA), and LPR (CP, 15.55% + AA content reduced proportionally to the control's CP). The corn-soybean meal diets are formulated according to the ideal AA model of goose and its nutritional requirements. The results indicated that the ADG and BW were the lowest, and the F: G was the highest in LPR (P < 0.05); the other three groups were not significantly different (P > 0.05). The ADFI and mortality were not different among all the groups (P > 0.05). Among the AA content in serum and breast muscle, lysine in serum significantly decreased compared with the control (P < 0.05). The UREA content was approximately 2-fold higher in the LPR group than in the LPM and LPA groups (P < 0.05). No difference in IgA, IgG, IgM, and IgE levels was observed among the groups (P > 0.05). The nitrogen excretion was decreased in LPM and LPA compared to the control and LPR (P < 0.05). Nitrogen deposition did not differ among groups (P > 0.05). Nitrogen utilization was highest in the LPA and LPM groups, followed by the control group and LPR (P < 0.05). In conclusion, the patterns of supplementation of major AA and all AA in low-protein diets (CP, 15.55%) had no adverse effect on the growth performance compared with the control (CP, 18.55%) of the goslings. Besides, the two patterns could decrease nitrogen excretion and increase nitrogen utilization. Furthermore, from the perspective of dietary cost and environmental protection, the pattern of supplementing major AA in a corn-soybean meal low-protein diet is suggested., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs)., Methods: To determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist. Panel-based targeted exome sequencing was performed on DNA extracted from blood samples, containing coding regions of 792 IED-causative genes and their flanking exons. All participants underwent genetic testing., Results: All proband-parent trios were divided into 22 subgroups, the overall diagnostic yield was 48.67% (605/1243), ranging from 4% to 94.44% for each of the subgroups. A total of 108 IED-causative genes were identified, with the top 24 genes explaining 67% of the 605 genetically solved trios. The genetic etiology of 6.76% (84/1243) of the trio was attributed to disease-causative DNMs, and the top 3 subgroups with the highest incidence of DNM were aniridia (n = 40%), Marfan syndrome/ectopia lentis (n = 38.78%), and retinoblastoma (n = 37.04%). The top 10 genes have a diagnostic yield of DNM greater than 3.5% in their subgroups, including PAX6 (40.00%), FBN1 (38.78%), RB1 (37.04%), CRX (10.34%), CHM (9.09%), WFS1 (8.00%), RP1L1 (5.88%), RS1 (5.26%), PCDH15 (4.00%), and ABCA4 (3.51%). Additionally, the incidence of DNM in offspring showed a trend of correlation with paternal age at reproduction, but not statistically significant with paternal (P = 0.154) and maternal (P = 0.959) age at reproduction., Conclusions: Trios-based genetic analysis has high accuracy and validity. Our study helps to quantify the burden of the full spectrum IED caused by each gene, offers novel potential for elucidating etiology, and plays a crucial role in genetic counseling and patient management.

Background: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES)., Methods and results: Overall, 5,112 patients were stratified (in kg/m 2 ) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes., Conclusions: Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.

A new monogonont rotifer, Cephalodellabinoculata sp. nov. , was described from a soil sample collected in Korea. The new species is morphologically similar to C.carina but is distinguished by having two frontal eyespots, a vitellarium with eight nuclei, and the shape of its fulcrum. We also described four other cephalodellid species collected in Korea; Cephalodellaauriculata , C.catellina , C.gracilis , and C.tinca . Of these four species, C.gracilis and C.tinca were newly recorded in Korea. We provided the morphological characteristics of the five Cephalodella species along with photographs of trophi observed with a scanning electron microscope. Furthermore, we provided the mitochondrial cytochrome c oxidase subunit I gene sequences of the five species., (Hee-Min Yang, Gi-Sik Min.)

The heuristic optimization algorithm is a popular optimization method for solving optimization problems. A novel meta-heuristic algorithm was proposed in this paper, which is called the Willow Catkin Optimization (WCO) algorithm. It mainly consists of two processes: spreading seeds and aggregating seeds. In the first process, WCO tries to make the seeds explore the solution space to find the local optimal solutions. In the second process, it works to develop each optimal local solution and find the optimal global solution. In the experimental section, the performance of WCO is tested with 30 test functions from CEC 2017. WCO was applied in the Time Difference of Arrival and Frequency Difference of Arrival (TDOA-FDOA) co-localization problem of moving nodes in Wireless Sensor Networks (WSNs). Experimental results show the performance and applicability of the WCO algorithm.

Background: Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI)., Objectives: This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function., Methods: We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up., Results: Prasugrel de-escalation was beneficial regardless of baseline renal function ( P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) ( P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) ( P for interaction = 0.119)., Conclusions: In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function., Competing Interests: This post hoc analysis was supported by research grants from the GENESIS registry (research ID: 620102880) and from Seoul National University Hospital (research ID: 03-2021-0030). Dr Kyung Woo Park has received speaker fees from Daiichi Sankyo, Sanofi, Bristol Myers Squibb, Bayer, Pfizer, InnoN Pharmaceutical, DaeWoong Pharmaceutical, and JW Pharmaceutical outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial., Methods: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group)., Results: During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P <0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P <0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P =0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P =0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period., Conclusions: During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02044250.

Background: Potent P2Y 12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS., Methods: The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting)., Results: A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56-2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups., Conclusions: Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI., Trial Registration: KCT0002356, registered June 13, 2017., (© 2023. The Author(s).)

The patient's medical health record (PMHR) has always provided a large amount of research data to medical institutions and pharmaceutical companies, etc., and has contributed to the development in medical research. However, such PMHR data contains the patient's personal privacy and should be shared under the control of the patients, not the hospital where this data is acquired. In order to protect the privacy of PMHR data while realizing efficient data sharing, this paper proposes a blockchain-based sharing and protection scheme. In this solution, the PMHR data are encrypted and stored in a cloud server, which is equipped with an access control scheme implemented as a smart contract on a blockchain. Different from previous works, in order to ensure efficient access and reduce the workload of patients, the types of users who can apply for access are limited to hospitals and pharmaceutical companies. In order to resist the potential Man-in-the-middle (MITM) attack, we have introduced an improved proxy re-encryption scheme to ensure the secrecy of PMHR data while reducing the computational complexity. The whole system is implemented using Solidity and tested on 10 nodes for function verification. Experimental result shows that the proposed system is more efficient than previous systems. Security under the MITM attack is also ensured by security analysis., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The retrodural space of Okada is a potential space posterior to the ligamentum flavum that allows communication with the bilateral facet joints. However, the actual anatomy of this space has not been clearly visualized to date. We sought to investigate the characteristics of patients showing contrast spreading to the facet joint space during epidural injection and to clarify the anatomical structures of the retrodural space and adjacent ligamentous tissues in cadaveric specimens., Methods: Fluoroscopic images of patients who underwent fluoroscopy-guided lumbar interlaminar epidural injection were assessed for contrast flow to the facet joints. Patient demographics, preprocedural imaging study findings, and epidural approaches were analyzed. The anatomical study included the sectional dissection, micro-CT imaging, and histological evaluation of lumbar spine specimens from 16 embalmed cadavers., Results: Fluoroscopic images of 605 epidural injections were analyzed. Among them, 36 with inadvertent spread into the facet joints (5.9%) were identified. Multivariate analysis revealed that facet joint pathologies were significantly associated with inadvertent spread into the facet joints (OR 4.382; 95% CI 1.160 to 16.558; p=0.029). Micro-CT and histological findings consistently showed a retrodural space between the ligamentum flavum and interspinous ligament. Various anatomical communication routes in the posterior ligamentous complex leading to this space were observed in specimens with degenerative and pathological changes., Conclusion: Degenerative and pathological facet joint changes were associated with a higher incidence of spread into the retrodural space during epidural injection. Our findings confirm anatomical evidence for a false loss of resistance before the needle enters the epidural space., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: One of the suggested mechanisms of obesity-induced insulin resistance is mitochondrial dysfunction in target tissues such as skeletal muscle. In our study, we examined whether resistin, an adipokine associated with obesity-mediated insulin resistance, induced metabolic disorders by impairing mitochondrial homeostasis., Methods: The morphology and function of mitochondria of skeletal muscle were examined in resistin-knockout and humanized resistin mice that were subjected to high-fat diet for 3 months. Morphology was examined by transmission electron microscopy. Mitochondria bioenergetics of skeletal muscle were evaluated using a Seahorse XF96 analyzer. Human skeletal myoblasts were used for in vitro studies on signaling mechanisms in responses to resistin., Results: A high-fat diet in humanized resistin mice increased fragmented and shorter mitochondria in the skeletal muscle, whereas resistin-knockout mice had healthy normal mitochondria. In vitro studies showed that human resistin treatment impaired mitochondrial homeostasis by inducing mitochondrial fission, leading to a decrease in ATP production and mitochondrial dysfunction. Induction of mitochondrial fission by resistin was accompanied by increased formation of mitochondria-associated ER membranes (MAM). At the same time, resistin induced up-regulation of the protein kinase A (PKA) pathway. This activation of PKA induced phosphorylation of Drp1 at serine 616, leading to Drp1 activation and subsequent induction of mitochondrial fission. The key molecule that mediated human resistin-induced mitochondrial fission was adenylyl cyclase-associated protein 1 (CAP1), which was reported as a bona fide receptor for human resistin. Moreover, our newly developed biomimetic selective blocking peptide could repress human resistin-mediated mitochondrial dysfunction. High-fat diet-fed mice showed lower exercise capacity and higher insulin resistance, which was prevented by a novel peptide to block the binding of resistin to CAP1 or in the CAP1-knockdown mice., Conclusions: Our study demonstrated that human resistin induces mitochondrial dysfunction by inducing abnormal mitochondrial fission. This result suggests that the resistin-CAP1 complex could be a potential therapeutic target for the treatment of obesity-related metabolic diseases such as diabetes and cardiometabolic diseases., Competing Interests: Conflict of interest The authors declare no other compelling interests., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Cochlear implantation is an effective treatment for children with deafness. Although the binaural effect of bilateral cochlear implantation on sound localization and speech perception in noisy environments has been demonstrated, the outcome and performance predictors of the second cochlear implant (CI2) remain uncertain for patients receiving sequential implantation. This study evaluated the hearing performance between the first cochlear implant (CI1), CI2, and bilateral cochlear implants (CI1+2) among children with sequential bilateral cochlear implantation., Methods: This single-center retrospective study enrolled 14 children and adolescents aged 8-18 years who underwent sequential bilateral cochlear implantation with a mean interimplant interval of 8.2 years. The Mandarin Lexical Neighborhood Test (M-LNT), the Mandarin Hearing in Noise Test (M-HINT), and the Comprehensive Cochlear Implant Questionnaire (CCIQ) scores of participants were evaluated. Mann-Whitney U tests and Spearman correlation analysis were performed to analyze factors associated with CI2 performance., Results: In the 1-year follow-up period after CI2 implantation, although the M-LNT mean score for CI2 was significantly lower than that for CI1, the M-LNT scores for CI2 and CI1+2 improved significantly over time. In a noisy environment, CI1+2 significantly outperformed CI1 in the M-HINT. The M-LNT score for CI2 was significantly associated with preoperative bimodal fitting, residual hearing of the second implanted ear, and CI2 daily-usage time. Specific to CI2, the CCIQ showed improvement 1 year after CI2 implantation., Conclusion: CI2 improved the hearing performance and quality of life of recipients with longer interimplant intervals, especially in noisy environments, and its efficacy was associated with preoperative bimodal fitting and regular daily use., (© 2022 S. Karger AG, Basel.)

Background: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated., Methods: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097-1140 days), and the primary endpoint was cardiac death at 3 years., Results: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and ST-segment elevation myocardial (STEMI) in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53-0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65-1.44, p = 0.884)., Conclusions: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality.

Background: Children's motor development is a crucial tool for assessing developmental levels, identifying developmental disorders early, and taking appropriate action. Although the Korean Developmental Screening Test for Infants and Children (K-DST) can accurately assess childhood development, its dependence on parental surveys rather than reliable, professional observation limits it. This study constructed a dataset based on a skeleton of recordings of K-DST behaviors in children aged between 20 and 71 months, with and without developmental disorders. The dataset was validated using a child behavior artificial intelligence (AI) learning model to highlight its possibilities., Results: The 339 participating children were divided into 3 groups by age. We collected videos of 4 behaviors by age group from 3 different angles and extracted skeletons from them. The raw data were used to annotate labels for each image, denoting whether each child performed the behavior properly. Behaviors were selected from the K-DST's gross motor section. The number of images collected differed by age group. The original dataset underwent additional processing to improve its quality. Finally, we confirmed that our dataset can be used in the AI model with 93.94%, 87.50%, and 96.31% test accuracy for the 3 age groups in an action recognition model. Additionally, the models trained with data including multiple views showed the best performance., Conclusion: Ours is the first publicly available dataset that constitutes skeleton-based action recognition in young children according to the standardized criteria (K-DST). This dataset will enable the development of various models for developmental tests and screenings., (© The Author(s) 2023. Published by Oxford University Press GigaScience.)

The radiological image of an intact tectorial membrane (TM) became an important favorable prognostic factor for craniovertebral instability. This study visualized the fascial layers of the TM and adjacent connective tissues with clinical significance by micro-CT and histological analysis. The TM firmly attached to the bony surface of the clivus, traversed the atlantoaxial joint posteriorly, and was inserted to the body of the axis showing wide distribution on the craniovertebral junction. The supradental space between the clivus, dens of the axis, anterior atlantooccipital membrane, and the TM contained profound venous networks within the adipose tissues. At the body of the axis, the compact TM layer is gradually divided into multiple layers and the deeper TM layers reached the axis while the superficial layer continued to the posterior longitudinal ligament of the lower vertebrae. The consistent presence of the fat pad and venous plexus in the supradental space and firm stabilization of the TM on the craniovertebral junction was demonstrated by high-resolution radiologic images and histological analysis. The evaluation of the TM integrity is a promising diagnostic factor for traumatic craniovertebral dislocation., (© 2022. The Author(s).)