Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients.

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Identification of TNFAIP6 as a reliable prognostic indicator of low-grade glioma.

Glioma is the most common primary malignant tumor in the brain, characterizing by high disability rate and high recurrence rate. Although low-grade glioma (LGG) has a relative benign biological behavior, the prognosis of LGG patients still varies greatly. Glioma stem cells (GSCs) are considered as the chief offenders of glioma cell proliferation, invasion and resistance to therapies. Our study screened a series of glioma stem cell-related genes (GSCRG) based on mDNAsi and WCGNA, and finally established a reliable single-gene prognostic model through 101 combinations of 10 machine learning methods. Our result suggested that the expression level of TNFAIP6 is negatively correlated with the prognosis of LGG patients, which may be the result of pro-cancer signaling pathways activation and immunosuppression. In general, this study revealed that TNFAIP6 is a robust and valuable prognostic factor in LGG, and may be a new target for LGG treatment.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

High-efficiency triplet-triplet annihilation upconversion microemulsion with facile preparation and decent air tolerance.

Current research of triplet-triplet annihilation upconversion (TTA-UC) faces difficulty such as overuse of organic solvents and quenching of excited triplet sensitizers by molecular oxygen. Herein, we propose an efficient and facile preparation strategy of TTA-UC microemulsion to overcome these issues. With simple device and short preparation process, air-stable TTA-UC with a high upconversion efficiency of 16.52% was achieved in microemulsion coassembled from TritonX114, tetrahydrofuran and upconverting chromophores (platinum octaethyl-porphyrin and 9,10-diphenylanthracene). This is comparable to the highest UC efficiency ever reported for TTA-UC microemulsion systems. The excellent UC performance of TX114-THF could be attributed to two perspectives. Firstly, small-size micelle accommodated chromophores up to high concentrations in organic phase, which promoted efficient molecular collision. Additionally, high absorbance at 532 nm ensured full use of excitation light, getting more long wavelength photons involved in the TTA-UC process. Moreover, air-stable TTA-UC also performed well in microemulsion with various surfactants, including nonionic surfactants (Tween 20, Tween 80, Triton X-110, Triton X-114), ionic surfactants (sodium dodecyl sulfate, cetyltrimethyl ammonium bromide) and block copolymers (pluronic F127, pluronic P123), through three conjectural assembly models according to the structural characteristics of surfactant molecules (concentrated, uncompacted and scattered). These discoveries could provide estimable reference for selection of surfactants in relevant fields of TTA-UC.

Radical Ring-Opening Fluorosulfonylation of Methylenecyclobutanols via Electron Donor-Acceptor Photoactivation.

A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.

Coverage of the Combined DTaP-IPV/Hib Vaccine Among Children Aged 2-18 Months - 9 PLADs, China, 2019-2021.

What is already known on this topic?: In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines. What is added by this report?: We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period. What are the implications for public health practice?: Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity.

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity.

A review of advancements in chitosan-essential oil composite films: Better and sustainable food preservation with biodegradable packaging.

In response to the environmental pollution caused by non-degradable and non-recyclable plastic packaging films (PPFs) and the resulting health concerns due to the migration of microplastics into food, the development of biodegradable food packaging films has gained great attention. Chitosan has been extensively utilized in the food industry owing to its abundant availability, exceptional biocompatibility, degradability, and antimicrobial properties. Chitosan-essential oil composite films (CEOs) represent a promising avenue to replace conventional PPFs. This review provides an overview of the advancements in CEOs over the past decade, focusing on the effects of essential oils (EOs) on CEOs in terms of antimicrobial activity, antioxidant effect, gas barrier, light barrier, and mechanical properties. It also offers insights into the controlled release of EOs in CEOs and summarizes the application of CEOs in fresh food preservation.

Comparison of Sleeve Gastrectomy with Loop Duodenojejunal Bypass Versus One Anastomosis Gastric Bypass for Type 2 Diabetes: The Role of Pylorus Preservation.

BACKGROUND: One anastomosis gastric bypass (OAGB) is recognized as a standard procedure in metabolic surgery. However, concerns about postoperative bile reflux and nutritional risks are prevalent. Comparatively, sleeve gastrectomy with loop duodenojejunal bypass (SG + LoopDJB) bypasses an equivalent length of the foregut as OAGB while maintaining pyloric function. The role of pylorus function remains to be further elucidated regarding these metabolic procedures' therapeutic outcomes and side effects. METHOD: A retrospective study was conducted in our center to compare the surgical safety and 1-year outcomes of OAGB and SG + LoopDJB regarding type 2 diabetes mellitus (T2DM) remission, weight loss, gastrointestinal disorders, and nutritional status in T2DM patients matched by gender, age, and BMI. RESULTS: The baseline characteristics were comparable between groups. Compared with OAGB, SG + LoopDJB had longer operative time and length of stay (LOS) but similar major postoperative complications. At 1-year follow-up, OAGB has similar diabetes remission (both 91.9%), weight loss effect (28.1 ± 7.1% vs. 30.2 ± 7.0% for %TWL), and lipidemia improvement to SG + LoopDJB (P > 0.05). However, OAGB presented a higher incidence of hypoalbuminemia (11.9% vs. 2.4%, P = 0.026) but a low incidence of gastroesophageal reflux disease (GERD) symptoms (9.5% vs. 26.2%, P = 0.046) than SG + LoopDJB. There was no statistical difference regarding other gastrointestinal disorders and nutritional deficiencies between groups. CONCLUSION: Both OAGB and SG + LoopDJB show comparable, favorable outcomes in weight loss, T2DM remission, and lipidemia improvement at the 1-year follow-up. Pylorus preservation, while increasing surgical difficulty and the risk of de novo GERD, may reduce the risk of postoperative hypoalbuminemia.

[Analysis and reflection on current situation of Chinese patent medicine for children in China].

This study took Chinese patent medicine for children included in Chinese Pharmacopoeia(2020 edition and the first supplement), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2022 edition), and National Essential Medicines List(2018 edition) as the research objects, so as to sort out the distribution situation, characteristics, and the problems of Chinese patent medicine for children(including child-specific medicines, common medicines for children and adults, and discretionary medicines for children). According to statistics and summary, Chinese patent medicine for children is mainly administered orally, and the dosage forms are mostly traditional dosage forms, such as tablets, granules, capsules, and oral liquids, with mostly bitter or sweet taste. Diseases are mainly classified into pulmonary diseases and spleen and stomach diseases, and varieties of medication without Children's medication safety information or "still unclear" account for a relatively large proportion of the medicines. There are relatively few varieties of Chinese patent medicines for children, poor compliance of child-specific medication, lack of refinement of Chinese patent medicines for children dosage, and lack of information about safe use of medication. It is recommended to update and improve the instruction manuals in a timely manner, develop new varieties of Chinese patent medicine for children, and actively carry out post-marketing evaluation and clinical comprehensive evaluation of Chinese patent medicine for children, so as to provide a reference for the supplement and improvement of the instructions, the comprehensive improvement, the formulation of the catalogue, and the research and development of new Chinese patent medicine for children and ensure the use of medicines for children.

Astragalus polysaccharide: implication for intestinal barrier, anti-inflammation, and animal production.

Intestine is responsible for nutrients absorption and plays a key role in defending against various dietary allergens, antigens, toxins, and pathogens. Accumulating evidence reported a critical role of intestine in maintaining animal and human health. Since the use of antibiotics as growth promoters in animal feed has been restricted in many countries, alternatives to antibiotics have been globally investigated, and polysaccharides are considered as environmentally friendly and promising alternatives to improve intestinal health, which has become a research hotspot due to its antibiotic substitution effect. Astragalus polysaccharide (APS), a biological macromolecule, is extracted from astragalus and has been reported to exhibit complex biological activities involved in intestinal barrier integrity maintenance, intestinal microbiota regulation, short-chain fatty acids (SCFAs) production, and immune response regulation, which are critical for intestine health. The biological activity of APS is related to its chemical structure. In this review, we outlined the source and structure of APS, highlighted recent findings on the regulation of APS on physical barrier, biochemical barrier, immunological barrier, and immune response as well as the latest progress of APS as an antibiotic substitute in animal production. We hope this review could provide scientific basis and new insights for the application of APS in nutrition, clinical medicine and health by understanding particular effects of APS on intestine health, anti-inflammation, and animal production.

Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis.

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Synthesis of Nano-Structured Conjugated Polymers with Multiple Micro-/Meso-Pores by the Post-Crosslinking of End-Functionalized Hyperbranched Conjugated Polymers.

A nano-structured conjugated polymer with multiple micro-/meso-pores was synthesized by post-crosslinking of an end-functionalized hyperbranched conjugated prepolymer. Firstly, an AB2 monomer 3-((3,5-dibromo-4-(octyloxy)phenyl)ethynyl)-6-ethynyl-9-octyl-9H-carbazole (PECz) was synthesized and polymerized by Sonogashira reaction to give the -Br end-functionalized hyperbranched conjugated prepolymer hb-PPECz. The photophysical and electrochemical properties of hb-PPECz were investigated. The λmax of absorption and emission of hb-PPECz in tetrahydrofuran (THF) solution was 313 and 483 nm, respectively. The optical energy bandgap, highest occupied molecular orbital (HOMO), and lowest unoccupied molecular orbital (LUMO) energy levels of hb-PPECz were 2.98, -5.81, and -2.83 eV, respectively. Then, the prepolymer hb-PPECz was post-crosslinked by Heck reaction with divinylbenzene to give the porous conjugated polymer c-PPECz. The effects of hb-PPECz concentration and added dispersant polyvinylpyrrolidone (PVP K-30) on the morphology and porosity of c-PPECz were investigated. The resulting c-PPECzs showed multiple porous structures mainly constructed by micropores and mesopores. Under a higher hb-PPECz concentration (4 wt/v%), a bulky gel product was obtained. Under lower hb-PPECz concentrations (0.6 wt/v%~2 wt/v%), the resulting c-PPECzs were mainly composed of nano-sized particles. Nearly spheric nanoparticles (200~300 nm) (c-PPECz-5) were obtained under the concentration of 1 wt/v% in the presence of PVP (10 wt% of hb-PPECz). The Brunauer-Emmett-Teller (BET) surface area, pore volume, average pore size, and percentage of pore size below 10 nm of c-PPECz-5 were 10.7781 m2·g-1, 0.0108 cm3·g-1, 4.0081 nm, and 94.47%, respectively.

Formation Mechanisms, Interrelationships, and Effects of Cognitive Factors on Diet and Physical Activity During the Post-Bariatric Surgery Period: A Cross-Sectional Study Based on Compensatory Carry-Over Action Model.

Background: Diet and physical activity (PA) are pivotal behaviors for managing energy balance post-bariatric surgery. Given the need for dual behavioral management, understanding the interplay of cognitive factors influencing these behaviors is crucial. This study applied the compensatory carry-over action model (CCAM) to explore the impact of cognitive factors on behaviors and their subsequent effects on subjective health outcomes. Methods: This cross-sectional study was conducted among patients at the third month after bariatric surgery in China. Data on diet and PA status, behavioral cognitive factors (intention, self-efficacy, compensatory belief, transfer cognition), and subjective health outcomes (perceived stress, well-being, quality of life) were collected. Structural equation model (SEM) was employed to test hypotheses in CCAM and assess mediation relationships. Results: Analysis of data from 239 patients revealed the following: (1) Among antecedent cognitive factors, only compensatory belief significantly influenced diet (P<0.001). (2) Intention and self-efficacy directly correlated with their respective behaviors, while compensatory belief affected intention, and transfer cognition impacted self-efficacy (P<0.05), aligning with CCAM hypotheses. (3) PA demonstrated significant influence only on perceived stress (P=0.004), whereas diet significantly affected all subjective health outcomes (P<0.05). (4) Mediation analysis indicated intention partially mediated the relationship between compensatory belief and diet and fully mediated the relationship between compensatory belief and PA. Self-efficacy completely mediated the relationship between transfer cognition and diet and PA. Conclusion: Transfer cognition's carry-over effect did not directly influence behaviors among antecedent cognitions. Interventions should primarily target improving diet by mitigating compensatory belief. Moreover, diet exhibited a more pronounced impact on overall health compared to PA. Consequently, prioritizing dietary intervention over PA intervention is warranted based on the analysis of CCAM and the aim of promoting joint behaviors post-bariatric surgery.

Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial.

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (-0.39 mmol), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison<0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (-29.1 U/L and - 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both p < 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.

Diagnostic performance of machine learning in systemic infection following percutaneous nephrolithotomy and identification of associated risk factors.

Objective: This study aims to investigate the predictive performance of machine learning in predicting the occurrence of systemic inflammatory response syndrome (SIRS) and urosepsis after percutaneous nephrolithotomy (PCNL). Methods: A retrospective analysis was conducted on patients who underwent PCNL treatment between January 2016 and July 2022. Machine learning techniques were employed to establish and select the best predictive model for postoperative systemic infection. The feasibility of using relevant risk factors as predictive markers was explored through interpretability with Machine Learning. Results: A total of 1067 PCNL patients were included in this study, with 111 (10.4 %) patients developing SIRS and 49 (4.5 %) patients developing urosepsis. In the validation set, the risk model based on the GBM protocol demonstrated a predictive power of 0.871 for SIRS and 0.854 for urosepsis. Preoperative and postoperative platelet changes were identified as the most significant predictors. Both thrombocytopenia and thrombocytosis were found to be risk factors for SIRS or urosepsis after PCNL. Furthermore, it was observed that when the change in platelet count before and after PCNL surgery exceeded 30*109/L (whether an increase or decrease), the risk of developing SIRS or urosepsis significantly increased. Conclusion: Machine learning can be effectively utilized for predicting the occurrence of SIRS or urosepsis after PCNL. The changes in platelet count before and after PCNL surgery serve as important predictors.

Machine learning models reveal the critical role of nighttime systolic blood pressure in predicting functional outcome for acute ischemic stroke after endovascular thrombectomy.

Background: Blood pressure (BP) is a key factor for the clinical outcomes of acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the effect of the circadian pattern of BP on functional outcome is unclear. Methods: This multicenter, retrospective, observational study was conducted from 2016 to 2023 at three hospitals in China (ChiCTR2300077202). A total of 407 patients who underwent endovascular thrombectomy (EVT) and continuous 24-h BP monitoring were included. Two hundred forty-one cases from Beijing Hospital were allocated to the development group, while 166 cases from Peking University Shenzhen Hospital and Hainan General Hospital were used for external validation. Postoperative systolic BP (SBP) included daytime SBP, nighttime SBP, and 24-h average SBP. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), Boruta were used to screen for potential features associated with functional dependence defined as 3-month modified Rankin scale (mRS) score ≥ 3. Nine algorithms were applied for model construction and evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Three hundred twenty-eight of 407 (80.6%) patients achieved successful recanalization and 182 patients (44.7%) were functional independent. NIHSS at onset, modified cerebral infarction thrombolysis grade, atrial fibrillation, coronary atherosclerotic heart disease, hypertension were identified as prognostic factors by the intersection of three algorithms to construct the baseline model. Compared to daytime SBP and 24-h SBP models, the AUC of baseline + nighttime SBP showed the highest AUC in all algorithms. The XGboost model performed the best among all the algorithms. ROC results showed an AUC of 0.841 in the development set and an AUC of 0.752 in the validation set for the baseline plus nighttime SBP model, with a brier score of 0.198. Conclusion: This study firstly explored the association between circadian BP patterns with functional outcome for AIS. Nighttime SBP may provide more clinical information regarding the prognosis of patients with AIS after EVT.

Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis.

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.